Contents
ProloguePart One: The Mystery of the Missing Fossils
1 - Darwin’s Nemesis
2 - The Burgess Bestiary
3 - Soft Bodies and Hard Facts
4 - The Not Missing Fossils?
5 - The Genes Tell the Story?
6 - The Animal Tree of Life
7 - Punk Eek!
Part Two: How to Build an Animal
8 - The Cambrian Information Explosion
9 - Combinatorial Inflation
10 - The Origin of Genes and Proteins
11 - Assume a Gene
12 - Complex Adaptations and the Neo-Darwinian Math
13 - The Origin of Body Plans
14 - The Epigenetic Revolution
Part Three: After Darwin, What?
15 - The Post-Darwinian World and Self-Organization
16 - Other Post-Neo-Darwinian Models
17 - The Possibility of Intelligent Design
18 - Signs of Design in the Cambrian Explosion
19 - The Rules of Science
20 - What’s at Stake
Notes
Bibliography
Credits and Permissions
Index
Acknowledgments

Photographic Insert
Copyright
About the Publisher

Prologue
When people today hear the term “information revolution,” they typicallythink of silicon chips and software code, cellular phones and supercomputers.
They rarely think of tiny one-celled organisms or the rise of animal life. But,
while writing these words in the summer of 2012, I am sitting at the end of anarrow medieval street in Cambridge, England, where more than half acentury ago a far-reaching information revolution began in biology. Thisrevolution was launched by an unlikely but now immortalized pair ofscientists, Francis Crick and James Watson. Since my time as a Ph.D. student
at Cambridge during the late 1980s, I have been fascinated by the way theirdiscovery transformed our understanding of the nature of life. Indeed, sincethe 1950s, when Watson and Crick first illuminated the chemical structure andinformation-bearing properties of DNA, biologists have come to understandthat living things, as much as high-tech devices, depend upon digital
information—information that, in the case of life, is stored in a four-characterchemical code embedded within the twisting figure of a double helix.
Because of the importance of information to living things, it has now
become apparent that many distinct “information revolutions” have occurredin the history of life—not revolutions of human discovery or invention, butrevolutions involving dramatic increases in the information present within theliving world itself. Scientists now know that building a living organism
requires information, and building a fundamentally new form of life from a
simpler form of life requires an immense amount of new information. Thus,
wherever the fossil record testifies to the origin of a completely new form ofanimal life—a pulse of biological innovation—it also testifies to a significant
increase in the information content of the biosphere.
In 2009, I wrote a book called Signature in the Cell about the first“information revolution” in the history of life—the one that occurred with theorigin of the first life on earth. My book described how discoveries inmolecular biology during the 1950s and 1960s established that DNA contains
information in digital form, with its four chemical subunits (called nucleotide
bases) functioning like letters in a written language or symbols in a computercode. And molecular biology also revealed that cells employ a complex
information-processing system to access and express the information stored inDNA as they use that information to build the proteins and protein machinesthat they need to stay alive. Scientists attempting to explain the origin of life
must explain how both information-rich molecules and the cell’s informationprocessing system arose.
The type of information present in living cells—that is, “specified”
information in which the sequence of characters matters to the function of thesequence as a whole—has generated an acute mystery. No undirected physicalor chemical process has demonstrated the capacity to produce specified
information starting “from purely physical or chemical” precursors. For thisreason, chemical evolutionary theories have failed to solve the mystery of theorigin of first life—a claim that few mainstream evolutionary theorists now
dispute.
In Signature in the Cell, I not only reported the well-known impasse inorigin-of-life studies; I also made an affirmative case for the theory ofintelligent design. Although we don’t know of a material cause that generates
functioning digital code from physical or chemical precursors, we do know—
based upon our uniform and repeated experience—of one type of cause thathas demonstrated the power to produce this type of information. That cause isintelligence or mind. As information theorist Henry Quastler observed, “Thecreation of information is habitually associated with conscious activity.”1
Whenever we find functional information—whether embedded in a radio
signal, carved in a stone monument, etched on a magnetic disc, or produced
by an origin-of-life scientist attempting to engineer a self-replicating molecule—and we trace that information back to its ultimate source, invariably wecome to a mind, not merely a material process. For this reason, the discovery
of digital information in even the simplest living cells indicates the prioractivity of a designing intelligence at work in the origin of the first life.
My book proved controversial, but in an unexpected way. Though I clearlystated that I was writing about the origin of the first life and about theories ofchemical evolution that attempt to explain it from simpler preexistingchemicals, many critics responded as if I had written another book altogether.
Indeed, few attempted to refute my book’s actual thesis that intelligent design
provides the best explanation for the origin of the information necessary to
produce the first life. Instead, most criticized the book as if it had presented a
critique of the standard neo-Darwinian theories of biological evolution—
theories that attempt to account for the origin of new forms of life from
simpler preexisting forms of life. Thus, to refute my claim that no chemical
evolutionary processes had demonstrated the power to explain the ultimate
origin of information in the DNA (or RNA) necessary to produce life from
simpler preexisting chemicals in the first place, many critics cited processes atwork in already living organisms—in particular, the process of natural
selection acting on random mutations in already existing sections of
information-rich DNA. In other words, these critics cited an undirected
process that acts on preexistent information-rich DNA to refute my argument
about the failure of undirected material processes to produce information in
DNA in the first place.2
For example, the eminent evolutionary biologist Francisco Ayala
attempted to refute Signature by arguing that evidence from the DNA ofhumans and lower primates showed that the genomes of these organisms had
arisen as the result of an unguided, rather than intelligently designed, process—even though my book did not address the question of human evolution or
attempt to explain the origin of the human genome, and even though theprocess to which Ayala alluded clearly presupposed the existence of anotherinformation-rich genome in some hypothetical lower primate.3
Other discussions of the book cited the mammalian immune system as an
example of the power of natural selection and mutation to generate new
biological information, even though the mammalian immune system can only
perform the marvels it does because its mammalian hosts are already alive,and even though the mammalian immune system depends upon an elaborately
preprogrammed form of adaptive capacity rich in genetic information—one
that arose long after the origin of the first life. Another critic steadfastly
maintained that “Meyer’s main argument” concerns “the inability of random
mutation and selection to add information to [preexisting] DNA”4 andattempted to refute the book’s presumed critique of the neo-Darwinianmechanism of biological evolution accordingly.
I found this all a bit surreal, as if I had wandered into a lost chapter from a
Kafka novel. Signature in the Cell simply did not critique the theory of
biological evolution, nor did it ask whether mutation and selection can add
new information to preexisting information-rich DNA. To imply otherwise, as
many of my critics did, was simply to erect a straw man.
To those unfamiliar with the particular problems faced by scientists trying
to explain the origin of life, it might not seem obvious why invoking natural
selection does not help to explain the origin of the first life. After all, if
natural selection and random mutations can generate new information inliving organisms, why can it also not do so in a prebiotic environment? But
the distinction between a biological and prebiotic context was crucially
important to my argument. Natural selection assumes the existence of livingorganisms with a capacity to reproduce. Yet self-replication in all extant cells
depends upon information-rich proteins and nucleic acids (DNA and RNA),and the origin of such information-rich molecules is precisely what origin-of-

life research needs to explain. That’s why Theodosius Dobzhansky, one of thefounders of the modern neo-Darwinian synthesis, can state flatly, “Prebiological natural selection is a contradiction in terms.”5 Or, as Nobel Prize–
winning molecular biologist and origin-of-life researcher Christian de Duveexplains, theories of prebiotic natural selection fail because they “needinformation which implies they have to presuppose what is to be explained in
the first place.”6 Clearly, it is not sufficient to invoke a process thatcommences only once life has begun, or once biological information has
arisen, to explain the origin of life or the origin of the information necessary
to produce it.
All this notwithstanding, I have long been aware of strong reasons for
doubting that mutation and selection can add enough new information of theright kind to account for large-scale, or “macroevolutionary,” innovations—the various information revolutions that have occurred after the origin of life.
For this reason, I have found it increasingly tedious to have to concede, if
only for the sake of argument, the substance of claims I think likely to befalse.
And so the repeated prodding of my critics has paid off. Even though I did
not write the book or make the argument that many of my critics critiqued in
responding to Signature in the Cell, I have decided to write that book. And
this is that book.
Of course, it might have seemed a safer course to leave well enough alone.
Many evolutionary biologists now grudgingly acknowledge that no chemical
evolutionary theory has offered an adequate explanation of the origin of lifeor the ultimate origin of the information necessary to produce it. Why press apoint you never made in the first place?
Because despite the widespread impression to the contrary—conveyed by
textbooks, the popular media, and spokespersons for official science—theorthodox neo-Darwinian theory of biological evolution has reached an
impasse nearly as acute as the one faced by chemical evolutionary theory.
Leading figures in several subdisciplines of biology—cell biology,
developmental biology, molecular biology, paleontology, and even
evolutionary biology—now openly criticize key tenets of the modern version
of Darwinian theory in the peer-reviewed technical literature. Since 1980,
when Harvard paleontologist Stephen Jay Gould declared that neo-Darwinism“is effectively dead, despite its persistence as textbook orthodoxy,”7 theweight of critical opinion in biology has grown steadily with each passingyear.
A steady stream of technical articles and books have cast new doubt on thecreative power of the mutation and selection mechanism.8 So well establishedare these doubts that prominent evolutionary theorists must now periodicallyassure the public, as biologist Douglas Futuyma has done, that “just because
we don’t know how evolution occurred, does not justify doubt about whether
it occurred.”9 Some leading evolutionary biologists, particularly those
associated with a group of scientists known as the “Altenberg 16,” are openly
calling for a new theory of evolution because they doubt the creative power ofthe mutation and natural selection mechanism.10
The fundamental problem confronting neo-Darwinism, as with chemical
evolutionary theory, is the problem of the origin of new biologicalinformation. Though neo-Darwinists often dismiss the problem of the originof life as an isolated anomaly, leading theoreticians acknowledge that neoDarwinism has also failed to explain the source of novel variation without
which natural selection can do nothing—a problem equivalent to the problemof the origin of biological information. Indeed, the problem of the origin of
information lies at the root of a host of other acknowledged problems incontemporary Darwinian theory—from the origin of new body plans to theorigin of complex structures and systems such as wings, feathers, eyes,
echolocation, blood clotting, molecular machines, the amniotic egg, skin,nervous systems, and multicellularity, to name just a few.
At the same time, classical examples illustrating the prowess of natural
selection and random mutations do not involve the creation of novel genetic
information. Many biology texts tell, for example, about the famous finches
in the Galápagos Islands, whose beaks have varied in shape and length overtime. They also recall how moth populations in England darkened and thenlightened in response to varying levels of industrial pollution. Such episodes
are often presented as conclusive evidence for the power of evolution. And
indeed they are, depending on how one defines “evolution.” That term has
many meanings, and few biology textbooks distinguish between them.
“Evolution” can refer to anything from trivial cyclical change within thelimits of a preexisting gene pool to the creation of entirely novel genetic
information and structure as the result of natural selection acting on random
mutations. As a host of distinguished biologists have explained in recent
technical papers, small-scale, or “microevolutionary,” change cannot be
extrapolated to explain large-scale, or “macroevolutionary,” innovation.11 For
the most part, microevolutionary changes (such as variation in color or shape)
merely utilize or express existing genetic information, while themacroevolutionary change necessary to assemble new organs or whole bodyplans requires the creation of entirely new information. As an increasingnumber of evolutionary biologists have noted, natural selection explains “onlythe survival of the fittest, not the arrival of the fittest.”12 The technicalliterature in biology is now replete with world-class biologists13 routinely
expressing doubts about various aspects of neo-Darwinian theory, andespecially about its central tenet, namely, the alleged creative power of thenatural selection and mutation mechanism.
Nevertheless, popular defenses of the theory continue apace, rarely if everacknowledging the growing body of critical scientific opinion about thestanding of the theory. Rarely has there been such a great disparity between
the popular perception of a theory and its actual standing in the relevant peerreviewed scientific literature. Today modern neo-Darwinism seems to enjoy
almost universal acclaim among science journalists and bloggers, biology
textbook writers, and other popular spokespersons for science as the great
unifying theory of all biology. High-school and college textbooks present its
tenets without qualification and do not acknowledge the existence of any
significant scientific criticism of it. At the same time, official scientificorganizations—such as the National Academy of Sciences (NAS), theAmerican Association for the Advancement of Sciences (AAAS), and the
National Association of Biology Teachers (NABT)—routinely assure thepublic that the contemporary version of Darwinian theory enjoys unequivocal
support among qualified scientists and that the evidence of biology
overwhelmingly supports the theory. For example, in 2006 the AAAS
declared, “There is no significant controversy within the scientific community
about the validity of the theory of evolution.”14 The media dutifully echothese pronouncements. As New York Times science writer Cornelia Dean
asserted in 2007, “There is no credible scientific challenge to the theory of
evolution as an explanation for the complexity and diversity of life onearth.”15
The extent of the disparity between popular representations of the status of
the theory and its actual status, as indicated in the peer-reviewed technicaljournals, came home to me with particular poignancy as I was preparing totestify before the Texas State Board of Education in 2009. At the time theboard was considering the adoption of a provision in its science education
standards that would encourage teachers to inform students of both thestrengths and weaknesses of scientific theories. This provision had become apolitical hot potato after several groups asserted that “teaching strengths andweaknesses” were code words for biblical creationism or for removing theteaching of the theory of evolution from the curriculum. Nevertheless, after
defenders of the provision insisted that it neither sanctioned teachingcreationism nor censored evolutionary theory, opponents of the provision
shifted their ground. They attacked the provision by insisting that there wasno need to consider weaknesses in modern evolutionary theory because, as
Eugenie Scott, spokeswoman for the National Center for Science Education,
insisted in The Dallas Morning News, “There are no weaknesses in the theoryof evolution.”16
At the same time, I was preparing a binder of one hundred peer-reviewed
scientific articles in which biologists described significant problems with thetheory—a binder later presented to the board during my testimony. So I knew
—unequivocally—that Dr. Scott was misrepresenting the status of scientificopinion about the theory in the relevant scientific literature. I also knew that
her attempts to prevent students from hearing about significant problems withevolutionary theory would have likely made Charles Darwin himself
uncomfortable. In On the Origin of Species, Darwin openly acknowledged
important weaknesses in his theory and professed his own doubts about key
aspects of it. Yet today’s public defenders of a Darwin-only sciencecurriculum apparently do not want these, or any other scientific doubts about
contemporary Darwinian theory, reported to students.
This book addresses Darwin’s most significant doubt and what has becomeof it. It examines an event during a remote period of geological history inwhich numerous animal forms appear to have arisen suddenly and without
evolutionary precursors in the fossil record, a mysterious event commonlyreferred to as the “Cambrian explosion.” As he acknowledged in the Origin,
Darwin viewed this event as a troubling anomaly—one that he hoped future
fossil discoveries would eventually eliminate.
The book is divided into three main parts. Part One, “The Mystery of theMissing Fossils,” describes the problem that first generated Darwin’s doubt—
the missing ancestors of the Cambrian animals in the earlier Precambrianfossil record—and then tells the story of the successive, but unsuccessful,attempts that biologists and paleontologists have made to resolve thatmystery.
Part Two, “How to Build an Animal,” explains why the discovery of theimportance of information to living systems has made the mystery of theCambrian explosion more acute. Biologists now know that the Cambrian
explosion not only represents an explosion of new animal form and structure
but also an explosion of information—that it was, indeed, one of the mostsignificant “information revolutions” in the history of life. Part Two examines
the problem of explaining how the unguided mechanism of natural selection
and random mutations could have produced the biological informationnecessary to build the Cambrian animal forms. This group of chaptersexplains why so many leading biologists now doubt the creative power of the
neo-Darwinian mechanism and it presents four rigorous critiques of themechanism based on recent biological research.
Part Three, “After Darwin, What?” evaluates more current evolutionary
theories to see if any of them explain the origin of form and information moresatisfactorily than standard neo-Darwinism does. Part Three also presents andassesses the theory of intelligent design as a possible solution to the Cambrian
mystery. A concluding chapter discusses the implications of the debate about
design in biology for the larger philosophical questions that animate humanexistence. As the story of the book unfolds, it will become apparent that aseemingly isolated anomaly that Darwin acknowledged almost in passing has
grown to become illustrative of a fundamental problem for all of evolutionary
biology: the problem of the origin of biological form and information.
To see where that problem came from and why it has generated a crisis inevolutionary biology, we need to begin at the beginning: with Darwin’s own
doubt, with the fossil evidence that elicited it, and with a clash between a pairof celebrated Victorian naturalists—the famed Harvard paleontologist Louis
Agassiz and Charles Darwin himself.

Part OneThe Mystery of the Missing Fossils

1
Darwin’s Nemesis
When Charles Darwin finished his famous book, he thought that he had
explained every clue but one.
By anyone’s measure, On the Origin of Species was a singularachievement. Like a great Gothic cathedral, the ambitious work integrated
many disparate elements into a grand synthesis, explaining phenomena infields as diverse as comparative anatomy, paleontology, embryology, andbiogeography. At the same time, it was impressive for its simplicity. Darwin’s
Origin explained many classes of biological evidence with just two central
organizing ideas. The twin pillars of his theory were the ideas of universal
common ancestry and natural selection.
The first of these pillars, universal common ancestry, represented Darwin’s
theory of the history of life. It asserted that all forms of life have ultimately
descended from a single common ancestor somewhere in the distant past. In afamous passage at the end of the Origin, Darwin argued that “all the organic
beings which have ever lived on this earth have descended from some one
primordial form.”1 Darwin thought that this primordial form graduallydeveloped into new forms of life, which in turn gradually developed into
other forms of life, eventually producing, after many millions of generations,
all the complex life we see in the present.
Biology textbooks today usually depict this idea just as Darwin did, with agreat branching tree. The trunk of Darwin’s tree of life represents the firstprimordial organism. The limbs and branches of the tree represent the many
new forms of life that developed from it (see Fig. 1.1). The vertical axis onwhich the tree is plotted represents the arrow of time. The horizontal axis
represents changes in biological form, or what biologists call “morphologicaldistance.”FIGURE 1.1
Darwin’s evolutionary tree of life, as depicted by the nineteenth-century
German evolutionary biologist Ernst Haeckel.
Biologists often call Darwin’s theory of the history of life “universal
common descent” to indicate that every organism on earth arose from a single
common ancestor by a process of “descent with modification.” Darwin argued
that this idea best explained a variety of biological evidences: the successionof fossil forms, the geographical distribution of various species (such as
Galápagos finches), and the anatomical and embryological similarities among
otherwise highly distinct organisms.
The second pillar of Darwin’s theory affirmed the creative power of aprocess he called natural selection, a process that acted on random variationsin the traits or features of organisms and their offspring.2 Whereas the theoryof universal common descent postulated a pattern (the branching tree) torepresent the history of life, Darwin’s idea of natural selection referred to aprocess that he said could generate the change implied by his branching treeof life.
Darwin formulated the idea of natural selection by analogy to a wellknown process, that of “artificial selection” or “selective breeding.” Anyone
in the nineteenth century familiar with the breeding of domestic animals—
dogs, horses, sheep, or pigeons, for example—knew that human breeders
could alter the features of domestic stock by allowing only animals withcertain traits to breed. A sheepherder from the north of Scotland might breed
for a woollier sheep to enhance its chances of survival in a cold northern
climate (or to harvest more wool). To do so, he would choose only thewoolliest males and woolliest ewes to breed. If generation after generation hecontinued to select and breed only the woolliest sheep among the resulting
offspring, he would eventually produce a woollier breed of sheep. In suchcases, “the key is man’s power of accumulative selection,” wrote Darwin.
“Nature gives successive variations; man adds them up in certain directions
useful to him.”3
Darwin noted that pigeons have been coaxed into a dizzying variety ofbreeds: the carrier, with its elongated eyelids and a “wide gape of mouth”; the“short-faced tumbler,” with its “beak in outline almost like that of a finch”;
the common tumbler, with its penchant for flying in close formation and“tumbling in the air head over heels”; and, perhaps strangest of all, the pouter,with its elongated legs, wings, and body overshadowed by its “enormously
developed crop, which it glories in inflating” for its astonished patrons.4
Of course, pigeon breeders achieved these startling metamorphoses bycarefully sifting and selecting. But, as Darwin pointed out, nature also has ameans of sifting: defective creatures are less likely to survive and reproduce,
while those offspring with beneficial variations are more likely to survive,
reproduce, and pass on their advantages to future generations. In the Origin,
Darwin argued that this process, natural selection acting on randomvariations, could alter the features of organisms just as intelligent selection byhuman breeders can. Nature itself could play the role of the breeder.
Consider once more our flock of sheep. Imagine that instead of a humanselecting the woolliest males and ewes to breed, a series of very cold winters
ensures that all but the very woolliest sheep in a population die. Now again
only very woolly sheep will remain to breed. If the cold winters continue over
several generations, will the result not be the same as before? Won’t the
population of sheep eventually become discernibly woollier?
This was Darwin’s great insight. Nature—in the form of environmental
changes or other factors—could have the same effect on a population oforganisms as the intentional decisions of an intelligent agent. Nature would

favor the preservation of certain features over others—specifically, those that
conferred a functional or survival advantage upon the organisms possessingthem—causing the features of the population to change. And the resulting
change will have been produced not by an intelligent breeder choosing adesirable trait or variation—not by “artificial selection”—but by a wholly
natural process. What’s more, Darwin concluded that this process of natural
selection acting on randomly arising variations had been “the chief agent ofchange” in generating the great branching tree of life in all its variety.
On the Origin of Species seized the attention of the scientific community
like a thunderclap. Darwin’s analogy to artificial selection was powerful, his
proposed mechanism of natural selection and random variation easily
grasped, and his skill in dispensing with potential objections unrivalled.
Moreover, the explanatory scope of his argument for universal common
descent constituted something of a tour de force. By the close of the Origin, it
seemed to many that Darwin had dispensed with every conceivable objection
to his theory but one.
THE ANOMALY: DARWIN’S DOUBT
Despite the scope of his synthesis, there was one set of facts that troubled
Darwin—something he conceded his theory couldn’t adequately explain, atleast at present. Darwin was puzzled by a pattern in the fossil record that
seemed to document the geologically sudden appearance of animal life in aremote period of geologic history, a period that at first was commonly called
the Silurian, but later came to be known as the Cambrian.
During this geological period, many new and anatomically sophisticatedcreatures appeared suddenly in the sedimentary layers of the geologic column
without any evidence of simpler ancestral forms in the earlier layers below, inan event that paleontologists today call the Cambrian explosion. Darwin
frankly described his concerns about this conundrum in the Origin: “Thedifficulty of understanding the absence of vast piles of fossiliferous strata,
which on my theory were no doubt somewhere accumulated before the
Silurian [i.e., Cambrian] epoch, is very great,” he wrote. “I allude to themanner in which numbers of species of the same group suddenly appear in thelowest known fossiliferous rocks.”5 The sudden appearance of animals soearly in the fossil record did not easily accord with Darwin’s new theory ofgradual evolutionary change, and there was one scientist who would not let
him forget it.
THE ANTAGONISTSwiss-born paleontologist Louis Agassiz, of Harvard University, was one of
the best-trained scientists of his age, and he knew the fossil record better than
any man alive. Hoping to enlist Agassiz as an ally, Darwin sent him a copy ofOn the Origin of Species and asked him to consider the argument with anopen mind (see Fig. 1.2). One can almost see the great, aging naturalist
receiving the unremarkable package from the postman, unwrapping the small
green volume that had stirred such a tempest on both sides of the Atlantic.
Perhaps he retired to his study the better to concentrate, scrutinizing thebook’s prepossessing title, recalling what he had already heard about thework. He read the book with deep interest, making notes in the margin as hemoved through it, but in the end his verdict would disappoint its author.
Agassiz concluded that the fossil record, particularly the record of the
explosion of Cambrian animal life, posed an insuperable difficulty for
Darwin’s theory.

FIGURE 1.2
Figure 1.2a (left): Louis Agassiz. Figure 1.2b (right): Charles Darwin.
THE TWO-PRONGED CHALLENGE
To see why, consider brachiopods and trilobites, two of the best-documented
creatures in the Cambrian fossil record by 1859. The brachiopod (see Fig.
1.3), with its two shells, looks like a clam or an oyster, but is very different
inside. As shown in the accompanying figure, it possesses a gonad, mantle,
mantle cavity, anterior body wall, body cavity, gut, and lophophore, the last ofwhich is a feeding organ like a ring of tentacles, usually in the shape of a coilor horseshoe, with a mouth inside the ring of tentacles, and an anus outside.
The brachiopod exhibits a highly complex overall body plan, with many
individually complex and functionally integrated anatomical systems andparts. Its tentacles, for instance, are covered by cilia precisely arranged togenerate and direct a current of water toward the mouth.6

FIGURE 1.3
Figure 1.3a (top): Brachiopod internal anatomy. Figure 1.3b (bottom, left):
Brachiopod fossil showing remains of internal structure. Courtesy Paul
Chien. Figure 1.3c (bottom, right): Fossil showing exterior structure ofbrachiopod shell. Courtesy Corbis.

FIGURE 1.4
Figure 1.4a (top): Trilobite anatomy. Figure 1.4b (bottom): Trilobite fossil ofthe species Kuanyangia pustulosa. Courtesy Illustra Media.
Even more sophisticated was the trilobite (see Fig. 1.4), with its threelongitudinal lobes across its head (a raised middle lobe and a flatter pleurallobe to either side) and a body divided into three parts—head, chest, and tail,the former two consisting of as many as thirty segments. It had a pair of legs
for every pleural groove and another three pairs for the head. Most dramaticof all were the compound eyes found on even some of the very early trilobites—eyes that afforded these not so primitive animals a 360-degree field ofvision.7
The abrupt appearance of such complex anatomical designs presented achallenge to each of the two main parts of Darwin’s theory of evolution.

THE CAMBRIAN EXPLOSION AND THE ACTION OF NATURALSELECTION
The Cambrian fossil evidence represented a significant challenge to Darwin’s
claim that natural selection had the capacity to produce novel forms of life.
As Darwin described it, the ability of natural selection to produce significant
biological change depends upon the presence of three distinct elements: (1)randomly arising variations, (2) the heritability of those variations, and (3) acompetition for survival, resulting in differences in reproductive successamong competing organisms.
According to Darwin, variations in traits arise randomly. Some variations(such as thicker fleece) might confer advantages in the competition forsurvival in particular environmental conditions. Those variations that are
heritable and that impart functional or survival advantage will be preserved in
the next generation. As nature “selects” these successful variations, thefeatures of a population change.
Darwin conceded that the beneficial variations responsible for permanentchange in species are both rare and necessarily modest. Major variations informs, what later evolutionary biologists would term “macromutations,”
inevitably produce deformity and death. Only minor variations meet the testof viability and heritability.
It followed that, over human timescales, the benefits of this evolutionary
mechanism would be difficult or impossible to spot. But given enough time,
favorable variations would gradually accumulate and give rise to new species
and, given more time, even fundamentally new groups of organisms and bodydesigns. If artificial selection could conjure so many strange breeds from awild strain in a few centuries, Darwin argued, imagine what natural selection
could achieve over many millions of years. Even the origin of complex
structures such as the mammalian eye—which seemed at first to present asignificant challenge to his theory—could be explained if one postulated theexistence of an initially simpler structure (such as a light sensitive spot) that
could be gradually modified over long periods of time.
And that was the rub. Darwin’s mechanism of natural selection andrandom variation necessarily required a lot of time to generate wholly novel
organisms, creating a dilemma that Agassiz was keen to expose.
In an 1874 Atlantic Monthly essay titled “Evolution and the Permanence ofType,” Agassiz explained his reasons for doubting the creative power ofnatural selection. Small-scale variations, he argued, had never produced a“specific difference” (i.e., a difference in species). Meanwhile, large-scalevariations, whether achieved gradually or suddenly, inevitably resulted insterility or death. As he put it, “It is a matter of fact that extreme variations
finally degenerate or become sterile; like monstrosities they die out.”8
Darwin himself insisted that the process of evolutionary change heenvisioned must occur very gradually for the same reason. Thus, Darwin
realized that building, for instance, a trilobite from single-celled organisms bynatural selection operating on small, step-by-step variations would require
countless transitional forms and failed biological experiments over vast
stretches of geologic time. As University of Washington paleontologist Peter
Ward would later explain, Darwin had very specific expectations for what
paleontologists would find below the lowest known strata of animal fossils—in particular, “intervening strata showing fossils of increasing complexity
until finally trilobites appeared.”9 As Darwin noted, “If my theory be true, it
is indisputable that before the lowest Silurian [Cambrian] stratum wasdeposited, long periods elapsed, as long as, or probably far longer than, thewhole interval from the Silurian age to the present day; and that during thesevast, yet quite unknown, periods of time, the world swarmed with living
creatures.”10
The mechanism of natural selection necessarily had to work gradually onsmall incremental variations. And, indeed, the kinds of variations that Darwin
actually observed and described in developing his analogy between naturaland artificial selection were in every case minor. Only by selecting andaccumulating minor variations over many generations were breeders able toproduce the striking changes in the features of a breed, changes that were,
nevertheless, extraordinarily modest compared to the radical differences inform between, say, Precambrian and Cambrian forms of life. At the end of theday, as Agassiz hastened to note, the pigeons Darwin cited in support of thecreative power of artificial and, by analogy, natural selection were still
pigeons. More significant changes to the form and anatomical structure oforganisms would, by the logic of Darwin’s mechanism, require untold
millions of years, precisely what seemed unavailable in the case of theCambrian explosion.
THE CAMBRIAN EXPLOSION AND THE TREE OF LIFE
The abrupt appearance of the Cambrian fauna also posed a separate but
related difficulty for Darwin’s picture of a continuously branching tree of life.
To produce truly novel animal forms, the Darwinian mechanism would—by
its own internal logic—require not only millions of years, but untold
generations of ancestors. Thus, even the discovery of a handful of plausible
intermediates allegedly linking a Precambrian ancestor to a Cambriandescendant wouldn’t come close to fully documenting Darwin’s picture of thehistory of life. If Darwin is right, Agassiz argued, then we should find not justone or a few missing links, but innumerable links shading almost
imperceptibly from alleged ancestors to presumed descendants. Geologists,
however, had found no such myriad of transitional forms leading to theCambrian fauna. Instead, the stratigraphic column seemed to document theabrupt appearance of the earliest animals.
Agassiz thought the evidence of abrupt appearance, and the absence ofancestral forms in the Precambrian, refuted Darwin’s theory.11 Of these earlier
forms, Agassiz asked, “Where are their fossilized remains?” He insisted thatDarwin’s picture of the history of life “contradict[ed] what the animal forms
buried in the rocky strata of our earth tell us of their own introduction andsuccession upon the surface of the globe. Let us therefore hear them;—for,after all, their testimony is that of the eye-witness and the actor in thescene.”12
MURCHISON, SEDGWICK, AND THE CAMBRIAN FOSSILS OF
WALES
Darwin, for his part, responded with more than civility. Far from dismissing
Agassiz, he conceded that his objection carried considerable force. Nor was
Agassiz alone in pressing these concerns. Other leading naturalists thought
the fossil evidence presented a significant obstacle to Darwin’s theory. At thetime, perhaps the best place to investigate the lowest known strata of fossils
was Wales, and one of its leading experts was Roderick Impey Murchison,
who named the earliest geologic period the Silurian after an ancient Welsh
tribe. Five years before On the Origin of Species, he called attention to thesudden appearance of complex designs like the compound eyes of the first
trilobites, creatures already thriving at the apparent dawn of animal life. For
him, this discovery ruled out the idea that these creatures had evolved
gradually from some primitive and relatively simple form: “The earliest signsof living things, announcing as they do a high complexity of organization,
entirely exclude the hypothesis of a transmutation from lower to higher gradesof being.”13
The other pioneering explorer of Wales’s rich fossil record, Adam
Sedgwick, also thought that Darwin had leaped beyond the evidence, as hetold him in a letter in the fall of 1859: “You have deserted—after a start inthat tram-road of all solid physical truth—the true method of induction.”14
Sedgwick might have had in mind the same evidence the two men had studied
together some twenty-eight years before when the Cambridge professor hadbrought Darwin along as his field assistant to explore, in the Upper Swansea
Valley in northwestern Wales, the very strata that seemed to testify sopowerfully to the sudden appearance of animal life. It was these strata that
Sedgwick named after a Latinized English term for the country of Wales—“Cambria,” a designation that eventually replaced “Silurian” as the namefor the earliest strata of animal fossils.

FIGURE 1.5
Three organisms that first appear in the Ordivician period: eurypterans (seascorpions), starfish, and tetracoral.
Sedgwick emphasized that these Cambrian animal fossils appeared to pop
out of nowhere into the geological column. But he also stressed what heviewed as a broader reason to doubt Darwin’s evolutionary model: the sudden
appearance of the Cambrian animals was merely the most outstanding
instance of a pattern of discontinuity that extends throughout the geologic
column. Where in the Ordovician strata, for instance, are many of the familiesof the trilobites and brachiopods present in the Cambrian just below it?15
These creatures along with numerous other types suddenly disappear. But justas suddenly one finds newcomers in the Ordovician strata like the eurypterans(sea scorpions), starfish, and tetracorals (see Fig. 1.5).16 In a later Paleozoic
period called the Devonian, the first amphibians (e.g., Ichthyostega) arise.
Much later, many staples of the Paleozoic era (which encompasses theCambrian, Ordovician, and four subsequent periods) suddenly go extinct in aperiod called the Permian.17 Then, in the Triassic period that follows,completely novel animals such as turtles and dinosaurs emerge.18 Suchdiscontinuity, Sedgwick argued, is not the exception, but the rule.
DATING BY DISCONTINUITY
Already by Sedgwick’s time, the various strata of fossils had proved so
distinct one from another that geologists had come to use the sharp
discontinuities between them as a key means for dating rocks. Originally, thebest tool for determining the relative age of various strata was based on thenotion of superposition. Put simply, unless there is a reason to believe
otherwise, a geologist provisionally assumes that lower rocks were put down
before the rocks above them. Now, contrary to a widespread caricature, norespected geologist, then or now, adopts this method uncritically. The mostbasic training in geology teaches that rock formations can be twisted,
upended, even mixed pell-mell by a variety of phenomena. This is why
geologists have always looked for other means to estimate the relative age ofdifferent strata.
In 1815, Englishman William Smith had hit upon just such an alternativemeans.19 While studying the distinct fossil strata exposed during canalconstruction, Smith noted that so dissimilar are the fossil types among
different major periods and so sharp and sudden the break between them, thatgeologists could use this as one method for determining the relative age ofstrata. Even when layers of geological strata are twisted and turned, the clear
discontinuities between the various strata often allow geologists to discern theorder in which they were deposited, particularly when there is a broad enoughsampling of rich geological sites from the period under investigation to study
and cross-reference. Although not without its pitfalls, this approach has
become a standard dating technique, used in conjunction with superpositionand other more recent radiometric dating methods.20

FIGURE 1.6
The geological timescale.
Indeed, it’s difficult to overemphasize how central the approach is tomodern historical geology. As Harvard paleontologist Stephen Jay Gould
explains, it is the phenomenon of fossil succession that dictates the names ofthe major periods in the geological column (see Fig. 1.6). “We might take thehistory of modern multi-cellular life, about 600 million years, and divide thistime into even and arbitrary units easily remembered as 1–12 or A-L, at 50
million years per unit,” Gould writes. “But the earth scorns our
simplifications, and becomes much more interesting in its derision. The
history of life is not a continuum of development, but a record punctuated bybrief, sometimes geologically instantaneous, episodes of mass extinction andsubsequent diversification.”21 The question that Darwin’s early critics posed
was this: How could he reconcile his theory of gradual evolution with a fossil
record so discontinuous that it had given rise to the names of the majordistinct periods of geological time, particularly when the first animal forms
seemed to spring into existence during the Cambrian as if from nowhere?
A SOLUTION UNSEENOf course, Darwin was well aware of these problems. As he noted in theOrigin, “The abrupt manner in which whole groups of species suddenly
appear in certain formations has been urged by several paleontologists—for
instance, by Agassiz, Pictet, and Sedgwick—as a fatal objection to the belief
in the transmutation of species. If numerous species, belonging to the samegenera or families, have really started into life all at once, the fact would befatal to the theory of descent with slow modification through natural
selection.”22 Darwin, however, proposed a possible solution. He suggested
that the fossil record may be significantly incomplete: either the ancestralforms of the Cambrian animals were not fossilized or they hadn’t been foundyet. “I look at the natural geological record, as a history of the world
imperfectly kept, and written in a changing dialect,” Darwin wrote. “Of thishistory we possess the last volume alone, relating only to two or three
countries. Of this volume, only here and there a short chapter has beenpreserved; and of each page, only here and there a few lines. . . . On this view,the difficulties above discussed are greatly diminished, or even disappear.”23
Darwin himself was less than satisfied with this explanation.24 Agassiz, for
his part, would have none of it. “Both with Darwin and his followers, a greatpart of the argument is purely negative,” he wrote. They “thus throw off the
responsibility of proof. . . . However broken the geological record may be,
there is a complete sequence in many parts of it, from which the character ofthe succession may be ascertained.” On what basis did he make this claim?
“Since the most exquisitely delicate structures, as well as embryonic phasesof growth of the most perishable nature, have been preserved from very early
deposits, we have no right to infer the disappearance of types because theirabsence disproves some favorite [i.e., Darwinian] theory.”25
Though Darwin himself was less than enthusiastic about his response toAgassiz’s objection, it seemed adequate to satisfy the needs of the moment.
The overwhelming preponderance of evidence that Darwin had marshaled
seemed to support his theory. In any case, many leading naturalists—Joseph
Hooker, Thomas Huxley, Ernst Haeckel, and Asa Gray—all younger thanAgassiz, quickly aligned themselves with his evolutionary line of thinking.
True, some scientists, notably the Scottish engineering professor Fleeming
Jenkin and (later) the English geneticist William Bateson, expressed persistent
doubts about the efficacy of natural selection. But despite the views of some

weighty scientific critics, Darwin’s revolutionary theory won increasingly
wide support and soon defined the terms of the debate about the history oflife. Those who rejected it wholesale, as Agassiz did, consigned themselves toincreasing irrelevance.
AGASSIZ UNDER THE MICROSCOPE
So did Agassiz identify a genuine problem for Darwin’s theory, a mystery, atleast, waiting to be solved? If so, whatever became of this problem? And if
not, how could such a brilliant and knowledgeable scientist, someone so
steeped in the evidence, fall so far outside the mainstream of scientificopinion?
Historians of science in the post-Darwinian era have typically attempted toanswer this later question by portraying Agassiz as a brilliant and respectedscientist who nevertheless was too ossified to catch the new wave, a figure
past his prime and mired in philosophical prejudice.26 Biographer Edward
Lurie describes the Harvard naturalist as a “giant of the nineteenth century . . .
a person deeply involved in his surroundings, a man who understood thepossibilities of life with an uncommon awareness.”27 Similarly, historian
Mabel Robinson says that she long awaited a biography of Agassiz that“would re-create this man of genius and his headlong splendid race throughlife.” He was, she said, “a man to remember because genius is rare,” “animmortal Pied Piper.”28 These scholars are merely echoing what Agassiz’s
contemporaries, even Darwin himself, said. “What a set of men you have at
Harvard!” Darwin told the American poet Henry Wadsworth Longfellow.
“Both our universities put together cannot furnish the like. Why, there is
Agassiz—he counts for three.”29
Even so, many historians argue that Agassiz was too infected by German
idealism to properly assess the factual basis of Darwin’s case. According toidealist philosophers of biology, living forms exemplified transcendent ideas
and in their organization provided evidence of purposive design in nature.
Comments historian A. Hunter Dupree, “Agassiz’s idealism was of course thebasis of his concepts of species and their distribution,” of his insistence that adivine or intellectual cause must stand behind the origin of each type.30 The
ship of science was transitioning from idealism to modern empiricism.
Agassiz had fallen overboard, since he had imbibed too deeply an outmoded
idealism from his teacher, the French anatomist Georges Cuvier, and fromphilosophers like Friedrich Schelling, who “ran wild in trying to put all nature
into a unified and absolute system of ideas.”31 Agassiz wasn’t merely wrong,Dupree explains, but an annoying obscurantist, actively fighting “against theextension of empiricism into natural history.”32
Edward Lurie offers a similar if somewhat more nuanced assessment:
although “quite capable of making the most admirable scientific discoveriesreflecting complete devotion to scientific method,” Agassiz “would theninterpret the data through the medium of what seemed to be the most absurd
metaphysics.”33 The very man who made “the most careful, exact, and precise
descriptions” of the natural world would, in his generalizations from thoseobservations, “indulge in flights of idealistic fancy.”34 In short, Lurie thoughtthat “Agassiz’s cosmic philosophy shaped his entire reaction to the evolution
idea.”35
As science advanced in the late nineteenth century, it increasingly
excluded appeals to divine action or divine ideas as a way of explaining
phenomena in the natural world. This practice came to be codified in a
principle known as methodological naturalism. According to this principle,
scientists should accept as a working assumption that all features of thenatural world can be explained by material causes without recourse topurposive intelligence, mind, or conscious agency.
Proponents of methodological naturalism argue that science has been so
successful precisely because it has assiduously avoided invoking creative
intelligence and, instead, searched out strictly material causes for previously
mysterious features of the natural world. In the 1840s, the French philosopher
August Comte argued that science progresses through three distinct phases. In
its theological phase, it invokes the mysterious action of the gods to explain
natural phenomena, whether thunderbolts or the spread of disease. In asecond, more advanced metaphysical stage, scientific explanations refer toabstract concepts like Plato’s forms or Aristotle’s final causes. Comte taughtthat science only reaches maturity when it casts aside such abstractions andexplains natural phenomena by reference to natural laws or strictly materialcauses or processes. Only in this third and final stage, he argued, can scienceachieve “positive” knowledge.
During the late nineteenth century, scientists increasingly embraced this“positivistic” vision.36 Agassiz, by insisting that the Cambrian fossils pointed
to “acts of mind”37 and an “intervention of an intellectual power,” stoodfirmly against this new vision. For many, his reference to the work of atranscendent mind merely demonstrated that he was unable to abandon an
outmoded idealistic approach. The train of scientific progress had left Agassiz
behind.

AN OLD FOSSIL RECOVERED
Though clearly Agassiz did reject the principle of methodological naturalism,
as it is now named, there are problems with portraying him as a fossil of
another age. First, Agassiz was unsurpassed in his commitment to theempirical method. It is Agassiz about whom the story is told of the professor
instructing one of his students to observe a fish for three arduous days, a story
iconic enough that it is reprinted in freshman composition textbooks. In thestory, the student, Samuel Scudder, pulls out his hair trying to see anything
new about the slimy creature, wondering why Professor Agassiz is torturing
him with this “hideous fish.” But in the end Scudder breaks through to newlevels of observational depth and precision. Mabel Robinson notes that if suchteaching methods seem less revolutionary to contemporary readers than they
did to Scudder, that’s because Agassiz trained an army of able young
naturalists who took his method to other universities, and they in turn passed
them on to their students, themselves future professors.38
William James, the founder of American pragmatism, extolled Agassiz’s
commitment to empirical rigor in a letter he wrote to his father while on an
expedition with Agassiz in 1865 to South America. In the letter the young
man commented that he felt a “greater feeling of weight and solidity about thepresence of this great background of special facts than about the mind of any
other man I know,”39 a storehouse of precise data made possible by “arapidity of observation, and a capacity to recognize them again and remember
everything about them.”40 James would eventually enter the field of
psychology, but he took with him the empirical approach to problem solving
that Agassiz had modeled so impressively.41
As Lurie concedes, Agassiz’s stature among American scientists grew outof his unrivaled knowledge of geology, paleontology, ichthyology,
comparative anatomy, and taxonomy. So passionate was Agassiz for theparticulars of the natural world that he began organizing a system of
information-sharing among naturalists, sailors, and missionaries around theworld. He collected more than 435 barrels of specimens, among them anextremely rare group of fossil plants.42 In a single year, Agassiz amassed
more than 91,000 specimens and identified close to 11,000 new species,43
making Harvard’s natural history museum preeminent among such museumsin the world.
He also appears to have gone to great lengths, literally and figuratively, toassess On the Origin of Species empirically, going so far as to make a
research voyage retracing Darwin’s trip to the Galápagos Islands. As he
explained to German zoologist Carl Gegenbauer, he “wanted to study theDarwin theory free from all external influences and former prejudices.”44
The idea that religious or philosophical prejudice compromised Agassiz’s
scientific judgment raises other questions. As historian Neal Gillespie
explains, Agassiz was “second to no man in his opposition to sectarianreligious interference with science.”45 Moreover, Agassiz showed himself
perfectly willing to accept natural mechanisms where before supernaturalintervention had been the preferred explanation. Since he regarded material
forces, and the laws of nature that described them, as the products of anunderlying design plan, he saw any creative work they did as deriving
ultimately from a creator. For instance, he assumed this was the case with thedevelopment of embryos: he attributed their natural evolution from zygote toadult as a natural phenomenon and considered this no threat to his belief in acreator.46 He also readily accepted the notion of a naturally evolving solar
system.47 He thought a skillful cosmic architect could work throughsecondary natural causes every bit as effectively as through direct acts ofagency. The marginalia in his copy of On the Origin of Species suggest that
he had this same attitude concerning biological evolution. “What is the great
difference,” he wrote, “between supposing that God makes variable species orthat he makes laws by which species vary?”
A third problem with the official portrait of Darwin’s chief rival concerns
Lurie’s suggestion that Agassiz was a master of particulars, but not ofgeneralizing from those particulars. The historical record suggests otherwise.
For example, Agassiz was the man who ably generalized from a wide array ofparticular clues in his work on the ice age, winning over the geologicalestablishment by demonstrating how a range of facts were best explained by
the action of retreating glaciers.
Here a direct comparison between Darwin and Agassiz is possible. Eachsearched for an explanation of a curious geological phenomenon in the
Scottish Highlands, the parallel roads of Glen Roy. Glen Roy is the valley of
the River Roy and, although it’s a place of breathtaking beauty, what visitors
found most intriguing about it over the years were its three parallel roads thatwind along the canyon wall on either side of the river (see Fig. 1.7).48
Scottish legend held that they were hunting paths built for use by early
Scottish kings or perhaps even for the mythical warrior Fingal. Scientists later
argued that the roads were natural rather than artificial. Darwin and Agassiz
were both convinced that natural processes were the cause, but they
nevertheless arrived at different explanations. What was the end of thematter? In his autobiography, Darwin explained, “Having been deeply
impressed with what I had seen of the elevation of the land in S. America, Iattributed the parallel lines to the action of the sea; but I had to give up thisview when Agassiz propounded his glacier-lake theory.”49 Subsequent
investigations in the late nineteenth and early twentieth centuries confirmedthat Agassiz’s interpretation was the correct one.50
Agassiz, then, was far more than just a walking encyclopedia or an
insatiable gatherer of fossils who couldn’t see the proverbial forest for thetrees. Those who insist otherwise can point to but one example to support
their position, namely, his rejection of Darwin’s theory; but they cannot usethat example to establish his general inability to interpret evidence and thenturn around and use that supposed inability to explain his failure to accept
Darwin’s theory. That is to argue in a circle.
There is a far more obvious solution to the historical puzzle posed by thegreat Agassiz’s objection to Darwin’s theory: the fossils of the Cambrianstrata do, in fact, arise abruptly in the geological record, in clear defiance ofwhat Darwin’s theory would lead us to expect. In short, a genuine mystery isat hand.

FIGURE 1.7
Parallel roads of Glen Roy.
Two final considerations lend support to this view. First, as already noted,
Darwin himself accepted the validity of Agassiz’s objection.51 As he
acknowledged elsewhere in the Origin, “To the question why we do not findrich fossiliferous deposits belonging to these assumed earliest periods prior to
the Cambrian system, I can give no satisfactory answer. . . . The case atpresent must remain inexplicable; and may be truly urged as a valid argument
against the views here entertained.”52
Second, Darwin’s attempt to account for the absence of the expected fossil
ancestors of the Cambrian forms failed to address the full strength andsubtlety of Agassiz’s objection. As Agassiz explained, the problem with
Darwin’s theory was not just the general incompleteness of the fossil recordor even a pervasive absence of ancestral forms of life in the fossil record.
Rather, the problem, according to Agassiz, was the selective incompletenessof the fossil record.
Why, he asked, does the fossil record always happen to be incomplete at
the nodes connecting major branches of Darwin’s tree of life, but rarely—in
the parlance of modern paleontology—at the “terminal branches”
representing the major already known groups of organisms? These terminal
branches were well represented (see Fig. 1.8), often stretching over many
generations and millions of years, while the “internal branches” at theconnecting nodes on Darwin’s tree of life were nearly always—andselectively—absent. As Agassiz explained, Darwin’s theory “rests partly upon
the assumption that, in the succession of ages, just those transition types have
dropped out from the geological record which would have proved theDarwinian conclusions had these types been preserved.”53 To Agassiz, it
sounded like a just-so story, one that explains away the absence of evidence
rather than genuinely explaining the evidence we have.
Was there any easy answer to Agassiz’s argument? If so, beyond his statedwillingness to wait for future fossil discoveries, Darwin didn’t offer one.

FIGURE 1.8
The vertical lines in these diagrams represent known animal phyla. The dots
within the vertical lines represent animals from those phyla that have beenfound fossilized in different strata. The diagram on the left shows the animal
tree of life as expected based upon Darwinian theory. The diagram on theright shows a simplified representation of the actual pattern of thePrecambrian–Cambrian fossil record. Notice that fossils representing theinternal branches and nodes, but not the terminal branches, are missing.
AN ENDURING MYSTERYIn the years immediately following the publication of On the Origin ofSpecies, many of Agassiz’s concerns were temporarily swept aside as public
and scientific fascination with Darwin’s ideas grew. Even so, a persistent
mystery lay at the feet of biologists, one that subsequent generations ofscientists would revisit and repeatedly seek to resolve. As Darwin noted, in
his time, the fossils of the Cambrian were relatively few, and the period of the
explosion only vaguely understood. But perhaps future scientists would cometo his rescue with fresh discoveries.
The story of the successive attempts to solve the Cambrian mystery
stretches from Darwin’s time to the present, and from the Swansea Valley insouthern Wales to remote fossil sites in southern China. In the next chapter,the work of detection moves from the late nineteenth century to the earlytwentieth, from the British Isles to British Columbia, and to a fossil site above
the Kicking Horse River so astonishing that, even today, paleontologists andsome of the most skeptical and hardened of scientific rationalists speak its
name with childlike reverence.

2
The Burgess Bestiary
Only in fiction can we expect such fine orchestration of setting and dramatic
action. Gothic tales haunted by demons of the past have their thunderstorms
and crumbling mansions, the existentialist novel its disorienting cityscapes,
the romance its unattainable balconies laced with jasmine. In ordinary life, thestaging is usually less precise. Intricate family tragedies unravel in tidy
suburban ranch-style homes, while enchanted romances blossom over cubicle
walls. But the twentieth century’s most revolutionary fossil discovery was
more like fiction: the setting was commensurate with the moment.
Photographs taken during the summer’s expedition show a lean andbalding man with pleasant crinkles at the corners of his eyes and a deep
thought line slashing down between his brows; he stands precariously on
rocky ascents, pick and hoe at hand, gazing far into the distance from a stony
peak, at ease among the forbidding slopes and treacherous ridges. Working
his way over one ridge and then above the tree line of the next, Charles
Doolittle Walcott reached a place where he could see for miles. To thenorthwest, the crude arrowhead of Mount Wapta jutted skyward. Below lay
Emerald Lake, its waters green from the mineral-rich glacial till. To the east
and west, snowy peaks stretched to the horizon (see Figs. 2.1 and 2.2). Only
the view to the northeast lacked a vista. Here was the homely shale of abarren ridge. Of course, as in any fairy tale, there lay the real prize, a hidden
vista measured not in miles, but in ages.

FIGURE 2.1
The scenery of the Burgess Shale and surrounding area. Courtesy Corbis.

FIGURE 2.2
Charles Doolittle Walcott in the field (c. 1911). Courtesy Smithsonian
Institution Archives.
Walcott, already the director of the Smithsonian Institution, was about toenter the most significant phase of his professional life. More than this, he
was about to make perhaps the most dramatic discovery in the history of
paleontology, a rich trove of middle Cambrian–era fossils, including many
previously unknown animal forms, preserved in exquisite detail, suggesting
an event of greater suddenness than had been known even in Darwin’s timeand detailing a greater diversity of biological form and architecture than had
hitherto been imagined.
Where did this wealth of biological form come from, and why, again, did it
seem to arise so suddenly during the Cambrian period? Walcott was the firstto explore the Burgess Shale, and he would be the first to suggest an answer
to the questions it raised.

THE BESTIARY
Among paleontologists, the fateful clue that led to the Burgess Shale’s
discovery is the stuff of legend. Paleontologist Stephen Jay Gould considered
it to have been rendered best in an obituary of Charles Walcott written by
Walcott’s former research assistant, Charles Schuchert:
One of the most striking of Walcott’s faunal discoveries came at the endof the field season of 1909, when Mrs. Walcott’s horse slid on going
down the trail and turned up a slab that at once attracted her husband’s
attention. Here was a great treasure—wholly strange Crustacea ofMiddle Cambrian time—but where in the mountain was the mother rockfrom which the slab had come? Snow was even then falling, and thesolving of the riddle had to be left to another season, but next year the
Walcotts were back again on Mount Wapta, and eventually the slab wastraced to a layer of shale—later called the Burgess Shale—3000 feetabove the town of Field.1
Gould quotes the legend to celebrate its archetypal appeal even as hedebunks it: “Consider the primal character of this tale—the lucky breakprovided by the slipping horse, . . . the greatest discovery at the very lastminute of a field season (with falling snow and darkness heightening thedrama of finality), the anxious wait through a winter of discontent, thetriumphant return and careful, methodical tracing of errant block to motherlode.”2 A compelling story, Gould concludes, but pure fiction. Walcott’s own
diaries reveal that his team had plenty of time to begin excavating the site thatvery summer amid cooperative weather and even warm nights. As for theirreturn the following summer, locating the mother lode was apparently thework of a single day rather than a full week, a conclusion Gould drew fromboth Walcott’s diaries and his knowledge of Walcott’s expertise as ageologist.3
The motifs of the lucky break, the frustrating delay, and the final andfortuitous triumph will resurface later (see Chapter 7) as a tall tale of Gould’sown, but for now consider only the scientific community’s weakness forstaging the Burgess discovery with various fictional props, as if the stunning
scenery around it were not setting enough. This weakness for theater isunderstandable, considering what Walcott and later investigators found there.
Over the next several years, Walcott’s team alone collected more than 65,000
specimens, many of them astonishingly well preserved, some so bizarre that
paleontologists would cast about for more than half a century for the propercategories in which to contain them.
Consider just one odd couple from Walcott’s quarry, Marrella andHallucigenia. Marrella, also called a lace crab, is an unusual form. Walcott
described it as a type of trilobite, but later studies by Cambridge
paleontologist Harry Whittington classified it not as a trilobite, nor achelicerate (the subgroup of arthropods that includes spiders), and not even asa crustacean, but rather as a fundamentally distinct form of arthropod.4 The
creature is divided into twenty-six segments, each with a jointed leg forwalking and a feathery gill branch for swimming. Its head shield has two longpairs of spikes directed backwards, and the underside of the head features twopairs of antennae. One is short and stout, the other long and sweeping (seeFig. 2.3).
Hallucigenia belongs to a genus and family of one. It has a rounded massat one end (possibly the head) connected to a cylinder-shaped trunk sporting
seven pairs of spines projecting upward and to either side, each of themalmost as long as the trunk itself (see Fig. 2.4). On the underside of thecreature are seven pairs of limbs, each corresponding in position to one of thepairs of spines on the back, though with the tentacle farthest back offset. The
underbelly also features three pairs of shorter tentacles before the trunk tapers
and curves upward in what was probably a flexible extension from the body.
Each of the larger tentacles appears to have a hollow tube connected to the gut
and a pincer at the tip. This ancient creature was so peculiar that
paleontologists feigned disbelief at what they saw, giving it its memorable
name.

FIGURE 2.3
Figure 2.3a (left): Artist rendering of Marrella splendens. Figure 2.3b (right):
Photograph of Marrella splendens fossil. Courtesy Wikimedia Commons, user
Smith609.

FIGURE 2.4
Figure 2.4a (top): Artist rendering of Hallucigenia sparsa. Figure 2.4b(bottom): Photograph of Hallucigenia sparsa fossil. Courtesy Smithsonian
Institution.
The term “Cambrian explosion” was to become common coin, because
Walcott’s site suggested the geologically abrupt appearance of a menagerie ofanimals as various as any found in the gaudiest science fiction. During this
explosion of fauna, representatives of about twenty of the roughly twenty-six
total phyla present in the known fossil record made their first appearance onearth (see Fig. 2.5).5
The term “phyla” (singular: “phylum”) refers to divisions in the biologicalclassification system. The phyla constitute the highest (or widest) categories
of biological classification in the animal kingdom, with each exhibiting aunique architecture, organizational blueprint, or structural body plan. Familiar
examples of phyla are cnidarians (corals and jellyfish), mollusks (squid andclams), echinoderms (sea stars and sea urchins), arthropods (trilobites andinsects), and the chordates, to which all vertebrates including humans belong.
The animals within each phylum exhibit distinguishing features that enabletaxonomists to divide and group them further into other, progressively smaller
divisions, beginning with classes and orders, and eventually coming tofamilies, genera, and individual species. The broadest and highest categories
within the animal kingdom—such as phyla and classes—designate the major
categories of animal life, typically designating unique body plans. Lower
taxonomic categories—like genus and species—designate smaller degrees ofdifference among organisms that typically exemplify similar overall ways oforganizing their body parts and structures.
Throughout the book I will use these conventional categories ofclassification, as do most Cambrian paleontologists. Nevertheless, I am awarethat some paleontologists and systematists (experts in classification) today
prefer “phylogenetic classification,” a method that often uses a “rank-free”
classification scheme.6 Advocates of modern phylogenetic classification
argue that the traditional classification system lacks objective criteria bywhich to decide whether a certain group of organisms should be assigned aparticular rank of, for example, phylum or class or order.7 Proponents of rankfree classification attempt to eliminate subjectivity in classification (andranking) by grouping together animals that are thought, based upon studies ofsimilar molecules in different groups, to share a common ancestor. Thismethod of classification treats groups that emerge at roughly the same time on
the tree of life as equivalent. Nevertheless, even proponents of phylogeneticclassification often use the conventional taxonomic categories in theirtechnical discussions of specific organisms because of their common
scientific usage. So despite my own sympathy with some of the concerns ofrank-free advocates (see below), I have chosen to do the same.

FIGURE 2.5
Figure 2.5a (top): Chart showing when representatives of the different animal
phyla first appeared in the fossil record. According to Darwinian theory,
differences in biological form should increase gradually, steadily increasing
the number of distinct body plans and phyla, over time. References for first
appearances are found in note 5 of this chapter. Figure 2.5b (bottom, left)
expresses that expectation graphically, showing the number of new phyla
increasing steadily as members of one phylum diversify and give rise to newphyla. Figure 2.5c (bottom, right) shows the actual pattern of first appearance
showing a spike in the number of phyla that first appear in the Cambrian,followed by either few or no new phyla arising in subsequent periods ofgeological history.
In any case, it’s worth noting that using a rank-free classification systemdoes not minimize the mystery of the Cambrian explosion. The Cambrian
explosion presents a puzzle for evolutionary biologists, not just because of thenumber of phyla that arise, but rather because of the number of unique animal
forms and structures that arise (as measured, perhaps, by the number of phyla)—however biologists decide to classify them. Thus, whether scientists decide
to use newer rank-free classification schemes or older, more conventional,
Linnaean categories, the “evolutionary novelties”—that is, the newanatomical structures and modes of organization—that arise suddenly with
the Cambrian animals remain as facts of the fossil record, requiringexplanation. (For an expanded technical discussion of these issues, go to thisendnote.)8
One especially dramatic fact of the Cambrian explosion is the first
appearance of many novel marine invertebrate animals (representatives ofseparate invertebrate9 phyla, subphyla, and classes in the traditionalclassification scheme). Some of these animals have mineralized exoskeletons,
including those representing phyla, such as echinoderms, brachiopods, andarthropods, and each represent clearly distinct and novel body plans. Further,
these are just three of dozens of novel body plans exemplified by the Burgess
animals—animals in which both soft and hard parts are well preserved (seeFig. 2.6).

FIGURE 2.6
Representatives of some of the major animal groups that first appeared in thesedimentary rock record during the Cambrian period.
The variety in the Burgess Shale was so extreme it took several decades
for paleontologists to grasp it fully. Walcott, for instance, attempted to fit allof the new forms into existing phyla. However, even in the midst of thisattempt, he realized that this revolutionary quarry posed a problem more
fundamental than a need to tidy up the existing taxonomy. He had met LouisAgassiz at a young age, having sold him some of his first fossils, and later
described him as “a guide in whom I could trust and follow,” one in whose
work “I find this tribute to the Great Mind that created the objects of his
study.”10 But in the great debate between Agassiz and Darwin, Walcott sided
with the Englishman. Thus, the Burgess Shale struck Walcott as not only
fascinating, but puzzling.
A PUZZLING PATTERNOver the years, as paleontologists have reflected on the overall pattern of the
Precambrian–Cambrian fossil record in light of Walcott’s discoveries, they
too have noted several features of the Cambrian explosion that are unexpectedfrom a Darwinian point of view11 in particular: (1) the sudden appearance ofCambrian animal forms; (2) an absence of transitional intermediate fossils
connecting the Cambrian animals to simpler Precambrian forms; (3) astartling array of completely novel animal forms with novel body plans; and(4) a pattern in which radical differences in form in the fossil record arise
before more minor, small-scale diversification and variations. This pattern
turns on its head the Darwinian expectation of small incremental change only
gradually resulting in larger and larger differences in form.
THE MISSING TREE
Figures 2.7 and 2.8 illustrate the difficulty posed by the first two of thesefeatures: sudden appearance and missing intermediates. These diagrams graphmorphological change over time. The first shows the Darwinian expectationthat changes in morphology should arise only as tiny changes accumulate.
This Darwinian commitment to gradual change through microevolutionary
variations produces the classic representation of evolutionary history as abranching tree.
Now compare this branching tree pattern with the pattern in the fossil
record. The bottom part of Figure 2.7 and Figure 2.8 show that the
Precambrian strata do not document the expected transitional intermediates
between Cambrian and Precambrian fauna. Instead, the Precambrian–Cambrian fossil record, especially in light of the Burgess Shale after Walcott,points to the geologically sudden appearance of complex and novel bodyplans.

FIGURE 2.7
The origin of animals. Darwinian theory (top) predicts gradual evolutionarychange in contrast to the fossil evidence (bottom), which shows the abrupt
appearance of the major animal groups.

FIGURE 2.8
According to Darwinian theory, the strata beneath the Cambrian rocks should
evidence many ancestral and intermediate forms. Such forms have not beenfound for the vast majority of animal phyla. These anticipated but missing
forms are represented by the gray circles. Lines and dark circles depict
fossilized representatives of phyla that have been found.
Of course, the fossil record does show an overall increase in thecomplexity of organisms from Precambrian to Cambrian times, as Darwin
expected. But the problem posed by the Burgess Shale is not the increase incomplexity, but the sudden quantum leap in complexity. The jump from thesimpler Precambrian organisms (further explored in the next chapters) to theradically different Cambrian forms appears to occur far too suddenly to bereadily explained by the gradual activity of natural selection and randomvariations. Neither the Burgess Shale nor any other series of sedimentarystrata known in Walcott’s day recorded a pattern of novel body plans arising
gradually from a sequence of intermediates. Instead, completely uniqueorganisms such as the bizarre arthropod Opabinia (see Fig. 2.9)—with its
fifteen articulated body segments, twenty-eight gills, thirty flipper-likeswimming lobes, long trunk-like proboscis, intricate nervous system, and five
separate eyes12—appear fully formed in the Cambrian strata along withrepresentatives of other fundamentally different body plans and designs ofequal complexity.
Darwin, as we know, regarded the sudden appearance of the Cambriananimals as a significant challenge to his theory.13 Where natural selection had
to bridge yawning chasms from relatively simple life-forms to exquisitely
complex creatures, it would require great expanses of time.14

FIGURE 2.9
Figure 2.9a (top): Artist rendering of Opabinia. Figure 2.9b (bottom):Photograph of Opabinia fossil.
Darwin’s recognition15 of this constraint was prescient. Geologists in his
day employed relative dating methods. They did not have modern radiometricmethods for determining the “absolute” ages of rocks. For this reason, they
did not yet fully understand how long it would have taken to accumulate thegreat columns of sedimentary rock and, thus, the great expanses of time thatwere available to the evolutionary process. Neither had scientists yet
discovered the sophisticated inner workings of the cell, and the informationrich structures (DNA, RNA, and proteins) that had to be significantly alteredto achieve even modest evolutionary changes. Nevertheless, Darwin was able—based upon what he knew of the complexity of organisms and his own
understanding of how the mechanism of natural selection must operate—to
deduce that descent with modification required time, and lots of it.
Recalling the context of Darwin’s original argument reveals why. In theOrigin, he sought to counter the famous watch-to-watchmaker design
argument offered by theologian William Paley. Paley had argued that just ascomplex structures such as watches necessarily issue from intelligent
watchmakers, the complex structures in living organisms must likewise owe
their origin to a designing intelligence. With natural selection, Darwin
proposed a purely natural mechanism for constructing the complex organs
and structures (such as eyes) present in many forms of life. His mechanism ofnatural selection worked by constructing such systems one tiny step at a time,
discarding the harmful variations and seizing upon the rare improvement. If
evolution progressed by “whole watches”—that is, by entire anatomicalsystems like the trilobite’s eye—then biology would have fallen back to theold absurdity of imagining that a watch could fall together purely at random
and all at once. Thus, unless Darwin’s evolutionary mechanism worked
gradually by preserving the tiniest of random changes over many millions ofyears, it didn’t work at all.
MORE MISSING LINKS
Two other features of the Cambrian explosion revealed in the Burgess Shale,features (3) and (4) described earlier, not only confirmed the reality of theCambrian mystery, but broadened and deepened it—and at just the time when
paleontologists were looking to resolve the mystery with new fossil
discoveries.
First, the great profusion of completely novel forms of life in the Burgess
assemblage (feature 3) demanded even more transitional forms than had
previously been thought missing. Each new and exotic Cambrian creature—
the anomalocarids (see Fig. 2.10), Marrella, Opabinia, and the bizarre andappropriately named Hallucigenia—for which there were again no obvious
ancestral forms in the lower strata, required its own series of transitional
ancestors. But where were they?

FIGURE 2.10
Figure 2.10a (top): Artist rendering of Anomalocaris. Figure 2.10b (bottom):Photograph of Anomalocaris fossil. Courtesy J. Y. Chen.
Darwin had hoped that later fossil discoveries would eventually eliminatewhat he regarded as the one outstanding anomaly associated with his theory.
Walcott’s discovery was not that discovery. Not only did the Burgess Shale
fail to reveal the expected ancestral precursors of the known Cambrian animal
forms, but it revealed a motley crew of previously unknown animal forms andbody plans that now demanded their own lengthy chain of evolutionary
precursors, only complicating the task of explaining the Cambrian explosionin Darwinian terms.
ORDERS FROM THE TOP
The Burgess Shale raised an additional difficulty (feature 4, discussed earlier),though not one that Walcott recognized during his lifetime. Instead, its
exposition would await a later generation of Cambrian experts, particularly
Stephen Jay Gould. Darwin’s theory implied that as new animal forms firstbegan to emerge from a common ancestor, they would at first be quite similar
to each other, and that large differences in the forms of life—whatpaleontologists call disparity—would only emerge much later as the result of
the accumulation of many incremental changes. In its technical sense,
disparity refers to the major differences in form that separate the higher-leveltaxonomic categories such as phyla, classes, and orders. In contrast, the term
diversity refers to minor differences among organisms classified as different
genera or species. Put another way, disparity refers to life’s basic themes;
diversity refers to the variations on those themes. The more body plans in a
fossil assembly, the greater the disparity. And the animal forms preserved in
the Burgess Shale display considerable disparity. Further, the large differencesin form between the first animals appeared suddenly in the Burgess Shale, andthe appearance of such disparity arose before, not after, the diversification ofmany representatives of lower taxonomic categories (such as species orgenera) within each higher category, designating a new body plan.
The site of the Burgess Shale and its setting nicely illustrates the difference
between diversity and disparity. Walcott’s celebrated quarry is tucked away in
the Canadian Rockies near the Continental Divide. Reaching it involves a sixmile hike through the picturesque scenery of Yoho National Park—Takakkaw
Falls, Emerald Lake, and glaciers and glacier-cut mountain peaks thrusting
into view at almost every turn. In this ecologically diverse setting, hikers havea chance of spotting squirrels, marmots, deer, moose, elk, wolves, andmountain goats. Rare sightings might include a grizzly bear or Canadian lynx,
while alert birdwatchers might glimpse a horned lark, a white-tailed
ptarmigan, the rare water pipit, or a gray-crowned rosy finch; an eagle, hawk,
or grassland falcon; dippers, jays, migrating warblers, or harlequin ducks.16

As richly various as this array of animals is, all of them come from a single
phylum, Chordata—and even from a single subphylum, Vertebrata. Imagine
hiking to the quarry to excavate it and, on the hike, being lucky enough tospot every one of these animals along the way. After having feasted your eyeson such animal variety, when you arrive at Walcott’s quarry, it yields not
merely dozens of fossilized species from a single subphylum, but wildly
disparate creatures from dozens of phyla.
According to Darwin’s theory, the differences in form, or “morphologicaldistance,” between evolving organisms should increase gradually over time as
small-scale variations accumulate by natural selection to produce increasingly
complex forms and structures (including, eventually, new body plans). In
other words, one would expect small-scale differences or diversity among
species to precede large-scale morphological disparity among phyla. As theformer Oxford University neo-Darwinian biologist Richard Dawkins puts it,“What had been distinct species within one genus become, in the fullness oftime, distinct genera within one family. Later, families will be found to havediverged to the point where taxonomists (specialists in classification) prefer tocall them orders, then classes, then phyla.”17
Darwin himself made this point in On the Origin of Species. Explaining
his famous tree diagram (see Fig. 2.11a), he noted that it illustrated more thanjust the theory of universal common descent. The tree diagram also illustrated
how higher taxa should emerge from lower taxa by the accumulation ofnumerous slight variations. He said, “The diagram illustrates the steps bywhich small differences distinguishing varieties are increased into larger
differences distinguishing species.”18 He went on to assert that the process ofmodification by natural selection would eventually move beyond theformation of species and genera to form “two distinct families, or orders,according to the amount of divergent modification supposed to be represented
in the diagram.”19 In his view, this process would continue until it produced
differences in form that were great enough that taxonomists would classify
them as new classes or phyla. In short, diversity would precede disparity, andphyla-level differences in body plan would emerge only after species-, genus-,family-, order-, and class-level differences appeared.
The actual pattern in the fossil record, however, contradicts thisexpectation (compare Fig. 2.12 to Fig. 2.11b). Instead of more and more
species eventually leading to more genera, leading to more families, orders,classes, and phyla, the fossil record shows representatives of separate phyla
appearing first followed by lower-level diversification on those basic themes.
This is nowhere more dramatically apparent than in the Cambrian period
explains Roger Lewin in the journal Science: “Several possible patterns exist

for the establishment of higher taxa, the two most obvious of which are thebottom-up and the top-down approaches. In the first, evolutionary novelties
emerge, bit by bit. The Cambrian explosion appears to conform to the second
pattern, the top-down effect.”20 Or as paleontologists Douglas Erwin, James
Valentine, and Jack Sepkoski note in their study of skeletonized marine
invertebrates: “The fossil record suggests that the major pulse ofdiversification of phyla occurs before that of classes, classes before that oforders, orders before that of families. . . . The higher taxa do not seem to havediverged through an accumulation of lower taxa.”21 In other words, instead ofa proliferation of species and other representatives of lower-level taxa
occurring first and then building to the disparity of higher taxa, the highest
taxonomic differences such as those between phyla and classes appear first(instantiated by relatively few species-level representatives). Only later, inmore recent strata, does the fossil record document a proliferation ofrepresentatives of lower taxa: different orders, families, genera, and so on. Yet
we would not expect the neo-Darwinian mechanism of natural selection
acting on random genetic mutations to produce the top-down pattern that we
observe in the history of life following the Cambrian explosion.

FIGURE 2.11
Figure 2.11a (top): Darwin’s theory of common descent illustrated here withhis famous branching tree of life diagram reproduced from the Origin ofSpecies, 1859. Figure 2.11b (bottom): Growth of the tree of life over time in
the manner envisioned by Darwin with new species giving rise to new genera
and families, eventually giving rise to new orders, classes, and phyla (thesehigher taxonomic categories not depicted).
Of course, advocates of modern phylogenetic classification, with their“rank-free” approach, don’t describe this phenomenon as a “top-down”
pattern, because their system of classification dispenses with taxonomic ranks
and hierarchies. In their system, there is no “top” and no “down.”
Nevertheless, advocates of phylogenetic classification do acknowledge thatdifferent combinations of “character” states (characteristics or features oforganisms) can mark either bigger or smaller morphological differences
between clades (closely related groups of organisms that presumably share acommon ancestor). And some leading advocates of phylogeneticclassification have noted that the fossil record exhibits a pattern in which a
few character traits marking large morphological differences between cladesarise first, followed later in each clade by the addition of other combinationsof characters that mark smaller differences within those clades. Larger
differences between clades arise first, smaller differences within them arose
later—the themes precede the variations.

FIGURE 2.12
The top-down pattern of appearance in the fossil record: disparity precedes
diversity.
The founder of the modern phylogenetic classification, Willi Hennig, forexample, noted that once particular groups arise, the range of allowablevariability within those groups narrows. In his classic work Phylogenetic
Systematics, Hennig quoted another paleontologist approvingly who
observed: “The breadth of evolution of successive groups shows a distinct
narrowing, since the basic divergences of organization became progressively
smaller. The type of mammals is more uniform and closed than that of thereptiles, which in turn is unquestionably uniform compared to that of theAmphibia-Stegocephalia.” Hennig goes on to explain that “the same
phenomenon is repeated in every systematic unit of higher or lower order.”22
Yet, on a Darwinian view, small-scale variations and differences shouldarise first, gradually giving rise to larger-scale differences in form—just the
opposite of the pattern evident in the fossil record. Thus, the discovery, andlater analysis, of the Burgess revealed another puzzling feature of the fossil
record from a Darwinian point of view, regardless of which system ofclassification paleontologists prefer to use. Indeed, Walcott’s discovery turnedDarwin’s anticipated bottom-up—or small changes first, big changes later—
pattern on its head.
FIRST IMPRESSIONSThe extraordinary conditions at work in the preservation of the Burgess fauna
helped to reveal the extent of the rich diversity (and disparity) of form present
in the Cambrian period. On shale of a very fine grain, the Burgess fossils look
like lithographic pictures, dark on light (see color insert plates 15 and 16).
Even the soft parts like the gills and guts are sometimes preserved. This is not
the norm in the world of paleontology. Usually soft tissues decay before they
can be fossilized, leaving behind only harder parts, such as bone, teeth, andshells, to be preserved. The Burgess event that captured the Cambrian fauna
for future discovery was different. Although it took the lives of untold
Cambrian animals, it did so with an exquisite delicacy that preserved soft
tissue.
Visualizing how this occurred will drive home why the conditions were so
unusual. All of the fossilized animals of the Burgess Shale were sea creaturesliving near an enormous carbonate reef that later was thrust upward by plate
tectonic activity to form what is now called the Cathedral Escarpment. Long
after the sea creatures of the Burgess Shale were entombed, these tectonic
forces drove the fossils upward from the seafloor carrying them many miles
eastward along faults, at the same time building the mountains that Walcottwould climb millions of years later.
Thanks to this tectonic movement of earth’s major plates, the continents
are now located in very different places than they were millions of years ago.
At the time these Cambrian creatures were alive, the land masses that would
later form North America lay on the equator.
Plate tectonic activity explains why a trove of sea creatures were foundfossilized in the mountains of Yoho National Park rather than along a seafloor
somewhere. But there’s still the question of why so many different types ofmarine invertebrates, including soft-bodied ones, were so unusually wellpreserved. Paleontologists think they know the answer. They think the marine
animals that were later fossilized in the Burgess Shale lived near the bottomof an ancient sea in front of an underwater cliff or escarpment. Due to tectonic
activity, blocks at the edge of this underwater cliff began to break off. These
blocks slumped, creating underwater mudflows in their wake. These slumps
and flows transported the Burgess animals several kilometers into deeper
waters where they were buried in such a way as to leave them not only
undamaged, but also protected from scavengers and bacteria. Very probably,the mudflows were highly turbulent, for paleontologists found the creaturesdumped and preserved in a variety of angles in relation to the bedding. The
speed and pressure of these mudflows quickly produced a preservationfriendly, oxygen-free environment. Then the turbulent and muddy currents
pressed fine silt and clay into the crevices of the bodies at just the rightconsistency and pressure to fossilize them without tearing their delicate
appendages, an ideal set of circumstances for ensuring later observation by
future paleontologists.23
Due in part to the unusual circumstances under which these fossils were
preserved, there’s now little doubt about the unparalleled disparity of theCambrian fauna. Based on available evidence from the Burgess Shale andother sites around the world, the Cambrian period witnessed the appearanceof, arguably, more disparate body plans than ever before or since. And thisdisparity arose at a most unexpected time, assuming Darwinian theory,
namely, right at the dawn of animal life.
THE ARTIFACT HYPOTHESIS
Walcott grasped these difficulties, and had a deep enough professional
commitment to Darwinism, to search for a solution. He realized that the
Precambrian fossil record could, in principle, assist in explaining the patternof the Cambrian fossil record. The discovery of a rich Precambrian fossil
history detailing variations accumulating little by little would serve to cast thepattern of the Burgess in a different light. Yet the Precambrian strata of his
day showed no signs of providing any obvious transitional forms, much less awell-articulated bottom-up pattern of animals representing lower taxa
proliferating into forms exemplifying higher and higher taxonomic categories.
Nevertheless, an idea occurred to Walcott that gave him fresh hope.
Perhaps his awareness of the dramatic ways that the surface of the earth
had changed over geologic time, making preservation of the Burgess fauna
itself possible, inspired him. Finding marine animals so high above sea levelno doubt made Walcott acutely aware of the way in which continents and seas
had changed locations over the course of geological time. And so, Walcott,ever the geologist, proposed an ingenious geological solution to the biologicalproblem of the origin of animal life. He noted that the Precambrian period
was a period of dramatic continental uplift. He then suggested that theancestors of the trilobites first evolved at a time when the Precambrian seas
had receded from the landmasses. Then, at the beginning of the Cambrian, theseas again rose, covering the continents and depositing recently evolved
trilobites. Thus, according to Walcott, ancestral precursors to the trilobites andother distinctive Cambrian forms had existed, but they were not fossilized in
sediments that would later be elevated above sea level until early in the
Cambrian; instead, before the Cambrian, during a period when sea levels werelower, trilobites and their ancestral forms were being deposited offshore inwhat are now only deep-sea sediments.24 Walcott named this cryptic period oftime in which trilobites and other animals were rapidly evolving offshore as
the “Lipalian interval.” (The term “Lipalian” is derived from the Greek word
for lost.) In this view, the abrupt appearance of the Cambrian body plans in
the geological column was merely an “artifact” of incomplete sampling of thefossil record and, indeed, the inability to access the undersea sedimentarylayers where the ancestors of the Cambrian fauna presumably lay encased. In
short, the transgression and regression of ancient seas made the ancestral
precursors of the Cambrian fauna inaccessible to discovery.
His artifact hypothesis (also known as the “Lipalian interval” hypothesis)
was a distinct advance over Darwin’s unadorned claim that the fossil
ancestors of the Cambrian animals had not yet been discovered. Walcott’s
hypothesis had the advantage of accounting for the sudden appearance of thetrilobites and the absence of ancestral and transitional forms by reference toknown geological processes. It also could be tested, at least once offshore
drilling technology advanced to allow for the sampling of the buried offshore
sedimentary rocks.
Although Walcott conceded that his hypothesis was essentially a negativeargument that attempted to explain away the absence of evidence, he insisted
that it was a sensible inference from his broad sampling of the paleontological
data. “I fully realize that the conclusions above outlined are based primarilyon the absence of a marine fauna in Algonkian [Precambrian] rocks,” hewrote, “but until such is discovered I know of no more probable explanationof the abrupt appearance of the Cambrian fauna than that I have presented.”25
LUMPING AND SPLITTING
Walcott used another strategy for squaring the Burgess Shale with Darwin’s
theory of evolution. Taxonomists, tasked with identifying and naming distinctgroups of life-forms, have been divided into two types: “lumpers” and“splitters.” “Lumpers” tend to group disparate organisms together in the samelarge classificatory categories and then make distinctions between them atlower taxonomic levels. “Splitters” tend to separate similar organisms into
numerous higher taxonomic divisions. Walcott favored lumping, and his
doing so with the Burgess fossils seemingly minimized the difficulties
associated with the sudden proliferation of so many new Cambrian forms.

On his return to the Smithsonian, he placed all of the exotic forms of the
Burgess into modern phyla. One of his efforts at lumping placed Marrella
splendens not only in the same phylum, but also in the same class (Trilobita)
as the trilobites, despite obvious morphological differences. He justified thisclassification by arguing that the organism foreshadowed the trilobite(compare Figs. 1.4 and 2.3). Gould later criticized Walcott’s method ofclassification as “shoehorning.” He noted that even one of Walcott’s fellow
lumpers, Yale paleontologist Charles Schuchert, called the classification of
Marrella into question.26 Gould also noted that Walcott used this strategy tominimize the challenge posed by the morphological disparity of the Burgess
forms.27
Some paleontologists today reject Gould’s criticism of Walcott’s inclusionof so many Burgess animal forms into existing taxonomic
categories.Nevertheless, few paleontologists think Walcott’s use of lumping
explained away the Cambrian explosion. Most, for example, classify Marrella
splendens within an existing modern phylum, namely, Arthropoda, even if
they also classify it within a new and separate class, Marrellomorpha. Yet,whether Marrella, for example, falls within a novel phylum or class, mattersless than explaining why so many clearly novel forms, and the novel
structures these forms exhibit, first arose with such apparent suddenness.
RESOLUTION—FOR A TIME
Walcott thought that he had solved the mystery of the Cambrian explosion, as
did many other Darwinists who gratefully adopted both his taxonomy and his
version of the artifact hypothesis. And since Walcott’s approach held out hopeof one day uncovering evidence of a Precambrian trunk for the animal phyla
along with its primary limbs, adherents could not be accused of moving the
paleontological case for Darwinism into the realm of untestable dogma. They
had only to wait for the technologies of seafloor drilling to emerge and hopethat nature had seen fit, unmolested under the ocean deeps, to leave concrete
evidence of the gradual emergence of the major Cambrian body plans.
Walcott’s theoretical accomplishment was no mean feat. His discovery of
the Burgess Shale was like a defense attorney with absolute faith in his client
stumbling upon a room stuffed with clues that would seem to discredit him.
Through his grouping of disparate body types into existing phyla and his
ingenious version of the artifact hypothesis, Walcott had found an elegant way
to explain all this seemingly uncooperative evidence in a Darwinian way.
In defending Walcott for overlooking significant features of the Burgess
fossils, Gould points out that Walcott’s multiple and growing administrativedemands hardly left time to revisit the foundational categories of animal
taxonomy. How much less, then, was Walcott likely to revisit the mostfundamental assumption of all—the assumption that animals originatedgradually in a Darwinian way as the result of natural selection acting on small
incremental variations? Consideration of that possibility would come decades
later, only after Walcott’s version of the artifact hypothesis had itself
exploded.

3Soft Bodies and Hard Facts
In the spring of 2000, Discovery Institute, where I do my research, sponsoreda lecture at the University of Washington geology department by renowned
Chinese paleontologist J. Y. Chen (see Fig. 3.1). As the result of his role inexcavating a new discovery of Cambrian-era fossils in southern China,
Professor Chen’s standing in the scientific world was on the rise. The
discovery, near the town of Chengjiang in the Kunming Province, revealed atrove of early Cambrian animal forms. After Time magazine mentioned theChengjiang discovery in a 1995 cover story about the Cambrian explosion,1interest in the fossils surged. When he came to Seattle, Professor Chen had
already published numerous scientific papers about this profusion of novel
life-forms and had established himself as one of the foremost experts on thefossils in this unique geological setting.
Not surprisingly, Chen’s visit generated considerable interest among the
University of Washington faculty. He came bearing intriguing photographs
and samples of the oldest and most exquisitely preserved Cambrian fossils in
the world from an exotic site halfway around the globe, a site, moreover, thatwas now widely acknowledged to surpass even the legendary Burgess Shaleas the most extensive and significant Cambrian-era locality.
The fossils from the Maotianshan Shale near Chengjiang (see Fig. 3.2) had
established an even greater variety of Cambrian body plans from an evenolder layer of Cambrian rock than those of the Burgess, and they did so withan almost photographic fidelity. The Chinese fossils also helped to establishthat the Cambrian animals appeared even more explosively than previously
realized.

FIGURE 3.1
J. Y. Chen.

FIGURE 3.2
Figure 3.2a (left) shows the Moatianshan Shale outcrop. Courtesy Illustra
Media. Figures 3.2b and c (center and right) show a Precambrian-Cambrianboundary marker at the Moatianshan site. Courtesy Paul Chien.
So there was little doubt about the significance of the discoveries that
Chen came to report that day. What was soon in doubt, however, was Chen’sscientific orthodoxy. In his presentation, he highlighted the apparent
contradiction between the Chinese fossil evidence and Darwinian orthodoxy.
As a result, one professor in the audience asked Chen, almost as if in warning,
if he wasn’t nervous about expressing his doubts about Darwinism so freely—
especially given China’s reputation for suppressing dissenting opinion. I
remember Chen’s wry smile as he answered. “In China,” he said, “we cancriticize Darwin, but not the government. In America, you can criticize thegovernment, but not Darwin.”Nevertheless, those in the audience that day soon learned that Professor
Chen had good reasons for questioning Darwin’s picture of the history of life.
As Chen explained, the Chinese fossils turn Darwin’s tree of life “upside
down.” They also cast doubt on a surviving version of Charles Walcott’s
artifact hypothesis, a crucial prop in the case for Darwinian gradualism.
BURGESS REVISITED
By the time Charles Walcott finished his last excavation of the Burgess Shalein 1917, he and his team had collected over 65,000 fossil specimens, all ofwhich were shipped to the Natural History Museum at the Smithsonian
Institution for cataloguing. In 1930, another American paleontologist,
Harvard professor Percy Raymond, initiated another investigation of the
Burgess. His specimens were also eventually stored in the United States.
As a result of these two prominent American-led excavations, there were
initially no collections of Burgess fossils on public display in Canada. Many
Canadian scientists regarded this as a national embarrassment, so in the 1960s
the Canadian Geological Survey commissioned a British team to resume
digging at the Walcott quarry, in order to “repatriate the Burgess Shale” bykeeping most of the newly discovered fossils on permanent display in
Canada.2 The team was led by paleontologist Harry Whittington (see Fig.
3.3), of the University of Cambridge, who was assisted by two of his graduate
students, Simon Conway Morris and Derek Briggs, both of whom would
eventually distinguish themselves as internationally renowned experts on the
Burgess Shale.

FIGURE 3.3
Harry Whittington. Courtesy Archives of the Museum of Comparative
Zoology, Ernst Mayr Library, Harvard University.
As Whittington analyzed the Cambrian fauna at the Burgess, he realizedthat Walcott had grossly underestimated the morphological disparity of thisgroup of animals. Many of the creatures in the assemblage featured uniquebody designs, unique anatomical structures, or both.3 Opabinia, with its fiveeyes, fifteen distinct body segments, and a claw at the end of a long proboscis,
exemplified the unique forms on display in the Burgess. But so did
Hallucigenia, Wiwaxia, Nectocaris, and many other Burgess animals. To thisday, paleontologists describing Nectocaris, for example, can’t decide whether
it more closely resembles an arthropod, a chordate, or a cephalopod (a class ofmollusk; see Fig. 3.4).
Whittington found that grouping such forms within well-establishedtaxonomic categories, even higher taxonomic categories such as the class or
phylum, strained the limits of these classifications. Even many of thoseanimals that fell easily into existing phyla represented clearly uniquesubphyla or classes of organisms. Anomalocaris (literally, “abnormal
shrimp”) and Marrella, for example, both had hard exoskeletons and clearly
represent either arthropods or creatures closely related to them. Yet each ofthese animals possessed many distinct anatomical parts and exemplified
different ways of organizing these parts, thus clearly distinguishingthemselves from better-known arthropods such as the previous staple ofCambrian paleontological studies, the trilobite.
Whittington, a trilobite expert, understood this as well as anyone. In 1971,
he published the first comprehensive taxonomic review of the Burgess biota.
In his review, he broke decisively with Walcott’s previous attempt to lump all
Cambrian forms into a few preexisting taxonomic categories.

FIGURE 3.4
Figure 3.4a (left): Artist rendering of Nectocaris. Figure 3.4b (middle, right):
Photograph of Nectocaris fossil. Reprinted by permission from Macmillan
Publishers Ltd.: Nature, Martin R. Smith and Jean-Bernard Caron, “Primitive
Soft-Bodied Cephalopods from the Cambrian,” Nature, 465 (May 27, 2010):
469–72. Copyright 2010.
In so doing, he reemphasized the morphological disparity present in the
Burgess animal biota and, in the process, deprived evolutionary biologists of
one part of Walcott’s two-part strategy for minimizing the Cambrian problem.
By lumping all Burgess animals into existing phyla and classes, Walcott had
seemingly diminished the problem of disparity by reducing the number ofnovel phyla for which connecting intermediates were required. By
recognizing the disparity clearly on display in the Burgess, Whittington
partially undercut Walcott’s solution to the Cambrian mystery and highlighted
what would become its central unsolved problem: the origin of novel
biological form.
SOUNDING THE SEAFLOOR
Although Whittington, and later Gould, rejected Walcott’s early attempt to“shoehorn” all the animals of the Burgess Shale into preexisting taxonomic

categories, many paleontologists now also reject Stephen Jay Gould’scharacterization of many Burgess Shale creatures as being so exotic as to defy
affinity in classification with any modern groups.4 Many of thesepaleontologists would also recognize fewer total phyla first appearing in the
Cambrian than Gould did, and perhaps even as few as Walcott did. As
discussed in the previous chapter, still other paleontologists now favor “rankfree” approaches to classification.
Regardless, most paleontologists recognize that the Burgess Shale attests
to an extraordinary profusion of new animal forms—including many
manifesting unique anatomical structures and arrangements of body parts.
Thus, whatever differences of opinion exist about how to classify theseanimals—and any five-year-old child can distinguish them from each otherand from all previously known forms of life—their origin still requires
explanation. Thus, as noted, Walcott’s use of “lumping” did not solve theCambrian mystery.5
But what of the second part of Walcott’s proposal, the artifact hypothesis?
To evaluate this hypothesis, Walcott devised a more clear-cut and lesssubjective test. Recall that Walcott argued that the ancestral precursors of theCambrian animals were missing from the Precambrian fossil record becauseof the transgression and regression of seas. He posited an interval of geologic
time in which the ancestors of the Cambrian fauna were evolving offshore in
a Precambrian ocean and being deposited only in layers of marine
sedimentary rock. In this hypothesis, only after the ancient ocean rose andcovered the continent were the remains of Cambrian sea animals preserved in
sediment that today is above sea level.
When Walcott proposed his ingenious geological scenario, it could not yet
be tested. But with the development of offshore drilling technology in the
1940s, 1950s, and 1960s, oil companies began to drill through thousands offeet of marine sedimentary rock.6 As geologists evaluated the contents ofthese drill cores, they did not find Walcott’s predicted Precambrian fossils.
Instead, an even more fundamental problem for the hypothesis arose. At
the time that Walcott proposed his version of the artifact hypothesis,
geologists considered the oceanic and continental plates to be essentiallystable and fixed with respect to one another. Mountain building, faulting, andother geologic processes were attributed to worldwide changes in sea level,
accumulating troughs of sediment called geosynclines, rising mounds of
igneous rocks from beneath the earth’s crust, and even a shrinking earth.7
The idea that enormous, solid plates actually move, recycling themselves
through the plate-tectonic processes of subduction and seafloor spreading, hadnot yet been proposed. Yet modern plate tectonic theory now affirms that
oceanic crustal material eventually plunges back into the earth and melts in aprocess known as subduction. After surface rocks melt during subduction,
they form a new supply of molten magma. Eventually, magma from otherlocations deep in the earth wells up at mid-oceanic ridges to form new
igneous rocks, in a process known as seafloor spreading. It follows that any
oceanic sediments deposited atop the oceanic igneous crust will have alimited “life span” on the surface of the earth. Eventually, these sedimentaryrocks collide with the continental margin, plunge deep into the upper mantle,
and melt to form magma.
As a consequence of this cycle, the maximum age of any marine sedimentis strictly limited. And according to modern estimates, the oldest section ofoceanic crust has existed only since the Jurassic (or about 180 million yearsago8)—far too young to contain fossil ancestors of the trilobites. As theevidence for plate tectonics mounted, scientists discarded Walcott’s artifact
hypothesis and Lipalian interval as nonstarters. Paleontologists today do not
expect to find any Precambrian ancestors of the trilobites in oceanic
sediments, since they realize that there are no Precambrian sediments in theocean basins. If Precambrian strata are to be found anywhere, continents are
the place.
OTHER VERSIONS OF THE ARTIFACT HYPOTHESIS
Although Walcott’s proposals to explain away the absence of fossilized
ancestors of the Cambrian animals came to naught, other versions of theartifact hypothesis continued to circulate. These proposals take two basic
forms. Some scientists claimed, though for different reasons, that the expected
Precambrian fossil ancestors had simply not yet been found—that missing
fossils were an artifact of the incomplete sampling of the fossil record. Otherssuggested that Precambrian sedimentary rocks had not preserved the missing
fossils—that the incomplete preservation of the Precambrian animals meant
the missing fossils were no longer there to be found.
Walcott rejected the idea that paleontologists simply had not looked in, or
sampled, enough places. He noted that geologists already had extensively
investigated “the great series of Cambrian and Precambrian strata in eastern
North America.” Though they had looked “from Alabama to Labrador; inwestern North America [and] from Nevada and California far into Alberta andBritish Columbia, and also in China” their investigations had turned up
nothing of significant interest.9 In Walcott’s view the continents simply had
not preserved the fossilized remains of the Cambrian ancestors.

Before Walcott, some geologists had gone a step farther and suggested that
all Precambrian sedimentary rocks had been destroyed via extreme heat andpressure, a process called “universal metamorphism.” Walcott rejected thishypothesis, since he himself had encountered a “great series of pre-Cambriansedimentary rocks on the North American continent” among other places.
Other geologists suggested that major bursts of evolutionary innovation
occurred only during periods when sedimentary deposition had ceased, thus
again resulting in a lack of fossil preservation. But, as Gould remarked of
Walcott’s artifact hypothesis, this explanation also appeared to many scientists“forced and ad hoc . . . born of frustration, rather than the pleasure of
discovery.”10
CONTEMPORARY VERSIONS OF THE ARTIFACT HYPOTHESIS:TOO SOFT OR TOO SMALL
After the demise of the “universal metamorphism” idea, some paleontologists
proposed simpler, more intuitively plausible versions of the artifact
hypothesis. They claimed that the proposed intermediate forms leading to theCambrian animals may have been either too small or too soft, or both, to havebeen preserved.
Developmental biologist Eric Davidson, of California Institute ofTechnology, has suggested that the transitional forms leading to the Cambriananimals were “microscopic forms similar to modern marine larvae” and werethus too small to have been reliably fossilized.11 Other evolutionary scientists,such as Gregory Wray, Jeffrey Levinton, and Leo Shapiro, have suggested
that the ancestors of the Cambrian animals were not preserved, because they
lacked hard parts such as shells and exoskeletons.12 They argue that since
soft-bodied animals are difficult to fossilize, we shouldn’t expect to find theremains of the supposedly soft-bodied ancestors of the Cambrian fauna in the
Precambrian fossil record. University of California, Berkeley, paleontologist
Charles R. Marshall summarizes these explanations:[I]t is important to remember that we see the Cambrian “explosion”
through the windows permitted by the fossil and geological records. So
when talking about the Cambrian “explosion,” we are typicallyreferring to the appearance of large-body (can be seen by the nakedeye) and preservable (and therefore largely skeletonized) forms. . . . If
the stem lineages were both small and unskeletonized, then we would
not expect to see them in the fossil record.13

Though intuitively plausible, several discoveries call into question both ofthese versions of the artifact hypothesis. As for the idea that the ancestors of
the Cambrian animals were too small to be preserved, paleontologists have
known for some time that the cells of filament-shaped microorganisms(probably cyanobacteria) have been preserved in ancient Precambrian rocks.
Paleobiologist J. William Schopf, of the University of California, Los
Angeles, has reported an extremely ancient example of these fossils in the
Warrawoona Group strata of western Australia. These fossilizedcyanobacteria are preserved in 3.465-billion-year-old bedded cherts(microcrystalline sedimentary rocks).14 The same strata have also preserved
stromatolite mats, an organic accretionary growth structure usually indicating
the presence of bacteria, within slightly younger dolostone sediments ofroughly 3.45 billion years in age (see Fig. 3.5).15

FIGURE 3.5
Figure 3.5a (left): Photographs of Cambrian-age fossil stromatolites.
Courtesy Wikimedia Commons, user Rygel, M. C. Figure 3.5b (right):
Alternating fine- and coarse-layered structure of Precambrian stromatolite
fossils shown in cross section. Courtesy American Association for the
Advancement of Science, Figure 2B, Hoffman, P., “Algal Stromatolites: Usein Stratigraphic Correlation and Paleocurrent Determination,” Science, 157(September 1, 1967): 1043–45. Reprinted with permission from AAAS.
These discoveries pose a problem for the idea that the Cambrian ancestors
were too small to survive in the fossil record. The sedimentary rocks that
preserve the fossilized cyanobacteria and single-celled algae are far older and,
therefore, far more likely to have been destroyed by tectonic activity thanthose later sedimentary rocks that should have preserved the near-ancestors of
the Cambrian animals. Yet these rocks, and the fossils they contain, havesurvived just fine. If paleontologists can find tiny fossilized cells in these far
older and rarer formations, shouldn’t they also be able to find some ancestralforms of the Cambrian animals in younger and more abundant sedimentary

rocks? Yet few such precursors have been found.
There are also several reasons to question the second version of thishypothesis—the idea that the presumed Cambrian ancestors were too soft tobe preserved. First, some paleontologists have questioned whether soft-bodied
ancestral forms of the hard-bodied Cambrian animals would have even been
anatomically viable.16 They argue that many animals representing phyla suchas brachiopods and arthropods could not have evolved their soft parts first andthen added shells later, since their survival depends upon their ability toprotect their soft parts from hostile environmental forces. Instead, they argue
that soft and hard parts had to arise together.17 As paleontologist James
Valentine, of the University of California, Berkeley, has noted in the case ofbrachiopods, “The brachiopod Bauplan [body plan] cannot function without adurable skeleton.”18 Or as J. Y. Chen and his colleague Gui-Qing Zhou
observe: “Animals such as brachiopods . . . cannot exist without a mineralized
skeleton. Arthropods bear jointed appendages and likewise require a hard,organic or mineralized outer covering.”19
Because these animals typically require hard parts, Chen and Zhou assume
that the ancestral forms of these animals should have been preserved
somewhere in the Precambrian fossil record if in fact they were ever present.
Thus, the absence of hard-bodied ancestors of these Cambrian animals in the
Precambrian strata shows that these animals first arose in the Cambrianperiod. As they rather emphatically insist: “The observation that such fossils
are absent in Precambrian strata proves that these phyla arose in the
Cambrian.”20
It should be pointed out that this argument cannot be made for all
Cambrian animal groups and, in my view, does not achieve the standing of a“proof” in any case. Many Cambrian phyla, including phyla characterized bymostly hard-shelled animals such as mollusks and echinoderms, do have softbodied representatives. The earliest known mollusk, Kimberella, for example,
lacked a hard external shell (though it did have other hard parts).21 So, clearly,
some mainly hard-shelled Cambrian groups could have had soft-bodied
ancestors.
It is also possible to postulate the existence of an arthropod or brachiopod
ancestor—especially some extremely distant ancestor—lacking a hard shell.
Soft-bodied onychophorans (velvet worms) were once proposed as ancestorsof the arthropods, though more recent studies challenge this idea.
Onychophorans themselves arise well after arthropods in the fossil record andcladistics analysis suggests that onychophorans may be a sister, rather than anancestral, group to arthropods.22 Even so, it’s difficult to disprove a negative:

in particular, to foreclose the possibility that arthropods or brachiopods might
have had a soft-bodied ancestor deep in the Precambrian.
Nevertheless, it seems unlikely on a Darwinian view of the history of lifethat all Cambrian arthropod or brachiopod ancestors, especially the relatively
recent ancestors of these animals, would have lacked hard parts entirely.
There are many types of arthropods that arise suddenly in the Cambrian—trilobites, Marrella, Fuxianhuia protensa, Waptia, Anomalocaris—and all ofthese animals had hard exoskeletons or body parts. Moreover, the only known
extant group of arthropods without a hard exoskeleton (the pentastomids)
have a parasitic relationship with arthropods that do.23 Thus, surely, it seems
likely that some of the near ancestors of the many arthropod animals that
arose in the Cambrian would have left at least some rudimentary remains of
exoskeletons in the Precambrian fossil record—if, in fact, such ancestral
arthropods existed in the Precambrian and if arthropods arose in a gradualDarwinian way.
Moreover, the arthropod exoskeleton is part of a tightly integrated
anatomical system. Specific muscles, tissues, tendons, sensory organs—and a
special mediating structure between the soft tissue of the animal and theexoskeleton called the endophragmal system—are all integrated to support theprocess of molting and exoskeletal growth and maintenance that is integral tothe arthropod mode of existence. A best-case Darwinian scenario for theorigin of such a system would, therefore, envision the “co-evolution” of theseseparate anatomical subsystems in a coordinated fashion, since some of theseanatomical subsystems confer a functional advantage to the animal largely bysupporting, and promoting, the growth and maintenance of the exoskeleton(and vice versa). Others would be vulnerable to damage without it. Thus, it
seems unlikely that these interdependent subsystems would evolve
independently first without an exoskeleton, only to have the exoskeleton arise
suddenly as a kind of accretion atop an already integrated system of soft partsat the end of a long evolutionary process.
This, again, makes it reasonable to expect that at least some rudimentary
arthropod hard parts would have been preserved in the Precambrian ifarthropods were present then. That such parts are unknown for all Cambrianarthropods (and brachiopods) in a fossil record that presumably favors hardpart preservation, seems at least curious. And it appears, on its face, tosupport the assertions of those Cambrian paleontologists such as Chen andZhou who take the absence of any hard parts in the Precambrian record as
evidence of the absence of those groups that typically depend on hard parts
for their existence.
In any case, advocates of the artifact hypothesis must at least explain aCambrian explosion of hard body parts, if not whole Cambrian animals. As
paleontologist George Gaylord Simpson noted in 1983, even if it’s true that
Precambrian ancestors were not preserved simply because they lacked hardparts, “there is still a mystery to speculate about: Why and how did many
animals begin to have hard parts—skeletons of sorts—with apparent
suddenness around the beginning of the Cambrian?”24
There is an additional, more formidable, difficulty for this version of theartifact hypothesis. Although the fossil record generally does not preserve softbody parts as frequently as hard parts, it has preserved many soft-bodied
animals, organs, and anatomical structures from both the Cambrian and thePrecambrian periods.
As we saw earlier, Precambrian sedimentary rocks in several places aroundthe world have preserved fossilized colonial blue-green algae, single-celledalgae, and cells with a nucleus (eukaryotes).25 These microorganisms were
not only small, but they also entirely lacked hard parts. Another class of late
Precambrian organisms called the Vendian or Ediacaran biota included thefossilized remains of many soft-bodied organisms, including many that may
well have been lichens, algae, or protists (microorganisms with cells
containing nuclei). Cambrian-era strata themselves preserve many soft-bodied
creatures and structures. The Burgess Shale in particular preserved the soft
parts of several types of hard-bodied Cambrian animals, such as Marrella
splendens,26 Wiwaxia,27 and Anomalocaris. The Burgess Shale also
documents entirely soft-bodied representatives28 of several phyla, including:Cnidaria (represented by an animal called Thaumaptilon, a feathershaped colonial organism formed from smaller soft sea anemone–likeanimals)29
Annelida (represented by the polychaete worms Burgessochaeta andCanadia)30
Priapulida (represented by Ottoia, Louisella, Selkirkia—all worms with adistinctive proboscis)31
Ctenophora (represented by Ctenorhabdotus, a gelatinous animal with atranslucent body similar to a modern comb jelly)32
Lobopodia (represented by Aysheaia and Hallucigenia, segmented softbodied animals with many legs)33
The Burgess also preserves soft-bodied animals of unknown affinities,
such as Amiskwia, a gelatinous air mattress–like animal;34 Eldonia, ajellyfish-like animal with a much more complex anatomy than a modern

jellyfish;35 and the aforementioned, difficult to classify, Nectocaris.36 As
Simon Conway Morris notes, “The existing [Burgess] collections represent
approximately 70,000 specimens. Of these, about 95 percent are either softbodied or have thin skeletons.”37
THE CHENGJIANG EXPLOSION
Any doubts about the ability of sedimentary rocks to preserve soft and small
body parts were permanently laid to rest by a series of dramatic fossil finds insouthern China beginning in the 1980s.
In June 1984, paleontologist Xian-Guang Hou journeyed to Kunming, insouthern China, to prospect for fossilized samples of a bivalved arthropod
called a bradoriid.38 The area around Kunming in the Yunnan Province waswell known for its lower Cambrian strata and typical Cambrian-era fossils,
such as bradoriids and trilobites, both of which were relatively easy topreserve because of their characteristically hard exoskeletons. In 1980, Hou
had found many bradoriid samples in a geological formation called the
Qiongzhusi Section near Kunming.
In the summer of 1984 Hou traveled to the town of Chengjiang to look forbradoriids in another geological formation called the Heilinpu Formation. His
efforts there yielded little success. As a result, he turned his attention toanother outcrop, a sedimentary sequence now called the Maotianshan Shale.
Hou’s team set farmworkers to digging out and scouring the mudstone blocks.
His book, The Cambrian Fossils of Chengjiang, China, describes what
happened next:
At about three o’clock in the afternoon of Sunday July 1, a semicircularwhite film was discovered in a split slab, and was mistakenly thought torepresent the valve of an unknown crustacean. With the realization that
this . . . represented a previously unreported species, breaking of therock in a search for additional fossils continued apace. With the find ofanother specimen, a 4–5 cm long animal with limbs preserved, it
became apparent that here was nothing less than a soft-bodied biota.39
Hou remembers the Cambrian specimen vividly, for it appeared “as if it
was alive on the wet surface of the mudstone.”40 Redoubling their efforts, theresearchers quickly uncovered the fossilized remains of one extraordinary
soft-bodied animal after another. Most of the fossils were preserved as
flattened two-dimensional imprints of three-dimensional organisms, although,as Hou observes, “some retain a low three-dimensional relief.”41 Most
important, he notes, “The remains of hard tissues, such as the shells ofbrachiopods or the carapaces of trilobites, are well represented in theChengjiang fauna, but less robust tissues, which are usually lost throughdecomposition, are also beautifully preserved.”42
As the result of the very fine, small-grained sediments in which they were
deposited, the Chengjiang fossils preserved anatomical details with a fidelity
surpassing even that of the Burgess fauna.43 The Maotianshan Shale alsopreserved an even greater variety of soft-bodied animals and anatomical parts
than the Burgess Shale had done. In the ensuing years, Hou and his closest
colleagues, J. Y. Chen and Gui-Qing Zhou, found many excellent examples ofwell-preserved animals lacking even a keratinized exoskeleton, including
soft-bodied members of phyla such as Cnidaria (corals and jellyfish),Ctenophora (comb jellies), Annelida (a type of “ringed” segmented worm),
Onychophora (segmented worms with legs), Phoronida (a tubular, filterfeeding marine invertebrate), and Priapulida (another distinctive type ofworm).44 (See Fig. 3.6.)
They found fossils preserving the anatomical details of numerous soft
tissues and organs such as eyes, intestines, stomachs, digestive glands,
sensory organs, epidermes, bristles, mouths, and nerves.45 They also
discovered jellyfish-like organisms called Eldonia, which exhibit delicate,soft body parts such as radiating water canals and nerve rings. Other fossils
even revealed the contents of the guts of several animals.46
The discoveries near Chengjiang demonstrated beyond any reasonable
doubt that sedimentary rocks can preserve soft-bodied fossils of great
antiquity and in exquisite detail, thereby challenging the idea that the absenceof Precambrian ancestors is a consequence of the fossil record’s inability topreserve soft-bodied animals from that period. At the same time, thesedimentary rocks near Chengjiang had other surprises in store.
PRECAMBRIAN SECRETSPaul Chien is a Chinese-American marine biologist who, as a boy, left
mainland China with his family to escape the 1949 Communist takeover
under Mao Tse-tung. Eventually, after completing Ph.D. studies in the UnitedStates, he became a biology professor at the University of San Francisco. He
first learned about the discoveries in southern China after reading the Timemagazine cover story in 1995. Then he learned, ironically, from a story inPeople’s Daily, the official newspaper of the Chinese Communist party, thatsome Chinese paleontologists thought that these discoveries challenged aDarwinian view of the history of life.
The great variety of the marine invertebrates present in Chengjiang
fascinated Chien and convinced him to return to the country of his birth. Aftermaking his first trip in the summer of 1996, he met J. Y. Chen. As Paul Chien
returned over several successive summers to do research of his own, he and J.
Y. Chen continued to share their findings and compare notes.
Upon arriving in China in 1998 for his third summer of research, Paul
Chien learned that Chen had discovered a fossil of an adult sponge in the late
Precambrian rocks of a sedimentary formation called the Doushantuo
Phosphorite—a formation that lies beneath the Maotianshan Shale. As the twoscientists examined the sediments that encased Chen’s fossil sponge, they
made a discovery that would doom the most popular remaining version of theartifact hypothesis.

FIGURE 3.6

Cambrian explosion fossils from Chengjiang fauna, artist depictions andfossil photos. Photos in 3.6a, b, e, and f courtesy J. Y. Chen. Photos in 3.6c
and d courtesy Paul Chien.
As J. Y. Chen began to examine the sedimentary rocks that enclosed his
fossilized sponge, he decided to look at them in a so-called thin section undera light microscope. Chen wondered whether smaller embryonic forms of these
Precambrian animals might also have been preserved in these phosphorite
rocks. Sure enough, under magnification he found little round balls that heand Paul Chien identified as sponge embryos. In 1999, at a majorinternational conference about the Cambrian explosion held near Chengjiang,
J. Y. Chen, Paul Chien, and three other colleagues presented their findings.47
A number of Chinese paleontologists questioned them at first, suggestingthat the little round balls were not sponge embryos at all, but instead theremains of brown and green algae.48 Here Paul Chien’s expertise came to thefore. Early in his career, Chien had perfected a technique for examining theembryos of living sponges under a scanning electron microscope. He now
adapted his technique to examine these microscopic fossilized structuresusing a more powerful microscope. What he found startled him and amazedother scientists.
Sponges are nature’s glassworks. They are made of a soft and flexible
lattice of cells from which protrude silica-encrusted “spicules.” Though
sponges come in a variety of shapes and sizes, they are one of the simplest
known forms of animal life, with between six and ten distinctive cell types.49
In comparison, the typical arthropod has between thirty-five and ninety cell
types.
As Chien examined the little balls of the Doushantuo Phosphorite under
the scanning microscope, he noticed what looked like cells undergoing cell
division. At first, he had no way to determine what type of cells they mightbe. But as he examined cross sections of these cells more carefully, heidentified a distinctive structure that he knew from his prior research.
Only sponges have spicules, and the fossilized cells he was examining
preserved microscopic spicules in the early stages of their development.50
Clearly, these were not algal balls; they were sponge embryos. Even more
surprising, Chien was able to observe the internal structure of theseembryonic cells, allowing him to identify the nuclei of some of these cells
within the fossilized remains of the larger outer cell membrane (see Fig. 3.7).
The discovery of these sponge embryos has proven decisive in the caseagainst the remaining versions of the artifact hypothesis, for several reasons.
First, though spicules in sponges are encased in a thin layer of glassysilica, sponges are generally considered to be a soft-bodied organism becauseof the predominantly soft tissues out of which the rest of their bodies are
made. Moreover, the cells of all embryos during their earliest embryonicstages are soft. Even in animals that have internal or external skeletons, thenascent forms of these hard parts do not emerge until gastrulation, partway
through the process of embryological development. Thus, discovery of anembryo in the earliest stages of cell division shows beyond a doubt that
Precambrian sedimentary rocks can, under the right circumstances, preserve
soft-bodied organisms.
It also established something else. J. Y. Chen found these sponge embryos
beneath the Cambrian–Precambrian boundary in late Precambrian rock. Yet
these Precambrian layers did not preserve remains of any clearly ancestral orintermediate forms leading to the other main groups of Cambrian animals.
This raised an obvious question. If the Precambrian sedimentary strata
beneath the Maotianshan Shale preserved the soft tissues of tiny, microscopic
sponge embryos, why didn’t they also preserve the near ancestors of thewhole animals that arose in the Cambrian, especially since some of thoseanimals must have had at least some hard parts as a condition of their
viability? If these strata could preserve embryos, then they should havepreserved fully developed animals—at least, if such animals were present at
the time. That well-developed, clearly ancestral animal forms were notpreserved, when tiny sponge embryos51 were, strongly indicates that suchforms were simply not present in the Precambrian layers.

FIGURE 3.7

Figure 3.7a (above): Photographs of fossilized sponge embryos in the earlystages of cell division, showing the sponge at the 8-cell stage of division, withfour of its cells marked in the foreground. Figure 3.7b (right): A close-up
image of a fossil of a sponge embryo cell revealing numerous yolk granules
inside. Courtesy Paul Chien.
Of course, there are conditions under which fossils are unlikely to bepreserved. We know, for example, that near-shore sands do not favorpreservation of detail, let alone the fine detail of very small organisms amillimeter or less in length.52 Even so, such considerations do little to bolster
the artifact hypothesis. The sedimentary environments that produced thecarbonates, phosphorites, and shales of the Precambrian strata beneath the
Maotianshan Shale, for example, would have provided a congenial
environment for fossilizing all sorts of creatures during Precambrian times.
Advocates of the artifact hypothesis need to show not just that certain
factors discourage preservation in general. No one disputes that. What theyneed to show is that these factors were ubiquitous in Precambrian depositional
environments worldwide. If near-shore sands characterized all Precambriansedimentary deposits, then paleontologists would not expect to find any
fossils there, at least not any tiny ones. Yet clearly this is not the case.
Precambrian strata include many types of sediments that can preserve—and in
the case of the Doushantuo formation in China, have preserved—animal
remains in fine detail, including small and vulnerable sponge embryos.
Moreover, geologists Mark and Dianna McMenamin have noted that inmany other Cambrian locales around the world, including one in
Newfoundland that they have studied extensively, the pattern of
sedimentation changes very little across the Cambrian–late Precambrianboundary, suggesting that many Precambrian environments would haveprovided equally good environments for the preservation of fossils.53
In their 2013 book, The Cambrian Explosion, paleontologists James
Valentine and Douglas Erwin go further. They note that many late
Precambrian depositional environments actually provide more favorable
settings for the preservation of fossils than those present in the Cambrianperiod. As they note, “a revolutionary change in the sedimentary environment—from microbially stabilized sediments during the Ediacaran [latePrecambrian] to biologically churned sediments as larger, more active animals
appeared—occurred during the early Cambrian. Thus, the quality of fossil
preservation in some settings may have actually declined from the Ediacaran
to the Cambrian, the opposite of what has sometimes been claimed, yet wefind a rich and widespread explosion of [Cambrian] fauna.”54

STATISTICAL PALEONTOLOGY
Recent work in a field known as statistical paleontology casts further doubt
on the artifact hypothesis. Since the discovery of the Burgess Shale,
Precambrian- and Cambrian-era discoveries have repeatedly uncovered fossil
forms that either establish radically disparate new forms of life or,increasingly, forms that fall into existing higher taxonomic groups (such asclass, subphylum, or phylum).
As a result, the fossil record amply documents organisms corresponding to
the terminal branches on the Darwinian tree of life (animal forms representing
new phyla or classes, for example), but it fails to preserve those organisms
representing the internal branches or nodes leading to these representatives ofnovel phyla and classes of Cambrian-era animals. Yet these intermediates are
the very forms required to connect the terminal branches to form a coherent
evolutionary tree and establish that the representatives of the Cambriananimals did arise by means of a gradual evolutionary process from simpler
Precambrian ancestors.
Recall that Louis Agassiz thought that this pattern could not be explainedby appealing to an incomplete fossil record, because the fossil record wasstrangely selective in its incompleteness, preserving abundant evidence of theterminal branches but consistently neglecting to preserve the representativesof the internal branches or nodes.
Contemporary paleontologists, such as Michael Foote at the University of
Chicago, have come to a similar conclusion. Foote has shown, using
statistical sampling analysis, that as more and more fossil discoveries fallwithin existing higher taxonomic groups (e.g., phyla, subphyla, and classes),
and as they fail to document the rainbow of intermediate forms expected in
the Darwinian view of the history of life, it grows ever more improbable thatthe absence of intermediate forms reflects a sampling bias—that is, an“artifact” of either incomplete sampling or preservation.
This kind of analysis merely quantifies what, in other circumstances, wewould sense intuitively. Imagine that you reach into an enormous barrel fullof marbles and randomly pull out a yellow, a red, and a blue marble. At thispoint your brief sampling should leave you undecided as to whether you havea representative sample of the barrel’s contents. You might at first imagine
that the barrel also contains marbles representing a rainbow of intermediatecolors. But as you continue to sample from every place in the barrel and findthat the barrel disgorges only those same three colors you begin to suspectthat it may offer a much more limited selection of colors than, say, the rack ofcolor samples at your local paint store.

Over the past 150 years or so, paleontologists have found many
representatives of the phyla that were well known in Darwin’s time (byanalogy, the equivalent of the three primary colors) and a few completely new
forms altogether (by analogy, some other distinct colors such as green andorange, perhaps). And, of course, within these phyla there is a great deal ofvariety. Nevertheless, the analogy holds at least insofar as the differences inform between any member of one phylum and any member of anotherphylum are vast, and paleontologists have utterly failed to find forms thatwould fill these yawning chasms in what biologists call “morphologicalspace.” In other words, they have failed to find the paleontological equivalentof the numerous finely graded intermediate colors (Pendleton blue, dustyrose, gun barrel gray, magenta, etc.) that interior designers covet. Instead,extensive sampling of the fossil record has confirmed a strikingly
discontinuous pattern in which representatives of the major phyla stand instark isolation from members of other phyla, without intermediate forms
filling the intervening morphological space.
Foote’s statistical analysis of this pattern, documented by an everincreasing number of paleontological investigations, demonstrates just how
improbable it is that there ever existed a myriad of as yet undiscovered
intermediate forms of animal life—forms that could close the morphologicaldistance between the Cambrian phyla one tiny evolutionary step at a time. In
effect, Foote’s analysis suggests that since paleontologists have reachedrepeatedly into the proverbial barrel, sampled it from one end to the other, andfound only representatives of various radically distinct phyla but no rainbow
of intermediates, we shouldn’t hold our breath expecting such intermediates
to eventually emerge. He asks “whether we have a representative sample ofmorphological diversity and therefore can rely on patterns documented in thefossil record.” The answer, he says, is yes.55
By this affirmation, he doesn’t mean that there are no biological forms left
to discover. He means, rather, that we have good reason to conclude that suchdiscoveries will not alter the largely discontinuous pattern that has emerged.
“Although we have much to learn about the evolution of form,” he writes, thestatistical pattern created by our existing fossil data demonstrates that “inmany respects our view of the history of biological diversity is mature.”56
CHENGJIANG AND THE CAMBRIAN CONUNDRUM57
The Cambrian and Precambrian fossils from southern China have rendered
the mystery associated with the Cambrian explosion more acute in other ways
as well. First, the fossil finds in southern China coupled with advances inradiometric dating techniques applied to other Cambrian-era strata haveallowed scientists to reassess the duration of the Cambrian explosion. As thename implies, the fossils documenting the Cambrian explosion appear withina relatively narrow slice of geologic time. Until the early 1990s, most
paleontologists thought the Cambrian period began 570 million and ended
510 million years ago, with the Cambrian explosion of novel animal forms
occurring within a 20- to 40-million-year window during the lower Cambrianperiod.
Two developments have led paleontologists and geochronologists to revise
those estimates downward. First, in 1993, radiometric dating of zircon
crystals from formations just above and below Cambrian strata in Siberia
allowed for a precise redating of Cambrian strata. Radiometric analyses ofthese crystals fixed the start of the Cambrian period at 544 million years
ago,58 and the beginning of the Cambrian explosion itself to about 530
million years ago (see Fig. 3.8). These studies also suggested that the
explosion of the novel Cambrian animal forms occurred within a window ofgeologic time much shorter than previously believed, lasting no more than 10
million years, and the main “period of exponential increase of diversification”
lasting only 5 to 6 million years.59

FIGURE 3.8
The Cambrian explosion occurred within a narrow window of geologicaltime.
Geologically speaking, 5 million years represents a mere 1/10 of 1 percent(0.11 percent, to be precise) of earth’s history. J. Y. Chen explains that“compared with the 3-plus-billion-year history of life on earth, the period [ofthe explosion] can be likened to one minute in 24 hours of one day.”60
Some geologists or evolutionary biologists dispute these numbers, but they
do so by redefining the Cambrian explosion as a series of separate events
rather than using the term to refer to the main radiation of new body plans in
the lower Cambrian. In 2009, I participated in a debate in which one of my
opponents, paleontologist Donald Prothero, from Occidental College, used
this common rhetorical strategy to minimize the severity of the Cambrian
mystery. In his opening statement, he claimed that the Cambrian explosion
actually took place over an 80-million-year period of time and thatconsequently those who cited the Cambrian as a challenge to the adequacy ofthe neo-Darwinian theory were mistaken. As I was listening to his opening
statement, I consulted his textbook to see how he had derived his 80-millionyear figure. Sure enough, he had included in the Cambrian explosion three
separate pulses of new innovation or diversification, including the origin of agroup of late Precambrian organisms called the Ediacaran or Vendian fauna.
He also included not only the origin of the animal body plans in the lower
Cambrian, but also the subsequent minor diversification (variations on thosebasic architectural themes) that occurred in the upper Cambrian. He included,
for example, not just the appearance of the first trilobites, which occurredsuddenly in the lower Cambrian, but also the origin of a variety of different
trilobite species later from the upper Cambrian.
In my response to Prothero, I noted that he was, of course, free to redefine
the term “Cambrian explosion” any way he liked, but that by using the term todescribe several separate explosions (of different kinds), he had done nothing
to diminish the difficulty of explaining the origin of the first explosive
appearance of the Cambrian animals with their unique body plans andcomplex anatomical features. Beyond this, as we’ll see in the next chapter, theVendian organisms may not have been animals at all, and they bear little
resemblance to any of the animals that arise in the Cambrian. We’ll also seethat most, if not all,61 of these organisms actually went extinct well before theorigin of the animals that first appear in the lower Cambrian and so they dolittle to minimize the problem of the explosive origin of animals.
In any case, expanding the definition of the Cambrian explosion only
obscures the real challenge posed by the event, a challenge underscored by
the discoveries at Chengjiang. An analysis by MIT geochronologist Samuel
Bowring has shown that the main pulse of Cambrian morphologicalinnovation occurred in a sedimentary sequence spanning no more than 6
million years.62 Yet during this time representatives of at least sixteen
completely novel phyla and about thirty classes first appeared in the rockrecord. In a more recent paper using a slightly different dating scheme,

Douglas Erwin and colleagues similarly show that thirteen new phyla appear
in a roughly 6-million-year window.63 As we’ve seen, among these animal
forms were the first trilobites, with their lens-focusing compound eyes among
other complex anatomical features. The problem of explaining how so many
new forms and structures arose so rapidly in the first explosive period of theCambrian remains, whether or not one decides to include within thedesignation “Cambrian explosion” other distinct events (see Part Two).
THE TOP-DOWN PATTERN IN STARK RELIEF
The Chengjiang fauna makes the Cambrian explosion more difficult toreconcile with the Darwinian view for yet another reason. The Chengjiang
discoveries intensify the top-down pattern of appearance in which individual
representatives of the higher taxonomic categories (phyla, subphyla, andclasses) appear and only later diversify into the lower taxonomic categories(families, genera, and species).
Discoveries at Chengjiang contradict the bottom-up pattern that neoDarwinism expects. The site does not show the gradual emergence of uniquespecies followed slowly but surely by the emergence of representatives ofever higher and more disparate taxa, leading to novel phyla. Instead, like theBurgess Shale, it shows body plan–level disparity arising first and suddenly,
with no evidence of a gradual unfolding and ranging through the lower
taxonomic groups.
Consider the case of the early chordates, a phylum consisting of creaturespossessing a flexible, rod-shaped structure called a notochord. Mammals, fish,
and birds are familiar members of this phylum. Prior to the discovery of theChengjiang biota, chordates were unknown in the Cambrian period and were
thought to have first appeared only much later, during the Ordovician
period.64 Now, following the discoveries at Chengjiang, the first appearanceof chordates in the Cambrian period has been amply documented.
For example, J. Y. Chen and several other Chinese paleontologists havefound a spindle-shaped eel-like animal called Yunnanozoon lividum, which
many paleontologists have interpreted as an early chordate because it
possesses, among other features, a digestive tract, branchial arches, and alarge notochord much like a spinal cord.65 In addition, J. Y. Chen andcolleagues have reported the discovery of a sophisticated craniate-likechordate called Haikouella lanceolata from the lower Cambrian Maotianshan
Shale. According to Chen and others, Haikouella has many of the samefeatures of Yunnanozoon lividum as well as several additional anatomical
features including a “heart, ventral and dorsal aorta, an anterior branchialarterial, gill filaments, a caudal (posterior) projection, a neural cord with arelatively large brain, a head with possible lateral eyes, and a ventrally
situated buccal cavity with short tentacles.”66

FIGURE 3.9
Figure 3.9a (top): Drawing of the Cambrian fish, Myllokunmingia fengjiaoa.
Figure 3.9b (bottom): Photograph of Myllokunmingia fengjiaoa fossil.
Reprinted by permission from Macmillan Publishers Ltd.: Nature, Shu et al.,“Lower Cambrian Vertebrates from South China,” Nature, 402 (November 4,1999): 42–46. Copyright 1999.
Simon Conway Morris, with D. G. Shu and several Chinese colleagues,
has reported an even more dramatic find. They have discovered the fossilized
remains of two small Cambrian fish, Myllokunmingia fengjiaoa andHaikouichthys ercaicunensis (see Fig. 3.9), suggesting a much earlier
appearance for both fishes and vertebrates (a class of chordates), both ofwhich were first thought to have originated in the Ordovician period, about
475 million years ago. Both of these taxa are jawless fish (agnathans) and areconsidered by Shu and others to be closely allied to modern lampreys.67
Finally, a paper by Shu and others reports the first convincing specimen ofanother type of chordate from the Cambrian, a urochordate (tunicate).68 This
specimen, Cheungkongella ancestralis, is likewise found in the early
Cambrian shales (Qiongzhusi Formation) near Chengjiang. These recent finds
demonstrate that not only did the phylum Chordata first appear in the
Cambrian, but also each one of the chordate subphyla (Cephalochordata,
Craniata, and Urochordata) first emerged then as well. In any case, thediscovery in China of chordates, and other previously undiscovered phyla in
the Cambrian, only accentuates the puzzling top-down pattern of appearance
that other Cambrian discoveries had previously established.69
MORE QUESTIONS THAN ANSWERS
Thus, despite the efforts to explain the Cambrian explosion using various
versions of the artifact hypotheses, the mystery of the Cambrian explosion has
only grown more acute as a result of the dramatic discoveries in southern
China that have turned Darwin’s tree of life upside down.
When I first heard J. Y. Chen describe these discoveries in 2000, I had
been investigating another unsolved question about the history of life: Whatcaused the first living cell, and the information it contains, to arise? As I
heard Dr. Chen speak that day in Seattle, my interest in another puzzlingquestion about the history of life began to germinate. Could it be that theorigin of animal life was in its own way just as difficult a problem as that of
the origin of life itself? Though I eventually concluded that the Cambrian
explosion does, indeed, present a profound challenge to contemporary
Darwinian theory, it didn’t take me long to discover that some scientists
believed that the mystery of the Cambrian explosion had already been
resolved by the discovery of some rather enigmatic Precambrian fossils. We
turn to those next.

4
The Not Missing Fossils?
The atmosphere in the auditorium of the Sam Noble Science Museum at the
University of Oklahoma was uncomfortably tense, with a security detail of
local Norman, Oklahoma, police officers on hand to keep the peace—aconspicuous change from the campus security guard who might be present at
a typical university event. The occasion? A new documentary, Darwin’s
Dilemma, that Jonathan Wells, a colleague of mine from the Discovery
Institute, and I were scheduled to show. The film would explore the challenge
to Darwin’s theory posed by the Cambrian fossil record.
For weeks before our event in September of 2009, outspoken evolutionary
biology students and an atheist student group, both egged on by militant offcampus bloggers, had threatened to disrupt the screening. Members of thebiology faculty pledged to come, so that well before the official start time alarge crowd had gathered.
The museum and the geology department, not wanting to complicate
matters in their own minds by watching the film first, decided to launch apreemptive first strike by issuing a disclaimer and scheduling an official
lecture designed to rebut the film. In the disclaimer the museum stated that,given its public funding, it had no choice but to rent the auditorium to groups
irrespective of their “religious beliefs” or “scientific literacy.” The disclaimer
further noted that the Sam Noble Science Museum did “not support
unscientific views masquerading as science, such as those of the Discovery
Institute.” The museum flyer also announced the lecture of one of theircurators, a paleontologist from the university, and mocked the topic of thefilm—the Cambrian “explosion”—with carefully placed scare quotes. The
lecture’s start time of 5:00 P.M. also ensured a confluence afterward of theaudience made upset by the lecture and the more friendly audience coming to
see the film.
Jonathan Wells, a biologist well known for his skepticism about
contemporary Darwinian theory, attended the pre-film lecture. Ignoring a few
hostile glares, he listened as the paleontologist from the university argued thatthe Cambrian explosion presented no actual dilemma for Darwinianevolution, and as this same paleontologist speculated that if Darwin had only
known what paleontologists today know of the Cambrian fossil record, he(Darwin) would have celebrated it as confirmation of his theory. Thisparticular paleontologist also denied that novel animal forms emerged
suddenly in the Cambrian. Instead, he argued that they arose in rudimentary
form much earlier in the late Precambrian. He noted that paleontologists had
discovered in late Precambrian sediments fossilized sponges, a type ofprimitive mollusk, and the burrows of worms.
He also laid particular stress on the significance of a group of enigmaticorganisms first discovered in the Ediacaran Hills in southern Australia datingfrom about 565 million years ago, in a Precambrian period known as theVendian or Ediacaran. Jonathan and I were well aware that most
paleontologists do not regard these fossilized organisms as plausible ancestors
to the Cambrian fauna. But on that evening the expert from the university
claimed the opposite. He also claimed that some obscure Ediacaran organisms(with exotic names such as Vernanimalcula, Parvancorina, and Arkarua)
represented early bilaterians (bilaterally symmetrical animals), arthropods,
and echinoderms. He insisted that these organisms pushed back the explosionof animal life by some 40 million years, establishing a “fuse” for the
Cambrian explosion in the form of primitive and presumably ancestral animal
forms for several of the most significant Cambrian phyla and body designs.
An hour before I was to walk over to lead a discussion and answer
questions about the Cambrian film from what proved to be an intensely
hostile audience, Jonathan Wells called me with a report on the museum’s
attempt to refute the film preemptively. The presentation claimed to haveresolved the Cambrian mystery—Darwin’s dilemma—by showing that theancestral precursors to the major groups of Cambrian animals had been foundafter all. But is this true?
THE EDIACARAN FAUNA AND VENDIAN RADIATIONIn the previous chapter, we saw that many prominent paleontologists havesought to explain the Cambrian explosion as an artifact of our incomplete
sampling of an incomplete fossil record. The lecture that my colleague heardthat night in Oklahoma took a very different approach, giving the strong
impression that the Precambrian fossil record actually does preserve theancestral forms of the Cambrian animals and that the Ediacaran fauna, inparticular, provide several striking examples of such forms.
In public presentations about the Cambrian explosion, I’ve often

encountered this claim, though usually in the form of an unfocused question:“What about the Ediacaran?” Nevertheless, in writing about the Cambrian, I
take care not to attribute the idea that the Ediacaran fauna represent Cambrianancestors to leading Ediacaran or Cambrian experts, lest I critique a straw
man. Most paleontologists doubt that well-known Ediacaran forms represent
ancestors of the Cambrian animals and few think the late Precambrian fossil
record as a whole makes the Cambrian explosion appreciably less explosive.
The claim is important to address, however, since it persists as a kind of
paleontological urban legend, one that even occasionally finds its way into themouths of paleontologists.
The Ediacaran fauna derive their name from their most notable discovery
site, the Ediacaran Hills in the outback of southeastern Australia. These faunadate from late Precambrian time, a period that the International Union of
Geological Sciences has recently renamed the “Ediacaran period.”1 Since
geologists used to call the last period of Precambrian time the “Vendian
period,” paleontologists also refer to the Ediacaran fauna as the Vendian fauna
or biota (see Fig. 1.6). Paleontologists have made additional discoveries ofEdicaran- or Vendian-era creatures in England, Newfoundland, the White Sea
in northwestern Russia, and the Namibian desert in southern Africa,
suggesting a near worldwide distribution. Although these fossils wereoriginally dated to between 700 and 640 million years old, volcanic ash beds
both below and above the Namibian site have recently provided moreaccurate radiometric dates. These studies fix the date for the first appearanceof the Ediacaran fauna at about 570–565 million years ago, and the lastappearance at the Cambrian boundary about 543 million years ago, or about
13 million years before the onset of the Cambrian explosion itself.2
The late Precambrian-era sediments around the world have yielded fourmain types of fossils, all of which are dated between about 570 and 543
million years ago. The first group consists of the Precambrian sponges
mentioned in the previous chapter. These animals first arose about 570 to 565
million years ago.

FIGURE 4.1
Examples of enigmatic Ediacaran fossils: Dickinsonia, Spriggina, andCharnia. Fossil photos in Figures 4.1a and 4.1b courtesy Peterson, K. J.,
Cotton, J. A., Gehling, J. G., and Pisani, D., “The Ediacaran Emergence of
Bilaterians: Congruence Between the Genetic and the Geological Fossil
Records,” Philosophical Transactions of the Royal Society B, 2008, 363(1496): 1435–43, Figure 2, by permission of the Royal Society.
The second is the distinctive group of fossils from the Ediacaran Hills. The
creatures fossilized there include such well-known forms as the flat, airmattress-like body of Dickinsonia; the enigmatic Spriggina, with its elongatedand segmented body and possible head shield; and the frond-like Charnia (seeFig. 4.1). These organisms were at least mostly soft-bodied and are large
enough to identify with the naked eye.
The third group includes what are called trace fossils, the possible remainsof animal activity such as tracks, burrows, and fecal pellets. Somepaleontologists have attributed these trace fossils to ancient worms.
The fourth group is the fossils of what may be primitive mollusks, apossibility that received support from a recent discovery in the cliffs along theWhite Sea in northwestern Russia. There, Russian scientists have discovered
thirty-five distinctive specimens of a possible mollusk called Kimberella,probably a simple animal form. These new White Sea specimens, dated to
550 million years ago, suggest that Kimberella “had a strong [though nothard], limpet-like shell, crept along the sea floor, and resembled a mollusk.”3
Paleontologist Douglas Erwin, of the Smithsonian Institution, hascommented: “It’s the first animal that you can convincingly demonstrate ismore complicated than a flatworm.”4 Additionally, seafloor tracks from
Precambrian sediments in both Canada and Australia have been attributed tomollusks, since the tracks resemble what might have been left by a row ofsmall teeth on the tongue-like ribbon of some mollusks as they scraped foodparticles off the seafloor. In this case, Kimberella may well have been the
track maker.5 The authors of the original descriptive paper in Nature, Mikhail
Fedonkin, from the Russian Academy of Sciences, and Benjamin Waggoner,
then at the University of California at Berkeley, conclude as much andsuggest that such creatures “began to diversify before the beginning of theCambrian.”6 Paleontologists, however, are still weighing the evidence.7
THE SIGNIFICANCE OF THE EDIACARAN
So do either the remains of the specific organisms from the Ediacaran Hills or
the Ediacaran or Vendian biota as a whole solve the problem of the Cambrian
explosion? Do these exotic forms represent a kind of fuse to the Cambrian
explosion that eliminates the need to explain the rapid emergence of novel
body plans and forms of animal life? There are many good reasons to doubt
this idea.
First, with the exception of sponges and the possible exception ofKimberella, the body plans of visibly fossilized organisms (as opposed to
trace fossils) bear no clear relationship to any of the organisms that appear in
the Cambrian explosion (or thereafter).8 The most noted Ediacaran organisms
such as Dickinsonia, Spriggina, and Charnia do not have an obvious head, amouth, bilateral symmetry (see below), a gut, or sense organs such as eyes.
Some paleontologists question whether these organisms even belong in the
animal kingdom.
Dickinsonia, for example, has been interpreted by University of Oregon
paleontologist Gregory Retallack as having “fungal-lichen” affinities, since its

mode of fossil preservation “is comparable not with that of soft-bodied
jellyfish, worms, and cnidarians, but with the fossil record of fungi andlichens.” Dickinsonia’s taxonomic position, Retallack notes, has long been an
unsolved puzzle. “Biological affinities of Dickinsonia remain problematic,”
he writes, since it has been “variously considered a polychaete, turbellarian or
annelid worm, jellyfish, polyp, xenophyophoran protist, lichen ormushroom.”9Similar disputes have characterized attempts to classify Spriggina. In
1976, Martin Glaessner, the first paleontologist to study the Ediacaran indetail, described Spriggina as a possible annelid polychaete worm basedlargely upon its segmented body. Nevertheless, Simon Conway Morris later
rejected that hypothesis because Spriggina shows no evidence of the
distinguishing “chaetes,” leg-like bristled protrusions that polychaete worms
possess. Glaessner himself later repudiated his original hypothesis that
Spriggina was ancestral to polychaetes, noting that Spriggina “cannot be
considered as a primitive polychaete, having none of the possible ancestralcharacters indicated . . . by specialists on the systematics and evolution of thisgroup.”10
In 1981, paleontologist Sven Jorgen Birket-Smith produced areconstruction of a Spriggina fossil showing that it possessed a head and legs
similar to those of trilobites, though examinations of subsequent Spriggina
specimens have shown no evidence of it possessing limbs of any kind.11 In
1984, Glaessner weighed in on this discussion as well. He argued that
“Spriggina shows no specific characters of the arthropods, particularly of thetrilobites.”12 He also noted that the body segmentation of Spriggina, and “itsknown appendages are at the level of polychaete annelids”13 (although, as
noted, by this time he had rejected Spriggina as a possible polychaete
ancestor). Instead, he proposed that Spriggina represented a side branch on
the animal tree of life—one that resulted, “metaphorically” perhaps, in “anunsuccessful attempt to make an arthropod.”
In a presentation to the Geological Society of America in 2003, geologist
Mark McMenamin revived the idea that Spriggina might represent a trilobite
ancestor. He argued that several features present in Spriggina fossils arecomparable to those in trilobites such as “the presence of genal spines” and an
effaced head or “cephalic region.”14 Nevertheless, many Ediacaran experts,
including McMenamin, have also noted that Spriggina specimens show noevidence of eyes, limbs, mouths, or anuses, most of which are known fromfossil trilobites.15 Other paleontologists remain skeptical about whether
Spriggina does in fact exhibit genal spines, noting that good specimens seem

to show relatively smooth edges with no protruding spines.16 In addition,
analysis of the best specimens of Spriggina shows that it does not exhibit
bilateral symmetry, undermining earlier attempts to classify it as a bilateriananimal, and by implication an arthropod.17 Instead, Spriggina exhibits
something called “glide symmetry” in which the body segments on either sideof its midline are offset rather than aligned.18 As geologist Loren Babcock of
Ohio State University notes, “The zipper-like body plans of some Ediacaran(Proterozoic) animals such as Dickinsonia and Spriggina involve right andleft halves that are not perfect mirror images of each other.”19 The lack ofsuch symmetry, a distinctive feature of all bilaterian animals, and the absencein Spriggina specimens of many other distinguishing features of trilobites, hasleft the classification of this enigmatic organism uncertain.
Paleontologists James Valentine, Douglas Erwin, and David Jablonski
distill the confusing welter of conflicting views about the Ediacaran fossils:“Although the soft-bodied fossils that appear about 565 million years ago areanimal-like, their classifications are hotly debated. In just the past few years
these fossils have been viewed as protozoans; as lichens; as close relatives of
the cnidarians; as a sister group to cnidarians plus all other animals; asrepresentatives of more advanced, extinct phyla; and as representatives of a
new kingdom entirely separate from the animals.”20 What’s more, Valentine,
Erwin, and Jablonski note that those paleontologists who do regard the
Ediacaran fauna as animals rarely classify them the same way, underscoring
their lack of clear affinities to any known animal groups. As they note, “Stillother specialists have parceled the fauna out among living phyla, with someassigned to the Cnidaria and others to the flatworms, annelids, arthropods andechinoderms.”21 The uncertain standing of these fossilized forms is partly due
to their early extinction, but it also stems from an absence of defining
characteristics shared with known groups. They conclude: “This confusingstate of affairs arose because these body fossils do not tend to share definitive
anatomical details with modern groups, and thus the assignments must be
based on vague similarities of overall shape and form, a method that has
frequently proved misleading in other cases.”22
Other leading paleontologists also doubt that the Cambrian animals
descended from these Ediacaran forms. In a phylogenetic diagram showing
the evolutionary relationship of Precambrian and Cambrian fossils, Oxford
biologists Alan Cooper and Richard Fortey depict the Ediacaran fauna aslying on a line of descent separate from the Cambrian animals rather thanbeing ancestral to them.23 In another paper, Fortey asserts that the beginningof the Cambrian “saw the sudden appearance in the fossil record of almost all

the main types of animals (phyla) that still dominate the biota today.” Heconcedes that there are a variety of fossils in older strata, but insist that “theyare either very small (such as bacteria and algae) or their relationships to theliving fauna are highly contentious, as is the case with the famous soft-bodied
fossils from the late Precambrian Pound Quartzite, Ediacara, South
Australia.”24
Similarly, paleontologist Andrew Knoll and biologist Sean B. Carroll haveargued: “It is genuinely difficult to map the characters of Ediacaran fossils
onto the body plans of living invertebrates.”25 Although many paleontologists
initially showed interest in the possibility that the Cambrian animal forms
might have evolved from the Ediacaran organisms, paleontologist Peter Ward
explains that “later study cast doubt on the affinity between these ancientremains preserved in sandstones [the Australian Ediacaran] and living
creatures of today” (that is, animals representing phyla that first arose in the
Cambrian).26 As Nature recently noted, if the Ediacaran fauna “were animals,
they bore little or no resemblance to any other creatures, either fossil or
extant.”27This absence of clear affinities has led an increasing number of
paleontologists to reject ancestor-descendant relationships between all but (atmost) a few of the Ediacaran and Cambrian fauna. Nevertheless, some havesuggested that trace fossils may establish a link. In an authoritative 2011
paper in the journal Science, Douglas Erwin and colleagues described thediscovery of Ediacaran trace fossils consisting of surface tracks, burrows,
fecal pellets, and feeding trails, which, they argue, though small, could only
have been made by animals such as worms with a relatively high degree ofcomplexity.28 On the basis of these findings, Erwin and other paleontologists
have argued that these trace fossils suggest the existence of organisms with ahead and tail, nervous systems, a muscular body wall allowing creeping or
burrowing, and a gut with mouth and anus.29 Other paleontologists suggestthat these characteristics may indicate the presence of a Precambrian mollusk
or a worm phylum.30
Graham Budd, a British paleontologist who works at Uppsala University
in Sweden, and others, have disputed these associations. Budd and geologist
colleague Sören Jensen argue that many alleged trace fossils actually show
evidence of inorganic origin: “There are numerous reports of older trace
fossils, but most can be immediately shown to represent either inorganic
sedimentary structures or metaphytes [land plants], or alternatively they havebeen misdated.”31 Still others have suggested that surface tracks and trails
could have been left by mobile single-celled organisms, including a known

form of a giant deep-sea protist that leaves bilaterian-like impressions. As one
paper explains, “Some such traces date back to 1.5 billion to 1.8 billion years
ago, which outdates even the boldest claims of the time of origin of animal
multi-cellularity and forces researchers to contemplate the possibility of an
inorganic or bacterial origin.”32
Even the most favorable interpretations of these trace fossils suggest thatthey indicate the presence of no more than two animal body plans (of largely
unknown characteristics). Thus, the Ediacaran record falls far short ofestablishing the existence of the wide variety of transitional intermediates thata Darwinian view of life’s history requires. The Cambrian explosion attests tothe first appearance of organisms representing at least twenty phyla and many
more subphyla and classes, each manifesting distinctive body plans. In a best
case, the Ediacaran forms represent possible ancestors for, at most, four
distinct Cambrian body plans, even counting those documented only by trace
fossils. This leaves the vast majority of the Cambrian phyla with no apparent
ancestors in the Precambrian rocks (i.e., at least nineteen of the twenty-threephyla present in the Cambrian have no representative in Precambrianstrata).33
Third, even if representatives of four animal phyla were present in the
Ediacaran period, it does not follow that these forms were necessarilytransitional or intermediate to the Cambrian animals. The Precambriansponges (phylum Porifera), for example, were quite similar to their Cambrianbrethren, thus demonstrating, not a gradual transformation from a simpler
precursor or the presence of an ancestor common to many forms, but quitepossibly only an earlier first appearance of a known Cambrian form. The
same may be true of whatever kind of worm may be attested by Precambriantracks and burrows.
Moreover, even assuming, as some evolutionary biologists do,34 that later
Cambrian animals had a sponge-like Precambrian ancestor, the gap incomplexity as measured by the number of cell types alone, to say nothing of
the specific anatomical structures and distinct modes of body plan
organization that are present in later animals but not in sponges, leaves a
massive discontinuity in the fossil record that requires explanation (much likethe morphological gap between Spriggina and actual arthropods).
AN EDIACARAN MINI-EXPLOSION
The Ediacaran fossils themselves provide evidence of a puzzling leap inbiological complexity, though not one nearly great enough (or of the rightkind) to account for the Cambrian explosion. Before organisms like

Kimberella, Dickinsonia, and sponges appeared, the only living forms
documented in the fossil record for over 3 billion years were single-celledorganisms and colonial algae. Producing sponges, worms, and mollusks fromsingle-celled organisms is a little like transforming a spinning top into abicycle. The bicycle isn’t remotely as complex as the automobile sitting
beside it, but it represents an enormous leap in technological sophistication
over the spinning top. Likewise, although the humble Ediacaran biota look
simple beside most of the Cambrian animals, they represent an enormous leapin functional complexity over the single-celled organisms and colonial algaethat preceded them.
Thus, the Ediacaran biota attest to a separate sudden increase in biologicalcomplexity within a short window of geological time (about 15 million
years), following roughly 3 billion years in which only single-celledorganisms inhabited the earth.35 This leap in complexity, in a relatively shortspan of geological time, may well exceed the explanatory resources of natural
selection working on random mutations. We will return to that question inPart Two.
The Ediacaran fossils therefore do not solve the problem of the sudden
increase in biological form and complexity during the Cambrian. Instead, they
represent an earlier, if less dramatic, manifestation of the same kind ofproblem. To biology’s “big bang,”36 the Ediacaran biota add a significant“pow.” As paleobiologist Kevin Peterson, of Dartmouth College, and hiscolleagues note, these fauna represent “an apparent quantum leap in
ecological complexity as compared with the ‘boring billions’ [of years] thatcharacterize Earth before the Ediacaran,” even if these organisms are “still
relatively simple when compared with the Cambrian,” which they
characterize as another “quantum leap in organismal and ecologicalcomplexity.”37
Many paleontologists now refer to the Ediacaran radiation as an explosionin its own right.38 This Precambrian “pow” makes the problem of fossil
discontinuity only more acute, since credible intermediates leading to the
Ediacaran layers are completely nonexistent in the even more sparsely
populated strata beneath them.
Finally, even if one regards the appearance of the Ediacaran fossils as
evidence of a “fuse” leading to the Cambrian explosion as some haveproposed,39 the total time encompassed by the Ediacaran and Cambrianradiations still remains exceedingly brief relative to the expectations andrequirements of a modern neo-Darwinian view of the history of life. As I will
explain in more detail in Chapter 8, neo-Darwinism is the modern version ofDarwin’s theory that invokes random genetic changes called mutations as thesource of much of the new variation upon which natural selection acts. Likeclassical Darwinism, the neo-Darwinian mechanism requires great stretchesof time to produce novel biological form and structure. Yet, current studies ingeochronology suggest that only 40 to 50 million years elapsed between the
beginning of the Ediacaran radiation (570–565 million years ago) and the endof the Cambrian explosion (525–520 million years ago).40 To anyone
unfamiliar with the equations of population genetics by which neo-Darwinianevolutionary biologists estimate how much morphological change is likely tooccur in a given period of time, 40 to 50 million years may seem like aneternity. But empirically derived estimates of the rate at which mutations
accumulate imply that 40 to 50 million years does not constitute anything likeenough time to build the necessary anatomical novelties that arise in the
Cambrian and Ediacaran periods. I will describe this problem in more detailin Chapter 12.
Until recently, radiometric studies had estimated the duration of theCambrian radiation itself at 40 million years, a period of time so brief,
geologically speaking, that paleontologists had already dubbed it an“explosion.” The relative suddenness of the Cambrian explosion, even on theearlier measure of its duration, had already raised serious questions about theadequacy of the neo-Darwinian mechanism; consequently, it had also raisedquestions about whether a Darwinian understanding of the history of life
could be reconciled with the Cambrian and Precambrian fossil record. Thus,
treating the Ediacaran and the Cambrian radiations as one continuous
evolutionary event (itself an unrealistically generous assumption) only returns
the problem to its earlier (pre-zircon redating) status.
For all these reasons, the late Precambrian fossils have not solved, butinstead have deepened, the mystery of the origin of animal form. And few
leading Cambrian paleontologists, of whom I was aware on that September
evening in 2009 while preparing to answer questions at the University ofOklahoma, thought otherwise.
EDIACARAN EXOTICA
So what about the claim that certain exotic Ediacaran fossils are plausible
ancestors to the Cambrian animal forms, even if better-known Ediacaran
forms such as Dickinsonia, Charnia, and Spriggina are probably not? Did
these exotic forms solve the mystery of the Cambrian explosion?
Only a few years before my visit to the University of Oklahoma, I had
written a scientific review article with research help from several colleagues,

including a paleontologist and a marine biologist.41 (The latter was Paul
Chien, who helped discover the Precambrian sponge embryos discussed in theprevious chapter.) In our review article, I explained many of the problems
with treating the Ediacaran as transitional intermediates discussed above. In
the process of doing the research for that article, my colleagues and I
encountered few paleontologists who thought that Parvancorina, Arkarua(see Fig. 4.2), or Vernanimalcula represented definitive ancestors of theCambrian bilaterians, arthropods, or echinoderms. Could we have missed
something?
In fact, leading Cambrian authorities have dismissed associations between
these odd fossil forms and the Cambrian animals. Nevertheless, in his talkbefore the showing of our film, the local professor from the University ofOklahoma asserted that the rather indistinct fossil form found in the Ediacaran
Hills called Parvancorina represented a plausible ancestor of the arthropods.
Some have described Parvancorina as a shield-shaped fossil form with araised anchor-shaped ridge impressed atop it, bearing a superficial
resemblance in its shape to that of a trilobite—thus, the claim that it might
have represented an early arthropod. Yet leading Cambrian paleontologists
dispute this association. Cambrian expert James Valentine has argued that
Parvancorina is not convincing as an arthropod ancestor, and for goodreason. Parvancorina fossils lack a head, jointed limbs, and compound eyes,
all distinctive features of arthropods. Thus, Valentine noted that Parvancorina
fossils “have not been shown to share derived features” with arthropods.42

FIGURE 4.2
Figure 4.2a (left): Photograph of Arkarua fossil, courtesy Taylor & Francis,

Ltd. Figure 4.2b (right): Photograph of Parvancorina fossil, courtesyPeterson, K. J., Cotton, J. A., Gehling, J. G., and Pisani, D., “The Ediacaran
Emergence of Bilaterians: Congruence between the Genetic and the
Geological Fossil Records,” Philosophical Transactions of the Royal Society
B, 2008, 363 (1496): 1435–43, Figure 2, by permission of the Royal Society.
Valentine makes much the same point about the small disc-like imprintcalled Arkarua, one of the other Ediacaran forms cited by the University ofOklahoma professor that night at the Sam Noble Museum. Valentine points
out that it too lacks many distinctive features of the animal phylum to which it
is typically assigned. Indeed, those who propose Arkarua as an ancestor of theCambrian animals usually claim that it represents an early echinoderm (as theprofessor in Oklahoma did). Echinoderms include starfish, sand dollars, andother animals with five-fold symmetry extending from a central body
cavity.43 Some have perceived five tiny segmented divisions within thecircular impressions left by Arkarua, making them seem roughly similar tosome modern echinoderms. But that similarity has proven superficial at best.
Other paleontologists observe that Arkarua lacks a stereom, or water vascularsystem, a definitive diagnostic feature of echinoderms; thus, its “echinodermspecific features are not readily visible.”44 Valentine has argued that, absent
such telltale features, the relationship of Arkarua to echinoderms “remains
uncertain.”45
In the case of Vernanimalcula, the story is more complicated but equallyproblematic. Vernanimalcula is the name that Chinese paleontologists gave toan imprint in phosphorite sediment found in the Doushantuo Formation in
2004. They found the structure in 580- to 600-million-year-old rocks, making
the impression even older than the Ediacaran strata. The paleontologist David
Bottjer of the University of Southern California, and some Chinese
paleontologists (at least, initially), speculated that the Vernanimalcula imprint
might be the remains of an early bilaterian.46
Recall that bilaterians are animals whose parts found on one side of the
body midline are also found in mirror image on the other (as opposed to, say,a radially symmetric animal47). Figure 4.3 shows a picture of the structure of
Vernanimalcula first found in the Doushantuo Phosphorite formation. Somepaleontologists think that Vernanimalcula exhibits such bilateral symmetry
and thus might be ancestral to the bilaterian animals that later first appeared in
the Cambrian period.
But problems have emerged with this argument. First, the form of the
Vernanimalcula does not resemble any specific bilaterian animal. In addition,
recent scientific analyses of these remains have questioned whether this

imprint preserves the remains of animals and, therefore, bilaterians at all. For
example, in 2004, Stefan Bengtson and Graham Budd, two paleontologists
and Cambrian experts, published a detailed chemical and microscopic
analysis of these fossils in the journal Science.48 They concluded that thestructures preserved in phosphorite rocks had undergone significant alteration
by so-called diagenesis and taphonomic processes. Diagenesis refers mainly
to processes of chemical alteration that occur after sediments are depositedand before sedimentary rocks are fully hardened, or “lithified.” Taphonomic
processes are those that alter once living organisms after burial andpreservation in sediments.

FIGURE 4.3
Photograph of Vernanimalcula fossil. Courtesy American Association for the
Advancement of Science, from Chen, J.-Y., Bottjer, D. J., Oliveri, P., Dornbos,
S. Q., Gao, F., Ruffins, S., “Small Bilaterian Fossils from 40 to 55 Million
Years Before the Cambrian,” Science, 305 (July 9, 2004): 218–22, Figure 1b.
Reprinted with permission from AAAS.
Based on their microscopic analysis, Bengtson and Budd rejected the
hypothesis that these structures preserved the remains of an animal form.
Instead, they argued that the phosphorite imprint exhibited distinctive featuresof the chemically altered remains of one-celled microfossils—microfossils
that had been encrusted with layers of chemical residue from various

diagenetic processes.49
More recently, in 2012, Bengtson and three other colleagues publishedanother paper sharply critical of the view that Vernanimalcula represents anancestor of the bilaterian animals—or even an animal. They show that the“structures key to animal identity are effects of mineralization that do not
represent biological tissues.” For this reason they conclude: “There is noevidential basis for interpreting Vernanimalcula as an animal, let alone abilaterian.”50
Though the paper was titled “A Merciful Death for the ‘Earliest
Bilaterian,’ Vernanimalcula,” the authors were anything but merciful inwielding their arguments. Their article upbraided David J. Bottjer, the main
paleontologist who has promoted the interpretation of Vernanimalcula as abilaterian ancestor, for seeing what he wanted to see and disregarding theclear evidence of nonbiological mineralization. In a 2005 Scientific American
article, Bottjer interpreted Vernanimalcula as the “oldest fossil animal with abilaterian body plan yet discovered.” In that article, Bottjer claimed that
Vernanimalcula confirmed the “suspicion that complex animals have a much
deeper root in time” and “that the Cambrian was less of an explosion andmore of a flowering of animal life.”51 After unequivocally rejecting Bottjer’s
interpretation on the basis of their geochemical analysis, Bengtson and his
coauthors rebuked Bottjer in rather personal terms:
It is likely that the fossils referred to [as] Vernanimalcula wereinterpreted as bilaterians because this was . . . the explicit quarry of its
authors. If you know from the beginning not only what you are looking
for, but what you are going to find, you will find it, whether or not it
exists. As Richard Feynman (1974) famously remarked: “The firstprinciple is that you must not fool yourself—and you are the easiest
person to fool.” . . . Once you have fooled yourself you will fool otherscientists.52
Bengtson and his colleagues insist that however much a few
paleontologists such as Bottjer might have wanted to “heap” “evolutionary
significance” on Vernanimalcula in order to relieve their cognitive dissonanceabout the Cambrian explosion, the evidence does not bear the weight ofinterpretation that had been placed upon it. Thus, they conclude
Vernanimalcula should be “laid to a merciful rest,” since the interpretation ofit had “taken on a life of its own, a life it never had.”53

A DEEPER PROBLEM
Though back in 2009, Jonathan Wells and I didn’t know about the most recent
critical analysis of Vernanimalcula’s pretentions, we did know that manyleading paleontologists had rejected attempts to identify Vernanimalcula as an
animal form. Thus, during the question-and-answer period following the film,
Jonathan Wells explained why these and other obscure and enigmatic
Precambrian fossils (or imprints) failed to qualify as convincing precursors to
any of the Cambrian animals, citing the work of leading authorities inpaleontology. In each case, he noted that similarities between the Ediacaran
forms and later Cambrian animals had proven superficial, because the
Ediacaran forms lacked many key diagnostic features of specific Cambrianphyla.
At the same time, as I later reflected on the lecture, I recognized a deeper
problem with attempts to resolve the mystery of the Cambrian explosion by
pointing to a few Precambrian fossils. Many defenders of the Darwinian
picture of the history of life seemed to assume that the discovery of any
alleged Precambrian animal forms, however implausible as ancestors ofspecific Cambrian animals or however sparsely distributed in the vast
sequences of Precambrian strata, would solve the mystery of the Cambrian
explosion, especially if these forms exemplified some abstractly perceived
commonality such as bilateral symmetry.
To see what’s wrong with this way of thinking, imagine an ambitious
distance swimmer claiming that it would be possible to swim between
California and Hawaii over a period of many months or years because of thesmall islands that provide way stations where he could eat, rest, and overnightat each stage along his marathon journey. But instead of showing that anarchipelago dotting the route between California and Hawaii at reasonably
accessible intervals actually exists, he points to a couple of barren atolls in theSouth Pacific far from the most likely course to Hawaii. Clearly, in that case,the claims of our intrepid hypothetical swimmer would not be credible. In asimilar way, the claims of those who assert that a few isolated andanatomically enigmatic forms of life in the Precambrian solve the problem of
the Cambrian explosion also lack credibility.
To appreciate another aspect of this problem, let’s revisit the claims about
Vernanimalcula as a possible ancestor of all the bilaterian phyla. On the one
hand, for such a form to qualify as the ancestor common to a large number of
specific phyla (such as the many bilaterian phyla that arise in the Cambrian),
it must exhibit the basic bilaterian characteristics such as bilateral symmetry
and what is called “triploblasty,” the presence of three distinct tissue layers

(endoderm, mesoderm, and ectoderm). At the same time, a viable candidate
for the role of common ancestor cannot by definition manifest any of thedifferentiating characteristics that distinguish the individual Cambrian phyla
and their respective body plans from each other. For example, any bilaterianthat manifests the characteristic exoskeleton of, say, an arthropod cannot also
qualify as a plausible ancestor of a chordate, because chordates have internal
skeletons or notochords. The logic of these distinct body designs precludes
sharing both anatomical characteristics. For this reason, any hypotheticalbilaterian common ancestor could only have existed as a kind of lowest
anatomical common denominator, or what evolutionary biologists call a“ground plan,” having only those few features that are common to all of theanimal forms that allegedly evolved from it.
But this creates a dilemma. If a fossilized form is simple enough to qualify
as the common ancestor of later highly differentiated bilaterian phyla, then it
will necessarily lack most of the important distinguishing anatomical featuresof those specific phyla. That means that all the interesting anatomical
novelties that differentiate one phylum from another must arise along theseparate lineages branching out from the alleged common ancestor well after
its origin in the fossil record. Heads, jointed limbs, compound eyes, guts,
anuses, antennae, notochords, stereoms, lophophores (a tentacled feedingorgan), and numerous other distinguishing characteristics of many different
animals must come later on many distinct lines of descent. Yet the gradualevolutionary origin of these characteristics is not documented in the
Precambrian fossil record. These characteristics do not appear until they arise
suddenly in the Cambrian explosion.
For this reason, indistinct fossils such as Vernanimalcula—even if we takethem as representing a common ancestor of many bilaterians—document littleof the Darwinian story of the history of animal life. Hugely significant gaps in
the fossil record would still remain, because the Precambrian fossil record
simply does not document the gradual emergence of the crucial distinguishing
characteristics of the Cambrian animals. The important anatomical novelties
that define the individual Cambrian phyla as well as their first clear
representatives arise as suddenly as ever.
To say that a form such as Vernanimalcula, or any of the other relatively
indistinct Ediacaran forms, solves the problem of the missing Precambrianfossil record would be a bit like saying that a metal cylinder demonstrates all
the steps involved in the construction of a toaster, automobile, submarine, or
jet airplane simply because all these technological objects utilize “metal
enclosures.” It’s true that each of these complex systems uses metal
enclosures, but the presence of an enclosed metal surface is only a necessary,and not nearly a sufficient, condition of the origin of these various
technological systems. Similarly, finding a simple but otherwise unadorned
bilaterally symmetric form of life would hardly solve the problem of fossil
discontinuity, because it would not by itself document the emergence of theunique characteristics of the individual bilaterian animals.
This paradox is well known to paleontologists who work on the Cambrianradiation. Charles Marshall and James Valentine, for instance, describe thedifficulty of attempting to characterize an “undiagnostic” group, by which
they mean a possible ancestral “stem” group that lacks the specialized
characteristics of its presumptive evolutionary progeny. They write:
When trying to unravel the origins of the animal phyla . . . the hardest
to examine is the phase between the actual cladogenic origin of aphylum and the time that it acquired its first phylum-specificcharacteristic(s). Even if we have fossils from this phase in a phylum’s
history, we will not be able to prove their kinships at the level ofphyla.54
Thus, even if Vernanimalcula, or some other fossil form, were simple enoughand animal-like enough to qualify as a so-called ur (or original) form ofanimal life, it would paradoxically, for just that reason, be incapable ofestablishing itself as an unequivocal common ancestor of some specificCambrian phylum.
And there’s no relief in the other direction. If an alleged ancestral form
manifests the distinguishing features of one of the specific Cambrian phyla—
if, for example, Vernanimalcula or some other isolated form presented aconvincing set of distinctively arthropod or chordate or echinoderm
characteristics, then the very presence of those features would necessarily
preclude the possibility of that specific animal form representing the common
ancestor of all other Cambrian forms. The more an animal form manifests thecharacteristics of one phylum or group within the phylum, the less plausible it
becomes as the ancestor of all the other animal phyla.
And that is the dilemma in a nutshell. Highly differentiated and complex
Precambrian forms by themselves could not have been ancestors common to
all the Cambrian phyla; whereas undifferentiated forms simple enough tohave been ancestral to all the Cambrian phyla leave no evidence, bythemselves, of the gradual emergence of the complex anatomical novelties
that define the Cambrian animals. Either way—whether the few alleged
Precambrian ancestors are viewed as simple and relatively undifferentiated orcomplex and highly differentiated—the fossil record, given its otherwise

pervasive pattern of discontinuity, does not establish the gradual evolution ofnumerous anatomical and morphological novelties. Instead, only a true seriesof transitional intermediates in which the fossil record documents both theexistence of an original animal form and the gradual appearance of the key
distinguishing anatomical features and novelties (and the Cambrian animals
themselves) would remedy this deficiency. And yet that is precisely what the
Precambrian fossil record has failed to document.
As Graham Budd and Sören Jensen state, “The known[Precambrian/Cambrian] fossil record has not been misunderstood, and there
are no convincing bilaterian candidates known from the fossil record until justbefore the beginning of the Cambrian (c. 543 Ma), even though there areplentiful sediments older than this that should reveal them.”55 Thus they
conclude, “The expected Darwinian pattern of a deep fossil history of thebilaterians, potentially showing their gradual development, stretching
hundreds of millions of years into the Precambrian, has singularly failed tomaterialize.”56
DILEMMA ON DISPLAY
During the question-and-answer session that followed the screening of
Darwin’s Dilemma, none of the University of Oklahoma Ph.D. students orscience faculty who attended the museum-sponsored lecture challenged mycolleague Jonathan Wells when he explained why leading paleontologists do
not think the exotic Precambrian forms cited in the lecture were ancestors ofCambrian forms. This nonreaction seemed a little odd given the stress themuseum’s own expert had laid on these claims, and given that he had madethese claims rather emphatically in the same building to many of the same
people just three hours earlier.
On our flight out of town the next day, Jonathan Wells told me somethingthat cast our experience there in an even odder light. He’d had a chance towalk around the Sam Noble Science Museum after the lecture and before our
event. He discovered that the museum has a display that vividly illustrates theseverity of what we called Darwin’s dilemma. Wells recorded some of his
observations on his return to Seattle. One part of the account of what he saw
while touring the museum’s own display about the Cambrian explosion is
worth quoting at length:[The display] seemed factually accurate for the most part, emphasizing(among other things) that many of the Cambrian explosion fossils were
soft-bodied—which puts the lie to the common explanation that theirprecursors are absent from the fossil record because they lacked hardparts. The exhibit also made it clear that the Ediacaran fossils went
extinct at the end of the pre-Cambrian, so (with a few possible
exceptions) they could not have been ancestral to the Cambrian phyla.
One particular panel in the exhibit caught my attention. It showed overa dozen of the Cambrian phyla at the top of a branching tree with asingle trunk, but none of the branch points corresponded to a real living
thing. Instead, the branch points were artificial technical categories
such as “Ecdysozoa,” “Lophotrochozoa,” “Deuterostomia,” and“Bilateria.” The artificiality of the branch points emphasized that thebranching-tree pattern imposed on the fossil evidence was itself an
artificial construct.
So, after all the controversy, it turned out that the museum that hadsponsored the lecture denying Darwin’s Cambrian dilemma itself has an
excellent display indicating that the expected ancestral forms of the Cambriananimals—the very ones that Darwin hoped to find a hundred and fifty years
ago—are still missing from the Precambrian fossil record. But then why
would the museum sponsor the presentation that it did? It’s hard to say, I
suppose, but I’ve seen this dynamic before in discussions about Darwinianevolution. Evolutionary biologists will acknowledge problems to each otherin scientific settings that they will deny or minimize in public, lest they aid
and abet the dread “creationists” and others they see as advancing the cause of
unreason. Perhaps just our presence on campus raising questions about
contemporary Darwinism made them feel defensive on behalf of “science.”
It’s an understandable, if ironic, human reaction, of course, but one that in theend deprives the public of access to what scientists actually know. It also
perpetuates the impression of evolutionary biology as a science that has
settled all the important questions at just the time when many new andexciting questions—about the origin of animal form, for example—arecoming to the fore.

5
The Genes Tell the Story?
Reconstructing the history of life has a lot in common with detective work.
Neither detectives nor evolutionary biologists can directly observe the eventsin the past that interest them most. Detectives typically did not see the crime
occur. Evolutionary biologists did not witness the origin of animals or othergroups of organisms. Yet this limitation doesn’t mean either group ofinvestigators lacks the evidence to determine with some confidence what
happened. Detectives and evolutionary biologists as well as many otherhistorical scientists—paleontologists, geologists, archeologists, cosmologists,and forensic scientists—do this regularly, based on careful inference from theclues or evidence left behind.
Many evolutionary biologists have commented on the forensic nature of
their work. Here’s how Richard Dawkins puts it: “I have used the metaphor ofa detective, coming on the scene of the crime after it is all over andreconstructing from the surviving clues what must have happened.”1
Perhaps the most obvious surviving traces of ancient life are fossils. But asevolutionary biologists and paleontologists have come to realize that the
Precambrian fossil record has not furnished the confirmation that Darwin
hoped it would, many have looked to other kinds of clues to establish thegradual emergence of Cambrian animal life from a common ancestor.
In this effort, contemporary evolutionary biologists have followed theexample of Darwin himself. Though Darwin argued that a general progressionof simpler to more complex forms of life in the fossil record meshed nicely
with his theory, he was acutely aware that the discontinuity of the fossil
record, particularly as evidenced in Precambrian and Cambrian strata, did not.
This is why he emphasized other types of evidence to establish his theory of
universal common descent.
In a famous chapter in On the Origin of Species titled “The Mutual
Affinities of Organic Beings,” Darwin made his case not on the basis of thefossil evidence, but on the basis of similar anatomical structures in many
distinct organisms. He noted, for example, that the forelimbs of frogs, horses,

bats, humans, and many other vertebrates exhibited a common five-digit(“pentadactyl”) structure or organization (see Fig. 5.1). To explain such“homologies,” as he called them, Darwin posited a vertebrate ancestor thatpossessed pentadactyl limbs in rudimentary form. As a menagerie of modern
vertebrates evolved from this common ancestor, each retained in its own way
the basic pentadactyl mode of organization. For Darwin, his theory of descentwith modification from a common ancestor explained these similarities better
than the received view of many older nineteenth-century biologists such as
Louis Agassiz or Richard Owen, both of whom thought homologies reflected
the common design plan of a creative intelligence.

FIGURE 5.1
The common five-digit pattern of the pentadactyl limb as manifested in four
modern animals. Copyright Jody F. Sjogren. Used with permission.
In reconstructing the evolutionary history of life, most evolutionary
biologists today emphasize the importance of homology. They assume thatsimilarities in anatomy and in the sequences of information-bearing
biomacromolecules such as DNA, RNA, and protein point strongly to acommon ancestor.2 They also assume that the degree of difference in suchcases is on average proportional to the time elapsed since the divergence froma common ancestor. The greater the difference in the common feature ormolecular sequence, the farther back the ancestor from which the feature orsequence arose.
Evolutionary biologists have used this approach to try to discern theevolutionary history of the Cambrian animals. If the Precambrian fossil record
refuses to disclose the secrets of Precambrian evolution, so goes the thinking,perhaps the study of comparative anatomy and molecular homologies will.
Given the well-established problem with the fossil evidence, many
evolutionary biologists now particularly emphasize the importance of clues
from molecular genetics. As evolutionary biologist Jerry Coyne, of the
University of Chicago, notes, “Now we have a powerful, new, andindependent way to establish ancestry: we can look directly at the genes
themselves. By sequencing the DNA of various species and measuring how
similar these sequences are, we can reconstruct their evolutionary
relationships.”3
There are two aspects of this endeavor. First, by analyzing the genes ofexisting animals representing phyla that first arose in the Cambrian, scientists
have attempted to establish when the common ancestor of the Cambriananimal forms lived. This effort has generated what is known as the “deepdivergence hypothesis,” which holds that the common ancestor of all animallife arose long before the Cambrian explosion. Second, by analyzing
anatomical and molecular similarities, biologists have attempted toreconstruct the Precambrian–Cambrian tree of life, mapping the course ofevolution during a cryptic period before the Cambrian.
Defenders of neo-Darwinism assert that these techniques have produced acoherent evolutionary picture of the early history of animal life. They assertthat clues from the realm of genetics point unequivocally to Precambrianancestral forms and to an evolutionary history that fossils have failed to
document.
This chapter will examine what genes tell us about the alleged universal
common ancestor of all animals; the next chapter will consider whether the
analysis of genes (and other features of organisms) yield a coherent treelike
picture of the Precambrian prehistory of animal life. Genetic analyses haveindeed revealed a trove of clues. The question is: Do those genetic clues
establish the Precambrian ancestor and history that fossils have failed to
document, or, as sometimes occurs in criminal investigations, has there been arush to judgment?
DEEP DIVERGENCE
Many paleontologists and evolutionary biologists now concede that the longsought-after Precambrian fossils, those necessary to document a Darwinianaccount of the origin of animal life, are missing.4 Scientists are especiallycandid about this when addressing each other in the technical peer-reviewed
literature. Often, however, defenders of evolutionary orthodoxy raise anotherpossibility—that the common ancestor of the Cambrian animals has been
documented after all, not by fossil evidence, but by molecular or genetic
evidence of what they call a “deep divergence” of animal life. In making suchclaims, these biologists clearly privilege molecular evidence over evidence
from the fossil record.
Proponents of deep divergence don’t deny that the fossil evidence hascome up short. Instead, they adopt one of the versions of the artifact
hypothesis to account for that missing evidence. They then argue that there
was no “explosion” of animal forms in the Cambrian, but rather a “long fuse”
of animal evolution and diversification lasting many millions of years leading
up to what only looks like an “explosion” of animal life in the Cambrian, but
this evolutionary history was hidden from the fossil record. Indeed, they argue
that molecular evidence establishes a long period of undetected or cryptic
evolution in Precambrian times, beginning from a common ancestor some 600
million to 1.2 billion years ago, depending upon which study of the molecular
genetic data they cite. If correct, the Cambrian phyla may have had many
hundreds of millions of years to evolve from a common ancestor.5
THE MOLECULAR CLOCK
Advocates of deep divergence use a method of analysis known as the“molecular clock.” Molecular clock studies also assume that the extent towhich sequences differ in similar genes in two or more animals reflects theamount of time that has passed since those animals began to evolve from acommon ancestor. A small difference means a short time; a big difference, along time. To determine exactly how short or long, these studies estimate themutation rate by analyzing genes in two species or taxa that are thought tohave evolved from an ancestor whose presence in the fossil record can bediscerned and dated accurately. For example, many molecular-clock studies ofbirds and mammals are calibrated based on the age of an early reptile thought
to be the most recent common ancestor of both.

FIGURE 5.2
The idea behind the molecular clock. The two animals and their homologous
gene sequences at the right of the figure show the molecular distance between
two present-day animals, that is, how many mutational differences haveaccumulated over time since they diverged on the tree of life. The animal at
the left of the figure (a mammal-like reptile) represents the common ancestor
from which these animals presumably evolved. Knowing how long ago thecommon ancestor (the mammal-like reptile) lived, and how many mutational
differences have accumulated in its descendants during that time, allows
scientists to calculate a mutation rate. In theory, once the mutation rate has
been determined, it can be used to calculate the divergence time of otherpresent-day species, after their homologous genes have been compared for
differences.
Genetic comparisons enable evolutionary biologists to estimate the numberof mutational changes since divergence, and dating of the strata containing
presumed fossil ancestors tells how long ago the divergence occurred.
Assuming that different lineages evolve at the same rate,6 together the twopieces of information enable evolutionary biologists to calculate a baseline
mutation rate. They can then use that rate to determine how long ago someother pair of animals diverged from each other on the evolutionary tree (seeFig. 5.2).7
Advocates of the deep-divergence hypothesis have applied this method toanalyzing similar genes, RNA molecules, or proteins in pairs of animals
belonging to phyla that first arose in the Cambrian period. In this way they
estimate how long it took for the different animal phyla to diverge from acommon Precambrian ancestor.
DEEP AND DEEPER: EVIDENCE FOR DEEP DIVERGENCE
In the 1990s, evolutionary biologists Gregory A. Wray, Jeffrey S. Levinton,and Leo H. Shapiro performed a major study of Cambrian-relevant molecularsequence data. In 1996, they published their results in a paper entitled“Molecular Evidence for Deep Precambrian Divergences Among Metazoan
Phyla.”8 Wray’s team compared the degree of difference between the aminoacid sequences of seven proteins9 derived from several different modern
animals representing five Cambrian phyla (annelids, arthropods, mollusks,
chordates, and echinoderms). They also compared the nucleotide basesequences of a ribosomal RNA molecule10 from the same animal
representatives of the same five phyla.
The Wray study concluded that the common ancestor of the animal forms
lived 1.2 billion years ago, implying that the Cambrian animals took some
700 million years to evolve from this “deep-divergence” point before first
appearing in the fossil record. Wray and his colleagues attempted to explain
the absence of fossil ancestral forms during this period of time by postulatingthat Precambrian ancestors existed in exclusively soft-bodied forms,
rendering their preservation unlikely.
More recently, Douglas Erwin and several colleagues performed a study
comparing the degree of sequence difference between other genes—sevennuclear housekeeping genes11 and three ribosomal RNA genes12 across 113
different species of living Metazoa. (The term “Metazoa” refers to animals
with differentiated tissue. The term “metazoan” refers to one such animal or
can be used as an adjective, as in “the metazoan phyla.”) They estimated that“the last common ancestor of all living animals arose nearly 800 million years
ago.”13
Many similar studies affirm a very ancient or “stratigraphically deep”
divergence of the animal forms, in opposition to those who claim that the
Cambrian animals appeared suddenly within just a few million years.14 Eachof these studies affirms the gradual emergence of animal life that mostresearchers expected to find on the basis of a Darwinian picture of the historyof animal life. Indeed, a major aim of the Wray study was to challenge theview “that the animal phyla diverged in an ‘explosion’ near the beginning of
the Cambrian period.”15 Wray and his colleagues argue instead that “all mean
divergence time estimates between these four phyla and chordates, based on
all seven genes, substantially predate the beginning of the Cambrianperiod.”16 They conclude: “Our results cast doubt on the prevailing notionthat the animal phyla diverged explosively during the Cambrian or late
Vendian, and instead suggest that there was an extended period of divergenceduring the mid-Proterozoic, commencing about a billion years ago.”17
From an orthodox Darwinian point of view, the conclusions of thesestudies seem almost unavoidable since (1) the neo-Darwinian mechanism
requires vast amounts of time to produce anatomical novelty and (2) such
phylogenetic analyses assume that all the animal forms descended from acommon ancestor. Many evolutionary biologists claim that clues long hidden
in DNA now confirm these Darwinian axioms and, consequently, theexistence of an extremely ancient, Precambrian ancestor of the Cambriananimals. As Andrew Knoll, a Harvard paleontologist, states, “The idea thatanimals should have originated much earlier than we see them in the fossil
record is almost inescapable.”18
REASONABLE DOUBT
Nevertheless, there is now good reason to doubt this allegedly overwhelming
genetic evidence. In the idiom of our forensic metaphor, other material
witnesses (fossils) have already come forward to testify, the testimony of thegenes (and other key indicators of biological history) is grossly inconsistent,
and that genetic testimony has come to us through a translator, who is shaping
the way the jury perceives the evidence. Let’s look at each of these problems
in turn.
Fossil Testimony
Recall that the deep-divergence hypothesis has two components. One of them—a version of the artifact hypothesis—provides an explanation for why the
Precambrian ancestral fossils are missing. And here the deep-divergence
hypothesis first runs into trouble. As we saw in Chapter 3, there is no
currently plausible version of the artifact hypothesis. The preservation ofnumerous soft-bodied Cambrian animals as well as Precambrian embryos andmicroorganisms undermines the idea of an extensive period of undetectedsoft-bodied evolution. In addition, the claim that exclusively soft-bodied
ancestors preceded the hard-bodied Cambrian forms remains anatomicallyimplausible. A brachiopod cannot survive without its shell. An arthropod
cannot exist without its exoskeleton. Any plausible ancestor to suchorganisms would have likely left some hard body parts, yet none have beenfound in the Precambrian. Yet the deep-divergence hypothesis, whatever its

other merits, requires a viable artifact hypothesis to explain the absence offossilized Precambrian ancestors.
The Testimony of Genes: Conflicting Stories
There is a second, more telling reason to doubt the deep-divergence
hypothesis: the results of different molecular studies have generated widely
divergent results. Yet presumably there was only one common ancestor of all
the Metazoa and only one ultimate divergence point.
For example, comparing the Wray-led study and the Erwin-led study
generates a difference of 400 million years. In the case of other studies, evengreater differences emerge. Many other studies have thrown their own widely
varying numbers into the ring, placing the common ancestor of animals
anywhere between 100 million and 1.5 billion years before the Cambrian
explosion (some molecular clock studies, oddly, even place the common
ancestor of the animals after the Cambrian explosion).19 As Douglas Erwin,
writing with fellow paleontologists James Valentine and David Jablonski,
acknowledged in 1999: “Attempts to date those branching[s]” from acommon Precambrian ancestor “by using molecular clocks have disagreed
widely.”20 How can this be?
In the first place, different studies of different molecules generate widely
divergent dates. In addition to the studies I have already cited, a 1997 paper
by Japanese biologist Naruo Nikoh and colleagues examined two genes(aldolase and triose phosphate isomerase), and dated the split between
eumetazoa and parazoa—animals with tissues (like cnidarians) from those
without (like sponges)—at 940 million years ago.21 Compare that to a 1999
paper by Daniel Wang, Sudhir Kumar, and S. Blair Hedges based on the studyof 50 different genes, showing that “the basal animal phyla (Porifera,
Cnidaria, Ctenophora) diverged between about 1200–1500 Ma.”22
Sometimes contradictory divergence times are reported in the same article.
For instance, a refreshingly forthright paper by evolutionary biologist Lindell
Bromham of Australian National University and colleagues in Proceedings of
the National Academy of Sciences USA analyzed two different molecules,
mitochondrial DNA and 18S rRNA, to yield individual gene-based
divergence dates that differed by as much as 1 billion years.23 Another study
investigating the divergence between arthropods and vertebrates found that
depending on which gene was used, the divergence date might be anywhere
between 274 million and 1.6 billion years ago, the former date falling almost
250 million years after the Cambrian explosion.24 That paper in its conclusionchose to split the difference, confidently reporting an arithmetic average ofabout 830 million years ago. Likewise, bioinformaticians Stéphane ArisBrosou, now at the University of Ottawa, and Ziheng Yang, at University
College London, found that depending on which genes and which estimation
methods were employed, the last common ancestor of protostomes ordeuterostomes (two broadly different types of Cambrian animals) might have
lived anywhere between 452 million and 2 billion years ago.25
A survey of recent deep-divergence studies, by molecular evolutionists
Dan Graur and William Martin, notes one study in which the authors claim tobe 95 percent certain that their divergence date for certain animal groups falls
within a 14.2-billion-year range—more than three times the age of the earthand clearly a meaningless result.26 Graur and Martin conclude that many
molecular-clock estimates “look deceptively precise,” but, given the nature ofthis field, their “advice to the reader is: whenever you see a time estimate in
the evolutionary literature, demand uncertainty!”27 The title of their paper,
published in Trends in Genetics, made the point still more vividly: “Reading
the Entrails of Chickens: Molecular Timescales of Evolution and the Illusionof Precision.”
Sometimes even different studies of the same or similar groups ofmolecules have generated dramatically different divergence times. For
example, Francisco Ayala and several colleagues have recalculated thedivergence times of Metazoan phyla, using mostly the same protein-coding
genes as Wray’s team.28 Correcting for “a host of statistical problems”29 in
the Wray study, Ayala and colleagues found that their own estimates “areconsistent with paleontological estimates”—not with the deep-divergence
hypothesis. “Extrapolating to distant times from molecular evolutionary rates
estimated within confined data-sets,” they conclude, is “fraught withdanger.”30 Or as Valentine, Jablonski, and Erwin conclude, “The accuracy ofthe molecular clock is still problematical, at least for phylum divergences, forthe estimates vary by some 800 million years depending upon the techniques
or molecules used.”31 Reported Precambrian divergence times would varyeven more dramatically were it not that evolutionary biologists and moleculartaxonomists ignore certain molecules in their studies to avoid grossly
contradictory results. Consider, for example, histones—proteins found in all
eukaryotes involved in packing DNA into chromosomes. Histones exhibit
little variation from one species to the next.32 They are never used as
molecular clocks. Why? Because the sequence differences between histones,
assuming a mutation rate comparable to that of other proteins, would generate
a divergence time at significant variance with those in studies of many otherproteins.33 Specifically, the small differences between histones yield anextremely recent divergence, contrary to other studies. Evolutionary biologists
typically exclude histones from consideration, because those times do notconfirm preconceived ideas about what the Precambrian tree of life ought tolook like.
But that raises obvious questions. If we don’t have fossils documenting acommon animal ancestor, and if genetic studies produce such different andcontradictory divergence times, how do we know what the tree of life shouldlook like and when the first animals began to diverge from a common
ancestor? If histones change too slowly to provide an accurate calibration of
the molecular clock, then which molecules do change at the correct rate—and
how do we know that they do? The answer to these questions for mostevolutionary biologists usually runs something like this. We already knowthat the animal phyla evolved from a common ancestor and we also knowroughly when they did; therefore, we must reject studies based on histone
sequences because the conclusions of these studies would contradict that date.
But do we really know these things, and if so how? Assumptions about thewindow of time in which the first metazoan, the ancestor of all animals, musthave lived are clearly not derived from the testimony of molecular genetics
alone, since the results of sequence comparisons vary so greatly and include
dates, depending upon the molecule studied, that fall outside that window.
Instead, as one widely used textbook euphemistically puts it, evolutionary
biologists must choose “phylogenetically informative” data.34 By this, theymean sequences that exhibit neither too little nor too much variation—where
too much and too little are determined by preconceived considerations ofevolutionary plausibility, rather than by reference to independent criteria for
determining the accuracy of molecular methods.
The subjective quality of these conclusions, where scientists “cherry-pick”
evidence that conforms to favored notions and discard the rest, casts further
doubt on the extent to which molecular comparisons yield any clear historicalsignal. Only one divergence point could represent the actual universal
common ancestor of all animals. If, however, comparative sequence analyses
generate divergence times that are consistent with nearly all possible
evolutionary histories, with the divergence event ranging from a few million
to a few billion years ago, then clearly most of these possible histories must
be wrong. They tell us little about the actual time of the Precambriandivergence, if such an event really happened.
Questionable Assumptions

Other problems run even deeper, having to do with the assumptions that makecomparative sequence analyses possible in the first place. These comparisonsassume the accuracy of molecular clocks—that mutation rates of organisms
have remained relatively constant throughout geological time. These studies
also assume, rather than demonstrate, the theory of universal common
descent. Both assumptions are problematic.
Even if we assume that mutation and natural selection (and other similarly
undirected evolutionary processes) can account for the emergence of novel
proteins and body plans, we cannot also assume that the protein molecular
clock ticks at a constant rate. Unlike radiometric dating methods, molecular
clocks depend on a host of contingent factors. As Valentine, Jablonski, andErwin note, “Different genes in different clades evolve at different rates,
different parts of genes evolve at different rates and, most importantly, rates
within clades have changed over time.”35 So great is this variation that one
paper in the journal Molecular Biology and Evolution cautions, “The rate ofmolecular evolution can vary considerably among different organisms,
challenging the concept of the ‘molecular clock.’ ”36
Keep in mind too that molecular clocks are calibrated based on theestimated age of presumably ancestral fossils. If, however, such estimates areincorrect by even a few million years, or if the fossil used to calibrate themutation rate does not lie at the actual divergence point on the tree of life, theestimated mutation rate may be badly skewed. Calibration of molecular
clocks depends on an accurate understanding of the ancestor-descendant
relationships between fossils and their presumed descendant taxa. If the fossil
used to calibrate the divergence time of two later groups was not actually atrue ancestor, then the mutation-rate calculation based on that fossil’s age may
be grossly inaccurate. As Andrew Smith and Kevin Peterson note: “Molecular
clocks are not error-free and come with their own suite of problems. . . . The
accuracy of the technique depends upon having an accurate calibration point
or points, and a reliable phylogeny with correct branching order and branchlength estimates.”37 Because these conditions are rarely met, “the idea that
there is a universal molecular clock ticking away has long since been
discredited.”38
Applying the molecular clock to dating the alleged Precambrian ancestorof the animals further complicates matters. Because there are so few fossils in
the Precambrian and no clear ancestor-descendant lineages, the calibration of
the molecular clock must be done on the basis of very different fossil lineages
arising hundreds of millions of years later. Indeed, without evidence from thefossil record (older than 550 million years ago) with which to calibrate themolecular clock, any attempt to date the origin of the Cambrian animal phyla
becomes highly questionable.39 Perhaps for this reason, Valentine, Jablonski,
and Erwin have wondered whether “molecular clock dates can ever be applied
reliably to such geologically remote events as Neoproterozoic branchings
within the Metazoa.”40 (The Neoproterozic is the last Precambrian era.) Thesemethodological problems may help account for the cacophony of conflicting
results.
SMUGGLING IN DARWIN
A second crucial assumption behind the deep-divergence hypothesis is theidea of the common descent of all the animal forms—i.e., that all theCambrian animals evolved from a common Precambrian ancestor. As the
textbook Understanding Bioinformatics admits, “The key assumption madewhen constructing a phylogenetic tree from a set of sequences is that they are
all derived from a single ancestral sequence, i.e., they are homologous.”41 Or
as the Harvard University Press textbook The Tree of Life states, “We are
obliged to assume at first that, for each character, similar states arehomologous,” whereby “homologous” the text means characters are similar
because they share a common ancestor.42
This assumption (of universal common descent) raises the possibility thatthe ancestral entities represented by divergence points in these studies are
artifacts of the assumptions by which molecular data are analyzed. Indeed, thecomputer programs that are used to compare molecular sequences have been
written to produce trees showing common ancestors and branching
relationships regardless of the extent to which the genes analyzed may or may
not differ. Phylogenetic studies compare two or more gene sequences andthen use degrees of difference to determine divergence points and nodes on aphylogenetic tree. Inherent in that procedure is the assumption that the nodes
and divergence points existed in the past.
Thus, the deep-divergence studies do not, in any rigorous sense, establish
any Precambrian ancestral forms. Did a single, original metazoan or bilaterianancestor of the Cambrian animals actually exist? The Precambrian–Cambrianfossil record taken on its face certainly doesn’t document such an entity. But
neither do deep-divergence studies. Instead, these studies assume theexistence of such ancestors, and then merely attempt, given that assumption,
to determine how long ago such ancestors might have lived. One could argue
that the conflicting divergence points do at least show that some common
ancestor existed in the Precambrian, since, despite their conflicting results, alldivergence studies indicate at least that. But, again, to invoke molecularstudies that assume the existence of a common ancestor as evidence for suchan entity only begs the question. Certainly it provides no reason for using
molecular evidence to trump fossil evidence. Perhaps the Precambrian rocks
do not record ancestors for the Cambrian animals because none existed. To
foreclose that possibility, and to resolve the mystery of the missing
Precambrian ancestral fossils, evolutionary biologists cannot use studies thatassume the existence of the very entity their studies are thought to establish.
THE “SHMOO”: A CATCH-22 REVISITED
The concept of deep divergence raises another issue related to my discussion
at the end of the previous chapter about what would be required to document
the missing ancestral forms of the Cambrian animals. Recall that I argued
there that any plausible postulated common ancestor to all the animal phyla
must have necessarily lacked most (or all) of the specific anatomical featuresthat distinguish one phylum from another. The more arthropod-like ahypothetical animal form, the less plausible it would have been as an ancestor
to the chordates, mollusks, echinoderms, annelid worms, and vice versa. In
each case, the design logic and arrangement of parts necessary to provide thefoundation for one mode of animal life preclude it from providing thefoundation for other modes of animal life—just as a system of parts providing
one mode of transportation (with a bicycle, for example) will typically
preclude functioning as another (as with a submarine, for example).43
For this reason, biologists thinking about the characteristics of the earliest
ancestor of all the metazoan phyla—the actual animal at the deep-divergencepoint—have typically postulated an extremely simple form of life—what one
evolutionary biologist described to me as a “shmoo,” after the blob-likecartoon character made famous by Al Capp in the 1940s and 1950s. Somehave proposed that the ur-animal might have been something like aplacozoan, a modern amorphous animal with only four cell types and nobilateral symmetry.44 Other paleontologists have mainly characterized the
hypothetical ur-metazoan negatively, by reference to the characteristics that it
must not have had to be a plausible common ancestral form to all othermetazoa. (This need to characterize the ur-metazoan negatively has led someleading paleontologists to question whether the ur-animal can be describedaffirmatively with any specificity.45)
In any case, the need to characterize the ur-animal as an extremely simple“shmoo-like” form, lacking the numerous characteristics and anatomical
novelties present in the Cambrian animals, highlights a deep dilemma forevolutionary theorists. On the one hand, to be plausible as a common ancestor

of all the animal phyla, a hypothetical ur-metazoan must have few
characteristics of later metazoan forms. Indeed, the more plausible thehypothetical ancestor, the simpler it must be, meaning it will lack more of thespecific distinguishing features of the individual animal phyla. But that means
any evolutionary scenario for the origin of the animals that postulates such a“stripped down” animal form as its starting point will need to envision thosedistinguishing characteristics arising later. And the fewer the number ofcharacteristics in the hypothetical common ancestor, the more suchcharacteristics will need to arise later. This logical requirement implies, inturn, the need for an even deeper divergence point in Precambrian history andthe need for more time to produce these specific anatomical novelties—in
turn, exacerbating the problem of fossil discontinuity. The more plausible thehypothetical common ancestor, the deeper the necessary divergence point andthe greater the morphological discontinuity in the fossil record.
On the other hand, proposing a more complex (and more anatomicallydifferentiated) common ancestor closer in its affinities to some Cambriananimal forms, would eliminate the need for so deep a divergence point.
Nevertheless, it would also diminish the plausibility of such a hypotheticalancestor as an ur-metazoan common to all the other Cambrian animals.
Again, the more a hypothetical form resembles one of the specific animal
forms or phyla, the less plausible it will be as an ancestor of all the others.
And that is the dilemma. Could there have been an animal form simple
enough to serve as a viable ancestor common to all the animal phyla?
Perhaps. But positing such a form only deepens the required depth of thedivergence point and intensifies the already significant problem ofPrecambrian–Cambrian fossil discontinuity.
DEEP TROUBLE
Comparative genetic analyses do not establish a single deep-divergence point,
and thus do not compensate for a lack of fossil evidence for key Cambrianancestors—such as the ur-bilaterian or ur-metazoan ancestor. The results ofdifferent studies diverge too dramatically to be conclusive, or evenmeaningful; the methods of inferring divergence points are fraught withsubjectivity; and the whole enterprise depends upon a question-begging logic.
Many leading Cambrian paleontologists, and even some leading evolutionary
biologists, now express skepticism about both the results and the significanceof deep-divergence studies. For example, Simon Conway Morris has rejected
the idea that such studies should trump fossil evidence of a more explosive,
shallow and rapid Cambrian radiation. After assessing the inconsistent trackrecord of deep-divergence studies, he concludes, “A deep history extending toan origination in excess of 1,000 Myr [million years] is very unlikely.”46
Conway Morris is one of several leading evolutionary biologists andCambrian paleontologists who have expressed skepticism about thesestudies.47 In any case, there is now little reason to regard the deep-divergence
hypothesis as a genuine solution to the Cambrian conundrum.

6
The Animal Tree of LifeIn 2009, in honor of the bicentennial anniversary of Darwin’s birth, a piece ofartwork was created to adorn the ceiling of an exhibit room at the Natural
History Museum in London. A paper in the journal Archives of Natural
History noted that the inspiration for the artwork, titled “TREE,” came from adiagram that Darwin had sketched in one of his notebooks—a diagram thatlater came to be known as the “tree of life” (see Fig. 2.11a). One BBC radio
program called the TREE exhibit the “Darwinian Sistine Chapel.”1 Anotherarticle in Archives of Natural History, a journal published by the University of
Edinburgh, remarked that, “TREE celebrates Darwinian evolutionism” and“secular science and reason.”2
For many biologists, the iconic image of Darwin’s tree of life represents
perhaps the single best distillation of what the science of evolutionary biology
has to teach, namely the “fact of evolution,”3 apart from which “nothing in
biology makes sense.”4 Though the fossil record does not directly attest to
many of the expected intermediate forms represented on Darwin’s tree,
leading authorities assert that other lines of evidence, particularly fromgenetics, firmly establish Darwin’s tree as the correct picture of the history oflife.
In the previous chapter, we saw that there are many good reasons to doubt
the deep-divergence hypothesis and its claim to have determined, based upon
genetic evidence, the time at which the Cambrian animals began to evolvefrom specific Precambrian ancestors. Indeed, the idea that these studies canpinpoint when an ur-metazoan, or an ur-bilaterian, arose has engendered
increasing skepticism among a growing number of evolutionary biologists
and paleontologists.
The tree of life as a whole, however, is another matter. Many evolutionary
biologists think the case for universal common descent is something close tounassailable because, they argue, analysis of both anatomical and genetic
similarities converges on the same basic pattern of descent from a universal
common ancestor. As Richard Dawkins asserts, “when we look comparatively

at . . . genetic sequences in all these different creatures—we find the samekind of hierarchical tree of resemblance. We find the same family tree—albeit
much more thoroughly and convincingly laid out—as we did with . . . thewhole pattern of anatomical resemblances throughout all the living
kingdoms.”5 Likewise, Jerry Coyne argues that gene sequences independently
confirm the same set of evolutionary relationships—the same basic tree—
established from the analysis of anatomy.6 Oxford University chemist Peter
Atkins is even more emphatic: “There is not a single instance of the molecular
traces of change being inconsistent with our observations of wholeorganisms.”7
As a result of this confidence, evolutionary biologists often dismiss themissing Precambrian fossil precursors and intermediates as a minor anomaly—one awaiting explanation by an otherwise completely adequate theory of
the history of life. Because most evolutionary biologists are confident that asingle continuous tree, with a single root, best represents the history of life—and explains so many other diverse facts of biology—they continue to think
the same tree-like pattern also accurately describes the Cambrian explosion
and the Precambrian history of animal life. Moreover, when evolutionary
biologists reconstruct the phylogenetic history of a group (including animals),
they typically do so in a time-independent manner. Their concern is usually toestablish a relative order of branching along the tree of life, not to establish or“pinpoint” a series of absolute dates at which divergences occurred. Thus,
although deep-divergence studies do not establish the existence ofPrecambrian animal ancestors for all the reasons argued in the previous
chapter, the uncertainty surrounding the dates in these studies has not, formost evolutionary biologists, undermined their confidence in the overall treelike pattern of animal life. Instead, many evolutionary biologists believe thestrength of the case for the tree of life as a whole, based on other phylogenetic
studies of similar genes and anatomical traits, indirectly establishes theexistence of the missing evolutionary precursors of the Cambrian animals. As
Coyne explains, “It stands to reason that if the history of life forms a tree,with all species originating from a single trunk, then one can find a common
origin for every pair of twigs (existing species) by tracing each twig backthrough its branches until they intersect at the branch they have in common.
This node, as we’ve seen, is their common ancestor.”8On the basis of similar logic, evolutionary biologists have typicallyassumed that what they think is true of all other forms of life is true of theCambrian forms—that there must be a universal animal tree, the absence offossil evidence, and the conflicting results of deep-divergence studies,notwithstanding.
To assess the other evidence from genetics that supports this conclusion,
it’s useful to review how the case for the universal animal tree is similar to the
deep-divergence hypothesis and also how it is different. To establish both thefact and shape of the Darwinian animal tree of life, evolutionary biologists
have long used methods that assume that both molecular sequences andanatomical similarities provide an accurate historical signal about the past.
Like deep-divergence studies, these methods of “phylogenetic” reconstruction
assume that the species or larger groupings (taxa) are related by descent froma common ancestor. (The term phylogeny, again, refers to the evolutionary
history of a group of organisms. Thus, a “phylogenetic reconstruction” is anattempt to determine that history.) Such studies assume that the degree ofdifference between molecular or anatomical features in pairs of organisms
indicates how long ago they diverged from a common ancestor. They also use
independent calibrations of the molecular clock to calculate the exact
divergence times.9
Unlike deep-divergence studies, however, which attempt to establish just asingle divergence time—such as that of the common ancestor of all the animal
phyla—these more detailed phylogenetic studies seek to establish thecontours of the Precambrian tree of animal life. This involves assessing
degrees of relatedness among representatives of all the Cambrian phyla toestablish multiple divergence points and times (nodes on the tree of life) as
well as the relationships of the major Cambrian groups.
Investigators employ these methods even in the absence of corroborating
fossil evidence. In his textbook on fossils and evolution, following a full-page
depiction of the discontinuous appearance of the Cambrian animals in thefossil record, Occidental College geologist Donald Prothero explains, “If thefossil record is poor in one particular group, we look to other sources of data.”
He concludes that two such sources of data, anatomical and molecular data,
now “converge on a common answer”—one “that is almost certainly ‘thetruth’ (as much as we can use that term in science).”10
But is all of this true? Does analysis of the genetic and anatomicalsimilarity of the Cambrian animals really establish that the history of animallife is best depicted as a continuously branching tree? Does the pattern of abranching tree accurately depict the history of Precambrian and Cambriananimal life, and in so doing establish the existence of Precambrian forms thatthe fossil record fails to document?
THE PRECAMBRIAN AND CAMBRIAN TREE OF ANIMAL LIFE

History happened once. And if Richard Dawkins is correct that “there is, after
all, one true tree of life, the unique pattern of evolutionary branchings that
actually happened,”11 then evolutionary history also happened once.
Consequently, if we think of evolutionary trees describing the relationships ofanimal groups as hypotheses about an unobserved history (which is what theyare), then having two or more conflicting hypotheses about only one history—
the history that actually happened—means that we haven’t figured out what
did happen. A widely used textbook on phylogenetic methods explains this:“The fact that there is only one true tree . . . provides the basis for testingalternative hypotheses. If two hypotheses are generated for the same group of
species, then we can conclude that at least one of these hypotheses is false. Of
course, it is possible that both are false and some other tree is true.”12
When a body of evidence supports multiple conflicting historicalhypotheses, the evidence cannot be sending a definitive historical signal about
what happened in the past. That raises the possibility that it may not besending a signal at all. Conversely, when the evidence leads investigators toconverge around a single historical hypothesis, when one hypothesis best
explains a whole group of clues, it is much more likely that the evidence istelling us what actually happened.
Consider, by way of illustration, a case in which we know a true history ofancestor–descendant relationships to see how evidence can converge around asingle (unequivocal) history. Between 1839 and 1856, Charles Darwin and his
wife, Emma, produced ten children, listed below in alphabetical order:
AnneCharles
Elizabeth
FrancisGeorgeHenrietta
HoraceLeonardMary
WilliamThis alphabetical listing, of course, is not their actual birth order. Instead, it
is one of a large number of possible birth orders for Darwin’s children, only
one of which is the correct sequence. Indeed, only one of these arrangements
can represent the actual Darwin family history.
Now, suppose I gave you and some friends a pile of historical evidence

about Darwin’s children, and asked you to “solve for their birth order.” No
one would consider the problem solved if you came back with more than one
order. On the other hand, if you came back and presented a single coherent
hypothesis of the birth order supported by evidence from birth records, family
letters, and photographs from the Darwin family archives, that would provide
persuasive evidence that you had obtained the correct solution. Since only one
true history exists, once you find it the evidence will tend to fall naturally into
place.
But does the evidence for a Precambrian animal tree of life fall similarly
into place or does it generate multiple conflicting histories? We’ve alreadyseen that fossil evidence does not point to a specific Precambrian tree ofanimal life, or perhaps to any tree at all. We’ve also seen that genetic evidence
by itself does not establish a single divergence point for animal evolution. But
what about the genetic and anatomical evidence taken together? Does that
evidence converge on a single history of animal life? If so, then it could wellmake up for a lack of fossil evidence. Otherwise, it would seem to raise an
obvious question: Are the observed genetic and anatomical “affinities” among
the Cambrian phyla sending reliable historical signals at all?
CONFLICTING HISTORIES
There are several reasons to doubt that evidence of genetic and anatomicalsimilarity is sending a reliable signal of the early history of animal life. First,
comparisons of different molecules frequently generate divergent trees.
Second, comparisons of anatomical characteristics and molecules frequently
produce divergent trees. Third, trees based solely on different anatomical
characteristics often contradict each other. Let’s examine each problem.
Molecules vs. Molecules
Just as the molecular data do not point unequivocally to a single date for thelast common ancestor of all the Cambrian animals (the point of deep
divergence), they do not point unequivocally to a single coherent tree
depicting the evolution of animals in the Precambrian. Numerous papers havenoted the prevalence of contradictory trees based on evidence from molecular
genetics. A 2009 paper in Trends in Ecology and Evolution notes that“evolutionary trees from different genes often have conflicting branchingpatterns.”13 Likewise, a 2012 paper in Biological Reviews acknowledges that“phylogenetic conflict is common, and frequently the norm rather than the
exception.”14 Echoing these views, a January 2009 cover story and review

article in New Scientist observed that today the tree-of-life project “lies intatters, torn to pieces by an onslaught of negative evidence.” As the article
explains, “Many biologists now argue that the tree concept is obsolete andneeds to be discarded,” because the evidence suggests that “the evolution ofanimals and plants isn’t exactly tree-like.”
The New Scientist article cited a study by Michael Syvanen, a biologist at
the University of California at Davis, who studied the relationships among
several phyla that first arose in the Cambrian.15 Syvanen’s study compared
two thousand genes in six animals spanning phyla as diverse as chordates,echinoderms, arthropods, and nematodes. His analysis yielded no consistenttree-like pattern. As the New Scientist reported, “In theory, he should havebeen able to use the gene sequences to construct an evolutionary tree showing
the relationships between the six animals. He failed. The problem was thatdifferent genes told contradictory evolutionary stories.” Syvanen himself
summarized the results in the bluntest of terms: “We’ve just annihilated thetree of life. It’s not a tree anymore, it’s a different topology [pattern of history]
entirely. What would Darwin have made of that?”16
Other studies trying to clarify the evolutionary history and phylogenetic
relationships of the animal phyla have encountered similar difficulties.
Vanderbilt University molecular systematist Antonis Rokas is a leader among
biologists using molecular data to study animal phylogenetic relationships.
Nevertheless, he concedes that a century and a half after The Origin ofSpecies, “a complete and accurate tree of life remains an elusive goal.”17 In
2005, during the course of an authoritative study he eventually copublished in
Science, Rokas was confronted with this stark reality. The study had sought todetermine the evolutionary history of the animal phyla by analyzing fifty
genes across seventeen taxa. He hoped that a single dominant phylogenetic
tree would emerge. Rokas and his team reported that “a 50-gene data matrix
does not resolve relationships among most metazoan phyla” because it
generated numerous conflicting phylogenies and historical signals. Theirconclusion was candid: “Despite the amount of data and breadth of taxa
analyzed, relationships among most metazoan phyla remained unresolved.”18
In a paper published the following year, Rokas and University of
Wisconsin at Madison biologist Sean B. Carroll went so far as to assert that“certain critical parts of the TOL [tree of life] may be difficult to resolve,
regardless of the quantity of conventional data available.”19 This problem
applies specifically to the relationships of the animal phyla, where “[m]any
recent studies have reported support for many alternative conflicting
phylogenies.”20 Investigators studying the animal tree found that “a largefraction of single genes produce phylogenies of poor quality” such that in one
case, a study “omitted 35% of single genes from their data matrix, because
those genes produced phylogenies at odds with conventional wisdom.”21
Rokas and Carroll tried to explain the many contradictory trees by proposingthat the animal phyla might have evolved too quickly for the genes to record
some signal of phylogenetic relationships into the respective genomes. In
their view, if the evolutionary process responsible for anatomical novelty
works quickly enough, there would not be sufficient time for differences toaccumulate in key molecular markers, in particular those used to infer
evolutionary relationships in different animal phyla. Then, given enough time,
whatever signal did exist might become lost. Thus, when groups of organisms
branch rapidly and then evolve separately for long periods of time, this “canoverwhelm the true historical signal”22—leading to the inability to determine
evolutionary relationships.
Their article brings the discussion of the Cambrian explosion full circle
from an attempt to use genes to compensate for the absence of fossil evidence
to the acknowledgment that genes do not convey any clear signal about theevolutionary relationships of the phyla first preserved by fossils in the
Cambrian. The logic of their analysis also leads them to a strangely familiar
conclusion. Since the analysis of key genetic markers—like the genes tracked
in molecular-clock studies that presumably accumulate mutations at aconstant rate—shows a low number of mutational differences between the
Cambrian animal phyla, Rokas and Carroll conclude from specifically genetic
evidence that the phyla must have diverged rapidly. As they put it in anotherpaper, “Inferences from these two independent lines of evidence (molecules
and fossils) support a view of the origin of Metazoa as a radiation compressedin time.”23 Thus, the inability to reconstruct the evolutionary history of theanimal phyla from the molecular data not only fails to establish a Precambrianpattern of descent; it ironically also reaffirms the extreme rapidity of theorigin of the Cambrian animal forms.
Molecules vs. Anatomy
In 1965, chemist Linus Pauling and biologist Emile Zuckerkandl, often hailed
as the fathers of the molecular-clock concept, proposed a rigorous way toconfirm evolutionary phylogenies. They suggested that if studies ofcomparative anatomy and DNA sequences generated similar phylogenetic
trees, then “the best available single proof of the reality of macroevolution
would be furnished.”24 As they went on to explain, “only the theory of
evolution . . . could reasonably account for such a congruence between lines

of evidence obtained independently.”25 By focusing attention on these two
independent lines of evidence and the possibility of their convergence (orconflict), Pauling and Zuckerkandl provided a clear and measurable way totest the neo-Darwinian thesis of universal common ancestry.
And according to some scientists, studies of molecular homologies haveconfirmed expectations about the history of the animal phyla derived fromstudies of comparative anatomy. After citing Pauling and Zuckerkandl’s test,
Douglas Theobald claims in his “29+ Evidences for Macroevolution” that“well-determined phylogenetic trees inferred from the independent evidenceof morphology and molecular sequences match with an extremely high degreeof statistical significance.”26
In reality, however, the technical literature tells a different story. Studies ofmolecular homologies often fail to confirm evolutionary trees depicting thehistory of the animal phyla derived from studies of comparative anatomy.
Instead, during the 1990s, early into the revolution in molecular genetics,
many studies began to show that phylogenetic trees derived from anatomy
and those derived from molecules often contradicted each other.
Probably the most protracted conflict of this type concerns a widely
accepted phylogeny for the bilaterian animals. This classification scheme wasoriginally the work of the influential American zoologist Libbie Hyman.27
Hyman’s view, generally known as the “Coelomata” hypothesis, was based onher analysis of anatomical characteristics, mainly germ (or primary tissue)
layers, planes of body symmetry, and especially the presence or absence of acentral body cavity called the “coelom,” which gives the hypothesis its name.
In the Coelomata hypothesis, the bilaterian animals were classified in threegroups, the Acoelomata, the Pseudocoelomata, and the Coelomata, eachencompassing several different bilaterian animal phyla.28 (See Fig. 6.1a.)Then, in the mid-1990s, a very different arrangement of these animalgroups was proposed based on the analysis of a molecule present in each (the18S ribosomal RNA; see Fig. 6.1b). The team of researchers who proposed
this arrangement published a groundbreaking paper in Nature with a title thatsurprised many morphologists: “Evidence for a Clade of Nematodes,
Arthropods and Other Moulting Animals.”29 The paper noted theconventional wisdom, based on Hyman’s hypothesis, that arthropods andannelids were closely related because both phyla had segmented body plans.30
But their study of the 18S ribosomal RNA suggested a different grouping, onethat placed arthropods close to nematodes within a group of animals that molt,
which they called “Ecdysozoa.” This relationship surprised anatomists, sincearthropods and nematodes don’t exactly look like kissing cousins. Arthropods

(such as trilobites and insects) have coeloms, whereas nematodes (such as thetiny worm Caenorhabditis elegans) do not, leading many evolutionary
biologists to believe nematodes were early branching animals only distantly
related to arthropods.31 The Nature paper explained how unexpected thisgrouping of arthropods and nematodes was: “Considering the greatly differingmorphologies, embryological features, and life histories of the molting
animals, it was initially surprising that the ribosomal RNA tree should groupthem together.”32

FIGURE 6.1
How scientists reconstruct evolutionary history depends on which similarities
they regard as revealing the true history of descent (homology) and whichsimilarities they regard as misleading (homoplasy). Advocates of the
Coelomata hypothesis (Figure 6.1a) regard the coelom (body cavity) as ahomologous feature. Thus, they think the presence of a coelom in botharthropods and vertebrates indicates a common ancestor that possessed a
coelom (indicated by the solid horizontal line in 6.1a). But advocates of theEcdysozoa hypothesis (6.1b) think the coelom evolved at least twice
independently (indicated by the two dashed horizontal lines in Figure 6.1b).
They regard the presence of the coelom as a historically misleading similarity—one that does not indicate the presence of that feature in the most recent
common ancestor of the groups possessing it. These two hypotheses and theirimplied histories are not congruent, and cannot both be true.
Since the Ecdysozoa hypothesis was first proposed, other scientists havevigorously opposed it, reaffirming the Coelomata hypothesis, based on theanalysis of other molecular evidence.33 Advocates of the Ecdysozoa grouping
pushed back hard, however,34 contending that, properly interpreted, availablegenetic evidence supports the Ecdysozoa, not the Coelomata hypothesis.35
My point in summarizing these disputes is simply to note that themolecular and anatomical data commonly disagree, that one can find partisanson every side, that the debate is persistent and ongoing, and that, therefore,
the statements of Dawkins, Coyne, and many others about all the evidence(molecular and anatomical) supporting a single, unambiguous animal tree aremanifestly false. As can readily be seen by comparing Figures 6.1a and6.1b,36 these hypotheses—Coelomata and Ecdysozoa—contradict each other.
Although both might be false, both cannot be true.
Various papers analyzing other groups have found similar discrepancies
between molecular and morphological versions of the animal tree. A paper by
Laura Maley and Charles Marshall in the journal Science noted, “Animal
relationships derived from these new molecular data sometimes are very
different from those implied by older, classical evaluations of morphology.”37
For example, when tarantulas were used as the representative of arthropods,
the arthropods were grouped more closely to mollusks than to deuterostomes(animals that develop anuses first and mouths later). This makes sense
because both mollusks and arthropods are protostomes (animals that develop
mouths first and anuses later). But when brine shrimp were used as therepresentative of the arthropods, the arthropods became the odd man out.
Now mollusks were grouped most closely to deuterostomes, far away fromarthropods—a result clearly at odds with the conventional phylogeny based
upon anatomical characteristics.38
Examples of similar conflicts abound. The traditional phylogeny placed
sponges at the bottom of the animal tree, with progressively more complex
phyla (e.g., cnidarians, flatworms, nematodes) branching off. But Valentine,
Jablonski, and Erwin note that molecules “indicate a very different
configuration” of the tree, where some higher deuterostome phyla branch offvery early and some comparatively less complex phyla branch very late.39
Likewise, morphological studies suggest phoronids (see Fig. 3.6) andbrachiopods (see Fig. 1.3), both marine filter-feeding animals, aredeuterostomes, but molecular studies classify them within protostomes.40
Morphological studies typically imply that sponges are monophyletic (all partof an exclusive branch on the tree of life) because of their distinctive bodyarchitecture, but molecular studies suggest that sponges don’t belong to asingle unified group, with some sponges more closely related to jellyfish thanthey are to other sponges.41 Cnidarians and ctenophores have similar bodyplans, leading many to expect they were closely related on the basis ofmorphology. But molecular data have distanced these phyla significantly.42

As a major review article in Nature in 2000 observes, “Evolutionary trees
constructed by studying biological molecules often don’t resemble thosedrawn up from morphology.”43 And the problem isn’t getting better over time.
A 2012 paper admits that larger datasets are not solving this problem:“Incongruence between phylogenies derived from morphological versus
molecular analyses and between trees based on different subsets of molecularsequences has become pervasive as datasets have expanded rapidly in bothcharacters and species.”44
Indeed, the widespread discrepancies between molecular data andmorphological data and between various molecule-based trees have led someto conclude that Pauling and Zuckerkandl were wrong to assume that thedegree of similarity indicates the degree of evolutionary relatedness.45 As
Jeffrey H. Schwartz and Bruno Maresca put it in the journal Biological
Theory: “This assumption derives from interpreting molecular similarity (ordissimilarity) between taxa in the context of a Darwinian model of continualand gradual change. Review of the history of molecular systematics and its
claims in the context of molecular biology reveals that there is no basis for the‘molecular assumption.’ ”46
Anatomy vs. Anatomy
Attempts to infer a consistent picture of the history of animal life based on
analyzing the anatomical characteristics of different animals have also provenproblematic. In the first place, there is a general and long-standing problem
with attempts to infer the evolutionary history of the animal phyla fromsimilar anatomical traits. At the level of the phyla—that is, when one
compares the phyla to each other and tries to determine their branching order—the number of shared anatomical characteristics available for inferring
evolutionary relationships drops off quite dramatically. There is an obvious
reason for this. For example, an anatomical character such as the “leg,” that isuseful for diagnosing and comparing arthropods, which possess legs, proves
useless for making comparisons between (for example) brachiopods or
bryozoans, which do not. In the same way, basic structural features of humandesigned systems, such as the distinctive submarine “trait” of an
encapsulating watertight hull, might help to distinguish it from a cruise ship,
which is only watertight on its underside. But this “trait” would be irrelevant
for comparing and classifying, say, suspension bridges, motorcycles, or flatscreen televisions. In a similar manner, biologists find that there are only ahandful of highly abstract characters, such as radial versus bilateral bodysymmetry, the number of fundamental tissue layers (triploblasty, three layers,versus diploblasty, two layers), or the type of body cavity present (truecoelom, pseudocoelom, or no coelom), available for morphologicalcomparisons of the many diverse animal forms. Yet evolutionary biologists
have often disputed the validity of these rather abstract traits as guides toevolutionary history.47 In addition, just as trees based upon the analysis ofdifferent sets of similar genes or proteins often conflict, trees constructed on
the basis of different developmental and anatomical characteristics often
conflict.
When biologists construct phylogenetic trees based upon anatomical
characteristics, they typically group the animal phyla according to thepresence or absence of several key characteristics. For example, the standard
version of the animal tree, based upon anatomy, groups animals according totheir style of body plan symmetry and by their mode of body plandevelopment. As noted earlier, animals with mirror symmetry along their
vertical head-to-tail axes all fall within the Bilaterian group. Animals withradial symmetry (or no symmetry) fall outside this group. Within the
Bilateria, taxonomists distinguish other main groups—protostomes anddeuterostomes—based upon their differing modes of body plan development—i.e., either “mouth first” or “anus first.”
Yet a significant difficulty arises when evolutionary biologists consider
how a particularly fundamental characteristic—the mode of germ-cellformation—is distributed among various groups on the canonical animal treeof life (see Fig. 6.2).48 Germ cells produce eggs and sperm (in any sexually
reproducing species) or gametes (in any asexually reproducing species),
giving rise to the next generation.49 Animals have two main ways ofgenerating germ cells. In one mode of germ-cell formation, known as
preformation, cells inherit internal signals from a region within their own cellstructure to become germ cells (illustrated by solid black squares on Fig.
6.3a). In the other main way of generating germ cells, known as epigenesis,
germ cells receive external signals from surrounding tissues to become
primordial germ cells (PGCs, illustrated by solid white squares in Fig. 6.3b).
Germ-cell formation has indisputable evolutionary importance. To evolve,
a population or a species must leave offspring; to leave offspring, species ofanimals must generate primordial germ cells. No PGCs, no reproduction; no
reproduction, no evolution.
One might expect, therefore, that if a group of animals is all derived from acommon ancestor (with a particular mode of gamete production), then themode of germ-cell formation should also be essentially the same from one
animal species to the next in that group. Further, assuming the common
ancestry of all animals, our expectation of homologous modes of germ-cellformation among the animals ought to be higher than for any other tissue
type, cell line, or mode of development. Why? Because mutations affecting
the developmental mechanisms that govern PGC formation inevitably disrupt
successful reproduction.50 Again, if a species cannot reproduce, it cannot
evolve.51
Thus, similar groups of animals—indeed, all animals, if they havedescended from a common ancestor—ought to exhibit the same basic mode ofgerm-cell formation. Further, that the evolutionary tree derived from ananalysis of the “mode of germ-cell formation” ought to be congruent with thetrees derived from other such fundamental characteristics (such as body-plansymmetry, mode of development, number of primary tissues, and so forth).
But the mode of germ-cell formation is nearly randomly distributed among
the different animal groups, making it impossible to generate a coherent tree
based on this characteristic, let alone making any comparison between such atree and the canonical tree. Note also the distribution of the two basic modesof germ-cell development within the animal phyla as depicted on the
canonical tree. Figure 6.4, derived from the work of Harvard developmental
biologist Cassandra Extavour,52 shows this distribution and provides anotherway of understanding the incongruence that arises when analyzing different
anatomical characteristics.

FIGURE 6.2
The canonical tree of the Metazoa as determined by the analysis of selected
anatomical characters and genes.

FIGURE 6.3
Two modes of germ-cell formation. Figure 6.3a (left): In fruit flies as the egg

is being formed, the mother’s nurse cells (the four cells on the left of the ovalshaped egg chamber, indicated by large black circles) deposit proteins andRNAs, which are transported to the posterior pole of the egg (indicated by thedark patch to the right of the large cell on the right). These maternallysynthesized molecules then trigger the development of the germ cells and sex
organs of the fly during embryogenesis. Figure 6.3b (right): In the eggs ofmice there are no maternally deposited products that determine germ-cellformation. Rather, as the embryo develops a subpopulation of cells(represented by the triangles on the left) express “germline competence
genes.” These cells then “read” signals that arrive from other tissues (seearrows), causing the cells to differentiate into primordial germ cells (asindicated by the stars on the right).
Notice the two modes of germ-cell formation do not cluster together inseparate parts of the canonical tree. Instead, they are distributed haphazardly
among various phyla on different branches of the tree. In the protostomes, forinstance, modes of germ-cell formation wink on and off between
preformation and epigenesis. The same is the case within the deuterostomes:
germ-cell formation varies almost randomly, and several groups exhibit bothmodes, rendering it difficult or impossible to determine which characteristic
was present at different ancestral branching points. Noting this pattern of
distribution, Cassandra Extavour concludes that “the data presently available
cannot suggest homologies of the somatic components of metazoan
gonads.”53

FIGURE 6.4
The distribution of modes of primordial germ-cell formation (epigenesis,
preformation, or both) among various animal groups. The solid thin lines
between the boxes on the right and the phyla names on the left show where
the different modes of germ-cell formation are present in different phyla. The
nearly random distribution of types of germ-cell formation among the various
animal groups makes it impossible to generate an animal phylogeny(evolutionary history) based upon this character that will match theevolutionary history implied by the canonical animal tree of life.

FIGURE 6.5
A selection of incompatible (mutually incongruent) phylogenetic trees
representing the history of the major groups of animals, drawn from thezoological and evolutionary literature (1940–present). Note: The definitionsof some taxonomic groups in some of these phylogenetic trees may havechanged significantly since the time those phylogenies were originallyconstructed. Branch lengths may not always be drawn to scale.
After completing a survey of many such difficulties, University of St.
Andrews zoologist Pat Willmer and Oxford University zoologist Peter
Holland, experts on invertebrate anatomy, draw this conclusion: “Taken
together, modern re-evaluations of traditional evidence support different andmutually exclusive subsets of [phylogenetic] relations.”54 They go on toobserve that “patterns of symmetry, the number of germ layers in the body,the nature of the body cavity, and the presence or type of serial repetition[segmentation] have all been used to infer common ancestry.” But, they

explain, the phylogenetic story these characteristics tell is “now either
unacceptable or at least controversial” because the data are, at best,
inconsistent.55
The historical record of ongoing uncertainty about the animal tree of life
since 1859 confirms, as one respected textbook on invertebrate animals
explains, that “phylogenetic analysis at the level of the phyla is highly
problematical.”56 As a result, “the study of higher level animal phylogeny has
yielded an expansive literature but relatively little detailed consensus. . . . In
point of fact, there exists no such thing as ‘the traditional textbook
phylogeny.’ A diversity of different schemes can be found.”57 To appreciate
this problem visually, look at Figures 6.1a and 6.1b as well as Figure 6.5.
These show some of the many metazoan phylogenies, based on anatomy,
published in the twentieth century. These branching patterns plainly do notagree with one other.
THE ASSUMPTIONS OF PHYLOGENETIC INFERENCE
All these problems underscore several fundamental difficulties with themethods of phylogenetic reconstruction. When biologists analyze multiple
anatomical traits or genes, the animal phyla consistently defy attempts toarrange them into the pattern of a single tree. Yet if there was a period of
hidden Precambrian evolution, and if comparative sequence analyses reveal
the actual history of animal life and, by implication, the existence ofPrecambrian animal forms, phylogenetic studies should converge more andmore around a single tree of animal life. Just as only one possible divergencepoint could represent the event at which animal forms began to evolve from acommon animal ancestor, only one of the many trees produced byphylogenetic analysis can represent the actual Precambrian history of animal
life. If, instead, phylogenetic analyses consistently generate different possible
evolutionary histories, it’s difficult to see how any one of them could beknown to be sending a reliable historical signal. Again, the history of animallife only happened once.
One could argue that these conflicting trees do, at least, show that sometree-like evolutionary pattern of common ancestry preceded the Cambrian,since all conflicting trees do affirm that. But, again, they all “show” thisbecause they all presuppose it, not because they demonstrate it.
CONVERGENT EVOLUTION
There is yet another reason to wonder whether studies of anatomical ormolecular homology convey anything definitive about the history of life.
Many animals have single traits or features in common with otherwise
decidedly different animals. In such cases, it makes no evolutionary sense toclassify these forms as closely related ancestors. For example, moles andmole crickets have remarkably similar forelimbs, though moles are mammals
and mole crickets are insects. No evolutionary biologist regards these two
animals as closely related, for understandable reasons.
The theory of universal common descent assumes that, generally, the moresimilar two organisms are, the more closely related they must be. Assuming
common descent, animals with wildly differing body plans should not be
closely related. The presence of nearly identical individual traits or structures
within organisms exemplifying otherwise different body plans cannot,
therefore, be attributed to evolution from a common ancestor. Instead,evolutionary biologists attribute similar traits or structures in such a context toso-called convergent evolution, the separate or independent origin of similar
characters emerging on separate lines of descent after the point at which thoselines diverged from their last common ancestor. Convergent evolution
demonstrates that similarity does not always imply homology, or inheritancefrom a common ancestor.
For this reason, the repeated need to posit convergent evolution (and otherrelated mechanisms)58 casts further doubt on the method of phylogenetic
reconstruction. Invoking convergent evolution negates the very logic of theargument from homology, which affirms that similarity implies common
ancestry, except—we now learn—in those many, many cases when it doesnot. Repeatedly invoking convergence negates the assumption that justified
the method of phylogenetic reconstruction in the first place, namely, thatsimilarity is a reliable historical signal of common ancestry.
A FAMILY REUNION?
So what lesson should we draw from these many conflicting trees? Clearly,
these contradictory results call into question the existence of a canonical treeof animal life. To see why, imagine being invited to an event billed as anextended-family reunion where you’ve been told you will encounter hundredsof your relatives, most of whom you have never met. Let’s call the description
in the invitation the “reunion hypothesis.” The invitation says that a group
photograph is planned, for which relatives will be grouped together according
to their degree of relationship (first cousins with first cousins, and so on).
You show up and grab a coleslaw, eager to meet these many previously
unknown relatives. You see the hundreds gathered and have every reason tobelieve that the “reunion hypothesis” is true. After all, the invitation in yourmailbox described the event as a family reunion.
As the day goes on, however, something seems amiss. Here and there, you
see familiar facial features—“Yes,” you think, that person could be mycousin”—but the majority of attendees and all the strangers you engage inconversation exhibit no discernible family resemblances. Nor does anyone
seem to share any personal relationships with anyone else at the reunion, no
matter how long they chat and try to establish points of commonality. What’smore, each person tells a different story of his or her family history. You try togroup the strangers by physical characteristics (height, hair color, body type,and so on), but the characteristics that you find fail to yield evidence of familyties or genealogical connections. Whatever points of commonality you findrefuse to assemble into a coherent, consistent story. The pedigrees are unclear.
The reunion hypothesis is under major strain.
When the photographer arrives, she gamely tries to draw everyone
together for the planned photograph. Chaos ensues. No one knows where to
stand, because the family relationships are so unclear, if they exist at all. Aftermilling around hopelessly for half an hour or so, people depart for their cars,
wondering why they bothered to attend the picnic, and indeed why they wereinvited in the first place.
Do you now have good reasons to doubt the “reunion hypothesis”? You
do. If the family reunion hypothesis were true, it would have been
increasingly confirmed, because the evidence would have converged on asingle consistent pattern. Had there been a true pattern of family relationships,
the longer everyone talked, the more a single coherent pattern of relationshipwould have become apparent. But the people at the picnic were not yourrelatives, at least not in any way you could determine to be true. Instead of
converging on a single pattern, the “evidence” was all over the map.
A FOREST OF TREES
Of course, my family reunion illustration breaks down as an analogy to thehistory of animal life, because if we could trace the history of all the people atthe reunion back far enough we would find that they are all related bycommon ancestry. Though we can choose to assume that the same is true of
the Cambrian animals, neither the fossil evidence nor the evidence of genetics
and comparative anatomy actually establishes that. These three classes ofevidence either provide no compelling evidence for Precambrian animal
ancestors (in the case of fossils), or they provide question-begging andconflicting evidence (in the case of genes and anatomy).

And that is the point of my story. Since there can be only one true historyof the Cambrian animals, the evidence should converge on a common family
tree—if indeed we are looking at evidence of true history. The picture givenby the evidence should be stable, not constantly changing. But the evidence
from a variety of quarters has instead continually generated new, conflicting,and incoherent pictures of the history of animal life. As with the “cousins” inmy illustration, there seems to be no consistent and coherent way to organize
the animal groups into a family tree.
But if the genes don’t tell the story of Precambrian ancestral forms, if they
don’t compensate for a dearth of fossil evidence and establish a unequivocal
long cryptic history of animal life from an original animal, an ur-metazoan,
then logically we are back to taking the fossil record at face value. In thatcase, the mystery of the missing ancestral fossils remains. If so, is there any
way to explain the abrupt appearance of new forms of life in the fossil record
within an evolutionary framework? During the 1970s, two young
paleontologists thought that there just might be a way to do exactly that.

7
Punk Eek!
Scientific discoveries are rarely made in Laundromats, but at least one greatscientific breakthrough—an “aha” moment—occurred in one. The year was
1968, more than a decade before the discovery of the first Chengjiang fossils.
The scientist overtaken by the muses was paleontologist Niles Eldredge. One
day while standing in a Michigan Laundromat, following months of collecting
trilobite fossils for his Ph.D. research, Eldredge happened to reach into his
pocket. He removed one of the fossils he had been collecting, a specimen of atrilobite species called Phacops rana. Initially, as he examined the specimen,
he felt “depressed.” The fossil closely resembled many others that he hadfound across layers of strata during his fieldwork in the Midwest. His
trilobites showed no evidence of gradual change, as classical neo-Darwinism
had taught him to expect.1
As Eldredge explained in a lecture at the University of Pittsburgh in 1983,
he then experienced a kind of scientific epiphany. He realized that the“absence of change itself” was “a very interesting pattern.” Or as he later put
it, “Stasis is data.”2 “Stasis” is the term that Eldredge and his scientificcollaborator, Stephen Jay Gould (see Fig. 7.1), later gave to the pattern inwhich most species, “during their geological history, either do not change inany appreciable way or else they fluctuate mildly in morphology, with noapparent direction.”3 As Eldredge examined that solitary trilobite, he realizedthat he had been observing evidence of stasis for some time—however muchhe might have wanted it otherwise. As he explained, “Stasis . . . was by far themost important pattern to emerge from all my staring at Phacops specimens.”
He continued, “Traditionally seen as an artifact of a poor record, as theinability of paleontologists to find what evolutionary biologists going back to
Darwin had told them must be there, stasis was, as Stephen Jay Gould put it,‘paleontology’s trade secret’—an embarrassing one at that.”4This embarrassing realization proved pivotal, eventually leading Eldredge
and Gould to reject both the gradualistic picture of evolutionary change
articulated by Darwin and the neo-Darwinian understanding of themechanism by which such change allegedly takes place. It also led them toformulate, in a series of scientific papers from 1972 to 1980, a new theory of
evolution known as “punctuated equilibrium.”5
As a consequence of this theory, neither Gould nor Eldredge expected tofind a wealth of transitional intermediate forms in the fossil record. In theirview, the main periods of biological innovation simply occurred too rapidly toleave many fossil intermediates behind.6
Gould and Eldredge sought to explain the occurrence of the rapid periods7
of change (i.e., the punctuations) as the by-product of different kinds ofevolutionary mechanisms or processes of change. They proposed, first, amechanism called “allopatric speciation” to explain the rapid generation of
new species. Gould, Eldredge, and another early advocate of punctuatedequilibrium named Steven Stanley, a paleontologist at Johns Hopkins
University, also proposed that natural selection operated on higher levels.
Rather than natural selection favoring the fittest individual organisms within a
species—as it does in classical Darwinism and neo-Darwinism—thesepaleontologists proposed that it often selected the most fit species among agroup of competing species. Because they thought that speciation occurred
more rapidly, and because they thought that natural selection acted on whole
species and not just individual organisms, the advocates of punctuatedequilibrium theorized that morphological change typically occurs in larger,
more discrete jumps than Darwin first envisioned.

FIGURE 7.1
Figure 7.1a (left): Stephen Jay Gould. Courtesy Getty Images. Figure 7.1b

(right): Niles Eldredge. Copyright © Julian Dufort 2011. Used withpermission.
Thus, in one sense, the theory of punctuated equilibrium, like the artifact
hypothesis, sought to explain the absence of the transitional intermediate
forms that were expected based on Darwin’s theory. By repudiating
Darwinian gradualism, the advocates of punctuated equilibrium sought toaccount for the absence of transitional forms in the fossil record apart fromthe artifact hypothesis or, at best, using what they imagined as a more modest
version of it. But in repudiating Darwinian gradualism, punctuatedequilibrium also represented a radically different view of the pace and modeof evolution—a new theory of evolution that purported to identify a newmechanism of evolutionary change. As historian of science David Sepkoski
explains, “Gould and Eldredge proposed a radical revision of this standard[neo-Darwinian] narrative. They argued that the pattern of evolutionary
history really was composed of fits and starts, consisting of long periods ofevolutionary stasis (or ‘equilibrium’) ‘punctuated’ by shorter periods of rapid
speciation.”8
During the 1970s and 1980s, the theory of punctuated equilibrium, or“punk eek” as it is affectionately known, generated both intense scientificdebate and extensive media coverage.9 Critics called the model “evolution byjerks,” leading Gould to reply that proponents of gradualism were offering“evolution by creeps.”10 Though initially Eldredge played more of a role informulating the theory, Stephen Jay Gould emerged as the leading spokesman
for it. As a result of his advocacy of the theory as well as his popular science
writing, Gould achieved immense celebrity—celebrity that has in turn secured
an enduring place for punctuated equilibrium in scientific awareness.
So what has become of this bold scientific proposal? Does punctuatedequilibrium solve the problems that traditional neo-Darwinism does not?
Does it help explain the Cambrian explosion and the missing fossil
intermediates that render it so mysterious?
WANTED: FAST ENGINE
Once they decided to take the fossil record at face value, the question for
Gould and Eldredge was obvious: What could generate evolutionary change
so rapidly? To explain the short bursts or punctuations, Gould and Eldredge
proposed a mechanism of rapid speciation to which Stanley added (with theiragreement) a new understanding of the mechanism of natural selection.11
Whereas the neo-Darwinian mechanism of natural selection acting onrandom mutations necessarily acts slowly and gradually, Gould and Eldredge
invoked a process called “allopatric speciation” to explain how new species
might arise quickly. The prefix allo means “other” or “different,” and thesuffix patric means “father.” Thus, allopatric speciation refers to processes
that generate new species from separate parent (or “father”) populations.
Allopatric speciation typically occurs when part of a population of organisms
becomes geographically isolated—perhaps by the emergence of a mountain
range or the shifting of a river’s course—from a larger parent population andthen a daughter population changes in response to differing environmentalpressures.
Gould and Eldredge drew on insights from population genetics to explain
why new genetic traits were more likely to spread and establish themselves
within these smaller subpopulations. Population genetics, a subject to which
I’ll return in Chapter 12, describes the processes by which genetic traits
change and become fixed in a population of organisms. It teaches that intypically large populations of organisms, it is difficult for a newly arising
genetic trait to spread throughout an entire population. Yet for any
evolutionary change to occur in a population, new genetic traits must become
widespread, or “fixed,” by a process called “fixation.”
In smaller populations, however, the probability of a newly arising trait
becoming fixed is much higher, since the new trait needs to spread to fewerorganisms. By way of illustration, consider a bag containing fifty red and fifty
blue marbles. Suppose that, by removing individual marbles at random, youseek to change the “population” of mixed-color marbles to one in which all
the marbles are red. To produce a completely red “species,” we must generate
a population in which all the blue marbles have been eliminated. If someone
randomly picks half of the one hundred marbles out of the bag, it is extremely
improbable that all of the marbles thus eliminated will be of just one color.
Indeed, there is less than 1 chance in 1030 that all of the marbles selected forremoval will be blue.12 Conversely, there is an extremely high probability thatthe remaining batch will still include both blue and red marbles.
In a much smaller group of, say, eight marbles, evenly divided between
four red and four blue, the probability of selecting four blue marbles at
random and leaving only red marbles, though unlikely, is not prohibitively
small. There’s now a much higher chance—1 in 70—that the remaining
population of marbles will be all red.13 By starting with a smaller number ofmarbles, the probability that random selection will result in a population of
uniform color is much higher. In a similar way, the probability of fixing a
genetic trait in a population of organisms decreases exponentially with thesize of the population.

In formulating punctuated equilibrium, Gould realized that new species
would inevitably have to arise in smaller populations, where random
processes could have a greater chance of fixing traits. Prominent among thoserandom processes is one called genetic drift. This occurs when genetic
changes spread or disappear randomly through a population, without regard
for their effect on survival and reproduction.
In Gould and Eldredge’s view, allopatric speciation helped to explain how
evolution could occur in larger, more discrete jumps than Darwinian
gradualism predicts (see Fig. 7.2). As allopatric speciation occurs, it cangenerate what Gould and Eldredge conceived as sibling or offspring species.
They thought that the processes that drive these speciation events occur
relatively quickly in smaller populations, thus helping to explain the sudden
jumps in the fossil record. As they put it: “Small numbers and rapid evolution
virtually preclude the preservation of speciation events in the fossil record.”14
As they envisioned the evolutionary process working, the branches on the treeof life would split off so abruptly that they would appear as virtually“horizontal” lines, producing sudden discontinuities in the fossil record andtherefore fewer fossilized intermediates. Eldredge and Gould explained it thisway: “The theory of allopatric (or geographic) speciation suggests a different
interpretation of paleontological data. If new species arise very rapidly insmall, peripherally isolated populations, then the expectation of insensibly
graded fossils is a chimera. A new species does not evolve in the area of its
ancestors; it does not arise from the slow transformation of all its forbears.”Thus, they concluded, “Many breaks in the fossil record are real.”15

FIGURE 7.2

Two views of the history of life. Figure 7.2a (left): The traditional Darwinian
picture showing slow, gradual change. Figure 7.2b (right): The history of life
as depicted by the theory of punctuated equilibrium showing rapid speciation.
Gould, Eldredge, and Stanley thought that members of these sibling or
offspring species would, subsequent to their origin by allopatric speciation,compete against each other for resources and survival, just as, in neoDarwinism, individual organisms or siblings may compete to survive andreproduce within a population. In their view, if members of one species
succeed over another because of some selective advantages they possess, thenthat species will survive and predominate, passing on its traits. This processof interspecies or interpopulation competition (as opposed to intraspecies
competition) Gould called “species selection.”16
As Gould himself explained: “I propose, as the central proposition ofmacroevolution, that species play the same role of fundamental individual thatorganisms assume in microevolution. Species represent the basic units intheories and mechanisms of macroevolutionary change.”17 Since natural
selection then would act upon large differences in overall biological form—
differences between whole species as opposed to individuals within species—
evolutionary change would take place in bigger, more discrete jumps.18
Gould and Eldredge thus did not expect the fossil record to document
many intermediates. Instead, they thought the “gaps” in the fossil record were“the logical and expected result of the allopatric model of speciation” as wellas the closely related mechanism of species selection.19 Species selection
made “the species” the unit of selection; the allopatric model of speciation
asserted that new species quickly arise from smaller populations oforganisms. Both mechanisms implied that fewer fossil intermediates would bepreserved. According to punctuated equilibrium, the long “missing”
transitional intermediates are not missing after all. In the process of species
selection, the species, rather than the individual organism, competes forsurvival and thus becomes—in the jargon of evolutionary biology—the main
“unit of selection” in macroevolution.
“PUNK EEK” AND THE FOSSIL RECORD
Eldredge and Gould devised the theory of punctuated equilibrium to eliminate
the conflict between the fossil record and evolutionary theory. Nevertheless,
punctuated equilibrium has its own problems accounting for the fossil record.
In particular, the pattern of fossil appearance in the Cambrian period isinconsistent with both the way in which punctuated equilibrium depicts thehistory of life and with the idea that allopatric speciation and species selection
are responsible for that pattern. There are several reasons for this.
First, the top-down pattern of appearance of Cambrian animal forms that
we saw in Chapter 2 contradicts punctuated equilibrium’s depiction of thehistory of life almost as much as it does the Darwinian picture (see Fig. 2.11).
Recall that Darwin thought that the first representatives of the higher
taxonomic categories emerged after the first appearance of representatives ofeach of the lower level taxa—that small differences distinguishing, forexample, one species from another should gradually accumulate until they
produced organisms different enough to be classified, first, as different
genera, then, as different families, and eventually as different orders, classes,
and so on. Instead, the first Cambrian animal forms are different enough fromeach other to justify classifying them as separate classes, subphyla, and phyla
from their first appearance in the fossil record (see Fig. 7.3).
This pattern creates an acute difficulty for the theory of punctuatedequilibrium., First, due to the action of allopatric speciation and species
selection, advocates of punctuated equilibrium envision morphologicalchange (represented as horizontal distance in Figure 7.2) arising in larger,
more discontinuous increments of change. Nevertheless, like neo-Darwinists,they too see phyla-level differences arising from the “bottom up,” startingwith lower level taxonomic differences—albeit occurring in increments
involving whole new species rather than individuals or varieties within
species. Indeed, according to the theory of punctuated equilibrium, allopatricspeciation first produces new species in smaller geographically isolated
populations. For representatives of higher taxonomic categories to arise, these
new species must accumulate new traits and evolve further. For this reason,
punctuated equilibrium also expects small-scale diversity and differentiationof new species to precede the emergence of larger-scale morphologicaldisparity and taxonomic differences. It also expects a “bottom-up” rather thana “top-down” pattern of appearance (see Fig. 7.3).
Second, for species selection to produce many new species, such as thosethat arise in the Cambrian explosion, a large pool of different species mustfirst exist. The Precambrian fossil record does not document, however, theexistence of such a large and diverse pool of competing Precambrian species
upon which species selection (via allopatric speciation) might operate.
Paleontologists Douglas Erwin and James Valentine exposed this problem
in 1987 in a seminal paper titled “Interpreting Great Developmental
Experiments: The Fossil Record.”20 They questioned the ability of both of themain evolutionary theories of the time—punctuated equilibrium and neoDarwinism—to explain the pattern of fossil appearance in the Precambrian–Cambrian fossil record.21 Clearly, neo-Darwinism does not explain thispattern. But, as Valentine and Erwin argue, neither does punctuatedequilibrium. As they conclude, the mechanism of species selection requires alarge pool of species upon which to act. Thus, Valentine and Erwin conclude:“The probability that species selection is a general solution to the origin of
higher taxa is not great.”22

FIGURE 7.3
This figure shows that the theory of punctuated equilibrium (on left), like neoDarwinism, anticipates small-scale diversity preceding large-scale disparity inform in contrast to the pattern in the fossil record (shown on right).
Punctuated equilibrium also anticipates a “bottom-up,” rather than a “topdown,” pattern.
The late-Precambrian and Cambrian fossil records present anotherdifficulty for punctuated equilibrium. Though Gould and Eldredge envisioned
new traits becoming fixed in small isolated populations where speciation
eventually occurs, they envisioned these traits first arising during periods ofstasis in the large populations from which the smaller populations later
separated. Gould realized that only stable large populations would affordenough opportunities for mutations to generate the new traits thatmacroevolution requires.23 At the same time, he recognized that these newtraits would have a far greater chance of being fixed into small, isolated
populations where the random loss of some traits makes the fixation of others
more likely (recall the marble example). By relying on large populations togenerate new traits and small populations to fix them throughout a population,

Gould wanted to provide both a plausible (if finely tuned) mechanism to
explain both macroevolutionary change and the absence of fossil
intermediates.24 The late University of Chicago paleontologist Thomas J. M.
Schopf described the balance this way, under punctuated equilibrium,
evolution proceeds “in populations large enough to be reasonably variable,
but small enough to permit large changes in gene frequencies due to random
drift.”25
But by relying on the accumulation of new traits within large parent
populations, Gould undercut his own rationale for concluding that the fossil
record should not preserve many intermediate forms. The reason for this is
obvious: if novel genetic traits arise and spread within a large population oforganisms, they are more likely to leave behind fossil evidence of their
existence. Organisms with new and unique combinations or mosaics of traits
represent nothing less than new forms of life. Thus, the process by which
Gould envisions new genetic traits arising in large populations implies thatnew forms of life—some presumably transitional to other forms—should bepreserved in the fossil record. Yet the Precambrian fossil record fails topreserve such a wealth of biological experiments during the long periods ofrelative stability in large populations that Gould’s theory envisions.
THE TESTIMONY OF STATISTICAL PALEONTOLOGY
Studies in statistical paleontology have raised additional questions about
whether the fossil record documents enough transitional intermediates torender punctuated equilibrium credible. In Chapter 3, I discussed the work of
the statistical paleontologist Michael Foote. Foote used sampling theory toargue that the fossil record provides a reasonably complete picture of theforms of life that have existed on earth and to suggest that paleontologists areunlikely to find the many intermediate forms that neo-Darwinian theory
requires.
Foote has also analyzed the question of whether the fossil record
documents the number of intermediate forms that punctuated equilibrium
requires. His answer: it depends.
Foote notes that whether a particular version of evolutionary theory canaccount for patterns in the fossil record depends upon the kind of mechanismof change it invokes. Neo-Darwinism relies upon a slow, gradually acting
mechanism of change and, thus, has difficulty accounting for evidence ofsudden appearance. Foote analyzes whether the number of proposedtransitional species in the fossil record is consistent with punctuatedequilibrium and concludes that it depends upon how fast the mechanisms

upon which it relies can generate new forms of life. Though its proponents
envision the evolution of new forms of life arising more abruptly than do the
neo-Darwinists, they would still expect that the fossil record should havepreserved some transitional fossils. Does the fossil record preserve even therelatively few intermediate forms that the theory of punctuated equilibrium
implies that it should?
To answer that question, Foote developed a statistical method of testing theadequacy of different evolutionary models against several variables.26 He
observed that for punctuated equilibrium to succeed as an explanation for thedata of the fossil record, it needs a mechanism capable of producing major
evolutionary change quickly, because only such fast-acting change could
account for the relative paucity of transitional forms in the fossil record. As
Foote explained (writing with Gould in fact), the adequacy of punctuatedequilibrium as an account of the fossil record depends upon the existence of amechanism “of unusual speed and flexibility.”27
But does the theory identify such a mechanism?
FROM WHENCE NEW TRAITS AND FORM?
Neither allopatric speciation nor species selection can generate the new
genetic and anatomical traits necessary to produce animal forms, let alone in
the relatively brief time of the Cambrian explosion. As conceived by Gould
and the other advocates of punctuated equilibrium, allopatric speciation justallows for the possibility of the rapid fixation of preexisting traits, not thegeneration of new traits. When a parent population splits into two or moredaughter populations, each of the daughter populations retains a part, but
usually not the whole, of the gene pool of the original population. No new
genetic traits are generated by the geographical isolation of one part of a
population from another.
It could be argued, of course, that mutations might occur during theprocess of speciation, thus generating new genetic traits. But as Gould andEldredge conceived of it, allopatric speciation occurs much too rapidly tohave a reasonable chance of mutations generating anything fundamentallynew. Darwin recognized in On the Origin of Species that evolution is anumbers game: larger population sizes and more generations offer more
opportunities for favorable new variations to arise. As he explained: “Forms
existing in larger numbers will always have a better chance . . . of presenting
further favourable variations for natural selection to seize on, than will therarer forms which exist in lesser numbers.”28 Yet for the mechanism ofallopatric speciation to generate new traits, it would need to generatesignificant changes in form in small “peripherally isolated” populations overrelatively few generations.29 Because of these constraints, many biologists
have concluded that allopatric speciation requires too much change tooquickly to provide the theory of punctuated equilibrium with a biologicallyplausible mechanism for producing new traits or forms of animal life.
And that is why Gould and Eldredge, especially in their later formulationsof the theory, envisioned new traits arising during long periods of stasis inlarger populations rather than during short bursts of speciation. But a process
in which traits arise “during long periods of stasis” does not constitute a“mechanism of unusual speed and flexibility,” though that is precisely what,
according to Gould and Foote, punctuated equilibrium requires in order toexplain the abrupt appearance of new animal forms.
If allopatric speciation does not produce a fast-acting trait-generating
mechanism, does species selection? Again, the answer is no. Species selection
does not account for the origin of the different anatomical traits that
distinguish one species from another. Species selection, as conceived by the
proponents of punctuated equilibrium, acts on species and traits that alreadyexist. Indeed, when Stanley, Gould, and Eldredge envisioned natural selection
acting to favor the most fit species over another in a competition for survival,
they presupposed the existence of a pool of different species and, therefore,
also the existence of some mechanism for producing the traits thatcharacterize those different species. That mechanism, however, would
necessarily need to generate those differentiating traits before species could
enter into competition with each other. Species selection eliminates less fit
species in a competition for survival; it does not generate the traits that
distinguish species and establish the basis for interspecies competition.
So where do these traits come from? When pressed, Gould eventuallyacknowledged that the origin of anatomical traits themselves result fromgood, old-fashioned natural selection acting on random mutations andvariations—that is, from the neo-Darwinian mechanism acting over long
periods of time on large relatively stable populations. But that meant thatpunctuated equilibrium, to the extent it relies on mutation and natural
selection, is subject to the same evidential and theoretical problems as neoDarwinism. And one of those problems is that the neo-Darwinian mechanism
does not act quickly enough to account for the explosive appearance of new
fossil forms in the Cambrian period. Like allopatric speciation, species
selection does not qualify as the kind of rapid and flexible mechanism that
Gould elsewhere insisted his theory must have in order to explain the abrupt
appearance of animal forms in the fossil record.

NOVEL FORM AND MECHANISM
An even more profound difficulty with punctuated equilibrium as an
explanation for the Cambrian explosion remains. Neither species selection nor
allopatric speciation explains the origin of the representatives of the higher
taxonomic categories—that is, the new animals representing new phyla andclasses. Nor does it explain the structural and morphological features that
distinguish animals from one another and earlier forms of life. Allopatricspeciation explains how populations get separated from each other to form
different species. Species selection describes how more fit species
predominate over other species in a competition for survival. Neither
mechanism gives any account of how the animals representing thespecifically higher taxa or their distinctive anatomical novelties arose. Neither
mechanism accounts, for example, for the origin of the compound eye of atrilobite, nor the gills of a Cambrian fish,30 nor the echinoderm body plan.
Many critics of punctuated equilibrium have noted this problem. As
Richard Dawkins wrote in 1986: “What I mainly want a theory of evolution to
do is explain complex, well-designed mechanisms like hearts, hands, eyes andecholocation. Nobody, not even the most ardent species selectionist, thinksthat species selection can do this.”31 Or as paleontologist Jeffrey Levinton
argued in 1988, “It is inconceivable how selection among species can produce
the evolution of detailed morphological structures. . . . Species selection did
not form an eye.”32
So where do these intricate structures come from? Again, when pressed,
Gould resorted to the alleged power of the neo-Darwinian mechanism. As hewrote in his magisterial tome The Structure of Evolutionary Theory, publishedin 2002, the year of his death: “I do not deny either the wonder, or the
powerful importance, of organized adaptive complexity.” He went on toconcede, “I recognize that we know no mechanism for the origin of suchorganismal features other than conventional natural selection at theorganismic level.”33
For this reason, few if any evolutionary biologists now regard punctuatedequilibrium as a solution to the problem of the origin of biological form andnovelty. As the evolutionary biologists Brian Charlesworth, Russell Lande,
and Montgomery Slatkin have concluded, “genetic mechanisms that havebeen proposed [by proponents of punctuated equilibrium] to explain theabrupt appearance and prolonged stasis of many species are conspicuously
lacking in empirical support.”34

BURST OF INTEREST AND GRADUAL DECLINE
Still, it may not be entirely fair to criticize punctuated equilibrium for failingto account for the Cambrian explosion. Gould, in particular, equivocatedabout whether he meant punctuated equilibrium to serve as a comprehensive
theory of macroevolutionary change or just an account of how new species
emerged from a pool of preexisting species. Strictly speaking, themechanisms of allopatric speciation and species selection sought to explain
the pattern of stasis and discontinuity among different species and not among
the higher taxa. Thus, near the end of his career, Gould complained about his
critics “misunderstanding” his theory by asserting that he “proclaimed thetotal overthrow of Darwinism” and “intended punctuated equilibrium as boththe agent of destruction and the replacement.”35
Yet Gould and Eldredge, at least initially, advanced punctuated equilibrium
as a bold new theory of evolutionary biology, giving the impression that itprovided an ambitious solution to the problem of macroevolution and, by
implication, events such as the Cambrian explosion. From 1972 to 1980,
Eldredge and Gould presented a series of provocative scientific papers that
portrayed punctuated equilibrium as a bold, and even revolutionary,alternative theory of macroevolution. Indeed, Gould himself referred to it
explicitly as “a speciational theory of macroevolution.”36
In their second main paper, published in 1977, Gould and Eldredge madeexplicit their intention to position their theory as a “radical”37 challenge to
neo-Darwinian gradualism and to replace it with a completely different
understanding of the mode and mechanism of evolutionary change. Sepkoski
notes that in this 1977 article “the authors were more explicit about the exact
nature of the conceptual reconfiguration their theory brought tomacroevolution.”38 In particular, he argues that Gould and Eldredge“extended their model to propose a new and ‘general philosophy of change’ inthe natural world.”39 Gould was no less radical in a widely cited 1980 paperin the journal Paleobiology in which he offered punctuated equilibrium as “anew and general theory” of evolution. There he also famously declared thesynthetic theory of neo-Darwinism “effectively dead, despite its persistence as
textbook orthodoxy.”40
Only after critics exposed punctuated equilibrium for lacking an adequate
mechanism did Gould retreat to a more conservative formulation of thetheory, making its reliance upon the neo-Darwinian mechanism explicit. Fromthe early 1980s until his death in 2002, Gould made a series of concessions inparticular about the inadequacy of speciation and species selection asmechanisms for generating complex adaptations. Thus, as Sepkoski notes,

“Despite the brashness of many of his claims on behalf of punctuatedequilibrium over the years, one is brought time and again back to thereconciliatory, even conservative justifications Gould made for his theory,”
particularly, he notes, in The Structure of Evolutionary Theory, written in theyears just before Gould’s death.41
In the end, Gould’s concessions to neo-Darwinism brought his thinking
back into conflict with the pattern of sudden appearance in the fossil recordthat the theory of punctuated equilibrium was designed to explain. If Gould
and Eldredge were right about the abrupt appearance of new forms of life in
the fossil record, and if the neo-Darwinian mechanism needs as much time as
evolutionary biologists and population geneticists (see Chapters 8 and 12)
calculate, then the mutation and selection mechanism does not have enoughtime to produce the new traits needed to build the forms of life that first
appear in the Cambrian period. But punctuated equilibrium, as initiallyformulated to rely mainly on allopatric speciation and species selection, fared
no better, since neither mechanism gives any explanation for the origin of
new traits. And so, in the end, punctuated equilibrium highlighted rather thanresolved a profound dilemma for evolutionary theory: neo-Darwinism
allegedly has a mechanism capable of producing new genetic traits, but it
appears to produce them too slowly to account for the abrupt appearance of
new form in the fossil record; punctuated equilibrium attempts to address thepattern in the fossil record, but fails to provide a mechanism that can produce
new traits whether abruptly or otherwise. No wonder, then, that leading
Cambrian paleontologists such as James Valentine and Douglas Erwin
concluded in 1987, that “neither of the contending theories of evolutionarychange at the species level, phyletic gradualism or punctuated equilibrium,seem applicable to [explaining] the origin of new body plans.”42
SPINNING IN CIRCLES
In a sudden flash of insight in the humdrum of a Laundromat, Niles Eldredge
realized that stasis in the fossil record represented evidence rather than mere
investigative failure. But like laundry spinning around in a washing machine,
the theory of punctuated equilibrium itself became caught in a dreary cycle ofcontradiction. On the one hand, “punk eek” made a bold attempt to describe
more accurately, and even explain, the decidedly discontinuous pattern of thefossil record. On the other, its advocates were forced to concede both theinadequacy of their proposed mechanisms and their need to rely upon the neoDarwinian process of mutation and selection in order to account for the originof new genetic traits and anatomical innovations. After Gould appeared tojettison both gradualism and a reliance on the neo-Darwinian mechanism inorder to bring evolutionary theory into conformity with the fossil record, heeventually acknowledged that he could not explain the origin of the forms oflife documented in the fossil record apart from that same slow and graduallyacting mechanism. Thus, though the theory of punctuated equilibrium wasinitially presented as a solution to the mysterious and sudden origin of animal
forms, upon closer inspection, it failed to offer such a solution.
Nevertheless, the failure of punctuated equilibrium to provide a sufficientmechanism has raised questions about the adequacy of the mechanism that
Gould ultimately did reaffirm as the explanation for the origin of novel
biological form. Can the neo-Darwinian mechanism of natural selection
acting on random mutations build new forms of animal life with all theircomplex adaptations? If so, is it possible that it could do so in the brief timeallowed by the fossil record? If not, is it reasonable to think that it could build
new forms of animal life if only more time were available? If so, how muchtime would the Darwinian mechanism need to build complex adaptations andnew forms of animal life? In the next several chapters, I will address thesefundamental questions at the heart of the Cambrian mystery—questions, inbrief, about how to build an animal.

Part Two

How to Build an Animal

8
The Cambrian Information Explosion
When I was a college professor, I used to ask my students a question: “If you
want your computer to acquire a new function or capability, what do you haveto give it?” Typically, I would hear a smattering of similar answers from theclass: “code,” “instructions,” “software,” “information.” Of course, all these
are correct. And thanks to discoveries in modern biology, we now know thatsomething similar is true of life: to build a new form of life from a simpler
preexisting form requires new information.
To this point I’ve examined one main aspect of the mystery surrounding
the Cambrian explosion: the mystery of the missing Precambrian ancestralforms expected on the basis of Darwin’s theory. The next group of chapterswill examine a second, and perhaps more profound, aspect of the Cambrian
mystery: that of the cause of the Cambrian explosion. By what means orprocess or mechanism could something as complex as a trilobite have arisen?
Could natural selection have accomplished such a feat? To answer thisquestion we will have to look more closely at what it takes to build a newform of animal life. And we’ll see that an important part of the answer to thatquestion will have something to do with the concept of information.
THE DARWINIAN ACCOUNT OF THE ORIGIN OF ANIMAL FORM
As Darwin envisioned the process, natural selection can accomplish nothing
without a steady supply of variation as a source of new biological traits,
forms, and structures. Only after useful new variations arise can natural
selection sift them from the chaff of unhelpful variations. If, however, theamount of variation available to natural selection is limited, then natural
selection will encounter limits on how much new biological form andstructure it can build.
Even in the late nineteenth century, many leading scientists recognized
this. For this reason, there has been a long history of scientific controversy
about just how much novelty natural selection can produce and about whether
natural selection is a truly creative process. In fact, between 1870 and 1920

classical Darwinism entered a period of eclipse, because many scientists
thought that it could not explain the origin and transmission of new heritablevariation.1
Darwin favored a theory of blended inheritance that seemed to imply
limitations on the amount of genetic variability.2 He thought that when
parents with different traits combined germ cells during sexual reproduction,
the resulting offspring would receive not one or the other set of their differing
traits, but instead a compromise version. For example, if a male bird with redfeathers on its wings mated with a female bird of the same species with whitewing feathers, the theory implied that the two would likely produce offspringwith pink wing feathers. As many of Darwin’s contemporaries pointed out,
such instances of blending inheritance involved strict limitations on the rangeof traits that could possibly arise, depriving natural selection of the wideranging supply of variation it would need to produce truly fundamental
changes in the form of animals. The pink-feathered offspring might later
reproduce with a white- or red-feathered bird of the same species, producing aslightly lighter or darker shade of pink feathers. Nevertheless, descendants of
the original white- and red-feathered pair would never produce green, blue, or
yellow feathers in subsequent generations. If correct, blending inheritancewould eventually lead to a bland, homogenous, variationless state in a
population.
In the 1860s, the Austrian monk Gregor Mendel, widely regarded as thefounder of modern genetics, showed in his work on garden peas that Darwin’s
assumptions about blending inheritance were incorrect. The results of his
studies created, at least initially, more problems for Darwinism. Mendel
showed that the genetic traits of organisms typically have an integrity that
resists blending. He showed this by cross-pollinating plants with yellow peas
and plants with green peas. The plants in the subsequent generations produced
either yellow or green peas, but nothing in between and nothing with analtogether different color.3
He also showed that the plants carried some kind of signal or instructions
for building different traits even when the trait was not on display in aparticular plant. He noticed, for example, that when he crossed pea plants
with green and yellow seeds, the next generation had only yellow seeds,
almost as if the capacity for generating green peas had been lost. But when hecross-pollinated the second-generation plants, the ones with only yellow peas,
he found that both yellow and green peas emerged in the third generation, in aratio of 3 to 1. From this Mendel hypothesized that the second-generation
plants continued to carry signals, which he called “factors,” and laterscientists called genes, for generating green peas even when those plants

themselves did not display that trait.
The classical Mendelian genetics that replaced Darwin’s blending theoryof inheritance also suggested limitations on the amount of genetic variability
available to natural selection. If plant reproduction produced either green or
yellow peas but never some intermediate form, and if the signals for
producing the green traits and yellow traits persisted unchanged fromgeneration to generation, it was difficult to see how sexual reproduction andgenetic recombination could produce anything more than unique
combinations of already existing traits.
In the decades immediately after Mendel’s work, geneticists came tounderstand genes as discrete units or packets of hereditary information that
could be independently sorted and shuffled within the chromosome. This too
suggested that a significant, but still strictly limited, amount of genetic
variation could arise by genetic recombination during sexual reproduction.
Thus, Mendelian genetics raised significant questions about whether theprocess of natural selection has access to enough variation (which, after
Mendel, was conceived as genetic variation) to allow it to produce any
significant morphological novelty. For a time, Darwin’s theory was in retreat.
DARWINISM MUTATESDuring the 1920s, 1930s, and 1940s, however, developments in genetics
revived natural selection as the main engine of evolutionary change.
Experiments performed by Hermann Muller in 1927 showed that X-rays
could alter the genetic composition of fruit flies, resulting in unusual
variations.4 Muller called these X-ray-induced changes “mutations.” Other
scientists soon reported that they had produced mutations in the genes ofother organisms, including humans. Whatever genes were made of—andbiologists then still did not know—these developments suggested they could
vary more than either Darwin or classical Mendelian genetics had assumed.
Geneticists at the time also discovered that these small-scale changes in genes
were potentially heritable.5 But if variant versions of genes were heritable,
then presumably natural selection could favor advantageous gene variants andeliminate the others. These mutations could then influence the future directionof evolution and, in theory at least, provide an unlimited supply of variation
for natural selection’s workshop.
The discovery of genetic mutations also suggested a way to reconcile
Darwinian theory with insights from Mendelian genetics. During the 1930s
and 1940s, a group of evolutionary biologists, including Sewall Wright, Ernst
Mayr, Theodosius Dobzhansky, J. B. S. Haldane, and George Gaylord

Simpson, attempted to demonstrate this possibility using mathematicalmodels to show that small-scale variations and mutations could accumulate
over time in whole populations, eventually producing large-scalemorphological change.6 These mathematical models formed the basis of a
subdiscipline of genetics known as population genetics. The overall synthesisof Mendelian genetics with Darwinian theory came to be called “neoDarwinism” or simply the “New Synthesis.”
According to this new synthetic theory, the mechanism of natural selection
acting upon genetic mutations suffices to account for the origin of novel
biological forms. Small-scale “microevolutionary” changes can accumulate toproduce large-scale “macroevolutionary” innovations. The neo-Darwinists
argued that they had revived natural selection by discovering a specificmechanism of variation that could generate new forms of life from simpler
preexisting ones. By the centennial celebration of Darwin’s Origin of Species
in 1959, it was widely assumed that natural selection and random mutations
could indeed build new forms of life over the course of time with their
distinctive body plans and novel anatomical structures. At the celebration,
Julian Huxley, the grandson of T. H. Huxley, summarized this optimism in a
grand proclamation:
Future historians will perhaps take this Centennial Week as epitomizing
an important critical period in the history of this earth of ours—theperiod when the process of evolution, in the person of inquiring man,began to truly be conscious of itself. . . . This is one of the first public
occasions on which it has been frankly faced that all aspects of reality
are subject to evolution, from atoms and stars to fish and flowers, fromfish and flowers to human societies and values—indeed, that all reality
is a single process of evolution . . .7
In a television broadcast leading up to the Centennial celebration, Huxley
captured the optimistic mood more succinctly: “Darwinism has come of age,so to speak. We are no longer having to bother about establishing the fact ofevolution.”8
VARIATION AS INFORMATION
Initially, the elucidation of the structure of DNA by James Watson and Francis
Crick in 1953 contributed to this euphoria.9 Indeed, it seemed to lift themechanism of genetic variation and mutation out of the mist and into the clear
light of the emerging science of molecular biology. Watson and Crick’s

elucidation of the double helix structure of DNA suggested that DNA stored
genetic information in the form of a four-character digital and chemical code
(see Fig. 8.1). Later, following the formulation of Francis Crick’s famed“sequence hypothesis,” molecular biologists confirmed that the chemical
subunits along the spine of the DNA molecule called nucleotide bases
function just like alphabetic characters in a written language or digitalcharacters in a machine code. Biologists established that the precise
arrangement of these nucleotide bases conveyed instructions for building
proteins.10 (See Fig. 8.2.) Molecular biologists also determined that this store
of genetic information in DNA is transmitted from one generation of cells andorganisms to another. In short, it was established that DNA stores hereditary
information for building proteins and thus, presumably, for building higherorder anatomical traits and structures as well.
The elucidation of the double helix seemed to resolve some long-standing
issues in evolutionary biology. Darwinists had long maintained that natural
selection produced new forms by separating the proverbial wheat from thechaff of genetic variation, but they didn’t know where the raw material for allof the competing variations resided. Neither did they know how genes stored
information for producing the traits associated with them. Further, even aftergeneticists discovered that stable genetic traits could be altered by mutations,they remained uncertain about what exactly it was that was being “mutated.”
Consequently, biologists were uncertain about exactly where variations andmutations occurred.

FIGURE. 8.1
James Watson (left) and Francis Crick (right) presenting their model of thestructure of the DNA molecule in 1953. Courtesy A. Barrington

Brown/Science Source.
Watson and Crick’s model suggested an answer to that question: genes
correspond to long sequences of bases on a strand of DNA. Building on that
insight, evolutionary biologists proposed that new variations arose, first, fromthe genetic recombination of different sections of DNA (different genes)
during sexual reproduction and, second, from a special kind of variation
called mutations that occur from random changes in the arrangement of
nucleotide bases in DNA. Just as a few typographical errors in an English
sentence might alter the meaning of a few words or even the whole sentence,
so too might a change in the sequential arrangement of the bases in thegenetic “text” in DNA produce new proteins or morphological traits.

FIGURE 8.2
The model (or structural formula) of the DNA molecule showing the digital or
alphabetic character of the nucleotide bases stored along the sugar-phosphatebackbone of the molecule.
Watson and Crick’s discovery also raised new questions—in particular,
questions about the information necessary to build completely new forms oflife during the course of biological evolution. True, mutations play a role inthis process, but could they generate enough information to produce novel
forms of animal life such as those that arose in the Cambrian period, an
explosion—a vast proliferation—of new biological information?
THE CAMBRIAN INFORMATION EXPLOSION
Consider choanoflagellates, a group of single-celled eukaryotic organisms
with a flagellum. What separates such organisms from a trilobite or a mollusk
or even a lowly sponge? Clearly, all three of these higher forms of life are
more complex than any one-celled organism. But exactly how much more
complex?
James Valentine has noted that one useful way of comparing degrees ofcomplexity is to assess the number of cell types in different organisms (seeFig. 8.3).11 Though a single-celled eukaryote has many specialized internal
structures such as a nucleus and various organelles, it still, obviously,
represents just a single type of cell. Functionally more complex animals
require more cell types to perform their more diverse functions. Arthropods
and mollusks, for example, have dozens of specific tissues and organs, eachof which requires “functionally dedicated,” or specialized, cell types.
These new cell types, in turn, require many new and specialized proteins.
An epithelial cell lining a gut or intestine, for example, secretes a specificdigestive enzyme. This enzyme requires structural proteins to modify its
shape and regulatory enzymes to control the secretion of the digestive enzyme
itself. Thus, building novel cell types typically requires building novel
proteins, which requires assembly instructions for building proteins—that is,
genetic information. Thus, an increase in the number of cell types implies anincrease in the amount of genetic information.

FIGURE 8.3
Biological complexity scale as measured in number of cell types of different
organisms.
Applying this insight to ancient life-forms underscores just how dramaticthe Cambrian explosion was. For over 3 billion years, the living world
included little more than one-celled organisms such as bacteria and algae.12
Then, beginning in the late Ediacaran period (about 555–570 million yearsago), the first complex multicellular organisms appeared in the rock strata,
including sponges and the peculiar Ediacaran biota discussed in Chapter 4.13
This represented a large increase in complexity. Studies of modern animals
suggest that the sponges that appeared in the late Precambrian, for example,
probably required about ten cell types.14
Then 40 million years later, the Cambrian explosion occurred.15 Suddenly
the oceans swarmed with animals such as trilobites and anomalocaridids thatprobably required fifty or more cell types—an even greater jump incomplexity. Moreover, as Valentine notes, measuring complexity differencesby measuring differences in the number of cell types probably “greatly
underestimate[s] the complexity differentials between bodyplans.”16
One way to estimate the amount of new genetic information that appearedwith the Cambrian animals is to measure the size of the genomes of modern
representatives of the Cambrian groups and compare that to the amount of
information in simpler forms of life. Molecular biologists have estimated thata minimally complex single-celled organism would require between 318,000
and 562,000 base pairs of DNA to produce the proteins necessary to maintainlife.17 More complex single cells might require upwards of a million basepairs of DNA. Yet to assemble the proteins necessary to sustain a complex

arthropod such as a trilobite would need orders of magnitude more proteincoding instructions. By way of comparison, the genome size of a modern
arthropod, the fruit fly Drosophila melanogaster, is approximately 140
million base pairs.18 Thus, transitions from a single cell to colonies of cells tocomplex animals represent significant—and in principle measurable—
increases in genetic information.
During the Cambrian period a veritable carnival of novel biological forms
arose. But because new biological form requires new cell types, proteins, andgenetic information, the Cambrian explosion of animal life also generated an
explosion of genetic information unparalleled in the previous history of life.19(In Chapter 14, we’ll see that building a new animal body plan also requires
another type of information, not stored in genes, called epigenetic
information.)
So can the neo-Darwinian mechanism explain the dramatic increase in
genetic information that appears in the Cambrian explosion? Before
addressing that question, it will help to define the concept of information andidentify the kind of information that DNA contains.
BIOLOGICAL INFORMATION: SHANNON OR OTHERWISE?
Scientists typically recognize at least two basic types of information,functional (or meaningful) information and so-called Shannon information,
which is not necessarily meaningful or functional. The distinction has arisen
in part because of developments in a branch of applied mathematics known as
information theory. During the late 1940s, mathematician Claude Shannon,
working at the Bell Laboratories, developed a mathematical theory of
information. Shannon equated the amount of information transmitted by asequence of symbols or characters with the amount of uncertainty reduced oreliminated by the transmission of that sequence.20
Shannon thought that an event or communication that didn’t eliminatemuch uncertainty was also not very informative. Consider an illustration. In
the 1970s, when I was a teenager, if someone made a completely obvious
statement, we would say, “Tell me something else I didn’t know.” Imagine
that one of my classmates on the baseball team has just rushed up tobreathlessly “inform” me that our team’s star pitcher is planning to throw theball to the catcher in the next game. Such a statement would earn the scornful
reply, “Tell me something else I didn’t know.”
The obvious statement about the pitcher’s intentions also illustrates why
Shannon equated the elimination of uncertainty with the transmission of
information. Since star pitchers who want to go on being star pitchers have nochoice but to throw the ball across the plate to the catcher, the statement of
my overwrought friend eliminated no previous uncertainty. It was not
informative in the least. If, on the other hand, after days of speculation on
campus about which one of our team’s four pitchers the baseball coach would
choose to pitch in the championship game, my friend had rushed up to me andrevealed the identity of the starting pitcher, that would be different. In thatcase, he would have eliminated some significant uncertainty on my part witha decidedly informative statement.
Shannon’s theory quantified the intuitive connection between reduced
uncertainty and information by asserting that the more uncertainty an event orcommunication eliminated, the more information it conveyed. Imagine thatafter revealing to me the identity of the starting pitcher before thechampionship baseball game in the spring, he then also revealed to me theidentity of the starting quarterback before the upcoming football season.
Imagine as well that our baseball team had four equally competent pitchers
and the football team had just two equally competent quarterbacks. Given
these facts, my friend’s decision to inform me of the identity of the starting
pitcher eliminated more uncertainty than his decision to reveal to me theidentity of the starting quarterback.
To assign precise quantitative measures of information, Shannon further
linked the reduction of uncertainty and information to quantitative measuresof probability (or improbability). Notice that in my illustration, the more
informative communication reduced more uncertainty and also described amore improbable event. The probability of any one of the four pitchers being
selected was 1 in 4. The probability of one of the quarterbacks being selected,
given the same assumption, was only 1 in 2. The more improbable event
eliminated more possibilities and more uncertainty. Thus, it conveyed more
information.
Shannon applied these intuitions to quantify the amount of information
present in sequences of symbols or characters stored in texts or codes ortransmitted across communications channels. Thus, in his theory the presenceof an English letter in a sequence of other such letters transmits more
information than a single binary digit (a zero or one) in a section of computercode. Why? Again, the letter in the English alphabet reduces uncertainty
among twenty-six possibilities, whereas a single binary digit reduces
uncertainty among only two. The probability of any one character from theEnglish alphabet occurring in a sequence of other such letters (disregarding
the need for spaces and punctuation) is 1 in 26. The probability of either azero or one arising in a sequence of binary characters is 1 in 2. In Shannon’s
theory the presence of the more improbable character conveys more

information.
Yet even a binary alphabet can convey an unlimited amount of information
because, in Shannon’s theory, additional information is conveyed as
improbabilities multiply. Imagine a grab bag of tiles with either zero or one
etched onto each. Imagine someone producing a series of zeros and ones byreaching into the bag and placing them one by one on a game board. The
probability of choosing a zero on the first pick is just 1 in 2. But theprobability of choosing two consecutive zeros after placing the first back in
the grab bag (and shaking the tiles) is 1 chance in 2 × 2, or 1 chance in 4. Thisis because there are four possible combinations of digits that could have beenchosen—00, 01, 10, or 11. Similarly, the probability of producing any threeletter sequence as a result of choosing consecutively in this manner is 1 in 2 ×
2 × 2, or 1 in 23 (or 1 in 8). The improbability of any specific sequence ofcharacters increases exponentially with the number of characters in thesequence. Thus, longer and longer sequences can generate larger and larger
amounts of information even using a simple binary alphabet.
Information scientists measure such informational increases through a unit
they call a bit. A bit represents the minimum amount of information that canbe conveyed (or uncertainty reduced) by a single digit in a two-characteralphabet.21
Biologists can readily apply Shannon’s information theory to measure theamount of Shannon information in a sequence of DNA bases (or the sequenceof amino acids in a protein) by assessing the probability of the sequenceoccurring and then converting that probability to an information measure in
bits.22 DNA conveys information, in Shannon’s sense, in virtue of its
containing long improbable arrangements of four chemicals—the four basesthat fascinated Watson and Crick—adenine, thymine, guanine, and cytosine(A, T, G, and C). As Crick realized in formulating his sequence hypothesis,
these nucleotide bases function as alphabetic or digital characters in a linear
array. Since each of the four bases has an equal 1 in 4 chance of occurring at
each site along the spine of the DNA molecule, biologists can calculate theprobability, and thus the Shannon information, or what is technically known
as the “information-carrying capacity,” of any particular sequence n bases
long. For instance, any particular sequence three bases long has a probabilityof 1 chance in 4 × 4 × 4, or 1 chance in 64, of occurring—which corresponds
to 6 bits of Shannon information. (Indeed, each base in a DNA sequence
conveys 2 bits of information, since 1 in 4 is equal to 1 chance in 2 × 2.)
Yet the applicability of Shannon information theory to molecular biology
has, to some degree, obscured a key distinction concerning the type of
information that DNA possesses. Although Shannon’s theory measures theamount of information in a sequence of symbols or characters (or chemicals
functioning as such), it doesn’t distinguish a meaningful or functionalsequence from useless gibberish. For example:“we hold these truths to be self-evident”“ntnyhiznslhtgeqkahgdsjnfplknejmsed”
These two sequences are equally long and equally improbable if we imagine
them being drawn at random. Thus, they contain the same amount of Shannon
information. Yet clearly there is an important qualitative distinction between
them that the Shannon measurement does not capture. The first meaningful
sequence performs a communication function, while the second does not.
Shannon emphasized that the kind of information his theory described
needs to be carefully distinguished from our common notions of information.
As Warren Weaver, one of Shannon’s close collaborators, made clear in 1949,“The word ‘information’ in this theory is used in a special mathematical sensethat must not be confused with its ordinary usage.”23 By ordinary usage,
Weaver, of course, was referring to the idea of meaningful or functional
communication.
Webster’s dictionary defines information as “the communication or
reception of knowledge or intelligence.” It also defines information as “theattribute inherent in, and communicated by, alternative sequences orarrangements of something that produce a specific effect.” A sequence ofcharacters possessing a large amount of Shannon information may convey
meaning (as in an English text) or perform a function that “produces a
specific effect” (as do both English sentences and computer codes, forexample) or it may not (as would be the case with a meaningless pile of lettersor a screen of scrambled computer code). In any case, Shannon’s purely
mathematical theory of information does not distinguish the presence of
meaningful or functional sequences from merely improbable, thoughmeaningless ones. It only provides a mathematical measure of the
improbability—or information-carrying capacity—of a sequence ofcharacters. In a sense, it provides a measure of a sequence’s capacity to carryfunctional or meaningful information. It does not, and cannot, determine
whether the sequence in question does convey meaning or generate afunctionally significant effect.
Strands of DNA contain information-carrying capacity—something
Shannon’s theory can measure.24 But DNA, like natural languages andcomputer codes, also contains functional information.25
In languages such as English, specifically arranged characters convey

functional information to conscious agents. In computer or machine code,
specifically arranged characters (zeros and ones) produce functionallysignificant outcomes within a computational environment without a conscious
agent receiving the meaning of the code inside the machine. In the same way,
DNA stores and conveys functional information for building proteins or RNA
molecules, even if it is not received by a conscious agent. As in computercode, the precise arrangement of characters (or chemicals functioning as
characters) allows the sequence to “produce a specific effect.” For this reason,
I also like to use the term specified information as a synonym for functional
information, because the function of a sequence of characters depends upon
the specific arrangement of those characters.
And DNA contains specified information, not just Shannon information or
information-carrying capacity. As Crick himself put it in 1958, “Byinformation I mean the specification of the amino acid sequence in protein.
. . . Information means here the precise determination of sequence, either ofbases in the nucleic acid or on amino acid residues of the protein.”26
THE MESSAGE AS THE MYSTERY
So if the origin of the Cambrian animals required vast amounts of new
functional or specified information, what produced this information
explosion? Since the molecular biological revolution first highlighted theprimacy of information to the maintenance and function of living systems,
questions about the origin of information have moved decidedly to theforefront of discussions about evolutionary theory. What’s more, therealization that specificity of arrangement, rather than mere improbability,
characterizes the genetic text has raised some challenging questions about theadequacy of the neo-Darwinian mechanism. Is it plausible to think thatnatural selection working on random mutations in DNA could produce thehighly specific arrangements of bases necessary to generate the proteinbuilding blocks of new cell types and novel forms of life? Perhaps nowhere
do such questions pose more of a challenge to neo-Darwinian theory than in
discussions of the Cambrian explosion.

9
Combinatorial Inflation
Murray Eden (see Fig. 9.1), a professor of engineering and computer scienceat MIT, was accustomed to thinking about how to build things. But when hebegan to consider the importance of information to building living organisms,
he realized something didn’t add up. His critics said that he knew just enoughbiology to be dangerous. In retrospect, they were probably right.
In the early 1960s, just as molecular biologists had confirmed Francis
Crick’s famed sequence hypothesis, Eden began to think about the challengeof building a living organism. Of course, Eden wasn’t contemplating building
a living organism himself. Rather, he was thinking about what it would takefor the neo-Darwinian mechanism of natural selection acting on random
mutations to do the job. He wondered whether mutation and selection could
generate the needed functional information.
To his way of thinking, specificity was a big part of the problem.
Obviously, if DNA contained an improbable sequence of nucleotide bases inwhich the arrangement of bases does not matter to the function of themolecule, then random mutational changes in the sequence of bases would
not have a detrimental effect on the function of the molecule. But, of course,
sequence does affect function. Eden knew that in all computer codes or
written text in which the specificity of sequence determines function, randomchanges in sequence consistently degrade function or meaning. As he
explained, “No currently existing formal language can tolerate randomchanges in the symbol sequences which express its sentences. Meaning isalmost invariably destroyed.”1 Thus, he suspected that the need for specificity
in the arrangement of DNA bases made it extremely improbable that random
mutations would generate new functional genes or proteins as opposed todegrading existing ones.
But how improbable? How difficult would it be for random mutations togenerate, or stumble upon, the genetically meaningful or functional sequences
needed to supply natural selection with the raw material—the genetic
information and variation—it needed to produce new proteins, organs, andforms of life? Eden wasn’t the only mathematician or scientist asking thesequestions. But the mathematically based challenge to evolutionary theory thathe helped to initiate would indeed prove dangerous to neo-Darwinianorthodoxy.
THE WISTAR INSTITUTE CONFERENCE
During the early 1960s, Eden began discussing the plausibility of the neoDarwinian theory of evolution with several MIT colleagues in math, physics,
and computer science. As the discussion grew to include mathematicians andscientists from other institutions, the idea of a conference was born. In 1966, adistinguished group of mathematicians, engineers, and scientists convened a
conference at the Wistar Institute in Philadelphia called “Mathematical
Challenges to the Neo-Darwinian Interpretation of Evolution.” Prominent
among the attendees were Marcel-Paul Schützenberger, a mathematician andphysician at the University of Paris; Stanislaw Ulam, the codesigner of thehydrogen bomb; and Eden himself. The conference also included a number ofprominent biologists, including Ernst Mayr, an architect of modern neoDarwinism, and Richard Lewontin, at the time a professor of genetics andevolutionary biology at the University of Chicago.

FIGURE 9.1
Murray Eden. Courtesy MIT Museum.

Sir Peter Medawar, a Nobel laureate and the director of the North London
Medical Research Council’s laboratories, chaired the meeting. In his opening
remarks, he said, “The immediate cause of this conference is a pretty
widespread sense of dissatisfaction about what has come to be thought of as
the accepted evolutionary theory in the English-speaking world, the so-called
neo-Darwinian theory.”2
For many, doubts about the creative power of the mutation and selection
mechanism stemmed from the elucidation of the nature of genetic information
by molecular biologists in the late 1950s and early 1960s.
The discovery that the genetic information in DNA is stored as a linear
array of precisely sequenced nucleotide bases at first helped to clarify thenature of many mutational processes. Just as a sequence of letters in an
English text might be altered either by changing individual letters one by one
or by combining and recombining whole sections of text, so too might thegenetic text be altered either one base at a time or by combining andrecombining different sections of genes in various ways at random. Indeed,
modern genetics has established various mechanisms of mutational change—
not only “point mutations,” or changes in individual bases, but also
duplications, insertions, inversions, recombinations, and deletions of whole
sections of the genetic text.
Although fully aware of this range of mutational options at nature’s
disposal, Eden argued at Wistar that such random changes to written texts or
sections of digital code would inevitably degrade the function of informationbearing sequences, particularly when allowed to accumulate.3 For example,
the simple phrase “One if by land and two if by sea” will be significantly
degraded by just a handful of random changes such as those in bold: “Ine if
bg lend and two ik bT Nea.” At the conference the French mathematician
Marcel Schützenberger agreed with Eden’s concerns about the effect ofrandom alterations. He noted that if someone makes even a few randomchanges in the arrangement of the digital characters in a computer program,“we find that we have no chance (i.e., less than 1/101000) even to see what themodified program would compute: it just jams.”4 Eden argued that much thesame problem applied to DNA—that insofar as specific arrangements ofbases in DNA function like digital code, random changes to thesearrangements would likely efface their function, while attempts to generatecompletely new sections of genetic text by random means were likely doomed
to failure.5
The explanation for this inevitable diminution in function is found in abranch of mathematics called combinatorics. Combinatorics studies thenumber of ways a group of things can be combined or arranged. At one level,
the subject is fairly intuitive. If a thief slips round the corner of a dormitory
after hours looking for a bike to steal, he will scan the bike rack for an easytarget. If he spots a basic bicycle-style lock with only three dials of ten
numbers each, and on the rack beside it one with five dials of ten numbers
each, the thief wouldn’t need a degree in mathematics to realize which one heshould attempt to open. He knows that he would need to search fewer total
possibilities with the three-dial lock.
A straightforward calculation supports his intuition. The simpler lock has
only 10 × 10 × 10, or 1000, possible combinations of digits—or whatmathematicians refer to as “combinatorial” possibilities. The five-dial lockhas 10 × 10 × 10 × 10 × 10, or 100,000, combinatorial possibilities. With a lotof patience, the thief might elect to systematically work his way through thedifferent combinations of digits on the simpler lock, knowing that at somepoint he will stumble across the correct combination. He shouldn’t evenbother with the five-dial lock, since making his way through all of thepossible combinations on it would take 100 times as long. The five-dial lock
simply has too many possibilities for the thief to have a reasonable chance of
opening it by trial and error in the time available to him.
Several of the Wistar scientists noted that the mutation and selection
mechanism faces a similar problem. Neo-Darwinism envisions new genetic
information arising from random mutations in the DNA. If at any time frombirth to reproduction the right mutation or combination of mutations
accumulate in the DNA of cells involved in reproduction (whether sexual or
asexual), then information for building a new protein or proteins will pass onto the next generation. When that new protein happens to confer a survival
advantage on an organism, the genetic change responsible for the new protein
will tend to be passed on to subsequent generations. As favorable mutations
accumulate, the features of a population will gradually change over time.
Clearly, natural selection plays a crucial role in this process. Favorable
mutations are passed on; unfavorable mutations are weeded out. Nevertheless,the process can only select variations in the genetic text that mutations havefirst produced. For this reason, evolutionary biologists typically recognize that
mutation, not natural selection, provides the source of variation andinnovation in the evolutionary process. As evolutionary biologists Jack Kingand Thomas Jukes put it in 1969, “Natural selection is the editor, rather thanthe composer, of the genetic message.”6
And that was the problem, as the Wistar skeptics saw it: random mutations
must do the work of composing new genetic information, yet the sheer
number of possible nucleotide base or amino-acid combinations (i.e., the size

of the combinatorial “space”) associated with a single gene or protein of evenmodest length rendered the probability of random assembly prohibitively
small. For every sequence of amino acids that generates a functional protein,
there are a myriad of other combinations that don’t. As the length of therequired protein grows, the number of possible amino-acid combinations
mushrooms exponentially. As this happens, the probability of ever stumblingby random mutation onto a functional sequence rapidly diminishes.
Consider another illustration. The two letters X and Y can be combined infour different two-letter combinations (XX, XY, YX and YY). They can be
combined in eight different ways for three-letter combinations (XXX, XXY,
XYY, XYX, YXX, YYX, YXY, YYY), sixteen ways for four-letter
combinations, and so on. The number of possible combinations grows
exponentially—22, 23, 24, and so on—as the number of letters in the sequence
grows. Mathematician David Berlinski calls this the problem of“combinatorial inflation,” because the number of possible combinations“inflates” dramatically as the number of characters in a sequence grows (seeFig. 9.2).
The combinations of bases in DNA are subject to combinatorial inflationof just this sort. The information-bearing sequences in DNA consist of
specific arrangements of the four nucleotide bases. Consequently, there are
four possible bases that could occur at each site along the DNA backbone and4 × 4, or 42, or 16 possible two-base sequences (AA AT AG AC TA TG TC
TT CG CT CC CA GA GG GC GT). Similarly, there are 4 × 4 × 4, or 43, or
64 possible three-base sequences. (I’ll refrain from listing them all.) That is,increasing the number of bases in a sequence from 1 to 2 to 3 increases thenumber of possibilities from 4 to 16 to 64. As the sequence length continues
to grow, the number of combinatorial possibilities corresponding to sequencesof increasing length inflates exponentially. For example, there are 4100, or
1060, possible ways of arranging one hundred bases in a row.

FIGURE 9.2
The problem of combinatorial inflation as illustrated by bike locks of varying
sizes. As the number of dials on the bike locks increases, the number ofpossible combinations rises exponentially.
The amino-acid chains are also subject to such inflation. A chain of two
amino acids could display 202, or 20 × 20, or 400 possible combinations,since each of the twenty protein-forming amino acids could combine with any
one of that same group of twenty in the second position of a short peptide
chain. With a three-amino-acid sequence, we’re looking at 203, or 8,000,
possible sequences. With four amino acids, the number of combinations rises
exponentially to 204, or 160,000, total combinations, and so on.
Now, the number of combinatorial possibilities corresponding to a chain
with four amino acids only marginally outstrips the combinatorial possibilities
associated with the five-dial lock in my first illustration (160,000 vs.

100,000). It turns out, however, that many necessary, functional proteins incells require far, far more than just four amino acids linked in sequence, andnecessary genes require far, far more than just a few bases. Most genes—
sections of DNA that code for a specific protein—consist of at least one
thousand nucleotide bases. That corresponds to 41000—an unimaginably large
number—possible base sequences of that length.
Moreover, it takes three bases in a group called a codon to designate one of
the twenty protein-forming amino acids in a growing chain during protein
synthesis. If an average gene has about 1000 bases, then an average protein
would have over 300 amino acids, each of which are called “residues” byprotein chemists. And indeed proteins typically require hundreds of aminoacids in order to perform their functions. This means that an average-length
protein represents just one possible sequence among an astronomically large
number—20300, or over 10390—of possible amino-acid sequences of that
length. Putting these numbers in perspective, there are only 1065 atoms in our
Milky Way galaxy and 1080 elementary particles in the known universe.
That is what bothered Eden and other mathematically inclined scientists at
Wistar. They understood the immensity of the combinatorial spaces associatedwith even single genes or proteins of average length. They realized that if themutations themselves were truly random—that is, if they were neither
directed by an intelligence nor influenced by the functional needs of theorganism (as neo-Darwinism stipulates)—then the probability of the mutationand selection mechanism ever producing a new gene or protein could well bevanishingly small. Why? The mutations would have to generate, or “search”
by trial and error, an enormous number of possibilities—far more than wererealistic in the time available to the evolutionary process.
Eden pointed out in his Wistar presentation that the combinatorial spacecorresponding to an average-length protein (which he assumed to be about
250 amino acids long) is 20250—or about 10325—possible amino-acidarrangements. Did the mutation and selection mechanism have enough time—since the beginning of the universe itself—to generate even a small fraction of
the total number of possible amino-acid sequences corresponding to a single
functional protein of that length? For Eden, the answer was clearly no.
For this reason, Eden thought mutations had virtually no chance of
producing new genetic information. He likened the probability of producing
the human genome by relying on random mutations to that of generating alibrary of a thousand volumes by making random changes or additions to asingle phrase in accord with the following instructions: “Begin with ameaningful phrase, retype it with a few mistakes, make it longer by adding

letters [at random], and rearrange subsequences in the string of letters; thenexamine the result to see if the new phrase is meaningful. Repeat this processuntil the library is complete.”7 Would such an exercise have a realistic chanceof succeeding, even granting it billions of years? Eden thought not.
In addition, Schützenberger emphasized that randomly cutting and pastinglarger blocks of text, as evolutionary biologists often envision, would not
make any appreciable difference to the efficacy of a random search of
sequence space. Imagine a computer “mutating” at random the text of the play
Hamlet either by individual-letter substitutions or by duplicating, swapping,inverting, or recombining whole sections of Shakespeare’s text. Would such a
computer simulation have a realistic chance of generating a completely
different and equally informative text such as, say, The Blind Watchmaker by
Richard Dawkins, even granting multiple millions of undirected mutational
iterations?
Schützenberger didn’t think so. He noted that making random changes “atthe typographic level” in a computer program inevitably degrades its function
whether those changes are made “by letters or by blocks, the size of the unit
really does not matter.”8 Thus, he thought that a process of randomly
shuffling blocks of text in any “typographic typology” would inevitably
degrade meaning in much the same way that a series of individual-letter
substitutions will.
Schützenberger insisted that the evolutionary process faced similar
limitations. To him, it seemed extremely unlikely that random mutations ofwhatever sort would produce significant amounts of novel and functionallyspecified information within the time available to the evolutionary process.
Subsequent to the confirmation of Crick’s sequence hypothesis, all present
at Wistar understood that the entities that confer functional advantages onorganisms—new genes and their corresponding protein products—constitutelong linear arrays of precisely sequenced subunits, nucleotide bases in thecase of genes and amino acids in the case of proteins. Yet, according to neoDarwinian theory, these complex and highly specified entities must first arise
and provide some advantage before natural selection can act to preserve them.
Given the number of bases present in genes, and amino acids present infunctional proteins, a large number of changes in the arrangement of thesemolecular subunits would typically have to occur before a new functional andselectable protein could arise. For even the smallest unit of functionalinnovation—a novel protein—to arise, many improbable rearrangements ofnucleotide bases would need to occur before natural selection had anything
new and advantageous to select.
Eden and others questioned whether mutations provided an adequateexplanation for the origin of the genetic information necessary to build new
proteins, let alone whole new forms of life. As physicist Stanislaw Ulam
explained at the conference, the evolutionary process “seems to require many
thousands, perhaps millions, of successive mutations to produce even theeasiest complexities we see in life now. It appears, naïvely at least, that nomatter how large the probability of a single mutation is, should it be even as
great as one-half, you would get this probability raised to a millionth power,
which is so very close to zero that the chances of such a chain seem to bepractically non-existent.”9
LOOKING FOR A LOOPHOLE
In his presentation at the conference, Eden himself acknowledged a possible
way of resolving this dilemma. He suggested that it was at least possible that“functionally useful proteins are very common in this [combinatorial] space
so that almost any polypeptide one is likely to find [as the result of mutationand selection] has a useful function.”10 Many neo-Darwinian biologists
subsequently came to favor this possible solution. The solution was this: eventhough the size of the combinatorial space that mutations needed to search
was enormous, the ratio of functional to nonfunctional base or amino-acidsequences in their relevant combinatorial spaces might turn out to be muchhigher than Eden and others had assumed. If that ratio turned out to be highenough, then the mutation and selection mechanism would frequently stumble
onto novel genes and proteins and could easily leapfrog from one functional
protein island to the next, with natural selection discarding the nonfunctional
outcomes and seizing upon the rare (but not too rare) functional sequences.
As an electrical engineer who was used to working with computer code,
Eden was intuitively disinclined to embrace this possibility. He noted that allcodes and language systems can convey information precisely because they
have rules of grammar and syntax. These rules ensure that not just any
arrangement of characters will convey functional information. For this reason,
functional sequences in working communications systems are typicallysurrounded in the larger combinatorial space by a multitude of nonfunctionalsequences—sequences that don’t obey the rules.
In known codes and language systems, functional sequences do indeed
typically represent tiny islands of meaning amid a great sea of gibberish.
Geneticist Michael Denton has shown that in English meaningful words andsentences are extremely rare among the set of possible combinations of lettersof a given length, and they become proportionally rarer as sequence length
grows.11 The ratio of meaningful 12-letter words to 12-letter sequences is1/1014; the ratio of meaningful 100-letter sentences to possible 100-letter
strings has been estimated as 1/10100. Denton used these figures in 1985 to
explain why random letter substitutions inevitably degrade meaning in
English text after only a few changes and why the same thing might be true ofthe genetic text.
Given the alphabetic or “typographic” character of genetic information
stored in DNA, Murray Eden and others at Wistar suspected that the samekind of problems would affect random mutational changes in DNA. It seemed
logical that functional genes and proteins were also surrounded in theirrelevant combinatorial spaces by vast numbers of nonfunctional sequences—
and, further, that the ratio of functional to nonfunctional sequences would also
be exceedingly small.
Yet in 1966 none of the scientists on either side of the debates at Wistar
knew how rare or common functional gene and amino-acid sequences areamong the corresponding space of total possibilities. Do they occur with afrequency of 1 in 10, 1 in a million, or 1 in a million billion trillion? At thetime, these questions could not be answered.
Most evolutionary biologists remained optimistic that the answer to thisquestion would vindicate the neo-Darwinian model.12 And somedevelopments supported their confidence. During the late 1960s, molecularbiologists learned that most of the functional roles performed by proteins are
performed not just by one precise kind of protein, but by a wide variety, eachwith its own amino-acid sequence. This is unlike a bike lock, which has only
one functional combination. Indeed, molecular biologists learned that thoughsome amino acids at certain sites are absolutely essential for any particular
protein to work, most sites tolerate amino-acid substitutions without loss ofprotein function. For many biologists, this suggested that mutation andselection had a reasonable chance of generating functional sequences ofnucleotide bases or amino acids after all—that the ratio of functional to
nonfunctional sequences was much higher than skeptics had anticipated.
How much higher? How much variability is allowed in the amino-acidsequences in proteins? Are there enough functional proteins within a relevant
combinatorial space of possibilities to render a random mutational search for
new proteins plausible?
When Denton compared linguistic and genetic text to explain the potential
severity of the combinatorial inflation facing the neo-Darwinian mechanism,
he noted that biologists still didn’t know enough “to calculate with any degreeof certainty the actual rarity of functional proteins.” He concluded, however,that since future experiments surely would continue to deepen molecularbiology’s fund of knowledge, “it may be that before long quite rigorousestimates may be possible.”13
IN SEARCH OF THE RATIO
Denton’s prediction of imminent progress proved correct. During the late1980s and early 1990s, Robert Sauer, a molecular biologist at MIT, performeda series of experiments that first attempted to measure the rarity of proteins
within amino-acid sequence space.
Sauer’s work exploited, for the first time, new technology that allowed forthe systematic manipulation of gene sequences. Before the late 1970s,
scientists typically used radiation and chemicals to produce mutant forms ofDNA. Though these techniques sometimes paid off with dramatic results,
such as mutant fruit flies with legs growing out of their heads (the famed
Antennapedia mutation), they did not allow scientists to dictate or target any
specific change to a sequence of bases in DNA. The treatments used simply
replicated the conditions under which mutations occur naturally.
During the late 1970s and early 1980s, however, molecular biologists
developed technologies for making customized synthetic DNA molecules.
Robert Sauer used these techniques to make site-directed changes to DNA
sequences of specific genes of known function and then to insert thosevariants into bacterial cells. He could then evaluate the effect of various
targeted alterations to a DNA sequence on the function of their protein
products within a bacterial cell culture.
Sauer’s technique allowed him to begin to evaluate how many of thevariant sequences, as a percentage of the total, still produced a functional
form of the relevant protein (see Fig. 9.3). His initial results confirmed that
proteins could indeed tolerate a variety of amino-acid substitutions at many of
the sites in the protein chain. Yet his experiments also suggested thatfunctional proteins might be incredibly rare among the space of all possibleamino-acid sequences. Based on one set of mutagenesis experiments, Sauerand his colleagues estimated the ratio of functional to nonfunctional aminoacid sequences at about 1 to 1063 for a short protein of 92 amino acids inlength.14
This result was in rough agreement with an earlier estimate by information
theorist Hubert Yockey.15 Yockey did not perform experiments to derive hisestimate of the rarity of proteins in combinatorial sequence space. Instead, he
used already published data to compare variants of the similar cytochrome cproteins (proteins involved in the biochemical pathways that generate energy
in cells) in different species. He did this to see how much variability existed ateach amino-acid site in molecules performing the same function with thesame basic structure. Using this data about the allowable variability at eachsite, he estimated the probability of finding one of the allowable sequencesamong the total number of sequences corresponding to a cytochrome c protein
100 residues in length. He determined the ratio of functional to nonfunctionalsequences to be about 1 to 1090 for amino-acid chains of this length.16 So,
although Sauer’s experimentally derived results were numerically different
from Yockey’s, both approaches gave extremely low ratios suggesting thatfunctional proteins are indeed rare in sequence space, even if proteins do
admit significant variability in the specific amino acids present at various
positions.

FIGURE 9.3
Figure 9.3a (top) depicts the problem of combinatorial inflation as it applies
to proteins. As the number of amino acids necessary to produce a protein orprotein fold grows, the corresponding number of possible amino-acidcombinations grows exponentially. Figure 9.3b (bottom) poses graphically thequestion of the rarity of proteins in that vast amino-acid sequence space.
Taken at face value, Sauer’s experiments appeared to yield contradictory
conclusions. On the one hand, his results showed that many arrangements ofamino acids could produce the same protein structure and function—that
numerous amino-acid sequences populated amino-acid sequence space. On
the other hand, the ratio of functional sequences to the total number ofpossible sequences corresponding to a sequence of roughly 100 amino acids
appeared to be incredibly low, just 1 to 1063.
Nevertheless, it’s not hard to see how both of Sauer’s seemingly
contradictory conclusions could be true. Recall the locks confronting my
hypothetical bike thief. Commercially manufactured bike locks typically have
only one combination of digits that will allow them to be opened. The
combination that will open a typical bike lock specifies one digit on each dial.
No variability at any dial is allowed.
Now imagine a new kind of lock with three crucial differences from an
ordinary lock. First, with this new alternative lock, there are four positions on
every dial that may—in combination with other positions on other dials—
open the lock. My bike thief would like this feature of this kind of lock, since
it seems to allow more wiggle room at each dial. But he doesn’t like the twoother features of this lock. For one, each dial displays one of 20 letters rather
than one of 10 numeric digits. Second, instead of 5 dials, there are 100 dials.
On the upside, because 4 of the 20 letters on each of the 100 dials mightwork, there are 4100, or a whopping 1060, correct combinations that will open
the lock. That’s an astronomically large number of correct combinations. But,on the downside, there are 20 possible settings at each of 100 dials, which
computes to 20100, or 10130, possible combinations, a number that totally
dwarfs the number of correct combinations of dial settings.
The bike thief would be happy to learn that every dial has “only” four
possible correct positions on each dial, but in a trial-and-error process, he still
has only 1 chance in 5 (4 out of 20) of landing on a possibly functional dialposition for any dial; and this 1-in-5 chance must be negotiated 100 times. In
other words, the 1-in-5 chance must be multiplied by the 100 dials on themonster lock in order to arrive at the probability of the thief stumbling upon afunctional combination on a given try. The odds are 1 chance in 5100 or—if
we want to convert that to base 10—roughly 1 chance in 1070. The odds arethat slender because the functional combinations—numerous as they are—are
dwarfed by the number of total combinations.

In the same way, Sauer established that though many different
combinations of amino acids will produce roughly the same protein structureand function, the sequences capable of producing these functional outcomesare still extremely rare. He showed that for every functional 92-amino-acidsequence there are roughly another 1063 nonfunctional sequences of the samelength. To put that ratio in perspective, the probability of attaining a correct
sequence by random search would roughly equal the probability of a blind
spaceman finding a single marked atom by chance among all the atoms in the
Milky Way galaxy—on its face clearly not a likely outcome.17
UNCERTAIN SITUATION
Nevertheless, during the 1990s in the immediate wake of the publication of
Sauer’s results, the implications of his work for evolutionary theory were notentirely clear. Even in the scientific paper in which Sauer reported his work,
the abstract summarizing his results emphasized the tolerance to amino-acidsubstitution that proteins allow. Consequently, scientists on both sides of the
discussion about Darwinian evolution seized on different aspects of Sauer’s
findings either to support or challenge the plausibility of the neo-Darwinianaccount of the origin of genes and proteins.
Scientists sympathetic to neo-Darwinism emphasized the tolerance ofproteins to amino-acid substitution; critics of the theory emphasized the rarity
of proteins in sequence space. One scientist, Ken Dill, a biophysicist at
University of California, San Francisco, cited Sauer’s work to suggest thatnearly any amino acid would work at any site in a protein chain, provided theamino acids in question exhibited the correct hydrophobicity (water-repelling)or hydrophilicity (water-attracting) properties.18
Yet, at least one scientist, Lehigh University biochemist Michael Behe,cited Sauer’s quantitative estimate of the rarity of proteins as a decisive
refutation of the creative power of the mutation and selection mechanism
altogether.19 So by the mid-1990s, though Sauer and his group had initiated a
program of experimental research that addressed the key question that Murray
Eden raised at Wistar, that question had still not been completely settled. Did
the mutation and natural selection mechanism have a realistic chance offinding the new genes and proteins necessary to build, for example, a new
Cambrian animal? Answering that would await an even more systematic andcomprehensive experimental regime.

10
The Origin of Genes and ProteinsAs a Ph.D. student in chemical engineering at the California Institute ofTechnology in the late 1980s, Douglas Axe (see Fig. 10.1) became interested
in evolutionary theory after several fellow graduate students read the thenbestselling book by Richard Dawkins, The Blind Watchmaker. Axe’s
compatriots were quickly converted to zealous advocates of Dawkins’s
arguments and urged him to read the book for himself. Axe was impressed by
the clarity of Dawkins’s writing and illustrations, but he found his case for thecreative power of natural selection and random mutations unpersuasive.
Whether in the analogies he drew to animal breeding or the computer
simulations he used to demonstrate the supposed ability of mutation andselection to generate new genetic information, Dawkins repeatedly smuggled
in the very thing he insisted the concept of natural selection expressly
precluded: the guiding hand of an intelligent agent.
He found Dawkins’s computer simulation particularly interesting. In The
Blind Watchmaker, Dawkins described how he had programmed a computer
to generate the Shakespearean phrase: “Me thinks it is like a weasel.”1
Dawkins did this in order to simulate how random mutations and natural
selection could generate new functional information.
Dawkins programmed the computer first to generate many separate strings(sequences) of English letters. He then programmed it to compare each string
to the Shakespearean target phrase and select only the string that most closely
resembled that target.2 The program then generated variant versions of that
newly selected string and compared those sequences to the target, selecting,again, only the one that most closely resembled the desired target. This
eventually generated—after many iterations—a string that matched the target
perfectly.
Axe recognized immediately the role that Dawkins’s own intelligence had
played. Not only did Dawkins provide the program with the information that
he wanted it to generate (“Me thinks it is like a weasel”), he imbued thecomputer with a kind of foresight by directing it to compare the variantsequences of letters with the desired target. Axe realized that Dawkins’s
program did not simulate natural selection, which by definition is neither
guided toward nor given information about a desired outcome generations in
the future.
Axe began to wonder if there was some other way to assess the creative
power of the mutation and natural selection mechanism, not with cleveranalogies or simplistic computer simulations, but with experimental andmathematical rigor.
Axe realized that Dawkins was right about one thing: the importance ofgenetic information. Like his fellow engineer Murray Eden, Axe’s tendency
to view biology as an engineer led him to ask whether selection and mutation
could actually build new organisms. Axe’s own research explored theconnection between process control (a field of study in engineering) andgenetic regulation, a sophisticated version of automated process control atwork on a molecular scale inside living cells. Since cells use proteins toperform various feats of regulation, Axe was acutely aware that building neworganisms necessarily involved building new proteins, which would in turnrequire new genetic information.

FIGURE 10.1
Douglas Axe. Courtesy Brittnay Landoe.
But could mutation and selection generate the precise arrays of nucleotide
bases necessary to build fundamentally new protein structures? Axe’s interest

in this question eventually led him to the scientific papers of Robert Sauer andthe proceedings of a seemingly obscure 1966 Philadelphia conference called“Mathematical Challenges to the Neo-Darwinian Interpretation of Evolution.”
UNRESOLVED ISSUESAs Axe read the papers that Sauer’s research group had produced, he realized
their importance as a first step toward answering the questions Murray Eden
had raised at Wistar. If Sauer’s quantitative measures of rarity held up, thenAxe thought it obvious that mutation and selection could not adequately
search a space that large. If, on the other hand, subsequent mutagenesis
experiments overturned Sauer’s work and showed that protein function waslargely indifferent to changes in amino-acid sequence, then the number offunctional sequences might be large enough that mutation and selection
would have a good chance of finding new functional genes and proteins in areasonable amount of time.
After completing his Ph.D., Axe made inquiries about doing postdoctoral
research in a top research lab where he could address these unansweredquestions. He was soon invited by Alan Fersht, a professor at the Universityof Cambridge and director of the Centre for Protein Engineering, part of theworld-famous Medical Research Council (MRC) Centre at Cambridge, to join
his research group.
The decision to accept Fersht’s offer was an easy one. The star-studded
history of the adjoining Laboratory for Molecular Biology (LMB), arguably
the birthplace of molecular biology, included such luminaries as James
Watson, Francis Crick, Max Perutz, John Kendrew, Sidney Brenner, and Fred
Sanger. Starting in the chemistry department and then moving to the MRC
Centre, Axe hoped to apply his research training to resolve the uncertainty
that surrounded the interpretation of Sauer’s results. Specifically, he wanted toeliminate what he saw as two sources of error in Sauer’s method in order to
get a more definitive estimation of the frequency of functional sequences insequence space.
Axe thought, first, that Sauer’s team might have underestimated the rarityof functional proteins. In their experiments, Sauer’s group tested the toleranceof proteins to amino-acid substitution by changing amino acids at one or a
few consecutive sites without making any other changes to other sites at thesame time, much like a typist introducing an isolated typographic error in anotherwise accurately transcribed text. Not surprisingly, Sauer and hiscolleagues found that many sites along a protein chain could tolerate these
isolated amino-acid substitutions, just as the reader of a text with only a few

typos can often make out its meaning. Sauer’s team seemed to be assumingthat a similar tolerance would have emerged if they had changed many sites
simultaneously.
Axe thought that this assumption ignored the importance of the larger
context provided by the mostly unaltered protein. A single typographic error
typically will not totally destroy the meaning of a section of English text,
because of the surrounding context provided by the other words, as well as
the correct letters in the altered word. That does not mean, however, thatspecificity of sequence doesn’t matter. Instead, the meaning of a sentencewith a typographic error can be discerned only because the rest of the letters
are specifically arranged into meaningful words and phrases that provide acontext for determining the meaning of the incorrectly spelled word. For justthis reason, however, the meaning of a sentence is rapidly degraded if errors
are allowed to accumulate at multiple sites.
Axe wondered if much the same could be true of genes and proteins. He
wondered whether multiple, as opposed to single, position changes would
quickly degrade function and whether a tolerance for substitutions at
individual sites was itself context dependent—whether the tolerance for
substitution at one site might depend upon having highly specific sequences atother sites. Thus, without questioning Sauer’s experimental findings, Axethought Sauer’s result lent itself to misinterpretation. To many molecularbiologists, it suggested that proteins could readily accommodate many
simultaneous changes to their amino-acid sequences at many positions andremain functional.
As it turns out, Sauer recognized the potential for misinterpretation of his
results. As he explained in the very paper in which he developed hisquantitative estimate of rarity, “this calculation overestimates the number offunctional sequences, since changes at individual positions are less likely to
be independent of one another as more positions are allowed to vary.”3
Another assumption in Sauer’s approach had potentially the opposite effect—exaggerating the rarity of functional proteins. Axe thought the test that
Sauer and his colleagues used to decide whether their mutant proteins werefunctional required a higher level of function than natural selection might
require. Sauer and his team judged proteins with less than about 5–10 percentof the function seen in the natural protein to be nonfunctional. Yet Axe knewthat even damaged enzymes with less than 5 percent of normal activity could
add significantly more benefit than no enzymatic activity at all. Thus, from a
neo-Darwinian point of view, the emergence of even such handicapped
proteins might confer a selectable advantage on an organism. Axe thoughtthat by rejecting as nonfunctional such mutated sequences, Sauer’s teamprobably had introduced another estimation error. These competing errors
made it hard to know if the estimate made by Sauer’s team was too high or
too low or whether perhaps they might neatly cancel each other out. To
eliminate both sources of possible error, Axe carefully designed a new seriesof experiments.
THE IMPORTANCE OF FOLDSAxe had a key insight that animated the development of his experimental
program. He wanted to focus on the problem of the origin of new protein
folds and the genetic information necessary to produce them as a critical testof the neo-Darwinian mechanism. Proteins comprise at least three distinct
levels of structure:4 primary, secondary, and tertiary, the latter corresponding
to a protein fold. The specific sequence of amino acids in a protein or
polypeptide chain make up its primary structure. The recurring structural
motifs such as alpha helices and beta strands that arise from specificsequences of amino acids constitute its secondary structure. The larger folds
or “domains” that form from these secondary structures are called tertiary
structures (see Fig. 10.2).
Axe knew that as new life-forms arose during the history of life—in events
such as the Cambrian explosion—many new proteins must also have arisen.
New animals typically have new organs and cell types, and new cell types
often call for new proteins to service them. In some cases new proteins, while
functionally new, would perform their different functions with essentially thesame fold or tertiary structure as earlier proteins. But more often, proteinscapable of performing new functions require new folds to perform thesefunctions. That means that explosions of new life-forms must have involved
bursts of new protein folds as well.

FIGURE 10.2
Different levels of protein structure. The first panel at the top shows theprimary structure of a protein: a sequence of amino acids forming apolypeptide chain. The second panel depicts, in two different ways, twosecondary structures: an alpha helix (left), and beta strands forming a beta
sheet (right). The third panel at the bottom shows, in two different ways, atertiary structure—that is, a protein fold.
The late geneticist and evolutionary biologist Susumu Ohno noted that
Cambrian animals required complex new proteins such as, for example, lysyl
oxidase in order to support their stout body structures. When these molecules
originated in Cambrian animals, they also likely represented a completely
novel folded structure unlike anything present in Precambrian forms of life
such as sponges or one-celled organisms. Thus, Axe was convinced that
explaining the kind of innovation that occurred during the Cambrian
explosion and many other events in the history of life required a mechanismthat could produce, at least, distinctly new protein folds.
He had another reason for thinking that the ability to produce novel protein
folds provided a critical test for the creative power of the mutation andselection mechanism. As an engineer, Axe understood that building a new
animal required innovation in form and structure. As a protein scientist, heunderstood that new protein folds could be viewed as the smallest unit ofstructural innovation in the history of life.
It follows that new protein folds represent the smallest unit of structural
innovation that natural selection can select. Of course, natural selection canoperate on smaller units of change—individual amino-acid changes that resultin slight functional advantages or fitness gains, but not new folds, forexample. But what if the functional or fitness gains that natural selection
preserves and passes on never generate structural innovations? What if,
instead, it only preserves slight differences in the sequence or function ofproteins that confer an advantage without altering structure? Then, clearly,
fundamental changes in the form of an organism will not occur. Building
fundamentally new forms of life requires structural innovation. And new
protein folds represent the smallest selectable unit of such innovation.
Therefore, mutations must generate new protein folds for natural selection tohave an opportunity to preserve and accumulate structural innovations. Thus,
Axe realized that the ability to produce new protein folds represents a sinequa non of macroevolutionary innovation.
Could random mutations generate such novel protein folds? Axe realizedthat answering this question depended upon measuring the rarity of functional
genes and proteins in sequence space and determining whether random
genetic mutations would have enough opportunities to search the relevant
sequence spaces within evolutionary time.
AXE’S INITIAL RESULTS
Axe read the paper by Sauer and his colleague John Reidhaar-Olson that
estimated the proportion of functional protein sequences to be extremely low(1 in 1063). He noticed that the authors chose not to emphasize this measureof rarity, however, but instead the variety of amino-acid substitutions that theprotein under study could tolerate.
In their paper, Reidhaar-Olson and Sauer also repeated a then popular ideathat the amino acids buried in the interior of a folded protein (forming what is
known as the hydrophobic core) are most important for specifying thestructure, while the arrangement of the exterior amino acids did not matternearly as much.5 They thought that the amino acids buried within foldedproteins typically need only to be hydrophobic (water repelling), whereas theamino acids on the exterior, for the most part, need to be hydrophylic (water
attracting). In fact, some protein scientists thought that these simple
restrictions might be the whole story—that a functional protein fold might
require nothing more than an appropriate arrangement of hydrophobic andhydrophylic amino acids in a given sequence.
At Fersht’s lab in Cambridge, Axe conducted an experimental test of thisidea, and surprised himself with the first result. In a paper he coauthored in
the Proceedings of the National Academy of Sciences in 1996, he reported his
findings. When he replaced the entire thirteen-residue hydrophobic core of asmall enzyme with random combinations of other hydrophobic amino acids, ahigh fraction of the randomized proteins (about one-fifth) still performed their
original function. This suggested that proteins were, perhaps, less susceptible
to functional loss as a result of sequence changes than Axe had thought.
Next he focused on the exterior of proteins, randomizing portions of two
different proteins’ exteriors in much the same way that he had randomlychanged the interior of one of them. This time his approach failed to produce
any functional variants at all. Realizing that this seemed to contradict what
Sauer and others had supposed, Axe decided to make only much more
restrictive changes in the next trial. He replaced each exterior amino-acidresidue only with its most similar amino-acid alternative. Nevertheless, bothof the proteins that he studied still lost all function by the time he had
replaced one-fifth of their exterior residues. Thus he concluded that theexterior parts of the proteins were much more susceptible to functional loss asa result of amino-acid changes than had been widely assumed.
In all this work, Axe designed his experiments to remedy the two sourcesof estimation error inherent in Sauer’s method. First, by studying amino-acidchanges in combination rather than in isolation, he determined that thesurrounding context typically did influence whether a particular amino-acidchange at a particular site caused functional loss. In other words, hediscovered that the neglect of the influence of the surrounding context had theeffect of exaggerating the tolerance to amino-acid changes at particular sites,
as he (and Sauer) had suspected.
Second, the proteins that Axe chose for his study made it possible forfunction to be detected at much lower levels than was possible in Sauer’s
studies. For one protein Axe studied, the more sensitive test of function did
indeed allow a greater proportion of single mutants to retain some function,with about 95 percent of the mutant proteins achieving the designation“active.” This suggested that Sauer’s less sensitive screen did contribute toanother source of estimation error, this time in the opposite direction.

Nevertheless, Axe’s more sensitive screen also enabled him to establish thateven though single mutations allow many proteins to retain some function,
they still diminish or damage the function of the protein—often enough toensure that they will be eliminated by the purifying effect of natural selection.
Further, because of the extreme sensitivity of his test for function, Axelearned that any single mutation that failed his test was single-handedly
destroying function. He determined that fully 5 percent of such changes did
destroy protein function.
Overall, therefore, he showed that despite some allowable variability,
proteins (and the genes that produce them) are indeed highly specified relative
to their biological functions, especially in their crucial exterior portions. Axe
showed that whereas proteins will admit some variation at most sites if therest of the protein is left unchanged, multiple as opposed to single amino-acidsubstitutions consistently result in rapid loss of protein function. This was thecase even when these changes occur at sites that allow variation when alteredin isolation.6 His new experiment also roughly confirmed Sauer’s earlier
quantitative assessment of the rarity of functional proteins, despite theestimation errors inherent in Sauer’s method. Why? Because it appeared that
Sauer’s two estimation errors—ignoring context and using an insufficiently
sensitive screen for function—did, in fact, roughly cancel each other out.
Despite these advances in understanding, Axe had not yet determined
whether the greatly restricted picture of tolerance that his work had exposed
would cause problems for the evolution of new protein folds. In order toanswer that question he would need to obtain a more precise quantitative
estimate of the rarity of proteins in sequence space.
Having developed a method that eliminated the main sources of estimation
error in earlier mutagenesis experiments, Axe was now in a position to answer
that question with unprecedented rigor. Once he did, he could determine
whether random genetic changes would have enough opportunities—even on
the scale of evolutionary time—to search the relevant sequence spaces forfunctional genes and proteins.
DON’T LEAVE THE FOLD
Of course, Axe understood that neo-Darwinists do not envision a completely
random journey through nucleotide or amino-acid sequence space. They see
natural selection acting to preserve useful mutational variations and toeliminate deleterious ones. Richard Dawkins, for example, likens an organism
to a high mountain peak.7 He compares climbing the sheer precipice up thefront side of the mountain to building a new organism purely by chance—

random mutations alone. He acknowledges that this approach up “Mount
Improbable” will not succeed. Nevertheless, he asserts that there is a gradualslope up the back side of the mountain that can be climbed in small
incremental steps. In his analogy, the back side up “Mount Improbable”
corresponds to the process of natural selection acting on many small randomchanges in the genetic text. What chance alone cannot do, natural selection
acting on random mutations can accomplish through the cumulative effect ofmany slight successive steps.
Yet Axe’s experimental results presented a problem not only for scenarios
involving random mutations acting alone, but also for scenarios envisioning
selection and random mutation acting in concert. Further, his mutagenesis
experiments cast doubt on each of the two scenarios by which evolutionary
biologists might envision new protein folds (and the information necessary to
produce them) arising as the result of the mutation and selection mechanism.
In theory, new genes capable of producing a new protein fold might arise
either from (a) preexisting genes or from (b) nonfunctional sections of the
genome. That is—to adapt Dawkins’s visual analogy—mutation and natural
selection could conceivably generate a new functional gene starting fromeither (a) another mountain peak (a different preexisting functional gene) or(b) from the valley floor (a nonfunctional section of the genome). Yet Axe’s
experimental results would show that the action of natural selection would not
help solve the search problem confronting the mutation mechanism in eitherof these two cases. To see why, we need to understand a bit more about eachof these two possible neo-Darwinian scenarios as well as Axe’s subsequent
experimental findings.
FROM PEAK TO PEAK
In the first case, evolutionary biologists might envision mutation and selection
gradually altering a preexisting gene (and its protein product) to produce
another functional gene (and a different protein product). This scenario
involves moving metaphorically from one functional peak to another without
dipping into a valley (a zone of diminished fitness or nonfunction).
Most evolutionary biologists reject this first scenario.8 They do so because
they recognize that mutations in preexisting genes will typically degrade
functional genetic information. They know, too, that when genes losefunction, natural selection will eventually eliminate the organisms thatpossess these genes. Genes that contribute to the healthy function of anorganism, that have been mutated in such a way as to diminish that function,
will be subject to what evolutionary biologists call “purifying selection.” Thatis, natural selection will typically eliminate organisms possessing mutationinduced gene variants that diminish function or fitness. (When natural
selection preserves genetic changes that enhance function or fitness,
evolutionary biologists call that “positive selection.”)Axe’s mutagenesis experiments confirmed these reasons for doubting thefirst of the possible neo-Darwinian scenarios, at least as an explanation for theorigin of new protein folds. In work that he published in 2000, he showed that
it is, indeed, exceedingly difficult to make extensive changes to functionalamino-acid sequences without destabilizing a protein fold. Even best-casechanges involving the most chemically similar amino acids in the exterior ofproteins tended to destabilize protein folds.
In these experiments, Axe mutated a gene that produced a protein
exhibiting a single fold and function. He found that as he altered this protein,multiple position changes in the exterior of the protein molecule quickly
effaced or destroyed its function.9 Yet to turn one protein with a distinctive
folded structure into another with a completely novel structure and function
requires specified changes at many, many sites—far more than Axe altered in
his experiments.10 The number of changes necessary to produce a new protein
fold typically exceeds the number of changes that will result in functional
loss. Given this, the probability of the evolutionary process successfully
traversing a functional landscape from one functional peak to another—all thewhile escaping functional loss each step along the way—is extremely small,with the probability diminishing exponentially with each additional requisitechange.11 Indeed, by showing that functional proteins with distinct folds are
far more sensitive to functional loss than protein scientists had previously
assumed, Axe’s experiments confirmed what most evolutionary biologists
suspected—namely, that protein-to-protein (or functional gene–to–functional
gene) evolution is a no-go where the mutation and selection mechanism must
produce a new protein fold (see Fig. 10.3).
Axe had a more fundamental reason for considering the first evolutionary
scenario implausible. Based on the physical principles of protein function, thevast majority of protein functions simply cannot be performed by unfolded
proteins. In other words, stability of protein structure is a precondition ofprotein function. Destabilized protein folds not only lose the threedimensional structures they need to perform functional tasks, they are also
vulnerable to attack by other proteins called proteases that devour unfolded
proteins or polypeptides in the cell.12
As one structure is degraded as the result of multiple sequence changes, itwill necessarily lose structural stability, resulting in a catastrophic loss offunction. Yet any diminution in the function of a protein will also diminish
fitness in a way that will subject the protein (and its corresponding gene) tothe purifying action of natural selection.13 Indeed, according to the equationsof population genetics, the standard mathematical expression of neoDarwinian theory, even slight losses in fitness will subject thedisadvantageous traits that produce such losses to purifying selection, thus
eliminating them. That means that even many protein sequences that retain asignificant, though diminished, portion of their original function neverthelesswill not survive the winnowing effects of the neo-Darwinian mechanism.
Thus, the gradual transformation of one functional fold into another was acomplete nonstarter.

FIGURE 10.3
This figure illustrates why many evolutionary biologists reject the idea thatgenes and proteins under selection pressure will evolve into new functional
genes and proteins. Since genes, like English sentences, contain sequencespecific functional information, multiple changes in the genetic text will
inevitably degrade function (or fitness) long before a new functional sequence
will arise—just as random changes in a meaningful English sentence will
typically destroy meaning long before such changes produce a significantly
different meaningful sentence.
Research performed at the European Molecular Biology Laboratory bymolecular biologist Francisco Blanco has since confirmed this conclusion.
Using site-directed mutagenesis, Blanco’s team found that the sequence space
between two naturally occurring protein domains is not continuously
populated by folded or functional proteins. By sampling intermediate
sequences between two sequences that do adopt different folds, Blanco foundthat the intermediate sequences “lack a well-defined three-dimensional
structure.” Thus, he concluded that “the appearance of a completely new foldfrom an existing one is unlikely to occur by evolution through a route offolded intermediate sequences.”14

Thus, both experimental results and the physics of protein folding impliedthat random searches for novel proteins starting from preexisting proteincoding genes would result in functional loss long before a protein with anovel fold would emerge, as most evolutionary biologists already suspected.
Although the first of the two possible evolutionary scenarios has theadvantage of starting on a mountain peak—with a functional gene and protein—it also has a lethal disadvantage: randomly mutating the gene will soondestabilize a protein fold and/or generate nonfunctional intermediate
sequences and structures long before a new gene (capable of generating a newfold) would arise. For this reason, this scenario involves not so much a climb
up Mount Improbable, but a step out over Valley Impassable.
SCALING MOUNT IMPROBABLE
For all these reasons, like most evolutionary biologists, Axe thought thesecond neo-Darwinian scenario—in which new genes and proteins emerge
from nonfunctional or neutral regions of the genome—provides a much moreplausible means of producing the information necessary to construct novel
protein folds. It was to this scenario that Axe turned his experimental
energies.
In this scenario, neo-Darwinists envision new genetic information arisingfrom sections of the genetic text that can vary freely without consequence tothe organism. According to this scenario, noncoding sections of the genome
or duplicated sections of coding regions undergo a protracted period of“neutral evolution”15 in which alterations in nucleotide sequences have no
discernible effect on the fitness of the organism. Functional genes andproteins gradually rise from a nonfunctional valley floor to a functional
mountain peak—generating a new gene. Natural selection plays a role, but not
until a new functional gene has arisen.
Evolutionary biologists typically picture this process beginning with agene duplication event. Although several different mechanisms can generategene duplicates in DNA,16 the most common mechanism occurs during thecrossing-over step of meiosis (a kind of cell division that produces sex cells,
or gametes, in sexually reproducing organisms). During meiosis, homologous
chromosomes swap segments of DNA. In a normal crossing-over event,corresponding chromosomal segments of equal size are swapped between thetwo homologous chromosomes, ensuring that both chromosomes experienceno net gain or loss of genes. Sometimes, however, chromosomes swap genetic
material of unequal length. When this happens, one chromosome (the one thatgets the smaller piece) ends up losing some DNA, while the chromosome that

receives the larger segment of genetic material ends up with a new stretch ofchromosomal DNA—one that may include a gene or genes it already had.
This results in duplicate copies of a gene on one chromosome.
When this occurs, one of the two genes may begin to vary—to experiencemutations—without adversely affecting the function of the organism, while
the other performs the original function. In the jargon of evolutionary biology,
mutational changes in gene duplicates are “selectively neutral”—they initiallyprovide no advantage or disadvantage to an organism or population. These
gene-duplication events allow nature room to experiment safely. Unhelpful
but harmless genetic novelties can be passed on to future generations, where
additional mutations one day may render the evolving genetic material useful.
Eventually, as mutational changes accumulate, a new gene sequence mayarise in a new organism that can code for a novel protein fold and function. At
that point, natural selection can favor the new gene and its protein product,
preserving and passing it along to future generations—or so the story goes.
This scenario—which many evolutionary biologists now refer to as the“classical model” of gene evolution—has the advantage of allowing portionsof the genome to vary freely through many generations, giving mutations
many opportunities to “search” the space of possible base sequences without
being punished for drifting into valleys of lost or diminished function.
But this scenario faces an overriding problem: the extreme rarity ofsequences capable of forming stable folds and performing biological
functions. Since natural selection does nothing to help generate new folded,
functional sequences, but rather can only preserve such sequences once they
have arisen, random mutations alone must search for the exceedingly rare
folded and functional sequences within the vast sea of combinatorial
possibilities.
And that is the big story associated with Axe’s experiments. His researchshowed that folded, functional sequences of amino acids are indeed
exceedingly rare within sequence space. After his initial round ofexperiments, Axe performed another series of site-directed mutagenesis
experiments on a 150-amino-acid protein-folding domain within a βlactamase enzyme and published the results in the Journal of Molecular
Biology.17 Recall that a folding domain is a portion of a larger protein thatexhibits a distinctive fold. Since amino-acid chains must first fold into stable
three-dimensional structures, Axe performed experiments that enabled him toestimate the frequency of sequences that will produce stable folds—any stable
fold—before he estimated the frequency of sequences performing a specific(β-lactamase) function. His improved experimental method produced aprecise quantitative result. He estimated (a) the number of 150-amino-acid-long sequences capable of folding into stable “function-ready” folded
structures compared to (b) the whole set of possible amino-acid sequences ofthat length (recall Fig. 9.3). Based on his site-directed mutagenesis
experiments, he determined that ratio to be a vanishingly small 1 in 1074. Inother words, for sequences 150 amino acids long, only 1 in 1074 sequences
will be capable of folding into a stable protein.
For a sequence to achieve a protein fold is only a first step, however. A
protein must be folded to be functional, but a folded protein is not necessarily
a functional protein. And although sequences capable of forming stable
protein folds are necessary to any significant evolutionary innovation, natural
selection cannot select for the presence of a fold unless it also performs afunction that confers a specific functional advantage on an organism. Thus,
Axe also estimated (a) the number of proteins of modest length (150 residues)that perform a specified function via any folded structure compared to (b) thewhole set of possible amino-acid sequences of that size. Based on his
experiments and data about the number of stable folded proteins that exist,
Axe estimated that ratio to be about 1 to 1077. A telling conclusion follows
from this experimental data: The probability of any given mutational trial
generating (or “finding”) a specific functional protein among all the possible
150 residue amino-acid sequences is 1 chance in 1077—that is, one chance in
one hundred thousand, trillion, trillion, trillion, trillion, trillion, trillion.
That is obviously an incredibly small probability, but is it small enough tojustify rejecting the classical model of gene evolution? Or is it plausible tothink that random mutations in the nonfunctional part of the genome could
overcome these long odds to generate the genetic information necessary to
produce a novel protein fold with a specific selectable function?
HOW MANY TRIALS?
When statisticians or scientists assess whether a chance hypothesis provides aplausible explanation for the occurrence of an event, they do not just evaluate
the probability of that particular event occurring once; they evaluate theprobability of the event occurring given the number of opportunities it has tooccur.
For example, if our hypothetical bike thief from the previous chapter had
enough time to try more than half (more than 500 of the 1000) total
combinations of a three-dial bike lock, then the probability that he will
stumble upon the right combination will exceed the probability that he will
fail. In that case, it will be more likely than not that he will succeed in opening
the lock by chance. In that case, the chance hypothesis—the hypothesis that

he will succeed in opening the lock by chance—is more likely to be true thanfalse. On the other hand, if just after he started trying to crack the lock heheard a security guard coming around the corner and only had time to explore
a small fraction of the total number of possible combinations—far fewer thanhalf—then it will be much more likely than not that he will fail to open thelock by chance. Consequently, anyone who knew his situation could conclude
that the chance hypothesis is, in that case, much more likely to turn out false
than true.
When statisticians or scientists assess the probability of an event occurringby chance, they often assess what is called a conditional probability. In
deciding the plausibility of a chance hypothesis, they assess the probability ofthe event given or “conditioned on” what else we know, especially what else
is known about the number of opportunities the event has to occur. And theyrefer to the number of opportunities an event has to occur as “the probabilistic
resources.”18
If the conditional probability of the chance hypothesis, given the numberof opportunities it has to occur, is less than ½, then it is more likely than notthat the event will not happen by chance. It will be viewed as implausible—
more likely to be false than true. Conversely, if the conditional probability of
the chance hypothesis, given the number of opportunities it has to occur, ismore than ½, then it is more likely than not that the event in question will
occur by chance. It will be deemed plausible—more likely to be true thanfalse. And, of course, the smaller the conditional probability associated with ahypothesis, the more implausible the hypothesis—the more likely the chance
hypothesis is to be false than true.
How then should we assess the chance hypothesis for the origin of
biological information—in particular, the hypothesis that random mutations
generated the information necessary to produce a novel protein fold with aselectable function? What is the conditional probability that such a folded
protein could arise as the result of random mutations in duplicatednonfunctional sections of a genome? Axe realized that in order to answer thatquestion he needed a way to estimate the number of opportunities that random
mutations had for producing a new protein fold with a selectable function
during the whole history of life on earth.
THE BIOLOGICAL UNIVERSAL PROBABILITY BOUND
Here, evolutionary theory itself provides the answer. Axe was interested in thenumber of times that mutations might have produced new sequences of bases
in DNA that were capable of producing a new sequence of amino acids—one

of the 1077 possible sequences in the relevant sequence space. Yet not every
such sequence of bases that mutations might generate constituted a relevant
trial. In theory, mutations may alter a gene many times during the life cycle ofan organism. Nevertheless, natural selection can only act on the new sequenceof bases that is actually passed on to offspring. It might seem that it would be
difficult to quantify the number of mutational trials in each generation. But
even if we think of mutations repeatedly shuffling and reshuffling thearrangement of bases during the life cycle of an organism, only thosemutations in the genes (or DNA) in the reproductive cells of parent organisms
can have any effect on the next generation. Since Axe wanted to know how
many novel sequences capable of generating a selectable function might havearisen in the history of life, he only needed to concern himself with thosesequences that could be transmitted during reproduction.
This meant that if he could estimate the total number of organisms that had
lived during the history of life on earth and the number of new genes that
mutations might produce and pass on to the next generation, he could
establish an upper bound on the number of trials relevant to the evolutionary
process.
Axe knew that the huge population sizes of prokaryotes like bacteria dwarf
the population sizes of all other organisms combined. Thus, estimates for thesize of the bacterial population—plus a smidge for everything else—would
approximate the size of the number of organisms living at any given time.
Based on the average length of time of a bacterial generation and the timesince the first appearance of bacterial life on earth (3.8 billion years ago),scientists have estimated that a total of about 1040 organisms have lived onearth since life first appeared.19 Axe made the assumption that each neworganism received one new sequence of bases (one potential gene) capable ofgenerating one of the possible amino-acid sequences in sequence space per
generation.
This was an extremely generous assumption. Since mutations have to bequite rare for life to survive, most bacterial cells inherit an exact copy of theirparent’s DNA. Furthermore, the ones that differ from their parents are likely
to carry a mutation that has already occurred many times in other cells. For
these reasons, the actual number of new sequences sampled in the history oflife is much lower than the total number of bacterial cells that have existed.
Nevertheless, Axe assumed that one new gene per organism has beentransmitted to the next generation. Thus, he used 1040 gene sequences as aliberal estimate of the total number of gene sequences (evolutionary trials)
that have been generated to search sequence space in the history of life.

Even so, 1040 represents only a tiny fraction—1 ten trillion, trillion,
trillionth—of 1077. Thus, the conditional probability of generating a genesequence capable of producing a novel protein fold and function is still only 1
in 1037. This means that if every organism from the dawn of time had
generated, by random mutation, one new base sequence in the sequence spaceof interest, that would amount to only one 10 trillion, trillion, trillionth of thesequences in that space—the space that needs to be searched.And, sinceconditional probability of a new gene arising in the manner envisioned by theclassical model turns out to be almost unimaginably less than ½, the classicalmodel turns out to be vastly more likely to be false than true. Thus, Axe
concluded that a reasonable person should reject it. The probabilistic
resources available to the classical model of gene evolution are simply far too
small to tame 1 chance in 1077 (see Fig. 10.4).

FIGURE 10.4
The top panel in this diagram represents the results of Axe’s mutagenesis
experiments showing the extreme rarity of functional proteins in sequencespace. Based on his experiments Axe estimated that there are 1077 possible
sequences corresponding to a specific functional sequence 150 amino acids
long. The second panel shows that functional amino-acid sequences are
extremely rare even in relation to the total number of opportunities theevolutionary process would have had to generate novel sequences (on theassumption that each organism that has ever lived during the history of life
produced one such sequence per generation).
To appreciate why this model fails, consider the following
illustration.After the 1975 Steven Spielberg film Jaws became a big hit, onesmall-town motel advertised “Shark-Free Pool.” Proponents of the second
evolutionary scenario (gene duplication, followed by neutral evolution),envision an evolutionary pool where there are no consequences for mutational
missteps—by analogy, a pool with no predators. But to extend the illustration,
picture a predator-free pool the size of our galaxy. Now picture a blindfolded
man dropped into the middle of it. He must swim to the far side, to the one
spot on the edge of the pool where a ladder would give him a way out. He’s
safe from predators, but it will do him no good. He needs direction, some wayof gauging his progress, and an immense amount of time. But he has none ofthese and so he will arrive at the ladder in neither a hundred years, nor ahundred billion. Similarly, in the classical model of gene evolution, random
mutations must thrash about aimlessly in immense combinatorial space, aspace that could not be explored by this means in the entire history of life onearth, let alone in the few million years of the Cambrian explosion.
TO BUILD AN ANIMAL
Yet Axe’s calculations only hint at the full problem for neo-Darwinian theory.
By bending over backwards not to overstate the improbability of generating a
new protein fold and by focusing narrowly on that one aspect of the challenge
confronting evolutionary theory, his figures vastly understate theimprobability of building a Cambrian animal. There are several reasons for
this.
First, the Cambrian explosion as dated by fossil evidence took far less timethan has elapsed since the origin of life on earth until the present (about 3.8
billion years).20 Less time available for a given evolutionary transition means
fewer generations of new organisms and fewer opportunities to generate newgenes by which to search relevant sequence space. This makes it even harderto generate a new protein fold by chance in the relevant time period.
Second, bacteria are by far the most common type of organisms includedin Axe’s estimate of the total number of organisms that have lived on earth.
Yet no one thinks that Cambrian animals evolved directly from bacteria. Nordoes anyone think that the putative multicellular ancestors of the Cambrianforms would have been anywhere near as abundant as the bacterial
populations that Axe used as the main basis of his estimate. A more realistic
estimate for the number of possible animal ancestors would necessarily resultin a much lower estimate for the number of gene sequences available forsearching sequence space (corresponding to a single protein of modest length
in a single Cambrian animal). Recall that, based on Axe’s estimates, theprobability of generating just one gene (for a new functional protein fold)from all the bacteria (and other organisms) that have ever lived on earth is just
1 in 10 trillion, trillion, trillion. Consequently, the mechanism for searchingsequence space that Axe determined to be extremely implausible must be
judged far more implausible as a mechanism for producing the Cambrian
information explosion, since there were far fewer multicellular organisms
present in the Precambrian period than there have been total organisms
present in the entire history of life.
Third, building new animal forms requires generating far more than justone protein of modest length. New Cambrian animals would have required
proteins much longer than 150 amino acids to perform necessary, specialized
functions.21 For example, as previously noted, many of these Cambriananimals needed the complex protein lysyl oxidase to support their stout bodystructures. In addition to a novel protein fold, these molecules (in livingorganisms) comprise over 400 precisely sequenced (nonrepeating) aminoacids. Reasonable extrapolation from mutagenesis experiments done on
shorter protein molecules suggests that the improbability of randomly
producing functionally sequenced proteins of this length would be extremely
unlikely to occur given the probabilistic resources (and duration) of the entire
universe.22
The mutation and selection mechanism faces a related obstacle. The
Cambrian animals exhibit structures that would have required many new
types of cells, each requiring many novel proteins to perform their specialized
functions. But new cell types require not just one or two new proteins, butcoordinated systems of proteins to perform their distinctive cellular functions.
The unit of selection in such cases ascends to the system as a whole. Natural
selection selects for functional advantage, but no advantage accrues from a
new cell type until a system of servicing proteins is in place. But that means
random mutations must, again, do the work of information generation without
the help of natural selection—and, now, not simply for one protein, but for
many proteins arising together. Yet the odds of this occurring by chance alone
are, of course, far smaller than the odds of the chance origin of a single newgene or protein—so small as to render the chance origin of the informationneeded to build a new cell type fantastically improbable (and implausible)
given even the most optimistic estimates for the length of the Cambrian
explosion.
Richard Dawkins has noted that scientific theories can rely on only somuch “luck” before they cease to be credible.23 But the second scenario,
involving gene duplication and neutral evolution, by its own logic, precludes
natural selection from playing a role in generating genetic information until
after the fact. Thus, it relies entirely on “too much luck.” The sensitivity of

proteins to functional loss, the rarity of proteins within combinatorial
sequence space, the need for long proteins to build new cell types andanimals, the need for whole new systems of proteins to service new cell types,
and the brevity of the Cambrian explosion relative to rates of mutation—all
conspire to underscore the immense implausibility of any scenario for theorigin of Cambrian genetic information that relies upon random variation
alone, unassisted by natural selection.
Yet the classical model of gene evolution—which relies on neutral
evolution—requires novel genes and proteins to arise, precisely, by random
mutation alone. Adaptive advantage accrues after the generation of new
functional genes and proteins. Natural selection cannot play a role until new
functional information-bearing molecules have independently arisen. Thus, toreturn to Dawkins’s imagery, evolutionary theorists envisioned the need toscale the steep face of a precipice of which there is effectively no graduallysloping back side, since the smallest increment of structural innovation in thehistory of life—a new protein fold—itself presents a formidable Mount
Improbable.
By the way, Axe’s later experiments establishing the extreme rarity ofprotein folds in sequence space also show why random changes to existing
genes inevitably efface or destroy function before they generate
fundamentally new folds or functions (scenario one). If only one out of every
1077 of the alternate sequences are functional, an evolving gene will
inevitably wander down an evolutionary dead-end long before it can ever
become a gene capable of producing a new protein fold. The extreme rarity ofprotein folds also entails their isolation from each other in sequence space.
A CATCH-22
Douglas Axe’s results highlight an acute dilemma for neo-Darwinism, a“catch-22.” On the one hand, if natural selection plays no role in generating
new genes, as the idea of neutral evolution implies, then mutations alone must
climb a Mount Improbable in a single leap—a situation that, given Axe’s
results and Dawkins’s own logic, is probabilistically untenable. On the other
hand, any model for the origin of genetic information that envisions asignificant role for natural selection, by assuming a preexisting gene orprotein under selective pressure, encounters other equally intractabledifficulties. The evolving genes and proteins will range over a series of
disadvantageous or nonfunctional intermediates that natural selection will notfavor or preserve, but will, instead, eliminate. At that point, selection-driven
evolution will cease, locking existing genes and proteins into place.

Thus, whether one envisions the evolutionary process beginning with apreexisting functional gene or a duplicated non-coding region of the genome,
the results of mutagenesis experiments present a precise quantitative
challenge to the efficacy of the neo-Darwinian mechanism. Indeed, ourgrowing knowledge about the rarity and isolation of proteins and functional
genes in sequence space implies that neither neo-Darwinian scenario for
producing new genes is at all plausible. Thus, neo-Darwinism does not
explain the Cambrian information explosion.

11
Assume a Gene
When I first heard that Douglas Axe had succeeded in making a rigorous
estimate of the rarity of proteins in sequence space, I wondered what neoDarwinists would say in response. Given the experimental rigor andmathematical precision of the work he reported in the Journal of Molecular
Biology in 2004, and the long odds against mutation and selection everfinding a novel gene or functional protein, what could they say? That theprobability of a successful search for new genes and proteins was higher thanAxe’s experiments suggested? That his methods or calculations were flawed?
That no one else had gotten similar results? Since Axe’s work confirmed
other analyses and experiments, and since his paper had passed through thecareful scrutiny of peer review, none of those responses seemed plausible. Yet
defenders of the adequacy of the neo-Darwinian mechanism were far fromadmitting defeat, as I would soon find out.
The same year, I published a peer-reviewed scientific article about the
Cambrian explosion and the problem of the origin of the biologicalinformation needed to explain it.1 In the paper, I cited Axe’s results andexplained why the rarity of functional proteins in sequence space posed sucha severe challenge to the adequacy of the neo-Darwinian mechanism. The
article appeared in a biology journal, Proceedings of the Biological Society ofWashington, published out of the Smithsonian Institution by scientists
working for the Smithsonian’s National Museum of Natural History(NMNH). Because the article also argued that the theory of intelligent design
could help explain the origin of biological information (see Chapter 18), itspublication created a firestorm of controversy.
Museum scientists and evolutionary biologists from around the country
were furious with the journal and its editor, Richard Sternberg, for allowing
the article to be peer-reviewed and then published. Recriminations followed.
Museum officials took away Sternberg’s keys, his office, and his access toscientific samples. He was transferred from a friendly to a hostile supervisor.
A congressional subcommittee staff later investigated and found that museum

officials initiated an intentional disinformation campaign against Sternberg in
an attempt to get him to resign. His detractors circulated false rumors:“Sternberg has no degrees in biology” (actually he has two Ph.D.’s, one inevolutionary biology and one in systems biology); “He is a priest, not ascientist” (Sternberg is not a priest, but a research scientist); “He is a
Republican operative working for the Bush campaign” (he was far too busy
doing scientific research to be involved in political campaigns, Republican orotherwise); “He’s taken money to publish the article” (not true); and so on.
Eventually, despite the demonstrable falsehood of the charges, he wasdemoted.2
Major news stories about the controversy appeared in Science, Nature, The
Scientist, and the Chronicle of Higher Education.3 Then articles appeared in
the mainstream press, including the Washington Post and the Wall Street
Journal.4 A major story aired on National Public Radio.5 Sternberg himself
even appeared on The O’Reilly Factor.
Despite the intense furor, there was no formal scientific response to myarticle: neither the Proceedings nor any other scientific journal published ascientific refutation. The members of the Council of the Biological Society ofWashington who oversaw the publication of the journal insisted that they
didn’t want to dignify it by responding.
Eventually two scientists and a science education policy advocate—each
associated with the National Center for Science Education, a group thatlobbies for teaching evolution in the public schools—stepped forward. The
three authors—geologist Alan Gishlick, education policy advocate Nicholas
Matzke, and wildlife biologist Wesley R. Elsberry—published a response to
my article on TalkReason.org, a prominent atheistic website.6 Although thewebsite’s guidelines prohibit “ad hominem arguments,” the rule wassomewhat loosely enforced in the case of Gishlick, Matzke, and Elsberry’s
response, which they titled “Meyer’s Hopeless Monster.”
Gishlick, Matzke, and Elsberry attempted to refute my central argument byciting a scientific paper that they said solved the problem of the origin ofgenetic information. The paper, a scientific review essay titled “The Origin of
New Genes: Glimpses from the Young and Old,” had appeared in Nature
Reviews Genetics in 2003. Gishlick, Matzke, and Elsberry asserted that thispaper—coauthored by Manyuan Long, an evolutionary biologist at the
University of Chicago, and several colleagues—was representative of an
extensive “scientific literature documenting the origin of new genes.”7
Other biologists echoed Gishlick, Matzke, and Elsberry’s claim in thecontext of another public controversy. During the 2005 Kitzmiller v. Dovertrial about an ill-advised attempt to require teachers in a Pennsylvania school
district to read a statement about intelligent design, Brown University
biologist Kenneth Miller cited Long’s paper in his testimony. He said that it
shows how new genetic information evolves. The judge in the case, John E.
Jones, then cited Miller’s testimony about Long’s article in his own decision.
Judge Jones asserted there are “more than three dozen peer-reviewed
scientific publications showing the origin of new genetic information by
evolutionary processes.”8 Elsewhere Matzke, along with biologist Paul Gross,stated that the paper by Long “reviews all the mutational processes involvedin the origin of new genes and then lists dozens of examples in which
research groups have reconstructed the genes’ origins.”9 In their view,“Competent scientists know how new genetic information arises.”10
But do evolutionary biologists really know this?
Let’s take a closer look at the article that allegedly shows “how new
genetic information arises.”11
ONCE UPON A GENE
The oft-cited Long paper points to a variety of studies that purport to explain
the evolution of various genes. These studies typically begin by taking a geneand then seeking to find other genes that are similar (or homologous) to it.
They then seek to trace the history of slightly different homologous genes
back to a hypothetical common ancestor gene (or genes). To do this, thestudies survey databases of gene sequences looking for similar sequences in
representatives of different taxonomic groups—often in closely related
species. Some studies also attempt to establish the existence of a common
ancestor gene on the basis of similar genes within the very same organism.
They then typically propose evolutionary scenarios in which an ancestral gene
duplicates itself,12 and then the duplicate and the original evolve differently as
the result of subsequent mutations in each gene.
Next, these scenarios invoke various kinds of mutations—duplication
events, exon shuffling, retropositioning, lateral gene transfer, and subsequent
point mutations—as well as the activity of natural selection (see Fig. 11.1).
The evolutionary biologists conducting these studies postulate that modern
genes arose as the result of these various mutational processes—processes
that they envision as having shaped genes during a long evolutionary history.
Since the information in modern genes is presumably different from theinformation in the hypothetical ancestor genes, they regard the mutational
mechanisms that are allegedly responsible for these differences as theexplanation for the origin of genetic information.
Upon closer examination, however, none of these papers demonstrate how
mutations and natural selection could find truly novel genes or proteins insequence space in the first place; nor do they show that it is reasonably
probable (or plausible) that these mechanisms would do so in the time
available. These papers assume the existence of significant amounts ofpreexisting genetic information (indeed, many whole and unique genes) andthen suggest various mechanisms that might have slightly altered or fusedthese genes together into larger composites. At best, these scenarios “trace”
the history of preexisting genes, rather than explain the origin of the original
genes themselves (see Fig. 11.2).
This kind of scenario building can suggest potentially fruitful avenues ofresearch. But an obvious error comes in mistaking a hypothetical scenario for
either a demonstration of fact or an adequate explanation. None of the
scenarios that the Long paper cites demonstrate the mathematical orexperimental plausibility of the mutational mechanisms they assert as
explanations for the origin of genes. Nor do they directly observe thepresumed mutational processes in action. At best, they provide hypothetical,
after-the-fact reconstructions of a few events out of a sequence of many
supposed events, starting with the existence of a presumed common ancestor
gene. But that gene itself does not represent a hard data point. It is inferred tohave existed on the basis of the similarity of two or more other existing genes,
which are the only actual pieces of observational evidence upon which theseoften elaborate scenarios are based.

FIGURE 11.1
Various types of mutations that are alleged to result in the modification of genes: exon shuffling, retropositioning, lateral gene transfer, and gene fusion.

FIGURE 11.2
Depiction of how gene duplication and subsequent gene evolution might takeplace. While the gene on the bottom remains under selective pressure andcannot experience many mutations without loss of fitness or function (seeFigure 10.3), the duplicated gene at the top can in theory vary withoutdeleterious consequences to the organism.
That these scenarios depend on various inferences and postulations
doesn’t, by itself, disqualify them from consideration. Nevertheless, whether
they adequately explain the origin of genetic information depends upon theevidence for the existence of the entities they infer (the ancestral genes) andthe plausibility of the mutational mechanisms they postulate. Let’s look atboth parts of these scenarios.
COMMON ANCESTOR GENES?
Nearly all of the scenarios developed in the papers that Long cites start withan inferred common ancestral gene from which two or more modern genes
diverged and developed. These scenarios treat the similarity of sequence (theinformation) in two or more genes as unequivocal evidence for a common
ancestral gene (see Fig. 11.2). As I noted in Chapters 5 and 6, standard
methods of phylogenetic reconstruction presuppose, rather than demonstrate,that biological similarity results from shared ancestry. Yet, as we saw in
Chapter 6, similarity of sequence by itself is not always an unequivocal
indicator of common ancestry. Sometimes similarity appears between species
where it cannot be explained by inheritance from a common ancestor (e.g.,
the similar forelimbs on moles and mole crickets) and, at the very least, there
are other possible explanations for sequence similarity.
In the first place, similar gene sequences might have evolved
independently on two parallel lines of descent starting with two different
genes, as the hypothesis of convergent evolution asserts. Recent examples of
convergent genetic evolution now abound in the literature of molecular andevolutionary biology.13 For example, molecular biologists have discoveredthat both whales and bats use similar systems—involving similar genes andproteins—for echolocation. The striking similarity of these systems used in
two otherwise disparate mammalian species has led biologists to posit theparallel evolution of echolocation, including the gene sequences and proteinsthat make it possible, from a common ancestor that did not possess thissystem.14
In addition, it is possible that similar genes might have been separately
designed to meet similar functional needs in different organismal contexts.
Viewed this way, similarity of sequence does not necessarily reflect descentwith modification from a common ancestor, but could reflect design in accord
with common functional considerations, constraints, or goals. I recognize, ofcourse, that to this point I have not given any independent reasons forconsidering the design hypothesis, and that, as a hypothesis for sequencesimilarity by itself, intelligent design may not seem compelling. (For morecompelling reasons to consider intelligent design, see Chapters 17 through19.) Nevertheless, I mention both these other possible explanations for thesimilarity of gene sequences in order to demonstrate that sequence similarity
does not necessarily indicate, or derive from, a common ancestral gene.
ORFAN GENES
Some genes, and the information-rich sequences they contain, most certainly
cannot be explained by reference to the kind of scenarios that Long cites. Allof these scenarios attempt to explain the origin of two similar genes byreference to descent with modification (via mutation) from common ancestralgenes. Yet genomic studies are now turning up hundreds of thousands ofgenes in many diverse organisms that exhibit no significant similarity insequence to any other known gene.15 These “taxonomically restricted genes”
or “ORFans” (for “open reading frames of unknown origin”) now dot thephylogenetic landscape. ORFans have turned up in every major group oforganisms, including plants and animals as well as both eukaryotic andprokaryotic one-celled organisms. In some organisms, as much as one-half ofthe entire genome comprises ORFan genes.16
Thus, even if it could be assumed that similar gene sequences always point
to a common ancestor gene, these ORFan genes cannot be explained using thekind of scenarios that Long’s article cites. Since ORFans lack sequencesimilarity to any known gene—that is, they have no known homologs in evendistantly related species—it is impossible to posit a common ancestral genefrom which a particular ORFan and its homolog might have evolved.
Remember: ORFans, by definition, have no homologs. These genes are
unique—one of a kind—a fact tacitly acknowledged by the increasing numberof evolutionary biologists who attempt to “explain” the origin of such genes
through de novo (“out of nowhere”) origination.
Some might argue that as biologists map the sequence of more genomes
and add more gene sequences to protein databases, homologs of these
ORFans will eventually turn up, thus gradually eliminating the mysterysurrounding the ORFan phenomenon. Yet to date the trend has gone in the
opposite direction. As scientists have explored and sequenced more genomes,
they have discovered more and more ORFans without finding anything like acorresponding number of homologs. Instead, the number of “unpaired”
ORFan genes continues to grow with no sign of the trend reversing itself.17

THE PLAUSIBILITY OF THE MUTATIONAL PROCESSES
Even if evolutionary biologists could establish the existence of the common
ancestral genes from which their scenarios begin, that would not establish theplausibility of a neo-Darwinian mechanism for generating genetic informationfrom that ancestor. Moreover, the term “plausibility” in this context has a
specific scientific and methodologically significant meaning. Studies in thephilosophy of science show that successful explanations in historical sciencessuch as evolutionary biology need to provide “causally adequate”
explanations—that is, explanations that cite a cause or mechanism capable ofproducing the effect in question. In On the Origin of Species, Darwin
repeatedly attempted to show that his theory satisfied this criterion, which
was then called the vera causa (or “true cause”) criterion. In the third chapterof the Origin, for example, he sought to demonstrate the causal adequacy ofnatural selection by drawing analogies between it and the power of animal
breeding and by extrapolating from observed instances of small-scaleevolutionary change over short periods of time.
In this, Darwin hewed to a principle of scientific reasoning that one of his
scientific role models, the great geologist Charles Lyell, used as a guide forreasoning about events in the remote past. Lyell insisted that good
explanations for the origin of geological features should cite “causes now in
operation”—causes known from present experience to have the capacity to
produce the effects under study.18
Do the scenarios developed by various evolutionary biologists cited in theLong review essay meet this criterion? Duplication mutations and various
other modes of random mutational change along with natural selection clearly
constitute “causes now in operation.” No one disputes that. But have theseprocesses demonstrated the capacity to produce the effect in question, namely,
the genetic information necessary to structural innovation in the history oflife? There are several good reasons to think that they have not.
BEGGING QUESTIONSFirst, most of the mutational processes that evolutionary biologists invoke inthe scenarios cited in the Long essay presuppose significant amounts ofpreexisting genetic information on preexisting genes or modular sections of
DNA or RNA. The Long essay highlights seven main mutational mechanisms
at work in the sculpting of new genes: (1) exon shuffling, (2) gene
duplication, (3) retropositioning of messenger RNA transcripts, (4) lateralgene transfer, (5) transfer of mobile genetic units or elements, (6) gene fission

or fusion, and (7) de novo origination (see Fig. 11.1). Yet each of thesemechanisms, with the exception of de novo generation, begins withpreexisting genes or extensive sections of genetic text. This preexisting
functionally specified information is in some cases enough to code for theconstruction of an entire protein or a distinct protein fold. Moreover, thesescenarios not only assume unexplained preexisting sources of biologicalinformation, they do so without explaining or even attempting to explain how
any of the mechanisms they envision could have solved the combinatorial
search problem described in Chapters 9 and 10.
A closer look at each of these mechanisms will show why scenarios that
rely on them beg important questions about the origin of genetic information.
Advocates of exon shuffling envision modular sections of a genome
randomly arranging and rearranging themselves to generate entirely new
genes, not unlike rearranging whole paragraphs in an essay to generate a new
article. In genomes that have regions that code for the production of proteinsinterspersed with regions that do not code for proteins, the term “exon” refers
to a protein-coding region of the genome. These protein-coding regions of the
genome are often interrupted by nonprotein-coding sections of the genome(called introns) that serve other functions, such as coding for the productionof regulatory RNAs. In any case, exons store significant quantities ofpreexisting functionally specified information.
Though most proteins are encoded by multiple exons, a single exon may
encode a substantial unit of protein structure, such as a functional protein fold—a fact that advocates of exon shuffling count in their own attempts to
explain novel proteins. They assume that exons can be blindly shuffled andmixed around to form genes. Nevertheless, this mechanism cannot produce
new protein folds. Either an exon is large enough that it already encodes aprotein fold—in which case it’s not creating a new fold—or it’s too small,small enough that multiple exons must be combined in order to form a stable
protein fold. In this latter case, other problems—in particular, somethingcalled adverse side-chain interaction—will preclude success, as we will see.
Evolutionary scenarios envisioning other mutational mechanisms alsopresuppose important sources of preexistent genetic information. Geneduplication, as the name implies, involves the production of a duplicate copyof a preexisting gene, already rich in functionally specified information.
Retropositioning of messenger RNA transcripts occurs when an enzyme
called reverse transcriptase takes a preexisting strand of messenger RNA andinserts its corresponding DNA sequence into a genome, also producing a
duplicate of the coding portion of a preexisting gene. Lateral gene transfer
involves transferring a preexisting gene from one organism (usually abacterium) into the genome of another. The transfer of mobile genetic
elements likewise occurs when preexisting genes enclosed in circular strandsof DNA called plasmids enter one organism from another and eventually findthemselves incorporated into a new genome. This process also mainly occurs
in single-celled organisms. A similar process can occur in eukaryotes, where
mobile genetic elements called transposons—often called “jumping genes”19—can hop from place to place in the genome. Gene fusion occurs when two
adjacent preexisting genes, each rich with specified genetic information, link
together after the deletion of intervening genetic material.”20
Each of these six mutational mechanisms presupposes preexisting modulesof specified genetic information. Some of these mutational mechanisms also
depend upon sophisticated preexistent molecular machines such as the reverse
transcriptase enzyme used in retropositioning or other complex cellularmachinery involved in DNA replication. Since building these machinesrequires other sources of genetic information, scenarios that presuppose theavailability of such molecular machines to assist in the cutting, splicing, or
positioning of modular sections of genetic information clearly beg thequestion.
Overall, what evolutionary biologists have in mind is something like trying
to produce a new book by copying the pages of an existing book (geneduplication, lateral gene transfer, and transfer of mobile genetic elements),
rearranging blocks of text on each page (exon shuffling, retropositioning, andgene fusion), making random spelling changes to words in each block of text
(point mutations), and then randomly rearranging the new pages. Clearly,
such random rearrangements and changes will have no realistic chance ofgenerating a literary masterpiece, let alone a coherent read. That is to say,these processes will not likely generate specificity of arrangement andsequence and, therefore, do not solve the combinatorial search problem. In
any case, all such scenarios also beg the question. There is a big difference
between shuffling and slightly altering preexisting sequence-specific modulesof functional information and explaining how those modules came to possess
information-rich sequences in the first place.
EVOLUTION EX NIHILO?
Long does cite at least one type of mutation that does not presuppose existing
genetic information, the de novo origination of new genes. For example, one
paper he discusses sought to explain the origin of a promoter region for agene (the part of the gene that helps initiate the transcription of the gene’s
instructions) and found that “this unusual regulatory region did not really‘evolve.’ ” Instead, it somehow snapped into being: “It was aboriginal, createdde novo by the fortuitous juxtaposition of suitable sequences.”21
Many other papers invoke de novo origination of genes. Long mentions,for example, a study seeking to explain the origin of an antifreeze protein in
an Antarctic fish that cites “de novo amplification of a short DNA sequence tospawn a novel protein with a new function.”22 Likewise, Long cites an article
in Science to explain the origin of two human genes involved inneurodevelopment that appealed to “de novo generation of building blocks—
single genes or gene segments coding for protein domains,” where an exon
spontaneously “originated from a unique noncoding sequence.”23 Other
papers make similar appeals. A paper in 2009 reported “the de novo origin of
at least three human protein-coding genes since the divergence withchimp[s],” where each of them “has no protein-coding homologs in any othergenome.”24 An even more recent paper in PLoS Genetics reported “60 new
protein-coding genes that originated de novo on the human lineage since
divergence from the chimpanzee,”25 a finding that was called “a lot higher
than a previous, admittedly conservative, estimate.”26
Another 2009 paper in the journal Genome Research was appropriately
titled “Darwinian Alchemy: Human Genes from Noncoding RNA.” It
investigated the de novo origin of genes and acknowledged, “The emergenceof complete, functional genes—with promoters, open reading frames (ORFs),
and functional proteins—from ‘junk’ DNA would seem highly improbable,
almost like the elusive transmutation of lead into gold that was sought by
medieval alchemists.”27 Nonetheless, the article asserted without saying how
that: “evolution by natural selection can forge completely new functional
elements from apparently nonfunctional DNA—the process by whichmolecular evolution turns lead into gold.”28
The presence of unique gene sequences forces researchers to invoke denovo origin of genes more often than they would like. After one study of fruit
flies reported that “as many as ~12% of newly emerged genes in the
Drosophila melanogaster subgroup may have arisen de novo from noncoding
DNA,”29 the author went on to acknowledge that invoking this “mechanism”
poses a severe problem for evolutionary theory, since it doesn’t really explain
the origin of any of its “nontrivial requirements for functionality.”30 The
author proposes that “preadaptation” might have played some role. But that
adds nothing by way of explanation, since it only specifies when (before
selection played a role) and where (in noncoding DNA), not how the genes inquestion first arose. Details about how the gene became “preadapted” forsome future function is never explained. Indeed, evolutionary biologists

typically use the term “de novo origination” to describe unexplained increases
in genetic information; it does not refer to any known mutational process.
Taking stock, then, many of the mutational processes that Long cites
either: (1) beg the question as to the origin of the specified information
contained in genes or parts of genes, or (2) invoke completely unexplained denovo jumps—essentially evolutionary creation ex nihilo (“from nothing”).
Thus, ultimately, the scenarios featured in Long’s review essay do not
explain the origin of the specified information in either genes or sections ofgenes. That would require a cause capable of solving the combinatorial
inflation problem discussed in the previous chapters. But none of the
scenarios discussed in Long’s article even addresses this problem, let alone
demonstrates the mathematical plausibility of the mechanisms they cite. Yet,
Gishlick, Matzke, and Elsberry originally cited Long as a definitive refutationof my article—the one in which I argued that the rarity of genes and proteinsin sequence space cast doubt on the power of selection and mutations togenerate novel genetic information. Professor Miller, in his testimony at thecelebrated Dover trial, even convinced a federal judge to affirm that Long had
succeeded in demonstrating how genetic information originates in acelebrated legal ruling. Clearly, one cannot solve a problem or refute anargument by failing to address it.31
PROTEIN FOLDS: PLAUSIBLE BUT IRRELEVANT SCENARIOS
There is a second and closely related difficulty associated with the scenarios
cited by Long. Typically, they do not even try to explain the origin of new
protein folds, and few of them analyze genes different enough from each otherthat their protein products could, even conceivably, exemplify different folds.
Instead, they usually attempt to explain the origin of homologous genes—
genes that produce proteins with the same folded structure performing thesame function or a closely related one.
For example, Long cites one study comparing the two genes RNASE1 andRNASE1B, which code for homologous digestive enzymes.32 The two
proteins perform nearly the same function: breaking down RNA molecules inthe digestive tracts of colobine leaf-eating monkeys, though each does its job
at a slightly different optimal chemical pH. More important, given that theamino-acid sequences of the two enzymes are 93 percent identical, structural
biologists would expect both enzymes to utilize the same protein fold toaccomplish their closely related tasks.
Long also references a study of a gene that codes for a histone protein,
Cid, in two closely related species of fruit flies—Drosophila melanogasterand Drosophila simulans. The study didn’t try to explain the “origin” of thegene—it merely compared the gene in the two species, catalogued someminor differences between them, and asked how those differences arose. The
study identified some two dozen nucleotide differences between the genes for
Cid in the two species—only 17 of which might have changed an amino acidin the sequence out of 226 total amino acids in the Cid protein.33 Such a slight(7.5 percent) difference would be extremely unlikely to translate into different
protein folds. Indeed, natural sequences known to have different folds do nothave anything like the correspondingly high degree (92.5 percent) of
sequence identity. Instead, known natural sequences with this high level ofsequence identity have the same fold.
Long also cites two studies of FOXP2, a gene involved in regulating gene
expression in humans, chimps, other primates, and mammals. In humans andother mammals, this gene is involved in brain development.34 Nevertheless,according to one study, the protein coded for by this gene in humans acquired
just “two amino-acid changes on the human lineage”35 during the entire
course of its evolution from a common chimp-human ancestor—again, notlikely a sufficient enough change to generate a new protein fold.
The Long review essay cites numerous scenarios of this type—scenarios
attempting to explain the evolution of slight gene variants (and their similarproteins), not the origin of new protein folds. This is an important distinction
because, as we saw in Chapter 10, new protein folds represent the smallest
unit of selectable structural innovation, and much larger structural innovationsin the history of life depend upon them. Explaining the origin of structural
innovation requires more than just explaining the origin of variant versions of
the same gene and protein or even the origin of new genes capable of coding
for new protein functions. It requires producing enough genetic information—
truly novel genes—to produce new protein folds.
Thus, even where these scenarios are plausible, they are not relevant to
explaining the origin of the genetic information necessary to produce the kindof structural innovation that occurs in the Cambrian explosion (or many otherevents in the history of life).
PROTEIN FOLDS: RELEVANT BUT IMPLAUSIBLE SCENARIOS
In a few cases, the evolutionary scenarios cited in the Long paper appear to be
attempts to explain genes that are different enough from each other that they
could conceivably code for proteins with different folds. For example, Long
discusses several papers that equate exon shuffling with the shuffling ofprotein domains. Recall that a protein domain is a stable “tertiary” proteinstructure or fold made of many smaller “secondary” structures such as alphahelices or beta strands (see Fig. 10.2). Many complex proteins have numerous
domains, each exhibiting a unique fold or tertiary structure. One version of
the exon-shuffling hypothesis assumes that each exon codes for a specificprotein domain. It envisions random cutting and splicing—excising, shuffling,
and recombination—of the exon portions of the genome, resulting in themodular rearrangement of genetic information. The resulting composite gene
will then code for a new composite protein structure. As Long proposes,“Exon shuffling, which is also known as domain shuffling, often recombinessequences that encode various protein domains to create mosaic proteins.”36
Of the mechanisms that Long discusses, exon shuffling (and the closely
related idea of gene fusion) provides perhaps the most plausible means ofgenerating new (composite) proteins.37 Nevertheless, the idea that exon
shuffling can explain the origin of the genetic information necessary to
produce new protein folds or whole composite proteins is problematic forseveral reasons.
First, the exon-shuffling hypothesis seems to assume that each exon
involved in the process codes for a protein domain that folds into a distinctive
tertiary structure. To a protein scientist, a protein domain is equivalent to aprotein fold, though distinct protein structures (folds) may be composed ofseveral smaller domains (or folds). Thus, at the very least, the exon-shuffling
hypothesis presupposes the prior existence of a significant amount of genetic
information—enough information to build an independent protein domain or
fold. As such, it fails as an explanation for the origin of protein folds and theinformation necessary to produce them.
Some advocates of exon shuffling, however, may be using the term
“protein domain” in a slightly fuzzier way. They might be equating domains
with smaller structural units such as fragments of a fold made of several unitsof secondary structure such as alpha helices or beta strands. Conceived thisway, the exon-shuffling hypothesis would then entail the construction of anew protein structure by combining these smaller “fragments.”
But in most cases, if the amino-acid chain that forms a domain is chopped
into fragments, then the resulting isolated pieces would cease to retain their
original shapes. Why? Because the three-dimensional shape of one small
section of a protein is heavily dependent upon the overall structure and shapeof the rest of the protein. Snip out a section or fragment, or synthesize afragment in isolation from the rest of the protein, and a floppy amino-acidchain will result—one that has entirely lost its original shape, or ability toform a stable structure. Thus, this version of the exon-shuffling hypothesis
lacks credibility because it incorrectly assumes that shapeless protein

fragments can be mixed and matched in a modular fashion to form newstable, functional protein folds. Moreover, even if such shuffling were
physically plausible, this version of the hypothesis would have anotherproblem. It still presupposes unexplained functional information—inparticular, the information necessary to specify, not just the smaller fragments,
but also the information required to arrange these smaller units into stablefolds, and ultimately functional proteins.
Second, since the exon-shuffling hypothesis assumes that each exon
involved in the shuffling codes for a specific protein domain, it also assumes
that exon boundaries correspond to the boundaries of protein domains orfolds. In existing genes, however, exon boundaries do not typicallycorrespond to the boundaries of folded domains within the larger proteins.38 If
the shuffling of exons explained how actual proteins had come into existence,then there should be a clear correspondence or correlation between exonboundaries within genes and the corresponding protein domains within larger
composite structures (i.e., whole proteins). The absence of such a
correspondence suggests that exon shuffling does not account for the origin of
known compound protein structures.
Third, relying on exon shuffling to cobble together a new protein fold fromsmaller units of protein structure is physically implausible for another reason.
To see why, we need to examine what a “side chain” is. All twenty proteinforming amino acids have a common backbone (made of nitrogen, carbon,
and oxygen), but each one has a different chemical group called a side chain
sticking out at roughly right angles from that backbone. The interactions
between side chains determine whether secondary units of protein structure
made from chains of amino acids will fold into larger stable threedimensional folds.39 Though many different sequences will generatesecondary structures (alpha helices and beta strands), generating stable folds
is much more difficult and requires much more specificity in the arrangementof amino acids and their side chains. Specifically, since the elements insmaller secondary structural units in proteins are surrounded by side chains,
they cannot be combined into new folds unless the elements have thesequence specificity required for the side chains to complement one another.40
That means smaller secondary structural units will rarely41 fuse together toform stable tertiary structures or folds. Instead, attempts to form new folds
from smaller units of structure repeatedly encounter adverse interactions
between the side chains of the amino acids within units of secondary
structure.
The need for extreme specificity in the sequential arrangements of amino

acids, discussed in the previous chapter, means that the overwhelming
majority of amino-acid sequences in units of secondary structure will not
result in stable folds as these units of structure come into contact with eachother. As discussed in Chapter 10, the extreme rarity of functional proteins(with stable folds) in sequence space ensures that the probability of finding acorrect fold-stabilizing sequence will be astonishingly small. For this reason,even skilled protein scientists have struggled to design sequences that willproduce stable protein folds.42 Almost invariably the units of secondary
structure that they attempt to combine or otherwise place into stablecomposite structures will not fold because of the interactions of their aminoacid side chains.43 As molecular biologist Ann Gauger explains, “Thus,[alpha] helices and [beta] sheets are sequence-dependent structural elements
within protein folds. You can’t swap them around like Lego bricks.”44
Nor is it an easy matter to simply find different sequences of amino acids
that will stabilize folds from smaller secondary units of structure, again,
because of the extreme rarity of functional (and folding) sequences withinamino-acid sequence space. Generating specific sequences that will fold into
stable structures, whether in the lab or during the history of life, requires
solving the combinatorial inflation problem. Even small folds will require fiveor six units of secondary structure with 10 or so amino acids in each unit, thatis, 60 or more precisely sequenced amino acids. Modest-size folds will
require a dozen or more units of secondary structure and 150 to 200
specifically arranged amino acids in order to stabilize a fold. Larger protein
folds will require many more secondary units and specifically arranged aminoacids. Since, however, many mission-critical functions within even thesimplest cell require many folds (of at least 150 amino acids) working in close
coordination, the need to produce proteins of at least this length numerous
times through the history of life cannot be avoided.
All this requires searching for a functional needle in a vast haystack of
combinatorial possibilities. Recall that Douglas Axe estimated the ratio of
needles (functional sequences) to strands of straw in the haystack(nonfunctional sequences) to be 1 to 1077 for sequences of modest-length(150 amino acids).
Of course, in naturally occurring proteins, the interactions between side
chains in units of secondary structure do maintain stable folds. But these
proteins, with their stable three-dimensional folded structures, depend upon
exceedingly rare and precisely arranged sequences of amino acids. The
question is not whether the combinatorial search problem necessary to
produce stable protein folds has ever been solved, but whether a neo-

Darwinian mechanism relying on random mutations (in this case random
shuffling of exons) provides a plausible explanation for how it might havebeen solved.
The papers that Long cites give no reason to think that exon shuffling (orany other mutational mechanism) has solved this problem. The exon-shuffling
hypothesis ignores the need for side-chain specificity, though the need forsuch specificity has repeatedly defeated attempts in the laboratory to build
new proteins from units of secondary structure in the manner required.
But advocates of exon shuffling make no attempt to show how random
rearrangements of protein domains—whether the domains are conceived of as
fragments of a fold or whole folds—would solve the combinatorial problem.
Nor do they challenge Sauer’s or Axe’s experimentally derived quantitative
estimates of the rarity of functional genes or proteins. They do not challenge
the probability calculations based on these estimates. And they do not showthat a mechanism exists that can search amino-acid sequence spaces more
effectively or efficiently than random mutation and selection. Nor do they
demonstrate the efficacy of exon shuffling in a model system in thelaboratory. Instead, basic considerations of protein structure imply the
implausibility of exon shuffling as a means of generating the genetic
information necessary to produce a new protein fold.45 So, in the end, withfew words and with apparent confidence, advocates of exon shuffling simply
assert, as the Long paper does, that “exon shuffling often recombinessequences that encode various protein domains to create mosaic proteins.”
WORD SALAD
The assertion of Long and his colleagues about exon shuffling, like manyother statements about postulated mutational mechanisms, blurs thedistinction between theory and evidence. Despite the authoritative tone ofsuch statements, evolutionary biologists rarely directly observe the mutational
processes they envision. Instead, they see patterns of similarities anddifferences in genes and then attribute them to the processes they postulate.
Yet the papers that Long cites offer neither mathematical demonstration, nor
experimental evidence, of the power of these mechanisms to produce
significant gains in biological information.
In the absence of such demonstrations, evolutionary biologists have taken
to offering what one biologist I know calls “word salad”—jargon-laced
descriptions of unobserved past events—some possible, perhaps, but none
with the demonstrated capacity to generate the information necessary to
produce novel forms of life. This genre of evolutionary literature envisions

exons being “recruited”46 and/or “donated”47 from other genes or from an“unknown source”48; it appeals to “extensive refashioning”49 of genes; itattributes “fortuitous juxtaposition of suitable sequences”50 to mutations or“fortuitous acquisition”51 of promoter elements; it assumes that “radical
change in the structure” of a gene is due to “rapid, adaptive evolution”;52 it
asserts that “positive selection has played an important role in theevolution”53 of genes, even in cases when the function of the gene understudy (and thus the trait being selected) is completely unknown;54 it imagines
genes being “cobbled together from DNA of no related function (or nofunction at all)”;55 it assumes the “creation” of new exons “from a uniquenoncoding genomic sequence that fortuitously evolved”;56 it invokes “thechimeric fusion of two genes”;57 it explains “near-identical”58 proteins in
disparate lineages as “a striking case of convergent evolution”;59 and when nosource material for the evolution of a new gene can be identified, it assertsthat “genes emerge and evolve very rapidly, generating copies that bear little
similarity to their ancestral precursors” because they are apparently“hypermutable.”60 Finally, when all else fails, scenarios invoke the “de novo
origination” of new genes, as if that phrase—any more than the others justmentioned—constitutes a scientific demonstration of the power of mutational
mechanisms to produce significant amounts of new genetic information.61
These vague narratives resemble nothing so much as the naming games ofscholastic philosophers in the Middle Ages. Why does opium put people tosleep? Because it has a “dormative” virtue. What causes new genes to evolve
so rapidly? Their “hypermutability” or perhaps their ability to undergo “rapid,
adaptive evolution.” How do we explain the origin of two similar genes in
two separate, but otherwise widely disparate lineages? Convergent evolution,of course. What is convergent evolution? The presence of two similar genes
in two separate, but otherwise widely disparate lineages. How does
convergent evolution occur, given the improbability of finding even one
functional gene in sequence space, let alone the same gene arising twice
independently? No one knows exactly, but perhaps it was a “fortuitous
juxtaposition of suitable sequences,” or “positive selection,” or “de novo
origination.” Need to explain two similar genes in more closely related
lineages? Try “gene duplication,” or “chimerical gene fusion,” or“retropositioning,” or “extensive refashioning of the genome,” or some otherscientific-sounding combination of words.
The vagueness of these scenarios raises serious questions about how
scientists could regard them as decisive demonstrations or refutations ofanything—let alone refutations of the kind of experimentally based,mathematically precise challenges to mutation and selection described in theprevious chapter.
So despite the official pronouncement of a federal judge and claims ofextensive “scientific literature documenting the origin of new genes,”
evolutionary biologists have not demonstrated how new genetic informationarises, at least not in amounts sufficient to build protein folds, the crucial unitsof biological innovation. Biologists have not solved the problem ofcombinatorial inflation or refuted the precise quantitative argument against
the creative power of the selection and mutation mechanism presented in theprevious chapter (or in my 2004 article). Nor has anyone provided acompelling refutation of Douglas Axe’s assessment of the rarity of genes andproteins on which that argument is based.
In fairness, neo-Darwinian biologists have mathematical models of theirown—models indicating to them that nearly unlimited evolutionary change
can occur under the right conditions. The assumption that these models,
which are based on the equations of population genetics, accurately represent
how much evolution can occur has left many evolutionary biologists
confident in the creative power of various mutational mechanisms. But should
they be?
In the next chapter, I will take up this question. As I do, I’ll explain why
evolutionary biologists have been, heretofore, untroubled by mathematicalchallenges to neo-Darwinism. I’ll also show why that has begun to change as
new developments in molecular genetics have introduced another formidable
mathematical challenge to the creative power of the neo-Darwinianmechanism—a challenge that arises from within the neo-Darwinian
framework and raises yet new questions about the causal adequacy of the neoDarwinian mechanism.

12Complex Adaptations and the NeoDarwinian Math
University of Illinois biologist Tom Frazzetta knew the textbook story as wellas anyone. According to neo-Darwinian theory, organisms with all theircomplex systems came into existence via natural selection acting on randomly
arising, small-scale variations and mutations. As Frazzetta understood, thisevolutionary mechanism necessarily transforms organisms gradually, withmodifications parceled into increments “as a sort of continuous change, where
one structural condition melts gradually into another.”1
Frazzetta had his doubts, however. As an expert in functional
biomechanics—studying how animals actually work—he had dissected theskulls of rare snakes found only on the island of Mauritius, in the Indian
Ocean. These snakes, called bolyerines, are boa-like but have an anatomical
specialization found in no other vertebrate. Their maxilla, the tooth-bearing
bone of the upper jaw, is divided into two segments, linked by a flexible joint
and serviced by many specialized nerves, extra bones, tissues, and differently
arranged ligaments. This unique trait allows the snakes to bend the front halfof their upper jaw backwards when they attack prey (see Fig. 12.1).
Could this complex system of bones, joints, tissues, and ligaments have
evolved gradually? “A movable joint dividing the maxilla into two segments,”
observed Frazzetta, “seems to have either a presence or absence, with nointermediate to connect the two conditions.”2 That is, either the maxilla
occurs as one bone (as it does in every other vertebrate) or as two segmentswith all the accompanying joints, bones, ligaments, and tissues necessary to
make it work, as it does in the bolyerine snakes. No intermediate condition—a broken maxilla with two pieces of bone lacking the necessary joints, tissues,and ligaments, for example—appears viable. As Stephen Jay Gould asked of
the same system, “How can a jawbone be half broken?”3 Or as Frazzetta
himself observed, “I thus find it difficult to envision a smooth transition froma single maxilla to the divided condition seen in bolyerines.”4 Yet because theintermediate forms would not be viable, building a bolyerine jaw would
require all the necessary parts—the jointed maxilla, the adjoining ligaments,
and the necessary muscles and tissues—arising together.
Yet the problem for neo-Darwinian theory, Frazzetta realized, extended
well beyond the anatomical peculiarities of rare snakes. As a young
evolutionary biology professor, he had studied complex features in a wide
variety of species. He knew that almost any biological structure of interest—
the inner ear, the amniotic egg, eyes, olfactory organs, gills, lungs, feathers,
the reproductive, circulatory, and respiratory systems—possesses multiple
necessary components. To change such systems requires altering each of themany independent parts upon which their functions are based. This cannot bedone willy-nilly. For example, changing any of the three bones of the
mammalian inner ear—the incus, stapes, or malleus—will perforce require
corresponding changes in the other bones and in other parts of the ear as well,such as the tympanic membrane or the cochlea. Complex biological systems
depend for their functions on tens or hundreds of such independent, yet jointly
necessary parts. As the number of necessary components increases, therequisite number of coordinated changes increases too, rapidly driving up the
difficulty of maintaining the functional integrity of the system while
modifying any of its parts.

FIGURE 12.1
A complex adaptation: the jointed upper jaw of the bolyerine snake, madepossible by its accompanying tendons, ligaments, and musculature. The otherskull shows the single-boned jaw, found in other related snakes.
And that was the problem, as Frazzetta understood it. Any system that
depends for its function on the coordinated action of many parts could not bechanged gradually without losing function. But in the neo-Darwinian schemeof things, natural selection acts to preserve only functional advantages.
Changes that result in death or reduced function will not be preserved. The
integrated complexity of many biological systems thus imposes limitations on
the evolutionary process—limitations that human engineers do not face when

they design complex integrated systems. In 1975, Frazzetta wrote a minor
classic entitled Complex Adaptations in Evolving Populations explaining thisconcern. He wrote:
When modifying the design of a machine, an engineer is not bound by
the need to maintain a real continuity between the first machine and themodification. . . . But in evolution, transitions from one type to the next
presumably involve a greater continuity by means of a vast number ofintermediate types. Not only must the end product—the final machine—
be feasible, but so must be all the intermediates. The evolutionary
problem is, in a real sense, the gradual improvement of a machine
while it is running!5
Historically, evolutionary biologists tried to solve this problem one
advantageous variation or mutation at a time. Starting with Darwin himself,they have attempted to explain how natural selection and random variation
could build complex systems as the result of a series of incremental changes,
each of which might confer some selectable advantage. Darwin famously
employed this strategy to explain the origin of the eye, asking his readers toimagine a series of incremental, advantageous changes to a simple “nerve
sensitive to light.”6
As Frazzetta thought about the problem of explaining the origin ofcomplex systems, he came to doubt both the classical and the modern
Darwinian accounts of such systems. Frazzetta acknowledged that he was
influenced in part by the skepticism expressed by the Wistar “outsiders” (seeChapter 9). He admitted “revealing some hideous personalia” in confessingthat he was attracted to the worries about neo-Darwinism expressed by
Murray Eden and other Wistar skeptics.7
Frazzetta’s concerns about the adequacy of the neo-Darwinian mechanism,
like Eden’s, turned on the growing appreciation of the nature and importanceof genetic information. Though biologists then (as now) didn’t fully
understand how genetic information in DNA correlates or “maps” to thesehigher-level complex morphological structures, by 1975 they did know thatmany hundreds of genes can be involved in coding for a single complex
integrated structure. Thus, altering the anatomical structure of the mammalianear or the vertebrate eye, for example, would involve altering the genes thatcode for its constituents, which implies, most implausibly, that multiple
coordinated mutations would occur virtually simultaneously.
As Frazzetta explained, “Phenotypic alteration of integrated systems
requires an improbable coincidence of genetic (and hence, heritablephenotypic) modifications of a tightly specified kind.”8 Yet the extreme
specificity of the fit of the components and the functional dependence of thewhole system on this fit imply limits to allowable genetic change. Genetic
change affecting any one of the necessary components, unless matched bymany corresponding—and vastly improbable—genetic changes, will result infunctional loss and often death. For this reason, as Frazzetta concluded, “We
are still left with the unabating need to explain evolutionary changes insystems that have the operational integration characteristic of things we
recognize as ‘machines.’ ”9 At the time, the doubts he expressed gained little
traction in the evolutionary biology community, because neo-Darwinianevolutionary biologists assumed that mutation and selection had nearly
unlimited creative power, enough to generate even complex systems of thekind described in Frazzetta’s book.
The mathematical expression of neo-Darwinian theory, as represented in
the equations of a subdiscipline of biology known as population genetics,
seemed to confirm this conviction. Population genetics models how genefrequencies change as the result of processes such as mutation, genetic drift(neutral changes in the genome that natural selection neither favors nor
eliminates), and natural selection. On the assumption that advantageous
variations or traits will arise as the result of even single mutations, themathematical models of population genetics describe how much evolutionarychange can occur in a given period of time. These estimates are based upon,among others, three primary factors: mutation rates, effective population
sizes, and generation times. When evolutionary biologists plug estimates forthese factors into the equations of population genetics, their calculations seemto imply that standard evolutionary mechanisms could generate significant
amounts of evolutionary change in many groups of organisms—even enoughto build complex systems. As long as mutations generate a continuous supplyof new traits, any system, however complex, can be built one trait at a time—
trait upon trait—via the creative power of natural selection. Or so the story
goes.
Confidence in these mathematical models (and their underlying
assumptions) led many neo-Darwinists to disregard the need to give detailed
accounts of the specific evolutionary pathways by which complex systems
might have arisen. For example, in an evolutionary biology text widely used
about the time Frazzetta first posed this challenge, evolutionary biologists
Paul Ehrlich and Richard Holm advised:
One need not go into the details of the evolution of the bird’s wing, thegiraffe’s neck, the vertebrate eye, the nest building of some fish, etc., asthe selective origins of these and other structures and of behavioral
patterns may be assumed to be basically the same in outline as those,such as industrial melanism, which have already been discussed. Evena slight advantage or disadvantage in a particular genetic change
provides a sufficient differential for the operation of natural selection.10
The phrase “sufficient differential for the operation of natural selection” refers
to the equations of population genetics and one of the factors (the so-called
selection coefficient) that determines how rapidly particular traits would be
likely to disseminate through a population. The message was clear: the mathtells the story; the biological details of the origin of complex systems don’tmatter.
The neo-Darwinian focus on mathematical modeling helps to explain why
mainstream evolutionary biologists haven’t worried about the problem of theorigin of new genes and proteins or the problem of combinatorial inflation,
discussed in Chapters 9 and 10. Many contemporary evolutionary biologists,
like the founders of population genetics, assumed that some mechanism forbuilding new genes already existed. Indeed, they assumed that new traits (andthe genes for building them) can arise as the result of even single mutations(or a series of such mutations that each confer a small, incremental, selectableadvantage). Thus, the mathematical expression of neo-Darwinian theory
seemed to certify the plausibility of even large-scale evolutionary changes—
again, provided these changes could occur one mutation at a time.
But what if there are systems in living organisms that cannot be built one
mutation at a time, and instead must be built by simultaneous coordinatedchanges? What if building just a single new gene or protein requires such
coordinated mutational changes? What if individual genes turned out to becomplex adaptations?
Mathematical challenges of the kind first advanced at Wistar, and that
Douglas Axe’s experimental findings have exacerbated, initially did not dent
confidence in the adequacy of neo-Darwinian explanations. Many
evolutionary biologists have simply regarded mathematical challenges to thecreative power of the mechanism, coming as they mostly do from scientists
and engineers in other fields, as exotic or irrelevant.
That has begun to change. And it has begun to change in a way that has
not only introduced a new mathematical challenge to the creative power ofthe neo-Darwinian mechanism, but also in a way that indirectly confirms
Axe’s key insight about the rarity of genes and proteins. In the last decade,developments in molecular genetics and population genetics have exposed aconnection between the problem of the origin of new genes and proteins andthe origin of complex adaptations, a connection first perceived by Tom
Frazzetta back in 1975. As more biologists have recognized that connection,
they too have begun to share Frazzetta’s doubt.
POPULATION GENETICS AND THE ORIGIN OF GENETIC
INFORMATIONThe neo-Darwinian synthesis was formulated during the 1930s before theelucidation of the structure of DNA. Biologists at that time did not yet
understand the nature, structure, or precise location of genetic information.11
They did not associate genes with long strings of nucleotide bases along thespine of the DNA molecule. They did not think of genes as long sections ofdigital code stored in complex biomacromolecules. Instead, after Mendel, but
before Watson and Crick, genes were defined operationally as those entities,
associated with chromosomes, that produced specific visible or selectable
anatomical traits, such as eye color or beak shape.
The architects of neo-Darwinism working in the 1930s reformulated
evolutionary theory to emphasize the importance of mutations as the source ofgenetic variation. It followed, therefore, that the mutations—which they
regarded as the source of heritable variation—must operate on genes. Not
knowing the nature of genes, they also assumed that a single mutation could
alter a gene in such a way as to produce a new trait.
The equations of population genetics are predicated upon this assumption.
The rate of mutation thus emerges as an important factor in computing theamount of evolutionary change that can occur in any given population. If
every individual mutation can produce a new, potentially selectable trait, thenthe rate at which such variation accumulates partially determines how muchchange can occur in a given time.
After 1953, biologists no longer conceived of the gene as an abstract
entity. Watson and Crick showed that the gene had a definite locus andstructure and that individual genes contain hundreds or thousands of precisely
sequenced nucleotide bases, each functioning as digital characters in a larger
instruction set. Consequently, biologists changed their understanding of
mutations as well. Biologists came to understand mutations as something liketypographic errors in long strings of digital code. As a result, many scientists
began to realize that individual mutations were unlikely by themselves to
produce new beneficial traits. Some scientists realized that mutations wereinstead overwhelmingly more likely to degrade the information contained in agene than to produce a new function or trait, and that the accumulation of
mutations would eventually and typically result in the loss of function.

This change of perspective called for an explanation of how mutations
could generate new genes—an explanation that was provided beginning in the
1970s with the ideas of gene duplication, subsequent neutral evolution, andpositive selection.
Though the theory of gene duplication played no formal role in themathematical structure of population genetics, it did serve to buttress a criticalassumption of the whole enterprise. After the 1950s, evolutionary biologists
no longer assumed that single mutations would necessarily generate whole
new traits. That left a critical assumption of population genetics essentially
undefended. For many evolutionary biologists, the theory of gene duplication
closed that conceptual gap. After the theory was formulated, many
evolutionary biologists thought that a mechanism had been discovered bywhich sections of genetic text could accumulate multiple changes withoutcompromising the fitness of an organism, thus ensuring the eventual
production of new genes and a steady supply of new traits.
So when Frazzetta confronted evolutionary biology with the problem ofcomplex adaptations in the mid-1970s, most neo-Darwinian biologists
responded with a collective yawn, if they noticed it at all. His challenge wasno challenge after all. So implied the math of population genetics—provided
its assumptions about the ease with which new mutations could generate newtraits were valid.
But were they valid? Could a series of separate mutations generate the newgenes necessary to build new proteins and new traits, or did building genes
require multiple coordinated mutations?
ARE GENES COMPLEX ADAPTATIONS?
Classically, Darwinian biologists have assumed that small, separate step-bystep changes could produce all biological structures and features, provided
each change confers some survival or reproductive advantage. In his chapter
in the 1909 anthology Darwin and Modern Science, the British geneticist
William Bateson wryly described how this widespread assumption prevented
evolutionary biologists from confronting the real difficulty of explaining theorigin of complex adaptations:
By suggesting that the steps through which an adaptive mechanism
arises are indefinite and insensible, all further trouble is spared. While
it could be said that species arise by an insensible and imperceptible
process of variation, there was clearly no use in tiring ourselves bytrying to perceive that process. This labour-saving counsel foundgreat favor.12
One of the first prominent evolutionary biologists to consider the
possibility that building new genes and proteins might require multiple
coordinated mutations was John Maynard Smith. Maynard Smith worked as
an aeronautical engineer during World War II, but then took up the formal
study of evolutionary biology after the war. He eventually helped to found the
University of Sussex, where he also served as a distinguished professor of
biology until the mid-1980s.13
In 1970, Maynard Smith wrote an article in Nature responding to an earlier
article by Frank Salisbury, a biologist from Utah State University. Salisbury
had raised questions about whether random mutations could explain thespecificity of the arrangement of nucleotide bases necessary to producefunctional proteins. Salisbury worried, following discussions at Wistar, thatthe probability of random mutations generating functional arrangements ofbases or amino acids was prohibitively low. According to Salisbury’s
calculations, “The mutational mechanism as presently imagined could fallshort by hundreds of orders of magnitude of producing, in a mere four billion
years, even a single required gene.”14
To overcome this improbability, Maynard Smith proposed a model ofprotein evolution. While admitting that the origin of the first proteinsremained a mystery, he suggested that one protein could evolve into anotheras the result of small incremental changes in amino-acid sequences, provided
each sequence maintained some function at each step along the way. Maynard
Smith compared protein-to-protein evolution to changing one letter in an
English word in order to generate a different word (while at each step
generating a different meaningful word). He used this example to convey how
he thought protein evolution might work:
WORD → WORE → GORE → GONE → GENE
He explained:
The words [in this analogy] represent proteins; the letters represent
amino acids; the alteration of a single letter corresponds to the simplest
evolutionary step, the substitution of one amino acid for another; andthe requirement of meaning corresponds to the requirement that each
unit step in evolution should be from one functional protein
to another.15

As a self-professed “convinced Darwinist,” Maynard Smith realized thatnatural selection and random mutation could only build new biologicalstructures from preexisting structures if each intermediate structure along theway conferred some adaptive advantage. He thought that this requirement
applied as much to the evolution of new genes and proteins as it did to theevolution of new phenotypic traits or larger-scale anatomical structures.16
Nevertheless, the essentially digital or alphabetic character of the genetic
information that directs protein synthesis suggested a problem to Maynard
Smith. How, he asked, could one gene or protein evolve into another if such atransformation required multiple simultaneous changes in the bases of thegenetic text (or arrangement of amino acids)? If building new genes required
multiple coordinated mutations, then the probability of generating a new geneor protein would drop precipitously, since such a transformation would
require not just one improbable mutational event, but two or three or more,
occurring more or less at once. Here’s how he described the potential
problem:Suppose that a protein ABCD . . . exists, and that a protein abCD . . .
would be favoured by selection if it arose. Suppose further that theintermediates aBCD . . . and AbCD . . . are nonfunctional. These forms
would arise by mutation, but would usually be eliminated by selection
before a second mutation could occur. The double step from abCD . . .
to ABCD would thus be very unlikely to occur.17
In Maynard Smith’s view, the improbability associated with “double-step”
or multiple-step coordinated mutations presented a significant potential
problem for molecular evolution. In the end, however, he concluded that suchmutations were so improbable that they must not have played a significant
role in the evolution of novel structures. As he explained, “Such double steps. . . may occasionally occur, but are probably too rare to be important inevolution.”18
For several decades, the problem he flagged receded into obscurity. As
biochemist H. Allen Orr pointed out in 2005 in the journal Nature Reviews
Genetics, “Although Maynard Smith’s work appeared early in the molecularrevolution,” his ideas about problems facing protein evolution “were almost
entirely ignored for two decades.”19 Thus, Orr noted that evolutionary
biologists stopped thinking about molecular evolution as a consequence ofadaptive changes at the amino-acid level. Not until the first decade of thetwenty-first century would biologists confront the challenge of making a

rigorous quantitative analysis of the plausibility of protein-to-protein
evolution.
WAITING FOR COMPLEX ADAPTATIONSIn 2004, Lehigh University biochemist Michael Behe (see Fig. 12.2),
introduced briefly at the end of Chapter 9, and University of Pittsburgh
physicist David Snoke published a paper in the journal Protein Science that
returned to the problem first described by Maynard Smith.20 By this time,
Behe had established himself as a prominent critic of neo-Darwinism byarguing that the neo-Darwinian mechanism did not provide an adequate
explanation for the origin of functionally integrated “irreducibly complex”
molecular machines. In his 2004 paper, Behe sought to extend his critique of
neo-Darwinism by assessing its adequacy as an explanation for new genes
and proteins. He and Snoke attempted to assess the plausibility of protein
evolution in the case that it does indeed require multiple coordinatedmutations. They applied standard neo-Darwinian modes of analysis derived
from population genetics to make their evaluation. They considered theplausibility of the main neo-Darwinian model of gene evolution in which
evolutionary biologists envision new genes arising by gene duplication andsubsequent mutations in the duplicated gene.
Behe and Snoke assessed the plausibility of this model for multicellularorganisms in the case that multiple (two or more) point mutations must occur
simultaneously in order to generate a new selectable gene or protein. Whereas
Maynard Smith saw the need for multiple coordinated mutations as apotential problem, one that ultimately needn’t trouble evolutionary biologists,
Behe and Snoke argued that evolutionary biologists do need to worry about it,
and they quantified its severity.
Behe and Snoke first noted that many proteins, as a condition of theirfunction, require unique combinations of amino acids interacting in acoordinated way. For example, ligand binding sites on proteins—places where
small molecules bind to large proteins to form larger functional complexes—
typically require a combination of several amino acids. Behe and Snokeargued that in such cases the combinations of amino acids would have to arise
in a coordinated fashion since the capacity for ligand binding depends on all
the necessary amino acids being present together. In support of this inference,
they cited an authoritative textbook, Molecular Evolution, by University of
Chicago evolutionary biologist Wen-Hsiung Li. In it, Li notes that evolving
ligand binding capacity in proteins such as hemoglobin may require “manymutational steps,”21 even though the first steps on the way to building such

capacity would confer no selective advantage. As Li explains, “Acquiring a
new function may require many mutational steps, and a point that needs
emphasis is that the early steps might have been selectively neutral [nonadvantageous] because the new function might not be manifested until acertain number of steps had already occurred.”22

FIGURE 12.2
Michael Behe. Courtesy Laszlo Bencze.
Behe and Snoke point out that this observation implies that a series ofseparate mutations could not generate a ligand binding function in a proteinthat previously did not have this capacity, since individual amino-acidchanges would initially confer no selectable advantage on the protein lacking
this function. Instead, evolving ligand binding capability would require
multiple coordinated mutations. Behe and Snoke make a similar argument
about the requirements for the evolution of protein-to-protein interactions.
They note that for proteins to interact with each other in specific ways,
typically at least several individually necessary amino acids must be present
in combination in each protein, again, suggesting the need for multiple
coordinated mutations.

SO MANY CHANGES, SO LITTLE TIME
Behe and Snoke used the principles of population genetics to assess thelikelihood of various numbers of coordinated mutational changes occurring ina given period of time. They asked: Is it probable that there was enough timein evolutionary history to generate coordinated mutations? If so, how many
coordinated mutations is it reasonable to expect in a period of time given
various population sizes, mutation rates, and generation times? Then, fordifferent combinations of these various factors, they assessed how long it
would typically take to generate two or three or more coordinated mutations.
They determined that generally the probability of multiple mutations arisingin close (functionally relevant) coordination to each other was “prohibitively”
low—it would likely take an immensely long time, typically far longer than
the age of the earth.
THE POWERBALL LOTTERY—POPULATION GENETICS MADE
EASY
Before going on, it might be helpful to understand a bit more about how theequations and principles of population genetics can be used to calculate what
evolutionary biologists call “waiting times,” the expected time that it will takefor a given trait to arise by various evolutionary processes. In his book The
Edge of Evolution, Michael Behe illustrates these principles using a charming
analogy to the Powerball lottery game that many American state governments
use to raise money.
To win at Powerball, contestants must purchase tickets with six numbersthat match the numbers printed on six balls drawn from two drums. Five of
the balls are selected from a drum containing 59 white balls, numbered 1
through 59. A sixth red ball, the so-called power ball, is chosen out of a drumof 35 red balls numbered 1 to 35. To win the jackpot—which can exceed $100
million—a player must purchase a ticket listing all six of the chosen numbers
in any order. The Powerball website lists the probability of matching all six
balls at roughly 1 in 175 million. Depending on how many tickets have beenpurchased and how frequently drawings occur, it may take a very long time
for someone to win.
Behe asked his readers first to consider how long it will take, on average,
to generate a lottery ticket with the winning numbers. He notes that knowing
the probability of drawing such a winning ticket isn’t sufficient. The
calculation also requires knowing how often drawings occur and how manytickets are sold. As Behe explains: “If the odds of winning are one in ahundred million, and if a million people play every time, then it will take on
average about a hundred drawings for someone to win.” If there are about ahundred drawings per year, with a million people playing per drawing, “thenit would take about a year before someone won. But if there were only one
drawing per year, on average it would take a century to hit the jackpot.”23
More frequent drawings produce shorter waiting times. Less frequentdrawings tend to require longer waiting times. Similarly, more players will
decrease the average time necessary to produce a winner, while fewer players
result in longer waits.
Similar mathematical principles apply when calculating the expectedwaiting times for the evolution of biological features by mutation andselection. Biologists first need to assess the complexity of the system—or its
inverse, the improbability of the feature occurring. As in Powerball, however,knowing the probability of an event by itself does not allow someone tocalculate how long it will likely take for that event to occur. Such a
calculation requires also knowing the size of the population (equivalent to
how many people are playing Powerball) and how frequently new genetic
sequences arise (equivalent to how frequently drawings are held).
In Powerball, a new sequence of numbers arises in every drawing. But
when organisms reproduce, they do not always generate a new sequence of
nucleotide bases in their individual genes. For this reason, to calculate the rate
at which new sequences arise in living organisms requires knowing two
factors: the generation time and the mutation rate. More rapid rates ofmutation and/or shorter generation times will increase the rate at which new
genetic sequences arise, resulting in shorter waiting times. Slower rates ofmutation and/or longer times between generations produce longer waitingtimes. Also, as in Powerball, the number of “players” is important. Larger
populations generate new genetic sequences more frequently than smaller
ones and, thus, decrease expected waiting times. Smaller populations reduce
the rate at which new sequences are generated, increasing waiting times.
Now, under the rules of Powerball, you can “win” without picking all six
numbers correctly—you just won’t win the entire jackpot.24 If you pick justthe red “power ball” correctly, you win $4. Pick three white balls correctly,
and you win $7. If you correctly pick the numbers of four white balls, you
win $100. Guess all five white balls correctly (but not the red ball), and you
can win a cool $1 million.
With each additional ball necessary to secure a new level of winnings, theprobability of winning decreases exponentially, while the values of the prizes
increase dramatically. The Powerball website lists the probability of winning
a $4 prize at just 1 in 55, the probability of winning $1 million dollars at

roughly 1 in 5 million, and the probability of winning the jackpot as 1 in 175
million (see Fig. 12.3).25

FIGURE 12.3
A chart showing the probability of winning and the corresponding payouts fordifferent combinations of balls in the Powerball lottery game.
Neo-Darwinists have long assumed that biological evolution works
something like matching one number in Powerball. In their view, natural
selection acts to reward or preserve small but relatively probable changes ingene sequences—like winning the small but more likely $4 prize in Powerballover and over again. They assume the mutation and selection mechanism
doesn’t depend on winning extremely unlikely “prizes” (like the whole
Powerball jackpot) all at once.
But what if, to produce a functional advantage at the genetic level, themutation and selection mechanism had to generate the biological equivalentof all six (or more) correct balls in the Powerball lottery with no reward forguessing a smaller number of balls correctly first? Clearly, the probability ofthis would be extremely small. And the waiting time for winning such alottery could become prohibitively long.
BACK TO THE BIOLOGY
That brings us back to Behe and Snoke’s conclusion. In their 2004 paper, theyargued that generating a single new protein will often require many
improbable mutations occurring at once. They took into account the
improbability of multiple functionally necessary mutations appearing together—the equivalent of needing to get a Powerball ticket matching several
numbers to win any money at all. Then they sought to determine how long it
would take and/or how large the population sizes would need to be to
generate a new gene via multiple coordinated mutational changes—thegenetic equivalent of the “jackpot scenario.”Behe and Snoke found that if generating a new gene required multiple
coordinated mutations, then the waiting time would grow exponentially witheach additional necessary mutational change. They also assessed how
population sizes affected how long it would take to generate new genes, if
multiple coordinated mutations were necessary to produce those genes. They
found, not surprisingly, that just as larger populations diminished expectedwaiting times, smaller populations dramatically increased them.
More important, they found that even if building a new gene required justtwo coordinated mutations, the neo-Darwinian mechanism would likely either
require huge population sizes or extremely long waiting times or both. If
coordinated mutations were necessary, then evolution at the genetic level
faced a catch-22: for the standard neo-Darwinian mechanism to generate justtwo coordinated mutations, it typically either needed unreasonably longwaiting times, times that exceeded the duration of life on earth, or it needed
unreasonably large population sizes, populations exceeding the number ofmulticellular organisms that have ever lived. To get population sizes that werereasonable, they had to have waiting times that were unreasonable. To get
waiting times that were reasonable, they had to have population sizes thatwere unreasonable. As they put it, either way the “numbers seemprohibitive.”26
Behe and Snoke found that mutation and selection could generate twocoordinated mutations in a mere 1 million generations, a reasonable length oftime given the age of the earth. But that was only in a population of 1 trillion
or more multicellular organisms, a number that exceeds the size of theeffective breeding populations of practically all individual animal species thathave lived at any given time.27 Conversely, they found that mutation andselection could generate two coordinated mutations in a population of only 1
million organisms, but only if the mechanism had 10 billion generations at its
disposal. Yet on the assumption that each multicellular organism lived only
one year, 10 billion generations computes to 10 billion years—more than
twice the age of the earth. This is clearly an unreasonable length of time towait for the emergence of a single gene, let alone more significant
evolutionary innovations.
Behe and Snoke did, however, find one tiny “sweet spot” in which a gene
requiring only two coordinated mutations could arise (see Fig. 12.4). Such agene could conceivably arise from 1 billion organisms in a “mere”
100 million generations. Since many more than 1 billion multicellularorganisms have lived on earth during its history and since multicellular life onearth has existed for more than 500 million years, these numbers offer(assuming, again, one year per generation) the prospect of enough time andorganisms to generate one new gene—if only two coordinated mutations arenecessary. (Of course, if the population evolving a two-mutation trait had
fewer than 1 billion organisms, then the waiting times again increased tounreasonable lengths.)

FIGURE 12.4
This diagram shows the population sizes and times (measured in number ofgenerations) required to produce a gene or trait if building that gene or trait
requires multiple coordinated mutations. The shaded gray area shows the“sweet spot”—population sizes and available time sufficient to generate thecoordinated mutations necessary to produce a new gene. Note that any multimutation feature requiring more than two mutations could not, in allprobability, evolve by gene duplication and subsequent coordinated mutation
in a population of multicellular organisms, however large. Note also that formost normal population sizes and reasonable generation times, even evolving
two mutations lies beyond the reach of gene duplication, mutation, andselection. Courtesy John Wiley and Sons and The Protein Society.
Nevertheless, these numbers only apply to the case in which only two
coordinated mutations are necessary to build a new gene. Behe and Snokefound that if generating a new functional gene or trait required more than two
coordinated mutations, then excessively long waiting times were necessary
regardless of the size of the population. If three or more coordinatedmutations were necessary, their calculations generated no “sweet spots” at all.
Thus, they concluded that “the mechanism of gene duplication and point
mutation alone would be ineffective, at least for multicellular . . . species.”28
In summary, Behe and Snoke applied the principles derived from
population genetics to evaluate the creative power of the standard neo-

Darwinian model of gene evolution. They showed that the standard model
encounters clear probabilistic limits if the structures it needs to build require
more than two coordinated mutations in multicellular eukaryotic organisms.
THE EDGE OF EVOLUTION AND ITS CRITICS
Behe and Snoke are well-known critics of the creative power of the neoDarwinian mechanism, so their conclusion might seem suspect to someobservers. Nevertheless, evolutionary biologists attempting to defend thecreative power of the neo-Darwinian mechanism have inadvertently
confirmed Behe and Snoke’s conclusions.
Two recent scientific publications tell this story. First, in 2007, Michael
Behe published a book, The Edge of Evolution, amplifying the results of his
2004 paper with David Snoke. Using public-health data about a genetic trait—resistance to the antimalarial drug chloroquine in the one-celled organismthat causes malaria—Behe provided another line of evidence and argument tosupport the conclusion that multiple coordinated mutations are often
necessary to produce even minor genetic adaptations.
Based on public-health data, Behe determined that resistance tochloroquine only arises once in every 1020 malaria-causing cells. Beheinferred, by working the problem backwards, that the trait probably required
multiple—though not necessarily coordinated—mutations to develop. He
called this trait a “chloroquine complexity cluster,” or a “CCC.”29 Behewanted to explore what he called the “edge of evolution,” the limits to thecreative power of mutation and selection at the genetic level. Having
established that this trait could arise by random mutation in a reasonably shortperiod of time, he wondered how much time would be required to produce
traits of greater complexity in populations of various sizes.
He asked his readers to consider a hypothetical genetic trait twice ascomplex as a CCC cluster—a feature requiring the origin of two coordinatedtraits, each as complex as a CCC. In other words, Behe wondered how long it
would take to develop a hypothetical trait that required two genetic changes
as complex as a chloroquine complexity cluster, if both changes had to occur
together in the same organism—in a coordinated fashion—in order to produce
the trait. He then showed, using the principles of population genetics, thatmulti-mutation traits of that complexity—the molecular equivalent of twocoordinated CCCs—would require many more organisms or vastly more timethan was reasonable given the history of life. Remember the Powerballlottery: waiting times increase exponentially with each additional coordinatedchange or winning element needed. Behe showed, for example, that if 1020

organisms were required to obtain one CCC, then the square of that amount—1040 organisms—would be required to evolve a trait that required twocoordinated CCCs before providing any advantage.30 But, as we saw in
Chapter 10, only 1040 total organisms have ever existed on earth, implyingthat the entire history of the earth would barely provide enough opportunities
to generate a trait of this complexity.31
Similarly, Behe reasoned that for organisms in smaller population sizes,
developing a trait of twice the complexity of a CCC would require immensely
long waiting times. He also determined that exceedingly long waiting times
are typically required to generate even less complex genetic adaptations insmaller populations.
Behe showed that the problem of coordinated mutations was particularly
acute for longer-lived organisms with small population sizes—organisms suchas mammals or, more specifically, human beings and their presumed
prehuman ancestors. Behe estimated, based upon relevant mutation rates,
known human population sizes, and generation times, the time required fortwo coordinated mutations to occur in the hominid line. He calculated that
producing even such a modest evolutionary change would require many
hundreds of millions of years. Yet, humans and chimps are thought to havediverged from a common ancestor only 6 million years ago. Behe’s
calculation implied that the neo-Darwinian mechanism does not have thecapacity to generate even two coordinated mutations in the time available forhuman evolution—and thus does not explain how humans arose.
Here the story gets really interesting. Soon after the publication of The
Edge of Evolution, two Cornell University mathematical biologists, Rick
Durrett and Deena Schmidt, both defenders of neo-Darwinism, attempted torefute Behe’s conclusion by making their own calculations. Their paper,“Waiting for Two Mutations: With Applications to Regulatory Sequence
Evolution and the Limits of Darwinian Evolution,” also applied a model
based upon population genetics to calculate the amount of time necessary to
generate two coordinated mutations in the hominid line. Although theycalculated a shorter waiting time then Behe did, their result neverthelessunderscored the implausibility of relying on the neo-Darwinian mechanism togenerate coordinated mutations during the relevant evolutionary timescale.
Their calculation suggested that it would take not several hundred million
years, but “only” 216 million years to generate and fix two coordinatedmutations in the hominid line—more than thirty times the amount of time
available to produce humans and chimps and all their distinctive complex
adaptations and differences from their inferred common ancestor.

In seeking to refute Behe, Durrett and Schmidt inadvertently confirmed his
main contention. As they acknowledged, their calculation implies thatgenerating two or more coordinated mutations is “very unlikely to occur on areasonable timescale.”32 In sum, calculations performed by both critics anddefenders of neo-Darwinian evolution now reinforce the same conclusion: if
coordinated mutations are necessary to generate new genes and proteins, then
the neo-Darwinian math itself, as expressed in the principles of population
genetics, establishes the implausibility of the neo-Darwinian mechanism.
TESTING THE CO-OPTION OPTION
But does generating novel genes and proteins require coordinated mutations?
Behe and Snoke inferred as much based upon an undisputed fact of molecularbiology: many proteins rely on sets of amino acids acting in close
coordination in order to perform their functions. In addition, in The Edge of
Evolution, Behe argued on functional grounds that many complex biologicalsystems would require coordinated adaptive mutations since in these systems,
the absence of even one or a few gene products (proteins or traits) will cause
them to lose function. Behe specifically showed that several molecularmachines within cells (such as the cilium and intraflagellar transport system,and the bacterial flagellar motor33) require the coordinated interaction ofmultiple protein parts in order to maintain their function. Nevertheless, inmaking this argument, Behe did not address an alternative idea about thepathway by which new genes and proteins might have evolved, and thus did
not establish conclusively that new genes and proteins themselves represent
complex adaptations.
Some neo-Darwinists have proposed a model of protein evolution known
as “co-option.” In this model, a protein that performs one function istransformed, or “co-opted” to perform some other function. This model
envisions new features requiring multiple “mutations” arising in a step-bystep way to produce some protein, call it “Protein B,” from some other proteinthat lacked those features, call it “Protein A.” In proposing a series of single
separate mutations, advocates of co-option acknowledge that the initialindividual amino-acid changes, the first few steps in evolution, from Protein
A, the protein lacking the multisite feature, would not allow Protein A to
perform the function of Protein B. Nevertheless, they propose that these initialchanges might have allowed Protein A to perform some other advantageous
function, thus making it selectable and preventing protein evolution fromterminating due to diminution or loss of its initial function. Eventually, as
mutations continued to generate new proteins with slightly differentfunctions, they would have generated a protein close enough in sequence andstructure that just one or a very few additional changes would suffice toconvert it into Protein B.
Aware of these imaginative scenarios, Douglas Axe and his colleague,molecular biologist Ann Gauger (see Fig. 12.5), now working together at the
Biologic Institute in Seattle, decided to put them to an ingenious experimental
test.34 In so doing, they sought to determine whether the evolution of new
multisite features does indeed typically require multiple coordinatedmutations, or instead whether such a feature could arise by co-option.

FIGURE 12.5
Ann Gauger. Courtesy Laszlo Bencze.
Axe and Gauger scoured protein databases looking for proteins that are as
similar as possible in sequence and structure, but that nevertheless performdifferent functions. They identified two proteins that meet those criteria. Oneof these proteins (Kbl2) is needed for breaking down an amino acid called
threonine, and the other (BioF2) is needed for building a vitamin called biotin.
(See Fig. 12.6.)
Gauger and Axe realized that if they could transform Kbl2 into a protein
performing the function of BioF2 with just one or very few coordinatedamino-acid changes, then that might demonstrate (depending upon how few)that the two proteins were close enough in sequence that a conversion infunction of the kind envisioned by co-option advocates is plausible inevolutionary time. What’s more, because they knew the difficulty scientists
have had in showing any real change of protein function to be feasible, apositive result would suggest that they had at last discovered a functional gap
that one or very few mutations could plausibly jump—as co-option
envisioned.
If, however, they found that many coordinated mutational changes wereneeded, then that could establish—depending upon how many were needed—that the Darwinian mechanism could not accomplish the functional jump from
A to B in a reasonable time. That would imply that an even greater degree ofstructural similarity between proteins would be needed for the co-option
hypothesis to be plausible. Having carefully examined the structuralsimilarities between members of a large class of structurally similar enzymes,
they knew that Kbl2 and BioF2 were about as close in sequence and structure
as any two known proteins that performed different functions. Thus, if itturned out that converting one protein function into the other required many
coordinated mutations—more than could be expected to occur in a reasonable
time—then the outcome of their experiment would have devastating
implications for standard accounts of protein evolution. If proteins that
perform two different functions have to be even more similar than Kbl2 andBioF2 in order for mutational changes to convert the function of one to theother, then for all practical purposes co-option would not work. There simply
aren’t many known jumps that small.

FIGURE 12.6
The proteins, Kbl2 (left) and BioF2 (right) are enzymes that use similar
catalytic mechanisms to accelerate different chemical reactions in thebacterium E. coli. Courtesy Ann Gauger and Douglas Axe.
Axe and Gauger first identified those amino-acid sites that were most
likely, if mutated, to cause a change from Kbl2 function to BioF2 function.
They then systematically mutated those sites individually and in groups
involving various amino-acid combinations. Their results were unambiguous.

They found that they could not induce, with either one or a small number ofamino acids, the change in function they sought. In fact, they found that they
could not get Kbl2 to perform the function of BioF2, even if they mutatedlarger numbers of amino acids in concert—that is, even if they made many
more coordinated mutations than could plausibly occur by chance in all of
evolutionary history.
Although their attempts to convert Kbl2 to perform the function of BioF2
failed, their experiment did not. It allowed them to establish experimentallyfor the first time that the co-option hypothesis of protein evolution lacks
credibility—simply too many coordinated mutations would be required toconvert one protein function to another, even in the case of extremely similarproteins. That implied that generating new genes and proteins would require
multiple coordinated mutations, and thus, the waiting times that Behe andSnoke had calculated do present a problem for neo-Darwinian theory.
The experimental work also enabled Axe to calculate expected waitingtimes for various numbers of coordinated mutations given different variables
and factors. Axe developed a refined population-genetics mathematical model
to calculate various waiting times. His results roughly confirmed the previous
calculations of Behe and Snoke. He found, for example, that if he took into
account the probable fitness cost to an organism of carrying unnecessary gene
duplicates (as was necessary to give the evolution of a new gene a reasonablechance), that the probable waiting time for even three coordinated mutations
exceeded the duration of life on earth.
He therefore effectively determined an upper bound of two for the numberof coordinated mutations that could be expected to occur in a duplicate geneduring the history of life on earth (taking into account the negative effects ofcarrying gene duplicates in the evolutionary process). He also calculated six
coordinated mutations as an upper bound, neglecting the fitness cost of
carrying gene duplicates. Nevertheless, in their experiments, he and Gauger
could not induce a functional change in a single gene with more than six
coordinated mutations. So, even that more generous—and, again,
unrealistically generous upper bound—does little to render the co-option
hypothesis credible. Indeed, Axe and Gauger’s experiments showed that thesmallest realistically conceivable step exceeded what was plausible given thetime available to the evolutionary process. In their words, “evolutionary
innovations requiring that many changes . . . would be extraordinarily rare,
becoming probable only on timescales much longer than the age of life onearth.”

WHAT IT ALL MEANS
By showing the implausibility of the co-option model of protein evolution andthe need for multiple coordinated mutations in order to generate multisitefeatures in proteins, Axe and Gauger confirmed that genes and proteinsthemselves represent complex adaptations—entities that depend upon thecoordinated interaction of multiple subunits that must arise as a group to
confer any functional advantage.
The need for coordinated mutations means that evolutionary biologists
cannot just assume that mutations will readily generate new genes and traits,
as neo-Darwinists have long presupposed. Indeed, by applying mathematicalmodels based on the standard principles of population genetics to thequestions of the origin of genes themselves, Behe and Snoke, Durrett andSchmidt (inadvertently), Axe and Gauger, and other biologists35 have recently
shown that generating the number of multiple coordinated mutations needed
to produce even one new gene or protein is unlikely to occur within a realistic
waiting time. Thus, these biologists establish the implausibility of the neoDarwinian mechanism as a means of generating new genetic information.
There is one other aspect of this. The body of work published between
2004 and 2011 also provides additional confirmation of Axe’s researchshowing the rarity of genes and proteins in sequence space. In fact, that
research helps to explain why such long waiting times are necessary. Iffunctional sequences are rare in sequence space, it stands to reason thatfinding them by purely random and undirected means will take a long time.
Moreover, waiting times increase exponentially with each additional
necessary mutation. Thus, long waiting times for the production of new
functional genes and proteins is exactly what we should expect if indeedfunctional genes and proteins are rare, and if coordinated mutations arenecessary to produce them. Thus, the various experiments and calculations
performed between 2004 and 2011 indirectly confirm Axe’s earlier
conclusion about the rarity of functional genes and proteins and supply further
evidence that the neo-Darwinian mechanism cannot generate the informationnecessary to build new genes, let alone a new form of animal life, in the time
available to the evolutionary process.
THE MATH AND THE MECHANISM
There is a concluding irony in all this. The researchers calculating waitingtimes for the appearance of complex adaptations have in each case done sousing models based on the core principles of population genetics, themathematical expression of neo-Darwinian theory. In a real sense, therefore,
the neo-Darwinian math is itself showing that the neo-Darwinian mechanism
cannot build complex adaptations—including the new information-rich genes
and proteins that would have been necessary to build the Cambrian animals.
To adapt a metaphor that Tom Frazzetta might appreciate, the snake has eaten
its own tail.

13
The Origin of Body Plans
Rarely have the implications of a Nobel Prize–winning scientific discovery
received so little notice. Of course, the discovery itself received great acclaim.
But the deeper meaning was another matter.
Starting in the autumn of 1979, at the European Molecular Biology
Laboratory in Heidelberg, two venturesome young geneticists, Christiane
Nüsslein-Volhard and Eric Wieschaus (see Fig. 13.1), generated thousands ofmutations to investigate the genomes of tens of thousands of fruit flies(species: Drosophila melanogaster). They hoped to get them to divulge thesecrets of embryological development. In technical jargon, Nüsslein-Volhard
and Wieschaus performed “saturation mutagenesis” experiments. After
feeding male flies the potent mutation-causing chemical (i.e., mutagen) ethyl
methane sulphonate (EMS), Nüsslein-Volhard and Wieschaus bred the maleswith virgin females. They then examined the offspring larvae for visible
defects.
In generating many thousands of mutants, thereby “saturating” theDrosophila genome, Nüsslein-Volhard and Wieschaus induced variations inthe small subset of genes that specifically regulate embryonic development.
These regulatory genes normally control the expression of many other genesthat build the fly embryo, progressively subdividing it into regions that will
become the head, thorax, and abdomen of the adult fly. The EMS mutagen
disrupts DNA replication, thereby mutating genes. These mutations affect theprocess of development, leaving visible defects in the fly larvae. By observing
the damaged larvae, Wieschaus and Nüsslein-Volhard inferred how specificgenes regulate the development of different parts of the fly body plan. In
essence, Wieschaus and Nüsslein-Volhard reverse-engineered the fly’s
genome to determine the function of the different genes, including theregulatory genes crucial to fly development.1
The thoroughness and novelty of the “Heidelberg screens” (as theexperiments came to be known) and their importance for revealing themechanisms of regulatory control during animal embryogenesis won theattention of the Nobel committee. In 1995, the committee awarded the Nobel
Prize in Medicine or Physiology to Nüsslein-Volhard and Wieschaus. “Thiswork was revolutionary,” University of Cambridge geneticist Daniel St.
Johnston explained, “because it was the first mutagenesis in any multicellularorganism that attempted to find most or all of the mutations that affect . . . theessential patterning genes that are used throughout development.”2That’s the story as it is usually told. And it’s correct, as far as it goes. But
the mutant fruit flies obtained by Nüsslein-Volhard and Wieschaus tellanother story—one less widely known, but one containing important clues forthe unsolved mystery of the origin of animal body plans.
Wieschaus himself alluded to these clues in a memorable interaction at the1982 meeting of the American Association for the Advancement of Science(AAAS). After a session on the processes of macroevolution in which
Wieschaus had presented a paper, one audience member asked him what hemeant by the term “strong” as he used it to describe the mutations he andNüsslein-Volhard had induced in flies. Wieschaus explained with a laugh that“strong” certainly did not mean alive. Without exception, the mutants hestudied perished as deformed larvae long before achieving reproductive age.
“No, dead is dead,” he joked, “and you can’t be more dead.”3
Another questioner then asked Wieschaus about the implications of his
findings for evolutionary theory. Here Wieschaus responded more soberly,
wondering aloud about whether his collection of mutants offered any insights
into how the evolutionary process could have constructed novel body plans.
“The problem is, we think we’ve hit all the genes required to specify the bodyplan of Drosophila,” he said, “and yet these results are obviously notpromising as raw materials for macroevolution. The next question then, I
guess, is what are—or what would be—the right mutations for major
evolutionary change? And we don’t know the answer to that.”4
Thirty years later, developmental and evolutionary biologists still don’tknow the answer to that question. At the same time, mutagenesis experiments—on fruit flies as well as on other organisms such as nematodes(roundworms), mice, frogs, and sea urchins—have raised troubling questions
about the role of mutations in the origin of animal body plans. If mutating thegenes that regulate body-plan construction destroy animal forms as they
develop from an embryonic state, then how do mutations and selection build
animal body plans in the first place?
The neo-Darwinian mechanism has failed to explain the generation of new
genes and proteins needed for building the new animal forms that arose in the
Cambrian explosion. But even if mutation and selection could generate
fundamentally new genes and proteins, a more formidable problem remains.

To build a new animal and establish its body plan, proteins need to beorganized into higher-level structures. In other words, once new proteinsarise, something must arrange them to play their parts in distinctive cell types.
These distinctive cell types must, in turn, be organized to form distinctive
tissues, organs, and body plans. This process of organization occurs during
embryological development. Thus, to explain how animals are actually built
from smaller protein components, scientists must understand the process ofembryological development.

FIGURE 13.1
Figure 13.1a (left): Christiane Nüsslein-Volhard. Courtesy Wikimedia Commons, user Rama. Figure
13.1b (right): Eric F. Wieschaus.

THE ROLE OF GENES AND PROTEINS IN ANIMALDEVELOPMENT
As much as any other subdiscipline of biology, developmental biology hasraised disquieting questions for neo-Darwinism. Developmental biology
describes the processes, called ontogeny, by which embryos develop into
mature organisms. Within the past three decades the field has dramaticallyadvanced our understanding of how body plans arise during ontogeny. Muchof this new knowledge has come from studying so-called model systems—
organisms that biologists can easily mutate in the lab, such as the fruit fly
Drosophila and the nematode Caenorhabditis elegans.
Although the exact details of animal development can vary in bewildering
ways depending on the species, all animal development exemplifies a
common imperative: start with one cell, end with many different cells. In
most animal species, development begins with the fertilized egg. Once theegg divides into its daughter cells, becoming an embryo, the organism begins
heading toward a well-defined target, namely, an adult form that can
reproduce. Arriving at that distant target requires the embryo to produce many
specialized cell types, in the correct positions and at the right time.
Cell differentiation involves coordinating the expression of specific genes

in space and time, as the number of cells, taking on their different roles, rises
from one to two to four to eight, doubling and doubling until it reaches
thousands, millions, and even trillions, depending on the species. The numberof cell divisions and the total number of cells reflects the number of different
cell types the adult needs. This in turn requires producing different proteinsfor different cell types.
For example, the specialized digestive proteins that service the cells lining
the adult intestine differ from proteins expressed in a neuron found in thenerve tract of a limb. They must differ because each performs dramaticallydifferent functions. So, during development, the appropriate genes must be
turned on, or “up-regulated,” and turned off, or “down-regulated,” to ensure
the production of the correct protein products at the right time and in the rightcell types.
Specific proteins play active roles in regulating the expression of genes forbuilding other proteins. The protein actors playing these coordinating roles
are known as transcriptional regulators (TRs) or transcription factors (TFs).
TRs (or TFs) usually bind directly to specific sites in DNA, either preventing(repressing) or enabling (activating) the transcription of specific genes into
RNA. TRs or TFs convey instructions about which genes to turn on or turnoff. Their three-dimensional geometries exhibit characteristic DNA-binding
features, including a specific domain of 61 amino acids that wraps around the
DNA double helix. Other transcription factors include the zinc finger andleucine zipper motifs that also bind to DNA. Transcriptional regulators andfactors are themselves controlled by complex circuits and signals transmitted
by other genes and proteins, the overall complexity and precision of which isbreathtaking.
Painstaking genetic research—performed by Nüsslein-Volhard andWieschaus and many other developmental biologists5—has uncovered manyof the key embryonic regulatory genes that help switch cells into theirdifferentiated adult types. This research also uncovered a profound difficulty
cutting to the very core of the neo-Darwinian view of life.
EARLY-ACTING BODY-PLAN MUTATIONS AND EMBRYONICLETHALS
To create significant changes in the forms of animals requires attention totiming. Mutations in genes expressed late in the development of an animal
will affect relatively few cells and architectural features. That’s because bylate in development the basic outlines of the body plan have already been
established.6 Late-acting mutations therefore cannot cause any significant orheritable changes in the form or body plan of the whole animal. Mutations
that are expressed early in development, however, may affect many cells andcould conceivably produce significant changes in the form or body plan,
especially if these changes occur in key regulatory genes.7 Thus, mutations
that are expressed early in the development of animals have probably the only
realistic chance of producing large-scale macroevolutionary change.8 As
evolutionary geneticists Bernard John and George Miklos explain,“macroevolutionary change” requires changes in “very early
embryogenesis.”9 Former Yale University evolutionary biologist Keith
Thomson concurs: only mutations expressed early in the development oforganisms can produce large-scale macroevolutionary change.10
Yet from the first experiments by geneticist T. H. Morgan systematicallymutating fruit flies early in the twentieth century until today, as many model
species have been subjected to mutagenesis, developmental biology has
shown that mutations affecting body-plan formation expressed early indevelopment inevitably damage the organism.11 (See Fig. 13.2, for examples.)As one of the founders of neo-Darwinism geneticist R. A. Fisher noted, suchmutations are “either definitely pathological (most often lethal) in theireffects,” or they result in an organism that cannot survive “in the wildstate.”12
Normal development in any animal can be represented as an expanding
network of decisions, where the earliest (upstream) decisions have greater
impact than those occurring later. Regulatory genes and their DNA-binding
protein products help to control this unfolding network of decisions—suchthat if regulatory proteins are altered or destroyed by mutation, the effects
cascade downstream into the whole developmental process. The earlier the
failure, the more widespread the destruction. Geneticist Bruce Wallace
explains why early-acting mutations are thus overwhelmingly likely to disrupt
animal development. “The extreme difficulty encountered,” he observes,“when attempting to transform one organism into another . . . still functional
one lies in the difficulty in resetting a number of the many controlling
switches in a manner that still allows for the individual’s orderly (somatic)
development.”13
Nüsslein-Volhard and Wieschaus discovered this problem in experiments
performed on fruit flies after their first Nobel Prize–winning efforts. In theselater experiments they studied protein molecules that influence theorganization of different types of cells early in the process of embryologicaldevelopment. These molecules, called “morphogens,” including one called
Bicoid, are critical to establishing the fruit fly’s head-to-tail axis. They foundthat when these early-acting, body-plan-affecting molecules are perturbed,
development shuts down. When mutations occur in the gene that codes for
Bicoid, the resulting embryos die14—as they do in all other known cases inwhich mutations occur early in the regulatory genes that affect body-planformation.
There are good functional reasons for this, familiar to us from the logic ofother complex systems. If an automaker modifies a car’s paint color or seatcovers, nothing else needs to be altered for the car to operate, because thenormal function of the car does not depend upon these features. But if anengineer changes the length of the piston rods in the car’s engine, and does
not modify the crankshaft accordingly, the engine won’t run. Similarly,
animal development is a tightly integrated process in which various proteinsand cell structures depend upon each other for their function, and later events
depend crucially on earlier events. As a result, one change early in thedevelopment of an animal will require a host of other coordinated changes inseparate but functionally interrelated developmental processes and entities
downstream.15 This tight functional integration helps explain why mutations
early in development inevitably result in embryonic death and why evenmutations expressed somewhat later in development commonly leaveorganisms crippled.
Looking more closely at a specific experimental result of this kind further
illuminates the problem. A mutation in the regulatory Ultrabithorax gene
(expressed midway in the development of a fly) produces an extra pair ofwings on a normally two-winged creature. Although an extra set of wings
may sound like a useful piece of equipment, it’s not at all. This “innovation”
results in a crippled insect that cannot fly because it lacks, among otherthings, a musculature to support the use of its new wings. Because thedevelopmental mutation was not accompanied by the many other coordinateddevelopmental changes that were needed to make the wings useful, themutation is decidedly harmful.

FIGURE 13.2
Examples of deleterious macromutations produced by experiments on fruit
flies, including the “short wings,” “curly wings,” “eyeless,” and Antennapedia
mutants.
This problem has led to what Georgia Tech geneticist John F. McDonald
has called a “great Darwinian paradox.”16 He notes that the genes that are
obviously variable within natural populations seem to affect only minor
aspects of form and function—while those genes that govern major changes,
the very stuff of macroevolution, apparently do not vary or vary only to thedetriment of the organism. As he puts it, “Those [genetic] loci that are
obviously variable within natural populations do not seem to lie at the basis ofmany major adaptive changes, while those loci that seemingly do constitutethe foundation of many if not most major adaptive changes are not variable
within natural populations.”17 In other words, the kind of mutations theevolutionary process would need to produce new animal body plans—namely,
beneficial regulatory changes expressed early in development—don’t occur.
Whereas, the kind that it doesn’t need—viable genetic mutations in DNA
generally expressed late in development—do occur. Or put more succinctly,
the kind of mutations we need for major evolutionary change we don’t get;the kind we get we don’t need.
My Discovery Institute colleague Paul Nelson (see Fig. 13.3), a
philosopher of biology who specializes in evolutionary theory anddevelopmental biology, summarizes the challenge to neo-Darwinism posed byanimal development as three premises:1. Animal body plans are built in each generation by a stepwise process,from the fertilized egg to the many cells of the adult. The earliest stages inthis process determine what follows.
2. Thus, to evolve any body plan, mutations expressed early in development
must occur, must be viable, and must be stably transmitted to offspring.
3. Such early-acting mutations of global effect on animal development,
however, are those least likely to be tolerated by the embryo and, in fact,
never have been tolerated in any animals that developmental biologists
have studied.

FIGURE 13.3
Paul Nelson. Courtesy Paul Nelson.
Nelson came to appreciate the depth of the problem posed by these facts
after many years of discussion with two members of his University of
Chicago Ph.D. committee, evolutionary biologist Leigh Van Valen (1935–2010) and evolutionary theorist and philosopher of biology William Wimsatt.
Van Valen, famous for his “Red Queen hypothesis” about the need fororganisms to continue to evolve in order to maintain fitness, was passionatelyinterested in the mechanisms of macroevolution. Wimsatt originated thetheory of “generative entrenchment,” an account of the “causal asymmetries”
at work in complex systems, including those responsible for animal
development.18 Both acknowledged to Nelson that the scientific literatureoffers no examples of viable mutations affecting early animal development
and body-plan formation (Premise 3, on previous page) and also that themacroevolution of novel animal form requires just such early-acting

mutations (Premise 2, on previous page). Nevertheless, both Van Valen andWimsatt remained committed to the descent of animal forms from a common
ancestor via some kind of undirected mutations. Nelson argues, however, thatthose premises strongly imply that the neo-Darwinian mechanism does not—and indeed cannot—provide an adequate mechanism for producing new
animal body plans. As he has told me: “If the only kind of mutations that canconceivably produce enough morphological change to alter whole body plansnever causes beneficial and heritable changes, then it is difficult to see how
mutation and selection could ever produce new body plans in the firstplace.”19
Thus, he concludes:
Research on animal development and macroevolution over the last
thirty years—research done from within the neo-Darwinian framework—has shown that the neo-Darwinian explanation for the origin of new
body plans is overwhelmingly likely to be false—and for reasons thatDarwin himself would have understood.
Indeed, Darwin himself insisted that “nothing can be effected” by natural
selection, “unless favorable variations occur.”20 Or as Swedish evolutionary
biologist Søren Løvtrup succinctly explains: “Without variation, no selection;
without selection, no evolution. This assertion is based on logic of thesimplest kind. . . . Selection pressure as an evolutionary agent becomes voidof sense unless the availability of the proper mutations is assumed.”21 Yet the“proper” kind of mutations—the mutations that produce favorable changes toearly-acting, body-plan–shaping, regulatory genes—do not occur.
Microevolutionary change is insufficient; macromutations—large-scalechanges—are harmful. This paradox has beset Darwinism from its inception,
but discoveries about the genetic regulation of development in animals havemade this paradox more acute and cast serious doubt on the efficacy of themodern neo-Darwinian mechanism as an explanation for the new body plansthat arise in the Cambrian period.
DEVELOPMENTAL GENE REGULATORY NETWORKS
Another line of research in developmental biology has revealed a related
challenge to the creative power of the neo-Darwinian mechanism.
Developmental biologists have discovered that many gene products (proteins
and RNAs) needed for the development of specific animal body planstransmit signals that influence the way individual cells develop anddifferentiate themselves. Additionally, these signals affect how cells areorganized and interact with each other during embryological development.
These signaling molecules influence each other to form circuits or networks
of coordinated interaction, much like integrated circuits on a circuitboard. For
example, exactly when a signaling molecule gets transmitted often depends
upon when a signal from another molecule is received, which in turn affects
the transmission of still others—all of which are coordinated and integrated toperform specific time-critical functions. The coordination and integration ofthese signaling molecules in cells ensures the proper differentiation andorganization of distinct cell types during the development of an animal bodyplan. Consequently, just as mutating an individual regulatory gene early in thedevelopment of an animal will inevitably shut down development, so too will
mutations or alterations in the whole network of interacting signaling
molecules destroy a developing embryo.
No biologist has explored the regulatory logic of animal development
more deeply than Eric Davidson, at the California Institute of Technology.
Early in his career, collaborating with molecular biologist Roy Britten,
Davidson formulated a theory of “gene regulation for higher cells.”22 By“higher cells” Davidson and Britten meant the differentiated, or specialized,
cells found in any animal after the earliest stages of embryologicaldevelopment. Davidson observed that the cells of an individual animal, nomatter how varied in form or function, “generally contain identicalgenomes.”23 During the life cycle of an organism, the genomes of these
specialized cells express only a small fraction of their DNA at any given timeand produce different RNAs as a result. These facts strongly suggest thatsome animal-wide system of genetic control functions to turn specific genes
on and off as needed throughout the life of the organism—and that such asystem functions during the development of an animal from egg to adult as
different cell types are being constructed.
When they proposed their theory in 1969, Britten and Davidson
acknowledged that “little is known . . . of the molecular mechanisms bywhich gene expression is controlled in differentiated cells.”24 Nevertheless,they deduced that such a system must be at work. Given: (1) that tens or
hundreds of specialized cell types arise during the development of animals,and (2) that each cell contains the same genome, they reasoned (3) that some
control system must determine which genes are expressed in different cells at
different times to ensure the differentiation of different cell types from eachother—some system-wide regulatory logic must oversee and coordinate theexpression of the genome.25

Davidson has dedicated his career to discovering and describing themechanisms by which these systems of gene regulation and control work
during embryological development. During the last two decades, research ingenomics has revealed that nonprotein-coding regions of the genome control
and regulate the timing of the expression of the protein-coding regions of the
genome. Davidson has shown that the nonprotein-coding regions of DNA that
regulate and control gene expression and the protein-coding regions of the
genome together function as circuits. These circuits, which Davidson calls“developmental gene regulatory networks” (or dGRNs) control theembryological development of animals.

FIGURE 13.4
Developmental gene regulatory networks (dGRNs) and development in the
purple sea urchin, Strongylocentrotus purpuratus. Figure 13.4a (top, left):shows the actual embryo, starting at 6 hours and progressing through cell
division to 55 hours, when the larval skeleton appears. Figure 13.4b (bottom,

left): depicts the major classes of genes involved in specifying the larval
skeleton. Figure 13.4c (top, right): shows the detailed genetic circuitry
implicated in the overall “gene regulatory network” (“GRN”) that controls theconstruction of the larval skeleton. Courtesy National Academy of Sciences,
U.S.A.
On arriving at Caltech in 1971, Davidson chose the purple sea urchin,
Strongylocentrotus purpuratus, as his experimental model system. The
biology of S. purpuratus makes it an attractive laboratory subject: the species
occurs abundantly along the Pacific coast, produces enormous quantities of
easily fertilized eggs in the lab, and lives for many years.26 Davidson and his
coworkers pioneered the technology and experimental protocols required todissect the sea urchin’s genetic regulatory system.
The remarkable complexity of what they found needs to be depictedvisually. Figure 13.4a shows the urchin embryo as it appears six hours after
development has begun (top left of diagram). This is the 16-cell stage,
meaning that four rounds of cell division have already occurred (1 → 2 → 4→ 8 → 16). As development proceeds in the next four stages, both thenumber of cells and the degree of cellular specialization increases, until, at 55
hours, elements of the urchin skeleton come into focus. Figure 13.4b shows,corresponding to these drawings of embryo development, a schematic
diagram with the major classes of genes (for cell and tissue types) represented
as boxes, linked by control arrows. Last, Figure 13.4c shows what Davidson
calls “the genetic circuitry” that turns on the specific biomineralization genesthat produce the structural proteins needed to build the urchin skeleton.27
This last diagram represents a developmental gene regulatory network (ordGRN), an integrated network of protein and RNA-signaling molecules
responsible for the differentiation and arrangement of the specialized cells
that establish the rigid skeleton of the sea urchin. Notice that, to express thebiomineralization genes that produce structural proteins that make theskeleton, genes far upstream, activated many hours earlier in development,
must first play their role.
This process does not happen fortuitously in the sea urchin but via highly
regulated and precise control systems, as it does in all animals. Indeed, evenone of the simplest animals, the worm C. elegans, possessing just over 1,000
cells as an adult, is constructed during development by dGRNs of remarkable
precision and complexity. In all animals, the various dGRNs direct what
Davidson describes as the embryo’s “progressive increase in complexity”—anincrease, he writes, that can be measured in “informational terms.”28Davidson notes that, once established, the complexity of the dGRNs asintegrated circuits makes them stubbornly resistant to mutational change—apoint he has stressed in nearly every publication on the topic over the past
fifteen years. “In the sea urchin embryo,” he points out, “disarming any oneof these subcircuits produces some abnormality in expression.”29
Developmental gene regulatory networks resist mutational change because
they are organized hierarchically. This means that some developmental gene
regulatory networks control other gene regulatory networks, while someinfluence only the individual genes and proteins under their control. At thecenter of this regulatory hierarchy are the regulatory networks that specify theaxis and global form of the animal body plan during development. ThesedGRNs cannot vary without causing catastrophic effects to the organism.
Indeed, there are no examples of these deeply entrenched, functionallycritical circuits varying at all. At the periphery of the hierarchy are gene
regulatory networks that specify the arrangements for smaller-scale featuresthat can sometimes vary. Yet, to produce a new body plan requires altering theaxis and global form of the animal. This requires mutating the very circuitsthat do not vary without catastrophic effects. As Davidson emphasizes,
mutations affecting the dGRNs that regulate body-plan development lead to“catastrophic loss of the body part or loss of viability altogether.”30 He
explains in more detail:
There is always an observable consequence if a dGRN subcircuit isinterrupted. Since these consequences are always catastrophically bad,flexibility is minimal, and since the subcircuits are all interconnected,
the whole network partakes of the quality that there is only one way forthings to work. And indeed the embryos of each species develop in only
one way.31
ENGINEERING CONSTRAINTSDavidson’s findings present a profound challenge to the adequacy of the neoDarwinian mechanism. Building a new animal body plan requires not justnew genes and proteins, but new dGRNs. But to build a new dGRN from apreexisting dGRN by mutation and selection necessarily requires altering thepreexisting developmental gene regulatory network (the very kind of change
that, as we saw in Chapter 12, cannot arise without multiple coordinatedmutations). In any case, Davidson’s work has also shown that such alterations
inevitably have catastrophic consequences.
Davidson’s work highlights a profound contradiction between the neoDarwinian account of how new animal body plans are built and one of themost basic principles of engineering—the principle of constraints. Engineers
have long understood that the more functionally integrated a system is, themore difficult it is to change any part of it without damaging or destroying thesystem as a whole. Davidson’s work confirms that this principle applies todeveloping organisms in spades. The system of gene regulation that controls
animal-body-plan development is exquisitely integrated, so that significant
alterations in these gene regulatory networks inevitably damage or destroy thedeveloping animal.32 But given this, how could a new animal body plan, andthe new dGRNs necessary to produce it, ever evolve gradually via mutationand selection from a preexisting body plan and set of dGRNs?
Davidson makes clear that no one really knows: “contrary to classicalevolution theory, the processes that drive the small changes observed as
species diverge cannot be taken as models for the evolution of the body plansof animals.”33 He elaborates:
Neo-Darwinian evolution . . . assumes that all process works the sameway, so that evolution of enzymes or flower colors can be used as
current proxies for study of evolution of the body plan. It erroneously
assumes that change in protein-coding sequence is the basic cause ofchange in developmental program; and it erroneously assumes thatevolutionary change in body-plan morphology occurs by a continuous
process. All of these assumptions are basically counterfactual. Thiscannot be surprising, since the neo-Darwinian synthesis from whichthese ideas stem was a premolecular biology concoction focused on
population genetics and . . . natural history, neither of which have any
direct mechanistic import for the genomic regulatory systems that drive
embryonic development of the body plan.34
NOW AND THEN
Eric Davidson’s work, like that of Nüsslein-Volhard and Wieschaus,
highlights a difficulty of obvious relevance to the Cambrian explosion.
Typically, paleontologists understand the Cambrian explosion as thegeologically sudden appearance of new forms of animal life. Building these
forms requires new developmental programs—including both new earlyacting regulatory genes and new developmental gene regulatory networks.
Yet if neither early-acting regulatory genes nor dGRNs can be altered bymutation without destroying existing developmental programs (and thus
animal form), then mutating these entities will leave natural selection withnothing favorable to select and the evolution of animal form will, at thatpoint, terminate.
Darwin’s doubt about the Cambrian explosion centered on the problem of
missing fossil intermediates. Not only have those forms not been found, but
the Cambrian explosion itself illustrates a profound engineering problem thatfossil evidence does not address—the problem of building a new form ofanimal life by gradually transforming one tightly integrated system of genetic
components and their products into another. Yet, in the next chapter, we will
see that an even more formidable problem remains.

14
The Epigenetic Revolution
In 1924, two German scientists, Hans Spemann and Hilda Mangold, reported
an intriguing experiment, the significance of which could not have been fully
appreciated at the time, three decades before the discovery of the informationbearing properties of DNA. Using microsurgery, Spemann and Mangold
excised a portion of a newt embryo and transplanted that portion into anotherdeveloping newt embryo.1
They achieved a startling result. The second embryo produced two bodies,
each with a head and tail, joined together at the belly, not unlike Siamese
twins. Yet despite dramatically altering the anatomy of the embryo, Spemannand Mangold did not alter its DNA.
Their experiment later suggested a radical possibility: that something in
addition to DNA profoundly influences the development of animal bodyplans. Other experiments suggested as much. In the 1930s and 1940s,
American biologist Ethel Harvey showed experimentally that sea urchin
embryos could undergo development up to about 500 cells after removal of
their nuclei—in other words, without their nuclear DNA.2 In the 1960s,
Belgian scientists chemically blocked the transcription of DNA into RNA in
amphibian embryos and found that the embryos could still develop to thepoint of containing several thousand cells.3 In the 1970s, Canadian biologists
showed that a frog embryo could undergo early development without its
nucleus if the cell division apparatus from a sea urchin was injected into the
egg.4
None of these results indicate that embryos can develop fully without
DNA. In every case, DNA was eventually necessary to complete
embryological development. Yet these results suggest that DNA is not thewhole story, that other sources of information are playing important roles in
directing at least the early stages of animal development.
ABOVE AND BEYOND: EPIGENETIC INFORMATION

In 2003, MIT Press published a groundbreaking collection of scientific essays
titled Origination of Organismal Form: Beyond the Gene in Developmental
and Evolutionary Biology, edited by two distinguished developmental andevolutionary biologists, Gerd Müller, of the University of Vienna, and Stuart
Newman, of New York Medical College. In their volume, Müller andNewman included a number of scientific articles describing recent discoveries
in genetics and developmental biology—discoveries suggesting that genes
alone do not determine the three-dimensional form and structure of an animal.
Instead, many of the scientists in their volume reported that so-called
epigenetic information—information stored in cell structures, but not in DNA
sequences—plays a crucial role. The Greek prefix epi means “above” or“beyond,” so epigenetics refers to a source of information that lies beyond thegenes. As Müller and Newman explain in their introduction, “Detailed
information at the level of the gene does not serve to explain form.”5 Instead,as Newman explains, “epigenetic” or “contextual information” plays a crucialrole in the formation of animal “body assemblies” during embryologicaldevelopment.6
Müller and Newman not only highlighted the importance of epigenetic
information to the formation of body plans during development; they also
argued that it must have played a similarly important role in the origin andevolution of animal body plans in the first place. They concluded that recent
discoveries about the role of epigenetic information in animal development
pose a formidable challenge to the standard neo-Darwinian account of theorigin of these body plans—perhaps the most formidable of all.
In the introductory essay to their volume, Müller and Newman list a
number of “open questions” in evolutionary biology, including the question of
the origin of Cambrian-era animal body plans and the origin of organismal
form generally, the latter being the central topic of their book. They note thatthough “the neo-Darwinian paradigm still represents the central explanatory
framework of evolution,” it has “no theory of the generative.”7 In their view,neo-Darwinism “completely avoids [the question of] the origination ofphenotypic traits and of organismal form.”8 As they and others in theirvolume maintain, neo-Darwinism lacks an explanation for the origin oforganismal form precisely because it cannot explain the origin of epigenetic
information.
I first learned about the problem of epigenetic information and the
Spemann and Mangold experiment while driving to a private meeting of
Darwin-doubting scientists on the central coast of California in 1993. In the
car with me was Jonathan Wells (see Fig. 14.1), who was then finishing a

Ph.D. in developmental biology at the University of California at Berkeley.
Like some others in his field, Wells had come to reject the (exclusively)“gene-centric” view of animal development and to recognize the importanceof nongenetic sources of information.
By that time, I had studied many questions and challenges to standard
evolutionary theories arising out of molecular biology. But epigenetics was
new to me. On our drive, I asked Wells why developmental biology was soimportant to evolutionary theory and to assessing neo-Darwinism. I’ll neverforget his reply. “Because” he said, “that’s where the whole theory is going tounravel.”FIGURE 14.1
Jonathan Wells. Courtesy Laszlo Bencze.
In the years since, Wells has developed a powerful argument against theadequacy of the neo-Darwinian mechanism as an explanation for the origin ofanimal body plans. His argument turns on the importance of epigenetic
information to animal development. To see why epigenetic information poses
an additional challenge to neo-Darwinism and what exactly biologists meanby “epigenetic” information, let’s examine the relationship between biologicalform and biological information.
FORM AND INFORMATION

Biologists typically define “form” as a distinctive shape and arrangement ofbody parts. Organismal forms exist in three spatial dimensions and arise intime—in the case of animals during development from embryo to adult.
Animal form arises as material constituents are constrained to establish
specific arrangements with an identifiable three-dimensional shape or“topography”—one that we would recognize as the body plan of a particular
type of animal. A particular “form,” therefore, represents a highly specificarrangement of material components among a much larger set of possible
arrangements.
Understanding form in this way suggests a connection to the notion of
information in its most theoretically general sense. As I noted in Chapter 8,
Shannon’s mathematical theory of information equated the amount of
information transmitted with the amount of uncertainty reduced or eliminatedin a series of symbols or characters. Information, in Shannon’s theory, is thus
imparted as some options, or possible arrangements, are excluded and others
are actualized. The greater the number of arrangements excluded, the greater
the amount of information conveyed. Constraining a set of possible material
arrangements, by whatever means, involves excluding some options andactualizing others. Such a process generates information in the most general
sense of Shannon’s theory. It follows that the constraints that produce
biological form also impart information, even if this information is not
encoded in digital form.
DNA contains not only Shannon information but also functional or
specified information. The arrangements of nucleotides in DNA or of aminoacids in a protein are highly improbable and thus contain large amounts of
Shannon information. But the function of DNA and proteins depends upon
extremely specific arrangements of bases and amino acids.
Similarly, animal body plans represent, not only highly improbable, butalso highly specific arrangements of matter. Organismal form and function
depend upon the precise arrangement of various constituents as they arise
during, or contribute to, embryological development. Thus, the specificarrangement of the other building blocks of biological form—cells, clustersof similar cell types, dGRNs, tissues, and organs—also represent a kind of
specified or functional information.
In Chapter 8, I noted that the ease with which Shannon’s information
theory applies to molecular biology has sometimes led to confusion about thekind of information contained in DNA and proteins. It may have also createdconfusion about the places that specified information might reside inorganisms. Perhaps because the information-carrying capacity of the gene canbe so easily measured, biologists have often treated DNA, RNA, and proteins

as the sole repositories of biological information. Neo-Darwinists haveassumed that genes possess all the information necessary to specify the formof an animal. They have also assumed that mutations in genes will suffice togenerate the new information necessary to build a new form of animal life.9
Yet if biologists understand organismal form as resulting from constraints on
the possible arrangements of matter at many levels in the biological hierarchy—from genes and proteins, to cell types and tissues, to organs and body plans—then biological organisms may well exhibit many levels of information-rich
structure. Discoveries in developmental biology have confirmed thispossibility.
BEYOND GENES
Many biologists no longer believe that DNA directs virtually everything
happening within the cell. Developmental biologists, in particular, are now
discovering more and more ways that crucial information for building bodyplans is imparted by the form and structure of embryonic cells, including
information from both the unfertilized and fertilized egg.
Biologists now refer to these sources of information as “epigenetic.”10
Spemann and Mangold’s experiment is only one of many to suggest thatsomething beyond DNA may be influencing the development of animal bodyplans. Since the 1980s, developmental and cell biologists such as Brian
Goodwin, Wallace Arthur, Stuart Newman, Fred Nijhout, and Harold Franklin
have discovered or analyzed many sources of epigenetic information. Even
molecular biologists such as Sidney Brenner, who pioneered the idea thatgenetic programs direct animal development, now insist that the informationneeded to code for complex biological systems vastly outstrips theinformation in DNA.11
DNA helps direct protein synthesis. Parts of the DNA molecule also help
to regulate the timing and expression of genetic information and the synthesisof various proteins within cells. Yet once proteins are synthesized, they must
be arranged into higher-level systems of proteins and structures. Genes andproteins are made from simple building blocks—nucleotide bases and aminoacids, respectively—arranged in specific ways. Similarly, distinctive cell
types are made of, among other things, systems of specialized proteins.
Organs are made of specialized arrangements of cell types and tissues. And
body plans comprise specific arrangements of specialized organs. Yet theproperties of individual proteins do not fully determine the organization ofthese higher-level structures and patterns.12 Other sources of informationmust help arrange individual proteins into systems of proteins, systems ofproteins into distinctive cell types, cell types into tissues, and different tissues
into organs. And different organs and tissues must be arranged to form bodyplans.

FIGURE 14.2
The hierarchical layering or arrangement of different sources of information.
Note that the information necessary to build the lower-level electronic
components does not determine the arrangement of those components on thecircuit board or the arrangement of the circuit board and the other parts
necessary to make a computer. That requires additional informational inputs.
Two analogies may help clarify the point. At a construction site, builders
will make use of many materials: lumber, wires, nails, drywall, piping, andwindows. Yet building materials do not determine the floor plan of the houseor the arrangement of houses in a neighborhood. Similarly, electronic circuits
are composed of many components, such as resistors, capacitors, andtransistors. But such lower-level components do not determine their own
arrangement in an integrated circuit (see Fig. 14.2).
In a similar way, DNA does not by itself direct how individual proteins areassembled into these larger systems or structures—cell types, tissues, organs,and body plans—during animal development.13 Instead, the threedimensional structure or spatial architecture of embryonic cells plays
important roles in determining body-plan formation during embryogenesis.
Developmental biologists have identified several sources of epigenetic
information in these cells.

CYTOSKELETAL ARRAYS
Eukaryotic cells have internal skeletons to give them shape and stability.
These “cytoskeletons” are made of several different kinds of filaments
including those called the “microtubules.” The structure and location of the
microtubules in the cytoskeleton influence the patterning and development ofembryos. Microtubule “arrays” within embryonic cells help to distribute
essential proteins used during development to specific locations in these cells.
Once delivered, these proteins perform functions critical to development, butthey can only do so if they are delivered to their correct locations with thehelp of preexisting, precisely structured microtubule or cytoskeletal arrays(see Fig. 14.3). Thus, the precise arrangement of microtubules in thecytoskeleton constitutes a form of critical structural information.
These microtubule arrays are made of proteins called tubulin, which aregene products. Nevertheless, like bricks that can be used to assemble manydifferent structures, the tubulin proteins in the cell’s microtubules are identicalto one another. Thus, neither the tubulin subunits, nor the genes that produce
them, account for the differences in the shape of the microtubule arrays that
distinguish different kinds of embryos and developmental pathways. Instead,the structure of the microtubule array itself is, once again, determined by thelocation and arrangement of its subunits, not the properties of the subunits
themselves. Jonathan Wells explains it this way: “What matters in[embryological] development is the shape and location of microtubule arrays,
and the shape and location of a microtubule array is not determined by its
units.”14 For this reason, as University of Colorado cell biologist Franklin
Harold notes, it is impossible to predict the structure of the cytoskeleton of
the cell from the characteristics of the protein constituents that form thatstructure.15

FIGURE 14.3
Figure 14.3a (left) shows a still shot from an animation of microtubule (at thebottom of the image) made of tubulin proteins. Courtesy Joseph Condeelis.

Figure 14.3b (right) shows a microscopic image of a large section ofcytoskeleton made of many microtubules (and other elements) inside the cellin cross section. Courtesy The Company of Biologists and Journal of Cell
Science.
Another cell structure influences the arrangement of the microtubule
arrays and thus the precise structures they form and the functions they
perform. In an animal cell, that structure is called the centrosome (literally,“central body”), a microscopic organelle that sits next to the nucleus between
cell divisions in an undividing cell. Emanating from the centrosome is the
microtubule array that gives a cell its three-dimensional shape and provides
internal tracks for the directed transport of organelles and essential molecules
to and from the nucleus.16 During cell division the centrosome duplicatesitself. The two centrosomes form the poles of the cell-division apparatus, andeach daughter cell inherits one of the centrosomes; yet the centrosome
contains no DNA.17 Though centrosomes are made of proteins—geneproducts—the centrosome structure is not determined by genes alone.
MEMBRANE PATTERNSAnother important source of epigenetic information resides in the twodimensional patterns of proteins in cell membranes.18 When messenger RNAs
are transcribed, their protein products must be transported to the proper
locations in embryonic cells in order to function properly. Directed transport
involves the cytoskeleton, but it also depends on spatially localized targets inthe membrane that are in place before transport occurs. Developmental
biologists have shown that these membrane patterns play a crucial role in theembryological development of fruit flies.
Membrane Targets
For example, early embryo development in the fruit fly Drosophilamelanogaster requires the regulatory molecules Bicoid and Nanos (among
others). The former is required for anterior (head) development, and the latteris required for posterior (tail) development.19 In the early stages ofembryological development, nurse cells pump Bicoid and Nanos RNAs into
the egg. (Nurse cells provide the cell that will become the egg—known as theoocyte—and the embryo with maternally encoded messenger RNAs andproteins.) Cytoskeletal arrays then transport these RNAs through the oocyte,
where they become attached to specified targets on the inner surface of theegg.20 Once in their proper place—but only then—Bicoid and Nanos play
critical roles in organizing the head-to-tail axis of the developing fruit fly.
They do this by forming two gradients (or differential concentrations), onewith Bicoid protein most concentrated at the anterior end and another with
Nanos protein most concentrated at the posterior end.
Insofar as both of these molecules are RNAs—that is, gene products—
genetic information plays an important role in this process. Even so, theinformation contained in the bicoid and nanos genes does not by itself ensure
the proper function of the RNAs and proteins for which the genes code.
Instead, preexisting membrane targets, already positioned on the insidesurface of the egg cell, determine where these molecules will attach and how
they will function. These membrane targets provide crucial information—
spatial coordinates—for embryological development.
Ion Channels and Electromagnetic Fields
Membrane patterns can also provide epigenetic information by the precise
arrangement of ion channels—openings in the cell wall through whichcharged electrical particles pass in both directions. For example, one type ofchannel uses a pump powered by the energy-rich molecule ATP to transport
three sodium ions out of the cell for every two potassium ions that enter thecell. Since both ions have a charge of plus one (Na+, K+), the net difference
sets up an electromagnetic field across the cell membrane.21
Experiments have shown that electromagnetic fields have“morphogenetic” effects—in other words, effects that influence the form of adeveloping organism. In particular, some experiments have shown that thetargeted disturbance of these electric fields disrupts normal development inways that suggest the fields are controlling morphogenesis.22 Artificiallyapplied electric fields can induce and guide cell migration. There is also
evidence that direct current can affect gene expression, meaning internallygenerated electric fields can provide spatial coordinates that guideembryogenesis.23 Although the ion channels that generate the fields consist ofproteins that may be encoded by DNA (just as microtubules consist of
subunits encoded by DNA), their pattern in the membrane is not. Thus, inaddition to the information in DNA that encodes morphogenetic proteins, thespatial arrangement and distribution of these ion channels influences thedevelopment of the animal.
The Sugar Code

Biologists know of an additional source of epigenetic information stored in
the arrangement of sugar molecules on the exterior surface of the cell
membrane. Sugars can be attached to the lipid molecules that make up themembrane itself (in which case they are called “glycolipids”), or they can be
attached to the proteins embedded in the membrane (in which case they arecalled “glycoproteins”). Since simple sugars can be combined in many more
ways than amino acids, which make up proteins, the resulting cell surface
patterns can be enormously complex. As biologist Ronald Schnaar explains,“Each [sugar] building block can assume several different positions. It is as if
an A could serve as four different letters, depending on whether it wasstanding upright, turned upside down, or laid on either of its sides. In fact,
seven simple sugars can be rearranged to form hundreds of thousands ofunique words, most of which have no more than five letters.”24
These sequence-specific information-rich structures influence thearrangement of different cell types during embryological development. Thus,
some cell biologists now refer to the arrangements of sugar molecules as the“sugar code” and compare these sequences to the digitally encoded
information stored in DNA.25 As biochemist Hans-Joachim Gabius notes,
sugars provide a system with “high-density coding” that is “essential to allow
cells to communicate efficiently and swiftly through complex surface
interactions.”26 According to Gabius, “These [sugar] molecules surpass aminoacids and nucleotides by far in information-storing capacity.”27 So theprecisely arranged sugar molecules on the surface of cells clearly represent
another source of information independent of that stored in DNA basesequences.
NEO-DARWINISM AND THE CHALLENGE OF EPIGENETIC
INFORMATION
These different sources of epigenetic information in embryonic cells pose anenormous challenge to the sufficiency of the neo-Darwinian mechanism.
According to neo-Darwinism, new information, form, and structure arise fromnatural selection acting on random mutations arising at a very low levelwithin the biological hierarchy—within the genetic text. Yet both body-planformation during embryological development and major morphologicalinnovation during the history of life depend upon a specificity of arrangement
at a much higher level of the organizational hierarchy, a level that DNA alone
does not determine. If DNA isn’t wholly responsible for the way an embryo
develops—for body-plan morphogenesis—then DNA sequences can mutate
indefinitely and still not produce a new body plan, regardless of the amount of

time and the number of mutational trials available to the evolutionary process.
Genetic mutations are simply the wrong tool for the job at hand.
Even in a best-case scenario—one that ignores the immense improbabilityof generating new genes by mutation and selection—mutations in DNA
sequence would merely produce new genetic information. But building a new
body plan requires more than just genetic information. It requires both genetic
and epigenetic information—information by definition that is not stored in
DNA and thus cannot be generated by mutations to the DNA. It follows thatthe mechanism of natural selection acting on random mutations in DNA
cannot by itself generate novel body plans, such as those that first arose in the
Cambrian explosion.
GENE-CENTRIC RESPONSES
Many of the biological structures that impart important three-dimensional
spatial information—such as cytoskeletal arrays and membrane ion channels—are made of proteins. For this reason, some biologists have insisted that thegenetic information in DNA that codes for these proteins does account for the
spatial information in these various structures after all. In each case, however,this exclusively “gene-centric” view of the location of biological information—and the origin of biological form—has proven inadequate.
First, in at least the case of the sugar molecules on the cell surface, geneproducts play no direct role. Genetic information produces proteins and RNA
molecules, not sugars and carbohydrates. Of course, important glycoproteinsand glycolipids (sugar-protein and sugar-fat composite molecules) are
modified as the result of biosynthetic pathways involving networks ofproteins. Nevertheless, the genetic information that generates the proteins inthese pathways only determines the function and structure of the individual
proteins; it does not specify the coordinated interaction between the proteinsin the pathways that result in the modification of sugars.28
More important, the location of specific sugar molecules on the exterior
surface of embryonic cells plays a critical role in the function that these sugar
molecules play in intercellular communication and arrangement. Yet theirlocation is not determined by the genes that code for the proteins to whichthese sugar molecules might be attached. Instead, research suggests that
protein patterns in the cell membrane are transmitted directly from parent
membrane to daughter membrane during cell division rather than as a resultof gene expression in each new generation of cells.29 Since the sugar
molecules on the exterior of the cell membrane are attached to proteins andlipids, it follows that their position and arrangement probably result from

membrane-to-membrane transmission as well.
Consider next the membrane targets that play a crucial role inembryological development by attracting morphogenetic molecules tospecific places on the inner surface of the cell. These membrane targets
consist largely of proteins, most of which are mainly specified by DNA. Evenso, many “intrinsically disordered”30 proteins fold differently depending on
the surrounding cellular context. This context thus provides epigenetic
information. Further, many membrane targets include more than one protein,
and these multiprotein structures do not automatically self-organize to form
properly structured targets.31 Finally, it is not only the molecular structure ofthese membrane targets, but also their specific location and distribution that
determines their function. Yet the location of these targets on the inner surfaceof the cell is not determined by the gene products out of which they are madeany more than, for example, the locations of the bridges across the River
Seine in Paris are determined by the properties of the stones out of which they
are made.
Similarly, the sodium-potassium ion pumps in cell membranes are indeed
made of proteins. Nevertheless, it is, again, the location and distribution of
those channels and pumps in the cell membrane that establish the contours of
the electromagnetic field that, in turn, influence embryological development.
The protein constituents of these channels do not determine where the ionchannels are located.
Like membrane targets and ion channels, microtubules are also made ofmany protein subunits, themselves undeniably the products of genetic
information. In the case of microtubule arrays, defenders of the gene-centric
view do not claim that individual tubulin proteins determine the structure ofthese arrays. Nevertheless, some have suggested that other proteins, or suites
of proteins, acting in concert could determine such higher-level form. For
example, some biologists have noted that so-called helper proteins—which
are gene products—called “microtubule associated proteins” (MAPs) help toassemble the tubulin subunits in the microtubule arrays.
Yet MAPs, and indeed many other necessary proteins, are only part of thestory. The locations of specified target sites on the interior of the cell
membrane also help to determine the shape of the cytoskeleton. And, as
noted, the gene products out of which these targets are made do not determine
the location of these targets. Similarly, the position and structure of thecentrosome—the microtubule-organizing center—also influences the
structure of the cytoskeleton. Although centrosomes are made of proteins, theproteins that form these structures do not entirely determine their location andform. As Mark McNiven, a molecular biologist at the Mayo Clinic, and cell

biologist Keith Porter, formerly of the University of Colorado, have shown,centrosome structure and membrane patterns as a whole convey threedimensional structural information that helps determine the structure of thecytoskeleton and the location of its subunits.32 Moreover, as several otherbiologists have shown, the centrioles that compose the centrosomes replicate
independently of DNA replication: daughter centrioles receive their form
from the overall structure of the mother centriole, not from the individual
gene products that constitute them.33
Additional evidence of this kind comes from ciliates, large single-celled
eukaryotic organisms. Biologists have shown that microsurgery on the cell
membranes of ciliates can produce heritable changes in membrane patterns
without altering the DNA.34 This suggests that membrane patterns (asopposed to membrane constituents) are impressed directly on daughter cells.
In both cases—in membrane patterns and centrosomes—form is transmitted
from parent three-dimensional structures to daughter three-dimensional
structures directly. It is not entirely contained in DNA sequences or theproteins for which these sequences code.35
Instead, in each new generation, the form and structure of the cell arises as
the result of both gene products and the preexisting three-dimensional
structure and organization inherent in cells, cell membranes, and cytoskeletons. Many cellular structures are built from proteins, but proteins findtheir way to correct locations in part because of preexisting three-dimensional
patterns and organization inherent in cellular structures. Neither structuralproteins nor the genes that code for them can alone determine the threedimensional shape and structure of the entities they build. Gene products
provide necessary, but not sufficient, conditions for the development of threedimensional structure within cells, organs, and body plans.36 If this is so, thennatural selection acting on genetic variation and mutations alone cannot
produce the new forms that arise in the history of life.
EPIGENETIC MUTATIONSWhen I explain this in public talks, I can count on getting the same question.
Someone in the audience will ask whether mutations could alter the structuresin which epigenetic information resides. The questioner wonders if changes in
epigenetic information could supply the variation and innovation that natural
selection needs to generate new form, in much the same way that neoDarwinists envision genetic mutations doing so. It’s a reasonable thing to ask,
but it turns out that mutating epigenetic information doesn’t offer a realistic

way of generating new forms of life.
First, the structures in which epigenetic information inheres—cytoskeletal
arrays and membrane patterns, for example—are much larger than individual
nucleotide bases or even stretches of DNA. For this reason, these structures
are not vulnerable to alteration by many of the typical sources of mutationthat affect genes such as radiation and chemical agent.
Second, to the extent that cell structures can be altered, these alterations
are overwhelmingly likely to have harmful or catastrophic consequences. The
original Spemann and Mangold experiment did, of course, involve forcibly
altering an important repository of epigenetic information in a developing
embryo. Yet the resulting embryo, though interesting and illustrative of theimportance of epigenetic information, did not stand a chance of surviving in
the wild, let alone reproducing.
Altering the cell structures in which epigenetic information inheres will
likely result in embryo death or sterile offspring—for much the same reason
that mutating regulatory genes or developmental gene regulatory networks
also produces evolutionary dead ends. The epigenetic information provided
by various cell structures is critical to body-plan development, and many
aspects of embryological development depend upon the precise threedimensional placement and location of these information-rich cell structures.
For example, the specific function of morphogenetic proteins, the regulatory
proteins produced by master regulatory (Hox) genes, and developmental gene
regulatory networks (dGRNs) all depend upon the location of specific,
information-rich, and preexisting cell structures. For this reason, altering
these cell structures will in all likelihood damage something else crucial
during the developmental trajectory of the organism. Too many different
entities involved in development depend for their proper function upon
epigenetic information for such changes to have a beneficial or even neutral
effect.
In Chapter 16 I will examine several new theories of evolution, including
one known as “epigenetic inheritance.” We’ll see that there are some
additional difficulties associated with the idea that mutations in epigenetic
structures can produce significant evolutionary innovation.
DARWIN’S GROWING ANOMALYWith the publication of On the Origin of Species in 1859, Darwin advanced,
first and foremost, an explanation for the origin of biological form. At thetime, he acknowledged that the pattern of appearance of the Cambriananimals did not conform to his gradualist picture of the history of life. Thus,he regarded the Cambrian explosion as primarily a problem of incompletenessin the fossil record.
In Chapters 2, 3, and 4, I explained why the problem of fossil discontinuity
exemplified by the Cambrian forms has, since Darwin’s time, only intensified.
Yet clearly a more fundamental problem now afflicts the whole edifice ofmodern neo-Darwinian theory. The neo-Darwinian mechanism does notaccount for either the origin of the genetic or the epigenetic informationnecessary to produce new forms of life. Consequently, the problems posed tothe theory by the Cambrian explosion remain unsolved. But further, thecentral problem that Darwin set out to answer in 1859, namely the origin ofanimal form in general, remains unanswered—as Müller and Newman inparticular have noted.37
Contemporary critics of neo-Darwinism acknowledge, of course, that
preexisting forms of life can diversify under the twin influences of natural
selection and genetic mutation. Known microevolutionary processes canaccount for small changes in the coloring of peppered moths, the acquisitionof antibiotic resistance in different strains of bacteria, and cyclical variationsin the size of Galápagos finch beaks. Nevertheless, many biologists now
argue that neo-Darwinian theory does not provide an adequate explanation forthe origin of new body plans or events such as the Cambrian explosion.
For example, evolutionary biologist Keith Stewart Thomson, formerly of
Yale University, has expressed doubt that large-scale morphological changes
could accumulate by minor changes at the genetic level.38 Geneticist George
Miklos, of the Australian National University, has argued that neo-Darwinism
fails to provide a mechanism that can produce large-scale innovations in formand structure.39 Biologists Scott Gilbert, John Opitz, and Rudolf Raff haveattempted to develop a new theory of evolution to supplement classical neoDarwinism, which, they argue, cannot adequately explain large-scale
macroevolutionary change. As they note:
Starting in the 1970s, many biologists began questioning its [neoDarwinism’s] adequacy in explaining evolution. Genetics might beadequate for explaining microevolution, but microevolutionary changes
in gene frequency were not seen as able to turn a reptile into a mammal
or to convert a fish into an amphibian. Microevolution looks at
adaptations that concern the survival of the fittest, not the arrival of thefittest. As Goodwin (1995) points out, “the origin of species—Darwin’s
problem—remains unsolved.”40

Gilbert and his colleagues have tried to solve the problem of the origin ofform by invoking mutations in genes called Hox genes, which regulate theexpression of other genes involved in animal development—an approach that
I will examine in Chapter 16.41 Notwithstanding, many leading biologists andpaleontologists—Gerry Webster and Brian Goodwin, Günter Theissen, Marc
Kirschner, and John Gerhart, Jeffrey Schwartz, Douglas Erwin, EricDavidson, Eugene Koonin, Simon Conway Morris, Robert Carroll, Gunter
Wagner, Heinz-Albert Becker and Wolf-Eckhart Lönnig, Stuart Newman andGerd Müller, Stuart Kauffman, Peter Stadler, Heinz Saedler, James Valentine,
Giuseppe Sermonti, James Shapiro and Michael Lynch, to name several—
have raised questions about the adequacy of the standard neo-Darwinianmechanism, and/or the problem of evolutionary novelty in particular.42 For
this reason, the Cambrian explosion now looks less like the minor anomalythat Darwin perceived it to be, and more like a profound enigma, one thatexemplifies a fundamental and as yet unsolved problem—the origination ofanimal form.

Part Three

After Darwin, What?

15
The Post-Darwinian World and SelfOrganization
The year 2009 marked the 150th anniversary of the publication of The Origin
of Species. In that year, the renowned Cambrian paleontologist Simon
Conway Morris published an essay in the journal Current Biology titled“Walcott, the Burgess Shale and rumours of a post-Darwinian world,”
assessing the current state of evolutionary biology. “Everywhere elsewhere in
the Origin the arguments slide one by one skillfully into place, the towering
edifice rises, and the creationists are left permanently in its shadow,” hewrote. “But not when it comes to the seemingly abrupt appearance of animal
fossils.”1 Instead, unresolved problems exposed by the Cambrian explosion
have, in Conway Morris’s view, “opened the way to a post-Darwinian
world.”2 The evidence we reviewed in the previous sections of the book—evidence for a real, rather than merely apparent, explosion of animal form in
the fossil record, and against the neo-Darwinian mechanism as an explanation
for the origin of form and information—may help to explain why biology has
begun to enter such a world.
Moreover, any doubts that at least some biologists have begun to embracea post-Darwinian perspective should have been laid to rest in the summer of
2008, when sixteen influential evolutionary biologists met for a private
conference at the Konrad Lorenz Institute in Altenberg, Austria. The
scientists, whom the science media later dubbed the “Altenberg 16,”3 met to
explore the future of evolutionary theory. These biologists had many different,
and sometimes conflicting, ideas about how new forms of life might have
evolved. But all were united by the conviction that the neo-Darwinian
synthesis had run its course and that new evolutionary mechanisms wereneeded to explain the origin of biological form. As paleontologist Graham
Budd, who was in attendance, explained, “When the public thinks about
evolution, they think about [things like] the origin of wings. . . . But these arethings that evolutionary theory has told us little about.”4

Of course, explaining the origin of form is precisely what has made theCambrian explosion so mysterious. In Chapter 7, in discussing the idea ofpunctuated equilibrium, I quoted Cambrian paleontologists James Valentine
and Douglas Erwin, who concluded exactly that. They argued that neither
punctuated equilibrium nor neo-Darwinism has accounted for the origin of
new body plans and that, consequently, biology needs a new theory to explain“the evolution of novelty.”5
The Altenberg 16 sought to address this challenge. Since the conference,and for nearly two decades preceding it, many evolutionary biologists havebeen working to formulate new theories of evolution, or at least new ideas
about evolutionary mechanisms with more creative power than mutation andnatural selection alone. Each of these new theories attempts to answer theincreasingly urgent question: After Darwin—or neo-Darwinism—what?
THE NEO-DARWINIAN TRIAD
The neo-Darwinian mechanism rests on three core claims: first, thatevolutionary change occurs as the result of random, minute variations (ormutations); second, that the process of natural selection sifts among thosevariations and mutations, such that some organisms leave more offspring thanothers (differential reproduction) based on the presence or absence of certain
variations; and third, favored variations must be inherited faithfully insubsequent generations of organisms, thus causing the population in which
they reside to change or evolve over time.6 Biologists Marc Kirschner andJohn Gerhart call these three elements—variation, natural selection, andheritability—the “three pillars” of neo-Darwinian evolution.7
Those evolutionary biologists who now doubt orthodox neo-Darwinian
theory typically question or reject one or more of the elements of this neoDarwinian triad (see Fig. 16.1). Eldredge and Gould questioned Darwinian
gradualism, which led them to reject the idea that mutational change occurs inminute increments (i.e., the first element of the neo-Darwinian triad justmentioned). Other evolutionary biologists have since rejected other coreelements of the neo-Darwinian mechanism and sought to replace them withother mechanisms or processes. This chapter will examine a new class of
post-neo-Darwinian evolutionary models that attempt to explain the origin of
biological form by deemphasizing the role of random mutations. Thesemodels instead emphasize the importance of “self-organizational” laws orprocesses to the evolution of biological form.

SELF-ORGANIZATIONAL MODELS
Well before the Altenberg 16 convened, a significant number of evolutionary
theorists had already begun to explore alternatives to the neo-Darwinian
synthesis. Punctuated equilibrium was one such alternative. But as scientificcriticisms of that theory began to mount during the 1980s and 1990s, a groupof scientists associated with a think tank in New Mexico, the Santa Fe
Institute, developed a new theoretical approach. They called it “selforganization.”
Whereas neo-Darwinism explains the origin of biological form andstructure as the consequence of natural selection acting on random mutations,self-organizational theorists suggest that biological form often arises (or “selforganizes”) spontaneously as a consequence of the laws of nature (or “laws ofform”). Natural selection, they theorize, acts to preserve this spontaneously
arising order. They think spontaneous self-organizing order, not random
genetic mutations, typically provides the ultimate source of new biologicalform. Thus, they deemphasize two of the three parts of the classical neoDarwinian triad: random mutations and, to a lesser extent, natural selection.
In 1993, the most prominent scientist associated with the Santa Fe
Institute, former University of Pennsylvania biochemist Stuart Kauffman (seeFig. 15.1), released an eagerly awaited treatise, The Origins of Order: SelfOrganization and Selection in Evolution.8 Kauffman articulated a trenchantcritique of the creative power of the mutation and selection mechanism,emphasizing some of the criticisms described here in previous chapters.
Kauffman advanced a comprehensive alternative theory to account for the
emergence of new form. In addition, he advanced a specific proposal for
explaining the Cambrian explosion.9

FIGURE 15.1
Stuart Kauffman. Courtesy Wikimedia Commons, user Teemu Rajala.
Kauffman notes that the development of animal body plans involves twophases: cell differentiation and body-plan morphogenesis (cell organization).
He explores the possibility that self-organizational processes at work today—
specifically in cell differentiation and body-plan formation—might help
explain how new animal forms originated in the past.
Kauffman proposes, first, that gene regulatory networks in animal cells—
genes that regulate other genes—influence cell differentiation. They do thisby generating predictable “pathways of differentiation,”10 patterns by which
one type of cell will emerge from another over the course of embryologicaldevelopment as cells divide. For example, early in embryologicaldevelopment, one type of cell (call it cell type “A”) will divide and give riseto two other types of cells (call them types “B” and “C”), which will
eventually generate cell types “D” and “E,” and “F and G,” respectively, andmany other cell types as the process continues. Kauffman suggests that thesepathways of differentiation “may reflect self-organizing features of complex
genomic regulatory networks.”11 In other words, networks of regulatory genes
in embryonic cells determine the pathways by which cells divide anddifferentiate. Since these patterns of cell differentiation may be determined byregulatory genes, Kauffman regards them as the inevitable by-products ofself-organizational processes. Moreover, since “pathways of celldifferentiation [have been] present in all multicellular organisms presumablysince the Precambrian,”12 he suggests that self-ordering properties “inherent
in a wide class of genomic regulatory networks”13 played a significant role in
the origin of the animal forms.
Kauffman makes a similar case for the importance of self-organizational
processes during body-plan morphogenesis, the second phase of animal
development. This phase involves not so much the differentiation of one cell
type from another, but the arrangement and organization of different cell types
into the distinct tissues and organs that jointly constitute various animal bodyplans.
Kauffman again points to known processes of body-plan development andsuggests that they could have played an important role in the formation of thefirst animal body plans. He cites the importance of the structural or“positional”14 information in cells and cell membranes as the crucial
determinants of how different cell types are organized into different animal
forms. I discussed the importance of such “epigenetic” information to animal
development in Chapter 14 and explained why it poses a problem for neoDarwinian theory. By recognizing the importance of such information,
Kauffman also rejects the neo-Darwinian assumption that a “genetic
program” entirely determines animal development. He further regards thepatterns of development that result from this positional information as
evidence of self-ordering tendencies in matter and the existence of laws of
biological form.
Do these self-ordering tendencies or laws of form, if they exist, explain theorigin of animal body plans and the information necessary to build them?
They don’t.
Self-Organization and Epigenetic Information
To see why let’s look first at how Kauffman attempts to explain the epigenetic“positional” information that directs the organization of cells in the second
phase of animal development. Kauffman attempts to explain this “positional”
information by offering an entirely hypothetical and, ultimately, questionbegging proposal. He invokes an idea sketched out in the 1940s by the
famous English mathematician Alan Turing.15 Turing proposed that specificarrangements of cells in animal development might ultimately derive from thediffusion and specific arrangement of crucial molecules—presumably
something like the morphogen proteins present in embryonic cells. (Recall
that morphogens, or morphogen proteins, influence cell differentiation andorganization during animal development.) Rather than attributing the
distribution of these morphogenic proteins to preexisting genetic andepigenetic information in cells, as occurs during development in modern
animals, Turing postulated that the distribution of these molecules might haveoriginated in the first place independently of such information as the result ofsimple chemical reactions. He imagined one molecule producing both a copyof itself (“autocatalyzing”) and, in addition, producing a different molecule aswell. Then he envisioned one of these molecules inhibiting the production of
the other, thus allowing, through repeated cycles, the production of more andmore of one molecule and less and less of the other. Turing thought theresulting nonuniformities in the patterns of distribution of those molecules
would eventually result in nonuniform patterns in the distributions of different
cells, possibly resulting in different animal forms.
Kauffman expanded upon this proposal as a way of understanding how
crucial positional information might organize as the result of chemicalinteractions of different molecules. Nevertheless, his proposal suffers from an
obvious difficulty: it lacks any chemical or biological specificity. In
explaining the proposal, Kauffman does not mention any specific chemicals
or proteins that would behave in the way he envisions. Instead, he describes
the behavior of hypothetical molecules that he labels with the indistinct
monikers “X” and “Y.” More important, Kauffman offers no evidence thatchemicals interacting in the way he envisions could create specificbiologically relevant configurations or distributions of morphogen proteins—apart, that is, from the processes that generate specifically arranged
distributions of these proteins in preexisting information-rich embryonic cells
today.
Instead, it is inherently implausible to think that the specificity necessary
to coordinate the movements and arrangements of the billions or trillions ofcells present in adult animal forms could be established by the interactions of
one or two simple chemicals, even if they formed autocatalytic cycles.
Kauffman himself seems tacitly to acknowledge the difficulty of generating
biological specificity from the reactions of chemicals alone. He notes, incritique of his own model, that patterns of molecular diffusion produced bychemical autocatalysis would depend crucially upon “the initial conditions.”16
In other words, getting a biologically relevant information-rich arrangementof morphogenic proteins would require starting with a very specific(presumably information-rich) arrangement of autocatalyzing molecules.
Kauffman encounters this same problem in attempting to explain the originof the first life as the result of autocatalytic reactions starting from a prebiotic
soup. In The Origins of Order, he acknowledges that generating an
autocatalytic, or self-reproducing, set of molecules—a crucial step in his
origin-of-life scenario—would require “high molecular specificity”17 in theinitial set of peptides or RNA molecules. In other words, it would require
specificity of arrangement and structure, that is to say, functional information.
Self-Organization and Genetic Information
And what about the specifically genetic information necessary to the earlier
phase of animal development? Does Kauffman’s self-organizational theory
explain the origin of the “genetic regulatory networks” necessary to celldifferentiation? Again, it does not. Instead, in an even more obvious way, itbegs the question of the origin of these regulatory networks. Indeed, though
Kauffman discusses cell differentiation as a kind of “self-ordering” or selforganizational process, he acknowledges that the predictable pathways ofdifferentiation that characterize this process derive from preexisting gene
regulatory networks. As Kauffman notes, the spontaneous ordering tendencies
in cell differentiation are “inherent in a wide class of genomic regulatory
networks.”18 Indeed, the genetic information in the gene regulatory networks
does not come from self-ordering processes of cell differentiation. Instead,cell differentiation, to the extent that it can be properly described as “selfordering,” results from preexisting genetic sources of information. Thus, theself-organizational process that Kauffman cites cannot explain the origin ofgenetic information, because it derives from it, as Kauffman’s own
description reveals.
In a later book, At Home in the Universe: The Search for the Laws of SelfOrganization and Complexity, Kauffman does offer computer simulations of
two “model systems”19 that seek to explain, at least in principle, how genetic
information might have self-organized. In one example, he describes a systemof buttons connected by strings.20 The buttons represent novel genes orproteins and the strings represent self-organizational forces of attraction
between the proteins. Kauffman suggests that when the complexity of thissystem reaches a critical threshold (as represented by the number of buttons
and strings), new modes of organization might arise in the system “for free”21—without intelligent guidance—similar to the way that water spontaneously
changes to ice or vapor under specific conditions.
Kauffman asks his readers to imagine a system of many interconnected
lights. Each light can flash in a variety of states—on, off, twinkling, and soon. Since each light can adopt more than one possible state, the system may
adopt a vast number of possible states. Further, in his system, rules determine
how past states influence future states. Kauffman asserts that, as a result of
these rules, the system would, if properly tuned, eventually produce a kind oforder in which a few basic patterns of light activity recur with greater thanrandom frequency. Since these patterns represent a small portion of the total
number of possible states in which the system can reside, Kauffman suggeststhat self-organizational laws might similarly find highly improbablebiological outcomes—perhaps even functional sequences of bases or aminoacids within a much larger sequence space of possibilities.22
It’s not hard to see why these simulations also would fail to account for theorigin of the new genes and proteins needed to produce the Cambriananimals. In both of his examples Kauffman presupposes significant sources ofpreexisting information. In his buttons and strings simulation, he intends the
buttons to represent proteins, themselves the result of preexisting genetic
information. Where did that information come from? Kauffman doesn’t say,but it is an essential part of what needs explanation in the history of life.
Similarly, in his light system, the order that allegedly arises “for free”—that
is, apart from an intelligent input of information—only does so if, as
Kauffman acknowledges, the programmer “tunes” the system to keep it fromeither (a) generating an excessively rigid order or (b) devolving into chaos.23
This tuning presumably involves an intelligent programmer selecting certain
parameters and excluding others—that is, inputting information. In fact, insummarizing the import of this illustration, Kauffman insists that it shows
how the “orderliness of the cell, long attributed to the honing of Darwinianevolution, seems instead likely to arise from the dynamics of the genome
network,”24 that is, from preexisting—unexplained—sources of genetic
information.
In addition, Kauffman’s model systems are not analogous to biologicalsystems because they are not constrained by functional considerations. A
system of interconnected lights governed by preprogrammed rules may wellsettle into a small number of patterns within a much larger space ofpossibilities. But since these patterns have no function and need not meet any
functional requirements, they have no specificity analogous to that in thegenes of actual organisms. Kauffman’s model systems do not produce
sequences or systems characterized by specified complexity or functional
information. They produce modules of repetitive order distributed in an
aperiodic manner, yielding mere complexity (i.e., information only in the
Shannon sense).25 Getting a law-governed system to generate repetitive
patterns of flashing lights, even with a certain amount of variation, isinteresting, but not biologically relevant. A system of lights flashing “Vote for
Jones,” on the other hand, would model a biologically relevant outcome, atleast, if such a functional sequence of letters arose without intelligent agentsprogramming the system with equivalent amounts of functionally specifiedinformation.
Kauffman on the Cambrian
Kauffman also proposes a specific self-organizational mechanism to explainsome aspects of the Cambrian explosion. According to Kauffman, newCambrian animals emerged through “long-jump” mutations that established
new body plans in a discrete rather than gradual fashion.26 He recognizes that
mutations affecting early development are almost inevitably harmful.27 Thus
he concludes that body plans, once established, will not change, whateversubsequent evolution may occur. This keeps his proposal consistent with a
top-down pattern in the fossil record in which higher taxa (and the body plans
they represent) appear first, only later to be followed by the multiplication oflower taxa representing variations within those original body designs.
Even so, Kauffman’s proposal begs the most important question: What
produces the new Cambrian body plans in the first place? By invoking “longjump mutations,” he identifies no specific self-organizational process that can
produce such changes. Moreover, he concedes a principle that undermines his
own proposal. As noted above, Kauffman acknowledges that mutations earlyin development are almost inevitably deleterious. Yet developmental
biologists know that these are the only kind of mutations that have a realistic
chance of producing large-scale evolutionary change—the big jumps that
Kauffman invokes. Though Kauffman repudiates the neo-Darwinian reliance
upon random mutations, he must invoke the most implausible kind of random
mutation to provide a self-organizational account of the new Cambrian bodyplans.
DEVELOPMENTAL TOOLKITS AND SELF-ORGANIZATIONAL
PROCESSES
More recently, another advocate of self-organization, Stuart Newman, a cellbiologist at the New York Medical College, has published several papers
suggesting that self-organizational processes can help explain the origin ofbody plans. In a paper in the volume produced from the Altenberg 16
conference, Newman develops a model that resembles Kauffman’s, but one
that offers more biological specificity.28
Newman, like Kauffman, invokes self-organizational processes. But
Newman sees these processes acting dynamically and in coordination with agenetic “toolkit.” His model emphasizes the importance of a highly conserved(i.e., similar) set of regulatory genes in all the major Cambrian taxa. In hisview, this common “developmental genetic toolkit”29 has been used “togenerate animal body plans and organ forms for more than half a billion
years”30 since the inception of the animal kingdom.
But if all the animal taxa have the same toolkit, why are the various formsof animals and higher metazoan taxa so different from one another? For
Newman, the answer to this question requires understanding how selforganizing processes influence the interaction of cells during development
and how they cause genes to acquire different functions affecting theinteractions of cells.
For example, he attributes the emergence of multicellularity to cells
acquiring the capacity “to remain attached to one another after dividing.”31
This capacity in turn derives not from generating new genes and proteins (asneo-Darwinism would assume). Instead, it derives from the repurposing ofold genes and proteins in response to specific self-organizational (andepigenetic) processes such as the “physical force of adhesion.”32 Newman
proposes, further, that once the first multicellular organisms had arisen, theywould have “set the stage for additional physical processes to come intoplay”33—processes that could alter the expression and function of still othergenes in the developmental genetic toolkit, resulting in wholly new anddifferent body plans. As Newman explains, “The phenomenon ofmulticellularity opened up possibilities for these molecules to become
involved in the molding of bodies and organs.”34
Newman envisions new animal body plans resulting from different cells
sticking to each other in different configurations because of different forces of
attraction between molecules on the surface of cells and because of different
patterns of distribution of crucial molecules within cells. He calls these selforganizational forces and factors “dynamical patterning modules” (orDPMs).35 Figure 15.2 shows some typical ways that cells cluster together or
arrange themselves as the result of these self-organizational forces. Newman
lists many “dynamical patterning modules,” or self-organizational forces,
responsible for the spontaneous emergence of these different cell clusters,
including “adhesion, shape and surface polarization, switching between
alternative biochemical states, biochemical oscillation, and the secretion ofdiffusible and nondiffusible factors.”36

FIGURE 15.2
Dynamical Patterning Modules (DPMs), showing the different ways that,
according to biologist Stuart Newman, cells can stick to one another(“aggregate”) and form structures during animal development.
To get a handle on what Newman has in mind, think of cells as Legoblocks. There are many different ways of connecting Lego blocks, dependingon the shape of the blocks and the pattern of raised bumps and indentations on
the blocks. These patterns allow small groups of Legos to be arranged into
different modular structures: cubes, walls, circular rings, and so forth. Each ofthese smaller modular structures can then be combined to make manydifferent larger structures, from airplanes and skyscrapers to submarines andcastles. In a similar way, Newman suggests that different forces of adhesion
between cells and different patterns of molecular diffusion within andbetween cells will generate many different patterns or motifs of multicellularorganization, which in turn function as modular elements that can be
combined in various ways to make diverse animal forms.37
Do these self-organizational processes account for the origin of animal
body plans in the Cambrian explosion or the information necessary to produce
new animal forms? Again, they do not. Instead, Newman, like Kauffman,either fails to offer an adequate mechanism for generating crucial sources of
biological information, or he begs the question by presupposing the existenceof various sources of information.

ASSUME A TOOLKITIn the first place, Newman obviously presupposes the existence of a“developmental genetic toolkit,” that is, a whole set of genes, including
regulatory genes, that help to direct the development of animal body plans.
Where does this genetic information come from? He doesn’t specify, though
presumably he might be assuming the neo-Darwinian mechanism somehow
produced the genetic information in the toolkit. If so, he leaves his model
vulnerable to the criticisms outlined in Chapters 9 through 12. He certainly
does not cite any specifically self-organizational process to explain the originof the genetic toolkit. He also incorrectly seems to presuppose that the genes
present in this common toolkit provide all the genetic information necessary
to specify individual body plans. But this overlooks a host of recent findings
showing that individual species within specific taxa often require genes fordevelopment that are specific to those species and taxa.38 Thus, these genes
would not have been present in a common metazoan toolkit of the kind
Newman postulates.
Second, Newman does not account for the origin of the informationnecessary to organize modular arrangements or groups of cells into wholeanimal body plans. The forces at work in his dynamical patterning modules
explain, at best, only the arrangements of small groups of cells, not thearrangements of those modular cell clusters into tissues, organs, and wholebody plans.
Think, again, of arranging Lego blocks. There are many ways of arranging
small numbers of Lego blocks. These various arrangements form common
structural motifs such as: two blocks stuck together at right angles; several
curved blocks forming circular rings, stacked blocks forming hollow squares
or walls or cube-like shapes; blocks arranged as prisms or cylinders; flat
layers of blocks stacked two bumps thick or three bumps thick or more.
Though these structural elements stick together because of interactions
between the bumps and indentations on each block, those bumps andindentations themselves do not specify any particular larger structure—acastle or an airplane, for example—because each motif may be combined orrecombined with many other structural motifs in numerous different ways.
The shape and properties of the modular elements do not dictate the type oflarger structure that must be built from them. Instead, to build a particular
structure, the modular elements must be arranged in particular ways. And
since there are many possible ways to arrange these modular elements, only
one or a few of which will result in a desired structure, every Lego set
includes a blueprint with step-by-step instructions—in other words, additionalinformation.
In a similar way, producing a body plan from the different types of cellclusters generated by Newman’s dynamical patterning modules (DPMs),would also require additional information. Newman does not account for thisinformation. He correctly highlights the way certain recurrent motifs fororganizing groups of cells seem to form spontaneously as the result ofphysical interactions between individual cells (his DPMs). He does not,however, establish that these groups of cells must arrange themselves into
specific tissues, organs, or body plans in response to any known physicalprocess or law. Instead, it seems entirely possible that these modular elements(cell clusters) have many “degrees of freedom” and can be arranged ininnumerable ways. If so, then some additional information—an overall
organismal blueprint or set of assembly instructions—would need to direct
the arrangement of these modular elements. Newman does not consider thispossibility. Nor does he cite any law-like self-organizational process thatwould eliminate the need for such information to direct animal development.
There is yet a further problem with Newman’s proposal. Even the capacity
for cells to self-organize into dynamical patterning modules probably derives
from prior unexplained sources of information. Newman’s DPMs
undoubtedly form as the result of interactions between molecules on thesurface of cells, and as the result of chemical gradients between cells—with
the specific configuration and properties of those molecules determining theexact structure of the individual DPMs. In that sense, the DPMs do, of course,
self-organize, but clearly the specific ways that cells typically cluster together
will depend upon highly specific and complex forces of interaction between
the molecules and groups of molecules on the surface of these cells. Many ofthe molecules that contribute to these interactions are no doubt proteins,obvious products of genetic information. But, in addition, cell-to-cellinteractions are affected by the arrangement of proteins and other moleculeson the surface of cells (such as the sugars in the sugar code, see Chapter 14)
as well as by the arrangement of structures made of proteins. But thesemolecular arrangements are, in turn, specified by either preexisting genetic or,more probably, epigenetic sources of information and structure. Thus,
Newman’s analysis shows that the self-ordering tendencies (or biological lawsof form), to the extent they exist, depend upon preexisting sources of
biological information. Newman, again, does not explain where that
information comes from.
Newman does emphasize how epigenetic sources of information affect theexpression and the function of gene products during the process of animal
development. He notes that different gene products may perform differentfunctions depending upon the organismal context in which they findthemselves. But Newman does not explain with any specificity how the genes
in the common toolkit acquire different functions in response to selforganizational processes or where the epigenetic information comes from that
determines those functions. Yet, clearly context-dependent gene expression
depends upon a host of other preexisting epigenetic sources of informationand structure.
Recall, for example, the discussion of cell membrane targets from Chapter
14. These targets provide an important source of epigenetic information by
influencing the positioning of crucial morphogenic proteins. Yet, thearrangements of the targets on the cell membrane do not self-organize as theresult of simple chemical interactions between the proteins out of which they
are made39—that is, the proteins do not determine the location of themembrane targets on the interior of the cell. Instead, the location and thestructure of membrane targets are transmitted from parent membrane todaughter membrane, a process that transmits preexisting epigenetic structural
information from the parent membrane. Newman does not attempt to explain
the origin of this information or structure by any known self-organizational
process. Instead, the evidence indicates that interior and exterior membranetargets, cytoskeletal arrays, the sugar code, and many other sources of
epigenetic structural information do not self-organize as the result of physicalinteractions between their respective molecular subunits.40
ORDER VS. INFORMATION
Self-organizational theorists face, in addition, a conceptual distinction that has
cast doubt on the relevance of their theories to biological systems. Selforganizational theorists seek to explain the origin of “order” in living systems
by reference to purely physical or chemical processes (or laws describing
those processes). But what needs to be explained in living systems is not
mainly order in the sense of simple repetitive or geometric patterns. Instead,what requires explanation is the adaptive complexity and the information,
genetic and epigenetic, necessary to build it.
Yet advocates of self-organization fail to offer examples of either
biological information or complex anatomical structures arising from physics
and chemistry alone. They either point, as Newman and Kauffman do, toembryological development unfolding predictably as the result of preexisting
information-rich gene products, cell membranes, and other cell structures. Or
they offer examples of purely physical and chemical processes generating akind of order that has little relevance to the features of living systems thatmost need explanation.
In the latter case, self-organizational theorists often point to simple
geometric shapes or repetitive forms of order arising from or being modified
by purely physical or chemical processes. They suggest that such orderprovides a model for understanding the origin of biological information or
body-plan morphogenesis.41 Self-organizational theorists have cited crystals,
vortices, and convection currents (or stable patterns of flashing lights) toillustrate the supposed power of physical processes to generate “order for
free.” Crystals of salt do form as the result of forces of attraction between
sodium and chloride ions; vortices can result from gravitational and otherforces acting on water in a draining bathtub; convection currents do emerge
from warm air (or molten rock) rising in enclosed spaces. And somemolecules found in living systems do adopt highly ordered structures andrecognizable geometric shapes as the result of the physical interactions of
their constituent parts alone. Nevertheless, the type of order evident in thesemolecules or physical systems has nothing to do with the specific “order” ofarrangement—the information or specified complexity—that characterizes thedigital code in DNA and other higher-level information-rich biologicalstructures.
This is easiest to see in the case of the information encoded in DNA andRNA. Some of what follows may be familiar from my discussion in Chapter
8, but it bears repeating. The bases in the coding region of a section of DNA
or in an RNA transcript are typically arranged in a nonrepetitive or aperiodic
way. These sections of genetic text display what information scientists call“complexity,” not simple “order” or “redundancy.”
To see the difference between order and complexity consider the difference
between the following sequences:
Na-Cl-Na-Cl-Na-Cl-Na-ClAZFRT<MPGRTSHKLKYR
The first sequence, describing the chemical structure of salt crystals,
displays what information scientists call “redundancy” or simple “order.”That’s because the two constituents, Na and Cl (sodium and chloride), arehighly ordered in the sense of being arranged in a simple, rigidly repetitive
way. The sequence on the bottom, by contrast, exhibits complexity. In thisrandomly generated string of characters, there is no simple repetitive pattern.
Whereas the sequence on the top could be generated by a simple rule orcomputer algorithm, such as “Every time Na arises, attach a Cl to it, and viceversa,” no rule shorter than the sequence itself could generate the second

sequence.
The information-rich sequences in DNA, RNA, and proteins, by contrast,
are characterized not by either simple order or mere complexity, but insteadby “specified complexity.” In such sequences, the irregular and unpredictablearrangement of the characters (or constituents) is critical to the function thatthe sequence performs. The three sequences below illustrate these
distinctions:
Na-Cl-Na-Cl-Na-Cl-Na-Cl (Order)AZFRT<MPGRTSHKLKYR (Complexity)
Time and tide wait for no man (Specified complexity)
What does all this have to do with self-organization? Simply this: the lawlike, self-organizing processes that generate the kind of order present in a
crystal or a vortex do not also generate complex sequences or structures; stillless do they generate specified complexity, the kind of “order” present in agene or functionally complex organ.
Laws of nature by definition describe repetitive phenomena—order in thatsense—that can be described with differential equations or universal “if-then”
statements. Consider, for example, these informal expressions of the law ofgravity: “All unsupported bodies fall” or “If an elevated body is left
unsuspended, then it will fall.” These statements represent reasonably
accurate law-like descriptions of natural gravitational phenomena precisely
because we have repeated experience of unsupported bodies falling to theearth. In nature, repetition provides grist for lawful description.
The information-bearing sequences in protein-coding DNA and RNA
molecules do not exhibit such repetitive “order,” however. As such, thesesequences can be neither described nor explained by reference to a naturallaw or law-like “self-organizational” process. The kind of non-repetitive“order” on display in DNA and RNA—a precise sequential “order” necessary
to ensure function—is not the kind that laws of nature or law-like selforganizational processes can—in principle—generate or explain.
Otherwise, the nucleotide bases would repeat rigidly—such as
ACACACACACACACACAC—in a way that would not allow DNA to store
or convey specified information. A curious feature of the chemistry of DNA
allows any one of the four nucleotide bases to attach to any site on the interior
backbone of the DNA molecule. This chemical indeterminacy makes it
possible for DNA and RNA to store any one of a virtually unlimited numberof different arrangements of nucleotide bases—in effect, to encode any
genetic message. But this indeterminacy also categorically defies explanation

by deterministic law-like forces of chemical attraction. And because forces of
attraction do not determine the sequence of nucleotide bases in DNA or RNA,the origin of the specific arrangement of the bases—the information in DNA
and RNA—cannot be attributed to self-organizing forces of attraction either.
Hubert Yockey, a leading innovator in the application of information
theory to molecular biology, first recognized the problems associated withinvoking self-organization to explain the origin of biological information.
These theories fail, he argued, for two reasons. First, they do not distinguishorder from information. And, second, the information in the DNA molecule
does not derive from law-like forces of attraction.42 As he explained in 1977:“Attempts to relate the idea of order . . . with biological organization or
specificity must be regarded as a play on words that cannot stand careful
scrutiny. Informational macromolecules can code genetic messages andtherefore can carry information because the sequence of bases or residues isaffected very little, if at all, by [self-organizing] physicochemical factors.”43
Much the same thing is true of many vital sources of epigenetic
information. The forces of attraction between constituent proteins inmembrane targets or cytoskeletal arrays, for example, do not determine thestructure or location of these epigenetic structures and the positional
information they provide. The origin of these structures cannot be attributed
to self-organizing forces of attraction either. Instead, in each case,information-rich epigenetic structures are generated from preexisting sourcesof epigenetic information.
Thus, self-organizational theories explain well what does not mainly need
explaining in biology, namely, repetitive or simple geometric forms of order.
Self-organizational theorists do cite structures that might have self-organized.
But these examples are typically extremely modest in scope. They include
repeating patterns of atoms in crystals; simple geometric figures; patterns oflines, triangles, and streaks; vortices; spiral wave currents; and simple shapesthat glide across computer screens.44 None exhibit the specified complexitythat characterizes the digital information in DNA and RNA or the complex
arrangements of proteins, cells, tissues, and organs necessary to build afunctioning form of animal life.
NATURAL MAGIC OR TRUE CAUSE?
In 2007, I participated in a private meeting of evolutionary biologists andother scientists who shared the conviction that a new theory of biologicalorigins is now needed. In attendance were several prominent advocates of theself-organization approach. During the meeting, these scientists presented

intriguing analogies from physics and chemistry to show how order might
have arisen “for free”—that is, without intelligent guidance—in the biologicalrealm. Yet the order they described in these analogies seemed to have no
direct relevance to the complexity—indeed the specified complexity—ofgenes or cell membranes or animal body plans. Other scientists at theconference challenged the advocates of self-organization to cite known
processes that could produce biologically relevant form and information.
Near the end of the meeting one advocate of self-organization privately
acknowledged to me the validity of these critiques, admitting that, for now,
“self-organization is really more of a slogan than a theory.” Stuart Kauffman,perhaps attempting to make a virtue of the necessity of accepting this
explanatory deficit, has recently celebrated the self-organizational perspective
for embracing what he calls “natural magic.” In a lecture at MIT, heconcluded: “Life bubbles forth in a natural magic beyond the confines ofentailing law, beyond mathematization.”45 He went on to explain that one
benefit of the self-organizational perspective is that it allows us to be“reenchanted” with nature and to “find a way beyond modernity.”46
Since the beginning of modern science, scientists have championed acommonsense principle of scientific reasoning known as the vera causa
principle. This principle holds that explaining a particular phenomenon or
event requires identifying a “true cause” that is known from experience tohave the power to produce the event or phenomenon in question. The earlymodern scientists affirmed this principle as one of the key aspects of ascientific approach to understanding nature. This stood in opposition to themagical thinking that had gone before in which people attributed powers tonature that they had never observed it manifesting. As the scientificrevolution matured, endeavors such as alchemy, for example, were eventually
rejected precisely because the alchemists could not identify a cause that could
effect the transformation they were seeking to demonstrate.
Self-organizational theories have clearly failed to provide a vera causa forthe origin of biologically relevant forms of “order”—the functional
complexity and specified information present in living systems. Instead, theyeither beg the question as to the ultimate origin of biological information or
point to physical and chemical processes that do not produce the specifiedcomplexity that characterizes actual animals.
Viewed in this light, Kauffman’s recent discussion of natural magic andcalls for a “reenchantment” with nature sound less like a bold new initiative toreconcile science and spirituality (which is what he intended) than a tacit
admission that self-organizational theories have failed to identify known
physical and chemical processes capable of generating the form andinformation present in actual living systems. Indeed, after years of attempting
to solve the problem of the origin of form, Kauffman’s recent ruminations
about “natural magic” sound a lot like an admission that a profound mysteryremains.

16
Other Post-Neo-Darwinian Models
When Stephen Jay Gould was first wrestling with the question of how newforms of animal life could have arisen so quickly in the fossil record, heconsidered many possible mechanisms of change. In the famed 1980 paper inwhich he declared neo-Darwinism “effectively dead,”1 he didn’t just propose
allopatric speciation and species selections as new evolutionary mechanisms.
He also granted a rehearing to a long discredited idea. Specifically, he argued
that large-scale “macromutations” might generate significant innovations inform relatively quickly.2
In the 1930s and 1940s, this idea had been associated with University ofCalifornia at Berkeley geneticist Richard Goldschmidt. Aware of the many
discontinuities in the fossil record, Goldschmidt envisioned radicaltransformations in the form of animals arising in even one generation as theresult of such large-scale mutations. He endorsed, for instance, the view of theGerman paleontologist Otto Schindewolf (1896–1971) that “the first bird
hatched from a reptilian egg” and, thus, in Goldschmidt’s words, “that the
many missing links in the paleontological record are sought for in vain
because they have never existed.”3 If a bird hatched directly from a reptilian
egg as the result of heritable, large-scale mutations, then such a sudden leapor “saltation” would obviously leave no fossil intermediates behind.
Neo-Darwinists rejected this idea as biologically implausible in theextreme. They argued that changing so many functionally integrated
anatomical and physiological systems so quickly would inevitably result in
deformed mutants, not different integrated systems of organs constituting awhole new animal.4 Goldschmidt’s macromutations, they contended, would
produce not what Goldschmidt called “hopeful monsters,” but “hopelessmonsters”—that is, nonviable organisms.5
Though Gould wanted to reconsider a role for large-scale mutations, hecarefully disassociated his proposal from Goldschmidt’s much ridiculed idea.
Instead, he suggested that the mutations affecting genes in animal
development might generate larger increments of morphological innovation

than the mutations that affected other genes. These “developmental
mutations,” he thought, might generate modular parts of biological systems ina short time—without needing to generate whole new forms of life in a single
generation. He offered, as an example, the possibility that the gill arch bonesof ancient jawless fish, though not the whole fish, might have arisen in one
step as the result of a developmental macromutation. Gould explained: “I donot refer to the saltational origin of entire new designs, complete in all theircomplex and integrated features. . . . Instead, I envisage a potential saltational
origin for the essential features of key adaptations.”6
In response to heavy criticism from neo-Darwinists, Gould later
downplayed the role of such larger-scale developmental mutations in thetheory of punctuated equilibrium. Other evolutionary biologists, however,took his idea as an inspiration and developed theories that emphasize suchdevelopmental mutations as a driving force in macroevolution. Evolutionary
theorists and developmental biologists such as Rudolf Raff, Sean B. Carroll,and Wallace Arthur have developed a subdiscipline of biology known as
evolutionary developmental biology, or “evo-devo” for short. The
evolutionary developmental biologists have since formulated alternativemodels that challenge a key aspect of the neo-Darwinian triad. Whereas neoDarwinism envisions new form arising as the result of slow, incremental
accumulations of minor mutations, evolutionary developmental biologists
argue that mutations affecting genes involved in animal development cancause large-scale morphological change and even whole new body plans.
This chapter will not only examine the ideas of evolutionary
developmental biologists, but three of the other most prominent alternatives to
neo-Darwinism, some proposed by members of the Altenberg 16 (see Fig.
16.1). Each of these alternatives emphasizes certain elements of the “triad” atthe expense of others. Whereas the self-organizational alternatives that I
discussed in the last chapter emphasize the role of law-like processes overrandom mutations, these other new theories reaffirm the importance ofmutations, though each also reconceptualizes how mutations act. One
approach falls under the rubric of “evo-devo” and conceives of mutations
producing modifications in larger increments. Another, the neutral theory of
evolution, sees mutations acting absent selection. Another, neo-Lamarckian“epigenetic inheritance,” envisions heritable alterations in epigenetic
information influencing the future course of evolution. Still another, called“natural genetic engineering,” affirms that nonrandom genetic rearrangements
drive evolutionary innovation.7

FIGURE 16.1
The tenets of neo-Darwinian orthodoxy and the different ways that various
non-Darwinian models of evolution deviate from those tenets. The boxes
representing new evolutionary models are positioned under the headings ofthe neo-Darwinian tenets that they challenge.
Let’s see if one of these proposals solves the twin problems of the origin ofform and information and whether, therefore, it might also help to resolve themystery of the Cambrian explosion.8
EVO-DEVO AND ITS PROPOSALSThe neo-Darwinian synthesis has long emphasized that large-scale
macroevolutionary change occurs as the inevitable by-product of theaccumulation of small-scale “microevolutionary” changes within populations.
The consensus in support of this idea began to fray in evolutionary biology
during the early 1970s, when young paleontologists such as Gould, Niles
Eldredge, and Steven Stanley realized that the fossil record did not show apattern of gradual “micro-to-macro” change. In 1980, at a now famous
symposium on macroevolution at the Field Museum in Chicago, the rebellion
burst into full view, exposing what developmental biologist Scott Gilbertcalled “an underground current in evolutionary theory” among theorists who
had concluded that “macroevolution could not be derived frommicroevolution.”9At the conference, paleontologists who doubted the “micro-to-macro”

consensus found allies among younger developmental biologists. They weredissatisfied with neo-Darwinism in part because they knew that population
genetics, its mathematical expression, sought only to quantify changes in genefrequency rather than explain the origin of genes or novel body plans. Thus,
many developmental biologists thought that neo-Darwinism did not offer acompelling theory of macroevolution.10
To formulate a more robust theory, many developmental biologists, such as
Rudolf Raff, a developmental biologist at the University of Indiana and one of
the founders of “evo-devo,” urged evolutionary theorists to incorporate
insights from their discipline.11 For example, developmental biologists knowthat mutations expressed early in the development of animals are necessary toalter body-plan morphogenesis. Thus, they argue that these mutations musthave played a significant role in generating whole new animal forms during
the history of life. They assert that this understanding of developmental
processes is crucial to understanding animal evolution. Some evo-devo
advocates such as Sean B. Carroll and Jeffrey Schwartz have pointed
specifically to homeotic (or Hox) genes—master regulatory genes that affectthe location, timing, and expression of other genes—as entities capable ofproducing such large-scale change in animal form.12 These evo-devo
advocates have broken with classical neo-Darwinism primarily in theirunderstanding of the size or increment of mutational change.
MAJOR BUT NOT VIABLE, VIABLE BUT NOT MAJOR
Despite the enthusiasm surrounding the field, evo-devo fails, and for an
obvious reason: its main proposal, that early-acting developmental mutations
can cause stably heritable, large-scale changes in animal body plans,
contradicts the results of one hundred years of mutagenesis experiments.13 As
we saw in Chapter 13, the experiments of scientists such as Nüsslein-Volhard
and Wieschaus have shown definitively that early-acting body-plan mutations
invariably generate embryonic lethals—dead animals incapable of further
evolution. The results of these experiments have generated the dilemma forevolutionary biologists that geneticist John McDonald aptly described as the“great Darwinian paradox.” Recall that McDonald noted that early-acting
regulatory mutations do not produce viable alterations in form that will persist
in populations, as evolution absolutely requires. Instead, these mutations are
eliminated immediately by natural selection because of their invariably
destructive consequences. On the other hand, later-acting mutations cangenerate viable changes in the features of animals, but these changes do notaffect global animal architectures. This generates a dilemma: major changes

are not viable; viable changes are not major. In neither case do the kinds ofmutation that actually occur produce viable major changes of the kind
necessary to build new body plans.
In 2007, I coauthored a textbook with several colleagues titled Explore
Evolution. In it, we explained this “either/or” (“major-not-viable, viable-notmajor”) dilemma and suggested that it posed a challenge to theories that relyon the mutation and selection mechanism to explain the origin of major
morphological changes.14 The National Center for Science Education (NCSE)—an influential activist group that opposes allowing students to learn about
scientific criticisms of evolutionary theory—challenged our critique. They
charged that our textbook “fails to acknowledge the extensive research on
mutations in DNA sequences that do not encode proteins, but which haveimportant morphological effects.”15 In other words, they claimed that someviable mutations do produce major large-scale changes.

FIGURE 16.2
Superficial changes in insect wing coloration thought to be caused bymutations in cis-regulatory elements. Such examples show that mutations that
affect development and that also result in viable offspring tend to be minor.
Courtesy National Academy of Sciences, U.S.A.

The NCSE cited papers from the “evo-devo” literature claiming that a typeof mutation in the regulatory regions of the genome, “cis-regulatory” regions,have been shown to produce large-scale changes in winged insects. According
to the NCSE, mutations in these cis-regulatory elements (or CREs) are“considered by many evolutionary biologists to have the greatest potential for
generating evolutionary change.”16 What’s more, they insisted that “mutationsin CREs play an important role in morphological evolution.”17 The NCSE
cited a paper in the Proceedings of the National Academy of Sciences by threedevelopmental biologists, Benjamin Prud’homme, Nicolas Gompel, and Sean
B. Carroll.18
The paper did not show what the NCSE claimed, however. It did assertthat changes in regulatory DNA produce “both relatively modest
morphological differences among closely related species and more profoundanatomical divergences among groups at higher taxonomical levels.”19 But
the study only showed how changes in the cis-regulatory elements in fruit fly
DNA might have affected the coloration of wing spots in several different
types of flying insects. It did not report any significant change in the form or
body plan of these insects. Instead, the study highlighted a clear case of a
viable mutation generating merely a minor or superficial change (see Fig.
16.2).
Not surprisingly, many evolutionary biologists recognize that such
regulatory mutations do not explain the evolution of new body plans. For
example, Hopi Hoekstra, of Harvard University, and Jerry Coyne, two
traditional neo-Darwinists, have published an article reviewing various evodevo proposals in the journal Evolution. They note, “Genomic studies lend
little support to the cis-regulatory theory” of evolutionary change.
They also argue, tellingly, that most cis-regulatory mutations result in theloss of genetic and anatomical traits, including a famous case in which
evolutionary biologists attributed the loss of pelvic spines in stickleback fishto mutations in cis-regulatory elements.20 Yet, as they argue, “supporting the
evo-devo claim that cis-regulatory changes are responsible for morphologicalinnovations requires showing that promoters are important in the evolution of
new traits, not just the losses of old ones.” Hoekstra and Coyne conclude,“There is no evidence at present that cis-regulatory changes play a major role—much less a pre-eminent one—in adaptive evolution.”21 Given theircommitment to neo-Darwinism, it’s fair to assume that Hoekstra and Coyne
probably did not intend, in making this argument, to refute the NCSE’s
criticism of our textbook Explore Evolution. Nevertheless, science, likepolitics, sometimes makes for strange bedfellows.

WHAT ABOUT HOX GENES?
When biology students hear my colleague Paul Nelson describe the “great
Darwinian paradox” (see Chapter 13) in public lectures on university
campuses, they often ask, “What about Hox genes?” Recall that Hox (orhomeotic) genes regulate the expression of other protein-coding genes during
the process of animal development. Some biologists have likened them to the
conductor of an orchestra who plays the role of coordinating the contributionsof the players. And because Hox genes affect so many other genes, many evodevo advocates think that mutations in these genes can generate large-scalechanges in form.
For example, Jeffrey Schwartz, at the University of Pittsburgh, invokes
mutations in Hox genes to explain the sudden appearance of animal forms in
the fossil record. In his book Sudden Origins, Schwartz acknowledges thediscontinuities in the fossil record. As he notes, “We are still in the dark about
the origin of most major groups of organisms. They appear in the fossil record
as Athena did from the head of Zeus—full-blown and raring to go, in
contradiction to Darwin’s depiction of evolution as resulting from the gradualaccumulation of countless infinitesimally minute variations.”22
What resolves this mystery? Schwartz, an evo-devo advocate, reveals his
answer: “A mutation affecting the activity of a homeobox [Hox] gene canhave a profound effect—such as turning . . . larval tunicates into the firstchordates. Clearly, the potential homeobox genes have for enacting what wecall evolutionary change would seem to be almost unfathomable.”23
But can mutations in Hox genes transform one form of animal life—one
body plan—into another? There are several reasons to doubt that they can.
First, precisely because Hox genes coordinate the expression of so manyother different genes, experimentally generated mutations in Hox genes have
proven harmful. William McGinnis and Michael Kuziora, two biologists who
have studied the effects of mutations on Hox genes, have observed that infruit flies “most mutations in homeotic [Hox] genes cause fatal birthdefects.”24 In other cases, the resulting Hox mutant phenotype, while viable inthe short term, is nonetheless markedly less fit than the wild type. For
example, by mutating a Hox gene in a fruit fly, biologists have produced thedramatic Antennapedia mutant, a hapless fly with legs growing out of its head
where the antennae should be (see Fig. 16.3).25 Other Hox mutations haveproduced fruit flies in which the balancers (tiny structures behind wings thatstabilize the insect in flight, called “halteres”) are transformed into an extra
pair of wings.26 Such mutations alter the structure of the animal, but not in abeneficial or permanently heritable way. The Antennapedia mutant cannot

survive in the wild; it has difficulty reproducing, and its offspring die easily.
Similarly, fruit-fly mutants sporting an extra set of wings lack the musculature
to make use of them and, absent their balancers, cannot fly. As Hungarianevolutionary biologist Eörs Szathmáry notes with cautious understatement in
the journal Nature, “macromutations of this sort [i.e., in Hox genes] areprobably frequently maladaptive.”27

FIGURE 16.3
Photograph of an Antennapedia mutant with a pair of legs growing out of its
head, where antennae would normally develop. Such examples show that
mutations that occur early in animal development and that also produce majorchanges typically result in less fit offspring—in this case offspring that cannot
reproduce. Courtesy Elsevier, Inc.
Second, Hox genes in all animal forms are expressed after the beginning ofanimal development, and well after the body plan has begun to be established.
In fruit flies, by the time that Hox genes are expressed, roughly 6,000 cells
have already formed, and the basic geometry of the fly—its anterior,posterior, dorsal, and ventral axes—is already well established.28 So Hox
genes don’t determine body-plan formation. Eric Davidson and Douglas
Erwin have pointed out that Hox gene expression, although necessary forcorrect regional or local differentiation within a body plan, occurs much later
during embryogenesis than global body-plan specification itself, which isregulated by entirely different genes. Thus, the primary origin of animal bodyplans in the Cambrian explosion is not merely a question of Hox gene action,but of the appearance of much deeper control elements—Davidson’s“developmental gene regulatory networks” (dGRNs).29 And yet, as we saw in
Chapter 13, Davidson argues that it is extremely difficult to alter dGRNs
without damaging their ability to regulate animal development.
Third, Hox genes only provide information for building proteins that

function as switches that turn other genes on and off. The genes that they
regulate contain information for building proteins that form the parts of otherstructures and organs. The Hox genes themselves, however, do not contain
information for building these structural parts. In other words, mutations in
Hox genes do not have all the genetic information necessary to generate newtissues, organs, or body plans.
Nevertheless, Schwartz argues that biologists can explain complex
structures such as the eye just by invoking Hox mutations alone. He assertsthat “[t]here are homeobox genes for eye formation and that when one ofthem, the Rx gene in particular, is activated in the right place and at the righttime, an individual has an eye.”30 He also thinks that mutations in Hox genes
help arrange organs to form body plans.
In a review of Schwartz’s book, Eörs Szathmáry finds Schwartz’s
reasoning deficient. He too notes that Hox genes don’t code for the proteinsout of which body parts are made. It follows, he insists, that mutations in Hox
genes cannot by themselves build new body parts or body plans. As he
explains, “Schwartz ignores the fact that homeobox genes are selector genes.
They can do nothing if the genes regulated by them are not there.”31 Though
Schwartz says he has “marveled” at “the importance of homeobox genes in
helping us to understand the basics of evolutionary change,”32 Szathmáry
doubts that mutations in these genes have much creative power. After asking
whether Schwartz succeeds in explaining the origin of new forms of life byappealing to mutations in Hox genes, Szathmáry concludes, “I’m afraid that,in general, he does not.”33
Nor, of course, do Hox genes possess the epigenetic information necessary
for body-plan formation. Indeed, even in the best of cases mutations in Hox
genes still only alter genes. Mutations in Hox genes can only generate new
genetic information in DNA. They do not, and cannot, generate epigenetic
information.
Instead, epigenetic information and structures actually determine thefunction of many Hox genes, and not the reverse. This can be seen when thesame Hox gene (as determined by nucleotide sequence homology) regulates
the development of different anatomical features found in different phyla. For
instance, in arthropods the Hox gene Distal-less is required for the normal
development of jointed arthropod legs. But in vertebrates a homologous gene(e.g., the Dlx gene in mice) builds a different kind of (nonhomologous) leg.
Another homologue of the Distal-less gene in echinoderms regulates thedevelopment of tube feet and spines—anatomical features classically thought
not to be homologous to arthropod limbs, nor to limbs of tetrapods.34 In eachcase, the Distal-less homologues play different roles determined by thehigher-level organismal context. And since mutations in Hox genes do notalter higher-level epigenetic contexts,35 they cannot explain the origin of thenovel epigenetic information and structure that establishes the context andthat is necessary to building a new animal body plan.36
NEUTRAL OR NONADAPTIVE EVOLUTION
Michael Lynch, a geneticist at Indiana University, has offered a different
mechanism of evolutionary change, and a different explanation for the origin(or growth) of the genome as well as the origin of anatomical novelty. Lynch
proposes a neutral or “non-adaptive” theory of evolution in which natural
selection plays a largely insignificant role. His theory is based on contrastingobservations about the features and strength of evolutionary mechanisms at
work in populations of different sizes.
He observes, first, that in general, the larger the population of organisms,
the lower the mutation rate and (in sexually reproducing eukaryotes) the
higher the rate of genetic recombination. He notes that the genomes oforganisms in larger populations (such as those of bacteria and unicellular
eukaryotic organisms) tend to be smaller and more streamlined—meaning
they have fewer intervening nonprotein-coding sequences (i.e., introns). Most
important, he notes that in large populations, natural selection tends to berelatively effective in eliminating deleterious mutations and fixing beneficial
ones, whereas the process of genetic drift (the tendency for gene variants tobe lost through random processes) plays a relatively less significant role.
By contrast, Lynch observes that small populations—which would include
almost all animal groups—are characterized by higher mutation rates andlower rates of genetic recombination. They also tend to have large genomes
with a lot of nonprotein-coding DNA—introns, pseudogenes, transposons andvarious repetitive DNA elements—as well as gene duplicates. Lynch argues
that in these small populations, natural selection tends to be weak—unable toremove mildly deleterious mutations or to fix mildly beneficial ones
efficiently. As Lynch summarizes, “Three factors (low population sizes, low
recombination rates and high mutation rates) conspire to reduce the efficiencyof natural selection with increasing organism size.”37 Consequently,
nonprotein-coding elements are not removed from the genome, but instead
tend to accumulate, causing the genomes of organisms living in small
populations to grow—even though these sequences may be neutral or evendeleterious. Moreover, in small populations, “neutral” processes such as
random mutation, genetic recombination, and genetic drift predominate intheir effects over natural selection.
What does all this have to do with the origin of animals and the Cambrian
explosion? Evolutionary biologists think that the ancestral groups of theCambrian animals would likely have existed in relatively small populations.
Lynch argues that in small populations, animal genomes will inevitably growover time as nonprotein-coding sections of DNA (as well as gene duplicates)
accumulate due to the weakness of natural selection. He thinks these neutral
mutations drive the evolution and growth of genomic and phenotypiccomplexity in animals. In short, Lynch attempts to explain the expansion of
the genome and the origin of anatomical complexity as the result of neutral,
non-adaptive processes of genetic accretion, rather than as an adaptive
process involving natural selection acting on random mutations. As he states,“Many of the unique complexities of the eukaryotic gene arose by semineutral processes with little, if any, direct involvement of positive
selection.”38
In his work, Lynch has also advanced a powerful mathematical critique ofthe efficacy of the neo-Darwinian mechanism. He has argued that natural
selection plays a lesser role in shaping the features of evolving populations
than many evolutionary theorists have previously assumed—especially in thecase of relatively small populations. Lynch has argued, instead, that random
environmental factors—an organism being in the right place at the right time(near an abundant food source, for example) or in the wrong place at thewrong time (in a drought-stricken region or near an erupting volcano, forexample)—will play a more important role in determining reproductive
success than variations in the fitness of organisms within the same population.
COUNTERINTUITIVE APPROACH
Lynch develops his mathematical critique of the creative power of natural
selection based on the principles of population genetics. Nevertheless, it does
not follow from his analysis showing the weakness of natural selection thatneutral processes alone are sufficient to build new functional genes andproteins. Nor does it follow that neutral processes alone can account for the
many complex anatomical systems that require new sources of genetic (andepigenetic) information for their construction. Indeed, it may seemcounterintuitive, at least from a neo-Darwinian point of view, to think that theaccumulation of random mutations alone can accomplish what neoDarwinists have long invoked both mutations and natural selection to do. In
effect, Lynch’s theory attempts to explain the origin of anatomical complexity
by reference to what would seem on its face to be a less—not a more—potent

mechanism than the one offered by neo-Darwinism. Could such a
counterintuitive theory be correct?
Perhaps, but as a comprehensive theory of how biological information andanatomical complexity arises, Lynch’s neutral theory leaves much to be
desired.
In the first place, Lynch’s theory offers no explanation for some of the
crucial molecular machinery present in eukaryotes—machinery that isnecessary to rendering his mechanism for the accumulation and subsequent
expression of genetic information credible. Recall that Lynch thinks that small
populations of multi-cellular organisms in particular would have inevitably
accumulated many insertional genomic elements. But for the functional
information in these growing genomes to be expressed, the cell must havesome way of excising the non-functional randomly accreting genetic elements—at least, until some of them mutate to the point that they contribute toproducing functional genes and proteins.
Extant eukaryotic organisms depend on a sophisticated molecular machinecalled a spliceosome—a machine that excises introns and fuses together
exons (the portions of the genome that code for proteins) before gene
expression takes place. “This large complex,” observes cell biologist Melissa
Jurica, is “composed of over 150 individual proteins” and several structuralRNAs, and thus “may indeed deserve the moniker ‘the most complicatedmacromolecular machine in the cell.’ ”39
So where do spliceosomes, and the genes necessary to produce them, comefrom? Lynch doesn’t say, though he recognizes, of course, the importance of
this molecular machinery to gene expression and to his scenario. As he
explains, “The problem is that introns are inside genes and get transcribed tomRNA but then have to be spliced out perfectly. If you’re one nucleotide off,
you get a dead transcript.”40 Nevertheless, Lynch’s theory presupposes, butdoes not explain, the origin of the genetic information necessary to produce
the spliceosomes that perform this function. He certainly does not explain theorigin of these massive multi-protein, multi-RNA complexes by reference to
any neutral evolutionary process. Nor can he, since his theory of genomic
accretion and expression presupposes the existence of precisely such intricate
machines. Instead, as my colleague Paul Nelson has put it rather colorfully,“to get Lynch’s theory of genomic accretion up and running, a great deal ofcomplicated molecular machinery must be rolled in from offstage.”
Of course, it could be argued that these machines and systems arose muchearlier with the origin of the eukaryotic cell as the result of selection-driven
evolution in the large populations of simpler unicellular organisms in which,according to Lynch’s theory, natural selection played a more significant role.

Nevertheless, Lynch does not make that argument—and for good reason.
Most evolutionary biologists today recognize the origin of the eukaryotic cell
as a completely unsolved problem—unexplained by either neutral or adaptive
theories of evolution.41
Of course, insofar as these molecular machines are present in even onecelled eukaryotic organisms, they would have arisen, presumably, well before
the origin of animals. Thus, explaining their origin is not, strictly speaking,directly relevant to explaining the Cambrian explosion. Nevertheless, Lynch’s
inability to account for their origin reflects directly on the credibility of his
theory—at least insofar as it seeks to offer a comprehensive account of themechanisms by which biological information and complexity arise during thehistory of life.
Drifting In and Out
In any case, there are good reasons to doubt that Lynch’s neutral mechanism
could generate the novel biological information and form necessary to explain
the origin of animals, even granting the prior existence of the molecularmachinery (in small populations of eukaryotic organisms) that his scenario
requires.
First, Lynch assumes a false gene-centric view of the origin of biologicalform. As he writes: “Most of the phenotypic diversity that we perceive in thenatural world is directly attributable to the peculiar structure of the eukaryotic
gene.”42 His view overlooks the crucial role of epigenetic information andstructure in the origin of animal form discussed in Chapter 14 and, therefore,
does nothing to explain its origin.
Second, neutral processes such as genetic drift do not favor beneficial
mutations, and thus do not fix, with any efficiency, those mutation-induced
genetic traits in small populations.43 Natural selection, as we saw in Chapter
10, is something of a double-edged sword. On the one hand, natural selection
helps to fix beneficial traits in a population. On the other hand, natural
selection also makes it difficult for functional genes to vary widely without
being eliminated. Neutral theories of evolution attempt to avoid the latterproblem by invoking gene duplication and other processes that can add
nonfunctional sequences to the genome—sequences that are unaffected, atleast initially, by selective pressure. In so doing, however, these theoreticalformulations significantly diminish the role of natural selection as amechanism that can fix beneficial mutations in place once they have arisen.
Thus, in all neutral theories, including Lynch’s, any beneficial mutations thatarise and begin to drift through a population, can just as readily—without asignificant influence from natural selection to impede it—drift out of a
population as well. This limitation vastly increases the time it will take forneutral processes to fix beneficial genetic changes in a population. Bothskeptics and proponents of neo-Darwinism have recognized this deficiency in
Lynch’s model.44
Third, and most important, Lynch’s theory not only fails to account for the
fixation of new genes and traits in small populations, it also fails to accountfor their origin. Lynch’s mechanism of neutral mutational change does
envision the addition of brute genomic complexity as the result of theaccretion of preexisting genetic elements (introns, transposons, pseudogenes
and gene duplicates). Nevertheless, the addition of these elements does not
generate any novel functional (or specified) genetic information. Instead, it
merely transfers preexisting genetic sequences from one organismal context
where those sequences may have performed a function, to another where they
likely will not. Indeed, the point of neutral theory is to postulate the additionof genetic elements that, initially, do not perform crucial functions such thatthey can experience mutations without deleterious consequence to theorganism. Lynch himself assumes that these added elements will not performfunctions in their new context, which is why he envisions the need for
spliceosomes to excise them, at least initially.
Instead, for Lynch’s theory to explain the origin of new and functional
genes and proteins (and the anatomical complexities that depend on them), histheory would have to solve the problem of combinatorial inflation discussed
in Chapter 10. He would have to show that purely random mutations could
efficiently search the relevant combinatorial space of possible sequences
corresponding to a given novel functional gene or protein.
Nevertheless, Lynch does not even address the problem of combinatorial
inflation or the closely related problem of the rarity of genes and proteins insequence space. He provides no experimental evidence that recombination
and/or mutation (given genetic drift) will actually produce functional or
specified genetic complexity. Instead, the examples he provides are entirely
hypothetical. In addition, he offers no reason to think that the probability of a
successful search for functional genes or proteins would be any higher (i.e.,
more likely to occur) than the probabilities calculated in Chapter 10. He does
not, therefore, answer the challenge of the problem of combinatorial inflationand the rarity of functional genes and proteins in sequence space.
Lynch does provide, perhaps, a more detailed characterization than otherneutral theories of where neutral, nonadaptive processes must predominate.
Nevertheless, he does not show that such processes—random genetic
mutations unhinged from natural selection—are sufficient to generate novel

functional genes and proteins, let alone complex anatomical novelties
requiring the origin of many such genes and proteins. Instead, as Axe’s
experimental results have shown, random mutations of whatever kind will notgenerate enough trials to render probable (or plausible) a successful search of
the sequence space corresponding to a given functional gene or protein.
LYNCH AND WAITING TIMES
Lynch does argue in one paper that neutral evolutionary processes cangenerate new complex adaptations—adaptations requiring multiple
coordinated mutations—within realistic waiting times. In particular, writing ina recent paper with colleague Adam Abegg of St. Louis University, he argues
that “conventional population genetic mechanisms” such as random mutationand genetic drift can cause the “relatively rapid emergence of specificcomplex adaptations.”45 Lynch makes two specific claims in this regard. First,
he claims that in large populations, arbitrarily complex adaptations can occur
if the mutational intermediates are neutral in their effects on the organism.
That is, Lynch purports to show that in large microbial populations, complex
adaptations requiring a virtually unlimited number of mutations can occur
within realistic waiting times. According to Lynch, this can occur provided
that each mutation in a series of mutations has neutral (but not deleterious)
effects on the organism. Second, Lynch argues that even though it generally
takes longer to build complex traits in small populations, such traits can still
evolve within realistic waiting times provided, again, that the mutational
intermediates are neutral in their effects. In fact, he concludes that “theelevated power of both random genetic drift and mutation may enable theacquisition of complex adaptations in multicellular species at rates that are notappreciably different from those achievable in enormous microbial
populations.”46
Though Lynch makes these assertions in the context of a densely
mathematical scientific article, the significance of his claims, if true, canhardly be overstated. In essence, he claims that his population genetics–based
mathematical model shows that purely random mutations and genetic drift
can generate extremely complex adaptations in realistic waiting times—that
his neutral evolutionary theory solves the problem of complex adaptations andlong expected waiting times discussed in Chapter 12.
But some things are just too good to be true, and it turns out that Lynch
and Abegg made a subtle but fundamental mathematical error in coming totheir conclusion. Appropriately, perhaps, the first person to demonstrate that
Lynch’s incredible claim was problematic was Douglas Axe. Although Axe

could see that much of the math in Lynch’s paper with Abegg was correct,
Axe suspected from his own calculations and experiments that they had madesome crucial error. In the end, he traced Lynch and Abegg’s claims to twoerroneous equations, both of which were based on an erroneous assumption.
In essence, Lynch and Abegg assumed that organisms will acquire a given
complex adaptation by traversing a direct path to the new anatomical
structure. Each mutation would build on the previous one in the most efficientmanner possible—with no setbacks, false starts, aimless wandering, or
genetic degradation—until the desired structure or system (or gene) isconstructed. Thus, they formulated an undirected model of evolutionarychange, and one that assumes, moreover, that there is no mechanism available(such as natural selection) that can lock in potentially favorable mutationalchanges on the way to some complex advantageous structure. Nevertheless,they calculated the waiting times required to produce such structures as if aprocess for locking in potentially advantageous changes did exist, and as if
their undirected and purely random mechanism was in some way directed tothese functionally propitious outcomes. As Axe notes in a trenchantmathematical critique of Lynch and Abegg’s argument, “Of all the possible
evolutionary paths a population can take, the analysis of Lynch and Abegg
considers only those special paths that lead directly to the desired end—thecomplex adaptation.”47
Yet nothing in Lynch’s neutral model ensures that potentially advantageous
mutations will remain in place while other mutations accrue. As Axe explains,“Productive changes cannot be ‘banked’, whereas Equation 2 [one of Lynch’s
equations] presupposes that they can.”48 Instead, Axe shows, mathematically,that degradation (the fixation of mutational changes that make the complex
adaptation less likely to arise) will occur much more rapidly than constructive
mutations, causing the expected waiting time to increase exponentially.
The illustration I developed in Chapter 10 to explain the problem facing
neutral models of gene evolution may help illuminate the mistaken
assumption underlying Lynch and Abegg’s calculations. Recall from thatchapter that my hypothetical blindfolded man dropped in the middle of anenormous shark-free pool did not face any predators (by analogy the purifying
effects of natural selection). But he still faced the problem of finding theladder at the edge of the enormous body of water (by analogy, the need tosearch an enormous number of possible mutational paths and possible
sequences to find the rare functional ones). Now suppose someone were to
calculate how long on average it would take for the blindfolded man to swim
to the ladder at the edge of the enormous pool. If someone simply divided the
distance to the ladder at the edge of the pool by the maximum speed that man

could swim, he or she would get a fantastically optimistic estimate of theseverity of the problem facing our unfortunate swimmer. Why? Because
calculating the probable waiting time in this manner would overlook the main
problem the man faced, namely, the man does not know where the ladder is or
how to get there. Nor does he have any way to gauge his progress.
Thus, any realistic estimate of how long it will actually take him to swim
to the ladder—as opposed to an estimate of the theoretically fastest routepossible—must take into account his probable aimless wandering, fits andstarts, swimming in circles and drifting in various directions. Similarly, Lynch
and Abegg fail to reckon in their calculation on the random, undirected and,literally, aimless nature of the mechanism that they propose. Instead, they
mistakenly assume that neutral processes of evolution will make a beeline forsome specific complex adaption. In fact, these processes will—in allprobability—also wander aimlessly in a vast sequence space of neutral,
functionless possibilities with nothing to direct them, or preserve them in any
forward progress they happen to make, toward the rare and isolated islands offunction represented by complex adaptations. For this reason, Lynch vastly
underestimates the waiting times required to generate complex adaptations
and, therefore, does not solve the problem of the origin of genes and proteinsor any other complex adaptation. Instead, Axe shows in his own mathematicalmodel, which accompanies his critique of Lynch, that the waiting times
problem is just as severe as he (Axe) had previously calculated.
NEO-LAMARCKIAN EPIGENETIC INHERITANCE
The third element of the neo-Darwinian triad concerns the transmission andinheritance of genetic information. Not surprisingly, a new version ofevolutionary theory questions the neo-Darwinian understanding of heredity as
well.
Darwin himself lacked an accurate theory of how features of organisms aretransmitted from one generation to the next. He thought that changes inorganisms that occurred during their lifetimes, as the result of the “use anddisuse” of different organs and anatomical systems, would be transmitted tooffspring through reproduction.49 In this respect, his theory of inheritanceresembled that of an earlier evolutionary theorist, Jean-Baptiste de Lamarck(1744–1829), who also believed in the inheritance of acquired characteristics.
Lamarckian mechanisms, although unsupported by any evidence at thetime, came to play an increasingly important role in Darwin’s thinking, as
criticisms of natural selection caused Darwin to place more weight on the
direct influence of the environment in evolutionary change. Indeed, by thesixth edition of the Origin (1872), Darwin specifically emphasized theimportance of these modes of inheritance.50
But with the rediscovery of Mendel’s laws in 1900 and the identification ofchromosomes as the material entity responsible for the transmission of
inheritance, Lamarckian theories of inheritance fell out of favor. Following
the rise of the neo-Darwinian synthesis, most evolutionary biologists came toregard the gene as the locus of all heritable change in the organism. And after
1953, biologists equated the gene with specifically arranged nucleotide bases
within the DNA molecule.
Recently, however, as more biologists have recognized that somebiological information—epigenetic information—resides in structures outsideof DNA, interest has grown in the possibility that these nongenetic sources of
information may influence the course of evolution. The discovery that
epigenetic information can be altered and directly inherited independently of
DNA has attracted further attention. This discovery has, in turn, led to theformulation of a contemporary “neo-Lamarckian”51 theory that envisionschanges in the nongenetic structures of an organism affecting subsequent
generations.
Today, prominent defenders of neo-Lamarckism include Eva Jablonka, of
Tel Aviv University, and Massimo Pigliucci, of the City University of New
York. Lamarck, of course, knew nothing about the role of genes and believedthat inheritance of acquired characteristics was an important driving force inevolution. Modern neo-Lamarckians, fully apprised of the reality of genetic
inheritance, nevertheless think that nongenetic sources of information andstructure may play some role in the evolution of biological form. According
to Jablonka, neo-Lamarckism “allow[s] evolutionary possibilities denied bythe ‘Modern Synthesis’ version of evolutionary theory, which states thatvariations are blind, are genetic (nucleic acid–based), and that saltational
events do not significantly contribute to evolutionary change.”52
Jablonka has collected several categories of evidence in support of what
she calls “epigenetic inheritance systems.” In the first place, in some singlecelled organisms (such as E. coli and yeast) environmentally induced changes
in metabolic pathways can be transmitted to the next generation
independently of any changes in the cell’s DNA. Second, she notes thatstructural information mediating organismal form (and function) does passfrom parent to offspring independently of DNA, via membranes and otherthree-dimensional cellular patterns.
Third, she discusses the process of DNA methylation—a process in which
special enzymes attach a methyl group (CH3) to nucleotide bases within thedouble helix. Processes like this can alter gene regulation and chromatin
structure. Jablonka notes that the changes produced by processes that alter
gene regulation are often transmitted to subsequent generations of cells
without any changes to DNA base sequences. Finally, she cites a process
called “RNA-mediated” epigenetic inheritance, a recently discovered
phenomenon. Here, small RNAs, again acting in concert with special
enzymes, affect gene expression and chromatin structure, and thesemodifications appear to be heritable independently of genes.
Can any of these mechanisms help to explain the origin of animal form in
the Cambrian explosion? Not really.
By its nature, macroevolution requires stable—meaning permanently
heritable—changes. But Jablonka’s evidence shows that where nongenetic
inheritance occurs in animals, it involves structures that either (a) do notchange (such as membrane patterns and other persistent templates ofstructural information), or (b) do not persist over more than several
generations. And neither case generates significant evolutionary innovation in
animal form. Instead, for directional evolutionary change to occur in a
population of organisms, changes must not only be heritable, but permanent.
Stability—the irreversible and enduring heritability of traits—is a logicallyinescapable requirement for any theory of evolution. This is precisely what“descent with modification” means.
And here Jablonka’s evidence for stable nongenetic inheritance isequivocal at best, as she readily admits. Reviewing Jablonka’s assembled data
for animals reveals no case where an induced epigenetic change persisted
permanently in any population. The heritability of such changes is transient,lasting (depending on the species in question) from a few generations up to
forty.
Jablonka candidly addresses this lack of evidence for stability, noting, “We
believe that epigenetic variants in every locus in the eukaryotic genome canbe inherited, but in what manner, for how long, and under what conditions,
has yet to be qualified.”53 Consequently, despite its intriguing aspects, theevolutionary significance of neo-Lamarckian epigenetic inheritance remains
uncertain or, in Jablonka’s own words, “inevitably, somewhat speculative.”54
NATURAL GENETIC ENGINEERING
University of Chicago geneticist James Shapiro has formulated another postDarwinian perspective on how evolution works that he calls “natural genetic
engineering.” Shapiro has developed an understanding of evolution that takes
account of the integrated complexity of organisms as well as the importanceof nonrandom mutations and variations in the evolutionary process.
He observes that organisms within a population often modify themselvesin response to different environmental challenges. He cites evidence showingthat when populations are challenged by environmental stresses, signals, ortriggers, organisms do not generate mutations or make genetic changes
randomly, that is, without respect to, or unguided by, their survival needs.
Instead, they often respond to environmental stresses or signals by inducing
mutations in a directed or regulated way. As he explains, “The continued
insistence on the random nature of genetic change by evolutionists should be
surprising for one simple reason: empirical studies of the mutational process
have inevitably discovered patterns, environmental influences, and specificbiological activities at the roots of novel genetic structures and altered DNA
sequences.”55
The depth of Shapiro’s challenge to orthodox neo-Darwinism is profound.
He rejects the randomness of novel variation that Darwin himself emphasized
and that neo-Darwinian theorists throughout the twentieth century havereaffirmed.56 Instead, he favors a view of the evolutionary process thatemphasizes preprogrammed adaptive capacity or “engineered” change, whereorganisms respond in a “cognitive” way to environmental influences,
rearranging or mutating their genetic information in regulated ways tomaintain viability.
As an example, Shapiro notes that—contrary to the neo-Darwinianassumption that “DNA alterations are accidental”57—all organisms possess
sophisticated cellular systems for proofreading and repairing their DNA
during its replication. He notes that these systems are “equivalent to a qualitycontrol system in human manufacturing,” where the “surveillance andcorrection” functions represent “cognitive processes, rather than mechanicalprecision.”58
As an example of regulated mutation, Shapiro observes that in response toenvironmental assault—UV damage from sunlight or the presence of an
antibiotic, for instance—bacteria activate what is known as the “SOS
response” system. This system makes use of specialized error-prone DNApolymerases, normally left unexpressed, that are synthesized and set into
action, allowing the population to generate a much wider range of genetic
variation than usual. Bacterial cells regulate this process using a DNAbinding protein known as LexA, which normally represses the error-prone
polymerases. When the SOS system is activated by environmental damage,the production of LexA first drops dramatically, allowing expression of theerror-prone polymerases, but then rises, which “ensures that as soon as DNA

repair occurs . . . LexA [will] reaccumulate and repress the SOS genes.”59
This system allows cells to “replicate DNA that carries unrepaired damage,”60
keeping their essential replication machinery moving past a stall, in theabsence of which the bacterium would die.
An analogy may help to illustrate what the cell is doing when confronted
with an environmental challenge. Imagine a military unit, a combined armor
and infantry battalion, crossing an open plain. Suddenly, the battalion falls
under a fierce, unrelenting enemy artillery barrage, wounding many of its
soldiers. To keep the wounded alive until the barrage ceases or reinforcements
arrive, the commander instructs certain members of the unit with destructive
skills to disassemble (in military jargon, “cannibalize”) a few of the tanks toprovide temporary armored cover from further incoming shells. His order tells
them, however, to cease their tank-modifying actions as soon as the barrageends. That is, the unit as a whole tolerates “damage” to some of its equipment
to save as many of its members as possible.
In the same way, while at one level their “error-prone” role may appear
counterintuitive, these mutation-generating DNA polymerases of the SOS
system actually constitute essential hardware in the cell’s defensive armory.61
From Shapiro’s perspective, this survival strategy does not exemplify
Darwinian randomness, but rather sophisticated preprogramming, an“apparatus that even the smallest cells possess” to maintain viability.62 What’smore, the carefully regulated expression of the SOS response provides
evidence that cells employ the system only when needed.63
In addition to ramping up their mutation rates in specific sections of the
genome, cells may also change the way they express the genetic informationthat they already carry, expressing some genes that were previously
unexpressed and suppressing others. Organisms in populations underparticular stresses may retrieve and access modular elements of genetic
information stored in disparate locations on the genome or even on different
chromosomes. Cells will then assemble, or concatenate, those modular
elements to form a new gene or RNA-transcript capable of directing thesynthesis of a novel protein or proteins that can help the organism survive.
Shapiro argues that these and other kinds of directed, rather than random,
genetic changes and responses to stimuli occur under “algorithmic control.”He describes the cell as “a powerful real-time distributed computing
system”64 implementing various “if-then” subroutines. This emphaticallychallenges one of the three key elements of the neo-Darwinian triad: the claimthat mutations and variations occur in a strictly random way.
During the last fifteen years, Shapiro has published a series of fascinatingpapers about the newly discovered capacities of cells to direct or “engineer”
the genetic changes they need to remain viable in a range of environmental
conditions. His work represents a promising avenue of new biologicalresearch, bringing insight into how the cell’s information-processing systemmodifies and directs the expression of its genetic information in real time inresponse to different signals. Shapiro’s work also provides new insights into
how observable evolutionary changes occur in living populations.
Could it, then, also provide a solution to the problem of the origin of theinformation necessary to build an animal body plan? It could, except for one
question that Shapiro’s otherwise brilliant characterization of how organisms
modify themselves doesn’t address.
Where does the programming come from that accounts for the“preprogrammed adaptive capacity” of living organisms? If, as James Shapiro
argues, natural selection and exclusively random mutations don’t produce thisinformation-rich pre-programming, then what did? In the next chapters, I’ll
propose an answer to precisely this question.

17
The Possibility of Intelligent Design
The owner of a remote island estate has been murdered while out riding.
When the local sheriff arrives, he learns there are several obvious suspects:
the volatile gamekeeper, the owner of a neighboring estate with whom themurder victim has had a long-running feud, and the estate owner’s estranged
wife, who had been living on the island in a small mother-in-law cottage. The
sheriff quickly learns the basic facts of the case. The victim was found dead,facedown on the beach, with his horse standing nearby. Any one of the threesuspects could have taken a rifle, from an unlocked shed at the edge of theproperty. All were healthy enough to have hiked to the scene of the crime.
Each of them has a motive. And none has an alibi.
But as the investigation unfolds additional facts come to light. Most
importantly, when the coroner arrives, he determines that although the victim
was shot in the stomach and then his head was harshly bludgeoned by the buttof the rifle, these injuries served merely to conceal the bullet wound that
actually killed the estate owner. The man was dead when he hit the ground.
What killed him was a perfect shot entering the head just behind the right ear,exactly where an expert marksman would place a bullet. Moreover, ballistics
shows that this bullet came from a different gun altogether from the one
stored in the shed, a weapon likely fired from quite a distance.
The sheriff then returns to the list of suspects and, one by one, eliminates
them. Abundant evidence shows that none of the three prime suspects is aparticularly good shot, much less a world-class marksman. The landowner’s
estranged wife has a shaky hand and no experience with firearms. The volatile
gamekeeper has extremely poor eyesight. And the neighboring landowner
turns out to have an alibi after all—as well as a broken arm, which would
have prevented him from holding the kind of rifle from which the bullet was
fired. There is, however, one other person living on the estate, though noteven the other suspects suspect him. He is the victim’s loyal and longtime
personal assistant, a timorous older man much beloved by both the family andthe other servants. No one wants to consider him as a possible suspect. But isit possible that he could have had something to do with the crime after all?
Might an unexpected suspect—indeed “the butler”—have done it?
Clearly, standard evolutionary theory has reached an impasse. Neither neoDarwinism nor a host of more recent proposals (punctuated equilibrium, selforganization, evolutionary developmental biology, neutral evolution,
epigenetic inheritance, natural genetic engineering) have succeeded in
explaining the origin of the novel animal forms that arose in the Cambrianperiod. Yet all these evolutionary theories have two things in common: they
rely on strictly material processes, and they also have failed to identify acause capable of generating the information necessary to produce new formsof life.
This raises a question. Is it possible that a different or unexpected kind of
cause might provide a more adequate explanation for the origin of the newform and information—as well as the other distinctive features—present in
the Cambrian explosion? In particular, is it possible that intelligent design—
the purposeful action of a conscious and rational agent—might have played arole in the Cambrian explosion?
INTRODUCING INTELLIGENT DESIGN
When the case for intelligent design is made, it’s often hard to get
contemporary evolutionary biologists to see why such an idea should even beconsidered or why discussions of design should play any role in biology at all.
Though many biologists now acknowledge serious deficiencies in current
strictly materialistic theories of evolution, they resist considering alternatives
that involve intelligent guidance, direction, or design.
Much of this resistance seems to come simply from not understanding
what the theory of intelligent design is. Many evolutionary biologists see
intelligent design as a religiously based idea—a form of biblical creationism.
Others think the theory denies all forms of evolutionary change. But contrary
to media reports, intelligent design is not a biblically based idea, but instead
an evidence-based theory about life’s origins—one that challenges some, but
not all, meanings of the term “evolution.”
Perhaps the best way to explain the theory of intelligent design is tocontrast it with the specific aspect of the theory of Darwinian evolution that it
directly challenges. Recall from our opening discussion in Chapter 1 that theterm “evolution” has many different meanings and that Darwin’s theory of
evolution by natural selection affirmed several of them: first, change overtime; second, universal common descent; and third, the creative power ofnatural selection acting on random variations. In affirming this third meaning

of evolution, both classical Darwinism and modern neo-Darwinism alsoaffirm what neo-Darwinist Richard Dawkins has called the “blindwatchmaker” hypothesis. This hypothesis holds that the mechanism of natural
selection acting on random genetic variations (and mutations) can produce notjust new biological form and structure, but also the appearance of design inliving organisms.1
Darwin argued for this idea in The Origin of Species as well as in his
letters. Recall the sheep breeding illustration from Chapter 1 where I
described how both intelligent human breeders and environmental change (aseries of bitterly cold winters) might produce an adaptive advantage in a
population of sheep. During the nineteenth century, biologists regarded theadaptation of organisms to their environment as one of the most powerfulpieces of evidence of design in the living world. By observing that natural
selection had the power to produce such adaptations, Darwin not only
affirmed that his mechanism could generate significant biological change, butthat it could explain the appearance of design—without invoking the activityof an actual designing intelligence. In doing so, he sought to refute the design
hypothesis by providing a materialistic explanation for the origin of apparent
design in living organisms. Modern neo-Darwinists also affirm that organisms
look as if they were designed. They also affirm the sufficiency of anunintelligent natural mechanism—mutation and natural selection—as an
explanation for this appearance. Thus, in both Darwinism, and neoDarwinism, the selection/variation (or selection/mutation) mechanism
functions as a kind of “designer substitute.” As the late Harvard evolutionary
biologist Ernst Mayr explains: “The real core of Darwinism . . . is the theoryof natural selection. This theory is so important for the Darwinian because it
permits the explanation of adaptation, the ‘design’ of the natural theologian,by natural means.”2 Or as another prominent evolutionary biologist, Francisco
Ayala, has put it succinctly, natural selection explains “design without adesigner.”3
Other contemporary neo-Darwinian biologists including Richard Dawkins,
Francis Crick, and Richard Lewontin have also emphasized that biologicalorganisms only appear to have been designed.4 They recognize that many
biological structures—whether the chambered nautilus, the compound eye ofa trilobite, the electrical system of the mammalian heart, or numerous
molecular machines—attract our attention because the sophisticatedorganization of such systems is reminiscent of our own designs. Dawkins has
noted, for example, that the digital information in DNA bears an uncanny
resemblance to computer software or machine code.5 He explains that manyaspects of livings systems “give the appearance of having been designed for a
purpose.”6
Nevertheless, neo-Darwinists regard that appearance of design as entirely
illusory, as did Darwin himself, because they think that purely mindless,materialistic processes such as natural selection and random mutations can
produce the intricate designed-like structures in living organisms. In this view,
natural selection and random mutation mimic the powers of a designing
intelligence without themselves being intelligently directed or guided in any
way.
That’s where the theory of intelligent design comes into play. Intelligent
design challenges the idea that natural selection and random mutation (andother similarly undirected materialistic processes) can explain the moststriking appearances of design in living organisms. Instead, it affirms that
there are certain features of living systems that are best explained by thedesign of an actual intelligence—a conscious and rational agent, a mind—as
opposed to a mindless, materialistic process. The theory of intelligent design
does not reject “evolution” defined as “change over time” or even universal
common ancestry, but it does dispute Darwin’s idea that the cause of major
biological change and the appearance of design are wholly blind andundirected.
Nor does the theory seek to insert into biology an extraneous religious
concept. Intelligent design addresses a key scientific question that has long
been part of evolutionary biology: Is design real or illusory? Indeed, part ofwhat Darwin set out to explain was precisely the appearance of design. Withcurrent materialistic evolutionary theories now failing to explain many of themost striking appearances of design in the Cambrian animals, including thepresence of digital information as well as other complex adaptations, thepossibility emerges that these appearances of design may not be justappearances after all. The Darwinian formulation of evolutionary theory in
opposition to the design hypothesis,7 coupled with the inability of neoDarwinian and other materialistic theories to account for salient appearancesof design, would seem logically to reopen the possibility of actual (as opposed
to apparent) design in the history of animal life.
Either life arose as the result of purely undirected material processes or a
guiding or designing intelligence played a role. Advocates of intelligent
design favor the latter option and argue that living organisms look designed
because they really were designed. Design proponents argue that living
systems exhibit telltale indicators of prior intelligent activity that justify thisclaim, indicators that make intelligent design scientifically detectable fromthe evidence of the living world.

But that, for many evolutionary biologists, is precisely the rub. Because
they think of intelligent design as a religiously based idea, they understandthat people might want to affirm the intelligent design of life as part of theirreligious beliefs—but not as a consequence of scientific evidence. Indeed,most evolutionary biologists don’t see how the idea of intelligent design could
contribute to a scientific explanation of life’s origins, nor do they see how
intelligent design could ever be detected or inferred scientifically fromevidence in nature. Exactly how would researchers justify such an inference?
MY STORY
When I left for my graduate studies in England in 1986, I was asking a similar
set of questions. At that time, I wasn’t thinking about the scientific legitimacyof the intelligent design hypothesis as an explanation for the origin ofanimals. Instead, I wanted to know if intelligent design could help explain theorigin of life itself. My questions eventually led me to learn about adistinctive method of historical scientific inquiry. That discovery led me to amethod of reasoning that allows for the detection or inference of past causes,
including intelligent causes.
A year earlier, in 1985, I had met one of the first contemporary scientists torevive the idea that intelligent design might have played a causal role in theorigins of life. Chemist Charles Thaxton (see Fig. 17.1) had recently
published a book, The Mystery of Life’s Origin. His coauthors were polymer
scientist and engineer Walter Bradley and geochemist Roger Olsen. Theirbook received acclaim as a groundbreaking critique of current theories ofchemical evolution. They showed that attempts to explain the origin of thefirst living cell from simpler nonliving chemicals had failed and that these
theories had specifically failed to explain the origin of the informationnecessary to produce the first life.
But it was in the book’s epilogue that the three scientists proposed aradical alternative. There they suggested that the information-bearing
properties of DNA might point to the activity of a designing intelligence—tothe work of a mind, or an “intelligent cause” as they put it.8 Drawing on theanalysis of the British-Hungarian physical chemist Michael Polanyi, theyargued that chemistry and physics alone could not produce the information in
DNA any more than ink and paper alone could produce the information in a
book. Instead, they argued that our uniform experience suggests a cause-andeffect relationship between intelligent activity and the production of
information.9

FIGURE 17.1
Charles Thaxton. Courtesy Charles Thaxton.
At the time the book appeared, I was working as a geophysicist for an oil
company in Dallas where Thaxton happened to live. I met him at a scientificconference and became intrigued by his work. Over the next year, I began
dropping by his office to discuss his book and the radical idea he wasdeveloping about DNA.
The first part of Thaxton’s argument made sense to me. Experience does
indeed seem to affirm that (specified or functional) information typicallyarises from the activity of intelligent agents, from minds as opposed tomindless, material processes. When a “tweet” appears on your smart phone’s
Twitter feed (if you’re into that kind of thing), it clearly originated first in themind of a person who created a Twitter account, scripted the “tweet,” andthen sent it out across the Internet. Information does arise from minds.
But Thaxton went further. He acknowledged that most branches of science
didn’t consider intelligent activity as an explanation because, he thought,
intelligent agents don’t usually generate repeatable or predictable phenomena
and because they are difficult to study under controlled laboratory conditions.
Nevertheless, Thaxton argued that scientists might propose an intelligent
cause as a positive scientific explanation for some events in the past, as part ofa special mode of scientific inquiry he called origins science. He noted thatscientific disciplines such as archaeology, evolutionary biology, cosmology,
and paleontology often infer the occurrence of singular, nonrepeatable eventsand that the methods used to make such inferences could help scientists
identify positive indicators of intelligent causes in the past as well.
Here I wasn’t initially so sure. Thaxton’s ideas about a distinctive methodof science concerned with origins, or at least with the past generally, seemed
intuitively plausible. After all, evolutionary biologists and paleontologists doseem to use a method of investigation different from that employed bylaboratory chemists. Nevertheless, I wasn’t exactly sure what those methods
were, how they were different from those used in other sciences, and whether
using them in any way justified considering intelligent design as a scientifichypothesis.
So the next year when I left Dallas, Texas, for Cambridge, England, topursue my studies in the history and philosophy of science, I had a lot on mymind. Is there a distinctive method of historical scientific inquiry? If so, doesthat method of reasoning and investigation justify a scientific reformulation of
the design hypothesis? In particular, does the intuitive connection between
information and the prior activity of a designing intelligence justify a positive(historical) scientific inference to intelligent design? Does it make intelligent
design detectable?
HISTORICAL SCIENTIFIC METHOD AND THE DESIGNHYPOTHESISIn my research, I discovered that historical scientists often do make inferenceswith a distinctive logical form. This type of inference is known technically as
an abductive inference.10 During the nineteenth century, American logician C.
S. Peirce characterized this mode of reasoning and distinguished it from twobetter-known forms, inductive and deductive reasoning. He noted that in
inductive reasoning, general rules are inferred from particular facts, whereas
in deductive reasoning, general rules are applied to particular facts in order todeduce specific outcomes. In abductive reasoning, however, inferences areoften made about past events or causes based on present clues or facts.11
To see the difference between these three types of inference, consider thefollowing argument forms:
Inductive argument:
A1 is B.
A2 is B.
A3 is B.
A4 is B.

An is B.
All A’s are B.
Deductive argument:
MAJOR PREMISE: If A has occurred, then B will follow as a matter of course.
MINOR PREMISE: A has occurred.
CONCLUSION: Hence, B will follow as well.

Abductive argument:
MAJOR PREMISE: If A occurs, then B would be expected as a matter ofcourse.
MINOR PREMISE: The surprising fact B is observed.
CONCLUSION: Hence, there is reason to suspect that A has occurred.

Note the difference between deductive and abductive forms of inference.
In deduction, the minor premise affirms the antecedent variable (“A”), while
the conclusion deduces the consequent variable (“B”), an anticipatedoutcome. In this sense, deductive inferences look forward to something thatwill happen in the future. A classic illustration of deductive reasoning has thischaracter:
MAJOR PREMISE: All men are mortal.
MINOR PREMISE: Socrates is a man.
CONCLUSION: Therefore, Socrates is a mortal (i.e., he will die).

In an abductive argument, the minor premise affirms the consequentvariable (“B”) and its conclusion infers the antecedent variable (“A”)—thevariable referring to something that went before, either logically or
temporally. Abductive reasoning, thus, often affirms a past occurrence. For
this reason, forensic or historical scientists such as geologists, paleontologists,archaeologists, and evolutionary biologists often use abductive reasoning toinfer past conditions or causes from present clues. As Stephen Jay Gould
notes, historical scientists typically “infer history from its results.”12
For example, a geologist might reason as follows:
MAJOR PREMISE: If a mudslide occurred, we would expect to find felledtrees.

MINOR PREMISE: We find evidence of felled trees.
CONCLUSION: Therefore, we have reason to think that a mudslide may haveoccurred.
In the deductive form, if the premises are true, the conclusion follows withcertainty. The logic of the abductive arguments is different, however.
Abductive arguments do not produce certainty, but instead merely plausibility
or possibility. To see why, consider the following variation of the preceding
abductive argument:
MAJOR PREMISE: If a mudslide occurred, we would expect to find felledtrees.
MINOR PREMISE: We find felled trees.
CONCLUSION: Therefore, a mudslide occurred.

or symbolically:
MAJOR PREMISE: If MS, then FT.
MINOR PREMISE: FT.
CONCLUSION: Therefore, MS.

Notice that unlike the first version of the abductive argument in which theconclusion was stated tentatively (“We have reason to think that a mudslide
may have occurred”), in this version the conclusion is affirmed definitively(“A mudslide occurred”). Obviously, this latter form of argument has aproblem. It does not follow that, because the trees have fallen, a mudslide
necessarily occurred. The trees may have fallen for some other reason. A
hurricane may have blown them down; perhaps an ice storm occurred and thetrees fell under the weight of accumulating ice; or loggers may have cut them
down. In logic, affirming the consequent variable of a minor premise (withcertainty) constitutes a formal fallacy—a fallacy that derives from the failure
to acknowledge that more than one cause (or antecedent) might produce thesame evidence (or consequent).
Even so, the presence of downed timber might indicate that a mudslide has
occurred. Thus, amending the above argument to conclude: “We have reason
to think that a mudslide may have occurred” does not commit a fallacy. Even
if we may not affirm the consequent with certainty, we may affirm it as apossibility. This is precisely what abductive reasoning does. It provides areason for considering that a hypothesis—and often a hypothesis about the
past—might be true, even if one cannot affirm the hypothesis (or conclusion)

with certainty.13
THE METHOD OF MULTIPLE COMPETING HYPOTHESES
To address this limitation in abductive reasoning and to make it possible tostrengthen inferences about the past, the nineteenth-century geologist Thomas
Chamberlain developed a form of reasoning he called “the method of multiple
working hypotheses.”14 Historical and forensic scientists employ this method
when more than one cause or hypothesis can account for the same evidence.
They use it to adjudicate between competing hypotheses by comparing themto see which one best explains not just one piece of evidence but, usually, awider class of relevant facts.
For example, consider how this method of reasoning was used to establish
the hypothesis of continental drift as the best explanation for a wide range of
geological observations. During the early 1900s, a German geologist andmeteorologist named Alfred Wegener became fascinated with the way theAfrican and South American continents fit together on the map like pieces ofa jigsaw puzzle.15 He proposed that the continents had once been fused
together as a single giant continent that he called “Pangea,” which later
separated and drifted apart.
Initially, many geologists ridiculed Wegener’s idea. They thought that—given the vast distances separating the continents—the matching shapes weremost likely just a coincidence. Wegener’s critics dismissed his theory ofcontinental drift as “delirious ravings,” “Germanic pseudo-science,” or a“fairy tale.”16 But Wegener cited other evidence that he thought continental
drift could explain that the coincidence hypothesis could not. He noted thatfossil forms discovered on the east coast of South America matched those on
the west coast of Africa in corresponding places and sedimentary strata. This
fact seemed too coincidental to him to be explained away by chance alone.
Nevertheless, other geologists attempted to explain matching fossil forms anocean apart not as the result of the movement of the continents, but instead as
the result of the migration of flora and fauna—either across oceans or overancient land bridges.17 This introduced a third hypothesis into the mix, one
that, in conjunction with the coincidence hypothesis, could explain each of thesame facts that Wegener’s hypothesis could.
Later, however, an additional set of facts came to light—one that helped
scientists to decide between the competing hypotheses. During World War II,
the United States Navy surveyed the seafloor topography and measured theearth’s magnetic field across the oceans. These magnetic surveys showedparallel stripes of magnetized rock, each with the same polarity on either sideof mountain ridges running down the middle of the ocean floor at equal
distances from the mid-oceanic mountain ranges.18 Geologists also learned
that magma was continually seeping out at the middle of these mid-oceanic
mountain ranges. They discovered that as the magma cools, it “acquires” acharacteristic magnetic signature reflecting the polarity of the earth’s
magnetic field at that location at the time of its cooling. When ships towing
sensitive magnetometers measured this “remanent magnetization,” scientists
learned that the magnetization of the seafloor alternated between sections of“normal” and “reverse” polarity as the magnetometer was towed away from a
mid-ocean ridge in each direction. This led to the discovery of a famous
symmetrical “piano key” pattern on each side of a mid-ocean ridge, seen in
Figure 17.2.
To explain this symmetrical pattern of alternating magnetism, geologists
proposed that the magnetic stripes were formed as the result of the seafloor
spreading away from the mid-ocean ridge as magma was extruded and cooledin the presence of earth’s changing magnetic field—in other words, that thecontinents were literally drifting apart. This hypothesis not only explained thesymmetrical pattern of magnetic stripes but also other relevant evidence.
Although the other hypotheses could explain (or explain away) the fit of thecontinents and/or the similar pattern of fossilization across the oceans, only
continental drift (driven by seafloor spreading) could explain the magnetic
seafloor stripes and these other pieces of evidence. Consequently, as the resultof its superior explanatory power, a decisive case for continental drift wassoon established, strengthening a merely plausible abductive inference about
the past movement of the continents by showing that this inference provided
the best (and only adequate) explanation of all the relevant facts.19

FIGURE 17.2
This diagram shows the symmetrical pattern of alternating magnetic stripes ofeither “normal” or “reversed” polarity on either side of a mid-ocean ridge.
Because this “piano key” pattern could only be explained by plate tectonics
and seafloor spreading, it contributed to the widespread acceptance of thosetheories within contemporary geology.
Contemporary philosophers of science such as Peter Lipton have called
this method of reasoning “inference to the best explanation.”20 Scientists
often use this method when trying to explain the origin of an event or
structure from the past. They compare various hypotheses to see which
would, if true, best explain it.21 They then provisionally affirm the hypothesisthat best explains the data as the one that is most likely to be true.
Obviously, saying, “The best explanation is the one that best explains thefacts or that best explains the most facts,” begs an important question. What
does it mean to explain something well or best?
As it happens, historical scientists have developed criteria for deciding
which explanation, among a group of competing possible hypotheses,
provides the best explanation for some event in the remote past. The mostimportant of these criteria is “causal adequacy.” As a condition of formulating
a successful explanation, historical scientists must identify causes that are
known to have the power to produce the kind of effect, feature, or event inquestion. In seeking to identify such causes, historical scientists evaluate
hypotheses in light of their present knowledge of cause and effect. Causes thatare known to produce the effect in question (or are thought capable of doingso) are judged to be better candidates than those that are not. For instance, avolcanic eruption provides a better explanation for an ash layer in the earth
than an earthquake or a flood, because eruptions have been observed to
produce ash layers, whereas earthquakes and floods have not.
One of the first historical scientists to develop the criterion of causal
adequacy was the geologist Charles Lyell (1797–1875), who in turninfluenced Charles Darwin. Darwin read Lyell’s magnum opus, The
Principles of Geology, during his voyage on the HMS Beagle and employed
Lyell’s principles of reasoning in On the Origin of Species. The subtitle of
Lyell’s book summarized his central methodological principle: Being an
Attempt to Explain the Former Changes of the Earth’s Surface, by Reference
to Causes Now in Operation (1830–1833). Lyell argued that when scientists
seek to explain events in the past, they should not invoke some unknown typeof cause, the effects of which we have not observed. Instead, they should citecauses that are known from our uniform experience to have the power toproduce the effect in question.22 Historical scientists should cite presently
acting causes, that is, “causes now in operation.” This was the idea behind hisuniformitarian method and its famous dictum: “The present is the key to thepast.” According to Lyell, our present experience of cause and effect should
guide our reasoning about the causes of past events. Darwin adopted thismethodological principle as he sought to demonstrate that natural selection
qualified as a vera causa, that is, a true, known, or actual cause of significant
biological change.23 In other words, he sought to show that natural selection
was “causally adequate” to produce the effects he was trying to explain.
THE ONLY KNOWN CAUSE
Both philosophers of science and leading historical scientists haveemphasized causal adequacy as the key criterion by which competing
hypotheses are judged. But philosophers of science have insisted thatassessments of explanatory power lead to conclusive inferences only when
there is just one known cause for the effect or evidence24 (see Fig. 17.3) inquestion. If there are many causes that can produce the same effect, then thepresence of the effect does not definitively establish the cause. Whenscientists know of only one cause for a given effect, however, they can inferthat cause and yet avoid the fallacy of affirming the consequent—the error of
ignoring other possible causes with the power to produce the same effect.25 Inthat case, they can infer or detect a uniquely plausible past cause from theclues that are left behind.
This can happen in one of two ways. First, historical scientists might focus
their investigation on a single fact (in isolation) for which only one cause
happens to be known. In such a case, they can quickly and decisively infer thecause from the effect alone—without risk of affirming the consequent,because no other known cause produces the same effect. For example,
because a volcanic eruption is the only known cause of a volcanic ash layer,
the presence of such a layer at an archeological site strongly indicates theprior eruption of a volcano.

FIGURE 17.3
Schematic of the logical problem of retrodiction. Whether it is possible toreconstruct the past definitively or not depends upon whether there is a single
cause or condition that gives rise to a present state or whether there are many
possible past causes or conditions that give rise to a given present state. The
diagram on the left portrays an information-destroying situation in which
many past causes (or conditions) correspond to a given present state. The
diagram on the right portrays an information-preserving situation in which
only one past cause (or condition) corresponds to a present state. Adaptedfrom Sober, Reconstructing the Past, 4.
In other cases where historical scientists encounter evidence for which
there are many known causes, they will often broaden their investigation
beyond an initial fact or set of facts. In such cases, they will use the strategy
described above (as part of the method of multiple competing hypotheses), bylooking for additional evidence until they find a piece for which there is only
one known cause. They can then compare the explanatory power of thecompeting hypotheses. Using this strategy, historical scientists will choose theproposed cause with the demonstrated power to produce all the relevant
evidence, including the new fact or piece of evidence for which there is only
one known cause. For example, the discovery of the symmetrical pattern ofocean-floor magnetism on opposite sides of a mid-oceanic ridge allowed for acomparison of the explanatory power of the three hypotheses underconsideration, leaving only seafloor spreading as a causally adequate
explanation of all the relevant facts.
Such an approach often allows historical scientists to pick out a piece ofevidence (from some combination of effects) for which there is only one
known (or theoretically plausible) cause, thus making it possible to establish apast cause decisively. Though this strategy involves looking at a wider classof facts than the first strategy, the logical status of the inferences involved isthe same. In each case, the presence of a fact (either standing on its own or in
combination with other facts) for which only one cause is known allows
historical scientists to make a definitive inference about the causal history inquestion without committing the fallacy of affirming the consequent.
Logically, if a postulated cause is known to be a necessary condition or causeof a given event or effect, then historical scientists can validly infer thatcondition or cause from the presence of the effect. If it’s true that where there
is smoke there is always first fire, then the presence of smoke wafting up overa distant mountain range decisively indicates the prior presence of a fire on
the other side of the ridge.

HISTORICAL INFERENCE AND INTELLIGENT DESIGN
What does all this have to do with the Cambrian explosion?
Quite a lot. In my investigation of the historical scientific method, I foundthat whether they always realize it or not, historical scientists typically use themethod of inference to the best explanation. They make abductive inferences
about past causes from present clues, evidence, or effects. This later suggested
to me that if there were features of the Cambrian explosion or the Cambriananimals that would be “expected as a matter of course” if an intelligent
designer had played a role in that event, then it was at least possible toformulate the hypothesis of intelligent design as a historical (abductive)
scientific inference. An advocate of intelligent design could reason in astandard historical scientific way:
MAJOR PREMISE: If intelligent design played a role in the Cambrian

explosion, then feature (X) known to be produced by intelligent activity
would be expected as a matter of course.
MINOR PREMISE: Feature (X) is observed in the Cambrian explosion ofanimal life.
CONCLUSION: Hence, there is reason to suspect that an intelligent cause
played a role in the Cambrian explosion.
Of course, a historical scientist would only be justified in making such an
abductive inference to the past activity of an intelligent cause if “feature X” isevident in the Cambrian explosion and if intelligent design is known to
produce “feature X.” Moreover, just because the Cambrian explosion may
exhibit some feature or features for which intelligent design is a known cause
does not mean that intelligent design was necessarily the actual cause (or thebest explanation) of those features. Only if the Cambrian event and animals
exhibit features for which intelligent design is the only known cause may a
historical scientist make a decisive inference to a past intelligent cause.
We are left with two crucial questions. Are there in fact such features
present in the record of the Cambrian explosion or in the animals that arise in
it—features that are known from our experience to be produced by intelligent
causes such that they would justify making a tentative abductive inference tointelligent design? Are there also perhaps features of the Cambrian event thatare known from our experience to be produced by intelligent causes, and only
intelligent causes, justifying a more definitive inference to past intelligent
activity as the best explanation for the relevant evidence? Might “the butler”
have done it after all?

18
Signs of Design in the Cambrian Explosion
Well-crafted mystery novels, like real-world crime investigations, unfold witha distinctive logic. There is a death to be explained and, at the start, an
indefinitely large universe of possible causes. That universe can be madesmaller, narrowing to the one true cause, as more and more clues come tolight. Those clues typically come in two forms: positive evidence, orindicators of what likely happened (e.g., .38 caliber shell casings on the
ground and bullet wounds in a body) and negative evidence, or indicators ofwhat could not have happened.
Let’s say that the local sheriff who discovered the body of the estate owner(from my illustration in the previous chapter), did so as he was making his
rounds on a dirt road that makes a close approach to the beach at the end of
the estate where the owner died. And let’s say that, as a result, the sheriff justhappened to find the body soon after the murder had taken place. Let’s
suppose, further, that the sheriff had the presence of mind to immediately
measure the temperature of the body only to find that the victim was still
warm, indeed almost as warm as a living person. Clearly, in this situation, thesheriff would conclude that the victim had just died. At that point in theinvestigation, a physical regularity would govern the sheriff’s reasoning, onethat tells a lot about who didn’t commit the murder. Following death, thehuman body cools to the surrounding temperature at a known rate. So,
making allowances for vehicular transport, whoever committed the murder
could not have gone beyond a certain distance from the remote estate at thetime the body was found.
These facts would immediately provide a rock-solid alibi to the vast
majority of humanity, anyone located safely outside that radius when the bodywas discovered. Of course, calling this information a negative clue is really
only a convention of naming. “Negative” and “positive” refer to how weconceive of the implications of a fact, but not to the fact itself: the evidence,
after all, is what it is. Even so, facts both exclude and allow competing
possible hypotheses. As they accumulate, they typically paint a picture, aprofile, of the actual cause of the event in need of explanation. Thus, when we
say “the body temperature of the deceased rules out the 7 billion people who
were well beyond the radius set by the cooling rate,” we could equally wellhave said, “the body temperature implicates some person within 30 miles ofthe estate when the sheriff arrived,” a population of possible suspects muchsmaller than when we started.
As I have described the many attempts to explain the scientific enigma
motivating this book, that mystery has, in one sense, progressively deepened.
As more and more attempts to explain the Cambrian explosion of animal life
have failed, the evidence that these various competing theories fail to explain
may be considered a set of negative clues—evidence that effectively
precludes certain possible causes or explanations. I’ve already explained why
the received version of evolutionary theory, neo-Darwinism, fails to accountfor the explosion of information and form in the Cambrian period. I’ve also
examined more recent evolutionary theories and shown why they too fail toexplain key aspects of the evidence. To this point, then, much of the evidence
has returned a negative verdict. It has told us a lot about what, in allprobability, did not cause the Cambrian explosion. But, as in our hypotheticalmurder case, an accumulating body of evidence that makes one set of
explanations less and less plausible may also begin to paint a picture of analternative cause and the true explanation.
PROFILE OF THE SUSPECTLong before detectives know the actual identity of a suspect, they will often
compose a profile of the person they are seeking. One leading paleontologist
has used this strategy to begin to draw a bead on the cause responsible for the
Cambrian explosion. Douglas Erwin has dedicated his career to solving the
problem of the origin of animal body plans (see Fig. 18.1). Trained at the
University of California by James Valentine, another Cambrian expert, Erwin
has worked closely over the past decade with Eric Davidson, whom we firstmet in Chapter 13, trying to determine what happened to cause dozens ofnovel body plans to appear—and appear rapidly—in the Cambrian period.
Both Erwin and Davidson have now ruled out standard neo-Darwinian
theory—vehemently in Davidson’s case. He says that the standard theory“gives rise to lethal errors.”1 But Erwin and Davidson go further. They haveassembled what is, in essence, a clue sheet—a list of key evidences that must
be explained. Using that list, they have begun to sketch, at least in outline, aprofile of the cause behind the Cambrian explosion.
On the positive side of the ledger, they conclude that this cause must haveseveral attributes in order to explain key facts about the fossil record as wellas what it takes to build animals. In particular, the cause must be capable ofgenerating a top-down pattern of appearance; it must be capable of generating
new biological form relatively rapidly; and it must be capable of constructing,not merely modifying, complex integrated genetic circuits (specifically, thedevelopmental gene regulatory networks discussed in Chapter 13).
On the negative side, Davidson and Erwin rule out both observed
microevolutionary processes and postulated macroevolutionary mechanisms(such as punctuated equilibrium and species selection) as explanations for theorigin of the key features of the Cambrian explosion. They insist that therequirements for constructing animal body plans de novo “cannot be
accommodated by microevolutionary [or] macroevolutionary theory.”2

FIGURE 18.1
Douglas Erwin. Courtesy UPHOTO/Cornell University.
In Chapter 13, I discussed their reason for coming to this conclusion:developmental gene regulatory networks, once in place, cannot be perturbed(or mutated) without “catastrophic”3 consequences to the developing animal.
Thus, fundamentally new gene regulatory networks (dGRNs) cannot evolve
gradually from preexisting dGRNs, if those evolutionary changes require
perturbing the deepest nodes of the earlier dGRNs. Yet building new dGRNs
capable of producing new animals requires precisely such fundamental
alterations in preexisting dGRNs. But then how would new regulatory
networks ever arise? Davidson and Erwin insist that no current theory of
evolution explains the origin of these systems. Thus, they conclude that thecause of the Cambrian explosion is not described by any currently proposed
theory of micro- or macroevolution.
In saying this, Erwin emphasizes the uniqueness of the innovations that
occurred in the Cambrian explosion. He explains: “Unlike later events, themost significant developmental events of the Cambrian radiation involved theproliferation of cell types, developmental hierarchies and epigenetic
cascades.”4 Consequently, he concludes, “The crucial difference between thedevelopmental events of the Cambrian and subsequent events is that theformer involved the establishment of these developmental patterns, not theirmodification.”5 For this reason, Erwin denies that the central event of theCambrian explosion—the origin of novel body plans—has any parallel tocurrently observed biological processes. Rather, he insists that the events ofthe past were fundamentally different—that profound asymmetries exist
between evolution then, and evolution now.6 Thus, he amplifies his denial of
the sufficiency of current evolutionary theory by adding one additional
attribute, albeit a negative one, to his portrait of “the suspect”: the cause
responsible for generating the new animal forms, whatever it was, must havebeen unlike any observed biological process operating in actual living
populations today.
PROFILING A CAUSE
All of this raises an obvious question. Could the negative clues that
increasingly disconfirm materialistic evolutionary theories also be positive
indicators of a different kind of cause—perhaps even an intelligent cause?
By sketching the profile of the kind of cause needed to explain the originof animal life, Davidson, Erwin, and many other evolutionary biologists may
have, inadvertently, rendered the idea of intelligent design a bit lessinconceivable. To see why, let’s quickly review Erwin and Davidson’s profileof the suspect. They have concluded that the cause of the origin of the new
animal forms in the Cambrian explosion must be capable of:generating new form rapidly
generating a top-down pattern of appearance
constructing, not merely modifying, complex integrated circuits
They have also concluded that this cause is:
not described by any currently proposed theory of micro- or
macroevolution
unlike any observed biological process operating in actual living
populations today
Erwin and Davidson, no friends of intelligent design, have sketched apartial profile of an adequate cause as befits their particular interest in theimportance of gene regulatory networks (Davidson) and fossil discontinuity(Erwin). But other evolutionary biologists have contributed to this picture as
well. Simon Conway Morris marvels at “the uncanny ability of evolution tonavigate to the appropriate solution through immense ‘hyperspaces’ of
biological possibility.”7 As a result, he argues that evolution may in some way
be “channeled” toward propitious functional and/or structural end points—
without specifying any known evolutionary mechanism that can so direct
evolution to such end points.8 James Shapiro proposes a mechanism of
evolutionary change that relies on preprogrammed adaptive capacity—
without explaining where such preprogramming comes from.9 Several of the
new evolutionary theories discussed in the previous chapters presuppose, but
do not explain, the existence of both genetic and epigenetic forms of
information, highlighting the need for a cause capable of generating suchinformation in the first place.
Erwin and Davidson have made a bold start with their clue list ruling out
neo-Darwinism. But the evidence explored in these pages suggests additional
attributes that need to be added to their profile of the actual cause of theCambrian explosion. Our previous investigations have suggested that building
an animal requires specified or functional information and that any
explanation for the origin of the Cambrian animals must identify a cause
capable of generating:digital information
structural (epigenetic) information
functionally integrated and hierarchicallyinformation

organized

layersofStill, do any or even all of these clues add up to a reason for consideringthat an alternative kind of cause—a designing intelligence—might haveplayed a role in the origin of animal life?
They do. As it turns out, each of the features of the Cambrian animals andthe Cambrian fossil record that constitute negative clues—clues that renderneo-Darwinism and other materialistic theories inadequate as causal
explanations—also happen to be features of systems known from experienceto have arisen as the result of intelligent activity. In other words, standard
materialistic evolutionary theories have failed to identify an adequate
mechanism or cause for precisely those attributes of living forms that weknow from experience only intelligence—conscious rational activity—iscapable of producing. That suggests, in accord with the method of historicalscientific reasoning elucidated in the previous chapter, the possibility ofmaking a strong historical inference to intelligent design as the best
explanation for the origin of those attributes.
Let’s have a look at each of these features of the Cambrian event, startingwith key features of the Cambrian animals themselves, to see how they might
point to the past activity of a designing intelligence, thereby making
intelligent design scientifically detectable.
THE CAMBRIAN INFORMATION EXPLOSION
We have seen that building a Cambrian (or any other) animal would require
vast new, functionally specified digital information. Moreover, the presenceof such digitally encoded information in DNA presents, at least, a striking
appearance of design in all living organisms. As Richard Dawkins observes,for example, “The machine code of the genes is uncannily computer-like.”10
Similarly, biotechnology pioneer Leroy Hood refers to the information stored
in DNA as “digital code” and describes it in terms reminiscent of computer
software.11 And as we have seen, Microsoft’s Bill Gates notes: “DNA is like acomputer program but far, far more advanced than any software evercreated.”12
Yet we’ve also seen that neither neo-Darwinism nor any other materialistic
evolutionary model or mechanism explains the origin of the genetic
information (the digital code) necessary to produce the Cambrian animals oreven the simplest structural innovations that they exhibit. Could this—from amaterialistic point of view—unexplained appearance of design point insteadto actual intelligent design?
I think it does. But to explain why, I need to tell a bit more about the“evolution” of my own thinking on the matter.
After learning about how historical scientists make inferences about thecauses of events in the remote past, I first applied these methods of reasoning
to the question of the origin of the information necessary to produce the firstliving cell. My book Signature in the Cell used the method of multiplecompeting hypotheses (or inference to the best explanation) to evaluate the“causal adequacy” of proposed explanations for the ultimate origin of
biological information. I showed that chemical evolutionary models (whether
based upon chance, physical-chemical necessity, or the combination of thetwo) failed to identify a cause capable of producing the digital information in
DNA and RNA. Yet we do know of a cause that has demonstrated the causal
power to produce digital code. That cause is intelligent agency. Since
intelligent agency is the only cause known to be capable of generating
information (at least starting from nonliving chemicals), intelligent designoffers the best explanation for the origin of the information necessary to
produce the first organism.
The case for intelligent design in Signature was carefully limited as achallenge to chemical evolution. Many evolutionary biologists acknowledge
that chemical evolutionary theory has failed to account for the origin of thefirst life. Many cite its inability to account for the origin of biologicalinformation as one of the main reasons for that failure. Moreover, because
they do not think that natural selection could have played a significant role inevolution until after the first self-replicating organisms had arisen, mostevolutionary biologists also think that explaining the origin of information ina prebiotic context is much more difficult than explaining the origin of new
information in already living organisms.
For this reason, in Signature I did not try to argue that intelligent design
might help explain the origin of the information necessary to account for theorigin of new animals from simpler preexisting forms of life. That would haverequired a separate demonstration showing the inadequacy of natural selection
and mutation as a mechanism for generating new genetic information inalready living organisms. This book—in Chapters 9–14—has provided that
demonstration. These chapters show how neo-Darwinism fails to explain theorigin of genetic information—at least, in amounts necessary to build a newprotein fold. Chapters 15 and 16 showed, in addition, that the other mainmaterialistic evolutionary theories also fail to account for the informationnecessary to build new forms of animal life. These theories presuppose, rather
than explain, the origin of the information necessary for structural innovationin the history of life. And since the Cambrian explosion of animal life is an
explosion of information and structural innovation, that raises a question. Is it
possible that this increase of biological information not only represents
evidence against materialistic theories of biological evolution, but also
positive evidence for intelligent design?
A Cause Now in Operation
It does. Intelligent agents, due to their rationality and consciousness, havedemonstrated the power to produce specified or functional information in theform of linear sequence-specific arrangements of characters. Digital andalphabetic forms of information routinely arise from intelligent agents. A
computer user who traces the information on a screen back to its source
invariably comes to a mind—a software engineer or programmer. The
information in a book or inscription ultimately derives from a writer or scribe.
Our experience-based knowledge of information flow confirms that systems

with large amounts of specified or functional information invariably originate
from an intelligent source. The generation of functional information is“habitually associated with conscious activity.”13 Our uniform experience
confirms this obvious truth.
It also suggests, therefore, that intelligent design meets the key “causal
adequacy” requirement of a good historical scientific explanation. Certainly,
intelligence is a “cause now in operation” capable of generating functional or
specified information in a digital form. As I write this, my mind is generating
specified information. Intelligent agents generate information in the form ofsoftware code, ancient inscriptions, books, encrypted military codes, andmuch else. And since we know of no “presently acting” materialistic causethat also generates large amounts14 of specified information (especially in adigital or alphabetic form), only intelligent design meets the causal adequacy
requirement of a historical scientific explanation. In other words, our uniform
experience of cause and effect shows that intelligent design is the only known
cause of the origin of large amounts of functionally specified digital
information. It follows that the great infusion of such information in the
Cambrian explosion points decisively to an intelligent cause.
Intelligent design stands alone as an explanation for the origin of genetic
information for another reason: purposive agents have just those necessary
powers that natural selection lacks as a condition of its causal adequacy. We
have seen that natural selection lacks the ability to generate novel information
precisely because it can only act after new functional information has arisen.
Natural selection can favor new proteins and genes, but only after they
perform some function (influencing reproductive output). The job ofgenerating new functional genes, proteins, and systems of proteins therefore
falls entirely to random mutations. Yet without functional criteria to guide asearch through the space of possible sequences, random variation isprobabilistically doomed. What is needed is not just a source of variation (i.e.,
the freedom to search a space of possibilities) or a mode of selection that canoperate after the fact of a successful search, but instead a means of selectionthat (a) operates during a search—before success—and that (b) is guided byinformation about or knowledge of a functional target.
Demonstration of this requirement has come from an unlikely quarter:
genetic algorithms. Genetic algorithms are programs that allegedly simulate
the creative power of mutation and selection. Richard Dawkins, Bernd-Olaf
Küppers, and others have developed computer programs that putatively
simulate the production of genetic information by mutation and natural
selection.15 Yet these programs succeed only by the illicit expedient ofproviding the computer with a “target sequence” and then treating proximity

to future function (i.e., the target sequence), not actual present function, as aselection criterion. As mathematician David Berlinski shows, genetic
algorithms need something akin to a “forward-looking memory” in order tosucceed.16 Yet such foresighted selection has no analogue in nature. In
biology, where differential survival depends upon maintaining function,
natural selection cannot occur before new functional sequences arise. Natural
selection lacks foresight; the process, as evolutionary theorists Rodin andSzathmáry note, works strictly “ ‘in the present moment,’ right here and rightnow . . . lacking the foresight of potential future advantages.”17
What natural selection lacks, intelligent design—purposive, goal-directed
selection—provides. Rational agents can arrange both matter and symbols
with distant goals in mind. They also routinely solve problems ofcombinatorial inflation. In using language, the human mind routinely “finds”
or generates highly improbable linguistic sequences to convey an intended or
preconceived idea. In the process of thought, functional objectives precedeand constrain the selection of words, sounds, and symbols to generatefunctional (and meaningful) sequences from a vast ensemble of meaninglessalternative possible combinations of sound or symbol.18 Similarly, theconstruction of complex technological objects and products, such as bridges,
circuit boards, engines, and software, results from the application of goaldirected constraints.19 Indeed, in all functionally integrated complex systems
where the cause is known by experience or observation, designing engineersor other intelligent agents applied constraints on the possible arrangements ofmatter to limit possibilities in order to produce improbable forms, sequences,or structures. Rational agents have repeatedly demonstrated the capacity toconstrain possible outcomes to actualize improbable but initially unrealized
future functions. Repeated experience affirms that intelligent agents (minds)
uniquely possess such causal powers.
Analysis of the problem of the origin of biological information, therefore,
exposes a deficiency in the causal powers of natural selection and other
undirected evolutionary mechanisms that corresponds precisely to powers thatagents are uniquely known to possess. Intelligent agents have foresight. Such
agents can determine or select functional goals before they are physicallyinstantiated. They can devise or select material means to accomplish thoseends from among an array of possibilities. They can then actualize those goals
in accord with a preconceived design plan or set of functional requirements.
Rational agents can constrain combinatorial space with distant informationrich outcomes in mind. The causal powers that natural selection lacks—bydefinition—are associated with the attributes of consciousness and rationality

—with purposive intelligence. Thus, by invoking intelligent design toovercome a vast combinatorial search problem and to explain the origin of
new specified information, contemporary advocates of intelligent design are
not positing an arbitrary explanatory element unmotivated by a considerationof the evidence. Instead, we posit an entity possessing precisely the causal
powers that a key feature of the Cambrian explosion—the explosive increasein specified information—requires as a condition of its production andexplanation.
INTEGRATED CIRCUITRY: DEVELOPMENTAL GENE
REGULATORY NETWORKS
Keep in mind, too, that animal forms have more than just genetic information.
They also need tightly integrated networks of genes, proteins, and othermolecules to regulate their development—in other words, they requiredevelopmental gene regulatory networks, the dGRNs that Eric Davidson has
so meticulously mapped over the course of his career. Developing animals
face two main challenges. First, they must produce different types of proteinsand cells and, second, they must get those proteins and cells to the right placeat the right time.20 Davidson has shown that embryos accomplish this task by
relying on networks of regulatory DNA-binding proteins (called transcription
factors) and their physical targets. These physical targets are typicallysections of DNA (genes) that produce other proteins or RNA molecules,
which in turn regulate the expression of still other genes.
These interdependent networks of genes and gene products present a
striking appearance of design. Davidson’s graphical depictions of thesedGRNs look for all the world like wiring diagrams in an electricalengineering blueprint or a schematic of an integrated circuit, an uncanny
resemblance Davidson himself has often noted. “What emerges, from theanalysis of animal dGRNs,” he muses, “is almost astounding: a network oflogic interactions programmed into the DNA sequence that amounts
essentially to a hardwired biological computational device.”21 Thesemolecules collectively form a tightly integrated network of signaling
molecules that function as an integrated circuit. Integrated circuits inelectronics are systems of individually functional components such astransistors, resistors, and capacitors that are connected together to perform an
overarching function. Likewise, the functional components of dGRNs—the
DNA-binding proteins, their DNA target sequences, and the other moleculesthat the binding proteins and target molecules produce and regulate—also
form an integrated circuit, one that contributes to accomplishing the overall

function of producing an adult animal form.
Yet, as explained in Chapter 13, Davidson himself has made clear that thetight functional constraints under which these systems of molecules (thedGRNs) operate preclude their gradual alteration by the mutation andselection mechanism. For this reason, neo-Darwinism has failed to explain theorigin of these systems of molecules and their functional integration. Like
advocates of evolutionary developmental biology, Davidson himself favors amodel of evolutionary change that envisions mutations generating large-scale
developmental effects, thus perhaps bypassing nonfunctional intermediate
circuits or systems. Nevertheless, neither proponents of “evo-devo,” norproponents of other recently proposed materialistic theories of evolution, haveidentified a mutational mechanism capable of generating a dGRN or anythingeven remotely resembling a complex integrated circuit. Yet, in our experience,complex integrated circuits—and the functional integration of parts incomplex systems generally—are known to be produced by intelligent agents—specifically, by engineers. Moreover, intelligence is the only known causeof such effects. Since developing animals employ a form of integrated
circuitry, and certainly one manifesting a tightly and functionally integrated
system of parts and subsystems, and since intelligence is the only known
cause of these features, the necessary presence of these features in developing
Cambrian animals would seem to indicate that intelligent agency played a rolein their origin (see Fig. 13.4).
THE HIERARCHICAL ORGANIZATION OF GENETIC AND
EPIGENETIC INFORMATION
In addition to the information stored in individual genes and the information
present in the integrated networks of genes and proteins in dGRNs, animal
forms exemplify hierarchical arrangements or layers of information-richmolecules, systems, and structures. For example, developing embryos require
epigenetic information in the form of specifically arranged (a) membranetargets and patterns, (b) cytoskeletal arrays, (c) ion channels, and (d) sugar
molecules on the exterior of cells (the sugar code). As noted in Chapter 13,
much of this epigenetic information resides in the structure of the maternal
egg and is inherited directly from membrane to membrane independently ofDNA.
This three-dimensional structural information interacts with otherinformation-rich molecules and systems of molecules to ensure the properdevelopment of an animal. In particular, epigenetic information influences theproper positioning and thus the function of regulatory proteins (includingDNA-binding proteins), messenger RNAs, and various membranecomponents. Epigenetic information also influences the function ofdevelopmental gene regulatory networks. Thus, information at a higher
structural level in the maternal egg helps to determine the function of bothwhole networks of genes and proteins (dGRNs) and individual molecules(gene products) at a lower level within a developing animal. Genetic
information is necessary to specify the arrangement of amino acids in a
protein or bases in an RNA molecule. Similarly, dGRNs are necessary to
specify the location and/or function of many gene products. And, in a similarway, epigenetic information is necessary to specify the location and determine
the function of lower-level molecules and systems of molecules, including thedGRNs themselves.
Furthermore, the role of epigenetic information provides just one of many
examples of the hierarchical arrangement (or layering) of information-rich
structures, systems, and molecules within animals. Indeed, at every level ofthe biological hierarchy, organisms require specified and highly improbable(information-rich) arrangements of lower-level constituents in order tomaintain their form and function. Genes require specified arrangements ofnucleotide bases; proteins require specified arrangements of amino acids; cellstructures and cell types require specified arrangements of proteins or systems
of proteins; tissues and organs require specific arrangements of specific cell
types; and body plans require specialized arrangements of tissues and organs.
Animal forms contain information-rich lower-level components (such asproteins and genes). But they also contain information-rich arrangements of
those components (such as the arrangement of genes and gene products in
dGRNs or proteins in cytoskeletal arrays or membrane targets). Finally,animals also exhibit information-rich arrangements of higher-level systems
and structures (such as the arrangements of specific cell types, tissues, andorgans that form specific body plans).
The highly specified, tightly integrated, hierarchical arrangements ofmolecular components and systems within animal body plans also suggest
intelligent design. This is, again, because of our experience with the featuresand systems that intelligent agents—and only intelligent agents—produce.
Indeed, based on our experience, we know that intelligent human agents havethe capacity to generate complex and functionally specified arrangements ofmatter—that is, to generate specified complexity or specified information.
Further, human agents often design information-rich hierarchies, in which
both individual modules and the arrangement of those modules exhibit
complexity and specificity—specified information as defined in Chapter 8.
Individual transistors, resistors, and capacitors in an integrated circuit exhibit

considerable complexity and specificity of design. Yet at a higher level oforganization, the specific arrangement and connection of these components
within an integrated circuit requires additional information and reflects further
design (see Fig. 14.2).
Conscious and rational agents have, as part of their powers of purposive
intelligence, the capacity to design information-rich parts and to organize
those parts into functional information-rich systems and hierarchies. We knowof no other causal entity or process that has this capacity. Clearly, we havegood reason to doubt that mutation and selection, self-organizational
processes, or any of the other undirected processes cited by other materialistic
evolutionary theories, can do so. Thus, based upon our present experience ofthe causal powers of various entities and a careful assessment of the efficacy
of various evolutionary mechanisms, we can infer intelligent design as thebest explanation for the origin of the hierarchically organized layers of
information needed to build the animal forms that arose in the Cambrianperiod.
LOCATION, LOCATION, LOCATION
There is another remarkable aspect of the hierarchical organization of
information in animal forms. Many of the same genes and proteins play very
different roles, depending upon the larger organismal and informational
context in which they find themselves in different animal groups.22 For
example, the same gene (Pax-6 or its homolog, called eyeless), helps toregulate the development of the eyes of fruit flies (arthropods) and those ofsquid and mice (cephalopods and vertebrates, respectively). Yet arthropod
eyes exemplify a completely different structure from vertebrate or cephalopod
eyes. The fruit fly possesses a compound eye with hundreds of separate lenses(ommatidia), whereas both mice and squid employ a camera-type eye with asingle lens and retinal surface. In addition, although the eyes of squid andmice resemble each other optically (single lens, large internal chamber, single
retinal surface), they focus differently. They undergo completely different
patterns of development and utilize different internal structures and nerve
connections to the visual centers of the brain. Yet the Pax-6 gene and its
homologs play a key role in regulating the construction of all three of thesedifferent adult sensory structures. Moreover, evolutionary and developmental
biologists have found that this pattern of “same genes, different anatomy”
recurs throughout the bilaterian phyla, for features as fundamental as
appendages, segmentation, the gut, heart, and sense organs (see Fig. 18.2).23
This pattern contradicts the expectations of textbook evolutionary theory.

Neo-Darwinism predicts that disparate adult structures should be produced bydifferent genes. This prediction follows directly from the neo-Darwinianassumption that all evolutionary (including anatomical) transformations begin
with mutations in DNA sequences—mutations that are fixed in populations by
natural selection, genetic drift, or other evolutionary processes. The arrow of
causality flows one way from genes (DNA) to development to adult anatomy.
Thus, if biologists observe different animal forms, it follows that they should
expect that different genes will specify those forms during animal
development. Given the profound differences between the fruit-fly compound
eye and the vertebrate camera eye, neo-Darwinian theory would not predictthat the “same” genes would be involved in building different eyes inarthropods and chordates.24

FIGURE 18.2
The same genes can be used in different animals to produce dramaticallydifferent structures, contradicting neo-Darwinian expectations.
Many leading evolutionary theorists have acknowledged this problem.
University of Wisconsin evo-devo researcher Sean B. Carroll has noted thatthe neo-Darwinian prediction of similar genes producing similar structures is“entirely incorrect.”25 Stephen Jay Gould described the discovery of thepolyfunctional role of similar genes as “explicitly unexpected” and“discombobulat[ing] the confident expectations of orthodox theory.”26
The theory of intelligent design suggests a solution to the problem—asolution familiar to us from the construction and operation of our own
artifacts. Figure 18.3 shows a general-purpose switching transistor. Theseelectronic components can be used to help build many electronic systems,
from a computer to a microwave oven to a radio. And the exact functionalrole that the transistor will play will be governed by the system in which it
finds itself. (One must, of course, make allowances for the particularspecifications of the transistor itself; a transistor cannot function as a battery).
Nowhere, however, is this feature of polyfunctional modularity more

intuitively clear than in our use of natural languages, such as English. To
illustrate this, my colleague Paul Nelson once “disassembled” the last fortyfour words of Abraham Lincoln’s Gettysburg Address (see Fig. 18.4) into alexicon. Using the same words, at roughly the same frequency, he then wrote
an “Anarchist’s Manifesto,” with a meaning diametrically opposite to that of
Lincoln’s. What had changed were not the words—that is, the lower-level
modules. Rather, the higher-level context, or the system as a whole, differed.
Lincoln wrote with one meaning in mind, the anarchist with another—andthat made all the difference to the functions of the elements, or modules,
within the respective systems. Nelson calls this context dependency “theorganismal context principle” when it occurs in biology and he likens it to thecontext dependence of words in language or low-level parts in a technologicalsystem.

FIGURE 18.3
A general purpose transistor—an example of a component that can be used toperform different functions in different designed systems. Courtesy
iStockphoto.com/S230.

FIGURE 18.4
This comparison of Lincoln’s Gettysburg Address and an “Anarchist’s
Manifesto” shows how the same modular elements (words) can performdifferent functions depending on their surrounding context, just as many
genes do in biological systems. Courtesy Paul Nelson.
He also argues that intelligent design provides a compelling explanation
for the presence of polyfunctional modularity in living systems. Why? Not
only is the polyfunctionality of genetic modules unexpected in a neoDarwinian view, it is a common feature of intelligently designed systems. As
Nelson and Jonathan Wells note, “An intelligent cause may reuse or redeploy
the same module in different systems, without there necessarily being any
material or physical connection between those systems.”27 They also observethat intelligent agents “can generate identical patterns independently” and put
them to different uses in different systems of parts:

If we suppose that an intelligent designer constructed organisms using
a common set of polyfunctional genetic modules—just as humandesigners, for instance, may employ the same transistor or capacitor ina car radio or a computer, . . . then we can explain why we find the“same” genes expressed in the development of what are very different
organisms. . . . A particular gene, employed for its DNA-binding
properties, finds its functional role in a higher-level system whose
ultimate origin was intelligently caused.28
Wells and Nelson go on to explain that “the overall system, not the geneitself” determines the ultimate functional significance of the lower level
modules, just as it does in all human technological or communication
systems. Certainly, both the computer software and computer hardware(integrated circuits) exhibit this feature—what might be called “contextdependent, polyfunctional modularity.” Similarly, in information-rich texts—
such as the Gettysburg Address or the Anarchist’s Manifesto—humans
convey different meanings with the same low-level modules (words)
depending upon their surrounding context. Experience shows that when weknow how systems possessing this feature arose, invariably they arose byintelligent design.
FEATURES OF THE PRE-CAMBRIAN–CAMBRIAN FOSSIL
RECORD
Intelligent design not only helps to explain many key features of theCambrian animals themselves; it also helps to explain many otherwise
anomalous features of the Cambrian fossil record.
An Inverted Cone: Disparity Preceding Diversity
As discussed in Chapter 2, the fossil record shows a “top-down” pattern inwhich phyla-level morphological disparity appears first followed only later byspecies-level diversity. Major innovations in body plans precede minor
variations on basic designs.29 This “inverted cone of diversity” also suggests
intelligent design.
Neo-Darwinism seeks to explain the origin of novel body plans by startingwith simpler body plans and gradually assembling animals with more
complex body plans via the gradual accumulation of small successive
material variations. Thus, neo-Darwinism employs a “bottom-up” mode ofcausation. With a bottom-up approach, small-scale diversification shouldeventually produce large-scale morphological disparity—differences in bodyplan. The “bottom-up” metaphor thus describes a kind of self-assembly inwhich the gradual production of the material parts eventually generates theorganization of the whole. This suggests in turn that the parts stand causallyprior to the organization of the whole. As I have argued, however, thisapproach encounters both paleontological and biological difficulties: the fossil
record leaves no evidence of such a process and the morphological innovationand transformations that it requires are, in any case, biologically implausible.
But if a bottom-up approach fails, perhaps a “top-down” approach will
succeed. “Top-down” causation begins with a basic architecture, blueprint, orplan and then proceeds to assemble parts in accord with it. The blueprint
stands causally prior to the assembly and arrangement of the parts. But where
could such a blueprint come from? One possibility involves a mental mode ofcausation. Intelligent agents often conceive of plans prior to their material
instantiation—that is, the preconceived design of a blueprint often precedes
the assembly of parts in accord with it. An observer touring the parts sectionof a General Motors plant will see no direct evidence of a prior blueprint for
GM’s new models, but will perceive the basic design plan immediately uponobserving the finished product at the end of the assembly line. Designed
systems, whether automobiles, airplanes, or computers, invariably manifest adesign plan that preceded their first material instantiation. But the parts do not
generate the whole. Rather, an idea of the whole directed the assembly of theparts.
This form of causation can certainly explain the pattern in the fossil
record. As new species appear in the Cambrian, they manifest completely
novel, morphologically disparate, and functionally integrated body plans.
Thus, although the fossil record does not directly establish the existence of aprior mental plan or blueprint, such a plan could certainly explain, or beinferred from, the top-down pattern of fossil evidence. In other words, if the
body plans of the Cambrian animals did arise as the result of a “top-down”
mode of causation involving a preconceived design plan, we would expect,based on our experience of complex designed systems, to find precisely thepattern of evidence that we do see in the fossil record. Further, materialistic“bottom-up” models of causation fail to explain this same pattern of fossil
evidence. Thus, intelligent design provides a better explanation of this featureof the Cambrian fossil record than do competing materialistic evolutionary
theories.
The design hypothesis can also explain why smaller-scale diversity arises
after, not before, morphological disparity in the fossil record or, to put it more
poetically, why the basic themes of life precede the variation on those themes.

Complex designed systems have a fundamental functional integrity thatmakes their alteration difficult. For this reason, we should not expect gradualmechanisms of change to produce new body plans or alter them
fundamentally after they have arisen. We might, however, expect to findvariations on these basic themes within the functional limits established by abasic architecture or body plan. Fundamentally new forms of organization
require design from scratch. For example, airplanes did not arise gradually or
incrementally from automobiles. Nevertheless, new innovations often accrete
to novel designs provided the fundamental organizational plan is not altered.
Since the invention of the automobile, all cars have included the same
basic structural and functional elements, including a motor, at least three (andusually four) wheels, a carriage with seats for passengers, a structure
connecting the wheels to the carriage, a steering wheel and column (oranalogous mechanism), and a means of translating energy generated by the
motor to the wheels. These are minimal requirements, of course; many cars
have used axles to connect the wheels, though some have not and a “stretch”
limousine may need additional axles or wheels. Indeed, though many new
variations on the original model have arisen after the invention of the basic
automobile design, all exemplify this same basic design. Interestingly, we also
observe this pattern in the fossil record. The major animal body plans appear
first instantiated by a single (or very few) species or genera. Then, later, manyother varieties arise with many new features, yet all still exhibit the same
basic body plan.
Experience shows a hierarchical relationship between functionallynecessary and functionally optional features in designed systems. An
automobile cannot function without a motor or steering mechanism; it canfunction with or without twin I-beam suspension, antilock brakes, or “stereo
surround sound.” This distinction between functionally necessary andoptional features suggests the possibility of future innovation and variation on
basic design plans, even as it imposes limits on the extent to which the basic
designs themselves can be altered. The logic of designed systems, therefore,suggests precisely the kind of top-down pattern that we see in both the historyof our own technological innovation30 and in the history of life following theCambrian explosion (compare Figs. 18.5a and 18.5b). On the other hand,competing materialistic evolutionary theories would not lead us to expect thefossil record to manifest such a “top-down” pattern, but the opposite.
Sudden Appearance and Missing Ancestors
The theory of intelligent design can also help to account for the abrupt

appearance of complex anatomical structures and animal body plans in thefossil record. Intelligent agents sometimes produce material entities through aseries of gradual modifications (as when a sculptor shapes a sculpture overtime). Nevertheless, intelligent agents also have the capacity to introduce
complex technological systems into the world fully formed. Often such
systems bear no resemblance to earlier technological systems—their invention
occurs without a material connection to earlier, more rudimentary
technologies. When the radio was first invented, it was unlike anything that
had come before, even other forms of communication technology. For thisreason, although intelligent agents need not generate novel structures
abruptly, they can do so. Thus, invoking the activity of a mind provides acausally adequate explanation for the pattern of abrupt appearance in the
Cambrian fossil record.

FIGURE 18.5
Figure 18.5a (top): A top-down pattern of appearance found in the history ofanimal life. Figure 18.5b (bottom): A top-down pattern of appearance inhuman technology.
On the other hand, strictly materialistic theories of evolution necessarily
envision a “bottom-up” mode of causation in which material parts ormaterially instantiated intermediate forms of organization necessarily precede
the emergence of fully developed body plans. For this reason, the sudden
appearance of novel animal forms contradicts the expectations of mostmaterialistic evolutionary theories. Neo-Darwinism, in particular, would not
expect the sudden appearance of animal forms. As Darwin himself insisted:“Natura non facit saltum” (“Nature takes no leaps”). Yet intelligent agentscan act suddenly or discretely in accord with their powers of rational choiceor volition, even if they do not always do so. Thus, the sudden appearance of
the Cambrian animals does suggest, at least, the possibility of a volitional act
of a conscious agent—a designer.
Intelligent design likewise helps explain the absence of ancestral
precursors. If body plans arose as the result of an intelligent agent actualizing
an immaterial plan or idea, then an extensive series of material precursors to
the first animals need not exist in the fossil record, anymore than such a series
is always present in the history of technology. The radio did not evolve
gradually from the telegraph. Mental plans or concepts need not leave amaterial trace. Thus, intelligent design can account for the dearth of material
precursors in the Precambrian strata, whereas “bottom-up” materialistic
evolutionary theories cannot, especially given the failure of the artifact
hypothesis discussed earlier.
Stasis (or Persistent Morphological Isolation)
Finally, intelligent design also explains the observed stasis in the fossil record.
As advocates of punctuated equilibrium established, Cambrian species tend to
persist unchanged in their basic forms over time. Animal body plans thatdefine the higher taxa, including classes and phyla, also remain especiallystable in their basic architectural designs, showing “no directional change”31
over geological history after their first appearance in the Cambrian. As aresult, the morphological disparity between distinct animal body plans
remains unbridged. Moreover, as noted in Chapter 13, developmental
mechanisms constrain the degree to which organisms may vary without
deleterious consequences.

FIGURE 18.6
Comparison of persistent morphological isolation in two animal forms that first arose in the Cambrianperiod, and similar morphological isolation in two technological systems.

The persistent morphological disparity and isolation of animal body plans
is completely unexpected by neo-Darwinian, and all other gradualist,
evolutionary theories, at least. Given such models of evolutionary change,
theorists should expect the fossil record to exhibit forms of life that grade
imperceptibly from one to another. Indeed, absent either a compelling versionof the artifact hypothesis or an adequate mechanism of punctuated large-scaleevolutionary change, “morphospace” should be mostly filled in. The fossil
record should not display mostly morphologically disparate or separate formsof animal life.
Yet, if living systems did arise as the result of intelligent design, then suchmorphological isolation, and such persistent isolation over time, is just what
we should expect to see—precisely because that is what we do see in thehistory of other intelligently designed systems (see Fig. 18.6). Indeed,experience suggests that designed objects have a functional integrity thatmakes the modification of some of their essential parts and their basicorganization and architecture difficult or impossible. Though the Model-A has
been replaced by everything from the Yugo to the Honda Accord, theautomobile “body plan” with several essential functional and/or structuralelements has remained unchanged from its first appearance in the latenineteenth century.
Further, despite the design of many innovative variations, automobiles
have retained their “morphological distance” or structural disparity from otherfunctionally distinct technological devices. Indeed, persistent morphologicaldisparity in biological systems (manifested as stasis in the fossil record) has adirect parallel in our own technology. In biology, what we recognize as
different organismal body plans are systems that differ fundamentally fromeach other in their overall organization. A crab and a starfish, for example,
may exhibit some similarities in their low-level protein parts, but they differ
fundamentally in their digestive and nervous systems and in the overall
organization of their organs and body parts. In the same way, automobiles andairplanes may have many similar parts, even as they differ in the compositionof their distinguishing parts and overall organization.
The presence of such structural disparities and isolation among complex
functionally integrated systems represents another distinctive feature of theintelligently designed systems known from our own world of technology. For
example, the basic technology of the CD-ROM (as employed in audio
systems and computers) did not “evolve” incrementally from earlier
technologies, such as magnetic media (e.g., digital tape or disc storage) or
analog systems such as the once standard long-playing (LP) record. Indeed, it
could not. In an analog recording, information is stored as three-dimensional
microscopic grooves in a vinyl surface and is detected mechanically by adiamond stylus. This means of storing and detecting information differs
fundamentally, as a system, from the digitally encoded pits storing data in thesilvered surface of a CD-ROM, where information is detected optically, notmechanically, by a laser beam. The CD-ROM had to be engineered fromscratch and, as a result, displays a striking structural difference and isolationfrom other technological devices, even those that perform roughly the samefunction. Although minor new features may “accrete” to its basic design
architecture, a deep and impassable functional gulf separates the CD-ROM asa system from other technological systems. As biologist Michael Denton
expresses it, “What is true of sentences and watches is also true of computer
programs, airplane engines, and in fact of all known complex systems.
Almost invariably, function is restricted to unique and fantasticallyimprobable combinations of subsystems, tiny islands of meaning lost in an
infinite sea of incoherence.”32 In fact, such structural disparity ormorphological isolation constitutes a diagnostic of designed systems—that is,a feature of systems for which only one kind of cause—an intelligent cause—
is known.
ACTS OF MIND
Studies in the history and philosophy of science have shown that to explain an
event or a set of facts, scientists must typically cite a cause capable ofproducing that event or those facts. When scientists do not have the luxury of
directly observing the cause of a particular event or effect under study, as
historical scientists typically do not, they must cite a cause that is otherwise
known to produce the facts in question. That means historical scientists mustshow that the event or facts of interest must in some way represent the
expected outcome of a particular cause having acted in the past—that theevent or facts should have occurred “as a matter of course.”
To many scientists, especially those steeped in the materialistic
assumptions of contemporary scientific culture, the idea of intelligent design
seems inherently implausible or even incoherent. Science to them involves
not only observing and studying material entities and phenomena, but
explaining them by reference to materialistic entities. For these scientists, it
makes no sense even to consider the idea of intelligent design, with its
explicit reference to the activity of a designing mind.
Yet it turns out that both the Cambrian animal forms themselves and theirpattern of appearance in the fossil record exhibit precisely those features that
we should expect to see if an intelligent cause had acted to produce them (seeFig. 18.7). Further, the Cambrian animal forms and their manner of
appearance contradict what we should expect to find in the fossil record andin the animal world given a purely materialistic “bottom-up” process ofevolution. Thus, despite its potential for disturbing the materialistic
sensibilities of many scientists, it is hard logically to avoid the conclusion thatthe design hypothesis actually provides a better, more casually adequate
explanation for key features of the Cambrian event.
When Darwin first acknowledged the problem of the Cambrian fossil
record, and the small but persistent doubt it raised for him about his theory,
his nemesis Louis Agassiz not only rejected his theory of evolution, but alsoaffirmed an alternative understanding of the nature and origin of animal life.
To Agassiz, the pattern of animal classification and the fossil record
reinforced the idea that living forms exemplified basic “types”—ideas that

had originated in the mind of a designing intelligence. Thus, he would argue
that the Cambrian fossils tell of “acts of mind.”33
As noted in Chapter 1, Darwin himself acknowledged both Agassiz’s
immense paleontological knowledge and the validity of the problems that
Agassiz raised. Even so, his affirmation of a positive alternative to Darwin’s
theory in the form a design hypothesis might well have seemed premature in
the 1860s and certainly did reflect something of the prejudice of the times.
But more than a century and a half later, after many failed attempts todiscover—and explain away—the missing fossil ancestors, and after
discoveries in molecular and developmental biology have revolutionized ourunderstanding of the complexity of animal life, continuing to regard theCambrian explosion as merely a niggling problem for established theory—alone question mark or negative clue—now seems not so much cautious, as
simply unresponsive to the evidence.

FIGURE 18.7

Both the Cambrian animal forms and their pattern of appearance in the fossil
record exhibit distinctive features or hallmarks of designed systems—featuresthat we should expect to see if an intelligence acted to produce them.
The animal forms that arose in the Cambrian not only did so without any
clear material antecedent; they came on the scene complete with digital code,
dynamically expressed integrated circuitry, and multi-layered, hierarchicallyorganized information storage and processing systems.
In light of these marvels and the persistent pattern of the fossil record,should we now continue, as Darwin did (who knew nothing of them), toregard the Cambrian explosion as just an anomaly? Or may we now consider
the features of the Cambrian event as evidence supporting another view of theorigin of animal life? If so, is there now a compelling logic for considering a
different kind of causal history?
In fact, there is. The features of the Cambrian event point decisively inanother direction—not to some as-yet-undiscovered materialistic process thatmerely mimics the powers of a designing mind, but instead to an actual
intelligent cause. When we encounter objects that manifest any of the key
features present in the Cambrian animals, or events that exhibit the patterns
present in the Cambrian fossil record, and we know how these features andpatterns arose, invariably we find that intelligent design played a causal rolein their origin. Thus, when we encounter these same features in the Cambrian
event, we may infer—based upon established cause-and-effect relationships
and uniformitarian principles—that the same kind of cause operated in thehistory of life. In other words, intelligent design constitutes the best, mostcausally adequate explanation for the origin of information and circuitry
necessary to build the Cambrian animals. It also provides the best explanation
for the top-down, explosive, and discontinuous pattern of appearance of theCambrian animals in the fossil record.

19
The Rules of Science
The argument of the previous chapter raises an obvious question. If intelligent
design provides such a clear and satisfying resolution to the mystery of theCambrian explosion, why have so many brilliant scientists missed it?
While reflecting on this question, I came across a short story by G. K.
Chesterton called “The Invisible Man,” which may cast some light on it. In“The Invisible Man,” Chesterton tells the story of someone who is murderedin an apartment with only one entrance, an entrance watched by four honestmen. These men insist that during their watch no one entered or left thebuilding. A brilliant French detective investigates the case, along with his
friend, a dusty little Catholic priest. They query the guards, each of whom
insists that no one entered or exited the building. But then the unimpressive
looking priest, Father Brown, all but forgotten in the background, pipes up toask, “Has nobody been up and down stairs, then, since the snow began to
fall?”“Certainly not,” they assure him.
“Then I wonder what that is?” Father Brown asks, gazing at the whitesnow on the outside entrance stairs. Everyone turns to find a “stringy patternof grey footprints” there.
“God!” one of them cries, “An invisible man!”After asking a few more questions, Father Brown quickly unravels themystery. “When those four quite honest men said that no man had gone into
the Mansions, they did not really mean that no man had gone into them,”
Father Brown explains to his detective friend. “They meant no man whomthey could suspect of being your man. A man did go into the house and didcome out of it, but they never noticed him.”“An invisible man?”“A mentally invisible man,” the priest explains.
What does a mentally invisible man look like?
“He is dressed rather handsomely in red, blue and gold,” the priest
explains, “and in this striking, and even showy, costume he entered Himylaya

Mansions [the name of the apartment complex] under eight human eyes; hekilled . . . [the murder victim] in cold blood, and came down into the street
again carrying the dead body. . . . You have not noticed such a man as this.”At that moment, he reaches out and puts his hand on “an ordinary passing
postman,” one who had almost slipped by them unnoticed.
“Nobody ever notices postmen somehow,” Father Brown muses. “Yet they
have passions like other men, and even carry large bags where a small corpse
can be stowed quite easily.”1
The passing postman, of course, is the murderer. He walked up and down
the stairs under the four men’s noses, but because of their mental blinders
telling them whom to consider and whom to ignore, they overlooked thepostman entirely.
The theme is a favorite of detective-story authors: the obvious possibility
missed by the experts, because their assumptions prevent them fromconsidering what might otherwise seem to be an obvious possibility. Could
something like that be at work in the investigation of the Cambrian
explosion? Could evolutionary biologists and paleontologists be wearing a setof mental blinders that keeps them from considering a possible explanation of
the Cambrian mystery?
Odd as it may seem, that is exactly what has been going on in theinvestigation of the Cambrian explosion. In this case, however, those wearing
the mental blinders have elevated an unwillingness to consider certain
explanations to a principle of scientific method. That principle is called“methodologicalnaturalism”
or“methodologicalmaterialism.”
Methodological naturalism asserts that to qualify as scientific, a theory must
explain phenomena and events in nature—even events such as the origin of
the universe and life or phenomena such as human consciousness—byreference to strictly material causes. According to this principle, scientists
may not invoke the activity of a mind or, as one philosopher of science puts it,
any “creative intelligence.”2
To see how adherence to this principle has prevented scientists fromconsidering a possibly true (even “causally adequate”) explanation for the
Cambrian explosion, let’s revisit the case reported in Chapter 11 of Richard
Sternberg (see Fig. 19.1), the evolutionary biologist at the Smithsonian’s
National Museum of Natural History. After Sternberg published my article
arguing for intelligent design as the best explanation of the Cambrian
information explosion in the technical journal Proceedings of the BiologicalSociety of Washington,3 he suffered professional retribution at the hands ofSmithsonian administrators.4 The Biological Society of Washington, thegoverning body that oversees the publication of the journal that Sternberg
then edited, also issued a public statement repudiating his decision.5 Its
statement did not, however, cite any factual errors in the article or seek torebut it. Further, the president of the society, Smithsonian zoologist Roy
McDiarmid, wrote Sternberg privately and told him that he (McDiarmid) had
reviewed the file containing the peer-review reports and had found everything
to be in order.6
What, then, had Sternberg done to deserve public rebuke?
Sternberg published a paper that violated a presumed rule of science:
methodological naturalism. Without saying it in so many words, theBiological Society made crystal clear that this was the crucial issue. When it
distanced itself from Sternberg and the review essay, it did not invite ascientific refutation of the article, as if the problem had been amisrepresentation or misinterpretation of the evidence. Instead, it attempted tosettle the issue by releasing a policy statement. As a writer in the Wall Street
Journal reported at the time, “The Biological Society of Washington releaseda vaguely ecclesiastical statement regretting its association with the article. It
did not address its arguments but denied its orthodoxy, citing a resolution of
the American Association for the Advancement of Science that defined ID[the theory of intelligent design] as, by its very nature, unscientific.”7

FIGURE 19.1
Richard Sternberg. Courtesy Laszlo Bencze.

The Biological Society of Washington “deemed the paper inappropriate forthe pages of the Proceedings.”8 The Society attempted to justify this claim,
first, on thin procedural grounds, claiming that a paper about the origin ofanimal body plans represented a “departure” from its more typical concern
with issues of animal classification. Second, and more tellingly, it cited thepolicy statement of the American Association for the Advancement of
Science (AAAS) “calling upon its members to understand the nature ofscience” and to recognize “the inappropriateness of ‘intelligent design theory’as subject matter for science education.”9 Setting aside the obvious point thatmy paper was written not as a curricular manifesto but as an evidence-based
scientific argument, the AAAS statement affirmed an implicitly and strictly
materialistic understanding of the nature of science. It did so to disqualify
intelligent design from consideration—not only in science education, but inscience itself.
The Sternberg case—like numerous others in which the academic freedomof scientists advocating intelligent design has been abridged10—goes a long
way to answering the question of why so many otherwise brilliant andknowledgeable scientists have overlooked such a seemingly obvious possible
answer to the Cambrian conundrum. As in Chesterton’s story about theinvisible postman, they have accepted a self-imposed limitation on the
hypotheses they are willing to consider. These scientists think they are doing
their duty to science. Yet if researchers refuse as a matter of principle toconsider the design hypothesis, they will obviously miss any evidence that
happens to support it. And the cultural pressure within biology to avoid
considering the intelligent design hypothesis has long been nontrivial. Francis
Crick, for example, famously admonished biologists to “constantly keep inmind that what they see was not designed, but rather evolved.”11 In 1997, inan article in the New York Review of Books, Harvard geneticist Richard
Lewontin made explicit a similar commitment to a strictly materialistic
explanation—whatever the evidence might seem to indicate. As he explainedin a now often quoted passage:
We take the side of science in spite of the patent absurdity of some of its
constructs, in spite of its failure to fulfill many of its extravagant
promises of health and life, in spite of the tolerance of the scientificcommunity for unsubstantiated just-so stories, because we have a priorcommitment, a commitment to materialism. It is not that the methods
and institutions of science somehow compel us to accept a material
explanation of the phenomenal world, but, on the contrary, that we areforced by our a priori adherence to material causes to create anapparatus of investigation and a set of concepts that produce material
explanations, no matter how counter-intuitive, no matter how
mystifying to the uninitiated. Moreover, that materialism is absolute, for
we cannot allow a Divine Foot in the door.12
The commitment to methodological naturalism that Lewontin describes, aswell as the behavior of scientists in cases such as Sternberg’s, leave no doubtthat many in science simply will not consider the design hypothesis as an
explanation for the Cambrian explosion or any other event in the history oflife, whatever the evidence. To do so would be to violate the “rules ofscience” as they understand them.
BUT IS IT SCIENCE?
But are these scientists right? Perhaps science must limit itself to purely
naturalistic or materialistic explanations. If so, are there perhaps good reasonsfor excluding the design hypothesis from consideration as a scientifichypothesis? Is methodological naturalism the correct policy for science?
Though scientists routinely assert methodological naturalism as a scientificnorm, that principle and its exclusion of the design hypothesis have provendifficult to justify. To claim that a specific theory does not qualify as scientificrequires a definition of science or a set of definitional criteria by which to
make that kind of a judgment. Some philosophers and scientists have asserted
that for a scientific theory to qualify as scientific, it must meet various criteriaof testability, falsifiability, observability, repeatability, and the like.
Philosophers of science call these “demarcation criteria,” because somescientists purport to use them to define or “demarcate” science and to
distinguish it from pseudo science or from other forms of inquiry such as
history, religion, or metaphysics.13
THE GENERAL PROBLEM OF DEMARCATION
The demarcation question has long been a vexing one. Historically, scientists
and philosophers of science have thought that science could be distinguishedby its especially rigorous method of study. But attempts to define science byreference to a distinctive method have proven problematic because different
branches and types of science use different methods.
For example, some scientific disciplines distinguish and classify natural
entities, while others attempt to formulate overarching laws that apply to allentities. Some disciplines perform laboratory experiments under controlled
and replicable conditions, while others attempt to reconstruct or explain
singular events in the past, often based on field studies of evidence or clues
rather than laboratory experiments. Some disciplines generate mathematicaldescriptions of natural phenomena without positing mechanisms to explainthem. Others look for mechanisms or explain law-like regularities byreference to underlying mechanisms. Some scientific disciplines makepredictions to test theories, while others test competing theories by comparing
their explanatory power. Some disciplines use both these methods, whilesome conjectures (particularly in theoretical physics) may not be testable atall. And on it goes.
An episode in the history of science illustrates the problem. During theseventeenth century, a group of scientists called the “mechanicalphilosophers” insisted, based largely on advances in early chemistry, thatscientific theories must provide mechanistic explanations. Such explanations
had to involve one material entity pushing or pulling another. Yet in physics,
Isaac Newton (1642–1727) formulated an important theory that provided nomechanistic explanation. His theory of universal gravitation describedmathematically, but did not explain in a mechanistic way, the gravitational
attraction between planetary bodies—bodies separated from each other by
miles of empty space with no means of mechanical interaction with eachother whatsoever.14 Despite provocation from the German mathematician
Gottfried Wilhelm Leibniz (1646–1716), who defended the mechanistic ideal,
Newton expressly refused to give any explanation, mechanistic or otherwise,
for the mysterious “action at a distance” that his theory described.15
Did that make Newton’s theory unscientific? Strictly speaking, the answer
depends upon which definition of science someone chooses to apply. Today
one would be hard-pressed to find anybody who denies that Newton’s famous
theory qualified as scientific. Yet we could easily find scientists still willing tosay scientific theories must provide mechanisms as well as others who would
deny as much.
And that is the problem. If scientists and philosophers of science do nothave an agreed-upon definition of science, how can they settle questions
about which theories do and do not qualify as scientific? If scientists lacksuch a definition, it’s difficult to argue that any particular theory is
unscientific by definition. For this reason, philosophers of science, thescholars who study the nature and definition of science, now almost
universally reject the use of demarcation arguments to decide the validity oftheories or settle competition between them.16 They increasingly regard
demarcation as an essentially semantic question and nothing more. Is theory

X scientific or not? Answer: that depends upon which definition of science isused to decide the question.
Moreover, as the philosopher of science Larry Laudan has shown in aseminal article, “The Demise of the Demarcation Problem,” attempts to apply
demarcation criteria to decide the scientific status of specific theories haveinvariably generated irreconcilable contradictions.17 The vortex theory ofgravity that Newton’s theory replaced envisioned planets swirling around thesun pushed by a substance called ether.18 It did provide a mechanistic
explanation for gravitational attraction. It failed, however, to explain theevidence and was judged by Newton and physicists following him to be
manifestly false. Nevertheless, because it proposed a mechanistic cause ofgravitation, it qualified as “scientific”—at least given the conception ofscience favored by Leibniz and the mechanical philosophers.19 Conversely,
Newton’s theory failed to as scientific by their definition, though it much
more accurately fit the evidence.
Such contradictions have long beset the whole enterprise of demarcation.
Theories that scientists have rejected as false because of their inability to
explain or describe the evidence often meet the very criteria or
methodological features (testability, falsifiability, repeatability, observability,etc.) that allegedly characterize true science. On the other hand, many highly
esteemed or successful theories often lack allegedly necessary features ofgenuine science.
Thus, philosophers of science generally think it much more important toassess whether a theory is true, or whether the evidence supports it, thanwhether it should or should not be classified as “science.” The question ofwhether a theory is “scientific” is really a red herring. What we really want toknow is whether a theory is true or false, supported by the evidence or not,worthy of our belief or not. And we cannot decide those questions byapplying a set of abstract criteria that purport to tell in advance what all goodscientific theories must look like.20
DEFINE AND DISMISS: DEMARCATION ARGUMENTS AGAINSTINTELLIGENT DESIGN
The rejection of demarcation arguments among philosophers of science has
not stopped critics of intelligent design from attempting to settle debates
about biological origins by the expedient of formulating such arguments
against intelligent design. Some use these arguments to justify
methodological naturalism (which has the same effect).
Advocates of methodological naturalism have argued that the theory ofintelligent design is inherently unscientific for some, or all, of the following
reasons: (a) is not testable,21 (b) is not falsifiable,22 (c) does not makepredictions,23 (d) does not describe repeatable phenomena, (e) does not
explain by reference to natural law,24 (f) does not cite a mechanism,25 (g)does not make tentative claims,26 and (h) has no problem-solving capability.27
They have also claimed that it is not science because it (i) refers to an
unobservable entity.28 These critics also assume, imply, or assert thatmaterialistic evolutionary theories do meet such criteria of proper scientificmethod.
Readers may wish to consult Signature in the Cell for a more detailed
response to these specific arguments. There I show that many of these claims
are simply false (e.g., contrary to the claims of its critics intelligent design is
testable; it does make predictions; it does formulate its claims tentatively; andit does have scientific problem-solving capability). But I also show that when
the claims of those making demarcation arguments are true—when intelligent
design doesn’t meet a specific criterion—that fact does not provide goodreason for excluding intelligent design from consideration as a scientifictheory. Why? Because the materialistic evolutionary theories that intelligent
design challenges, theories widely regarded by convention as “scientific,” failto meet the very same demarcation standard. In other words, there is no
defensible definition of science, and no specific demarcation criterion, thatjustifies both excluding intelligent design from science and including
competing materialistic evolutionary theories. Instead, attempts to use
demarcation criteria specifically to disqualify intelligent design as a scientifictheory have repeatedly failed to differentiate the scientific status of intelligent
design from that of competing theories. Depending upon which criteria areused to adjudicate their scientific status, and provided metaphysically neutral
criteria are selected to make such assessments, intelligent design andmaterialistic origins theories invariably prove equally scientific or
unscientific.
For example, some critics of intelligent design have argued that it fails toqualify as a scientific theory because it makes reference to an unseen or
unobservable entity, namely, a designing mind in the remote past. Yet many
accepted theories—theories assumed to be scientific—postulate unobservable
events and entities. Physicists postulate forces, fields, and quarks; biochemists
infer submicroscopic structures; psychologists discuss their patients’ mental
states. Evolutionary biologists themselves infer unobserved past mutations
and invoke the existence of extinct organisms and transitional forms forwhich no fossils remain. Such things, like the actions of an intelligent

designer, are inferred from observable evidence in the present, because of the
explanatory power they may offer.
If the demarcation criterion of observability is applied rigidly, then both
intelligent design and materialistic theories of evolution fail to qualify as
scientific. If the standard is applied more liberally (or realistically)—acknowledging the way in which historical scientific theories often infer
unobservable past events, causes, or entities—then both theories qualify as
scientific.
And so it goes with other such criteria as well. There is no specific (nonquestion-begging) demarcation criterion that succeeds in disqualifying thetheory of intelligent design from consideration as a scientific theory without
also doing the same to its materialistic rivals.
REASONS TO REGARD INTELLIGENT DESIGN AS A SCIENTIFIC
THEORY
Demarcation arguments fail to justify excluding intelligent design fromscience. But it turns out that there are some good—if convention-dependent—
reasons to regard intelligent design as a scientific theory.
For example, many scientists and philosophers of science regard testability
as an important feature of scientific inquiry. And intelligent design is testablein three specific and interrelated ways. First, like other scientific theories
concerned with explaining events in the remote past, intelligent design is
testable by comparing its explanatory power with that of competing theories.
Second, intelligent design, like other historical scientific theories, is tested
against our knowledge of the cause-and-effect structure of the world. As wehave discussed, historical scientific theories provide adequate explanations
when they cite causes that are known to produce the effects in question or“causes now in operation.”29 Because of this, the plausibility of historicalscientific theories, including intelligent design, can be tested by reference toindependent knowledge of cause-and-effect relationships. Third, although
historical scientific theories typically cannot be tested under controlledlaboratory conditions, they do sometimes generate predictions that enable
scientists to compare their merit to that of other theories. Intelligent design
has generated a number of specific empirical predictions that distinguish itfrom competing evolutionary theories and that serve to confirm the design
hypothesis over its competitors. (In Signature in the Cell, I described ten suchpredictions that the theory of intelligent design has generated).30
There is another compelling, if convention-dependent, reason to regard
intelligent design as a scientific theory. The inference to intelligent design isbased upon the same method of historical scientific reasoning and the same
uniformitarian principles that Charles Darwin used in On the Origin ofSpecies. The similarity in logical structure runs quite deep. Both the argument
for intelligent design and the Darwinian argument for descent withmodification were formulated as abductive inferences to the best explanation.
Both theories address characteristically historical questions; both employ
typically historical forms of explanation and testing; and both havemetaphysical implications. Insofar as we regard Darwin’s theory as ascientific theory, it seems appropriate to designate the theory of intelligent
design as a scientific theory as well.
Indeed, neo-Darwinism and the theory of intelligent design are not two
different kinds of inquiry, as some critics have asserted. They are twodifferent answers—formulated using a similar logic and method of reasoning—to the same question: “What caused biological forms and the appearance ofdesign to arise in the history of life?” It stands to reason that if we regard one
theory, neo-Darwinism or intelligent design, as scientific, we should regard
the other as the same. Of course, whether either theory is true or not is anothermatter. An idea may be scientific and incorrect. In the history of science,
many theories have proven to be so. The vortex theory of gravity, to which I
referred earlier, would be one of nearly countless illustrations.
For readers who would like to consider more detailed responses toarguments about whether intelligent design qualifies as “science,” I
recommend Chapters 18 and 19 in Signature in the Cell.31 In Signature, I
respond in detail to other philosophical objections to the case for intelligent
design. These include challenges such as: (a) intelligent design is religion, notscience,32 (b) the case for intelligent design is based on flawed analogicalreasoning, (c) intelligent design is a fallacious argument from ignorance,sometimes called the “God of the Gaps” objection, (d) intelligent design is ascience stopper, (e) the famous zinger, popularized by Richard Dawkins, thatasks “Who designed the designer?”33 and many others.
A NEW OBJECTION TO THE SCIENTIFIC STATUS OFINTELLIGENT DESIGN
Since the publication of Signature in the Cell, Robert Asher, a University ofCambridge paleontologist, has offered another reason to contest my
characterization of intelligent design as a scientific theory. In his book,
Evolution and Belief, he challenges my claim to have used the uniformitarian
method of Lyell and Darwin to develop the case for intelligent design. Since
his objection is new, published only in 2012 by Cambridge University Press,

it deserves discussion.
Asher characterizes my thinking as follows: “The processes we know andobserve today are relevant to explaining the phenomena of the past, and weknow that particularly complicated things we see today have an intelligencebehind them.”34 He notes that I argue certain complex technologies, such as
computer software, have “only one source: human ingenuity.”35 It follows,
according to Asher’s paraphrase of my argument that “a similarly complex
device we observe in the geological past must also have arisen as a result ofsomething like human ingenuity, i.e., intelligence.”36
Asher doesn’t seem to understand the importance of specified information,
as opposed to “complicated things,” as a key indicator of design. That aside,
he does claim to recognize the role of uniformitarian principles of reasoning
in my argument for intelligent design. In spite of this, Asher elsewhere
disputes that I employ the uniformitarian method of reasoning. Why?
According to Asher, the inference to intelligent design is actually “antiuniformitarian” because it doesn’t provide a “mechanism.” As he puts it, “byattempting to replace a causal mechanism (natural selection) with an
attribution of agency (design), ID advocates such as Meyer are decidedly antiuniformitarian. What process of today could possibly lead to his
understanding of the past?”37
The answer to Asher’s question seems pretty obvious. The answer is:
intelligence. Conscious activity. The deliberate choice of a rational agent.
Indeed, we have abundant experience in the present of intelligent agents
generating specified information. Our experience of the causal powers ofintelligent agents—of “conscious activity” as “a cause now in operation”—
provides a basis for making inferences about the best explanation of the originof biological information in the past. In other words, our experience of thecause-and-effect structure of the world—specifically the cause known to
produce large amounts of specified information in the present—provides abasis for understanding what likely caused large increases in specified
information in living systems in the past. It is precisely my reliance on such
experience that makes possible an understanding of the type of causes at workin the history of life. It also makes my argument decidedly uniformitarian—not “anti-uniformitarian”—in character.
Asher confuses the uniformitarian imperative in historical scientificexplanations (the need to cite a presently known or adequate cause) with ademand for citing a material cause, or mechanism. The theory of intelligent
design does cite a cause, and indeed one known to produce the effects inquestion, but it does not necessarily cite a mechanistic or materialistic cause.

Proponents of intelligent design may conceive of intelligence as a strictly
materialistic phenomenon, something reducible to the neurochemistry of abrain, but they may also conceive of it as part of a mental reality that is
irreducible to brain chemistry or any other physical process. They may also
understand and define intelligence by reference to their own introspective
experience of rational consciousness and take no particular position on themind-brain question.
Asher assumes that intelligent design denies a materialistic or “physicalist”
account of the mind (as I personally do, in fact) and rejects it as unscientificon that basis. But he offers no noncircular reason for making that judgment.
He cannot say that the principle of methodological naturalism requires that all
genuinely scientific theories invoke only mechanistic causes, because theprinciple of methodological naturalism itself needs justification. And
asserting that “all genuinely scientific theories must provide mechanisms” isjust to restate the principle of methodological naturalism in different words.
Indeed, to say that all scientific explanations must provide a mechanism isequivalent to saying that they must cite materialistic causes—precisely what
the principle of methodological naturalism asserts. Asher seems to be
assuming without justification that all scientifically acceptable causes aremechanistic or materialistic. His argument thus assumes a key point at issue,
which is whether there are independent—that is, metaphysically neutral—reasons for requiring historical scientific theories to cite materialistic causesin their explanations as opposed to explanations that invoke possibly
immaterial entities such as creative intelligence, mind, mental action, agency,
or intelligent design.
In any case, he confuses the logical requirement of citing a vera causa, atrue or known cause, with an arbitrary requirement to cite only materialistic
causes. He confuses uniformitarianism with methodological naturalism.38 He
then critiques my design argument for rejecting the former, though it only
rejects the latter. In so doing, he imposes an additional requirement on
explanations of past events that leads him to mistake my argument as antiuniformitarian and to miss the evidence for intelligent design. His implicit
commitment to methodological naturalism makes the evidence for intelligent
design—“the postman,” as it were—mentally invisible to him.
Nevertheless, the concern that he raises about the theory of intelligent
design not citing a mechanism still troubles people. In fact, I frequently getquestions about this issue. People will ask something like this: “I can see yourpoint about digital code providing evidence for intelligent design, but how
exactly did the designing intelligence generate that information or arrange
matter to form cells or animals?” Or: “How did the intelligent designer thatyou infer impress its ideas on matter to form animals?” As Asher puts it,“How could a biological phenomenon, even if designed, be simply willed into
existence without an actual mechanism?”39
To help clear things up, several points need to be considered. First, thetheory of intelligent design does not provide a mechanistic account of theorigin of biological information or form, nor does it attempt to. Instead, it
offers an alternative causal explanation involving a mental, rather than anecessarily or exclusively material, cause for the origin of that reality. It
attributes the origin of information in living organisms to thought, to therational activity of a mind, not a strictly material process or mechanism. That
does not make it deficient as a materialistic or mechanistic explanation. It
makes it an alternative to that kind of explanation. Advocates of intelligent
design do not propose intelligent causes because they cannot think of a
possible mechanistic explanation for the origin of form or information. They
propose intelligent design because they think it provides a better, morecausally adequate explanation for these realities. Given what we know fromexperience about the origin of information, materialistic explanations are thedeficient ones.
There is a different context in which someone might want to ask about amechanism. He or she may wish to know by what means the information,
once originated, is transmitted to the world of matter. In our experience,
intelligent agents, after generating information, often use material means totransmit that information. A teacher may write on a chalkboard with a pieceof chalk or an ancient scribe may have chiseled an inscription in a piece ofrock with a metal implement. Often, those who want to know about themechanism of intelligent design are not necessarily challenging the idea that
information ultimately originates in thought. They want to know how, or bywhat material means, the intelligent agent responsible for the information inliving systems transmitted that information to a material entity such as a
strand of DNA. To use a term from philosophy, they want to know about “theefficient cause” at work.
The answer is: We simply don’t know. We don’t have enough evidence orinformation about what happened, in the Cambrian explosion or other eventsin the history of life, to answer questions about what exactly happened, eventhough we can establish from the clues left behind that an intelligent designer
played a causal role in the origin of living forms.
An illustration from archaeology helps explain how this can be so (see Fig.
19.2). Years ago explorers of a remote island in the southwestern Pacific
Ocean discovered a group of enormous stone figures. The figures displayed
the distinctive shape of human faces. These figures left no doubt as to theirultimate origin in thought. Nevertheless, archeologists still don’t know theexact means by which they were carved or erected. The ancient head carvers
might have used metallic hammers, rock chisels, or lasers for that matter.
Though archaeologists lack the evidence to decide between various
hypotheses about how the figures were constructed, they can still definitely
infer that intelligent agents made them. In the same way, we can infer that an
intelligence played a causal role in the origin of the Cambrian animals, even if
we cannot decide what material means, if any, the designing intelligence used
to transmit the information, or shape matter, or impart its design ideas toliving form. Although the theory of intelligent design infers that an intelligent
cause played a role in shaping life’s history, it does not say how the intelligent
cause affected matter. Nor does it have to do so.

FIGURE 19.2
Group of carvings of giant heads, called “Moais,” on Easter Island. Courtesy
iStockphoto/Think-stock.
There is a logical reason we cannot without further information determine
the mechanism or means by which the intelligent agent responsible for lifetransmitted its design to matter. We can infer an intelligent cause from certain
features of the physical world, because intelligence is known to be anecessary cause, the only known cause, of those features. That allows us toinfer intelligence retrospectively as a cause by observing its distinctive
effects. Nevertheless, we cannot establish a unique scenario describing how
the intelligent agent responsible for life arranged or impressed its ideas on
matter, because there are many different possible means by which an idea inthe mind of an intelligent agent could be transmitted or instantiated in thephysical world.
There is another even more profound reason that intelligent design—indeed, science itself—may not be able to offer a completely mechanistic
account of the instantiation of thought into matter. Robert Asher worries
about how “a biological phenomenon, even if designed,” could be “simply
willed into existence without an actual mechanism.” In Asher’s
understanding, the uniformitarian principle asks for a precedent, a known
cause that not only generates information, but translates immaterial thought
into material reality, impressing itself on and shaping the physical world.
Asher complains that the argument for intelligent design cannot cite such a
precedent and is thus “anti-uniformitarian.”
Yet a precedent comes very readily to mind, an intimately familiar one for
us all. At present no one has any idea how our thoughts—the decisions andchoices that occur in our conscious minds—affect our material brains, nerves,and muscles, going on to instantiate our will in the material world of objects.
However, we know that is exactly what our thoughts do. We have no
mechanistic explanation for the mystery of consciousness, nor what is called
the “mind-body problem”—the enigma of how thought affects the material
state of our brains, bodies, and the world that we affect with them. Yet there is
no doubt that we can—as the result of events in our conscious minds called
decisions or choices—“will into existence” information-rich arrangements ofmatter or otherwise affect material states in the world. Professor Asher did
this when he wrote the chapter in his book—representing his ideas impressed
as words onto a material object, a printed page—attempting to refuteintelligent design. I am doing this right now. This example, representative ofcountless daily experiences in life, surely satisfies the demands ofuniformitarianism.
Though neuroscience can give no mechanistic explanation for
consciousness or the mind-body problem, we also know that we canrecognize the product of thought, the effect of intelligent design, in its
distinctive information-rich manifestations. Professor Asher recognizedevidence of thought when he read the text in my book; I did so when I readhis; you are doing so right now. Thus, even though it remains entirely possiblethat we may never know how minds affect matter and, therefore, that there
may always be a gap in our attempt to account for how a designing mind
affected the material out of which living systems were formed, it does notfollow that we cannot recognize evidence of the activity of mind in living
systems.

WHY IT MATTERS FOR SCIENCE
But if proponents of intelligent design admit that they do not, or perhaps evencannot, answer the question of how the mind responsible for the design ofanimal life impressed its ideas on matter, why does it matter that we recognize
the evidence for intelligent design at all? If intelligent design just replaces one
mystery with another, why not limit ourselves to materialistic explanations
after all, as methodological naturalism requires, and be content with accepting
the mystery we already have? Wouldn’t that be simpler and more
intellectually economical?
Perhaps. But it puts the mystery in the wrong place. We do know of acause that can produce the functional information necessary to build complex
systems. But we do not know exactly how mind interfaces with matter. If wewere to ask what caused the Rosetta Stone to arise, and then insist despite all
evidence to the contrary that a purely material process is capable of producing
the information-rich etchings on that stone, we would be deluding ourselves.
The information etched into that black slab of igneous rock at the British
Museum provides overwhelming evidence that an intelligent agent did cause
those inscriptions. Any rule that prevents us from considering such an
explanation diminishes the rationality of science, because it prevents
scientists from considering a possibly—and in this case obviously—true
explanation. And the truth matters, not least in science. For this reason, the“rules of science” should not commit us to rejecting possibly true theories
before we even consider the evidence. But that is exactly what
methodological naturalism does.
Moreover, adhering to methodological naturalism and refusing to consider
the evidence for intelligent design in life does not just affect the explanations
that we are willing to consider for the origins and history of life. They also
affect the questions we ask about life as it exists, and thus the entire biologicalresearch agenda that we pursue.
An analogy to a human artifact again shows why. If we ask exactly how
the scribe responsible for the inscriptions on the Rosetta Stone accomplished
his or her task—with a metal chisel, a sharpened piece of obsidian, a diamondstylus, or some other material means—we may not have enough evidence toanswer that question. Nevertheless, it will help archaeologists to know thatthey are looking at an artifact of intelligence, rather than a byproduct ofstrictly natural processes. This will lead them to ask other more relevant
questions about the stone, such as: “What do the inscriptions mean?” “Whowrote them?” and “What do they tell us about the surrounding cultures at the
time?” In a similar way, what we think about how animal life arose anddeveloped will lead us to ask different questions about living forms—
questions that we might never think to ask if we were assuming that they hadarisen by a purely undirected mechanism such as natural selection.
Intelligent agents and natural selection do their work very differently. The
mutation and selection mechanism is a blind, trial-and-error process, one thatmust maintain or optimize functional advantage through a series ofincremental steps. Given Darwinian assumptions, we would not expect to see
structures or systems in living organisms that required foresight. Nor would
we expect to see structures that needed to be produced all at once in large
jumps rather than by a series of function-preserving incremental steps. We
would, however, expect to see evidence of a trial-and-error process in the
genomes of organisms.
But what happens if we open ourselves to the possibility of detecting
design in life? We know a lot about how intelligent designers do their work.
Intelligent designers use many established design strategies (or “design
patterns,” as engineers would say). They also have foresight that allows themto reach functional goals without the need to maintain function through aseries of intermediate structures. They typically engineer new systems fromscratch without relying on random, incremental, trial-and-error modifications
in one system to produce another.
Because these two different types of causes operate differently and often
produce different types of structures and systems, scientists should expect
living systems (and the history of life) to look differently depending uponwhich type of cause produced the organisms or structures in question. And
these differing perspectives and expectations can lead scientists to ask
different research questions and make different predictions about what weshould find in the structure of life itself.
THE ENCODE PROJECT AND AN ID PREDICTION
In 2012, a dramatic confirmation of one such prediction made by advocates ofintelligent design occurred in the field of genomics. Three leading sciencejournals, Nature, Genome Research, and Genome Biology, published a seriesof groundbreaking papers reporting on the results of a massive study of thehuman genome called the ENCODE project (short for Encyclopedia of DNA
Elements).40 The conclusion: at least 80 percent of the genome performs
significant biological functions, “dispatching the widely held view that thehuman genome is mostly ‘junk DNA.’ ”41
The discovery challenged a long held neo-Darwinian interpretation of the
genome. According to neo-Darwinism, the genome as a whole should display

evidence of the random trial-and-error process that gave rise to new genetic
information. The discovery in the 1970s that only a small percentage of the
genome contains information for building proteins was hailed at the time as
powerful confirmation of the Darwinian view of life. The noncoding regionsof the genome were assumed to be nonfunctional detritus of the trial-and-error
mutational process—the same process that produced the functional code in
the genome. As a result, these noncoding regions were deemed “junk DNA,”
including by no less a scientific luminary than Francis Crick.42
Because intelligent design asserts that an intelligent cause produced the
genome, design advocates have long predicted that most of the nonproteincoding sequences in the genome should perform some biological function,even if they do not direct protein synthesis. Design theorists do not deny that
mutational processes might have degraded some previously functional DNA,but we have predicted that the functional DNA (the signal) should dwarf thenonfunctional DNA (the noise), and not the reverse. As William Dembski, aleading design proponent, predicted in 1998, “On an evolutionary view we
expect a lot of useless DNA. If, on the other hand, organisms are designed,
we expect DNA, as much as possible, to exhibit function.”43
The ENCODE project and other recent research in genomics haveconfirmed this prediction. As the lead article in Nature reported, ENCODE
has “enabled us to assign biochemical functions for 80 percent of the genome
in particular outside of the well-studied protein-coding regions.”44 Other
research in genomics has shown that, overall, the noncoding regions of the
genome function much like the operating system in a computer. Indeed, thenoncoding regions of the genome direct the timing and regulate theexpression of the data modules or coding regions of the genome, in addition
to possessing myriad other functions.45 Before ENCODE, neo-Darwinists
would often ask: If the information in DNA provides such compelling
evidence for the activity of a designing intelligence, why is over 90 percent of
the genome composed of functionless nonsense sequences? The latest
genomics research now provides a ready answer to this question: it isn’t.
The significance of these discoveries in genomics to the debate about
design has passed largely unnoticed in the media. But repeated attempts tostigmatize the ENCODE researchers as aiding and abetting “intelligent design
creationists” have inadvertently highlighted what is at stake. In this effort, abiochemist at the University of Toronto, Laurence A. Moran, emerged as
point man. The Moran strategy centered on tarring scientists and sciencejournalists who publicized ENCODE and its implications with the brush of“Intelligent Design Creationism”—an all too familiar conflation of intelligent

design with a very different idea, the biblical literalism of young-earth
creationism. When the distinguished journal Science selected ENCODE asone of the top ten science news stories of 2012, reminding readers that it had
detonated the notion of junk DNA by revealing overwhelming functionality inthe genome,46 Moran jeered, “Oh well, I guess I’ll just have to be content topoint out that many scientists are as stupid as many Intelligent Design
Creationists!”47 In the science world, as in the media, “creationist” is a dirty
word; it’s like calling someone a Communist used to be in the 1950s. Suchattempts to stigmatize results that challenge a favored theory illustrate how an
ideological monopoly in science can stifle inquiry and discussion.
The demise of the idea of junk DNA illustrates too, in a more positive way,
how a competing perspective can inspire research that contributes to new
discovery. Although clearly not every scientist who performed researchhelping to establish the functional significance of nonprotein-coding DNA
was inspired by the theory of intelligent design, at least one noteworthy
scientist was. During the early part of the decade, before ENCODE made theheadlines, this scientist published many articles challenging the idea of junk
DNA based on genomics research that he was conducting at the National
Institutes of Health. After the publication of ENCODE in 2012, his coauthor
on many of those articles, the prominent University of Chicago geneticist
James Shapiro, wrote an article in the Huffington Post commending thescientist for his groundbreaking research and for anticipating the ENCODE
results years before. In the article, Shapiro acknowledged that he and his
coauthor had “different evolutionary philosophies”—his charitable way ofreferring to his coauthor’s growing interest in the theory of intelligent design.
Who was that other scientist? None other than Richard Sternberg, theevolutionary biologist who was punished for his openness to intelligent
design while serving at the Smithsonian Institution (and the National
Institutes of Health) in 2004. Around that time, Sternberg’s doubts about neoDarwinism and his growing interest in intelligent design led him to consider
the possibility that the majority of the genome could really be functional.48
His research subsequently confirmed what was for him, an idea inspired inpart by intelligent design.
In Signature in the Cell, I described many other discriminating predictionsof the theory of intelligent design—predictions that differ from those ofcompeting materialistic evolutionary theories—and how those predictions
might help to guide new research in various subdisciplines of biology,
including some in medicine. These predictions may also lead scientists tomake new discoveries—discoveries that proponents of a competing
perspective might not have been inclined to make—or to accept.

OPEN VISTAS
By now it should be clear why so many brilliant scientists have missed theevidence of design in the Cambrian explosion. Scott Todd, a biologist writingin Nature, succinctly stated the reason: “Even if all the data point to an
intelligent designer, such a hypothesis is excluded from science because it is
not naturalistic.”49 When scientists decide by fiat that intelligent design lies
beyond the bounds of science, their decision will prevent them fromconsidering this possibly or probably true explanation for the origin of animal
form. But it will also deprive them of a new perspective that can generate newresearch questions and foster new avenues of discovery. Knowing this helps
solve the final mystery of this book, but it also suggests a more productive
way forward to address mysteries yet unsolved. Scientists committed tomethodological naturalism have nothing to lose but their chains—fetters thatbind them to a creaky and exhausted nineteenth-century materialism. The
future lies open before them, and us. As we in the intelligent design researchcommunity like to say, let’s break some rules and follow the evidence
wherever it leads.

20
What’s at StakeIn the summer of 2002, I had the opportunity to hike up to the Burgess Shalewith a group of geologists, geophysicists, and marine biologists. Our groupalso included my then eleven-year-old son and a teenage friend of his who
was interested in the Cambrian fossils and the debate about Darwinism anddesign.
When we got to the top of the mountain, I was unprepared for the impact
the fossils would have on me. I had seen many fossils before, of course. But
seeing these fossils—marine animals from the dawn of animal life at the topof a mountain with their beautifully preserved appendages and organs—rendered the idea of the “Cambrian explosion” a good deal less theoretical forme than it had been. These complex sea creatures, now brushed by the thin air
at an elevation of 7,500 feet in the middle of the Canadian Rockies, hadapparently arisen suddenly, almost from nothing by way of ancestral forms, inthe sedimentary record. Everything about them cried out for a story—a big
story. It set my mind and imagination racing (see Fig. 20.1).
As wonderful as the fossils were, our trip to see them was made morememorable by two things that happened en route—one on the way up themountain and one on the way down. As we were making our ascent, crossing
a large talus slope—a section of the mountain void of vegetation and covered
with only fragments of sedimentary rock—I heard my son unexpectedly callout to me from up at the front of our group. His voice had a trembling quality.
I looked forward to see him, normally a fearless kid blessed by energy
without bound, standing locked in place, pale and wide-eyed. I steppedaround several of the other hikers on the trail to catch up with him. It turned
out he was experiencing a kind of vertigo, though the mountain was notdangerously steep at that point (see Fig. 20.2). As he set out across the paththat cut through the rocky slope, he had made the mistake of looking down
the mountain. Without trees as a reference point and with hundreds of feet ofloose rock fragments above and beneath him, he became disoriented andfrightened. I steadied him as we walked in step, stride for stride, with medirectly behind him across that open stretch of the mountain. Before long wewere back to a place on the trail where trees and other plants appeared,
providing a steadying presence as a point of reference. My son’s perspective
quickly returned. He relaxed and soon was smiling and leaping confidently
ahead of me again.
On the way down the mountain, I had a striking interaction with a memberof our group, who gave voice to a different kind of disorientation. It began asa conversation between my son’s friend and our official field guide, who had
been assigned to us by the local Burgess Shale Geoscience Foundation. Ourguide was a paleontologist and did a terrific job. He told many a fine story
about the geological history of the surrounding formations, about thediscovery of the fossils, and of course about the evolutionary history ofanimal life. In fact, just before we turned the final corner on the trail to ascend
to a large collection of excellent fossils available for viewing at the top of themountain, he slipped a statement of support for evolutionary orthodoxy into
his description of the fossil site. Our guide was clearly unaware that many of
us in the group knew the fossils we were about to see challenged the standard
Darwinian story.

FIGURE 20.1
A trilobite fossil found at the Burgess Shale. Courtesy Michael
Melford/National Geographic Image Collection/Getty Images.

FIGURE 20.2
Figure 20.a (left): Photograph of the author and his son Jamie at the Walcott
Quarry of the Burgess Shale in British Columbia, Canada. Figure 20.2b(right): Pausing for a moment to reflect on the slope below the Burgess Shale
outcrop.
We hadn’t made an issue of our views, of course, but nearly all thescientists on the hike were skeptical of neo-Darwinism. Paul Chien, theUniversity of San Francisco marine biologist who had worked with J. Y. Chenin China on the sponge embryo fossils, was on the trip, and he had more thana passing acquaintance with Cambrian-era paleontology—as did several of
the Canadian geologists with us. Still, not wanting to introduce any needless
discord, we carefully avoided engaging the issue. We just wanted to see thefossils.
As we descended the mountain, however, my son’s young friend asked ourguide how he squared what we had just seen with his support for Darwinianevolution. The guide at first maintained his commitment to the Darwinianparty line. He said he thought that Darwin would feel “vindicated” by thediscovery of the Burgess fossils. This proved too much for the precocious,
intellectual teenager, who loudly blurted out, “What?! Darwin would feelvindicated? By the sudden appearance of all those animals without any
ancestors in the fossil record! Are you kidding?!”
You would have to know this endearing young man to understand how his
uninhibited outburst only charmed and amused our guide. But fortunately it
did. The rest of us, however, were initially mortified. This was the discussion
we were trying to avoid, knowing exactly the intense emotions it often

provokes. With scientists, it is generally safer to discuss religion and politics.
Nevertheless, to his credit, our guide took the challenge in stride. He
explained how the Burgess fossils demonstrated evidence of change overtime, how the rock column showed the great age of the earth, and how thediscovery of the fossils high on a mountain revealed the evolution of theplanet. Our young friend had spent too much time reading up on the subject to
let the point go at that. He brushed aside the issue of the earth’s age, whichlike our guide he reckoned in billions of years, and assured the man that heaccepted evidence for change over time in the sedimentary record. He didn’t
question evolution in that sense. He questioned Darwinian evolution. “Whereis the evidence of gradual change?” he demanded, as his teenage voicecracked with excitement as it moved into the upper register. He continued,“What mechanism could produce so many new animals so quickly?”An odd thing happened then. The paleontologist now leading us down the
trail suddenly ceased to act the part of “guide.” He dropped any pretense of
superior authority and said, “You know, I’ve wondered about that myself.” I
thought I could hear in his voice the candid amazement of the fourteen-yearold boy he once was.
“How do you explain it?” he asked my son’s friend.
Our young spokesman confidently piped up and asserted, “Intelligent
design, of course!”
At which point, our guide began to ask the probing questions. Soon myson’s friend had exhausted his store of knowledge and began to look to me tojoin the conversation. I did so, reluctantly at first. I explained the informationargument for intelligent design and how the Cambrian explosion contributed
to it. Our guide asked me the hard questions: How can we detect design? Is
intelligent design science? Aren’t we just arguing from ignorance and giving
up on science, or at least mainstream evolutionary science, too soon? He also
wanted to know who I personally thought the designer was. His challenges
were tough and honest. A terrific conversation ensued.
When we reached the trailhead, he surprised me, thanking me for theconversation—and thanking my young friend for starting it. He then spoke a
bit more personally and revealed that he sometimes found thinking about
biological origins disturbing. He said that as a scientist he was committed tothe evolutionary perspective. But he also found its denial of purpose
depressing. He wondered if there was some way to affirm both science andthe kind of purpose and meaning in life that religion speaks about. As weparted ways, he said he would like to learn more about intelligent design. He
told me he was intrigued by the perspective we were developing. I felt that we
had made a genuine human connection rather than, as sometimes happens inthe evolution debate, merely flinging assertions at one another.
Over the years, as I’ve researched and thought about biological origins, I
have had numerous similar conversations with people of many persuasions
and backgrounds: religious and nonreligious; scientists, engineers, medical
doctors; businessmen and -women, appliance repairmen and taxi drivers.
These conversations usually start innocently enough as the result of someone
asking me what I do for a living. Though I often euphemize my response (“Iwork for a research organization”) to avoid getting trapped in a heavy
conversation on an airplane or over a broken dishwasher, often theconversations come whether I want them or not. People are interested in howlife began and they instinctively understand that whatever theory we adopt
has larger philosophical, religious, or worldview implications. People areusually energized by considering those larger implications and questions.
Many would like to find a way to harmonize the evidence from science with aview of the world that addresses their deepest existential longings as humanbeings, their yearning for purpose and significance. But like our guide, many
have been frustrated by the difficulty of arriving at a coherent synthesis.
It’s not hard to see why. On the one hand, many people of faith have little
real interest in what science has to say about life’s origins. Indeed, many wellmeaning religious believers have adopted a view of the relationship between
science and faith that rejects the testimony of science as irrelevant or evendangerous and affirms that just reading the Bible will give all the insightneeded to understand how life came to be. Their approach does not reallyattempt to harmonize faith and science, since it takes faith in the Bible, andoften a particular interpretation of the Bible, as the only reliable source of
information about life’s origin.
On the other hand, many scientists and others who think that science hassomething to teach us about the big questions have started by assuming the
neo-Darwinian account of biological origins, despite its many scientificdifficulties—and despite its denial of any role for purposive intelligence in thehistory of life.
In particular, two popular ideas about how Darwinism informs worldview
have come to different conclusions about the worldview it affirms—or allows.
The first view, the “New Atheism,” has been articulated by spokesmen suchas Richard Dawkins in his book The God Delusion and the late Christopher
Hitchens in God Is Not Great.1 It purports to refute the existence of God as “afailed hypothesis,”2 as another New Atheist book puts it. Why? Because,
according to Dawkins and others, there is no evidence of design in nature.
Indeed, Dawkins’s argument for atheism hinges upon his claim that natural
selection and random mutation can explain away all “appearances” of design

in nature. And since, he asserts, the design argument always provided thestrongest argument for believing in God’s existence, belief in God, heconcludes, is extremely improbable—tantamount to “a delusion.” For the
New Atheists, Darwinism makes theistic belief both implausible andunnecessary. As Dawkins has famously put it, “Darwin made it possible to be
an intellectually fulfilled atheist.”3
The New Atheists took the publishing world by storm in 2006 when The
God Delusion first appeared. But nothing about the “New” Atheism wasactually “new.” Instead, it represents a popularization of a science-based
philosophy, called scientific materialism, that came into currency amongscientists and philosophers during the late nineteenth century in the wake of
the Darwinian revolution. For many scientists and scholars at the time, ascientifically informed worldview was a materialistic worldview in which
entities such as God, free will, mind, soul, and purpose played no role.
Scientific materialism, following classical Darwinism, denied evidence of any
design in nature and, therefore, any ultimate purpose to human existence. As
British philosopher and mathematician Bertrand Russell put it early in thetwentieth century, “Man is the product of causes which had no prevision of
the end they were achieving” and which predestine him “to extinction in thevast death of the solar system.”4
An alternative and increasingly popular view is known as theistic
evolution. Popularized by Christian geneticist Francis Collins in his book The
Language of God (also published in 2006),5 this perspective affirms theexistence of God and the Darwinian account of biological origins. Yet it
provides few details about how God might or might not influence theevolutionary process, or how to reconcile seemingly contradictory claims in
the Darwinian and Judeo-Christian accounts of origins. For example, Collins
has declined to say whether he thinks God in any way directed or guided theevolutionary process, though he affirms neo-Darwinism, which specificallydenies that natural selection is guided in any way. Darwinism and neoDarwinism insist that the appearance of design in living organisms is an
illusion because the mechanism that produces that appearance is unguided
and undirected. Does God, in Collins’s view, guide the unguided process ofnatural selection? He, and many other theistic evolutionists, don’t say. This
ambiguity has made an uneasy reconciliation of science and faith possible,
but it has also left many questions unanswered. In fairness, many theistic
evolutionists would argue that not all such questions can be answered,because science and faith occupy separate, non-overlapping realms of inquiry,
knowledge, and experience. But that answer itself underscores the limits of
the harmonization of science and faith that Collins and others holding hisview has achieved.
The argument of this book presents a scientific challenge to both of theseviews. In the first place, the evidence and arguments we have seen show thatthe scientific premise of the New Atheist argument is flawed. The mechanismof mutation and natural selection does not have the creative power attributed
to it and, thus, cannot explain all “appearances” of design in life. The neoDarwinian mechanism does not explain, for example, either the new genetic
or epigenetic information necessary to produce fundamentally new animal
body plans.
This book has presented four separate scientific critiques demonstrating
the inadequacy of the neo-Darwinian mechanism, the mechanism that
Dawkins assumes can produce the appearance of design without intelligent
guidance. It has shown that the neo-Darwinian mechanism fails to account forthe origin of genetic information because: (1) it has no means of efficiently
searching combinatorial sequence space for functional genes and proteins
and, consequently, (2) it requires unrealistically long waiting times to generate
even a single new gene or protein. It has also shown that the mechanism
cannot produce new body plans because: (3) early acting mutations, the only
kind capable of generating large-scale changes, are also invariably
deleterious, and (4) genetic mutations cannot, in any case, generate theepigenetic information necessary to build a body plan. Thus, despite thecommercial success of The God Delusion and its wide cultural currency, the
New Atheist philosophy lacks credibility because it has based its
understanding of the metaphysical implications of modern science on ascientific theory that itself lacks credibility—as even many leading
evolutionary biologists now acknowledge.6
Second, this book poses a strong challenge to theistic evolutionists such as
Francis Collins for many of the same scientific reasons. Collins places great
trust in modern Darwinism as the unifying theory of biology, but seems
completely unaware of the formidable scientific problems now afflicting thetheory—in particular, the challenges to the creative power of the natural
selection/mutation mechanism. He makes no attempt to address or answer anyof these challenges. In addition, many of his arguments for universal common
descent—the defense of which was his main concern in The Language of God—are based upon the alleged presence of nonfunctional or “junk” elements in
the genomes of different organisms. Though the theory of intelligent design,
which Collins says he opposes, does not necessarily challenge this part(common descent) of Darwinian theory, the factual basis of his arguments has
now also largely evaporated as the result of ENCODE and otherdevelopments in genomics.7 Thus, this popular view of biological origins, andits conception of God’s relationship to the natural world, now stands starkly atodds with the evidence. But why attempt to reconcile traditional Christiantheology with Darwinian theory, as Collins tries to do, if the theory itself has
begun to collapse?
The perspective of this book offers a potentially more coherent andsatisfying way of addressing the big questions, of synthesizing science andmetaphysics (or faith), than either of the currently popular views on offer. The
Cambrian explosion, like evolutionary theory itself, raises larger worldview
questions precisely because it raises questions of origins and of design, andwith them, the question that all worldviews must address: What is the thing or
the entity from which everything comes? But unlike strict Darwinian
materialism and the New Atheism built atop it, the theory of intelligent design
affirms the reality of a designer—a mind or personal intelligence behind life.
This case for design restores to Western thought the possibility that humanlife in particular may have a purpose or significance beyond temporary
material utility. It suggests the possibility that life may have been designed byan intelligent person, indeed, one that many would identify as God.
Unlike the theistic evolution of Francis Collins, however, the theory ofintelligent design does not seek to confine the activity of such an agency tothe beginning of the universe, conveying the impression of a decidedly
remote and impersonal deistic entity. Nor does the theory of intelligent design
merely assert the existence of a creative intelligence behind life. It identifies
and detects activity of the designer of life, and does so at different points in
the history of life, including the explosive show of creativity on display in the
Cambrian event. The ability to detect design makes belief in an intelligent
designer (or a creator, or God) not only a tenet of faith, but something towhich the evidence of nature now bears witness. In short, it brings scienceand faith into real harmony.
Just as importantly, perhaps, the case for design supports us in our
existential confrontation with the void and the seeming meaninglessness ofphysical existence—the sense of survival for survival’s sake that follows
inexorably from the materialist worldview. Richard Dawkins and other New
Atheists may find it untroubling, even amusing and certainly profitable, tomuse over the prospect of a universe without purpose. But for the vast
majority of thoughtful people, that idea is tinged with terror. Modern life
suspends many of us, so we feel, high over a chasm of despair. It provokes
feelings of dizzying anxiety—in a word, vertigo. The evidence of apurposeful design behind life, on the other hand, offers the prospect ofsignificance, wholeness, and hope.
As my son walked out across the mountain high above the Yoho Valley, hewas surrounded by many slabs of rock containing some of the very fossils we
had come to see. But as he surveyed that barren portion of landscape, he lost
perspective on where he was and what he had come to do. Without landmarks
or steadying points of reference, he felt as if he were lost in a sea of sensory
impressions. Without his sense of balance, he feared even to take a step. He
called out for his father.
It occurred to me only much later how closely his experience parallels ourown as human beings trying to make sense of the world around us. To gain atrue picture of the world and our place in it we need facts—empirical data.
But we also need perspective, sometimes called wisdom, the reference points
that a coherent view of the world provides. Historically, that wisdom wasprovided for many men and women by the traditions of Western monotheism—by our belief in God. The theory of intelligent design generates both
excitement and loathing because, in addition to providing a compelling
explanation of the scientific facts, it holds out the promise of help in
integrating two things of supreme importance—science and faith—that havelong been seen as at odds.8
The theory of intelligent design is not based upon religious belief, nor doesit provide a proof for the existence of God. But it does have faith-affirming
implications precisely because it suggests the design we observe in the natural
world is real, just as a traditional theistic view of the world would lead us to
expect. Of course, that by itself is not a reason to accept the theory. But
having accepted it for other reasons, it may be a reason to find it important.

Notes
Prologue
1. Quastler, The Emergence of Biological Organization, 16.
2. In fairness I should mention that a few of my critics did attempt to refutethe book’s actual arguments about the origin of life, and my colleagues and I
addressed those in several essays collected into a book called Signature ofControversy, ed. David Klinghoffer (Seattle: Discovery Institute Press, 2010;
http://www.discovery.org/f/6861).
3. See Francisco Ayala, “On Reading the Cell’s Signature,” Biologos.org,
January 7, 2010, http://biologos.org/blog/on-reading-the-cells-signature.
4. Venema, “Seeking a Signature,” 278.
5. Dobzhansky, “Discussion of G. Schramm’s Paper,” 310.
6. De Duve, Blueprint for a Cell, 187.
7. Gould, “Is a New and General Theory of Evolution Emerging?” 120.
8. For examples, see such books as Kauffman, The Origins of Order;
Goodwin, How the Leopard Changed Its Spots; Eldredge, Reinventing
Darwin; Raff, The Shape of Life; Müller and Newman, On the Origin ofOrganismal Form; Valentine, On the Origin of Phyla; Arthur, The Origin ofAnimal Body Plans; and Shapiro, Evolution, to name but a few.
9. Futuyma asserts, “There is absolutely no disagreement amongprofessional biologists on the fact that evolution has occurred. . . . But thetheory of how evolution occurs is quite another matter, and is the subject ofintense dispute” (“Evolution as Fact and Theory,” 8). Of course, to admit thatnatural selection cannot explain the appearance of design is in effect to admitthat it has failed to perform the role that is claimed for it as a “designer
substitute.”
10. See Scott Gilbert, Stuart Newman, and Graham Budd, as quoted in
Whitfield, “Biological Theory”; Mazur, The Altenberg 16.
11. See, e.g., Kauffman, 361; Raff, The Shape of Life; Miklos, “Emergenceof Organizational Complexities During Metazoan Evolution.”
12. Gilbert et al., “Resynthesizing Evolutionary and Developmental
Biology.”
13. Webster, How the Leopard Changed Its Spots, 33; Webster andGoodwin, Form and Transformation, x; Gunter Theissen, “The Proper Place

of Hopeful Monsters in Evolutionary Biology,” 351; Marc Kirschner and John
Gerhart, The Plausibility of Life, 13; Schwartz, Sudden Origins, 3, 299–300;
Erwin, “Macroevolution Is More Than Repeated Rounds of Microevolution”;
Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,” 35;
Koonin, “The Origin at 150,” 473–75; Conway Morris, “Walcott, the Burgess
Shale, and Rumours of a Post-Darwinian World,” R928-R930; Carroll,“Towards a New Evolutionary Synthesis,” 27; Wagner, “What Is the Promiseof Developmental Evolution?”; Wagner and Stadler, “Quasi-independence,
Homology and the Unity of Type”; Becker and Lönnig, “Transposons:
Eukaryotic,” 529–39; Lönnig and Saedler, “Chromosomal Rearrangements
and Transposable Elements,” 402; Muller and Newman, “Origination ofOrganismal Form,” 7; Kauffman, At Home in the Universe, 8; Valentine and
Erwin, “Interpreting Great Developmental Experiments,” 96; Sermonti, Why
Is a Fly Not a Horse?; Lynch, The Origins of Genome Architecture, 369;
Shapiro, Evolution, 89, 128. David J. Depew and Bruce H. Weber, writing in
the journal Biological Theory, are even more frank, “Darwinism in its current
scientific incarnation has pretty much reached the end of its rope” (89–102).
14. “Statement on Teaching Evolution by the Board of Directors of theAmerican Association for the Advancement of Science,” St. Louis, Missouri,
February 16, 2006;
www.aaas.org/news/releases/2006/pdf/0219boardstatement.pdf (accessed
October 26, 2012).
15. Dean, “Scientists Feel Miscast in Film on Life’s Origin.”
16. Eugenie Scott, quoted in Stutz, “State Board of Education Debates
Evolution Curriculum”; also requoted in Stoddard, “Evolution Gets Added
Boost in Texas Schools.”
Chapter 1: Darwin’s Nemesis
1. Darwin, On the Origin of Species, 484. In other places in The Origin,
Darwin hedged his bets, referring to life “having been originally breathed intoa few forms or into one.” Darwin, The Origin of Species, 490.
2. Though Darwin emphasized natural selection as the “chief agent ofchange,” he also emphasized “sexual selection”—the preference that sexually
reproducing animals have for some traits over others in prospective mates—
as a mechanism responsible for some changes in evolving populations.
3. Darwin, On the Origin of Species, 30.
4. Darwin, On the Origin of Species, 21.
5. Darwin, On the Origin of Species, 306–7.
6. See the University of California at Berkeley Museum of Paleontology,“Brachiopoda,” www.ucmp.berkeley.edu/brachiopoda/brachiopodamm.html

(accessed October 23, 2012).
7. See www.geo.ucalgary.ca/~macrae/trilobite/siluria.html (accessed
October 23, 2012), where Roderick Murchison’s skillful trilobite drawings are
reproduced.
8. Agassiz, “Evolution and the Permanence of Type,” 99.
9. Ward, On Methuselah’s Trail, 29.
10. Darwin, On the Origin of Species, 307. Darwin’s original quotation
used the “Silurian” rather than the “Cambrian,” because in Darwin’s time
what we now label as the Cambrian period was subsumed within the conceptof the lower Silurian. In a later sixth edition of the Origin, Darwin adopted
the term “Cambrian” in place of “Silurian.” See Darwin, On the Origin ofSpecies; sixth edition, 286.
11. Agassiz, Essay on Classification, 102.
12. Agassiz, “Evolution and the Permanence of Type,” 10.
13. Murchison, Siluria, 469.
14. Letter from Adam Sedgwick to Charles Darwin, November 24, 1859.
15. Between approximately 450 and 440 million years ago, many animal
species went extinct. Known as the Ordovician extinction, this event resulted
in the disappearance of a huge number of marine invertebrates. This was thesecond biggest extinction in the history of life, being superseded only by thegreat Permian extinction (about 252 million years ago). Dott and Prothero,
Evolution of the Earth, 259.
16. Mintz, Historical Geology, 146, 153–54, 124–27.
17. Prothero, Bringing Fossils to Life: An Introduction to Paleobiology,
84–85. Dott and Prothero, Evolution of the Earth, 376–79.
18. Dott and Prothero, Evolution of the Earth, 425–26; Li et al., “AnAncestral Turtle from the Late Triassic of Southwestern China”; Gaffney,“The Comparative Osteology of the Triassic Turtle Proganochelys.”
19. William Smith, 1815 Geological Map of England and Wales.
20. Radiometric dating methods estimate the age of rocks based uponmeasurements of the ratios of unstable radioactive isotopes and their daughter
products given known radioactive decay rates.
21. Gould, Wonderful Life, 54.
22. Darwin, On the Origin of Species, 302.
23. Darwin, On the Origin of Species, 311.
24. Gould, Wonderful Life, 57.
25. Agassiz, “Evolution and the Permanence of Type,” 97.
26. Robinson, Runner on the Mountain Tops, 215.
27. Lurie, Louis Agassiz, vii.
28. Robinson, Runner on the Mountain Tops, foreword.

29. Quoted in Holder, Louis Agassiz, 180.
30. Dupree, Asa Gray, 227.
31. Dupree, Asa Gray, 226. Though the German idealists believed thatliving forms reflected divine archetypes, they did not all oppose the idea ofthe transmutation of species. In Schelling’s view, for example, each species
reflected a pre-existing archetype, but emerged in time through a gradualtransition of form.
32. Dupree, Asa Gray, 260.
33. Lurie, Louis Agassiz, 284.
34. Lurie, Louis Agassiz, 88.
35. Lurie, Louis Agassiz, 282.
36. Gillespie, Charles Darwin and the Problem of Creation.
37. Agassiz, “Evolution and the Permanence of Type,” 101.
38. Robinson, Runner on the Mountain Tops, 231–34.
39. Quoted in Lurie, Nature and the American Mind, 41.
40. Quoted in Lurie, Nature and the American Mind, 42.
41. Thanks go to my former student Jack Ross Harris and his probing,unpublished 1993 essay “Louis Agassiz: A Re-evaluation of the Nature of His
Opposition to the Darwinian View of Natural History.” His work on thesubject first brought to my attention the way in which historians writing after
the widespread acceptance of Darwinism had attempted to minimize thescientific basis of Agassiz’s objections to his theory.
42. Lurie, Louis Agassiz, 244.
43. Lurie, Louis Agassiz, 246.
44. Quoted in Lurie, Louis Agassiz, 373.
45. Gillespie, Charles Darwin and the Problem of Creation, 51.
46. Agassiz, “Evolution and the Permanence of Type,” 92–101.
47. Gray, Darwiniana, 127.
48. See the parallel lines on the sides of the hills on either side of thevalley in this beautiful picture:
www.swisseduc.ch/glaciers/earth_icy_planet/icons-15/16.jpg (last accessed
Oct. 23rd, 2012). www.uh.edu/engines/epi857.htm (last accessed Oct. 23rd,2012). See also Tyndall, “The Parallel Roads of Glen Roy.”49. Darwin, Autobiography, 84. Also, Gertrude Himmelfarb notes thatDarwin took more than twenty years to concede his mistake. In his
autobiography, Darwin labeled it “one long gigantic blunder from beginningto end. . . . Because no other explanation was possible under our then state ofknowledge, I argued in favour of sea-action; and my error has been a good
lesson to me never to trust in science to the principle of exclusion.” See
Himmelfarb’s discussion in Darwin and the Darwinian Revolution, 107.

50. See Oosthoek, “The Parallel Roads of Glen Roy and Forestry.”
51. Darwin, On the Origin of Species, 307.
52. Darwin, On the Origin of Species, 308.
53. Agassiz, “Evolution and the Permanence of Type,” 97. That Agassiz’s
objection was first and foremost empirically driven can be seen from hiscomments elsewhere as well. For instance, in “Researches on the Fossil
Fishes,” he writes, “More than fifteen hundred species of fossil fishes, which I
have learned to know, tell me that species do not pass insensibly one intoanother, but that they appear and disappear unexpectedly, without direct
relations with their precursors; for I think no one will seriously pretend thatthe numerous types of Cycloids and Ctenoids, almost all of which arecontemporaneous with one another, have descended from the Placoids andGanoids. As well might one affirm that the Mammalia, and man with them,
have descended directly from fishes.” Quoted in Agassiz, Louis Agassiz andCorrespondence, 244–45.
Chapter 2: The Burgess Bestiary
1. Gould, Wonderful Life, 71. A slightly different version of this story isfound in Charles Schuchert, “Charles Doolittle Walcott,” 124. See also
Schuchert, “Charles Doolittle Walcott Paleontologist—1850–1927,” 455–58.
2. Gould, Wonderful Life, 71.
3. Gould, Wonderful Life, 71–75.
4. A distant relationship between Marrella and chelicerates is currently thefavored hypothesis. See García-Bellido, D. C., and Collins, D. H., “A New
Study of Marrella Splendens (Arthropoda, Marrelomorpha) from the Middle
Cambrian Burgess Shale, British Columbia, Canada,” 721–42; Hou, X. G.,
and Bergström, J., “Arthropods of the Lower Cambrian Chengjiang Fauna,Southwest China,” 109; Bergström, J., and Hou, X. G., “Arthropod Origins,”
323–34.
5. Other authorities, such as Douglas Erwin at the Smithsonian, arrive at aslightly higher total. By counting groups that some paleontologists count as
subphyla or classes as phyla, Erwin argues that about twenty-five phyla first
appear in the Cambrian out of about thirty-three total (by his way of counting)phyla known from the fossil record. [See Erwin et al., “The CambrianConundrum: Early Divergence and Later Ecological Success in the Early
History of Animals,” 1091–97.] I’ve used a slightly more conservative
method for estimating the total number of phyla that first appear in the
Cambrian (see Fig. 2.5). I came to my count consulting the following sources:
Phylum references listed in same order as they appear on the chart.
Cnidaria: Chen et al., “Precambrian Animal Life: ProbableDevelopmental and Adult Cnidarian Forms from Southwest China.”
Mollusca: Fedonkin and Waggoner. “The Late Precambrian Fossil
Kimberella Is a Mollusc-Like Bilaterian Organism.”
Porifera: Love, G. D. “Fossil steroids record the appearance of
Demospongiae during the Cryogenian period.”
Annelida: Conway Morris and Peel, “The Earliest Annelids: Lower
Cambrian Polychaetes from the Sirius Passet Lagerstätte, Peary Land, North
Greenland.”
Brachiopoda: Skovsted and Holmer, “Early Cambrian Brachiopods from
North-East Greenland.”Bryozoa: Landing et al., “Cambrian Origin of All Skeletalized Metazoan
Phyla—Discovery of Earth’s Oldest Bryozoans (Upper Cambrian, southern
Mexico).”Chaetognatha: Szaniawski, H. “Cambrian Chaetognaths Recognized inBurgess Shale Fossils.”
Chordata: Chen et al., “A Possible Early Cambrian Chordate”; Chen,“Early Crest Animals and the Insight They Provide into the Evolutionary
Origin of Craniates”; Janvier, “Catching the First Fish”; Monnereau, “An
Early Cambrian Craniate-Like Chordate”; Conway Morris and Caron, “Pikaia
gracilens Walcott, a Stem-Group Chordate from the Middle Cambrian ofBritish Columbia”; Sansom et al., “Non-Random Decay of Chordate
Characters Causes Bias in Fossil Interpretation”; Shu et al., “An Early
Cambrian Tunicate from China”; Shu et al. “Lower Cambrian Vertebrates
from South China.”
Coeloscleritophora: Bengtson and Hou, “The Integument of Cambrian
Chancelloriids.”
Ctenophora: Chen, J. Y. et al. “Raman Spectra of a Lower Cambrian
Ctenophore Embryo from Southwestern Shaanxi, China”; Conway Morris andCollins, “Middle Cambrian Ctenophores from the Stephen Formation, British
Columbia, Canada.”
Echinodermata: Foote, “Paleozoic Record of Morphological Diversity in
Blastozoan Echinoderms”; Shu et al., “Ancestral Echinoderms from theChengjiang Deposits of China”; Zamora et al., “Middle Cambrian Gogiid
Echinoderms from Northeast Spain: Taxonomy, Palaeoecology, andPalaeogeographic Implications.”
Entoprocta: Zhang et al., “A Sclerite-Bearing Stem Group Entoproct fromthe Early Cambrian and Its Implications.”
Euarthropoda: Cisne, J. L., “Trilobites and the Origin of Arthropods”;
Daley, “The Morphology and Evolutionary Significance of the
Anomalocaridids”; Grosberg, “Out on a Limb: Arthropod Origins”; Siveter,

“A Phosphatocopid Crustacean with Appendages from the Lower Cambrian.”
Hemichordata: Shu et al., “Reinterpretation of Yunnanozoon as the
Earliest Known Hemichordate”; Shu et al., “A New Species of Yunnanozoan
with Implications for Deuterostome Evolution.”
Hyolitha: Malinky and Skovsted, “Hyoliths and Small Shelly Fossils fromthe Lower Cambrian of North-East Greenland”; note that some authors
consider Hyolitha to belong to phylum Mollusca, whereas others consider
Hyolitha to represent an independent phylum.
Lobopodia: Liu et al., “A Large Xenusiid Lobopod with Complex
Appendages from the Lower Cambrian Chengjiang Lagerstätte”; Liu et al.,“Origin, Diversification, and Relationships of Cambrian Lobopods”; Liu etal., “An Armoured Cambrian Lobopodian from China with Arthropod-LikeAppendages”; Ou et al., “A Rare Onychophoran-Like Lobopodian from theLower Cambrian Chengjiang Lagerstätte, Southwestern China, and Its
Phylogenetic Implications.”
Loricifera: Peel, “A Corset-Like Fossil from the Cambrian Sirius Passet
Lagerstatte of North Greenland and Its Implications for Cycloneuralian
Evolution.”
Nematomorpha: Xian-guang and Wen-guo, “Discovery of Chengjiang
Fauna at Meishucun, Jinning, Yunnan.”
Phoronida: Erwin et al., “The Cambrian Conundrum: Early Divergenceand Later Ecological Success in the Early History of Animals.”
Priapulida: Wills et al., “The Disparity of Priapulid, Archaeopriapulid
and Palaeoscolecid Worms in the Light of New Data”; Hu et al., “A New
Priapulid Assemblage from the Early Cambrian Guanshan Fossil Lagerstätte
of SW China.”
Sipuncula: Huang et al., “Early Cambrian Sipunculan Worms fromSouthwest China.” Some consider sipunculan worms to be a subgroup of thephylum Annelida based on phylogenomic analyses. See Struck et al.,“Phylogenomic Analyses Unravel Annelid Evolution.”
Tardigrada: Muller et al., “ ‘Orsten’ Type Phosphatized Soft-Integument
Preservation and a New Record from the Middle Cambrian Kuonamka
Formation in Siberia.”
Vetulicolia: Shu, “On the Phylum Vetulicolia.”
Nematoda: Erwin et al., “The Cambrian Conundrum: Early Divergenceand Later Ecological Success in the Early History of Animals.”
Nemertea(?): Schram, “Pseudocoelomates and a Nemertine from theIllinois Pennsylvanian.” Note that the presence of Nemertea in the fossil
record is contested.
Platyhelminthes: Poinar, “A Rhabdocoel Turbellarian (Platyhelminthes,

Typhloplanoida) in Baltic Amber with a Review of Fossil and Sub-Fossil
Platyhelminths.”
Rotifera: Swadling et al., “Fossil Rotifers and the Early Colonization of
an Antarctic Lake.”
6. Erwin and Valentine, The Cambrian Explosion, 66–70.
7. Hennig, Phylogenetic Classification.
8. If anything, using a “rank-free” classification system may actuallyintensify the mystery of the Cambrian explosion. A single phylum may
include many unique modes of organizing tissues, organs, and body parts, andthese differences in organization may deserve to be recognized as different
body plans as much as the differences that distinguish different phyla. As one
proponent of the rank-free approach put it to me, “Why shouldn’t clams andsquids [both of which belong to the single phylum Mollusca] be recognized as
exemplifying unique body architectures every bit as much as trilobites andstar fish [which belong to two different phyla, the arthropods and theechinoderms]?” In the traditional system, however, both clams and squids,
and many other animals that exemplify equally pronounced differences inform within other phyla, will all fall within their respective individual phyla.
For this reason, measuring the explosiveness of the Cambrian radiation solely
by reference to the number of phyla that first appear in the Cambrian may
actually minimize the severity of the problem, whereas dispensing withtaxonomic ranking may actually tend to accentuate it.
9. In addition, in 1999 paleontologists in southern China also found fossil
remains of fish in the Cambrian period. Fish are vertebrates and members of
the phylum chordata. Shu et al., “Lower Cambrian Vertebrates from South
China,” 42–46; Shu et al., “Head and Backbone of the Early Cambrian
Vertebrate Haikouichthys.”
10. Quoted in Yochelson, Charles Doolittle Walcott, Paleontologist, 33.
11. Gould, Wonderful Life, 49.
12. Gould, Wonderful Life, 125–36; Budd, “The Morphology of Opabinia
Regalis and the Reconstruction of the Arthropod Stem-Group,” 1–14.
13. Darwin, On the Origin of Species, 307.
14. Ward, On Methuselah’s Trail, 29–30.
15. Darwin’s prediction is, of course, not a prediction in the narrow senseof forecasting a future event or process. But historical scientists regularly
speak of predictions in the sense of expectations about what will be revealed
about the past if and when the relevant body of evidence is uncovered.
16. Great Canadian Parks, Yoho National Park,
www.greatcanadianparks.com/bcolumbia/yohonpk/page3.htm (accessed
October 23, 2012).

17. Dawkins, Unweaving the Rainbow, 201.
18. Darwin, On the Origin of Species, 120.
19. Darwin, On the Origin of Species, 125.
20. Lewin, “A Lopsided Look at Evolution,” 292.
21. Erwin, Valentine, and Sepkoski, “A Comparative Study ofDiversification Events,” 1183. See also Erwin et al., “The CambrianConundrum: Early Divergence and Later Ecological Success in the Early
History of Animals,” 1091–97; Bowring et al., “Calibrating Rates of Early
Cambrian Evolution,” 1293–98.
22. Hennig, Phylogenetic classification, 219. Erwin and Valentine in their2013 book, The Cambrian Explosion, reaffirm the remarkable morphologicaldisparity present from the beginning of the Cambrian period despite low
species diversity. They note that since they first brought attention to the topdown pattern of Cambrian disparity preceding diversity using classical
Linnaean categories in 1987, paleontologists have developed measures ofdisparity within the phylogenetic classification system—measures that
reaffirm the same pattern within a rank-free classification system (217).
23. For a more technical description of the processes behind the Burgess
Shale fossil formation, see Briggs, Erwin, and Collier, The Fossils of the
Burgess Shale, 21–32; Conway Morris, The Crucible of Creation, 106–107.
24. Gould, Wonderful Life, 274–75.
25. Walcott, “Cambrian Geology and Paleontology II,” 15.
26. Gould, Wonderful Life, 108.
27. Gould, Wonderful Life, 273.
Chapter 3: Soft Bodies and Hard Facts
1. Nash, “When Life Exploded,” 66–74.
2. Today fossils from the Burgess can be viewed in Canada at the Royal
Ontario Museum in Toronto, the Tyrell Museum in Drumheller, Alberta, andat a smaller exhibition close to the Burgess Shale in Golden, British
Columbia.
3. Briggs, Erwin, and Collier, Fossils of the Burgess Shale.
4. Desmond Collins, Misadventures in the Burgess Shale, 952–53.
5. Some paleontologists have also gone so far as to argue that the
Cambrian explosion is nothing more than an artifact of classification, andtherefore does not require explanation. Budd and Jensen, for example, argue
that the problem of the Cambrian explosion resolves itself if one keeps inmind the cladistic distinction between “stem” and “crown” groups. Sincecrown groups arise whenever new characters are added to simpler, moreancestral stem groups during the evolutionary process, new phyla will

inevitably arise once a stem group has arisen. Thus, for Budd and Jensen,
what requires explanation is not the crown groups corresponding to the newphyla, but the earlier, less derived, stem groups that presumably arose deep in
the Precambrian. Yet since these earlier stem groups are by definition lessderived, explaining them will be, in their view, considerably easier than
explaining the origin of the Cambrian animals de novo. In any case, for Budd
and Jensen, the explosion of new phyla in the Cambrian does not require
explanation. As they put it, “given that the early branching points of major
clades is an inevitable result of clade diversification, the alleged phenomenonof phyla appearing early and remaining morphologically static does not seemto require particular explanation.” [Budd and Jensen, “A Critical Reappraisalof the Fossil Record of the Bilaterian Phyla,” 253.] Nevertheless, Budd andJensen’s attempt to explain away the Cambrian explosion begs crucial
questions. Granted, as new characters are added to existing forms, novel
morphology and greater morphological disparity will likely result. But whatcauses new characters to arise? And how does the biological informationnecessary to produce new characters originate? (See Chapters 9–16.) Budd
and Jensen do not specify. Nor can they say how derived the ancestral forms
are likely to have been, and what processes might have been sufficient toproduce them. Instead they simply assume the sufficiency of someunspecified evolutionary mechanisms. Yet, as I show in Chapters 10–16, thisassumption is now problematic. In any case, Budd and Jensen do not explain
what causes the origin of biological form and information in the Cambrian.
6. See Cloud, “The Ship That Digs Holes in the Sea,” 108. See also ahistory of offshore drilling on the website of the National Ocean Industries
Association, http://www.noia.org/website/article.asp?id=123 (accessed July 8,2011).
7. Schuchert and Dunbar, Textbook of Geology, Part II, Historical
Geology, 72–76, 125–30; Stokes, Essentials of Earth History: An Introduction
to Historical Geology, 162–64; Zumberge, Elements of Geology, 62–67, 214–
15; Dunbar, Historical Geology, 13–15, 129–33.
8. Müller et al., “Digital Isochrons of the World’s Ocean Floor,” 3212.
9. Walcott, “Cambrian Geology and Paleontology II,” 2–4.
10. Gould, Wonderful Life, 275.
11. Some have even suggested that the transitional intermediate forms
leading to the Cambrian animals only existed in the larval stage. See
Davidson, Peterson, and Cameron, “Origin of Bilaterian Body Plans,” 1319.
12. Wray, Levinton, and Shapiro, “Molecular Evidence for Deep PreCambrian Divergences Among Metazoan Phyla.” For other recent
expressions of this version of the artifact hypothesis, see Simpson, Fossils

and the History of Life, 72–74; Ward, Out of Thin Air, 5; Eldredge, The
Triumph of Evolution and the Failure of Creationism, 46; and Schirber,“Skeletons in the Pre-Cambrian Closet.” Though contemporary
paleontologists commonly attribute the absence of Precambrian ancestralforms to their alleged lack of hard parts or appreciable size, earlier geologists
and paleontologists have also employed this version of the artifact hypothesis.
For example, in 1941 Charles Schuchert and Carl Dunbar stated: “We may
infer, therefore, that life probably was abundant in the seas of Cryptozoic timeand especially during the Proterozoic, but was of a low order and doubtless
small and soft-tissued, so that there was little chance for actual preservation offossils” (Textbook of Geology, Part II, 124). And as early as 1894 W. K.
Brooks asserted: “the zoological features of the Lower Cambrian are of such acharacter as to indicate that it is a decided and unmistakable approximation to
the primitive fauna of the bottom, beyond which life was represented only byminute and simple surface animals not likely to be preserved as fossils” (“TheOrigin of the Oldest Fossils and the Discovery of the Bottom of the Ocean,”
360–61).
13. Marshall, “Explaining the Cambrian ‘Explosion’ of Animals,” 357,
372. For an authoritative refutation of this version of the artifact hypothesis,
see Conway Morris, The Crucible of Creation, 140–44; Conway Morris,“Darwin’s Dilemma: The Realities of the Cambrian ‘Explosion’,” 1069–83.
14. Schopf and Packer, “Early Archean (3.3-Billion to 3.5-Billion-YearOld) Microfossils from Warrawoona Group, Australia,” 70; Schopf,“Microfossils of the Early Archean Apex Chert.”
15. Schopf and Packer, “Early Archean (3.3-Billion- to 3.5-Billion-YearOld) Microfossils from Warrawoona Group, Australia,” 70; Hoffmann et al.,“Origin of 3.45 Ga Coniform Stromatolites in Warrawoona Group, Western
Australia.”
16. Jan Bergström states: “Animals such as arthropods and brachiopods
cannot exist without hard parts. The absence of remains of skeletons andshells in the Precambrian therefore proves that the phyla came into being with
the Cambrian, not before, even if the lineages leading to the phyla wereseparate before the Cambrian” (“Ideas on Early Animal Evolution,” 464).
17. Valentine and Erwin, “Interpreting Great Developmental
Experiments.”
18. Valentine, “Fossil Record of the Origin of Bauplan and Its
Implications,” especially 215.
19. Chen and Zhou, “Biology of the Chengjiang Fauna,” 21.
20. Chen and Zhou, “Biology of the Chengjiang Fauna,” 21. Or as
Valentine explains, “the interpretation of the explosion as an artifact of theevolution of durable skeletons has got it backward: the skeletons are artifacts,
more or less literally, of the evolutionary explosion.” Valentine, On the Originof Phyla, 181.
21. Ivantsov, “A New Reconstruction of Kimberella, a Problematic
Metazoan,” 3.
22. Edgecombe, “Arthropod Structure and Development,” 74–75.
23. Frederick Schram, The Crustacea.
24. Simpson, Fossils and the History of Life, 73. Indeed, an exoskeleton is
far more than a mere covering for the soft parts of, say, a chelicerate or
crustacean, because it provides the sites for the attachment of the muscles andvarious other tissues. Further, the limbs (including the mouthparts and insome instances certain reproductive components) are encased in exoskeletal
elements that can articulate, allowing the arthropod to move, feed, and mate.
An exterior skeleton of any shrimp, for example, also has interior projections
that comprise its endophragmal system, which provides support for the
animal’s internal musculature and organs. At the same time, the skeleton of
any arthropod is a product of, and in turn regulates, its metabolism andphysiology. In order for the first members of Fuxianhuia or Marrella to havegrown (and possibly metamorphosed during their development), they would
have had to have successively secreted a new skeleton beneath the old one; tohave shed the used exoskeletons; and to have hardened each new exoskeleton.
This tight functional integration suggests the implausibility of evolutionarymodels that envision the Arthropod exoskeleton arising late as a kind ofaccretion to an already integrated system of soft parts.
25. Brocks et al., “Archean Molecular Fossils and the Early Rise of
Eukaryotes.”
26. Conway Morris, The Crucible of Creation, 47–48; Gould, “TheDisparity of the Burgess Shale Arthropod Fauna and the Limits of Cladistic
Analysis.”
27. Wiwaxia is considered soft-bodied, but it does have harder scales andspines. See Conway Morris, The Crucible of Creation, 97–98.
28. Valentine, “The Macroevolution of Phyla,” sec. 3.2, “Soft-Bodied
Body Fossils,” 529–31.
29. Conway Morris, The Crucible of Creation, 82.
30. Conway Morris, The Crucible of Creation, 76, 99.
31. Conway Morris, The Crucible of Creation, 68, 73, 74; “Burgess Shale
Faunas and the Cambrian Explosion.”
32. Conway Morris, The Crucible of Creation, 107.
33. Conway Morris, The Crucible of Creation, 92, 184.
34. Conway Morris, “Burgess Shale Faunas and the Cambrian Explosion.”35. Conway Morris, The Crucible of Creation, 103; Conway Morris,“Burgess Shale Faunas and the Cambrian Explosion.”
36. A recent scientific paper reinterprets Nectocaris as a cephalopod
mollusk, though it also acknowledges the problems long associated with thedefinitive classification of this animal. See Smith and Caron, “Primitive SoftBodied Cephalopods from the Cambrian.”
37. Conway Morris, The Crucible of Creation, 140.
38. Hou et al., The Cambrian Fossils of Chengjiang, China, 10.
39. Hou et al., The Cambrian Fossils of Chengjiang, China, 10, 12.
40. Hou et al., The Cambrian Fossils of Chengjiang, China, 13.
41. Hou et al., The Cambrian Fossils of Chengjiang, China, 10, 12.
42. Hou et al., The Cambrian Fossils of Chengjiang, China, 23.
43. Bergström and Hou, “Chengjiang Arthropods and Their Bearing on
Early Arthropod Evolution,” 152.
44. Burgess Shale fossils from the middle Cambrian (515 million yearsago) confirm that many of these fully soft-bodied Cambrian organisms werelong-lived and geographically widespread.
45. Chen et al., “Weng’an Biota”; Chien et al., “SEM Observation ofPrecambrian Sponge Embryos from Southern China.”
46. Chen et al., The Chengjiang Biota: A Unique Window of the Cambrian
Explosion. This book is currently available only in the Chinese language. The
translated English version is being completed by Paul K. Chien, of the
University of San Francisco.
47. Chen et al., “Weng’an Biota”; Chien et al., “SEM Observation ofPrecambrian Sponge Embryos from Southern China.”
48. For other alternative interpretations, see Huldtgren et al., “Fossilized
Nuclei and Germination Structures Identify Ediacaran ‘Animal Embryos’ as
Encysting Protists,” 1696–99; Xiao et al., “Comment on ‘Fossilized Nuclei
and Germination Structures Identify Ediacaran ‘Animal Embryos’ as
Encysting Protists’,” 1169; Huldtgren et al., “Response to Comment on‘Fossilized Nuclei and Germination Structures Identify Ediacaran ‘Animal
Embryos’ as Encysting Protists’,” 1169.
49. Erwin and Valentine, The Cambrian Explosion, 778.
50. Chien et al., “SEM Observation of Precambrian Sponge Embryos fromSouthern China.” Sponges are assumed by most evolutionary biologists torepresent a side branch, not a node on evolutionary tree of life leading to theCambrian phyla. Thus, sponges are not regarded as plausible transitional
intermediates between Precambrian and Cambrian forms (nor are they
regarded as ancestral to other Cambrian animals).
51. Some have challenged the interpretation of these Precambrianmicrofossils as embryos, arguing that they are, instead, large microorganisms. For example, Therese Huldtgren and colleagues have argued thatthese fossils “have features incompatible with multicellular metazoan
embryos” and that “the developmental pattern is [more] comparable with
nonmetazoan holozoans,” a group that includes one-celled protozoans.
[Huldtgren et al., “Fossilized Nuclei and Germination Structures Identify
Ediacaran ‘Animal Embryos’ as Encysting Protists,” 1696–99.]
Critics of Huldtgren’s proposal instead think they may well be tinymetazoan embryos, though of unknown affiliation. [Xiao et al., “Comment on‘Fossilized Nuclei and Germination Structures Identify Ediacaran ‘Animal
Embryos’ as Encysting Protists’,” 1169. Huldtgren and colleagues havedefended their interpretation here: Huldtgren et al., “Response to Commenton ‘Fossilized Nuclei and Germination Structures Identify Ediacaran “Animal
Embryos” as Encysting Protists’,” 1169.]
Another interpretation is that the fossils represent giant sulphur bacteria,
since “sulphur bacteria of the genus Thiomargarita have sizes andmorphologies similar to those of many Doushantuo microfossils, including
symmetrical cell clusters that result from multiple stages of reductive divisionin three planes.” [Bailey et al., “Evidence of giant sulphur bacteria in
Neoproterozoic phosphorites,” 198–201.] Critics of this hypothesis doubt thatsulphur bacteria could be fossilized because they “collapse easily and have
only patchy biofilms that are limited to the multi-layered envelope.”[Cunningham et al., “Experimental taphonomy of giant sulphur bacteria:
implications for the interpretation of the embryo-like Ediacaran Doushantuo
fossils,” 1857–64.]
The debate over whether the Doushantuo microfossils should beinterpreted as metazoan embryos, protozoans, or giant sulphur bacteria will
doubtless continue. Whatever the outcome, however, the fact remains: small,fragile, and soft-bodied organisms of some kind have been found fossilized inthis Precambrian strata, raising the question of why the same layers of rockwere unable to preserve the immediate precursors to the numerous metazoan
phyla that emerge so abruptly in the Cambrian layers above them.
52. Similarly, paleontologists rarely find the remains of parasites that livein the soft tissues of other organisms (indeed, parasitic organisms represent
several of the phyla that have no fossil record). As noted, the geologicalrecord does preserve soft tissues, but only infrequently. When it does,
researchers fortunate enough to make such finds will rarely want to destroy
important specimens (of soft-tissue organs) in order to examine them fortraces of parasitic infection or habitation. Not surprisingly, therefore,
paleontologists have not found the remains of many parasitic organisms in thefossil record.
53. The Emergence of Animals, 91. This point is also based on personal
conversation with Professor (Mark) McMenamin.
54. Erwin and Valentine, The Cambrian Explosion, 8.
55. Foote, “Sampling, Taxonomic Description, and Our Evolving
Knowledge of Morphological Diversity,” 181. Another statistical
paleontologist, Michael J. Benton, and his colleagues have reached a similar
conclusion. They note that “if scaled to the . . . taxonomic level of the family[and above], the past 540 million years of the fossil record provide uniformly
good documentation of the life of the past” (Benton, Wills, and Hitchin,“Quality of the Fossil Record Through Time,” 534). In another article Benton
also writes: “It could be argued that there are fossils out there waiting to befound. It is easy to dismiss the fossil record as seriously, and unpredictably,incomplete. For example, certain groups of organisms are almost unknown as
fossils. . . . This kind of argument cannot be answered conclusively. However,an argument based on effort can be made. Paleontologists have been
searching for fossils for years and, remarkably, very little has changed since1859, when Darwin proposed that the fossil record would show us the patternof the history of life” (“Early Origins of Modern Birds and Mammals,” 1046).
56. Foote, “Sampling Taxonomic Description, and Our Evolving
Knowledge of Morphological Diversity,” 181. I should note that there is one
way in which my analogy to colored marbles in a barrel fails to capture thenature of the challenge of Cambrian fossil discontinuity. If after pullingsamples from a barrel for a while you finally came up with a green and orangeball to go along with the piles of red, blue, and yellow balls, you still
wouldn’t have much confidence that the barrel had a rainbow of ball colors
finely grading from one to another. Yet you could at least say that the orangeball stands between the yellow and red ball, and the green ball stands between
the blue and yellow balls (like the hybrid produced from two plants). But
many of the new Cambrian animal forms that have been discovered sinceDarwin’s time aren’t seen as intermediates between the previously known
animal forms representing known phyla. They aren’t evolutionary
intermediates between one existing phylum and another. Instead, scientists
consider them as existing out in morphological space all their own, standing
not as intermediates but as phyla that themselves are in need of intermediate
forms—almost as if, by stretching my analogy, some new primary color had
been discovered.
57. See Erwin et al., “The Cambrian Conundrum: Early Divergence andLater Ecological Success in the Early History of Animals,” 1091–97.
58. Bowring et al., “Calibrating Rates of Early Cambrian Evolution.”59. Bowring et al., “Calibrating Rates of Early Cambrian Evolution,”
1297.
60. Lili, “Traditional Theory of Evolution Challenged,” 10.
61. There are a few putative survivors of the Ediacaran fauna. For
example, the enigmatic and frond-like Thaumaptilon found in the Burgess
Shale might be a descendant of Ediacaran fronds, though this is contested.
Jensen et al., “Ediacara-Type Fossils Cambrian Sediment,” 567–69; Conway
Morris, “Ediacaran-like Fossils in Cambrian Burgess Shale-Type Faunas ofNorth America,” 593–635.
62. Bowring et al., “Calibrating Rates of Early Cambrian Evolution,”
1297. See also McMenamin, The Emergence of Animals.
63. Erwin et al., “The Cambrian Conundrum: Early Divergence and Later
Ecological Success in the Early History of Animals,” 1091–97.
64. Shu et al., “Lower Cambrian Vertebrates from South China.”
65. Chen et al., “A Possible Early Cambrian Chordate”; Chen and Li,“Early Cambrian Chordate from Chengjiang, China”; Dzik, “Yunnanozoon
and the Ancestry of Chordates.” Note, however, that the assertion thatYunnanozoon is a chordate has been challenged. See Shu, Zhang, and Chen,“Reinterpretation of Yunnanozoon as the Earliest Known Hemichordate”;
Shu, Morris, and Zhang, “A Pikaia-like Chordate from the Lower Cambrianof China.” Paleontologists also have found a single specimen of a possible
cephalchordate, Cathaymyrus, from the lower Cambrian Qiongzhusi
Formation near Chengjiang. The status of Cathaymyrus as a valid taxon has
also been challenged; some paleontologists argue that the single specimen of
Cathaymyrus may actually be a dorsoventrally compressed Yunnanozoon; see
Chen and Li, “Early Cambrian Chordate from Chengjiang, China.”
66. Chen, Huang, and Li, “An Early Cambrian Craniate-like Chordate,”
518.
67. Shu et al., “Lower Cambrian Vertebrates from South China.”
68. Shu et al., “An Early Cambrian Tunicate from China.”
69. The chordates discovered in the Cambrian strata near Chengjiang
represent just one of many new animal body plans found there, some of them
designated as new phyla, others as new subphyla, classes, or families within
existing phyla. For example, paleontologists classify Occacaris oviformis, around, egg-shaped animal with large forcep-like structures, as a member ofthe well-known phylum Arthropoda. [Hou et al., The Cambrian Fossils ofChengjiang, China, 130.] Nevertheless, Occacaris, which has been foundonly in the Maotianshan shale, clearly exemplifies a unique way of arranging
organs and tissue—one unlike any previously known arthropod outside theChengjiang biota. Arguably, it represents a unique body plan. In other cases,

Chinese paleontologists have discovered animals with such unusualmorphologies that they have been unable to classify them within any known
phylum. These so-called problematica, such as the mysterious Batofasciculus
ramificans, a hot-air-balloon-shaped cactus-like animal, has been given a
species and genus name, but as yet, no specific phyletic designation, though it
clearly exemplifies a unique body plan. [Hou et al., The Cambrian Fossils ofChengjiang, China, 196.] While such difficult-to-classify organisms do notincrease the official count of novel phyla that first arose during the Cambrian,they do frequently display novel body plans.
Chapter 4: The Not Missing Fossils?
1. Gradstein, Ogg, Schmitz, and Ogg, The Geological Time Scale 2012.
2. Grotzinger et al., “Biostratigraphic and Geochronologic Constraints on
Early Animal Evolution.” A few Ediacarans may have survived until the
middle Cambrian. See Conway Morris, “Ediacaran-like Fossils in Cambrian
Burgess Shale-Type Faunas of North America.”
3. Monastersky, “Ancient Animal Sheds False Identity.”
4. Monastersky, “Ancient Animal Sheds False Identity.”
5. Monastersky, “Ancient Animal Sheds False Identity.”
6. Fedonkin and Waggoner, “The Late Precambrian Fossil Kimberella is a
Mollusc-like Bilaterian Organism,” 868.
7. For example, Graham Budd, a Swedish paleontologist and Cambrianexpert, has expressed skepticism about this classification. He acknowledges
that “the strongest case for an Ediacaran bilaterian body fossil has been madeby Fedonkin and Waggoner (1997) for Kimberella,” but nevertheless disputes
the classification of Kimberella as a true mollusk. He argues that “Kimberella
does not possess any unequivocal derived molluscan features, and its
assignment to the Mollusca or even the Bilateria must be considered to be
unproven” (Budd and Jensen, “A Critical Reappraisal of the Fossil Record of
the Bilaterian Phyla,” 270).
8. Another reason the Ediacaran body fossils cannot be assigned to theanimal phyla in a decisive manner is because of the coarse grain size of thebeds in which they occur. Details of body form are too vague to allow a clear
decision, and until better means of analysis or new beds with finer grain
texture are found, these fossils will remain as intriguing “problematica,”
problematic forms about which it is not possible to come to a decision. See
Miklos, “Emergence of Organizational Complexities During Metazoan
Evolution.” See also Bergström, “Metazoan Evolution Around thePrecambrian–Cambrian Transition.”
9. Retallack, “Growth, Decay and Burial Compaction of Dickinsonia,”

215. As Retallack goes on to explain, “Like fungi and lichens, Dickinsonia
was firmly attached to its substrate, ground-hugging, moderately flexible, andvery resistant to burial compaction” (236).
10. Glaessner, The Dawn of Animal Life, 122.
11. Birket-Smith, “A Reconstruction of the Pre-Cambrian Spriggina,”
237–58.
12. Glaessner, The Dawn of Animal Life, 122.
13. Glaessner, The Dawn of Animal Life, 122.
14. McMenamin, “Spriggina Is a Trilobitoid Ecdysozoan,” 105.
15. Glaessner, The Dawn of Animal Life, 122–23. McMenamin, The
Emergence of Animals, 20, 24, 118.
16. In addition, a recent depiction of an Ediacaran organism closely related
to Spriggina, called Yorgia, by Ediacaran expert Andrey Ivantsov, shows it
exhibiting a smoother, less jagged edge than the bodies of trilobites with noprotruding spines. Ivantsov’s reconstruction seems to underscore a shift inopinion away from regarding Spriggina–like organisms as basal arthropods inpossession of distinctive arthropod characteristics (such as genal spines).
Ivantsov, “Giant Traces of Vendian Animals.” See also Ivantsov, “Vendia andOther Precambrian ‘Arthropods.’ ”
17. Brasier and Antcliffe, “Dickinsonia from Ediacara,” 312.
18. Brasier and Antcliffe, “Dickinsonia from Ediacara,” 312. Ivantsov,“Vendia and other Precambrian ‘Arthropods.’ ”
19. “Asymmetry in the Fossil Record,” 137.
20. Erwin, Valentine, and Jablonski, “The Origin of Animal Body Plans,”
132.
21. Erwin, Valentine, and Jablonski, “The Origin of Animal Body Plans,”
132.
22. Erwin, Valentine, and Jablonski, “The Origin of Animal Body Plans,”
132.
23. Cooper and Fortey, “Evolutionary Explosions and the Phylogenetic
Fuse,” 151–56.
24. Fortey, “Cambrian Explosion Exploded,” 438.
25. Knoll and Carroll, “Early Animal Evolution,” 2129.
26. Ward, On Methuselah’s Trail, 36.
27. “Life on Land,” 153–54. Recently, Gregory Retallack has published acontroversial hypothesis about the Ediacaran fauna. Retallack has studied thedepositional environments of key Ediacaran fossils such as Dickinsonia. He
has concluded that these organisms should not be classified as marine
animals, because they were deposited on land. According to Retallack, therocks that bore these Ediacaran fossils “have a variety of features that aremore like the biological soil crusts of desert and tundra than the parallel
wrinkled, and undulose hydrated microbial mats of intertidal flats and shallow
seas.” [Retallack, “Ediacaran Life on Land,” 89.] Retallack’s thesis hasreceived a cool reception from other Ediacaran experts, however. They have
not only questioned his analysis of ancient sediments but pointed out that the
Ediacaran forms that he analyzed from Australia are also preserved in clearlymarine sediments (from Newfoundland, for example) and that it is unlikelythat the same organisms would live both on land and in the sea. [Callow,
Brasier, Mcilroy, “Discussion: ‘Were the Ediacaran siliciclastics of South
Australia coastal or deep marine?’’’ 1–3.]
28. Erwin et al., “The Cambrian Conundrum.” Others believe that these
Precambrian “worm” trails could have been created by giant protists. See
Matz et al., “Giant Deep-Sea Protist Produces Bilaterian-like Traces,” 1849–
54.
29. Valentine, Erwin, and Jablonski, “Developmental Evolution of
Metazoan Body Plans”; Runnegar, “Evolution of the Earliest Animals.”
30. Runnegar, “Proterozoic Eukaryotes”; Gehling, “The Case for
Ediacaran Fossil Roots to the Metazoan Tree.”31. Budd and Jensen, “A Critical Reappraisal of the Fossil Record of the
Bilaterian Phyla,” 270.
32. See Matz et al., “Giant Deep-Sea Protist Produces Bilaterian-like
Traces.”33. Erwin et al., “The Cambrian Conundrum.”34. Sperling, Pisani, and Peterson, “Poriferan paraphyly and Its
Implications for Precambrian Palaeobiology”; Erwin and Valentine, The
Cambrian Explosion, 80.
35. Conway Morris, “Evolution: Bringing Molecules into the Fold,” 5.
36. McMenamin and McMenamin, The Emergence of Animals, 167–68.
37. Peterson et al., “The Ediacaran Emergence of Bilaterians.”
38. Shen et al., “The Avalon Explosion,” 81.
39. See, e.g., Cooper and Fortey, “Evolutionary Explosions and the
Phylogenetic Fuse.” The Cambrian period 543 mya is marked by theappearance of small shelly fossils consisting of tubes, cones, and possibly
spines and scales of larger animals. These fossils, together with trace fossils,
gradually become more abundant and diverse as one moves upward in theearliest Cambrian strata (the Manykaian Stage, 543–530 mya).
40. Bowring et al., “Calibrating Rates of Early Cambrian Evolution,”
1293–98; Erwin et al., “The Cambrian Conundrum: Early Divergence andLater Ecological Success in the Early History of Animals,” 1091–97.
41. Meyer et al., “The Cambrian Explosion: Biology’s Big Bang,” 323–

402.
42. Valentine, “Prelude to the Cambrian Explosion,” 289.
43. Animals with fivefold symmetry extending from a central body cavity
are described technically as radially symmetric “pentamerous” animals.
44. Budd and Jensen, “A Critical Reappraisal of the Fossil Record of the
Bilaterian Phyla,” 261. As Budd and Jensen explain in more detail: “although
this fossil possesses pentaradial symmetry, its small size, combined withpreservation in relatively coarse sand means that other echinoderm-specificfeatures are not readily visible. Its assignment to the Echinodermata thus
largely rests on this single character, and must be at present regarded as anopen question” (261).
45. Valentine, On the Origin of Phyla, 287, 397.
46. Bottjer, “The Early Evolution of Animals,” 47.
47. Cnidarians and ctenophores, for example, are radially symmetric. (Onemight think that echinoderms, which as adults have pentaradial [fivefold]symmetry, are not bilaterians, but “in early development, echinoderms arebilateral” and thus classed among the Bilateria.) For more discussion, see
Valentine, On the Origin of Phyla, 391.
48. Bengtson and Budd, “Comment on ‘Small Bilaterian Fossils from 40
to 55 Million Years Before the Cambrian,’ ” 1291a.
49. As Bengtson and Budd explain, “The specimens presented by Chen etal. represent a common mode of preservation of microfossils in phosphatic
sediments, including those of the Doushantuo.” In particular, they note that“the layers have a regular banding of color and thickness that is different
between the specimens but consistent within the individual specimens.” They
argue that “this pattern defies biological explanation but is easily explained as
representing two to three generations of diagenetic overgrowth.” They also
note that “rather than being sinuously folded, as would be expected fromdeformed tissue layers,” the layers in the imprint display features typical of(inorganic) diagenetic crusts. They conclude that although the imprint may
have encased the remains of eukaryotic microfossils, “their reconstructedmorphology as bilaterians is an artifact generated by cavities being lined bydiagenetic crusts. The appearance of the fossils now has little resemblance tothat of the living organisms that generated them” (“Comment on ‘Small
Bilaterian Fossils from 40 to 55 Million Years Before the Cambrian,’” 1291a).
50. Bengtson et al., “A Merciful Death for the ‘Earliest Bilaterian,’
Vernanimalcula,” 421.
51. Bottjer, “The Early Evolution of Animals,” 47.
52. Bengtson et al., “A Merciful Death for the ‘Earliest Bilaterian,’

Vernanimalcula,” 426.
53. Bengtson et al., “A Merciful Death for the ‘Earliest Bilaterian,’
Vernanimalcula,” 426.
54. Marshall and Valentine, “The Importance of Preadapted Genomes in
the Origin of the Animal Bodyplans and the Cambrian Explosion,” 1190,
emphasis added.
55. Budd and Jensen, “The Limitations of the Fossil Record and the Datingof the Origin of the Bilateria,” 183.
56. Budd and Jensen, “The Limitations of the Fossil Record and the Datingof the Origin of the Bilateria,” 168.
Chapter 5: The Genes Tell the Story?
1. Dawkins, The Greatest Show on Earth, 111.
2. According to Zvelebil and Baum, “The key assumption made whenconstructing a phylogenetic tree from a set of sequences is that they are allderived from a single ancestral sequence, i.e., they are homologous”(Understanding Bioinformatics, 239). Lecointre and Le Guyader note:“Cladistics can run into difficulties in its application because not all character
states are necessarily homologous. Certain resemblances are convergent—that
is, the result of independent evolution. We cannot always detect theseconvergences immediately, and their presence may contradict othersimilarities, ‘true homologies’ yet to be recognized. Thus, we are obliged toassume at first that, for each character, similar states are homologous, despiteknowing that there may be convergence among them” (The Tree of Life, 16).
3. Coyne, Why Evolution Is True, 10.
4. Budd and Jensen, “A Critical Reappraisal of the Fossil Record of the
Bilaterian Phyla,” 253–95; Budd and Jensen, “The Limitations of the Fossil
Record and the Dating of the Origin of the Bilateria,” 166–89 (“The expected
Darwinian pattern of a deep fossil history of the bilaterians, potentiallyshowing their gradual development, stretching hundreds of millions of years
into the Precambrian, has singularly failed to materialize . . . whatever the
resolution of the misfit between the fossil record and molecular evidence forthe origin of animals, it does not come about through a misunderstanding of
the known fossil record . . . The known fossil record has not been
misunderstood, and there are no convincing bilaterian candidates known fromthe fossil record until just before the beginning of the Cambrian (c. 543 Ma),even though there are plentiful sediments older than this that should reveal
them”); Jensen et al., “Trace fossil preservation and the early evolution ofanimals,” 19–29 (“A literal reading of the body fossil record suggests that thediversification of bilaterian animals did not significantly precede theNeoproterozoic–Cambrian boundary (ca. 545 Ma) . . . Despite reports to thecontrary, there is no widely accepted trace fossil record from sediments older
than about 560–555 Ma. . . . The above conclusions place serious constraints
on the time of appearance of bilaterian animals. For example, assuming thatkey bilaterian features could only have been acquired in moderately large
benthic animals, the absence of an ancient trace fossil record suggests that the
Cambrian ‘explosions’ are a reality in terms of the relatively rapid appearance
and diversification of macroscopic bilaterians”); Conway Morris, “Darwin’s
Dilemma: The Realities of the Cambrian ‘Explosion’,” 1069–83 (“The‘ancient school’ argues that animals evolved long before the Cambrian andthat the ‘explosion’ is simply an artefact, engendered by the breaching of
taphonomic thresholds, such as the onset of biomineralization and/or a sudden
increase in body size. The alternative ‘realist school’, to which I largely
subscribe, proposes that while the fossil record is far from perfect and isinevitably skewed in significant ways, none is sufficient to destroy a strong
historical signal”); Peterson et al., “MicroRNAs and Metazoan
Macroevolution: Insights into Canalization, Complexity, and the Cambrian
Explosion,” 736–47; Fortey, “The Cambrian Explosion Exploded?” 438–39;
Wray et al., “Molecular Evidence for Deep Precambrian Divergences Among
Metazoan Phyla,” 568–73 (“Darwin recognized that the sudden appearance ofanimal fossils in the Cambrian posed a problem for his theory of natural
selection. He suggested that fossils might eventually be found documenting a
protracted unfolding of Precambrian metazoan evolution. Many
paleontologists today interpret the absence of Precambrian animal fossils thatcan be assigned to extant clades not as a preservational artifact, but asevidence of a Cambrian or late Vendian origin and divergence of metazoan
phyla. This would make the Cambrian the greatest evolutionary cornucopia in
the history of the earth. Definitive representatives of all readily fossilizable
animal phyla (with the exception of bryozoans) have been found in Cambrianrocks, as have representatives of several soft-bodied phyla. Recent
geochronological studies have reinforced the impression of a ‘big bang ofanimal evolution’ by narrowing the temporal window of apparent divergences
to just a few million years”) (internal citations omitted); Erwin et al., “The
Cambrian Conundrum: Early Divergence and Later Ecological Success in the
Early History of Animals,” 1091–97 (“When Charles Darwin published The
Origin of Species (1), the sudden appearance of animal fossils in the rockrecord was one of the more troubling facts he was compelled to address. He
wrote: ‘There is another and allied difficulty, which is much graver. I allude to
the manner in which numbers of species of the same group, suddenly appear
in the lowest known fossiliferous rocks’ (306). Darwin argued that theincompleteness of the fossil record gives the illusion of an explosive event,
but with the eventual discovery of older and better-preserved rocks, theancestors of these Cambrian taxa would be found. Studies of Ediacaran andCambrian fossils continue to expand the morphologic variety of clades, but
the appearance of the remains and traces of bilaterian animals in the
Cambrian remains abrupt.”).
5. As Alan Cooper and Richard Fortey explain, “Molecular evidence
indicates that prolonged periods of evolutionary innovation and cladogenesis
lit the fuse long before the ‘explosions’ apparent in the fossil record.
(“Evolutionary Explosions and the Phylogenetic Fuse,” 151.) Also, according
to Welch, Fontanillas, and Bromham: “However, a wide range of moleculardating studies have suggested that the major lineages of animals arose long
before the Cambrian, at over 630 mya [million years ago]. This raises thepossibility that there was a long cryptic period of animal evolution preceding
the explosion of fossils in the Cambrian” (“Molecular Dates for the‘Cambrian Explosion,’ ” 672–73).
6. “The molecular clock . . . is the assumption that lineages have evolved
at equal rates” (Felsenstein, Inferring Phylogenies, 118).
7. Smith and Peterson, “Dating the Time and Origin of Major Clades,” 72.
8. Wray, Levinton, and Shapiro, “Molecular Evidence for Deep
Precambrian Divergences Among Metazoan Phyla”; for another similar studyof molecular sequence data that comes to the same conclusion, see Wang,
Kumar, and Hedges, “Divergence Time Estimates for the Early History of
Animal Phyla and the Origin of Plants, Animals and Fungi,” 163; see also
Vermeij, “Animal Origins”; and Fortey, Briggs, and Wills, “The Cambrian
Evolutionary ‘Explosion’ Recalibrated.”
9. These proteins were ATP-ase, cytochrome c, cytochrome oxidase I andII, alpha and beta hemoglobin, and NADH I.
10. The ribosomal RNA they used was 18S rRNA.
11. These proteins were aldolase, methionine adenosyltransferase, ATPsynthase beta chain, catalase, elongation factor 1 alpha, triosephosphate
isomerase, and phosphofructokinase.
12. The three RNA molecules they used were 5.8S rRNA, 18S rRNA, and
28S rRNA.
13. Erwin et al., “The Cambrian Conundrum,” 1092.
14. For example, Bronham and colleagues find that mitochondrial DNA
and 18S rRNA data yielded divergence dates that varied by more than 1billion years (“Testing the Cambrian Explosion Hypothesis by Using a
Molecular Dating Technique”); Xun suggests that from a total of 22 nuclear
genes the divergence time between Drosophila and vertebrates was about 830

mya (million years ago; “Early Metazoan Divergence Was About 830 Million
Years Ago”); Doolittle and colleagues date the protostome-deuterostome split
at 670 million years ago (“Determining Divergence Times of the Major
Kingdoms of Living Organisms with a Protein Clock”); Nikoh and colleagues
date the split between eumetazoa and parazoa—animals with tissues, such as
cnidarians, from those without, like sponges—at 940 mya, and the split
between vertebrates and amphioxus at 700 mya (“An Estimate of Divergence
Time of Parazoa and Eumetazoa and That of Cephalochordata and Vertebrataby Aldolase and Triose Phosphate Isomerase Clocks”); and Wang, Kumar,and Hedges suggest the basal animal phyla (Porifera, Cnidaria, Ctenophora)
diverged between about 1200–1500 mya, and that nematodes were found tohave diverged from the lineage leading to arthropods and chordates at 1177–
79 mya (“Divergence Time Estimates for the Early History of Animal Phyla
and the Origin of Plants, Animals and Fungi”).
15. Wray, Levinton, and Shapiro, “Molecular Evidence for Deep
Precambrian Divergences Among Metazoan Phyla,” 568.
16. Wray, Levinton, and Shapiro, “Molecular Evidence for Deep
Precambrian Divergences Among Metazoan Phyla,” 569.
17. Wray, Levinton, and Shapiro, “Molecular Evidence for Deep
Precambrian Divergences Among Metazoan Phyla,” 568.
18. Quoted in Hotz, “Finding Turns Back Clock for Earth’s First
Animals,” A1, A14.
19. See, e.g., Xun, “Early Metazoan Divergence Was About 830 Million
Years Ago”; Aris-Brosou and Yang, “Bayesian Models of Episodic Evolution
Support a Late Precambrian Explosive Diversification of the Metazoa.” Seealso an early study by Bruce Runnegar in 1982, which measured the percent
sequence difference between globin molecules in various animal phyla and,from this, postulated that “the initial radiation of the animal phyla occurred atleast 900–1000 million years ago” (Runnegar, “A Molecular-Clock Date for
the Origin of the Animal Phyla,” 199). For other examples, see Bronham etal., “Testing the Cambrian explosion hypothesis by using a molecular dating
technique,” 12386–12389 (finding that mitochondrial DNA and 18S rRNA
data yielded divergence dates that varied by more than 1 billion years); Xun,
“Early Metazoan Divergence Was About 830 Million Years Ago,” 369–71(suggesting “From a total of 22 nuclear genes, we estimate that the divergencetime between Drosophila and vertebrates was about 830 million years ago(mya)”); Doolittle, “Determining Divergence Times of the Major Kingdomsof Living Organisms with a Protein Clock,” 470–77 (dating the protostomedeuterostome split at 670 million years ago); Nikoh et al., “An Estimate ofDivergence Time of Parazoa and Eumetazoa and That of Cephalochordata

and Vertebrata by Aldolase and Triose Phosphate Isomerase Clocks,” 97–106(dating the split between eumetazoa and parazoa—animals with tissues fromthose without, like sponges—at 940 mya, and the split between vertebrates
and amphioxus at 700 mya); Wang et al., “Divergence Time Estimates for the
Early History of Animal Phyla and the Origin of Plants, Animals and Fungi,”
163–71 (suggesting “the basal animal phyla (Porifera, Cnidaria, Ctenophora)
diverged between about 1200–1500 Ma” and “Nematodes were found to havediverged from the lineage leading to arthropods and chordates at 1177–79
Ma”).
20. Valentine, Jablonski, and Erwin, “Fossils, Molecules and Embryos,”851.
21. Nikoh et al., “An Estimate of Divergence Time of Parazoa andEumetazoa and That of Cephalochordata and Vertebrata by Aldolase andTriose Phosphate Isomerase Clocks.”
22. Wang, Kumar, and Hedges, “Divergence Time Estimates for the Early
History of Animal Phyla and the Origin of Plants, Animals and Fungi,” 163.
23. Bronham et al., “Testing the Cambrian Explosion Hypothesis by Usinga Molecular Dating Technique.”
24. Xun, “Early Metazoan Divergence Was About 830 Million Years
Ago.”
25. Aris-Brosou and Yang, “Bayesian Models of Episodic Evolution
Support a Late Precambrian Explosive Diversification of the Metazoa.” Other
literature surveys report that molecular clock-based estimates of the split
between protostomes and deuterostomes have ranged from 588 million to 1.5
billion years ago. See Erwin, Valentine, and Jablonski, “The Origin of Animal
Body Plans”; and Benton and Ayala, “Dating the Tree of Life.”
26. Graur and Martin, “Reading the Entrails of Chickens: MolecularTimescales of Evolution and the Illusion of Precision.”
27. Graur and Martin, “Reading the Entrails of Chickens,” 85. Smith andPeterson also note: “The second area where molecules and morphology are inserious disagreement concerns the origins of the metazoan phyla. Although
the difference between the molecular and morphological estimates for bird
and mammal origins may be as much as 50 million years, the discord between
the two for the animal phyla may be as much as 500 million years, almost theentire length of the Phanerozoic” (“Dating the Time and Origin of Major
Clades,” 79).
28. Ayala, Rzhetsky, and Ayala, “Origin of the Metazoan Phyla.”
29. Ayala and his team eliminated the 18S rRNA, an RNA-coding genebecause of problems with obtaining a reliable alignment. They also added an
additional twelve protein-coding genes.

30. Ayala, Rzhetsky, and Ayala, “Origin of the Metazoan Phyla,” 611.
31. Valentine, Jablonski, and Erwin, “Fossils, Molecules and Embryos,”856.
32. Behe, “Histone Deletion Mutants Challenge the Molecular Clock
Hypothesis.”
33. Some evolutionary biologists have attempted to explain their extreme
conservation (similarity) by “strong selection” for their essential functionalrole: the close packing, or wrapping, of DNA in eukaryotic chromosomes.
This hypothesis is hard to square, however, with experimental data showingthat yeast tolerates dramatic deletions in their H4 histones. Behe, “Histone
Deletion Mutants Challenge the Molecular Clock Hypothesis.”
34. As Baverstock and Moritz explain in more detail: “The single mostimportant component . . . of a phylogenetic analysis is the decision as towhich method(s) or sequence(s) are appropriate to the phylogenetic questionat hand. The method chosen must yield sufficient variation as to bephylogenetically informative, but not so much variation that convergence andparallelisms overwhelm informative changes” (“Project Design,” 25).
35. Valentine, Jablonski, and Erwin, “Fossils, Molecules and Embryos,”856.
36. Ho et al., “Accuracy of Rate Estimation Using Relaxed-Clock Models
with a Critical Focus on the Early Metazoan Radiation,” 1355.
37. Smith and Peterson, “Dating the Time and Origin of Major Clades,”73.
38. Smith and Peterson, “Dating the Time and Origin of Major Clades,”73. Smith and Peterson elaborate: “All molecular clock approaches require
one or more calibration points using dates derived either from the fossil
record or from biogeographic constraints. There are two approaches—either
calibration can rely on one or a small number of ‘well documented’ dates
where paleontological evidence seems highly reliable, or calibration can beachieved using a large number of independent dates so that a range of
estimates is arrived at. The former approach has been criticized by both Lee(1999) and Alroy (1999) for placing too much reliance on a single
paleontological date without considering its error” (75). See Lee, “Molecular
Clock Calibrations and Metazoan Divergence Dates”; and Alroy, “The Fossil
Record of North American Mammals.” Dan Graur and William Martin
concur. They note that gross uncertainties often afflict assumptions about (1)the age of fossils used to calibrate the molecular clock, (2) the rate of
mutations in various genes, and (3) the conclusions of comparative sequence
analyses based upon the use of molecular clocks (“Reading the Entrails ofChickens”).

39. Conway Morris, “Evolution,” 5–6.
40. Valentine Jablonski, and Erwin, “Fossils, Molecules and Embryos,”856.
41. Zvelebil and Baum, Understanding Bioinformatics, 239.
42. Lecointre and Le Guyader, The Tree of Life, 16.
43. For a related discussion see Wagner and Stadler, “Quasi-Independence,
Homology and the Unity of Type.”
44. Osigus, Eitel, Schierwater, “Chasing the Urmetazoon: Striking a Blow
for Quality Data?” 551–57; Conway Morris, “The Cambrian ‘Explosion’ andMolecular Biology,” 505–506.
45. Osigus, Eitel, Schierwater, “Chasing the Urmetazoon: Striking a Blow
for Quality Data?” 551–57. As Osigus and colleagues note: “The sum of
molecular trees based on large numbers of gene sequences does not resolve
phylogenetic relationships at the base of the Metazoa. Conflicting scenarios
have been published in short sequence and each single analysis can be
criticized for one or the other reason. It is unclear to many whether the base of
Metazoa can ever be resolved by means of sequence data even if wholegenomes and extensive taxon sampling is used” (555).
46. Conway Morris, “Early Metazoan Evolution,” 870.
47. Graur and Martin, “Reading the Entrails of Chickens”; Smith andPeterson, “Dating the Time and Origin of Major Clades”; Valentine,
Jablonski, and Erwin, “Fossils, Molecules and Embryos.”
Chapter 6: The Animal Tree of Life
1. “The Darwinian Sistine Chapel,” April 14, 2009,www.bbc.co.uk/darwin/?tab=21 (accessed October 31, 2012).
2. Hellström, “The Tree as Evolutionary Icon,” 1.
3. Ruse, Darwinism Defended, 58.
4. Dobzhansky, “Nothing in Biology Makes Sense Except in the Light of
Evolution,” 125.
5. Dawkins, The Greatest Show on Earth, 315.
6. As Coyne has asserted, “both the visible traits of organisms and their
DNA sequences usually give the same information about evolutionary
relationships” (Why Evolution Is True, 10).
7. Atkins, Galileo’s Finger, 16.
8. Coyne, Why Evolution Is True, 7.
9. An enormous literature exists analyzing how “similarity,” which can bedirectly observed and measured, comes to be interpreted as “homology,” atheoretical construct that cannot be directly observed. The two terms should
not be equated. According to Van Valen, “For molecular biologists . . . a good

touchstone is that homology is always an inference, never an observation.
What we observe is similarity or identity, never homology” (“Similar, but Not
Homologous,” 664).
10. Prothero, Evolution, 140.
11. Dawkins, A Devil’s Chaplain: Reflections on Hope, Lies, Science, andLove, 112.
12. Wiley and Lieberman, Phylogenetics, 6.
13. Degnan and Rosenberg, “Gene Tree Discordance, Phylogenetic
Inference and the Multispecies Coalescent,” 332.
14. Dávalos et al., “Understanding Phylogenetic Incongruence: Lessons
from Phyllostomid Bats,” 993.
15. Syvanen and Ducore, “Whole Genome Comparisons Reveals a
Possible Chimeric Origin for a Major Metazoan Assemblage,” 261–75.
16. Quoted in Lawton, “Why Darwin Was Wrong About the Tree of Life,”
39.
17. Rokas, “Spotlight: Drawing the Tree of Life.”
18. Rokas, Krüger, and Carroll. “Animal Evolution and the MolecularSignature of Radiations Compressed in Time,” 1933–34.
19. Rokas and Carroll, “Bushes in the Tree of Life,” 1899–1904.
20. Rokas and Carroll, “Bushes in the Tree of Life,” 1899–1904 (internal
citations omitted).
21. Rokas and Carroll, “Bushes in the Tree of Life,” 1899–1904 (internal
citations omitted).
22. Rokas and Carroll, “Bushes in the Tree of Life,” 1899–1904.
23. Rokas, Krüger, and Carroll, “Animal Evolution and the MolecularSignature of Radiations Compressed in Time,” 1935.
24. Zuckerkandl and Pauling, “Evolutionary Divergence and Convergencein Proteins,” 101.
25. Zuckerkandl and Pauling, “Evolutionary Divergence and Convergencein Proteins,” 101.
26. Theobald, “29+ Evidences for Macroevolution.”
27. Hyman, The Invertebrates, vol. 1: Protozoa Through Ctenophora.
28. Holton and Pisani, “Deep Genomic-Scale Analyses of the Metazoa
Reject Coelomata.”
29. Aguinaldo et al., “Evidence for a Clade of Nematodes, Arthropods andOther Moulting Animals.” See also Telford et al., “The Evolution of theEcdysozoa”; Halanych and Passamaneck, “A Brief Review of Metazoan
Phylogeny and Future Prospects in Hox-Research”; and Mallatt, Garey, andShultz, “Ecdysozoan Phylogeny and Bayesian Inference.”
30. Aguinaldo et al., “Evidence for a Clade of Nematodes, Arthropods andOther Moulting Animals.” See also Halanych, “The New View of Animal
Phylogeny.”
31. Telford et al., “The Evolution of the Ecdysozoa.”
32. Aguinaldo et al., “Evidence for a Clade of Nematodes, Arthropods andOther Moulting Animals,” 492.
33. In 2004, for instance, researcher Yuri Wolf and his colleagues at the
National Center for Biotechnology Information (NCBI) published aphylogeny based on molecular data (500 sets of proteins as well as
insertion/deletion patterns in similar proteins) supporting the earlier
Coelomata hypothesis. Wolf’s team concluded, “All of these approaches
supported the coelomate clade and showed concordance between evolution ofprotein sequences and higher-level evolutionary events” (“Coelomata and Not
Ecdysozoa,” 29). Another NCBI study, by Jie Zheng and colleagues publishedin 2007, analyzed conserved intron positions in the genomes of various
animals; it supported the Coelomata clade and rejected Ecdysozoa (introns are
sections of the genome that do not encode information for building proteins
and occur in the genome between the regions, called exons, that do code forproteins; “Support for the Coelomata Clade of Animals from a Rigorous
Analysis of the Pattern of Intron Conservation”).
34. In 2008, for example, Scott Roy (who also works at the NCBI) andManuel Irimia (at the University of Barcelona) argued that the intron data
actually supported the Ecdysozoa hypothesis (“Rare Genomic Characters Do
Not Support Coelomata”).
35. Holton and Pisani, “Deep Genomic-Scale Analyses of the Metazoa
Reject Coelomata.”
36. In this tree, now generally known as the Ecdysozoa hypothesis, thebilaterians are divided first into the protostomes and deuterostomes. theprotostomes (or Protostomia) are then further subdivided into two distinctgroups: (1) the Lophotrochozoa (so called because of two distinctive
anatomical characters, a ciliated larva [trochophore] and a ciliated feeding
structure [lophophore]) and (2) the Ecdysozoa (the molting animals).
37. Maley and Marshall, “The Coming of Age of Molecular Systematics,”
505.
38. As Maley and Marshall conclude, “Different representative species, inthis case brine shrimp or tarantula for the arthropods, yield wildly different
inferred relationships among phyla” (“The Coming of Age of Molecular
Systematics,” 505).
39. According to Valentine, Jablonski, and Erwin, “Molecular evidence
has produced a new view of metazoan phylogeny, prompting new analyses ofmorphological, ultrastructural and developmental characters” (“Fossils,

Molecules and Embryos,” 854).
40. See Nielsen, Animal Evolution, 82.
41. Rokas et al., “Conflicting Phylogenetic Signals at the Base of theMetazoan Tree”; Halanych, “The New View of Animal Phylogeny”;
Borchiellini et al., “Sponge Paraphyly and the Origin of Metazoa.”
42. Rokas et al., “Conflicting Phylogenetic Signals at the Base of theMetazoan Tree”; Halanych, “The New View of Animal Phylogeny.”
43. Gura, “Bones, Molecules . . . or Both?” 230. A 2004 paper in the
Annual Review of Ecology and Systematics puts it this way: “Molecular tools
have profoundly rearranged our understanding of metazoan phylogeny.”(Halanych, “The New View of Animal Phylogeny,” 229.)
44. Dávalos et al., “Understanding Phylogenetic Incongruence: Lessons
from Phyllostomid Bats,” 993.
45. One might object here that building phylogenetic trees among thehigher taxonomic groups, such as the animal phyla, is an inherently tricky
business—but that phylogenetic trees describing lower taxonomic groups,
such as those within the phyla, show consistency among different kinds ofevidence. Of course, strictly speaking, even if there was evidence of a single
coherent tree connecting groups within a phylum, it would do nothing toestablish ancestors of the phyla themselves, but instead only members of thesmaller groups within specific phyla. Nevertheless, even among lower taxa
the primary literature on phylogenetic inference challenges the treelike pictureof animal history.
Consider the crustacea, for instance, a large group within the phylum
Arthropoda. The crustacea include such familiar creatures as shrimp andlobsters. (Darwin himself published his major technical work in biology on
the classification of barnacles, a group [Cirripedia] within the crustacea.)
Given the claims of Dawkins, Coyne, and Atkins, we might have expectedthat evolutionary biologists would have long ago established a single univocal
evolutionary history for a well-studied group such as the crustacea, and thatmolecular data would by now only be confirming what biologists have known
all along. But note, instead, that Ronald Jenner, a zoologist and expert on
crustacea at the British Museum of Natural History, describes crustacean
phylogeny as “essentially unresolved.” As he explains the situation, “Conflictis rife, irrespective of whether one compares different morphological studies,molecular studies, or both” (“Higher-Level Crustacean Phylogeny,” 143). The
area of study remains “intensely contentious,” he continues, and “publishedstudies show very few points of consensus, even if one constrains thecomparison to just the most comprehensive and careful analyses” (151).
Other studies of different classes of organisms within the arthropod phyla

introduce further uncertainty. Insects provide another important example ofsuch incongruity. Based on anatomical evidence, systematists have long heldthat insects are most closely related to the group that contains centipedes andmillipedes (called the myriapod group). Nevertheless, molecular studies by F.
Nardi and colleagues indicate that insects are more closely related tocrustaceans. Similarly, the same molecular study suggested that somewingless insects are more closely related to crustaceans than they are to otherinsects, though anatomical studies indicate the opposite for obvious reasons.
This led the authors of the paper to conclude that insects (hexapods) are notmonophyletic—a view never anticipated by most evolutionary biologists.
Because of incongruities between molecular and morphology-based trees, theNardi team offered a puzzled observation: “Although this tree shows many
interesting outcomes, it also contains some evidently untenable relationships,
which nevertheless have strong statistical support” (“Hexapod Origins,”
1887). But see Delsuc et al., “Comment on ‘Hexapod Origins: Monophyleticor Paraphyletic?’ ” 1482d; Nardi et al., “Response to Comment on ‘Hexapod
Origins: Monophyletic or Paraphyletic?’” 1482e.
Studies of vertebrates, a subphylum of another phylum, the chordates,
have revealed similar contradictory phylogenetic relationships. For example,
a recent paper on bat phylogenetics, noted that “For more than a decade,evolutionary relationships among members of the New World bat family
Phyllostomidae inferred from morphological and molecular data have been in
conflict.” The authors “ruled out paralogy, lateral gene transfer, and poor
taxon sampling and outgroup choices among the processes leading toincongruent gene trees in phyllostomid bats.” The authors further note that“differential rates of change and evolutionary mechanisms driving those rates
produce incongruent phylogenies. Incongruence among phylogenies
estimated from different sets of characters is pervasive. Phylogenetic conflicthas become a more acute problem with the advent of genome-scale data sets.
These large data sets have confirmed that phylogenetic conflict is common,and frequently the norm rather than the exception.” Dávalos et al.,“Understanding phylogenetic incongruence: lessons from phyllostomid bats,”
991–1024 (internal citations omitted). See also Patterson et al., “Congruence
Between Molecular and Morphological Phylogenies,” 153–88.
46. Schwartz and Maresca, “Do Molecular Clocks Run at All?” 357.
47. James Valentine, for example, disputes the reality of the coelom as ashared characteristic that defines a group, as advocates of the Coelomata
hypothesis contended. As Valentine notes, the “assumption of the monophylyof coelomic spaces” was one of the “major principles used to relate thephyla.” In his view, however, the coelom evolved multiple times

independently and thus cannot be used as a homologous character defining amonophyletic group. He argues, instead, that “coeloms are polyphyletic. Few
characters are simpler than fluid-filled cavities, and it is not difficult tovisualize them as evolving many times for a number of purposes” (On theOrigin of Phyla, 500).
48. Figure 6.2 derived from: Figure 1 of Edgecombe et al., “Higher-Level
Metazoan Relationships: Recent Progress and Remaining Questions.”
49. For further discussion of the central position of germ cells in evolution,
see Ewen-Campen, Schwager, and Extavour, “The Molecular Machinery ofGerm Line Specification.” As they explain: “Sexually reproducing animals
must ensure that one particularly important cell type is determined: the germ
cells. These cells will be the sole progenitors of eggs and sperm in thesexually mature adult, and as such, their correct specification during
embryonic development is critical for reproductive success and species
survival” (3).
50. As is the case with mutations affecting other major organismalfeatures, there is a remarkable absence of examples of successful (i.e., stablytransmitted) mutations that significantly modify PGC formation in any animalgroup. Searching the experimental literature of the model systems indevelopmental biology, such as fruit flies (Drosophila), mice (Mus), andnematodes (C. elegans), reveals instead many loss-of-function or loss-ofstructure examples, including total absence of egg cells (oocytes) in fruit flies(Lehmann, “Germ-Plasm Formation and Germ-Cell Determination in
Drosophila”), germ-cell reduction and sterility in mice (Pellas et al., “GermCell Deficient [gcd], an Insertional Mutation Manifested as Infertility inTransgenic Mice”), and oocyte elimination with consequent sterility inhermaphroditic nematodes (Kodoyianni, Maine, and Kimble, “Molecular
Basis of Loss-of-Function Mutations in the glp–1 Gene of Caenorhabditis
elegans”). See also Youngren, “The Ter mutation in the dead end gene causes
germ cell loss and testicular germ cell tumours,” 360–64. Such examples ofdeleterious or catastrophic mutations could be multiplied indefinitely fromthese and other model systems.
51. Andrew Johnson, associate professor and reader in genetics at the
University of Nottingham, and several coauthors frame the point this way:
“Germ cell development acting as a constraint on embryonic morphogenesis
is at first difficult to accept. However, the retention of a pool of PGCs, which
will later produce gametes, is a fundamental constraint on any sexually
reproducing organism, because the inability to pass inherited traits to
subsequent generations will terminate an individual’s lineage. Therefore,changes in developmental processes that endanger the maintenance of PGCs

will not be retained” (“Evolution of Predetermined Germ Cells in Vertebrate
Embryos: Implications for Macroevolution,” 425, emphasis added).
52. Extavour, “Evolution of the Bilaterian Germ Line,” 774. See Fig. 6.4.
53. Extavour, “Gray Anatomy,” 420. Instead, she postulates that“convergent evolution has resulted in many different morphological, andpossibly molecular genetic, solutions to the various problems posed by sexual
reproduction.”
54. Willmer and Holland, “Modern Approaches to Metazoan
Relationships,” 691, emphasis in original.
55. Willmer and Holland, “Modern Approaches to Metazoan
Relationships,” 690.
56. Brusca and Brusca, Invertebrates, 120; 2nd ed., 115.
57. Jenner, “Evolution of Animal Body Plans,” 209.
58. In addition to convergent evolution, evolutionary biologists haveoffered a whole host of explanations to account for the many instances where
shared anatomical and molecular similarity is not explicable by reference tovertical descent from a common ancestor, including: differing rates of
evolution (resulting from positive selection or purifying selection), long
branch attraction, rapid evolution, whole genome-fusion, coalescent (e.g.,incomplete lineage sorting), DNA contamination, and horizontal genetransfer.
Horizontal gene transfer (HGT) occurs when organisms (usuallyprokaryotes such as bacteria) transfer genes to neighboring individuals. Thismechanism provides a plausible explanation for some phylogenetic
incongruence in prokaryotes, although some mission-critical housekeeping
genes are thought to resist HGT. The mechanisms by which HGT occurs arewell characterized, and include transformation (incorporation of free DNA
from the environment into a recipient cell), transduction (transfer of DNA
from one cell to another by a bacterial virus called a bacteriophage), andconjugation (transfer of DNA by direct cell-to-cell contact via a pilus).
Horizontal gene transfer is less plausible however, in eukaryotes, where it
occurs much less frequently and potential mechanisms are far less wellcharacterized, although it is thought to occur in some rare cases between
eukaryotes and prokaryotes, though more rarely, if at all, between different
animals. [See Doolittle, “Phylogenetic Classification and the Universal Tree,”
2124–28; Hall, “Contribution of Horizontal Gene Transfer to the Evolution of
Saccharomyces cerevisiae,” 1102–15; Kondo, “Genome Fragment of
Wolbachia Endosymbiont Transferred to X Chromosome of Host Insect,”14280–85.]
Another proposed explanation of phylogenetic conflict is called long-branch attraction, an artifact of the phylogenetic algorithms, that results inpreferentially grouping together related lineages that diverged quickly, andthen evolved separately over long periods of time. [Bergsten, “A Review ofLong-Branch Attraction,” 163–93.]
Another proposed cause of incongruity is a phenomenon called incomplete
lineage sorting. This occurs when a lineage splits and then rapidly splits again
to yield three daughter species. This second split takes place before theprocess of sorting is complete (i.e., the process by which a daughter species
gradually acquires its own unique set of genetic variants). This event isfollowed by the loss of a random variant by genetic drift, and this may cause
two species to group together which otherwise would not. This process only
accounts for phylogenetic incongruity between closely related species,
however.
While some of these explanations may be plausible in some cases, theyremain what they are: attempts to explain how two similar genes or traits
could have arisen without those genes or traits having been inherited from acommon ancestor. Thus in each case they provide counter-examples to thepremise upon which all phylogenetic reconstruction is based—namely thatsimilarity is an indicator of common ancestry.
Chapter 7: Punk Eek!
1. Lecture Notes, Paul Nelson, University of Pittsburgh, 9-28-83.
2. Gould and Eldredge, “Punctuated Equilibrium: The Tempo and Mode of
Evolution Reconsidered,” 147.
3. Gould and Eldredge, “Punctuated Equilibrium: The Tempo and Mode of
Evolution Reconsidered,” 115.
4. Eldredge, The Pattern of Evolution, 21.
5. Sepkoski, “ ‘Radical’ or ‘Conservative’? The Origin and Early
Reception of Punctuated Equilibrium,” 301–25. Gould and Eldredge
continued to jointly offered papers elaborating and refining the theory ofpunctuated equilibrium until 1993. See Gould and Eldredge, “PunctuatedEquilibrium Comes of Age,” 223–27.
6. As the U.S. National Academy of Sciences explained, punctuatedequilibrium sought to account for the absence of transitional intermediates byshowing that “changes in populations might occur too rapidly to leave manytransitional fossils” (Teaching About Evolution and the Nature of Science,57).
7. Though Gould and Eldredge formulated punctuated equilibrium several
years before studies of the molecular evidence discussed in Chapter 6, their
theory could also help explain the conflicting phylogenetic histories discussedthere as well. As Rokas, Krüger, and Carroll would later argue (“Animal
Evolution and the Molecular Signature of Radiations Compressed in Time”),
if the evolutionary process acts quickly enough, leaving little time fordifferences to accumulate in key molecular markers, then biologists should
expect phylogenetic studies to generate conflicting trees.
8. Sepkoski, “ ‘Radical’ or ‘Conservative’?” 304.
9. Gould and Eldredge, “Punctuated Equilibrium Comes of Age”;
Theobald, “Punctuated Equilibrium” (“Punctuated equilibrium immediately
lit a scientific controversy that has smoldered ever since”); Bell, “Gould’s
Most Cherished Concept” (“Whether or not you agree with Gould thatpunctuated equilibrium has become the conventional wisdom, it certainly has
led to a healthy debate concerning the sufficiency of neo-Darwinian theory to
explain macroevolution, the analysis of biostratigraphic sequences, and theincreased incorporation of paleontological data into evolutionary theory”);
Dawkins, The Blind Watchmaker, 240–41; Dennett, Darwin’s Dangerous Idea,
282–99; Ridley, “The Evolution Revolution”; Gould, “Evolution: Explosion,
Not Ascent”; Boffey, “100 Years after Darwin’s Death, His Theory Still
Evolves”; Gleick, “The Pace of Evolution”; Maynard Smith, “Darwinism
Stays Unpunctured”; Levinton, “Punctuated Equilibrium”; Schopf, Hoffman,
and Gould, “Punctuated Equilibrium and the Fossil Record”; Lewin,“Punctuated Equilibrium Is Now Old Hat” (noting that “the tenor of thedebate” over punctuated equilibrium “at times has been strident”); Levinton,“Bryozoan Morphological and Genetic Correspondence”; Lemen andFreeman, “A Test of Macroevolutionary Problems with Neontological Data”;
Charlesworth, Lande, and Slatkin, “A Neo-Darwinian Commentary on
Macroevolution”; Douglas and Avise, “Speciation Rates and Morphological
Divergence in Fishes.”
10. Rose, ed. The Richness of Life: The Essential Stephen Jay Gould, 6.
See also Turner, “Why We Need Evolution by Jerks”; Rée, “Evolution by
Jerks.”
11. Sepkoski, “ ‘Radical’ or ‘Conservative’?”
12. For an urn with 100 balls, 50 being red and 50 being blue, theprobability of getting only blue balls by randomly taking 50 balls out of theurn is given by the following considerations:First, there’s only one way to select only blue balls. Second, in general foran urn with N balls, there are C(N,k) different ways of choosing k balls fromamong these N (with k greater than or equal to 0 but less than or equal to N).
C(N,k) is equal to N! divided by the product of k! and (N-k)!, where theexclamation mark is read “factorial” and equals the product of all numbers
less than or equal to the number in question down to 1. Thus “six factorial” =6! = 6 x 5 x 4 x 3 x 2 x 1 = 720. Factorials increase very quickly, faster than
exponentials. C(N,k) is read “N choose k.”
So for the problem above, the total number of ways to choose 50 specificballs out of 100 balls, ignoring color, is C(100,50), which equals 100! divided
by 50! times 50!, or 100!/(50! x 50!).
This number admits an exact calculation, which can be expressed in
Mathematica as the following:C(100,50) = 100,891,344,545,564,193,334,812,497,256 which isapproximately 1.00891 x 1029.
Thus, the probability of selecting k specific balls out of N total balls is ofcourse the inverse of that number, and can be distilled to the following
equation:p = k! x (N – k)! / N!
Applied to this problem, the odds of randomly selecting all 50 blue balls ina collection of 50 blue and 50 red balls is 1 divided by C(100,50), or
approximately 9.91165 x 10-30.
13. Using the same equation discussed in the above endnote, theprobability of selecting 4 specific balls out of 8 total balls is given by thesame equation as follows: 4! x (8 - 4)! / 8! = 1 in 70.
14. Gould and Eldredge, “Punctuated Equilibria: The Tempo and Mode of
Evolution Reconsidered,” 117.
15. Eldredge and Gould, “Punctuated Equilibria: An Alternative toPhyletic Gradualism,” 84.
16. Lieberman and Vrba, “Stephen Jay Gould on Species Selection: 30
Years of Insight”; Gould, “The Meaning of Punctuated Equilibrium and Its
Role in Validating a Hierarchical Approach to Macroevolution.”
17. Gould, The Structure of Evolutionary Theory, 703. As Gould andEldredge also emphasized elsewhere: “The main insight for revision [ofevolutionary theory] holds that all substantial evolutionary change must bereconceived as higher-level sorting based on differential success of certain
kinds of stable species, rather than as progressive transformation within
lineages [i.e., species]” (“Punctuated Equilibrium Comes of Age,” 224).
18. If natural selection acts upon a larger unit of selection, the species
rather than the individual, it followed logically that evolution would occur inlarger more discrete jumps. Nevertheless, Gould and Eldredge rarely
emphasized this implication of their conception of species selection explicitly,
instead highlighting allopatric speciation as the main reason for fossil
discontinuity. Stanley did, however, often draw a connection between theactivity of species selection as a mechanism of evolutionary change and fossil

discontinuity. As he noted, “The validity of the species as the fundamental
unit of large-scale evolution depends upon the presence of discontinuities
between many species in the tree of life” (Macroevolution, 3).
19. Schopf, Editorial Introduction to Eldredge and Gould, “PunctuatedEquilibria: An Alternative to Phyletic Gradualism,” 82; Stanley,
Macroevolution: Pattern and Process, 3.
20. Valentine and Erwin, “Interpreting Great Developmental
Experiments”; see diagram on p. 92.
21. Valentine and Erwin note that “transitional alliances are unknown or
unconfirmed for any of the [Cambrian] phyla,” and yet “the evolutionary
explosion near the beginning of Cambrian time was real and produced
numerous [new] body plans” (“Interpreting Great Developmental
Experiments,” 84, 89).
22. Valentine and Erwin, “Interpreting Great Developmental
Experiments,” 96.
23. Gould and Eldredge, “Punctuated Equilibrium Comes of Age.”
24. Gould and Eldredge, “Punctuated Equilibrium Comes of Age.”25. Schopf, Editorial Introduction to Eldredge and Gould, “PunctuatedEquilibria: An Alternative to Phyletic Gradualism,” 84.
26. Foote argued that “given estimates of [a] completeness [of the fossil
record], [b] median species duration, [c] the time required for evolutionarytransitions, and [d] the number of . . . higher-level transitions, we could obtainan estimate of the number of major transitions we should expect to see in thefossil record.” His method provided a way to evaluate, as he puts it, “whether
the small number of documented major transitions provides strong evidence
against evolution” (“On the Probability of Ancestors in the Fossil Record,”
148).
Because variables [a], [b], and [d] are reasonably well established, [c] thetime required for plausible mechanisms to produce macroevolutionarytransitions stands as the crucial variable in the analysis of any specificevolutionary model, including punctuated equilibrium. If the time required to
produce major evolutionary change is high, as it is for the neo-Darwinianmechanism of change, then given current estimates of [a], [b], and [d], neoDarwinism fails to account for the data of the fossil record. Conversely, if atheory such as punctuated equilibrium can identify a fast enough acting
mechanism, then it could account for the paucity of transitional intermediates.
27. Foote and Gould, “Cambrian and Recent Morphological Disparity,”1816.
28. Darwin, On the Origin of Species, 177.
29. As Gould and Eldredge explained: “Most evolutionary change, weargued, is concentrated in rapid (often geologically instantaneous) events ofspeciation in small, peripherally isolated populations (the theory of allopatricspeciation)” (“Punctuated Equilibria: The Tempo and Mode of Evolution
Reconsidered,” 116–17). See also Lewin, “Punctuated Equilibrium Is Now
Old Hat.”
30. Shu et al., “Lower Cambrian Vertebrates from South China.”
31. Dawkins, The Blind Watchmaker, 265.
32. Levinton, Genetics, Paleontology, and Macroevolution, 208.
33. Gould, The Structure of Evolutionary Theory, 710.
34. Charlesworth, Lande, and Slatkin, “A Neo-Darwinian Commentary on
Macroevolution,” 493. As David Jablonski concluded in 2008, “The extent
and efficacy of the specific processes [of species selection] remain poorly
known” (“Species Selection,” 501).
35. Gould, The Structure of Evolutionary Theory, 1005.
36. Gould, The Structure of Evolutionary Theory, 55, emphasis added.
37. Gould and Eldredge, “Punctuated Equilibria: The Tempo and Mode of
Evolution Reconsidered,” 134.
38. Sepkoski, “ ‘Radical’ or ‘Conservative’?” 307.
39. Sepkoski, “ ‘Radical’ or ‘Conservative’?” 7.
40. Gould, “Is a New and General Theory of Evolution Emerging?” 120.
Because his colleagues understood Gould to be offering a theory ofmacroevolution, many of Gould’s scientific colleagues at the time thought ofhim, as Sepkoski notes, as an “ardent proponent of a radical (and perhaps
misguided) view of evolutionary change” (“ ‘Radical’ or ‘Conservative’?”302).
41. Sepkoski, “ ‘Radical’ or ‘Conservative’?” 302.
42. Valentine and Erwin, “Interpreting Great Developmental
Experiments,” 96.
Chapter 8: The Cambrian Information Explosion
1. Bowler, Theories of Human Evolution, 44–50.
2. Vorzimmer, “Charles Darwin and Blending Inheritance,” 371–90.
3. Jenkins, Genetics, 13–15.
4. Muller, “Artificial Transmutation of the Gene,” 84–87.
5. As Mayr and Provine put it, “Various geneticists . . . demonstrated thatseemingly continuous variation is caused by discontinuous genetic factors[mutations] that obey the Mendelian rules in their mode of inheritance” (The
Evolutionary Synthesis, 31).
6. Bowler, Evolution: The History of an Idea, 331–39.
7. Huxley, “The Evolutionary Vision,” 249, 253.

8. Huxley, quoted in “ ‘At Random’: A Television Preview,” 45.
9. Watson and Crick, “A Structure for Deoxyribose Nucleic Acids,” 737–38.
10. For an animated demonstration, see the short video “Journey Inside theCell” on my website at SignatureintheCell.com.
11. Valentine, “Late Precambrian Bilaterians.”
12. Brocks et al., “Archean Molecular Fossils and the Early Rise of
Eukaryotes.”
13. Grotzinger et al., “Biostratigraphic and Geochronologic Constraints on
Early Animal Evolution.”
14. Ruppert et al, Invertebrate Zoology, 82.
15. Bowring et al., “Calibrating Rates of Early Cambrian Evolution.”
16. Valentine, Origin of the Phyla, 73.
17. Koonin, “How Many Genes Can Make a Cell?”
18. Gerhart and Kirschner, Cells, Embryos, and Evolution, 121; Adams etal., “The Genome Sequence of Drosophila melanogaster”; see also
www.ncbi.nlm.nih.gov/genome/?term=drosophila%20melanogaster (accessed
November 1, 2012).
19. Moreover, in addition to requiring a vast amount of new genetic
information, building a new animal from a single-celled organism also
requires a way of arranging gene products—proteins—into higher levels oforganization, including cell types, organs, and body plans. Later, in Chapter
14, I will discuss the importance of these higher-level arrangements and why
they also constitute a kind of information—one that, although not stored ingenes alone, nevertheless has to be explained as well.
20. Shannon, “A Mathematical Theory of Communication.”
21. To determine how much Shannon information is present in any
sequence of characters, information scientists use a formula that converts
probability measures into informational measures using a negative
logarithmic function. A simple form of that equation can be expressed as I = –log2 p, where the negative sign indicates the inverse relationship between
probability and information.
22. Yockey, Information Theory and Molecular Biology, 110.
23. Shannon and Weaver, The Mathematical Theory of Communication, 8.
24. Schneider, “Information Content of Individual Genetic Sequences”;
Yockey, Information Theory and Molecular Biology, 58–177.
25. DNA clearly does not convey meaningful information in the sense of“knowledge” conveyed to, and comprehended by, a conscious agent, although
the precise sequences of bases could be said to be meaningful in the sense thatthey are ‘significant’ to the function DNA performs. Clearly, however, thecellular machinery that uses and “reads” the information in DNA to build
proteins is not conscious. Nevertheless, semantically meaningful information—a message, the meaning of which is understood by a conscious agent—
represents only a special kind of functional information. And all sequences ofcharacters containing functional information can be distinguished from mere
Shannon information in that the precise arrangement of characters or symbols
in such sequences matters to the function that they perform.
26. Crick, “On Protein Synthesis,” 144, 153. See also Sarkar, “Biological
Information,” 191.
Chapter 9: Combinatorial Inflation
1. Eden, “Inadequacies of Neo-Darwinian Evolution as a Scientific
Theory,” 11.

2. The quotation and the historical material about the Geneva gathering are
drawn from G. R. Taylor, Great Evolution Mystery, 4.
3. Schützenberger, “Algorithms and the Neo-Darwinian Theory of
Evolution,” 73–75.
4. Schützenberger, “Algorithms and the Neo-Darwinian Theory of
Evolution,” 74–75.
5. Commenting on the symposium thirty years later in a now infamous
article in Commentary magazine, mathematician David Berlinski amplified
Eden’s argument. As he explains, “However it may operate in life,
randomness in language is the enemy of order, a way of annihilating meaning.
And not only in language, but in any language-like system” (“The Deniable
Darwin”).
6. King and Jukes, “Non-Darwinian Evolution,” 788.
7. Eden, “Inadequacies of Neo-Darwinian Evolution as a Scientific
Theory,” 110.
8. Schützenberger, “Algorithms and the Neo-Darwinian Theory of
Evolution,” 74.
9. Ulam, “How to Formulate Mathematically Problems of Rate of
Evolution,” 21.
10. Eden, “Inadequacies of Neo-Darwinian Evolution as a Scientific
Theory,” 7.
11. Denton, Evolution: A Theory in Crisis, 309–11.
12. Maynard Smith, “Natural Selection and the Concept of a Protein
Space.”
13. Denton, Evolution, 324.
14. Reidhaar-Olson and Sauer, “Functionally Acceptable Substitutions in
Two Alpha-Helical Regions of Lambda Repressor.”
15. Yockey, “On the Information Content of Cytochrome C.”
16. Yockey, “On the Information Content of Cytochrome C.”
17. Behe, “Experimental Support for Regarding Functional Classes ofProteins,” 66.
18. Lau and Dill, “Theory for Protein Mutability and Biogenesis.”
19. Behe, “Experimental Support for Regarding Functional Classes ofProteins.”
Chapter 10: The Origin of Genes and Proteins
1. Dawkins, The Blind Watchmaker: Why the Evidence of Evolution
Reveals a Universe Without Design, 46–47.
2. For a critique of Dawkins’ simulation see Chapter 13 of Signature in the
Cell. See also Ewert, et al., “Efficient Per Query Information Extraction froma Hamming Oracle,” 290–97; Dembski, No Free Lunch, 181–216. See also
Weasel Ware–Evolutionary Simulation at http://evoinfo.org/weasel.
3. Reidhaar-Olson and Sauer, “Functionally Acceptable Substitutions in
Two Alpha-Helical Regions of Lambda Repressor,” 315.
4. Protein scientists recognize an additional level of structure called
quaternary structure. Quaternary structures are formed from multiple protein
folds, or multiple whole proteins.
5. As Reidhaar-Olson and Sauer note: “At [amino-acid] positions that are
buried in the structure, there are severe limitations on the number and type ofresidues allowed. At most surface positions, many different [amino-acid]residues and residue types are tolerated” (“Functionally Acceptable
Substitutions in Two Alpha-Helical Regions of Lambda Repressor,” 306).
6. Axe, “Extreme Functional Sensitivity to Conservative Amino Acid
Changes on Enzyme Exteriors.”
7. Dawkins, Climbing Mount Improbable.
8. Jensen, “Enzyme Recruitment in Evolution of New Function,” 409–25.
9. Axe, “Extreme Functional Sensitivity to Conservative Amino Acid
Changes on Enzyme Exteriors.”
10. Axe, “Extreme Functional Sensitivity to Conservative Amino Acid
Changes on Enzyme Exteriors,” 585–96. Experimental work that Axe
performed with colleague Ann Gauger, published in 2011, also confirmed thisresult. See Gauger and Axe, “The Evolutionary Accessibility of New Enzyme
Functions: A Case Study from the Biotin Pathway.”
11. Axe, “Extreme Functional Sensitivity to Conservative Amino Acid
Changes on Enzyme Exteriors.”
12. Unfolded proteins also stick to other molecular entities within the cellor form what are called inclusion bodies, in both cases impeding proper
protein function. Moreover, even slight elevations in temperature will
accelerate the unfolding of already destabilized protein folds.
13. Axe’s experiments using a more sensitive screen for function had
shown him that even most single amino-acid changes will diminish thefunction of a protein enough to diminish its fitness, even in cases where suchchanges do not eliminate function altogether.
14. Blanco, Angrand, and Serrano, “Exploring the Conformational
Properties of the Sequence Space Between Two Proteins with Different Folds:
An Experimental Study.” As they explain, “Both the hydrophobic coreresidues and the surface residues are important in determining the structure of
the proteins” (741).
15. Neutral evolution in this context refers to a process alleged to explain
the origin of new functional genes and proteins from gene duplicatesunhinged from selection pressure. A neutral model of gene evolution is part ofa more expansive and general neutral theory of evolution proposed by Motoo
Kimura in 1968. As Long et al. explain, Kimura’s model helped “describe
how gene duplicates could acquire new functions and ultimately be preservedin a lineage” (“The Origin of New Genes,” 868). However, Kimura’s modelof neutral evolution attempted to explain facts and phenomena beyond just theorigin of new genes. Thus, not everyone who accepts a neutral model of geneorigins subscribes to the whole of Kimura’s theory. Kimura, The Neutral
Theory of Molecular Evolution.
16. Matthew Hahn notes that, “There appear to be 4 major mechanisms bywhich DNA is duplicated: (1) unequal crossing-over, (2) duplicative (DNA)transposition, (3) retrotransposition, and (4) polyploidization”(“Distinguishing Among Evolutionary Models for the Maintenance of Gene
Duplicates,” 606).
17. Axe, “Estimating the Prevalence of Protein Sequences Adopting
Functional Enzyme Folds.”
18. Dembski, The Design Inference, 175.
19. Michael Behe made this calculation in The Edge of Evolution based ona paper in Proceedings of the National Academy of Sciences U.S.A. thatobserved that approximately 1030 prokaryotes are formed on earth each year.
[Whitman, “Prokaryotes: The unseen majority,” 6578–83.] Since prokaryotes
make up the overwhelming majority of organisms, he multiplied that number
by 1010, which is about twice the number of years the age of the earth. This
allowed him to estimate the total number of organisms that have lived onearth as “slightly fewer than 1040 cells.” Behe, The Edge of Evolution, 64.
20. Bowring et al., “Calibrating Rates of Early Cambrian Evolution”; “A
New Look at Evolutionary Rates in Deep Time”; “Geochronology Comes ofAge”; Kerr, “Evolution’s Big Bang Gets Even More Explosive”;
Monastersky, “Siberian Rocks Clock Biological Big Bang.”
21. Ohno, “The Notion of the Cambrian Pananimalia Genome.”
22. Dembski, The Design Inference, 175–223. Dembski often uses thefigure 1 in 10150 as his universal probability bound, but this figure derives
from Dembski rounding up the exponent in the figure that he actuallycalculates. See my discussion of the derivation of Dembski’s universal
probability bound in Signature in the Cell, Chapter 10.
23. Dawkins, The Blind Watchmaker, 139.
Chapter 11: Assume a Gene
1. Stephen C. Meyer, “The Origin of Biological Information and theHigher Taxonomic Categories.”

2. For detailed discussions of facts of the Sternberg case, see “Smithsonian
Controversy,” www.richardsternberg.com/smithsonian.php; U.S. Office ofSpecial Counsel Letter (2005) at www.discovery.org/f/1488; United States
House of Representatives Committee on Government Reform, Subcommittee
Staff Report, “Intolerance and the Politicization of Science at theSmithsonian” (December 2006), at www.discovery.org/f/1489; Appendix,
United States House of Representatives Committee on Government Reform,
Subcommittee Staff Report (December 2006) at www.discovery.org/f/1490.
3. See Holden, “Defying Darwin”; Giles, “Peer-Reviewed Paper Defends
Theory of Intelligent Design,” 114; Agres, “Smithsonian ‘Discriminated’Against Scientist”; Stokes, “ . . . And Smithsonian Has ID Troubles”;
Monastersky, “Society Disowns Paper Attacking Darwinism.”
4. Powell, “Controversial Editor Backed”; Klinghoffer, “The Branding of a
Heretic.”
5. Hagerty, “Intelligent Design and Academic Freedom.
6. See www.talkreason.org/AboutUs.cfm.
7. Gishlick, Matzke, and Elsberry, “Meyer’s Hopeless Monster,”
www.talkreason.org/AboutUs.cfm.
8. Jones, Kitzmiller et al. v. Dover Area School District.
9. Matzke and Gross, “Analyzing Critical Analysis,” 42.
10. Matzke and Gross, “Analyzing Critical Analysis,” 42.
11. Matzke and Gross, “Analyzing Critical Analysis,” 42.
12. See Chapter 10, n. 15, for the four major mechanisms by which DNA
is duplicated.
13. For example, see Zhen et al., “Parallel Molecular Evolution in an
Herbivore Community”; Li et al., “The Hearing Gene Prestin Unites
Echolocating Bats and Whales”; Jones, “Molecular Evolution”; Christin,
Weinreich, and Bresnard, “Causes and Evolutionary Significance of Genetic
Convergence”; Rokas and Carroll, “Frequent and Widespread Parallel
Evolution of Protein Sequences.” According to Dávalos and colleagues, “Indepth analyses of specific genes in the context of multilocus phylogenies havealso shown that adaptive evolution leading to convergence, once thought to be
extremely rare, is as much a source of conflict among gene trees as it isbetween morphological and molecular phylogenies” (“Understanding
Phylogenetic Incongruence,” 993).
14. Shen et al., “Parallel Evolution of Auditory Genes for Echolocation in
Bats and Toothed Whales”; Li et al., “The Hearing Gene Prestin Unites
Echolocating Bats and Whales”; Jones, “Molecular Evolution.”
15. Khalturin et al., “More Than Just Orphans”; Merhej and Raoult,“Rhizome of Life, Catastrophes, Sequence Exchanges, Gene Creations, andGiant Viruses”; Beiko, “Telling the Whole Story in a 10,000-Genome World.”
16. Suen et al., “The Genome Sequence of the Leaf-Cutter Ant Atta
cephalotes Reveals Insights into Its Obligate Symbiotic Lifestyle” (“We also
found 9,361 proteins that are unique to A. cephalotes, representing over halfof its predicted proteome,” 5). See also Smith et al., “Draft Genome of the
Globally Widespread and Invasive Argentine Ant (Linepithema humile)” (“Atotal of 7,184 genes (45%) were unique to L. humile relative to these threeother species,” 2).
17. Tautz and Domazet-Lošo, “The Evolutionary Origin of Orphan
Genes”; Beiko, “Telling the Whole Story in a 10,000-Genome World”;
Merhej and Raoult, “Rhizome of Life, Catastrophes, Sequence Exchanges,
Gene Creations, and Giant Viruses.”
18. Lyell, Principles of Geology.
19. See Pray and Zhaurova, “Barbara McClintock and the Discovery ofJumping Genes (Transposons).”
20. Long et al., “The Origin of New Genes,” 867.
21. Nurminsky et al., “Selective Sweep of a Newly Evolved SpermSpecific Gene in Drosophila,” 574.
22. Chen, DeVries, and Cheng, “Evolution of Antifreeze Glycoprotein
Gene from a Trypsinogen Gene in Antarctic Notothenioid Fish,” 3816.
23. Courseaux and Nahon, “Birth of Two Chimeric Genes in the
Hominidae Lineage.”
24. Knowles and McLysaght, “Recent de Novo Origin of Human ProteinCoding Genes.”
25. Wu, Irwin, and Zhang, “De Novo Origin of Human Protein-Coding
Genes.”
26. Guerzoni and McLysaght, “De Novo Origins of Human Genes”; seealso Wu, Irwin, and Zhang, “De Novo Origin of Human Protein-Coding
Genes.”
27. Siepel, “Darwinian Alchemy.”
28. Siepel, “Darwinian Alchemy.”
29. Siepel, “Darwinian Alchemy.”
30. As Siepel notes, “These apparent de novo gene origins raise thequestion of how evolution by natural selection can produce functional genes
from noncoding DNA. While a single gene is not as complex as a complete
organ, such as an eye or even a feather, it still has a series of nontrivial
requirements for functionality, for instance, an ORF [an open reading frame],an encoded protein that serves some useful purpose, a promoter capable ofinitiating transcription, and presence in a region of open chromatin structurethat permits transcription to occur. How could all of these pieces fall into

place through the random processes of mutation, recombination, and neutral
drift . . . ?” (“Darwinian Alchemy”).
31. Of course, one could argue that the mutational processes that Long
invokes to explain the origin of new genes from preexisting cassettes ofgenetic information themselves explain the origin of the information in thosecassettes in the first place. This view would suggest that the scenarios thatLong cites do not so much beg the question as much as generate a regress of
explanation terminating with the ultimate origin of biological information at
the point of the origin of the first life. This view implies that, although theultimate origin of biological information and the closely associated questionof life’s first origin may remain a mystery, the processes that Long cites
account for all subsequent informational increases during the course of
biological evolution. But this view still does not explain how shufflingpreexisting cassettes of information generates the specific arrangements of thecharacters that make up those cassettes.
32. Zhang, Zhang, and Rosenberg, “Adaptive Evolution of a DuplicatedPancreatic Ribonuclease Gene in a Leaf-Eating Monkey.” The genes that codefor these two proteins differ by 12 nucleotides in their coding sequences.
Those nucleotide differences produce two proteins that differ from each otherin their overall electronegativity. This difference, in turn, allows the protein
RNASE1B to operate at a slightly lower pH than the other protein, RNASE1.
Since other primates have only the RNASE1 protein, Zhang, Zhang, andRosenberg hypothesize that the evolution of this second gene and protein
gave individuals within the species of monkey a selective advantage. To
explain the origin of the second gene, they posit a common ancestral gene, agene duplication event, and the accumulation of different mutations on the
duplicate copy (the RNASE1B) over time.
33. In this study (“Adaptive Evolution of Cid, a Centromere-SpecificHistone in Drosophila”), Malik and Henikoff infer that “adaptive evolution
has occurred on both the D. melanogaster and D. simulans lineages since
their split from a common ancestor.” They base this inference on an analysisof the ratio of “synonymous” and “nonsynonymous” mutations in the
genomes of these organisms. The study found that many of thedifferences/mutations in nucleotide base sequences changed amino-acidsequence (called “nonsynonymous” mutations), while some did not (calledsynonymous, or “silent,” mutations). A higher percentage of these differenceschanged the amino-acid sequence than would be expected from neutral
evolution alone, leading the authors to infer that “adaptive evolution has
occurred on both the D. melanogaster and D. simulans lineages since their
split from a common ancestor.” Since some of these differences exist in theregion of the protein that binds to the chromosome, they may have affected
the protein’s functional binding ability. But the authors of the paper identify
no specific functional effects of these amino-acid differences and base theirclaim of “strong evidence for the adaptive evolution of Cid” solely uponcomparisons of the relative numbers of a handful of synonymous andnonsynonymous differences between the genes.
34. Enard et al., “Molecular Evolution of FOXP2, a Gene Involved in
Speech and Language”; Zhang, Webb, and Podlaha, “Accelerated Protein
Evolution and Origins of Human-Specific Features.”35. Enard et al., “Molecular Evolution of FOXP2, a Gene Involved in
Speech and Language.”
36. Long et al., “The Origin of New Genes,” 866.
37. Darnell and Doolittle, “Speculations on the Early Course of
Evolution”; Hall, Liu, and Shub, “Exon Shuffling by Recombination Between
Self-Splicing Introns of Bacteriophage T4”; Rogers, “Split-Gene Evolution”;
Gilbert, “The Exon Theory of Genes”; Doolittle et al., “Relationships of
Human Protein Sequences to Those of Other Organisms.”
38. For example, Arli A. Parikesit and colleagues note that “Although
there is a statistically significant correlation between protein domainboundaries and exon boundaries, about two thirds of the annotated protein
domains are interrupted by at least one intron, and on average a domain
contains 3 or 4 introns” (“Quantitative Comparison of Genomic-Wide Protein
Domain Distributions,” 96–97; internal citations omitted).
39. Gauger, “Why Proteins Aren’t Easily Recombined.”
40. Axe, “The Limits of Complex Adaptation.” See also Voigt et al.,“Protein Building Blocks Preserved by Recombination.”
41. Experimental shuffling of genes has proven fruitful only when theparent genes are highly similar. See He, Friedman, and Bailey-Kellogg,“Algorithms for Optimizing Cross-Overs in DNA Shuffling.”
42. In 2012, a research group at the University of Washington reported
success in designing a few stable protein folds using a few rules, a lot ofcomputational analysis, and trial and error (only 10 percent of the designed
proteins folded as predicted). Though these proteins did form stable folds,
they did not perform any actual biological function. The researchers
acknowledge that there is likely a tradeoff between stability and functionality
in natural proteins. It remains to be seen whether these methods of sequenceengineering can create new, stable folds capable of enzymatic activity. What
this research highlights is the extreme difficulty of intelligently designing astable and functional protein from scratch, even with the best minds andcomputational resources working on the problem. There is, therefore, littlereason to think that unguided process of exon shuffling could generate both astable and functional protein. See Nobuyasu et al., “Principles for Designing
Ideal Protein Structures”; Marshall, “Proteins Made to Order.”43. Altamirano et al., “Directed Evolution of New Catalytic Activity Using
the Alpha/Beta-Barrel Scaffold.” See also Altamirano et al., “Retraction:
Directed Evolution of New Catalytic Activity Using the Alpha/Beta-Barrel
Scaffold.”
44. Gauger, “Why Proteins Aren’t Easily Recombined.”
45. Axe, “The Case Against Darwinian Origin of Protein Folds.”
46. See, e.g., Long and Langley, “Natural Selection and the Origin of
Jingwei, a Chimeric Processed Functional Gene in Drosophila”; Wang et al.,“Origin of Sphinx, a Young Chimeric RNA Gene in Drosophilamelanogaster”; Begun, “Origin and Evolution of a New Gene Descended
from Alcohol Dehydrogenase in Drosophila.”
47. Long et al., “Exon Shuffling and the Origin of the Mitochondrial
Targeting Function in Plant Cytochrome cl Precursor.”
48. Long et al., “The Origin of New Genes. See also Begun, “Origin and
Evolution of a New Gene Descended from Alcohol Dehydrogenase in
Drosophila.”
49. Nurminsky et al., “Selective Sweep of a Newly Evolved SpermSpecific Gene in Drosophila.”
50. Nurminsky et al., “Selective Sweep of a Newly Evolved SpermSpecific Gene in Drosophila.”
51. Brosius, “The Contribution of RNAs and Retroposition to
Evolutionary Novelties.”
52. Begun, “Origin and Evolution of a New Gene Descended from
Alcohol Dehydrogenase in Drosophila.”
53. Begun, “Origin and Evolution of a New Gene Descended from
Alcohol Dehydrogenase in Drosophila.”
54. Papers cited by Long where natural selection was invoked even though
the function of the gene and thus the function being selected for was unknown
include Begun, “Origin and Evolution of a New Gene Descended from
Alcohol Dehydrogenase in Drosophila”; Long and Langley, “Natural
Selection and the Origin of Jingwei, a Chimeric Processed Functional Gene in
Drosophila”; and Johnson et al., “Positive Selection of a Gene Family During
the Emergence of Humans and African Apes.”
55. Logsdon and Doolittle, “Origin of Antifreeze Protein Genes.”
56. Courseaux and Nahon, “Birth of Two Chimeric Genes in the
Hominidae Lineage.”
57. Paulding, Ruvolo, and Haber, “The Tre2 (USP6) Oncogene Is a

Hominoid-Specific Gene.”
58. Chen, DeVries, and Cheng, “Convergent Evolution of Antifreeze
Glycoproteins in Antarctic Notothenioid Fish and Arctic Cod.”
59. Logsdon and Doolittle, “Origin of Antifreeze Protein Genes.”
60. Johnson et al., “Positive Selection of a Gene Family During theEmergence of Humans and African Apes.”
61. See Nurminsky et al., “Selective Sweep of a Newly Evolved SpermSpecific Gene in Drosophila”; Chen, DeVries, and Cheng, “Evolution of
Antifreeze Glycoprotein Gene from a Trypsinogen Gene in Antarctic
Notothenioid Fish”; Courseaux and Nahon, “Birth of Two Chimeric Genes inthe Hominidae Lineage”; Knowles and McLysaght, “Recent de Novo Originof Human Protein-Coding Genes”; Wu, Irwin, and Zhang, “De Novo Originof Human Protein-Coding Genes”; Siepel, “Darwinian Alchemy.”
Chapter 12: Complex Adaptations and the Neo-Darwinian Math
1. Frazzetta, “From Hopeful Monsters to Bolyerine Snakes?” 62–63.
2. Frazzetta, “From Hopeful Monsters to Bolyerine Snakes?” 63.
3. Gould, “Return of the Hopeful Monsters,” 28.
4. Frazzetta, “From Hopeful Monsters to Bolyerine Snakes?” 63.
5. Frazzetta, Complex Adaptations in Evolving Populations, 20.
6. As Darwin wrote in the Origin, “If we must compare the eye to an
optical instrument, we ought in imagination to take a thick layer oftransparent tissue, with a nerve sensitive to light beneath, and then suppose
every part of this layer to be continually changing slowly in density, so as toseparate into layers of different densities and thicknesses, placed at different
distances from each other, and with the surfaces of each layer slowly
changing in form” (188–89).
7. Frazzetta, Complex Adaptations in Evolving Populations, 21.
8. Frazzetta, “Modeling Complex Morphological Change in Evolution,”
129.
9. Frazzetta, “Modeling Complex Morphological Change in Evolution,”
130.
10. Ehrlich and Holm, The Process of Evolution, 157.
11. Until a famous experiment performed by Oswald Avery of theRockefeller Institute in 1944, many biologists still suspected that proteinsmight actually be the repositories of genetic information. Meyer, Signature in
the Cell, 66. Avery, MacCleod, and McCarty, “Induction of Transformation
by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III.”
12. Bateson, “Heredity and Variation in Modern Lights,” 83–84.
13. Withgott, “John Maynard Smith Dies.”

14. Salisbury, “Natural Selection and the Complexity of the Gene,” 342–
43.
15. Maynard Smith, “Natural Selection and the Concept of a Protein
Space,” 564.
16. As Maynard Smith writes in Nature: “If evolution by natural selection
is to occur, functional proteins must form a continuous network which can betraversed by unit mutational steps without passing through nonfunctional
intermediates” (“Natural Selection and the Concept of a Protein Space,” 564).
17. Maynard Smith, “Natural Selection and the Concept of a Protein
Space,” 564, emphasis added.
18. Maynard Smith, “Natural Selection and the Concept of a Protein
Space,” 564.
19. Orr, “The Genetic Theory of Adaptation,” 123.
20. Behe and Snoke, “Simulating Evolution by Gene Duplication ofProtein Features That Require Multiple Amino Acid Residues.”
21. Wen-Hsiung, Molecular Evolution, 427
22. Wen-Hsiung, Molecular Evolution, 427.
23. Behe, The Edge of Evolution, 54.
24. “Powerball—Prizes and Odds,” Powerball,
http://www.powerball.com/powerball/pb_prizes.asp.
25. “Powerball—Prizes and Odds,” Powerball,
http://www.powerball.com/powerball/pb_prizes.asp.
26. Behe and Snoke, “Simulating Evolution by Gene Duplication ofProtein Features That Require Multiple Amino Acid Residues,” 2661.
27. Lynch and Conery, “The Origins of Genome Complexity,” 1401–02.
28. Behe and Snoke, “Simulating Evolution by Gene Duplication ofProtein Features That Require Multiple Amino Acid Residues,” 2661.
29. For the purpose of Behe’s argument it did not matter whether the
mutations involved in a single CCC trait arose in a stepwise, or coordinatedfashion. Behe was not calculating how long it would take for a single CCC
trait to arise. That chloroquine resistance only arises once in every 1020
malarial cells was an observed empirical fact based upon public healthstudies, not a calculation of waiting times based upon a population genetics
model. [See White, “Antimalarial Drug Resistance,” 1085.] What Behe wascalculating was how long it would take for a hypothetical trait to arise that
did require two coordinated mutations, each of the complexity of a single
CCC, in order to function—what he called a “double CCC.” Whether or not
generating a single CCC itself required coordinated mutations was irrelevant.
This aspect of his argument has been largely misunderstood by his critics.
[See Miller, “Falling Over the Edge,” 1055–56; Gross, “Design for Living,”

73; Coyne, “The Great Mutator (Review of The Edge of Evolution, byMichael J. Behe),” 40–42; Nicholas J. Matzke, “The Edge of Creationism,”566–67.] It’s worth noting that although Behe’s calculation was for ahypothetical trait, he went on to argue on independent biological grounds that“life is bursting” (63) with features that would require a double CCC to arise.
30. Behe, The Edge of Evolution, 135.
31. This assumes that every one of these organisms would be underselection for that particular trait—a completely unrealistic assumption.
32. Durrett and Schmidt, “Waiting for Two Mutations,” 1507.
33. Behe, The Edge of Evolution, 84–102.
34. Gauger and Axe, “The Evolutionary Accessibility of New Enzyme
Functions: A Case Study from the Biotin Pathway.”
35. Gauger et al., “Reductive Evolution Can Prevent Populations fromTaking Simple Adaptive Paths to High Fitness”; Durrett and Schmidt,“Waiting for Two Mutations.”
Chapter 13: The Origin of Body Plans
1. Nüsslein-Volhard and Wieschaus, “Mutations Affecting Segment
Number and Polarity”; Wieschaus, “From Molecular Patterns toMorphogenesis.” As he comments: “If transcription of a gene was essential
for embryonic development, homozygous embryos [i.e., those missing bothcopies of the gene] should develop abnormally when that gene waseliminated. . . . Based on these defects, it should be possible to reconstruct thenormal role of each gene” (316).
2. St. Johnston, “The Art and Design of Genetic Screens,” 177.
3. Quotes recorded in contemporaneous notes taken by philosopher ofbiology Paul Nelson, who was in attendance at this lecture.
4. Quotes recorded in contemporaneous notes taken by philosopher ofbiology Paul Nelson, who was in attendance at this lecture.
5. Arthur, The Origin of Animal Body Plans, 21; Cameron et al.,
“Evolution of the Chordate Body Plan: New Insights from Phylogenetic
Analyses of Deuterostome Phyla”; Michael, “Arthropods: Developmental
Diversity Within a (Super) Phylum”; Peterson and Davidson, “Regulatory
Evolution and the Origin of the Bilaterians”; Carroll, “Endless Forms: The
Evolution of Gene Regulation and Morphological Diversity”; Halder et al.,“Induction of Ectopic Eyes by Targeted Expression of the Eyeless Gene in
Drosophila.”
6. Arthur, The Origin of Animal Body Plans, 21.
7. Van Valen, “How Do Major Evolutionary Changes Occur?” 173.
8. Thomson, “Macroevolution,” 111.

9. John and Miklos, The Eukaryote Genome in Development and
Evolution, 309.
10. Thomson, “Macroevolution.”
11. See, e.g., the special issue of Development (December 1996) dedicatedto the large-scale mutagenesis of the model vertebrate Danio rerio (thezebrafish), especially Haffter et al., “The Identification of Genes with Uniqueand Essential Functions in the Development of the Zebrafish, Danio rerio”; orthe many fruit-fly mutagenesis experiments summarized in Bate and Arias,
eds., The Development of Drosophila melanogaster. Summarizing theevidence from a wide range of animal systems, Wallace Arthur writes, “Those
genes that control key early developmental processes are involved in theestablishment of the basic body plan. Mutations in these genes will usually be
extremely disadvantageous, and it is conceivable that they are always so”(The Origin of Animal Body Plans, 14, emphasis in original). Arthur goes onto speculate that because developmental regulatory genes often differ between
phyla, perhaps “mutations of these genes are sometimes advantageous” (15).
He offers no evidence for such mutations, however, other than as a deduction
from his prior assumption of common descent.
12. Fisher, The Genetical Theory of Natural Selection, 44.
13. Wallace, “Adaptation, Neo-Darwinian Tautology, and Population
Fitness,” 70.
14. Nüsslein-Volhard and Wieschaus, “Mutations Affecting Segment
Number and Polarity in Drosophila”; Lawrence and Struhl, “Morphogens,
Compartments and Pattern.”
15. Van Valen, “How Do Major Evolutionary Changes Occur?” 173.
16. McDonald, “The Molecular Basis of Adaptation,” 93.
17. McDonald, “The Molecular Basis of Adaptation,” 93.
18. Wimsatt, “Generativity, Entrenchment, Evolution, and Innateness:
Philosophy, Evolutionary Biology, and Conceptual Foundations of Science”;
Wimsatt and Schank, “Generative Entrenchment, Modularity and
Evolvability: When Genic Selection Meets the Whole Organism.”
19. Nelson notes that there is one noteworthy exception to thisgeneralization: the loss of structures. A wide range of well-documented cases—including cave animals, island birds and insects, and marine and freshwater
fishes—show that many animals will tolerate, or actually thrive, after losing
traits to mutation—as long as those traits are not essential for survival in somespecialized environment. For example, macromutations resulting in loss ofvision have had no deleterious effects on some species of now blind cave fishthat no longer have a need to see. Similarly, macromutations that disrupt wing
formation in an insect—ordinarily devastating in an environment wherefunctional wings are essential equipment—might well be tolerated in an
island setting where that species faces no need to fly. The processes thatgenerate these exceptions, however, do not help to explain the origin of form
such as occurs in the Cambrian explosion. Clearly, processes that result in aloss of form and structure cannot be credibly invoked to explain the origin ofform and structure in the first place.
20. Darwin, On the Origin of Species, 108.
21. Løvtrup, “Semantics, Logic and Vulgate Neo-Darwinism,” 162.
22. Britten and Davidson, “Gene Regulation for Higher Cells,” 57.
23. Britten and Davidson, “Gene Regulation for Higher Cells,” 57. One
exception to this rule are cells called “erythrocytes” in humans.
24. Britten and Davidson, “Gene Regulation for Higher Cells,” 57.
25. Britten and Davidson, “Gene Regulation for Higher Cells,” 353.
26. Cameron et al., “A Sea Urchin Genome Project,” 9514.
27. Oliveri, Tu, and Davidson, “Global Regulatory Logic for Specificationof an Embryonic Cell Lineage.”
28. Davidson, The Regulatory Genome, 16.
29. Davidson, The Regulatory Genome, 16.
30. Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,”38.
31. Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,”
40, emphasis added.
32. As Davidson explains, “Interference with expression of any [multiply
linked dGRNs] by mutation or experimental manipulation has severe effects
on the phase of development that they initiate. This accentuates the selective
conservation of the whole subcircuit, on pain of developmental catastrophe”(Davidson and Erwin, “An Integrated View of Precambrian Eumetazoan
Evolution,” 8).
33. Davidson, The Regulatory Genome, 195.
34. Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,”
35–36.
Chapter 14: The Epigenetic Revolution
1. Spemann and Mangold, “Induction of Embryonic Primordia by
Implantation of Organizers from a Different Species.”
2. Harvey, “Parthenogenetic Merogony or Cleavage Without Nuclei in
Arbacia punctulata”; “A Comparison of the Development of Nucleate andNon-nucleate Eggs of Arbacia punctulata.”
3. Brachet, Denis, and De Vitry, “The Effects of Actinomycin D and
Puromycin on Morphogenesis in Amphibian Eggs and Acetabularia

mediterranea.”
4. Masui, Forer, and Zimmerman, “Induction of Cleavage in Nucleatedand Enucleated Frog Eggs by Injection of Isolated Sea-Urchin Mitotic
Apparatus.”
5. Müller and Newman, “Origination of Organismal Form,” 8.
6. Müller and Newman, “Origination of Organismal Form,” 8.
7. Müller and Newman, “Origination of Organismal Form,” 7.
8. Müller and Newman, “Origination of Organismal Form,” 7. Or as
Müller also explains, the question of how “individualized constructional
elements” are organized during “the evolution of organismal form” is “notsatisfactorily answered by current evolutionary theories”; Müller,“Homology,” 57–58.
9. Levinton, Genetics, Paleontology, and Macroevolution, 485.
10. In 1942 Conrad Waddington coined the word “epigenetics” to refer tothe study of “the processes involved in the mechanism by which the genes of
the genotype bring about phenotypic effects” (“The Epigenotype,” 1). Some
more recent biologists have used it to refer to information in chromosomal
structures that do not depend on the underlying DNA sequence. I will use it torefer to any biological information that is not encoded in a DNA sequence.
11. Goodwin, “What Are the Causes of Morphogenesis?”; Nijhout,“Metaphors and the Role of Genes in Development”; Sapp, Beyond the Gene;
Müller and Newman, “Origination of Organismal Form”; Brenner, “TheGenetics of Behaviour”; Harold, The Way of the Cell.
12. Harold, The Way of the Cell, 125.
13. Harold, “From Morphogenes to Morphogenesis,” 2774; Moss, What
Genes Can’t Do. Of course, many proteins bind chemically with each other toform complexes and structures within cells. Nevertheless, these “selforganizational” properties do not fully account for higher levels oforganization in cells, organs, or body plans. Or, as Moss has explained“Neither DNA nor any other aperiodic crystal constitutes a unique repositoryof heritable stability in the cell; in addition, the chemistry of the solid state
does not constitute either a unique or even an ontologically or causallyprivileged basis for explaining the existence and continuity of order in theliving world . . .” Moss, What Genes Can’t Do, 76.
14. Wells, “Making Sense of Biology,” 121.
15. Harold, The Way of the Cell, 125.
16. Ally et al., “Opposite-Polarity Motors Activate One Another to Trigger
Cargo Transport in Live Cells”; Gagnon and Mowry, “Molecular Motors.”
17. Marshall and Rosenbaum, “Are There Nucleic Acids in theCentrosome?”18. Poyton, “Memory and Membranes”; Edidin, “Patches, Posts andFences.”19. Frohnhöfer and Nüsslein-Volhard, “Organization of Anterior Pattern in
the Drosophila Embryo by the Maternal Gene Bicoid”; Lehmann and
Nüsslein-Volhard, “The Maternal Gene Nanos Has a Central Role in Posterior
Pattern Formation of the Drosophila Embryo.”
20. Roth and Lynch, “Symmetry Breaking During Drosophila Oogenesis.”
21. Skou, “The Identification of the Sodium-Pump as the MembraneBound Na+ /K+-ATPase.”
22. Levin, “Bioelectromagnetics in Morphogenesis.”
23. Shi and Borgens, “Three-Dimensional Gradients of Voltage During
Development.”
24. Schnaar, “The Membrane Is the Message,” 34–40.
25. Schnaar, “The Membrane Is the Message,” 34–40; Gabius et al.,“Chemical Biology of the Sugar Code,” 740-764; Gabius, “Biological
Information Transfer Beyond the Genetic Code: The Sugar Code,” 108–121.
26. Gabius et al., “Chemical Biology of the Sugar Code,” 741. See also
Gabius, “Biological Information Transfer Beyond the Genetic Code: The
Sugar Code,” 108–21.
27. Gabius, “Biological Information Transfer Beyond the Genetic Code,”109; Gabius et al., “Chemical Biology of the Sugar Code,” 741.
28. Spiro, “Protein Glycosylation.”
29. Palade, “Membrane Biogenesis.”
30. Babu, Kriwacki, and Pappu, “Versatility from Protein Disorder”;
Uversky and Dunker, “Understanding Protein Non-Folding”; Fuxreiter andTompa, “Fuzzy Complexes.”
31. Wells, “Making Sense of Biology: The Evidence for Development by
Design,” 121.
32. McNiven and Porter, “The Centrosome.”
33. Lange et al., “Centriole Duplication and Maturation in Animal Cells”;
Marshall and Rosenbaum, “Are There Nucleic Acids in the Centrosome?”
34. Sonneborn, “Determination, Development, and Inheritance of theStructure of the Cell Cortex,” 1–13; Frankel, “Propagation of corticaldifferences in tetrahymena,” 607–623; Nanney, “The ciliates and thecytoplasm,” 163–170.
35. Moss, What Genes Can’t Do.
36. Harold, “From Morphogenes to Morphogenesis,” 2767.
37. See Müller and Newman, “The Origination of Organismal Form,” 7.
38. Thomson, “Macroevolution,” 107.
39. Miklos, “Emergence of Organizational Complexities During Metazoan

Evolution.”
40. Gilbert, Opitz, and Raff, “Resynthesizing Evolutionary andDevelopmental Biology,” 361. The Brian Goodwin quotation is from How the
Leopard Changed Its Spots.
41. Gilbert, Opitz, and Raff, “Resynthesizing Evolutionary andDevelopmental Biology.” Specifically, they argue that changes inmorphogenetic fields might produce large-scale changes in the developmental
programs and, ultimately, in the body plans of organisms. However, they offer
no evidence that such fields—if indeed they exist—can be altered to produce
advantageous variations in body plan, though such a condition is necessary to
any successful causal theory of macroevolution.
42. Webster, How the Leopard Changed Its Spots, 33; Webster andGoodwin, Form and Transformation, x; Gunter Theißen, “The Proper Placeof Hopeful Monsters in Evolutionary Biology,” 351; Marc Kirschner and John
Gerhart, The Plausibility of Life, 13; Schwartz, Sudden Origins, 3, 299–300;
Erwin, “Macroevolution Is More Than Repeated Rounds of Microevolution”;
Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,” 35;
Koonin, “The Origin at 150,” 473–5; Conway Morris, “Walcott, the Burgess
Shale, and Rumours of a Post-Darwinian World,” R928–R930; Carroll,“Towards a New Evolutionary Synthesis,” 27; Wagner, “What Is the Promiseof Developmental Evolution?”; Wagner and Stadler, “Quasi-independence,
Homology and the Unity-of Type”; Becker and Lönnig, “Transposons:
Eukaryotic,” 529–39; Lönnig and Saedler, “Chromosomal Rearrangements
and Transposable Elements,” 402; Müller and Newman, “Origination ofOrganismal Form,” 7; Kauffman, At Home in the Universe, 8; Valentine and
Erwin, “Interpreting Great Developmental Experiments,” 96; Sermonti, Why
Is a Fly Not a Horse?; Lynch, The Origins of Genome Architecture, 369;
Shapiro, Evolution, 89, 128.
The perspective of Eugene Koonin, a biologist at the National Center for
Biotechnology Information at the National Institutes of Health, provides justone good example of this skepticism. He argues: “The edifice of the modern
synthesis has crumbled, apparently, beyond repair . . . The summary of thestate of affairs on the 150th anniversary of the Origin is somewhat shocking.
In the postgenomic era, all major tenets of the modern synthesis have been, if
not outright overturned, replaced by a new and incomparably more complex
vision of the key aspects of evolution. So, not to mince words, the modern
synthesis is gone. What comes next? The answer suggested by the Darwinian
discourse of 2009 is a postmodern state, not so far a postmodern synthesis.
Above all, such a state is characterized by the pluralism of processes andpatterns in evolution that defies any straightforward generalization.” Koonin,

“The Origin at 150,” 473–75. David J. Depew and Bruce H. Weber, writing in
the journal Biological Theory, are even more frank: “Darwinism in its current
scientific incarnation has pretty much reached the end of its rope” (89–102).
Chapter 15: The Post-Darwinian World and Self-Organization
1. Conway Morris, “Walcott, the Burgess Shale and Rumours of a PostDarwinian World,” R928.
2. Conway Morris, “Walcott, the Burgess Shale and Rumours of a PostDarwinian World,” R930.
3. Mazur, The Altenberg 16: An Exposé of the Evolution Industry. See also
Whitfield, “Biological Theory.”
4. Budd, quoted in Whitfield, “Biological Theory,” 282.
5. Valentine and Erwin, “Interpreting Great Developmental Experiments,”
97.
6. Endler, Natural Selection in the Wild, 46, 248; Lewontin, “Adaptation,”
212–30.
7. Gerhart and Kirschner, The Plausibility of Life: Resolving Darwin’s
Dilemma, 10.
8. Kauffman, The Origins of Order: Self-Organization and Selection in
Evolution.
9. In The Origins of Order, Kauffman seeks to show that selforganizational processes could help account for both the origin of the first life
and the origin of subsequent forms of life, including new animal body plans.
In Signature in the Cell, I examined Kauffman’s specific proposal for
explaining the origin of the first life. Here I’ll examine his proposal for
explaining the origin of animal form.
10. Kauffman, The Origins of Order, 443.
11. Kauffman, The Origins of Order, 443.
12. Kauffman, The Origins of Order, 443.
13. Kauffman, The Origins of Order, 537.
14. Kauffman, The Origins of Order, 539.
15. Kauffman, The Origins of Order, 549–66.
16. Kauffman, The Origins of Order, 590.
17. Kauffman, The Origins of Order, 298.
18. Kauffman, The Origins of Order, 537, emphasis added.
19. Kauffman, At Home in the Universe, 68.
20. Kauffman, At Home in the Universe, 47–92.
21. Kauffman, At Home in the Universe, 71.
22. Kauffman, At Home in the Universe, 75–92.
23. Kauffman, At Home in the Universe, 86–88.

24. Kauffman, At Home in the Universe, 85, emphasis added.
25. Kauffman, At Home in the Universe, 53, 89, 102.
26. Kauffman, At Home in the Universe, 200.
27. Indeed, Kauffmann explicitly notes, “Mutants affecting early stages ofdevelopment disrupt development more than do mutants affecting late stagesof development. A mutation disrupting formation of the spinal column andcord is more likely to be lethal than one affecting the number of fingers thatform” (At Home in the Universe, 200).
28. Newman, “Dynamical Patterning Modules.”
29. Newman, “Dynamical Patterning Modules,” 296; see also “TheDevelopmental Genetic Toolkit and the Molecular Homology-Analogy
Paradox.”30. Newman, “Dynamical Patterning Modules,” 284.
31. Newman, “Dynamical Patterning Modules,” 284.
32. Newman, “Dynamical Patterning Modules,” 285.
33. Newman, “Dynamical Patterning Modules,” 285.
34. Newman, “Animal Egg as Evolutionary Innovation,” 570.
35. Newman, “Animal Egg as Evolutionary Innovation”; “Dynamical
Patterning Modules.”
36. Newman, “Animal Egg as Evolutionary Innovation,” 470–71; see also
Newman and Bhat, “Dynamical Patterning Modules: Physico-Genetic
Determinants.”
37. In a 2011 paper, Newman attempts to account for the origin of the
crucial egg stage in animal development, a long-unsolved puzzle for neoDarwinism. He does this by proposing, again, an interplay between thedevelopmental-genetic regulatory toolkit and a host of self-organizational andepigenetic processes. He envisions the egg stage arising in three steps. First,
he sees the interaction between “the metazoan developmental-genetic toolkit
and certain physical processes” organizing “primitive animal body plans
independently of an egg stage.” Second, he envisions the emergence of a“proto-egg” arising as the result of the “adaptive specialization of cells” asthey are released from aggregates of other cells. Third, he notes that sinceself-organizing processes (such as “egg-patterning processes”) are known toreorganize the contents of the cellular cytoplasm during development, thesesame processes could have done so in the past, further sculpting the proto-egg
into something more like the egg stage in animal development observed
today. He insists, moreover, that the structures induced by these eggpatterning processes are not adaptive “in the sense of having been gradually
arrived at through multiple cycles of selection,” but instead that they haveresulted from self-organizational physical and chemical processes. See

Newman, “Animal Egg as Evolutionary Innovation: A Solution to the‘Embryonic Hourglass’ Puzzle,” 467–83.
38. Khalturin et al., “More Than Just Orphans: Are TaxonomicallyRestricted Genes Important in Evolution?” 404–413; Tautz and DomazetLošo, “The evolutionary origin of orphan genes,” 692–70; Beiko, “Telling theWhole Story in a 10,000-Genome World,” 34.
39. See the discussion in Chapter 14, pages 277–81.
40. See the discussion in Chapter 14, pages 277–81.
41. Pivar, Lifecode; On the Origin of Form; Prigogine, Nicolis, andBabloyantz, “Thermodynamics of Evolution”; Wolfram, “A New Kind of
Science,” 398.
42. Meyer, Signature in the Cell, 254–55.
43. Yockey, “A Calculation of the Probability of Spontaneous Biogenesis
by Information Theory,” 380.
44. For example, see the popular computer game among amateur
programmers, the “Game of Life,” created by the British mathematician John
Horton Conway.
45. Kauffman, “The End of a Physics Worldview: Heraclitus and theWatershed of Life.”
46. Kauffman, “The End of a Physics Worldview: Heraclitus and theWatershed of Life.”
Chapter 16: Other Post-Neo-Darwinian Models
1. See Gould, “Is a New and General Theory of Evolution Emerging?”
120.
2. Gould does not use the term “macromutation” anywhere in his famous
1980 article (“Is a New and General Theory of Evolution Emerging?”). He
does, however, use the term “micromutation” (see 120) and challenges thesufficiency of accumulated micromutations to explain “macroevolution” (aterm used throughout the article).
3. Goldschmidt, The Material Basis of Evolution, 395.
4. The rejection of large-scale mutations affecting morphology andfunction as adaptive nonstarters emerged early and persisted as one of thedefining aspects of the neo-Darwinian synthesis. Neo-Darwinian
paleontologist and macroevolution theorist Jeffrey Levinton, for instance,
gives expression to the widely held skepticism about the evolutionary
plausibility of such mutants in his major textbook dealing withmacroevolution:
As a general rule, major developmental mutants give a picture of hopelessmonsters, rather than hopeful change. Epigenetic and genetic pleiotropy

[i.e., side effects] both impart great burden to any major developmental
perturbation. Thus it is unlikely that mutants affecting any fundamental
prepattern in development are likely to produce a functional organism.
Genes that activate switches in prepatterns are not sufficiently isolated in
effect on other parts of the phenotype to expect major saltations. The
cyclops mutant of the [brine shrimp] Artermia is lethal. The homeotic
mutants of Drosophila melanogaster suffer similar fates. . . . Disruptions,
i.e., mutants, have drastic effects on other parts of the phenotype. . . . Thus,
the accumulated evidence suggests that major developmental mutants are ofminor significance in evolution. The side effects are drastic. (Genetics,
Paleontology, and Macroevolution, 252–54)
5. The central difficulty with relying on developmental macro-mutations togenerate innovations in form, many neo-Darwinians noted, arises from theconsequence of rapidly changing a system of genetic and developmental
switches directed toward producing one “target” (stable adult form) to anothersystem of such switches directed toward producing another form. Geneticist
Bruce Wallace, trained by Theodosius Dobzhansky at Columbia University,
explains: “The Bauplan [body plan] of an organism . . . can be thought of as
the arrangement of genetic switches that control the course of the embryonicand subsequent development of the individual; such control must operateproperly both in time generally and sequentially in the separately
differentiated tissues. Selection, both natural and artificial, that leads tomorphological change and other developmental modification does so byaltering the settings and triggerings of these switches. . . . The extreme
difficulty encountered when attempting to transform one organism intoanother but still functioning one lies in the difficulty in resetting a number ofthe many controlling switches in a manner that still allows for the individual’sorderly (somatic) development” (“Adaptation, Neo-Darwinian Tautology, andPopulation Fitness,” 70). Our discussion in Chapter 13 suggests that the needto alter these functionally integrated switches also presents an obstacle to theefficacy of the neo-Darwinian mechanism.
6. Gould, “Is a New and General Theory of Evolution Emerging?” 127.
7. Of course, the range of post-neo-Darwinian theories is not exhausted bythis chapter’s survey of four prominent contenders. In a recent review paper,
evolutionary biologist Armin Moczek, of Indiana University, examined three
additional ideas attempting to move beyond what Moczek calls the“unrealistic and unproductive” assumptions of gene-centered neo-Darwinian
theory. Those ideas are, respectively: (1) the theory of “facilitated variation”(Gerhart and Kirschner, “The Theory of Facilitated Variation”), the theory of“genetic accommodation” and “niche construction theory.” See Moczek, “TheNature of Nurture and the Future of Evodevo.” Short explanations andcritiques of these models are posted on the website for this book,www.darwinsdoubt.com.
8. Gould, “Is a New and General Theory of Evolution Emerging?”
9. Gilbert, Opitz, and Raff, “Resynthesizing Evolutionary andDevelopmental Biology,” 362.
10. The assumption that evolutionary biologists could ignore the role ofdevelopmental biology derived in part from the need for population
geneticists to make simplifying assumptions in order “to keep themathematics tractable,” note developmental biologists Michael Palopoli andNipam Patel. As they explain, “It was assumed that evolutionary changes ingenotype are translated into phenotypic changes by an undefined set of
epigenetic laws; in other words, developmental evolution was ignored [byneo-Darwinism] in order to focus on the dynamics of allele frequencychanges in populations” (“Neo-Darwinian Developmental Evolution, 502).
11. Raff, The Shape of Life.
12. Schwartz, “Homeobox Genes, Fossils, and the Origin of Species”;
Schwartz, Sudden Origins; Goodwin, How the Leopard Changed Its Spots;
Carroll, Endless Forms Most Beautiful.
13. Experimental mutagenesis of fruit flies (Drosophila melanogaster)began in earnest at Columbia University, in the breeding laboratories ofThomas H. Morgan and others, during the first decade of the twentiethcentury.
14. Meyer et al., Explore Evolution, 108.
15. Body Plans, http://ncse.com/book/export/html/2585 (accessed
November 6, 2012).
16. Normal Protein, http://ncse.com/book/export/html/2580 (accessed
November 6, 2012).
17. Body Plans, http://ncse.com/book/export/html/2585 (accessed
November 6, 2012).
18. Prud’homme, Gompel, and Carroll, “Emerging Principles ofRegulatory Evolution.”
19. Prud’homme, Gompel, and Carroll, “Emerging Principles ofRegulatory Evolution,” 8605.
20. Hoekstra and Coyne note explicitly that the best examples of alleged
CRE-induced mutations showed “losses of traits rather than the origin of new
traits” (“The Locus of Evolution,” 1006).
21. Hoekstra and Coyne, “The Locus of Evolution,” 996.
22. Schwartz, Sudden Origins, 3.
23. Schwartz, Sudden Origins, 13. According to Schwartz, “At the genetic

level, major morphological novelty can indeed be accomplished in thetwinkling of an eye. All that is necessary is that homeobox genes are either
turned on or they are not” (362).
24. McGinnis and Kurziora, “The Molecular Architects of Body Design,”
58.
25. Lindsey and Grell, Guide to Genetic Variations of Drosophilamelanogaster.
26. Lewis, “A Gene Complex Controlling Segmentation in Drosophila”;
Peifer and Bender, “The Anterobithorax and Bithorax Mutations of the
Bithorax Complex”; Fernandes et al., “Muscle Development in the FourWinged Drosophila and the Role of the Ultrabithorax Gene.”
27. Szathmáry, “When the Means Do Not Justify the End,” 745.
28. Scott and Carroll, “The Segmentation and Homeotic Gene Network in
Early Drosophila Development.”
29. Davidson and Erwin, “An Integrated View of Precambrian
Eumetazoan Evolution.”
30. Schwartz, Sudden Origins, 362.
31. Szathmáry, “When the Means Do Not Justify the End,” 745.
32. Schwartz, Sudden Origins, 362.
33. Szathmáry, “When the Means Do Not Justify the End,” 745.
34. Panganiban et al., “The Origin and Evolution of Animal Appendages.”
35. Instead, epigenetic information and structures actually determine thefunction of many Hox genes. This can be seen dramatically when the sameHox gene (as determined by nucleotide sequence homology) regulates thedevelopment of the strikingly different (i.e., classically nonhomologous)
anatomical features found in different phyla. For instance, in arthropods, theHox gene Distal-less is required for the normal development of limbs, but
homologous genes are found in vertebrates (e.g., the Dlx gene in mice), where
the gene also plays a key role in limb development—albeit a vertebrate(internal skeleton), not arthropod (external skeleton) limb. Distal-lesshomologues in yet other phyla, such as echinoderms, regulate thedevelopment of tube feet and spines—again, anatomical features classicallynot homologous to arthropod or vertebrates limbs.
In each case, the roles of the Hox genes are governed “top-down” by thehigher-level organismal contexts in which they occur. Panganiban et al., “TheOrigin and Evolution of Animal Appendages.”
36. Despite all this, some evolutionary theorists have argued that the
emergence of Hox genes in Precambrian organisms may have triggered theCambrian explosion by providing the raw materials for the diversification ofbody plans (Carroll, Patterns and Processes of Vertebrate Evolution). Yet, inaddition to those difficulties already noted, recent studies have highlighted
another problem with attributing the origin of body plans to Hox genes. Hox
genes first emerged long before the diversification of the various bilaterian
phyla, suggesting—because of the length of the time lag—that something elsemust have responsible for the Cambrian explosion. As a paper in the journal
Science explains, “The temporal lag between the initial construction of these
networks and the eventual appearance of bilaterian fossils suggests that thesolution to the dilemma of the Cambrian explosion lies not solely with thisgenomic and developmental potential, but instead must also be found in theecology of the Cambrian radiation itself” (Erwin et al., “The CambrianConundrum,” 1095). See also de Rosa et al., “Hox Genes in Brachiopods andPriapulids and Protostome Evolution.”
37. Lynch, “The Origins of Eukaryotic Gene Structure,” 454.
38. Lynch, “The Origins of Eukaryotic Gene Structure,” 450. He actually
goes even further, contending that “random genetic drift can impose a strong
barrier to the advancement of molecular refinements by adaptive processes.”
Lynch, “Evolutionary Layering and the Limits to Cellular Perfection.”
39. Jurica, “Detailed Closeups and the Big Picture of Spliceosomes,” 315.
See also Butcher, “The Spliceosome as Ribozyme Hypothesis Takes a Second
Step,” 12211–12; Nilsen, “The Spliceosome: The Most Complex
Macromolecular Machine in the Cell?” 1147–49.
40. Quoted in Azar, “Profile of Michael Lynch,” 16015.
41. On my website for this book, www.darwinsdoubt.com, I explain why
the origin of the eukaryotic cell presents such a formidable challenge to all
theories of unguided evolution.
42. Lynch, “The Origins of Eukaryotic Gene Structure,” 450–68 (emphasis
added).
43. See Lynch, “The Frailty of Adaptive Hypotheses for the Origin ofOrganismal Complexity,” 8597–604.
44. Gauger points out that Lynch, “offers no explanation of how nonadaptive forces can produce the functional genomic and organismalcomplexity we observe in modern species.” [Ann Gauger, “The Frailty of the
Darwinian Hypothesis, Part 2.”] Jerry Coyne observes much the same: “Bothdrift and natural selection produce genetic change that we recognize as
evolution. But there’s an important difference. Drift is a random process,while selection is the anti-thesis of randomness. . . . As a purely random
process, genetic drift can’t cause the evolution of adaptations. It could neverbuild a wing or an eye. That takes nonrandom natural selection.” [Coyne, Why
Evolution Is True, 123.]
45. Lynch and Abegg, “The Rate of Establishment of Complex

Adaptations,” 1404.
46. Lynch and Abegg, “The Rate of Establishment of Complex
Adaptations,” 1414.
47. Axe, “The Limits of Complex Adaptation: An Analysis Based on a
Simple Model of Structured Bacterial Populations,” 3.
48. Axe, “The Limits of Complex Adaptation: An Analysis Based on a
Simple Model of Structured Bacterial Populations,” 3.
49. Darwin, On the Origin of Species, 134–38. Darwin’s own theory oftransmission genetics, dubbed “pangenesis,” postulated that a host of minute
heredity particles, which he called “gemmules,” accumulated in the
reproductive organs of organisms, carrying information about the life history
and environmental circumstances of the parent. This information would thenbe transmitted at reproduction to offspring, allowing the “inheritance” of“acquired” characteristics.
50. Darwin. The Illustrated Origin of Species (6th edition), 95, writes, “I
think there can be no doubt that use in our domestic animals has strengthened
and enlarged certain parts, and disuse diminished them; and suchmodifications are inherited.”
51. Some question exists about the historical accuracy of calling thesetwenty-first-century ideas “neo-Lamarckian” in light of the actual content ofJean-Baptiste de Lamarck’s views when compared with the enormous growthof knowledge about heredity over the past two hundred years. Given that
Jablonka adapts the term “Lamarckism” to her own position, however, I
follow that practice, with the caveats about differences in content noted.
52. Jablonka and Raz, “Transgenerational Epigenetic Inheritance,” 168.
53. Jablonka and Raz, “Transgenerational Epigenetic Inheritance,” 138,emphasis added.
54. Jablonka and Raz, “Transgenerational Epigenetic Inheritance,”162.
55. Shapiro, Evolution, 2.
56. Shapiro contends that the neo-Darwinian insistence on fundamental
randomness arose for philosophical, not empirical (or observational) reasons,having to do with the exclusion of “supernatural intervention” in the origin oforganisms.
57. Shapiro, Evolution, 12.
58. Shapiro, Evolution, 14.
59. Shapiro, Evolution, 14.
60. Shapiro, Evolution, 16.
61. Shapiro, Evolution, 16.
62. Shapiro, Evolution, 14.
63. As biologist Bénédicte Michel observes, “Clearly, it is important forbacteria to keep all levels of the SOS response under tight control. There is noutility to the organism of using error-prone polymerases longer thanabsolutely necessary” (“After 30 Years, the Bacterial SOS Response Still
Surprises Us,” 1175).
64. Shapiro, “Darwin’s Black Box: The Biochemical Challenge to
Evolution-Book Reviews.”
Chapter 17: The Possibility of Intelligent Design
1. As Dawkins explains: “Natural selection, the blind, unconscious,
automatic process which Darwin discovered and which we now know is the
explanation for the existence and apparently purposeful form of all life, has
no purpose in mind. It has no mind and no mind’s eye” (The Blind
Watchmaker, 5).
2. Mayr, Foreword, in Ruse, ed., Darwinism Defended, xi–xii.
3. Ayala, “Darwin’s Greatest Discovery,” 8572.
4. As Dawkins notes: “Biology is the study of complicated things that givethe appearance of having been designed for a purpose” (The Blind
Watchmaker, 1). Crick likewise explains: “Organisms appear as if they had
been designed to perform in an astonishingly efficient way, and the humanmind therefore finds it hard to accept that there need be no Designer toachieve this” (What Mad Pursuit, 30). Lewontin also observes that livingorganisms “appear to have been carefully and artfully designed”(“Adaptation”).
5. Dawkins, River Out of Eden, 17.
6. Dawkins, The Blind Watchmaker, 1.
7. Gillespie, Charles Darwin and the Problem of Creation, 83–108.
8. Thaxton, Bradley, and Olsen, The Mystery of Life’s Origin, 211.
9. We have observational evidence in the present that intelligent
investigators can (and do) build contrivances to channel energy downnonrandom chemical pathways to bring about some complex chemical
synthesis, even gene building. May not the principle of uniformity then be
used in a broader frame of consideration to suggest that DNA had an
intelligent cause at the beginning? (Thaxton, Bradley, and Olsen, The Mysteryof Life’s Origin, 211).
10. Peirce, Collected Papers, 2:372–88; Meyer, “Of Clues and Causes,”
25. See also Whewell, “Lyell’s Principles of Geology”; The Philosophy of theInductive Sciences.
11. Peirce, Collected Papers, 2:372–88. See also Fann, Peirce’s Theory of
Abduction, 28–34; Whewell, “Lyell’s Principles of Geology”; The Philosophyof the Inductive Sciences.

12. Gould, “Evolution and the Triumph of Homology,” 61. See also
Whewell, “Lyell’s Principles of Geology”; The Philosophy of the Inductive
Sciences.
13. Peirce, “Abduction and Induction,” 150–54.
14. Chamberlain, “The Method of Multiple Working Hypotheses.”
15. Conniff, “When Continental Drift Was Considered Pseudoscience.”
16. Conniff, “When Continental Drift Was Considered Pseudoscience.”
17. Oreskes, “From Continental Drift to Plate Tectonics,” 12.
18. Heirtzler, “Sea-Floor Spreading”; Hurley, “The Confirmation ofContinental Drift”; Vine, “Reversals of Fortune.”
19. For example, Xavier Le Pichon recalls: “I was progressively forced by
the convincing power of the magnetic [data]” (“My Conversion to Plate
Tectonics,” 212).
20. Lipton, Inference to the Best Explanation, 1.
21. Lipton, Inference to the Best Explanation, 1.
22. Lyell, Principles of Geology, 75–91.
23. Kavalovski, “The Vera Causa Principle,” 78–103.
24. Scriven, “Explanation and Prediction in Evolutionary Theory,” 480;
Gallie, “Explanations in History and the Genetic Sciences”; Sober,Reconstructing the Past, 1–5.
25. Meyer, “Of Clues and Causes,” 96–108.
Chapter 18: Signs of Design in the Cambrian Explosion
1. Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,”
35.
2. Erwin and Davidson, “The Evolution of Hierarchical Gene Regulatory
Networks,” 141.
3. Davidson, “Evolutionary Bioscience as Regulatory Systems Biology,” 6.
4. Erwin, “Early Introduction of Major Morphological Innovations,” 288.
5. Erwin, “Early Introduction of Major Morphological Innovations,” 288,
emphasis added.
6. As Erwin puts it: “There is every indication that the range ofmorphological innovation possible in the Cambrian is simply not possible
today” (“The Origin of Body Plans,” 626, emphasis added).
7. Conway Morris, Life’s Solution: Inevitable Humans in a Lonely
Universe, 327; see also “Evolution: Bringing Molecules into the Fold”; “The
Cambrian Explosion of Metazoans.”
8. Conway Morris, Life’s Solution, 327. See also Conway Morris,“Bringing Molecules into the Fold,” 8.
9. Shapiro, Evolution.

10. Dawkins, River Out of Eden, 17.
11. Hood and Galas, “The Digital Code of DNA.”
12. Gates, The Road Ahead, 188.
13. Quastler, The Emergence of Biological Organization, 16.
14. Of course, the phrase “large amounts of specified information” begs aquantitative question, namely, “How much specified information would theminimally complex cell have to have before it implied design?” In Signaturein the Cell, I give and justify a precise quantitative answer to this question. I
show that the de novo emergence of 500 or more bits of specified information
reliably indicates design. Meyer, Signature in the Cell, 294.
15. Dawkins, The Blind Watchmaker, 47–49; Küppers, “On the Prior
Probability of the Existence of Life”; Scheider, “The Evolution of Biological
Information”; Lenski, “The Evolutionary Origin of Complex Features.” For a
critique of these genetic algorithms and claims that they simulate the abilityof natural selection and random mutation to generate new biologicalinformation apart from intelligent activity, see Meyer, Signature in the Cell,
281–95.
16. Berlinski, “On Assessing Genetic Algorithms.”
17. Rodin, Szathmáry, and Rodin, “On the Origin of the Genetic Code andtRNA Before Translation,” 2.
18. Denton, Evolution: A Theory in Crisis, 309–11.
19. Polanyi, “Life Transcending Physics and Chemistry”; “Life’s
Irreducible Structure.”
20. Oliveri and Davidson, “Built to Run, Not Fail.” All animal embryos,
notes Davidson, must “turn on the right regulatory genes in the right place.
These genes must also be dynamically locked on; the regulatory state of cells
in a given spatial domain must further be made dependent on signaling among
them all; the expression of these same regulatory genes must be specificallyforbidden anywhere else; and then, on top of all that, specific alternative
states must be excluded. These components are of course interlinked. . . . In
the sea urchin embryo, where all of the above are to be found, disarming any
one of these subcircuits produces some abnormality in expression” (511;emphasis added).
21. Davidson, Genomic Regulatory Systems, 54.
22. “Sameness” (i.e., homology) is determined by nucleotide-sequenceconservation within a reading frame.
23. Newman, “The Developmental Genetic Toolkit and the Molecular
Homology-Analogy Paradox,” 12.
24. Within evolutionary theory, several proposals have attempted toresolve the paradox. Perhaps the most popular modifies the neo-Darwiniandefinition of the concept of “homology” by preceding it with the adjective“deep,” a verbal slipcover that—if one is cynically inclined—ought to elicit
sardonic commentary befitting a late-night comedy sketch. Strictly speaking,we should remember that the neo-Darwinian prediction about genes,
phenotypes, and homology was found to be wrong. Nothing wrong everturned out right by putting the adjective “deep” in front of it.
25. Carroll, Endless Forms Most Beautiful, 72.
26. Gould, The Structure of Evolutionary Theory, 1065. Stuart Newman
observes: “It came as a big surprise to workers in the fields of evolutionary
and developmental biology . . . that the Drosophila eyeless (ey) gene has
extensive DNA similarity to the mouse and human Pax-6 genes” because“evolutionary theory has traditionally held that very long periods of time wereneeded for natural selection to generate extreme differences in morphologicalorganization.” Yet, he notes, if over long periods of time, natural selection andmutation had produced extensive changes in morphology, it ought to haveproduced extensive changes in genes as well (“The Developmental Genetic
Toolkit and the Molecular Homology-Analogy Paradox,” 12).
27. Nelson and Wells, “Homology in Biology,” 316.
28. Nelson and Wells, “Homology in Biology,” 316.
29. Erwin, “Disparity.” Erwin observes: “The distribution of organic forms
is clumpy at any scale from populations to the highest taxonomic categories,
and whether considered within clades or within eco-systems. The fossil record
provides little support for expectations that the morphological gaps between
species or groups of species have increased through time as it might if thegaps were created by extinction of a more homogeneous distribution ofmorphologies. As the quantitative assessments of morphology have replacedcounts of higher taxa as a metric of morphological disparity, numerous studies
have demonstrated the rapid construction of morphospace early inevolutionary radiations” (57, emphasis added).
30. Dembski, “Intelligent Design as a Theory of Technological Evolution”;
Savransky, Engineering of Creativity, 8, 24; Bracht, “Inventions, Algorithms,
and Biological Design.”
31. Valentine, “Why No New Phyla After the Cambrian?”; see also
Bergström, “Ideas on Early Animal Evolution.” Bergström comments: “Thereis absolutely no sign of convergence between phyla as we follow thembackwards to the Early Cambrian. They were as widely apart from the
beginning as they are today. Hierarchical levels apparently include abiological reality, not only classificatory convention. In fact, theoverwhelming taxonomic difficulty is to recognize relationships between
phyla, not to distinguish between them” (464).

32. Denton, Evolution, 313.
33. Agassiz, “Evolution and the Permanence of Type,” 101.
Chapter 19: The Rules of Science

1. Chesterton, “The Invisible Man.”
2. Murphy, “Phillip Johnson on Trial,” 33. Nancey Murphy is aphilosopher and seminary professor who strongly affirms methodologicalnaturalism. Here’s what she says in full: “Science qua science seeks
naturalistic explanations for all natural processes. Christians and atheists alikemust pursue scientific questions in our era without invoking a Creator. . . .
Anyone who attributes the characteristics of living things to creative
intelligence has by definition stepped into the arena of either metaphysics ortheology.” See also Willey, “Darwin’s Place in the History of Thought,” 15(“Science must be provisionally atheistic, or cease to be itself”); Grizzle,“Some Comments on the ‘Godless’ Nature of Darwinian Evolution,” 176.
3. Meyer, “The Origin of Biological Information and the Higher
Taxonomic Categories.”
4. For detailed discussions of facts of the Sternberg case, see “Smithsonian
Controversy,” www.richardsternberg.com/smithsonian.php; U.S. Office ofSpecial Counsel Letter (2005) at www.discovery.org/f/1488; United States
House of Representatives Committee on Government Reform, Subcommittee
Staff Report, “Intolerance and the Politicization of Science at theSmithsonian” (December 2006), at www.discovery.org/f/1489; Appendix,
United States House of Representatives Committee on Government Reform,
Subcommittee Staff Report (December, 2006) at www.discovery.org/f/1490.
5. See “Statement from the Council of the Biological Society ofWashington,” originally at http://www.biolsocwash.org/id_statement.html;
now at http://ncse.com/news/2004/10/bsw-strengthens-statement-repudiatingmeyer-paper–00528 or
http://web.archive.org/web/20070926214521/http://www.biolsocwash.org/id_statement.htm
6. E-mail from Roy McDiarmid to Hans Sues, “Re: Request for
information” (January 28, 2005, 2:25 p.m.), cited in United States House ofRepresentatives Committee on Government Reform, “Intolerance and thePoliticization of Science at the Smithsonian,” available at
http://www.discovery.org/f/1489 (“I have seen the review file and commentsfrom 3 reviewers on the Meyer paper. All three with some differences among
the comments recommended or suggested publication. I was surprised but
concluded that there was not inappropriate behavior vs a vis [sic] the review
process”).
7. Klinghoffer, “The Branding of a Heretic.”

8. See “Statement from the Council of the Biological Society ofWashington,” originally at http://www.biolsocwash.org/id_statement.html;
now at http://ncse.com/news/2004/10/bsw-strengthens-statement-repudiatingmeyer-paper–00528 or
http://web.archive.org/web/20070926214521/http://www.biolsocwash.org/id_statement.htm
9. “AAAS Board Resolution on Intelligent Design Theory,” AAAS News
Archives, October 18, 2002, at
http://www.aaas.org/news/releases/2002/1106id2.shtml.
10. See Siegal, “Riled by Intelligent Design”; World Net Daily, “Intelligent
Design Torpedoes Tenure”; Brumfiel, “Darwin Sceptic Says Views Cost
Tenure”; Dillon, “Regents Deny Gonzalez’s Tenure Appeal”; Meyer, “A
Scopes Trial for the ’90s”; West, Darwin Day in America, 234–38;“Background to the Guillermo Gonzalez Story,” at
http://www.evolutionnews.org/gg-bckgrndr.final.pdf; “Intelligent Design Was
the Issue After All (Updated),” at
http://www.evolutionnews.org/ID_was_the_Issue_Gonzalez_Tenure.pdf;
LeVake v. Independent School District, 625 N.W.2d 502, 506 (Minn. Ct.
App. 2001), cert. denied, 534 U.S. 1081 (2002); Mims, “The Scientific
American Affair”; Crocker, Free to Think; Vedantam, “Eden and Evolution”;
Luskin, “Darwin’s Dilemma”; Anderson, “Cancellation of Darwin Film
Creates Uproar”; Reardon, “California Science Center to Pay $110,000
Settlement Over Intelligent Design Film”; Boehm, “California Science Center
Is Sued for Canceling a Film Promoting Intelligent Design”; Crowther,“Academic Freedom Expelled from Baylor University”; Briggs and Maaluf,“BU Had Role in Dembski Return”; Luskin, “Credibility Gap”; Black,“Intelligent Design Proponent Fired from NASA Lab”; Pitts, “Design Flaw?”;
Associated Press, “Former NASA Specialist Claims He Was Fired overIntelligent Design”; Associated Press, “JPL Worker Sues over Intelligent
Design Demotion”; Gallegos, “Intelligent Design Proponent Who Works at
JPL Says He Experienced Religious Discrimination”; Luskin, “Intelligent
Design Demoted.”
11. Crick, What Mad Pursuit, 138.
12. Lewontin, “Billions and Billions of Demons,” 28. The role ofmethodological materialism in artificially buttressing Darwin’s theory beganwith Darwin himself. According to historian of science Neal Gillespie: “Theuneasy reservations about natural selection among Darwin’s contemporaries
and the widespread rejection of it from the 1890s to the 1930s suggest that . . .
it was more Darwin’s insistence on totally natural explanations than on
natural selection that won their adherence. . . . The primary change had notbeen in speciation theory but in beliefs about the nature of science.” In short,Darwin’s new definition of science excluded “both direct and indirect design”
in living things and thereby protected it from competition (Charles Darwin
and the Problem of Creation, 123, 147, 152).
13. Laudan, “The Demise of the Demarcation Problem”; Meyer, “TheDemarcation of Science and Religion.”
14. Newton, Newton’s Principia, 543–44; Alexander, The Leibniz-Clarke
Correspondence, 92; Hutchison, “What Happened to Occult Qualities in the
Scientific Revolution?”; Leibniz, New Essays on Human Understanding, 61,
65–67.
15. As Newton wrote in his famous letter to Bishop Bentley: “The cause ofgravity is what I do not pretend to know” (Cohen, Isaac Newton’s Papers andLetters on Natural Philosophy, 302).
16. Laudan says, “There is no demarcation line between science andnonscience, or between science and pseudo-science, which would win assent
from a majority of philosophers” (Beyond Positivism and Relativism, 210).
17. Laudan, “The Demise of the Demarcation Problem.
18. Newton, Newton’s Principia, 543–44; Alexander, The Leibniz-Clarke
Correspondence, 92; Hutchison, “What Happened to Occult Qualities in the
Scientific Revolution?”; Leibniz, New Essays on Human Understanding, 61,
65–67.
19. Hutchison, “What Happened to Occult Qualities in the Scientific
Revolution?” Leibniz, New Essays on Human Understanding, 61, 65–67.
20. Laudan, “The Demise of the Demarcation Problem”; Eger, “A Tale of
Two Controversies.”
21. Gould, “Creationism”; Ruse, “Witness Testimony Sheet”; Ebert et al.,Science and Creationism, 8–10.
22. Kline, “Theories, Facts and Gods,” 42; Gould, “Evolution as Fact andTheory,” 120; Root-Bernstein, “On Defining a Scientific Theory,” 72.
23. Root-Bernstein, “On Defining a Scientific Theory,” 73; Ruse, “APhilosopher’s Day in Court,” 28; Ebert et al., Science and Creationism, 8–10.
24. Ruse, “Witness Testimony Sheet,” 301; “A Philosopher’s Day in
Court,” 26; “Darwinism: Philosophical Preference, Scientific Inference, and a
Good Research Strategy,” 1–6.
25. Ruse, Darwinism Defended, 59; “Witness Testimony Sheet,” 305;
Gould, “Evolution as Fact and Theory,” 121; Root-Bernstein, “On Defining a
Scientific Theory,” 74.
26. Kehoe, “Modern Anti-Evolutionism”; Ruse, “Witness Testimony
Sheet,” 305; “A Philosopher’s Day in Court,” 28; Ebert et al., Science andCreationism, 8.
27. Kitcher, Abusing Science, 126–27, 176–77.

28. Skoog, “A View from the Past”; Root-Bernstein, “On Defining a
Scientific Theory,” 74; Scott, “Keep Science Free from Creationism,” 30.
29. Lyell, Principles of Geology.
30. Meyer, Signature in the Cell, 481–97.
31. See Meyer, Signature in the Cell, 416–38; see also Meyer, “TheScientific Status of Intelligent Design: The Methodological Equivalence of
Naturalistic and Non-Naturalistic Origins Theories,” 151–212; Meyer, “TheNature of Historical Science and the Demarcation of Design and Descent”
91–130; Meyer, “Laws, Causes and Facts: A Response to Professor Ruse,”
29–40; Meyer, “Sauce for the Goose: Intelligent Design, ScientificMethodology, and the Demarcation Problem,” 95–131; Meyer, “The
Methodological Equivalence of Design and Descent,” 67–112.
32. See Meyer, Signature in the Cell, 441–42.
33. Meyer, Signature in the Cell, 373–95.
34. Asher, Evolution and Belief, 32.
35. Asher, Evolution and Belief, 32.
36. Asher, Evolution and Belief, 32.
37. Asher, Evolution and Belief, 32.
38. Oddly, also Asher observes that overall “Meyer professes a low regard
for naturalism, but high regard for uniformitarianism” (Evolution and Belief,
32). If by naturalism, he means treating the principle of methodologicalnaturalism as normative for all scientific inquiry, his characterization of myposition is, in this respect, accurate.
39. Asher, Evolution and Belief, 32.
40. Ecker et al., “Genomics.”
41. Ecker et al., “Genomics,” 52.
42. Orgel and Crick, “Selfish DNA.”
43. Dembski, “Science and Design,” 26.
44. The ENCODE Project Consortium, “An Integrated Encyclopedia of
DNA Elements in the Human Genome,” 57.
45. Shapiro and Von Sternberg, “Why Repetitive DNA is Essential to
Genome Function”; Von Sternberg and Shapiro, “How RepeatedRetroelements Format Genome Function”; Han, Szak, and Boeke,“Transcriptional Disruption by the L1 Retrotransposon”; Janowski et al.,“Inhibiting Gene Expression at Transcription Start Sites in Chromosomal
DNA with Antigene RNAs”; Goodrich and Kugel, “Non-coding-RNA
Regulators of RNA Polymerase II Transcription”; Li et al., “Small dsRNAs
Induce Transcriptional Activation in Human Cells”; Pagano et al., “New
Small Nuclear RNA Gene-like Transcriptional Units”; Van de Lagemaat et al.,“Transposable Elements in Mammals”; Donnelly, Hawkins, and Moss, “AConserved Nuclear Element”; Dunn, Medstrand, and Mager, “AnEndogenous Retroviral Long Terminal Repeat”; Burgess-Beusse et al., “TheInsulation of Genes from External Enhancers and Silencing Chromatin”;
Medstrand, Landry, and Mager, “Long Terminal Repeats Are Used as
Alternative Promoters”; Mariño-Ramírez et al., “Transposable Elements
Donate Lineage-Specific Regulatory Sequences to Host Genomes”; Green,“The Role of Translocation and Selection”; Figueiredo et al., “A Central Rolefor Plasmodium Falciparum Subtelomeric Regions”; Henikoff, Ahmad, andMalik, “The Centromere Paradox”; Bell, West, and Felsenfeld, “Insulators
and Boundaries”; Pardue and Debaryshe, “Drosophila Telomeres”; Henikoff,“Heterochromatin Function in Complex Genomes”; Schueler et al., “Genomic
and Genetic Definition of a Functional Human Centromere”; Jordan et al.,“Origin of a Substantial Fraction of Human Regulatory Sequences fromTransposable Elements”; Chen, DeCerbo, and Carmichael, “Alu ElementMediated Gene Silencing”; Jurka, “Evolutionary Impact of Human Alu
Repetitive Elements”; Lev-Maor et al., “The Birth of an Alternatively Spliced
Exon”; Kondo-Iida et al., “Novel Mutations and Genotype–Phenotype
Relationships in 107 Families”; Mattick and Makunin, “Non-coding RNA”;
McKenzie and Brennan, “The Two Small Introns of the Drosophila
affinidisjuncta Adh Gene”; Arnaud et al., “SINE Retroposons Can Be Used In
Vivo”; Rubin, Kimura, and Schmid, “Selective Stimulation of Translational
Expression by Alu RNA”; Bartel, “MicroRNAs”; Mattick and Makunin,“Small Regulatory RNAs in Mammals”; Dunlap et al., “Endogenous
Retroviruses Regulate Periimplantation Placental Growth andDifferentiation”; Hyslop et al., “Downregulation of NANOG Induces
Differentiation”; Peaston et al., “Retrotransposons Regulate Host Genes inMouse Oocytes and Preimplantation Embryos”; Morrish et al., “DNA Repair
Mediated by Endonuclease-Independent LINE–1 Retrotransposition”;
Tremblay, Jasin, and Chartrand, “A Double-Strand Break in a Chromosomal
LINE Element Can Be Repaired”; Grawunder et al., “Activity of DNA Ligase
IV Stimulated by Complex Formation with XRCC4 Protein in Mammalian
Cells”; Wilson, Grawunder, and Liebe, “Yeast DNA Ligase IV Mediates NonHomologous DNA End Joining”; Mura et al., “Late Viral Interference
Induced by Transdominant Gag of an Endogenous Retrovirus”; Goh et al., “A
Newly Discovered Human Alpha-Globin Gene”; Kandouz et al.,“Connexin43 Pseudogene Is Expressed”; Tam et al., “Pseudogene- Derived
Small Interfering RNAs Regulate Gene Expression in Mouse Oocytes”;
Watanabe et al., “Endogenous siRNAs from Naturally Formed dsRNAs
Regulate Transcripts in Mouse Oocytes”; Piehler et al., “The Human ABC
Transporter Pseudogene Family”; Mattick and Gagen, “The Evolution ofControlled Multitasked Gene Networks”; Pandey and Mukerji, “From‘JUNK’ to Just Unexplored Noncoding Knowledge”; Balakirev and Ayala,“Pseudogenes”; Pink et al., “Pseudogenes”; Wen et al., “Pseudogenes Are Not
Pseudo Any More”; Franco-Zorrilla et al., “Target Mimicry Provides a New
Mechanism for Regulation of MicroRNA Activity”; Colas et al., “WholeGenome MicroRNA Screening Identifies let-7 and miR-18 as Regulators”;
Carrier et al., “Long Non-Coding Antisense RNA Controls Uchl1
Translation”; Kelley and Rinn, “Transposable Elements Reveal a Stem Cell
Specific Class of Long Noncoding RNAs”; Wang et al., “Alternative Isoform
Regulation in Human Tissue Transcriptomes”; Louro et al., “Conserved
Tissue Expression Signatures of Intronic Noncoding RNAs”; Hoeppner et al.,
“Evolutionarily Stable Association of Intronic SnoRNAs and MicroRNAs
with Their Host Genes”; Monteys et al., “Structure and Activity of Putative
Intronic miRNA Promoters”; Mondal et al., “Characterization of the RNA
Content of Chromatin”; Rodriguez-Campos and Azorin, “RNA Is an Integral
Component of Chromatin That Contributes to Its Structural Organization”;
George et al., “Evolution of Diverse Mechanisms for Protecting Chromosome
Ends”; Von Sternberg, “On the Roles of Repetitive DNA Elements in theContext of a Unified Genomic-Epigenetic System.”
46. “Breakthrough of the Year Newsfocus: Genomics Beyond Genes,”
Science 338 (December 21, 2012): 1528.
47. Moran, “Intelligent Design Creationists Chose ENCODE as the #1
Evolution Story of 2012.”
48. Shapiro and von Sternberg, “Why Repetitive DNA Is Essential to
Genome Function”; Von Sternberg and Shapiro, “How RepeatedRetroelements Format Genome Function.” See also Von Sternberg, “On theRoles of Repetitive DNA Elements in the Context of a Unified GenomicEpigenetic System.”
49. Todd, “A View from Kansas on That Evolution Debate.”
Chapter 20: What’s at Stake
1. Dawkins, The God Delusion; Hitchens, God Is Not Great; Stenger,
God: The Failed Hypothesis.
2. Stenger, God: The Failed Hypothesis.
3. Dawkins, The Blind Watchmaker, 6.
4. Russell, quoted in Conant, Modern Science and Modern Man, 139–40.
5. Collins, The Language of God. See also Giberson, Saving Darwin;
Miller, Finding Darwin’s God.
6. For prominent critics of the neo-Darwinian consensus, see Chapter 14,
n. 42.

7. For some of the latest studies, see Chapter 19, n. 45.
8. As Alfred North Whitehead said, “When we consider what religion isfor mankind and what science is, it is no exaggeration to say that the future
course of history depends upon the decision of this generation as to therelations between them” (Science and the Modern World, 260).

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Credits and Permissions
The inclusion of any figures, illustrations, photographs, diagrams, charts, orother types of images in this book should not be construed as an endorsementof the ideas and arguments contained in this book on the part of any copyrightholders or creators of those images, other than the author of the book himself.
Illustrations © 2013 Ray Braun, Seattle, WA.
Cover photograph: Courtesy Chen, J. Y., G. Q. Zhou, M. Y. Zhu, and K. Y.
Yeh. The Chengjiang Biota—A Unique Window of the Cambrian Explosion.
Taichung, Taiwan: National Museum of Natural Science (1996), 149, Figure186. Used by permission.
Cover: Photograph of trilobite fossil courtesy of J. Y. Chen. Source: Figure
186, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The Chengjiang
Biota—A Unique Window of the Cambrian Explosion, 149. Taichung, Taiwan:
National Museum of Natural Science, 1996. Used with permission.
Figure 1.1: Tree of life image from Ernst Haeckel, Volume II of Generelle
Morphologie (1866). Public Domain.
Figure 1.2a: Louis Agassiz photograph courtesy of Wikimedia Commons.
Public Domain.
Figure 1.2b: Charles Darwin photograph courtesy of Wikimedia Commons.
Original photograph taken by Henry Maull and John Fox. Public Domain.
Figure 1.3a: Drawing of brachiopod by Ray Braun based on information from
Figure 18, Brusca, R. C., and Brusca, G. J. Invertebrates, 794. Sunderland,
MA: Sinauer Associates, 1990; Figure 7.55, Mintz, L. W. Historical Geology:
The Science of a Dynamic Earth, 130. 2nd ed. Columbus, Charles E. Merrill
Publishing, 1977.
Figure 1.3b: Brachiopod fossil photograph showing internal remains courtesyof Paul Chien. Used with permission.
Figure 1.3c: Brachiopod fossil photograph © Colin Keates / DK Limited /Corbis. Used with permission.
Figure 1.4a: Drawing of trilobite by Ray Braun based on information from

“Fossil Groups,” University of Bristol,
http://palaeo.gly.bris.ac.uk/palaeofiles/fossilgroups/trilobites/page2.htm.
Figure 1.4b: Trilobite fossil photograph courtesy of Illustra Media. Used withpermission.

Figure 1.5: Drawing of tetracoral by Ray Braun based on information from
“Convergence,”
http://www.znam.bg/com/action/showArticle;jsessionid=FA17A83CDA0EC25151F6B8086
encID=790&article=2059773460.
Figure 1.6: Drawing of geological timescale by Ray Braun based on
information from Mintz, L. W. Historical Geology: The Science of a Dynamic
Earth, back page. 2nd ed. Columbus, Charles E. Merrill Publishing, 1977;
Gradstein, F. M., Ogg, J. G., Schmitz, M. D., Ogg, G. M. The GeologicalTimescale 2012 Volumes 1 and 2. Elsevier, 2012.
Figure 1.7: Drawing by Sir Thomas Dick-Lauder and published in Tyndall, J.,“The Parallel Roads of Glen Roy.” In Fragments of Science: A Series of
Detached Essays, Addresses, and Reviews, Volume I. New York: D. Appleton
and Company, 1915. Courtesy of Wikimedia Commons. Public Domain.
Figure 1.8: Drawing by Ray Braun based on information from a fossil exhibitthat was on display at the California Academy of Sciences in the 1990s.
Figure 2.1: Photograph of the Burgess Shale © Thomas Kitchin & Victoria
Hurst/All Canada Photos/Corbis. Used with permission.
Figure 2.2: Photograph of Charles Doolittle Walcott courtesy of Smithsonian
Institution Archives. Image #84–16281. Used with permission.
Figure 2.3a: Drawing of Marrella by Ray Braun based on information from
Figure 3.12, Gould, S. J. Wonderful Life: The Burgess Shale and the Nature ofHistory, 114. New York: Norton, 1990.
Figure 2.3b: Photograph of Marrella fossil © User: Smith609 (Own Work) /Wikimedia Commons / CC-BY-SA–3.0. Used with permission; usage notintended to imply endorsement by the author/licensor of the work.
Figure 2.4a: Drawing of Hallucigenia by Ray Braun based on informationfrom Figure 14.6, Xian-guang, H., Aldridge, R. J., Bergström, J., Siveter, D.
J., Siveter, D. J., and Xiang-hong, F. The Cambrian Fossils of Chengjiang,
China: The Flowering of Early Animal Life, 88 Oxford: Blackwell
Publishing, 2004; Figure 19(b), Conway Morris, S., The Crucible of Creation:
The Burgess Shale and the Rise of Animals, 55. Oxford: Oxford University
Press, 2000.

Figure 2.4b: Photograph of Hallucigenia fossil courtesy of Smithsonian
Institution. Used with permission.
Figures 2.5a, 2.5b, and 2.5c: Chart drawn by Ray Braun based on datacompiled from references in Chapter 2, Endnote 5.
Figure 2.6: Diagram drawn by Ray Braun based on information from Figure
1, Meyer, S. C., Ross, M., Nelson, P. and Chien, P. “The Cambrian Explosion:
Biology’s Big Bang.” In Darwinism, Design and Public Education, edited byJohn Angus Campbell and Stephen C. Meyer, 325. East Lansing, MI:
Michigan State University Press, 2003. Courtesy of Brian Gage.
Figure 2.7: Diagram drawn by Ray Braun based on original drawing by Art
Battson. Courtesy of Art Battson.
Figure 2.8: Diagram drawn by Ray Braun based on Figure 1, Wiester, J., andDehaan, R. F., “The Cambrian Explosion: The Fossil Record and Intelligent
Design.” In Signs of Intelligence: Understanding Intelligent Design, 149.
William A. Dembski and James M. Kushiner, eds. Grand Rapids, MI: Brazos
Press, 2001. Courtesy also of Art Battson.
Figure 2.9a: Drawing of Opabinia by Ray Braun based on information from
Figure 3.21, Gould, S. J. Wonderful Life: The Burgess Shale and the Nature ofHistory, 126. New York: Norton, 1990; Figure 173, Briggs, D., Erwin, D., andCollier, F. The Fossils of the Burgess Shale, 210. Washington: Smithsonian
Institution Press, 1994.
Figure 2.9b: Photograph of Opabinia fossil from Walcott, C. D., “Middle
Cambrian Branchiopoda, Malacostraca, Trilobita, and Merostomata.”
Smithsonian Miscellaneous Collections, Volume 57, Number 6 (Publication
2051), City of Washington, Published by the Smithsonian Institution, March
13, 1912. Public Domain.
Figure 2.10a: Drawing of Anomalocaris by Ray Braun based on informationfrom Figure 264, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The
Chengjiang Biota—A Unique Window of the Cambrian Explosion, 197.
Taichung, Taiwan: National Museum of Natural Science, 1996.
Figure 2.10b: Photograph of Anomalocaris fossil courtesy of J. Y. Chen.
Source: Figure 265A, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y.
The Chengjiang Biota—A Unique Window of the Cambrian Explosion, 198.
Taichung, Taiwan: National Museum of Natural Science, 1996. Used withpermission.
Figure 2.11a: Tree of life diagram from Charles Darwin, Origin of Species,1859. Courtesy of Wikimedia Commons. Public domain.
Figure 2.11b: Diagram drawn by Ray Braun.
Figure 2.12: Diagram drawn by Ray Braun.
Figure 3.1: Photograph of J. Y. Chen from Icons of Evolution Documentary,
Coldwater Media, 2002. Copyright © Discovery Institute 2013. Courtesy of
Discovery Institute. Used with permission.
Figure 3.2a: Photograph from Chengjiang fossil site courtesy of Illustra
Media. Used With Permission.
Figure 3.2b: Photograph from Chengjiang fossil site courtesy of Paul Chien.
Used With Permission.
Figure 3.2c: Photograph from Chengjiang fossil site courtesy of Paul Chien.
Used With Permission.
Figure 3.3: Photograph of Harry Whittington from the Archives of theMuseum of Comparative Zoology, Ernst Mayr Library, Harvard University.
Used with permission.
Figure 3.4a: Drawing of Nectocaris by Ray Braun based on information from
Smith, M. R., and Caron, J.-B., “Primitive soft-bodied cephalopods from theCambrian,” Nature, 465 (May 27, 2010): 469–472; Nectocaris pteryx at
http://commons.wikimedia.org/wiki/File:Nectocaris_pteryx.JPG, courtesy ofuser: Stanton F. Fink at en.wikipedia / Wikimedia Commons / CC BY-SA 2.5.
Figure 3.4b: Photograph of Nectocaris fossil reprinted by permission from
Macmillan Publishers Ltd: Nature, Figure 1, Smith, M. R., and Caron, J.-B.,“Primitive soft-bodied cephalopods from the Cambrian,” Nature, 465 (May27, 2010): 469–472. Copyright 2010. Used with permission.
Figure 3.4c: Photograph of Nectocaris fossil reprinted by permission from
Macmillan Publishers Ltd.: Nature, Figure 1, Smith, M. R., and Caron, J.-B.,“Primitive soft-bodied cephalopods from the Cambrian,” Nature, 465 (May27, 2010): 469–472. Copyright 2010. Used with permission.
Figure 3.5a: Photograph of stromatolite fossil courtesy of user: Rygel, M. C.,
at en.wikipedia / Wikimedia Commons / CC-BY-SA–3.0. Used withpermission; usage not intended to imply endorsement by the author/licensor
of the work.
Figure 3.5b: Photograph of stromatolite fossil courtesy of American
Association for the Advancement of Science, Figure 2B, Hoffman, P., “Algal
Stromatolites: Use in Stratigraphic Correlation and Paleocurrent

Determination,” Science, 157 (September 1, 1967): 1043–45. Reprinted withpermission from AAAS. Used with permission.
Figure 3.6a–1: Drawing of ctenophore by Ray Braun based on informationfrom Figure 28, Chen, J. Y., and Zhou, G., “Biology of the Chengjiang
fauna.” In “The Cambrian Explosion and the Fossil Record,” 33, Bulletin of
the National Museum of Natural Science, 10:11–106. Edited by Chen, J. Y.,
Cheng, Y., and Iten, H. V., eds. Taiwan: National Museum of Natural Science,
1997.
Figure 3.6a–2: Photograph of ctenophorefossil courtesy of J. Y. Chen. Source:
Figure 102, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The
Chengjiang Biota—A Unique Window of the Cambrian Explosion, 96.
Taichung, Taiwan: National Museum of Natural Science, 1996. Used withpermission.
Figure 3.6b–1: Drawing of phoronid by Ray Braun based on information from
Figure 51, Chen, J. Y., and Zhou, G., “Biology of the Chengjiang fauna.” In“The Cambrian Explosion and the Fossil Record,”45, Bulletin of the National
Museum of Natural Science, 10:11–106. Edited by Chen, J. Y., Cheng, Y., andIten, H. V., eds. Taiwan: National Museum of Natural Science, 1997.
Figure 3.6b–2: Photograph of phoronid fossil courtesy of J. Y. Chen. Source:
Figure 49, Chen, J. Y., and Zhou, G., “Biology of the Chengjiang fauna.” In“The Cambrian Explosion and the Fossil Record,” 44, Bulletin of the National
Museum of Natural Science, 10:11–106. Edited by Chen, J. Y., Cheng, Y., andIten, H. V., eds. Taiwan: National Museum of Natural Science, 1997. Used
with permission.
Figure 3.6c–1: Drawing of Waptia by Ray Braun based on information from
Figure 110, Briggs, D., Erwin, D., and Collier, F. The Fossils of the Burgess
Shale, 157. Washington: Smithsonian Institution Press, 1994.
Figure 3.6c–2: Photograph of Waptia fossil courtesy of Paul Chien. Used withpermission.
Figure 3.6d–1: Drawing of priapulid worm by Ray Braun based on
information from Figures 32A and 32B, Chen, J. Y., and Zhou, G. “Biology of
the Chengjiang fauna.” In “The Cambrian Explosion and the Fossil Record,”
36, Bulletin of the National Museum of Natural Science, 10:11–106. Edited byChen, J. Y., Cheng, Y., and Iten, H. V., eds. Taiwan: National Museum of
Natural Science, 1997.
Figure 3.6d–2: Photograph of priapulid worm fossil courtesy of Paul Chien.
Used with permission.

Figure 3.6e–1: Drawing of Eldonia by Ray Braun based on information from
Figure 147, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The
Chengjiang Biota—A Unique Window of the Cambrian Explosion, 124.
Taichung, Taiwan: National Museum of Natural Science, 1996; “CambrianCafé,” http://cambrian-cafe.seesaa.net/archives/201003–1.html.
Figure 3.6e–2: Photograph of Eldonia fossil courtesy of J. Y. Chen. Source:
Figure 148, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The
Chengjiang Biota—A Unique Window of the Cambrian Explosion, 125.
Taichung, Taiwan: National Museum of Natural Science, 1996. Used withpermission.
Figure 3.6f–1: Drawing of hyolith by Ray Braun based on information from
Figure 172, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The
Chengjiang Biota—A Unique Window of the Cambrian Explosion, 132.
Taichung, Taiwan: National Museum of Natural Science, 1996.
Figure 3.6f–2: Photograph of hyolith fossil courtesy of J. Y. Chen. Source:
Figure 173A, Chen, J. Y., Zhou, G. Q., Zhu, M. Y., and Yeh, K. Y. The
Chengjiang Biota—A Unique Window of the Cambrian Explosion, 139.
Taichung, Taiwan: National Museum of Natural Science, 1996. Used withpermission.
Figure 3.7a–1: Photograph of sponge embryo fossil courtesy of Paul Chien.
Used with permission.
Figure 3.7a–2: Photograph of sponge embryo fossil courtesy of Paul Chien.
Used with permission.
Figure 3.7b: Photograph of sponge embryo fossil courtesy of Paul Chien.
Used with permission.
Figure 3.8: Diagram drawn by Ray Braun based on information in Figure 2,
Meyer, S. C., Ross, M., Nelson, P., and Chien, P. “The Cambrian Explosion:
Biology’s Big Bang.” In Darwinism, Design and Public Education, edited byJohn Angus Campbell and Stephen C. Meyer, 326. East Lansing, MI:
Michigan State University Press, 2003. Courtesy of Brian Gage.
Figure 3.9a: Drawing of Myllokunmingia by Ray Braun based on informationfrom Figure 2A, Shu, D. G., Lou, H. L., Conway Morris, S., Zhang, X. L.,
Hu, S. X., Chen, L., Han, J., Zhu, M., Li, Y., and Chen, L. Z., “Lower
Cambrian Vertebrates from South China.” Nature, 402 (1999): 42–46.
Figure 3.9b: Photograph of Myllokunmingia fossil reprinted by permission
from Macmillan Publishers Ltd.: Nature, Figure 2A, Shu, D. G., Lou, H. L.,

Conway Morris, S., Zhang, X. L., Hu, S. X., Chen, L., Han, J., Zhu, M., Li,
Y., and Chen L. Z., “Lower Cambrian Vertebrates from South China.” Nature,402 (1999): 42–46. Copyright 1999. Used with permission.
Figure 4.1a–1: Drawing of Dickinsonia by Ray Braun based on informationfrom “Les premiers animaux de la Terre,” L’Historie de la vie sur terre, April
23, 2009, http://titereine.centerblog.net/4-Les-premiers-animaux-de-la-Terre.
Figure 4.1a–2: Photograph of Dickinsonia fossil courtesy of Figure 2,
Peterson, K. J., Cotton, J. A., Gehling, J. G., and Pisani, D., “The Ediacaranemergence of bilaterians: congruence between the genetic and the geologicalfossil records,” Philosophical Transactions of the Royal Society B, 2008, 363(1496): 1435–43, by permission of the Royal Society.
Figure 4.1b–1: Drawing of Spriggina by Ray Braun based on informationfrom Spriggina flounensi C.jpg, Wikipedia,
http://en.wikipedia.org/wiki/File:Spriggina_flounensi_C.jpg.
Figure 4.1b–2: Photograph of Spriggina fossil courtesy of Figure 2, Peterson,
K. J., Cotton, J. A., Gehling, J. G., and Pisani, D., “The Ediacaran emergenceof bilaterians: congruence between the genetic and the geological fossil
records,” Philosophical Transactions of the Royal Society B, 2008, 363(1496): 1435–43, by permission of the Royal Society.
Figure 4.1c–1: Drawing of Charnia by Ray Braun based on information from
Charnia_Species_BW_by_avancna,
http://avancna.deviantart.com/art/Charnia-Species-BW-101515874.
Figure 4.1c–2: Photograph of Charnia masoni fossil courtesy of user:
Smith609 at en.wikipedia / Wikimedia Commons / CC-BY–2.5. Used withpermission; usage not intended to imply endorsement by the author/licensor
of the work.
Figure 4.2a: Photograph of Arkarua fossil courtesy of Figure 4B, Gehling, J.
G., “Earliest known echinoderm—a new Ediacaran fossil from the Pound
Subgroup of South Australia,” Alcheringa: An Australasian Journal of
Palaeontology, 11 (1987): 337–45. Used with permission; usage not intended
to imply endorsement by the author / licensor of the work.
Figure 4.2b: Photograph of Parvancorina fossil courtesy of Figure 2,
Peterson, K. J., Cotton, J. A., Gehling, J. G., and Pisani, D., “The Ediacaranemergence of bilaterians: congruence between the genetic and the geologicalfossil records,” Philosophical Transactions of the Royal Society B, 2008, 363(1496): 1435–43, by permission of the Royal Society.

Figure 4.3: Photograph of Vernanimalcula fossil courtesy of American
Association for the Advancement of Science, from Figure 1b, Chen, J.-Y.,
Bottjer, D. J., Oliveri, P., Dornbos, S. Q., Gao, F., Ruffins, S., “Small
Bilaterian Fossils from 40 to 55 Million Years Before the Cambrian,” Science,
305 (July 9, 2004): 218–22. Reprinted with permission from AAAS.
Figure 5.1: Pentadactyl limb drawing courtesy of Jody F. Sjogren and Figure
4-1, Wells, J., Icons of Evolution: Science or Myth? Washington D.C.:
Regnery, 2000. Copyright © Jody F. Sjogren 2000. Used with permission.
Figure 5.2: Drawing by Ray Braun based on information from Paul Nelson;
Smith, A. B., and Peterson, K. J., “Dating the Time and origin of Major
Clades,” Annual Review of Earth and Planetary Sciences, 30 (2002): 65–88.
Figure 6.1: Drawing by Ray Braun based on information from Telford, M. J.
et al. “The evolution of the Ecdysozoa,” Philosophical Transactions of theRoyal Society B, Vol. 363 (2008): 1529–37; Aguinaldo, A. M., Turbeville, J.
M., Linford, L. S., Rivera, M. C., Garey, J. R., Raff, R. A., and Lake, J. A.
“Evidence for a clade of nematodes, arthropods and other moulting animals,”Nature, 387 (1997): 489–93; Mallatt, J. M., Garey, J. R., and Shultz, J. W.,“Ecdysozoan phylogeny and Bayesian inference: first use of nearly complete
28S and 18S rRNA gene sequences to classify the arthropods and theirkin,”Molecular Phylogenetics and Evolution, 31 (2004): 178–91; Halanych,
K. M., “The New View of Animal Phylogeny,” Annual Review of Ecology
and Systematics, 35 (2004): 229–56; Roy, S. W., and Irimia, M., “Rare
Genomic Characters Do Not Support Coelomata: Intron Loss/Gain,”
Molecular Biology and Evolution, 25 (2008): 620–23; Hyman, L. H. The
Invertebrates. Vol. 1: Protozoa through Ctenophora. New York: McGrawHill, 1940; Holton, T. A., and Pisani, D., “Deep Genomic-Scale Analyses ofthe Metazoa Reject Coelomata: Evidence from Single- and Multigene
Families Analyzed Under a Supertree and Supermatrix Paradigm,” Genome
Biology and Evolution, 2 (2010): 310–24.
Figure 6.2: Drawing by Ray Braun and Paul Nelson based on informationfrom Figure 1, Edgecombe, G. D., Giribet, G., Dunn, C. W., Hejnol, A.,
Kristensen, R. M., Neves, R. C., Rouse, G. W., Worsaae, K., and Sørensen,
M. V., “Higher-level metazoan relationships: recent progress and remaining
questions,” Organisms, Diversification, & Evolution, 11 (June 2011): 151–72.
Figure 6.3: Drawing by Ray Braun and Paul Nelson based on informationfrom Extavour, C. G., and Akam, M., “Mechanisms of germ cell specification
across the metazoans: epigenesis and preformation,” Development, 130(2003): 5869–84.

Figure 6.4: Drawing by Ray Braun and Paul Nelson based on informationfrom Figure 1, Extavour, C. G. M. “Evolution of the bilaterian germ line:
lineage origin and modulation of specific mechanisms,” Integrative andComparative Biology, 47 (2007): 770–85.
Figure 6.5: Drawing by Ray Braun and Paul Nelson based on informationfrom Willmer, P. G. Invertebrate Relationships: Patterns in Animal Evolution,
2–14. Cambridge: Cambridge University Press, 1990.
Figure 7.1a: Photograph of Stephen Jay Gould courtesy of Steve Liss /TIME& LIFE Images / Getty Images. Used with permission.
Figure 7.1b: Photograph of Niles Eldredge © Julian Dufort 2011. Used withpermission.
Figure 7.2: Drawn by Ray Braun based on an original drawing by Brian Gage.
Courtesy of Brian Gage.
Figure 7.3: Drawn by Ray Braun based on an original drawing by Brian Gage.
Courtesy of Brian Gage.
Figure 8.1: Photograph of James Watson and Francis Crick courtesy of A.
Barrington Brown/Science Source. Used With Permission.
Figure 8.2: Drawn by Ray Braun based on an original drawing by Fred
Hereen. Courtesy of Fred Hereen.
Figure 8.3: Drawn by Ray Braun based on Figure 10, designed by BrianGage, in Meyer, S. C., Ross, M., Nelson, P., and Chien, P., “The Cambrian
Explosion: Biology’s Big Bang.” In Darwinism, Design and Public
Education, edited by John Angus Campbell and Stephen C. Meyer, 336. East
Lansing, MI: Michigan State University Press, 2003.Courtesy of Brian Gage.
Figure 9.1: Photograph of Murray Eden courtesy of MIT Museum. Used withpermission.
Figure 9.2: Drawn by Ray Braun.
Figure 9.3: Drawn by Ray Braun.
Figure 10.1: Photograph of Douglas Axe courtesy of Brittnay Landoe. Used
with permission.
Figure 10.2: Drawing by Ray Braun based on information from Figures 3.39,
3.40, and 3.44 in Berg, J. M., Tymoczko, J. L., Stryer, L. Biochemistry, 60–
61, 5th ed. New York, NY: W. H. Freeman and Co, 2002.
Figure 10.3: Drawing by Ray Braun based on information from Figure 21,

designed by Brian Gage, in Meyer, S. C., Ross, M., Nelson, P., and Chien, P.
“The Cambrian Explosion: Biology’s Big Bang.” In Darwinism, Design andPublic Education, edited by John Angus Campbell and Stephen C. Meyer,
374. East Lansing, MI: Michigan State University Press, 2003. Courtesy of
Brian Gage.
Figure 10.4: Drawn by Ray Braun.
Figure 11.1: Drawing by Ray Braun and Casey Luskin based on informationfrom Kaessmann, H., “Origins, evolution, and phenotypic impact of new
genes,” Genome Research, 20 (2010): 1313–26; Long, M., Betrán, E.,
Thornton, K., and Wang W., “The Origin of New Genes: Glimpses from theYoung and Old,” Nature Reviews Genetics, 4 (November 2003): 865–75.
Figure 11.2: Drawn by Ray Braun based on information from Luskin, C.,“The NCSE, Judge Jones, and Citation Bluffs about the Origin of New
Functional Genetic Information,” Discovery.org (March 2, 2010),
http://www.discovery.org/a/14251.
Figure 12.1: Drawn by Ray Braun based on information from Figure 27, in
Frazzetta, T. H. Complex Adaptations in Evolving Populations, 148.
Sunderland, MA: Sinauer Associates, 1975.
Figure 12.2: Photograph of Michael Behe courtesy of Laszlo Bencze. Used
with permission.
Figure 12.3: Drawing by Ray Braun based on information from “Powerball—Prizes and Odds,” PowerBall,
http://www.powerball.com/powerball/pb_prizes.asp.
Figure 12.4: Drawn by Ray Braun based on information from Figure 6, Behe,
M. J., and Snoke, D. W., “Simulating evolution by gene duplication of proteinfeatures that require multiple amino acid residues,” Protein Science, 13(2004): 2651–64. Original image courtesy of John Wiley and Sons andProtein Science. Original image Copyright © 2004 The Protein Society. Used
with permission.
Figure 12.5: Photograph of Ann Gauger courtesy of Laszlo Bencze. Used
with permission.
Figure 12.6: Drawn by Ray Braun based on information from Figure 5A,
Gauger, A. K., and Axe, D. D. “The Evolutionary Accessibility of New
Enzyme Functions: A Case Study from the Biotin Pathway.” BIO-Complexity,
2011 (1): 1–17. Original image courtesy of Ann Gauger and Douglas Axe.
Figure 13.1a: Photograph of Christiane Nüsslein-Volhard courtesy of

User:Rama / Wikimedia Commons / CC BY-SA 2.0 FR. Used withpermission; usage not intended to imply endorsement by the author/licensor
of the work.
Figure 13.1b: Photograph of Eric Wieschaus courtesy of Matthias Kubisch /Wikimedia Commons / CC0 1.0. Public domain; usage not intended to imply
endorsement by the author/licensor of the work.
Figure 13.2: Drawing by Ray Braun and Paul Nelson based on informationfrom “Mutant Fruit Flies,” Exploratorium,
http://www.exploratorium.edu/exhibits/mutant_flies/mutant_flies.html.
Figure 13.3: Photograph of Paul Nelson courtesy of Paul Nelson. Used withpermission.
Figure 13.4a: Copyright 2008 National Academy of Sciences U.S.A. Figure
1D, Oliveri, P., Tu, Q., and Davidson, E. H., “Global Regulatory Logic forSpecification of an Embryonic Cell Lineage,” Proceedings of the National
Academy of Sciences USA, 105 (2008): 5955–62. Use of PNAS material does
not imply any endorsement by PNAS or the National Academy of Sciences orthe authors. Used with permission.
Figure 13.4b: Copyright 2008 National Academy of Sciences U.S.A. Figure
1E, Oliveri, P., Tu, Q., and Davidson, E. H., “Global Regulatory Logic forSpecification of an Embryonic Cell Lineage,” Proceedings of the National
Academy of Sciences USA, 105 (2008): 5955–62. Use of PNAS material does
not imply any endorsement by PNAS or the National Academy of Sciences orthe authors. Used with permission.
Figure 13.4c: Copyright 2008 National Academy of Sciences U.S.A. Figure 7,
Oliveri, P., Tu, Q., and Davidson, E. H., “Global Regulatory Logic forSpecification of an Embryonic Cell Lineage,” Proceedings of the National
Academy of Sciences USA, 105 (2008): 5955–62. Use of PNAS material does
not imply any endorsement by PNAS or the National Academy of Sciences orthe authors. Used with permission.
Figure 14.1: Photograph of Jonathan Wells courtesy of Laszlo Bencze. Used
with permission.
Figure 14.2: Diagram drawn by Ray Braun based on PowerPoint slides
developed by Michael Keas.
Figure 14.3a: Drawn by Joseph Condeelis. Copyright © Discovery Institute2013. Used with permission.
Figure 14.3b: Courtesy of The Company of Biologists. Source: Figure 1B

from Smyth, J. T., DeHaven, W. I., Bird, G. S., and Putney, J. W., “Role of the
microtubule cytoskeleton in the function of the store-operated Ca2+ channel
activator STIM1,” Journal of Cell Science, 120 (November 1, 2007): 3762–
71. Used with permission.
Figure 15.1: Photograph of Stuart Kauffman courtesy of User: Teemu Rajala/
Wikimedia Commons / CC BY 3.0. Used with permission; usage not intended
to imply endorsement by the author/licensor of the work.
Figure 15.2: Drawing of DPMs by Ray Braun based on information from
Table 1, Stuart A. Newman and Ramray Bhat, “Dynamical patterning
modules: physico-genetic determinants of morphological development andevolution,” Physical Biology, 5 (1): 1–14 (April 9, 2008); Figure 11.1, Stuart
A. Newman, “Dynamical Patterning Modules,” in Evolution: The Extended
Synthesis, 294, Massimo Pigliucci and Gerd B. Muller eds. (The MIT Press,
2010); Stuart A. Newman, “Physico-Genetic Determinants in the Evolution of
Development,” Science, 338 (October 12, 2012): 217–19.
Figure 16.1: Drawn by Ray Braun and Paul Nelson.
Figure 16.2: Copyright 2007 National Academy of Sciences, U.S.A. Figure 1,
Prud’homme, B., Gompel, N., and Carroll, S. B., “Emerging principles ofregulatory evolution,” Proceedings of the National Academy of Sciences(PNAS), USA, 104 (May 15, 2007): 8605–12. Use of PNAS material does not
imply any endorsement by PNAS or the National Academy of Sciences or theauthors. Used with permission.
Figure 16.3: Reprinted from Current Biology, 11, Starling, E. B., and Cohen,
S. M., “Limb development: Getting down to the ground state,” R1025–
R1027, Figure 1, Copyright 2001, with permission from Elsevier.
Figure 17.1: Photograph of Charles Thaxton courtesy of Charles Thaxton.
Used with permission.
Figure 17.2: Drawing by Ray Braun based on information from Grotzinger, J.,
Jordan, T. H., Press, F., Siever, R. Understanding Earth, 32–33, 5th ed., New
York: W. H. Freeman, 2007; Cox., A., and Hart, R. B. Plate Tectonics: How It
Works, 19, Cambridge, MA: Blackwell Science, 1986; Lowrie, W.
Fundamentals of Geophysics, 18–19, Cambridge, UK: Cambridge University
Press, 1997.
Figure 17.3: Drawing by Ray Braun based on information from Sober, E.,
Reconstructing the Past, 4–5. Cambridge, MA: MIT Press, 1988.
Figure 18.1: Photograph of Douglas Erwin courtesy of Robyn Wishna /UPHOTO/Cornell University. Used with permission.
Figure 18.2: Drawn by Ray Braun based on information from Figure 2:2,
Meyer, S. C., Minnich, S., Moneymaker, J., Nelson, P. A., and Seelke, R.
Explore Evolution: The Arguments for and Against Neo-Darwinism, 44.
Melbourne and London: Hill House, 2007.
Figure 18.3: Photograph of transistors courtesy of iStockphoto.com/ S230. ©
iStockphoto.com/ S230. Used with permission.
Figure 18.4: Diagram drawn by Ray Braun based on information from Figure
2, Nelson, P., and Wells, J., “Homology in Biology: Problem for Naturalistic
Science and Prospect for Intelligent Design.” In Darwinism, Design andPublic Education, 317, edited by John Angus Campbell and Stephen C.
Meyer, 303–322. East Lansing, MI: Michigan State University Press, 2003.
Figure 18.5: Diagram drawn by Ray Braun based on PowerPoint slides
developed by Michael Keas.
Figure 18.6: Diagram drawn by Ray Braun based on PowerPoint slides
developed by Michael Keas.
Figure 18.7: Diagram drawn by Ray Braun based on PowerPoint slides
developed by Michael Keas.
Figure 19.1: Photograph of Richard Sternberg courtesy of Laszlo Bencze.
Used with Permission.
Figure 19.2: Photograph of Moais courtesy of iStockphoto/Think-stock. Used
with permission.
Figure 20.1: Photograph of trilobite fossil at Burgess Shale courtesy of
Michael Melford / NATIONAL GEOGRAPHIC IMAGE COLLECTION /Getty Images. Used with permission.
Figure 20.2a: Photograph of Stephen C. Meyer and family copyright © 2013
Stephen C. Meyer.
Figure 20.2b: Photograph of mountainside near Burgess Shale copyright ©
2013 Stephen C. Meyer.

IndexThe pagination of this electronic edition does not match the edition fromwhich it was created. To locate a specific passage, please use your ebook
reader’s search tools.
Page references followed by fig indicate an illustration.
abductive inference: definition of, 343; inductive and deductive arguments,
343–44; plausibility of, 345. See also causal adequacy
Abegg, Adam, 327–28
Agassiz, Louis: belief in a creative intelligence by, 100; “Evolution and thePermanence of Type” by, 11; extensive fossil specimens collected by, 21;
German idealism and cosmic philosophy of, 18–19, 20; on incomplete fossil
record challenging Darwin’s theory by, 8fig–10, 17, 18–24fig, 69, 379, 381;
photograph of, 7fig
allopatric speciation process: allowing for rapid fixation of preexisting traits,
146–47; theory of punctuated equilibrium and, 139–42
Altenberg 16, 291–92, 293, 313
American Association for the Advancement of Science (AAAS), 385
amino-acid sequences: combinatorial inflation problem applied to proteins,
173–74fig, 181fig; forming polypeptide chain, 190fig; ratio of functional to
nonfunctional, 178–79; responses to Sauer’s experiment on, 180–84, 187–
89, 192–94; Sauer’s experiments on, 180–83, 187–89, 192–94; technologies
for calculating functional, 180–83. See also proteins“Anarchist’s Manifesto” (Nelson), 370
anatomical characteristics: analysis of animal life histories using, 125–32;“Coelomata” hypothesis based on analysis of, 122
animal development: dGRNs (developmental gene regulatory networks)
required for, 264–69, 285, 319–20, 363–66; epigenetic information required
to complete, 271–87; dynamical patterning modules (DPMs) role during,
301fig–2, 303–4; early-acting body-plan mutations and embryonic lethals,
259–64; Hox genes expressed after the beginning of, 319–20; ontogeny
studies on, 258–69; principle of constraints and, 268–69; self-organizationalmodels on, 293–310; three challenges to neo-Darwinism posed by, 262–64;

understanding the Cambrian explosion in context of engineering, 270. See
also body plans; embryos; genetic information; genetic mutations; organisms
animal life histories: analysis of anatomical characteristics of different, 125–
32; attempts to confirm evolutionary phylogenies, 121–25; conflicting
molecular data, 119–21; fundamental difficulties with phylogenetic
reconstruction of, 132–33; molecular homologies studies on, 121–25
animal phyla: chart showing representatives in the fossil record, 32fig; debate
over Vernanimalcula fossil as bilaterian ancestor, 89, 90, 91fig–96;
description of, 31; diagrams representing, 24fig; Ediacaran mini-explosion of
fauna and, 86–88; Metazoan, 104, 107, 126–27, 128fig; “morphologicalspace” between, 70–71; Precambrian-era, 81–92; rapid divergence ofspecifically genetic evidence, 121; representatives of major animal groups,
33fig; selection of incompatible phylogenetic trees representing, 131fig;
stasis or persistent morphological isolation evidence in Cambrian fossil
record, 375–78; statistical paleontology casting doubt on animal tree of life,
69–71; Vernanimalcula bilaterian shape, 89, 90, 91fig–96. See also bilaterian
phyla; Cambrian phyla (animal groups); intermediate animal life forms;
organisms; phylogenetic classification
animal tree of life: Cambrian explosion and, 12–13; comparing actual animal
phyla pattern to one using Darwin’s, 24fig; conflicting histories ofanatomical characteristics, 119–32; convergent evolution invoked for, 133–
34; Darwin’s argument on similar anatomical structure of distinct organisms,
99fig–101; Darwin’s evolutionary, 3–5, 41–42fig; examining possibility ofPrecambrian and Cambrian, 117–32; iconic image and representation of
Darwin’s, 114–17; lack of convergent evidence supporting, 135; statistical
paleontology analysis failure to support, 69–71. See also Cambrian phyla(animal groups); evolutionary biology; universal common ancestry
Anomalocaris fossils, 38–39fig, 53, 60, 62
Antennapedia mutant, 318–19fig
Archives of Natural History journal, 114
Aris-Brosou, Stéphane, 106
Arkarua fossil, 89fig, 90
arthropods: exoskeleton of, 60–61; onychophorans once proposed asancestors of, 60
Arthur, Wallace, 275, 312
artifact hypothesis: contemporary versions of, 57–62, 105; other versions ofthe, 56–57; statistical paleontology failure to support, 69–71; Walcott’sconception of, 46–47, 49, 52, 55, 56. See also Darwinian evolutionary
theory; Lipalian interval hypothesis; Walcott, Charles Doolittle
Asher, Robert, 392, 393, 394, 397, 398

At Home in the Universe: The Search for the Laws of Self-Organization andComplexity (Kauffman), 297–98
Atkins, Peter, 115
Atlantic Monthly, 11
ATP, 280
Axe, Douglas, 185, 186fig–89, 191–95, 196, 198–200, 202–8, 226, 229, 235,
250–51, 253, 254, 327–28
Ayala, Francisco, 107
Babcock, Loren, 83
Bateson, William, 18, 237
Behe, Michael, 184, 240, 241fig, 242–43, 244–49, 253
Bengtson, Stefan, 90–91, 92
Berlinski, David, 362
bilaterian phyla: Coelomata hypothesis on three classifications of, 122,
123fig, 124; Ecdysozoa hypothesis on three classifications of, 122–23fig,
124; Vernanimalcula as possible ancestor of, 89, 90, 91fig–96. See also
animal phyla
Biological Society of Washington, 384–85
Biological Theory (journal), 125
Birket-Smith, Sven Jorgen, 82
Blanco, Francisco, 197
blended inheritance theory, 156–57
The Blind Watchmaker (Dawkins), 176, 185–86
body plans: dGRNs (developmental gene regulatory networks) role in, 264–
69, 285, 319–20, 363–66; DNA epigenetic information required for animal
development and, 271–87; embryonic lethals and early-acting mutations,
259–64; Heidelberg screens experiments on Drosophila melanogaster (fruit
flies), 255–57; Kauffman on self-organizational process of, 295; neoDarwinian failure to explain generation of new genes and proteins for, 257;
self-organizational to explain origin of, 300–302. See also animal
development; genetic mutations
Bottjer, David J., 90, 91–92
bottom-up pattern: Burgess Shale’s top-down pattern contradicting Darwin’s,
39–44; Cambrian top-down pattern contradicting punctuated equilibrium’s,
142–44fig; Chengjiang fauna fossil top-down pattern contradicting Darwin’s,
74–76; neo-Darwinism’s, 144fig, 145–46, 371. See also top-down pattern
Bowring, Samuel, 73
Brachiopod internal anatomy fossil, 8fig, 10
brachiopods, 8, 10, 59–61

Bradley, Walter, 341
Brenner, Sidney, 187, 275–76
Britten, Roy, 265
Bromham, Lindell, 106
Budd, Graham, 85, 90–91, 96, 291
Burgess Shale Geoscience Foundation, 405
Burgess Shale site (Canada): Anomalocaris fossils of, 53, 60, 62; artifact
hypothesis used to explain, 46–47, 49, 52, 55, 56, 105; author’s hike withson up to, 404–8, 412–13; Cambrian explosion features challenging
Darwinism, 34–44; Cambrian period diversity preserved at, 44–46;
discovery of, 26, 27fig–28; Hallucigenia sparsa fossils of, 29, 30fig, 38, 53;
lumping classification approach to, 47–48, 55; Marrella splendens fossils of,29, 30fig, 38, 48, 53, 60, 62; Nectocaris fossils of, 53, 54fig; Opabinia
fossils of, 36, 37fig, 38, 52–53; seafloor fossils of, 54–56; soft-bodied
representatives found at, 61–62; top-down pattern evidenced at, 39–44;
trilobite fossil found at, 405fig; variety of fossils found at the, 28–34;
Whittington’s analysis of, 52–54fig; Wiwaxia fossils of, 53, 62. See also
Cambrian period fossils; fossil record; Walcott, Charles Doolittle
Caenorhabditis elegans, 258, 267
Cambrian explosion: Chengjiang fauna fossils from, 62–64, 65fig, 73–76;
Darwin’s growing anomaly and failure to explain, 8fig–10, 13–17, 18–24fig,
34–44, 50–52, 69, 71–76, 286–87; deep-divergence hypothesis explanation
for the, 100, 101–13; evidence redefining the narrow geological time of,
72fig–74; examining the deep-divergence hypothesis used to dispute, 100,
101–13; features of, 34–44; firestorm around Smithsonian’s NMNH journal
article on, 209–11; fossils establishing a “fuse” for, 78; how Axe’s
experiments bear on problems for neo-Darwinian explanations of, 205–7;
intelligent design applied to, 351–52, 353–81; Kauffman’s selforganizational proposal on, 299–300; neo-Darwinism’s failure to explain,257, 286–87; new genetic information arising during, 161–64; serious andimportant questions raised by the, 411–13; statistical paleontology on patternof, 69–71; theory of punctuated equilibrium attempt to provide explanationof, 137–52; the tree of life and, 12–13; understood in context of engineering
animal development, 270; Walcott’s Burgess Shale’s fossil record of, 31, 33–
34. See also Cambrian phyla (animal groups)
The Cambrian Explosion (Valentine and Erwin), 69
Cambrian explosion features: completely novel animal forms, 34, 38–39fig;
radical differences before more minor, small-scale diversification, 34, 39–44;
sudden appearance and missing intermediates, 34–38

Cambrian explosion mystery: as acknowledged by Darwin, 23; as noted by
Agassiz, 17, 24; as made more acute by Burgess fauna, 34–44; as made moreacute by Chinese fossils, 62–69, 74–76; Cambrian information explosion
providing evidence on, 161–64, 358–63; considering intelligent design as
solution to, 378–81; dGRNs (developmental gene regulatory networks) rolein solving the, 363–66; distinctive features of design evidence in, 380fig;
examining evidence of design, 351–52; looking for evidence of design in thefossil record, 371–78; organismal and informational context considered inthe, 366–71; profile of the suspect in, 354–56; profiling a cause of the, 356–
58; stasis or persistent morphological isolation evidence, 375–78; top-down
pattern of fossil evidence, 39–44, 74–76, 142–44fig, 371–73, 374fig, 375
The Cambrian Fossils of Chengjiang, China (Hou), 63
Cambrian information explosion, 161–64, 358–63
Cambrian period fossils: Agassiz’s challenge to Darwin using record of, 8fig–
10, 17, 18–24fig, 69; Chengjiang discoveries (China), 62–64,
Cambrian period fossils (continued) 65fig, 71–76; Darwin’s Cambrian
dilemma display (Sam Noble Science Museum) on, 96–97; Darwin’s
Dilemma documentary challenging Darwin’s theory based on, 77–79;
Darwin’s explanation for discontinuity of, 6, 17–18, 23–24; Darwin’s theory
challenged by evidence of, 6–17; discontinuity evidence found in Wales, 13–14; examining the deep-divergence hypothesis to explain discontinuity of,100, 101–13; looking for evidence of design in the, 371–78; punctuatedequilibrium’s bottom-down pattern contradicted by top-down pattern of,
142–44fig; stasis or persistent morphological isolation evidence in, 375–78;
top-down pattern of, 39–44, 74–76, 142–44fig, 371–73, 374fig, 375. See also
Burgess Shale site (Canada); fossil record
Cambrian phyla (animal groups): Brachiopod internal anatomy fossil, 8fig,
10; chart showing representatives of, 32fig; diagrams representing, 24fig;
Ediacaran Hills exotic fossils as possible ancestors to, 88–92; examining thepossibility of tree of, 117–32; fossil record showing soft and hard body parts,
57–62, 105; how Axe’s experiments bear on problems for neo-Darwinian
explanations of, 205–7; “morphological space” between, 70–71;
representatives of, 33fig; soft-bodied representatives, 59–60, 105; statistical
paleontology casting doubt on Darwin’s tree of life, 69–71; Trilobite
anatomy fossil, 9fig, 10. See also animal phyla; animal tree of life; Cambrian
explosion
Cambrian radiation duration, 88
Cambrian strata: Agassiz’s challenge to Darwin using lack of fossil evidence,
8fig–10, 17, 18–24fig, 69; Darwin’s explanation for discontinuity evidencein, 6, 17–18, 23–24; discontinuity evidence found in Wales, 13–14;

geological time of Cambrian explosion evidenced in, 72fig–74; radiometricdating of zircon crystals in Siberia, 71–72fig
Carroll, Sean B., 84, 120, 121, 312, 314, 317, 368
causal adequacy: criteria of, 348; only known cause issue of, 349–51;
problem of retrodiction in testing, 349, 350fig; Signature in the Cell
proposed explanations for biological information, 359–60; vera causa (truecause) principle of, 216–17, 309–10. See also abductive inference
CD-ROM technology, 378
cell differentiation: description of, 258–59; epigenetic information role in,
276–77; self-organization models on, 294–95, 297–99; theory gene
regulation for higher cells for, 265–68
cells: biological complexity scale as measure in different organism, 162fig;
cytoskeletons of eukaryotic, 277–79; daughter, 258, 278; dGRNs(developmental gene regulatory networks) influencing development of, 264–
69, 285, 319–20, 363–66; DNA minimally required for complex singlecelled organisms, 163; epigenetic information in patterns of proteins in cell
membranes, 279–81, 305; epigenesis germ-cell mode, 129fig, 130fig;
primordial germ cells (PGCs), 127, 129fig; studies on ontogeny process of,
258–59; theory of gene regulation for higher cells, 265–68
Chamberlain, Thomas, 346
change hypothesis, 201–2
Charlesworth, Brian, 149
Charnia fossil, 80fig, 81, 82, 88
Chen, J. Y., 50, 51fig, 52, 59, 61, 63, 66, 67, 72, 76, 406
Chengjiang discoveries (China): Cambrian conundrum of the, 71–74;
Cambrian explosion fossils from fauna of, 62–64, 65fig, 73–76; story of the
discovery, 50–52; top-down pattern observed at, 74–76
Chesterton, G. K., 382, 385
Cheungkongella ancestralis, 75
Chien, Paul, 64, 66–67, 88, 406
chloroquine complexity cluster (CCC), 247–48
choanoflagellates, 161–62
Christian theology, 410–13
Chronicle of Higher Education, 210
cis-regulatory elements (CREs), 316, 317
Coelomata hypothesis, 122, 123fig, 124
Collins, Francis, 410, 411, 412
combinatorial inflation problem, 173–74fig, 181fig
combinatorics: used to calculate DNA mutations, 172–83; description of, 172;
looking for the functional sequences solution, 178–79; problem ofcombinatorial inflation, 173–74fig, 181fig
competition for survival, 10–11
Complex Adaptations in Evolving Populations (Frazzetta), 232
Comte, August, 19–20
conditional probability, 201
convergent evolution, 133–34
Conway Morris, Simon, 75, 113, 291, 357
Cooper, Alan, 84
co-option model of protein evolution, 249–54
coordinated mutations: chloroquine complexity cluster (CCC), 247–49;
complex adaptations explained by, 237–41; co-option model of protein
evolution, 249–54
Coyne, Jerry, 100, 115, 116, 124, 317“creationist” label, 401
creative intelligence, 100
Crick, Francis, 159, 160fig, 166, 168, 187, 236, 339, 385, 400
Current Biology, 291
Cuvier, Georges, 19cytoskeletons, 277–79
Darwin, Charles: countering Paley’s watch-to-watchmaker design argument,
37–38; explanation for discontinuity found in fossil record, 6, 17–18, 23–
24, 379, 381; Galápagos Islands trip by, 21; growing anomaly and failure
to explain Cambrian explosion, 8fig–10, 13–17, 18–24fig, 34–44, 50–52,
69, 71–76, 286–87; Lyell’s influence on, 348–49; on natural selection
requiring favorable variations, 264; photograph of, 7fig; ten children of,118; uniformitarian method used by, 391–92, 393. See also On the Origin
of Species (Darwin)
Darwin, Emma, 118
Darwin and Modern Science (Bateson), 237“Darwinian Alchemy: Human Genes from Noncoding RNA” (Genome
Research), 220
Darwinian evolutionary theory: Agassiz’s challenge to the, 8fig–10, 13–17,
18–24fig, 69, 379, 381; apparent design suggested by, 338–40; Burgess
Shale’s Cambrian explosion features challenging the, 34–44; China’s
Chengjiang fossils challenging the, 50–52, 71–76; comparing neoDarwinism with, 104; comparing punctuated equilibrium’s tree of life withtraditional one of, 141fig; Darwin’s Dilemma documentary challenging, 77–
78, 96; Darwin’s explanation for discontinuity issue of, 6, 17–18, 23–24, 99;
discontinuity of fossil record challenge to, 8fig–10, 13–17, 18–24fig, 69,

101, 379, 381; growing anomaly and failure to explain Cambrian explosion,
8fig–10, 13–17, 18–24fig, 34–44, 50–52, 69, 71–76, 286–87; introducing
natural selection idea of, 3, 5–6, 10–11; introducing universal common
ancestry idea of, 3–5, 12–13, 36fig, 41–42fig; Lamarckian mechanisms rolein, 329–30; theory of blended inheritance favored by, 155–57; Whittington’sanalysis challenging Walcott’s solution for, 52–54. See also artifact
hypothesis; evolutionary biology; neo-Darwinism
Darwin’s Cambrian dilemma display (Sam Noble Science Museum), 96–97
Darwin’s Dilemma (documentary film), 77–79, 96
daughter cells, 258, 278
Davidson, Eric, 57, 265, 267, 269, 270, 319–20, 355, 357, 363–64
Dawkins, Richard, 40–41, 98, 115, 117, 124, 148, 176, 185–86, 207, 339,
358–59, 361, 392, 409, 411
Dawkins’ Shakespearean “Methinks it is like a weasel” phrase experiment,
185–86
deductive argument, 343–44
deep-divergence hypothesis: common descent of all animal forms assumptionof, 110–11; description of the, 100, 101; fossil record bringing reasonable
doubt to, 105; gene sequencing studies bringing reasonable doubt to, 105–8;
molecular clock analysis used in, 102fig–3, 121; questionable assumptionsof, 109–10; “shmoo-like” catch–22 of the, 111–13; Wray study (1990s)
argument for, 103–4
degree of difference: deep-divergence explanation on missing fossils, 100,
101; description and assumptions about, 100; Wray study (1990s) on the,103–4. See also universal common ancestry
demarcation: arguments against intelligent design using, 389–90; criteria of,
386–87; general problem of, 387–89“The Demise of the Demarcation Problem” (Laudan), 388
de novo origination, 213fig, 217, 219–21
Denton, Michael, 178, 179, 180
design: CD-ROM technology, 378; distinctive hallmarks of, 380fig; looking
for evidence of Cambrian explosion, 351–52, 371–78. See also intelligent
designdevelopmental genetic toolkit, 300–305
Devonian period fossils, 14
dGRNs (developmental gene regulatory networks): as Cambrian explosion
evidence, 363–66; Davidson’s findings on principle of constraints inbuilding, 268; as dependent on preexisting cell structures, 825; difficulty toalter without damaging regulation ability, 319–20; principle of constraints
for engineering new, 268–69; research being conducted on, 264–68;

Strongylocentrotus purpuratus (purple sea urchin), 266fig, 267–68
Dickinsonia fossil, 80fig, 81, 82, 83, 86, 88
Dill, Ken, 183
discontinuity of fossil record: Agassiz’s challenge to Darwin’s theory using,
8fig–10, 13–17, 18–24fig, 69, 379, 381; of Cambrian period fossils in Wales,
13–14; Darwin’s explanation for, 6, 17–18, 23–24, 99; deep-divergence
hypothesis to explain, 101. See also fossil record
Discovery Institute, 50
Distal-less Hox gene), 321
DNA: Axe’s experiments on protein natural selection and, 187–200, 202–8;
Cambrian explosion of new genetic information, 161–64; combinatorics
used to calculate mutations in, 172–83; complexity characterizing
information in, 306–9; Crick’s sequence hypothesis on, 159, 169, 177; denovo origin of new genes in Drosophila melanogaster from noncoding, 220–
21; double helix structure of, 159; ENCODE project study of genome and,
400–402; functional information contained in, 164, 168, 178–84, 187–200,
202–8, 274–75; information and genetic variations of, 159–61fig; junk, 402;
mechanisms for generating gene duplicates in, 198–200; minimally requiredfor complex single-celled organisms, 163; model showing nucleotide bases
along sugar-phosphate molecule, 161fig; natural genetic engineering
understanding of, 332–35; neo-Lamarckian theory on, 330–32; organismal
form and function determined by, 274–75; Shannon information containedin, 164–68, 274, 275. See also epigenetic information; gene sequences; genesequencing; genetic mutations
Doushantuo Phosphorite formation (Maotianshan Shale), 64, 66–68, 90
Dover, Kitzmiller v., 211, 221
Drosophila melanogaster (fruit flies): base pairs of the, 163; de novo origin ofgenes from noncoding DNA, 220–21; epigenetic information role in embryo
development in, 279–80; examples of deleterious macromutations of, 260,
261fig; germ-cell formation in, 129fig; Heidelberg screens experiment on,
255–57; Hox genes causing fatal mutations in, 318–19; “morphogens”
influencing embryological development in, 260–61; ontogeny studies using
model system of, 258; study of a gene that codes for histone protein in, 222;
Ultrabithorax gene in, 261–62. See also morphological change
Drosophila simulans, 222
Dupree, A. Hunter, 19
Durrett, Rick, 249, 253
dynamical patterning modules (DPMs), 301fig–2, 303–4
Easter Island “Moais,” 396fig

Ecdysozoa hypothesis, 122–23fig, 124
Eden, Murray, 169–70fig, 171, 175, 176, 177, 178, 179, 183, 186
The Edge of Evolution (Behe), 242, 247, 249
Ediacaran Hills site (Australia): debate over Vernanimalcula fossil of, 89, 90,
91fig–96; Ediacaran fauna and Vendian radiation, 79–81; evidence of miniexplosion of organisms, 78, 86–88; exotic fossils as plausible ancestors to
Cambrian animal forms, 88–92; significance of findings of, 81–86; trace
fossils of, 81, 85–86
Ediacaran period, 79
Ehrlich, Paul, 234
Eldonia fossils, 64
Eldredge, Niles, 293, 314; photograph of, 137fig; theory of punctuatedequilibrium contributions by, 136–52
Elsberry, Wesley R., 210–11, 221embryos: Chengjiang embryo sponge fossils, 66–68, 67fig; dGRNs(developmental gene regulatory networks) role in development of, 264–69,
285, 319–20, 363–66; early-acting body-plan mutations in, 259–64;
epigenetic information role in development of, 279–80; how microtubules
influence development of, 277–79; Kauffman on genes generating“pathways of differentiation” in, 294–95; role of genes and proteins indevelopment of, 258–59; studies indicating the DNA is required to complete
development of, 271–72. See also animal development
ENCODE project, 400–402
epigenesis germ-cell mode, 129fig, 130fig
epigenetic information: cell differentiation role of, 276–77; challenge posed toneo-Darwinism by, 281–82; chemically blocking transcription of DNA into
RNA, 271; cytoskeleton, 277–79; description and function of, 275–77; earlyexperiments revealing, 271–72; hierarchical organization of, 364–66; issues
to consider for inheritance of, 286; making the case against “gene-centric”
using, 282–84; mutations of, 285–86; order vs. complexity of, 305–9;
Origination of Organismal Form essays on, 272–73; in patterns of proteinsin cell membranes, 279–81, 305; self-organization models on, 295–97; sugar
molecule, 280–81, 282–83. See also DNA; genetic information; information
Erwin, Douglas, 41, 69, 73, 81, 83–84, 104, 106, 107, 109, 110, 124, 143–44,
151, 292, 319, 354–55fig, 356, 357
ethyl methane sulphonate (EMS), 255
eukaryotic organisms: choanoflagellates, 161–62; cytoskeletons of, 277–79;
spliceosomes of, 323–24; transposons (“jumping genes”) of, 219“Evidence for a Clade of Nematodes, Arthropods and Other Moulting
Animals” (Nature journal), 122–23

evo-devo theory, 314–15, 316
Evolution and Belief (Asher), 392“Evolution and the Permanence of Type” (Agassiz), 11
evolutionary biology: Altenberg 16 exploring the future of, 291–92, 293, 313;
Darwin’s argument on similar anatomical structure of distinct organisms,
99fig–101; degree of difference concept of, 100, 101; evo-devo theory of,
314–15, 316; forensic nature of, 98–99; homology concept of, 100; how newmodels deviate from neo-Darwinism, 313fig–35; impasse reached bymodern, 337; natural genetic engineering, 332–35; neo-Lamarckism, 329–
32; neutral or nonadaptive evolutionary theory, 321–29; “phylogeneticallyinformative” data chosen or cherry picked by, 108; self-organizational
theories, 293–310; sequencing DNA to reconstruct evolutionary
relationships of species, 100–101; theory of punctuated equilibrium of, 137–
52. See also animal tree of life; Darwinian evolutionary theory; neoDarwinism; science
Evolution journal, 317
exon shuffling, 213fig, 217, 218, 219, 223–27
Explore Evolution, 315–17
Extavour, Cassandra, 129
fauna: Chengjiang evidence of Cambrian explosion, 62–64, 65fig, 71–76;
Ediacaran Hills site of Precambrian, 79–81, 80fig–86; Ediacaran miniexplosion of organisms and, 78, 86–88; top-down pattern of Chengjiang,
74–76
Fedonkin, Mikhail, 81
Fersht, Alan, 187, 192
Fisher, R. A., 260
Foote, Michael, 69–70, 145, 146
Fortey, Richard, 84
fossil record: chart showing when representatives of animal phyla appear in,
32fig; deep-divergence explanation for fossils missing from, 100, 101; deepdivergence hypothesis challenged by gene sequencing and, 105–13;
Ediacaran Hills site (Australia), 78–92; geological timescale, 15, 16fig; Hox
genes in the, 318; Ordovician period, 14fig; Paleozoic period, 14; theory ofpunctuated equilibrium (“punk eek”) problem with, 142–45; Triassic period,
14. See also Burgess Shale site (Canada); Cambrian period fossils;
discontinuity of fossil record; Precambrian-Cambrian fossil record
fossil succession phenomenon, 15–17
Franklin, Harold, 275
Frazzetta, Tom, 230–31, 232–33, 234, 235, 237

fruit flies. See Drosophila melanogasterfunctional information: amino-acid sequences ratio of nonfunctional to, 178–
79; Axe’s experiments on protein natural selection and, 187–200, 202–8;
description of, 164, 168; DNA inclusion of, 274–75; genes under selection
pressure and, 197fig; Sauer’s experiments on amino-acid sequence, 180–84,
187–89, 192–94; technologies to calculate, 180–83. See also genesequences; genetic information; information
Fuxianhuia protensa arthropods, 60
Gabius, Hans-Joachim, 281
Galápagos Islands, 21
Gates, Bill, 359
Gauger, Ann, 226, 250fig–51, 253
Gegenbauer, Carl, 21
gene duplication, 213fig, 217, 218, 219
gene expression: Hox genes coordination in, 285, 287, 314–15, 314–21; TFs(transcription factors) role in, 258–59; theory of gene regulation for higher
cells, 265–68; TRs (transcriptional regulators) role in, 258–59
gene fission/fusion, 213fig, 217, 219
genes: animal development and role of proteins and, 258–59; dGRNs(developmental gene regulatory networks), 264–69, 285, 319–20, 363–66;
different structures when used in different animals, 367fig; homeotic (Hox),
285, 287, 314–15; Long’s inferred common ancestral, 214–15; mutational
mechanisms of, 213fig, 216–19; neo-Darwinian failure to explain generationof new, 257; ORFans, 215–16; organismal and informational context
consideration of, 363–71
gene sequences: Axe’s experiments on protein natural selection and, 187–200,
202–8; combinatorics to calculate possible mutations, 172–83; depiction of
how gene duplication and subsequent gene evolution may occur, 214fig;
importance of protein folds in, 189–92; Long’s inferred common ancestral,
214–15; mechanisms for DNA generating duplicate, 198–200; problem ofcombinatorial inflation, 173–74fig, 181fig; “purifying selection” of, 195;
under selection pressure, 197fig. See also DNA; functional information
gene sequencing: deep-divergence hypothesis challenged by fossil record and,
105–13; deep-divergence hypothesis examined by, 100, 101, 103–4;
molecular clock analysis of, 102fig–3, 121; questionable assumptions of,
109–10. See also DNA
genetic information: arguments against a “gene-centric” view of, 282–84;
connecting process control and regulation over, 186–87; depiction of how
gene duplication and subsequent gene evolution may occur, 214fig; difficulty

of explaining the origin of complex adaptations to, 237–39; errors inhypothetical scenarios for origins or mutations of, 211–14; exon shuffling
hypothesis on creating, 213fig, 217, 218, 219, 223–27; hierarchicalorganization of, 364–66; mutational mechanisms assuming preexisting,
213fig, 216–27; population genetics and the origin of, 235–37; scientificdebate over origins of new, 209–11; self-organization models on, 297–99;“word salad” explanations for, 227–29. See also animal development;
epigenetic information; functional information
genetic mutations: Antennapedia, 318–19fig; argument that new proteinsrequire multiple improbable, 244–47; attempt to reconcile Darwinian theory
with Mendelian genetics, 158–59; Axe’s experiments on protein natural
selection and, 187–200, 202–8; cis-regulatory elements (CREs) theory of,
316–17; combinatorics used to calculate, 172–83; co-option model of protein
evolution, 249–54; coordinated chloroquine complexity cluster (CCC), 247–
49; difficulty of explaining the origin of complex adaptations, 237–39; DNA
genetic variation and, 159–61; embryonic lethals and early-acting body-plan,
259–64; epigenetic information, 285–86; exploring the process of, 169–70;
the “great Darwinian paradox” of, 262, 315, 317; Hox genes considered in,
317–21; insect wing coloration, 316fig, 317; looking for the functionalsequences solution, 178–79; multiple coordinated mutations required forcomplex adaptations, 240–41; mutational mechanisms of gene, 213fig, 216–
21; population genetics models to explain, 233–44fig; responses to Sauer’s
experiments on amino-acid sequences, 180–84, 187–89, 192–94; “sweetspot” for, 246fig; various types due to different mechanisms, 213fig;“waiting times” for, 240–42, 327–29; Wistar Institute conference (1966) on
mechanisms of, 170–77, 187; “word salad” explanations for, 227–29; X-rayinduced, 157–58. See also animal development; body plans; DNA; natural
selection; traits
Genome Biology journal, 400
Genome Research journal, 220, 400
genomes: ENCODE project study of, 400–402; Heidelberg screensexperiments of, 255–57fig; transposons (“jumping genes”) of
eukaryotic, 219
geologic timescale, 15, 16fig
Gerhart, John, 292
germ-cell formation modes: epigenesis, 129fig, 130fig; overview of, 127, 129;
preformation, 129fig, 130fig
Gettysburg Address (Lincoln), 368–69fig, 370
Gilbert, Scott, 287, 314
Gillespie, Neal, 21

Gishlick, Alan, 210–11, 221
Glaessner, Martin, 82–83
The God Delusion (Dawkins), 409, 411
God Is Not Great (Hitchens), 409“God of the Gaps” objection, 392
Goldschmidt, Richard, 311
Gompel, Nicolas, 317
Goodwin, Brian, 275
Gould, Stephen Jay, 15–16, 28–29, 39, 48, 54, 57, 231, 293, 311, 312, 314,
344, 368; photograph of, 137fig; theory of punctuated equilibrium
contributions by, 136–52
Graur, Dan, 107
Gray, Asa, 18“great Darwinian paradox,” 262, 315, 317
Gross, Paul, 211
Haeckel, Ernst, 4, 18
Haikouella lanceolata, 74
Haikouichthys ercaicunensis, 75fig
Hallucigenia sparsa fossils, 29, 30fig, 38, 53
Harvey, Ethel, 271
Hedges, S. Blair, 106
Heidelberg screens experiments, 255–57fig
Hennig, Willi, 44
heritability of variations, 10
histones, 107–8
Hitchens, Christopher, 409
Hoekstra, Hopi, 317
Holland, Peter, 132
Holm, Richard, 234
Hood, Leroy, 359
Hooker, Joseph, 18
Hou, Xian-Guang, 62–63
Hox genes: considering mutation role of, 317–21; Distal-less, 321; evo-devo
theorists on, 314–15; in the fossil record, 318; possible harmful effects of,
318–19; regulatory function of, 285, 287, 318
Huxley, Julian, 158–59
Huxley, T. H., 18, 158hydrophobic core, 192
Hyman, Libbie, 122hypotheses: abductive inference basis for developing, 343–45; method ofmultiple competing, 346–49; problem of retrodiction in testing, 349, 350fig.
See also specific hypothesis; vera causa (true cause) principle
inductive argument, 343, 344
information: hierarchical layering or arrangement of, 276fig; self-organization
issue of order vs., 305–9; Shannon information theory, 164–68, 274. See also
epigenetic information; functional information
insect wing coloration mutations, 316fig, 317
intelligent design: abductive inference arguments for, 344–45; applied toCambrian explosion, 351–52, 353–81; theological implications of, 410–13;
author’s story on examining, 340–43; commonalities with neo-Darwinism,
392; Cambrian explosion mystery solution, 378–81; attempt to define as
unscientific by AAAS, 385; demarcation arguments against, 389–90;
distinctive features of Cambrian explosion design evidence for, 380fig; earlyarguments supporting, 338–40; firestorm around Smithsonian’s NMNH
journal article on, 209–11; introducing, 337–40; New Atheists attacks
against, 409–10, 412; answers to new objections to scientific status of, 392–
98; reasons to regard as scientific theory, 391–92; arbitrary “rules ofscience” over seeking truth of, 398–400; Sternberg case controversy over,
384–85; what is at stake for honest consideration of, 404–13. See also designintermediate animal life forms: lack of Cambrian explosion evidence for, 34–
38; “morphological space” between, 70–71; statistical paleontology failingto find evidence of, 69–71; Wray study (1990s) explanation for missing,
103–4. See also animal phyla; universal common ancestry“Interpreting Great Developmental Experiments: The Fossil Record” (Erwin
and Valentine), 143“The Invisible Man” (Chesterton), 382–83
Jablonka, Eva, 330, 331–32
Jablonski, David, 83–84, 106, 107, 109, 110, 124James, William, 20–21
Jensen, Sören, 85, 96
John, Bernard, 259
Jones, Judge John E., 211
Journal of Molecular Biology, 209
Jukes, Thomas, 173
junk DNA, 402
Kauffman, Stuart, 293–300, 305, 309, 310
Kendrew, John, 187

Kimberella mollusk, 81, 82, 86
King, Jack, 173
Kirschner, Marc, 292
Kitzmiller v. Dover, 211, 221
Knoll, Andrew, 84, 104
Kumar, Sudhir, 106
Küppers, Bernd-Olaf, 361
Kuziora, Michael, 318
Laboratory for Molecular Biology (LMB), 187
Lamarckism, mechanisms of, 329–30
Lande, Russell, 149
The Language of God (Collins), 410, 411
lateral gene transfer, 213fig, 217, 218, 219
Laudan, Larry, 388
Leibniz, Gottfried Wilhelm, 387
Levinton, Jeffrey S., 57, 103, 148–49
Lewin, Roger, 41
Lewontin, Richard, 171, 339, 386
LexA (DNA-binding protein), 333
Li, Wen-Hsiung, 240–41
Lincoln, Abraham, 368–69fig, 370
Lipalian interval hypothesis, 46. See also artifact hypothesis
Lipton, Peter, 348
Long, Manyuan, 211, 214, 216, 220, 221–23, 226
Longfellow, Henry Wadsworth, 18
lumping classification approach, 47–48, 55
Lurie, Edward, 18, 19, 21, 22
Lyell, Charles, 348–49, 392
Lynch, Michael, 321–29
macromutations: description of, 11; Goldschmidt’s argument for, 311;
Gould’s argument for, 311, 312; neo-Darwinist rejection of, 312
magnetic seafloor stripe pattern explanation, 346–48
Maley, Laura, 124Mangold, Hilda, 271, 273, 275
Maotianshan Shale site (China): Cambrian explosion fossils from fauna of,
62–64, 65fig, 73–76; discovery of the, 50–52; Doushantuo Phosphorite
formation of, 64, 66–68, 90; top-down pattern observed at, 74–75
Maresca, Bruno, 125
Marrella splendens fossils, 29, 30fig, 38, 48, 53, 60, 62

Marshall, Charles R., 57–58, 124
Martin, William, 107
materialistic causes, 394“Mathematical Challenges to the Neo-Darwinian Interpretation of Evolution”
conference (1966), 170–77, 187
Matzke, Nicholas, 210–11, 221
Maynard Smith, John, 237–39, 240
Mayr, Ernst, 171, 339
McDiarmid, Roy, 384
McDonald, John F., 262, 315
McGinnis, William, 318
McMenamin, Dianna, 68
McMenamin, Mark, 68, 83
McNiven, Mark, 284
Medawar, Sir Peter, 171
Mendel, Gregor, 156–57, 236
Mendelian genetics, 156–59“A Merciful Death for the ‘Earliest Bilaterian,’ Vernanimalcula” (Bengtson
and colleagues), 91–92
Metazoan canonical tree, 126–27, 128fig
Metazoan phyla, 104, 107
method of multiple working hypotheses, 346–49
methodological naturalism, 19–20, 384–86
Meyer, Jamie, 404–8, 406fig, 412–13
Meyer, Stephen C.: anti-uniformitarianism of, 393; hiking up to Burgess
Shale, 404–8, 412–13; his story on examining intelligent design, 340–43;
photograph with son, 406fig; Signature in the Cell by, 359–60, 389, 391,
392, 402“Meyer’s Hopeless Monster” (Gishlick, Matzke, and Elsberry), 210–11
microtubule associated proteins (MAPs), 282–84
microtubules, 277–79
Miklos, George, 259, 287
Miller, Kenneth, 211, 221
Molecular Biology and Evolution journal, 109
molecular clock analysis, 102fig–3, 121“Molecular Evidence for Deep Precambrian Divergences Among Metazoan
Phyla” (Wary, Levinton, and Shapiro), 103–4
Molecular Evolution (Li), 240–41
molecular homologies studies, 121–25
Moran, Laurence A., 401

Morgan, T. H., 259–60
morphological change: Cambrian fossil record showing persistentmorphological isolation, 375–78; Darwin’s theory of descent with, 99–100;
Explore Evolution textbook discussion of, 315–16; “morphogens” molecules
critical for, 260–61; neo-Darwinian evolutionary estimates on, 87–88;
pentadactyl limb five-digit pattern example of, 99fig; statistical paleontology
failure to fill missing “space” of, 70. See also Drosophila melanogaster(fruit flies)
morphological space, statistical paleontology failure to fill, 70
Müller, Gerd, 272
Muller, Hermann, 157–58
Murchison, Roderick Impey, 13
mutations. See genetic mutations
The Mystery of Life’s Origin (Thaxton, Olsen, and Bradley), 341
National Center for Science Education (NCSE), 315–17
National Museum of Natural History (NMNH) [Smithsonian Institution],
209–11, 384
natural genetic engineering, 332–35“natural magic,” 309–10
natural selection: Axe’s conclusion that protein folds are preserved by, 199–
200, 202–8; Axe’s experiments on protein mutation and, 187–200, 202–8;
Cambrian fossil evidence challenging idea of, 8fig–10, 18–24fig; Darwin on
favorable variations required for, 264; Darwin’s theory of evolution on, 3;
Dawkins’ Shakespearean “Methinks it is like a weasel” phrase experimenton, 185–86; description of process of, 5–6; DNA genetic variation and, 159–
61fig; three discrete elements driving, 10–11; as understood by neoDarwinism, 194. See also genetic mutations
Nature journal, 122, 125, 210, 400, 402–3
Nature Reviews Genetics, 211, 239
Nectocaris fossils, 53, 54fig
Nelson, Paul, 262–63fig, 317, 368–70
neo-Darwinism: apparent design arguments offered by, 338–39; artifact
hypothesis of, 46–47, 49, 52, 55–62, 69–71, 105; bottom-up pattern of,
144fig, 145–46, 371; challenged posed by epigenetic information for, 281–
82; combinatorics used to calculate DNA mutations, 172–73; commonalities
of intelligent design and, 392; comparing orthodox Darwinian point of view
with, 104; co-option model of protein evolution, 249–54; estimates onmorphological change by, 87–88; examining the deep-divergence hypothesisof, 100, 101–13; failure to explain Cambrian explosion by, 257, 286–87;

focus on mathematical modeling by, 230–35; how Axe’s experiments onproteins are problematic for, 187–200, 202–8; how new evolutionary models
deviate from tenets of, 313fig, 314–35; macromutations rejected by, 312;
“Mathematical Challenges to the Neo-Darwinian Interpretation of
Evolution” conference (1996) on, 170–77; natural selection as understoodby, 194; problem of anatomical peculiarities for, 230–33; punctuatedequilibrium’s bottom-up pattern similar to, 144fig; responses to Sauer’s
experiment, 180–84, 187–89, 192–94; as synthesis of Mendelian genetics
with Darwinian theory, 158–59; theory of punctuated equilibrium (“punkeek”), 137–52; three challenges posed by animal development to, 262–64;
three core claims or pillars of, 292–93; Wells’ argument against animal bodyplans being adequately explained by, 273–74. See also Darwinianevolutionary theory; evolutionary biology; New Synthesis; “The Origin of
New Genes: Glimpses from the Young and Old” (Long and colleagues)
neo-Darwinism math: population genetics models of, 233–54; to solve
problem of anatomical peculiarities, 230–33
neo-Lamarckism, 329–32
Neoproterozic era, 110
neutral or nonadaptive evolutionary theory: critique of, 323–26; overview of,
321–23; on waiting times, 327–29“New Atheism,” 409–10, 412
Newman, Stuart, 272, 275, 300–305
New Scientist journal, 119, 120
New Synthesis, 158–59. See also neo-Darwinism
Newton, Isaac, 387–88
New York Review of Books, 385–86
Nijhout, Fred, 275
Nikoh Naruo, 106
Nüsslein-Volhard, Christiane, 255–56, 257fig, 260, 270, 315
Ohno, Susumu, 191
Olsen, Roger, 341
only known cause, 349–51
On the Origin of Species (Darwin): Agassiz’s challenge using the fossil
record, 8fig–10, 17, 18–24fig, 69; Centennial celebration of publishing, 158–
59; criticism regarding accurate tree of life goal of, 120; apparent design inliving organisms argument in, 338; expressing concerns over Cambrianperiod in, 7; growing anomaly of arguments set forth in, 286–87; on
Lamarckian mechanisms, 330; “The Mutual Affinities of Organic Beings”
on similar anatomical structures of distinct organisms, 99fig–100; natural

selection introduced in, 3, 5–6; uniformitarian principles used in, 391–92,
393; universal common ancestry introduced in, 3–5; vera causa (true cause)
criterion arguments made by, 216–17. See also Darwin, Charles
ontogeny studies: on dGRNs (developmental gene regulatory networks), 264–
69, 285, 319–20, 363–66; on early-acting body-plan mutations andembryonic lethals, 259–64; on principle of constraints, 268–69; on role ofgenes and proteins in animal development, 258–59
onychophorans (velvet worms), 60
Opabinia fossil, 36, 37fig, 38, 52–53
Opitz, John, 287
Ordivician period fossils, 14fig
The O’Reilly Factor (TV news show), 210
ORFan genes, 215–16
organismal form and function, 274–75
organisms: biological complexity scale as measure in cell types of different,
162fig; Cambrian explosion fossils of, 78; Cambrian explosion of DNA
information and new, 161–64; Darwin’s argument on similar anatomical
structure of distinct, 99fig–101; DNA information required for form andfunction of, 274–75; Ediacaran mini-explosion of, 78, 86–88; estimated
DNA required for minimally complex single-celled, 163; eukaryotic, 161–
62, 219, 277–79, 323–24; ontogeny studies on development of embryos into
mature, 258–69. See also animal development; animal phyla
Origination of Organismal Form: Beyond the Gene in Developmental and
Evolutionary Biology (Müller and Newman), 272–73“The Origin of New Genes: Glimpses from the Young and Old” (Long andcolleagues): common ancestor gene inferred in, 211–15; controversy over,211; on exon shuffling, 213fig, 217, 218, 219, 223–27; failure to explain
origin of new protein folds, 221–27; ORFans genes unexplained by, 215–16;
on plausibility of mutational processes, 216–21. See also neo-Darwinism
The Origins of Order: Self-Organization and Selection in Evolution(Kauffman), 293–94, 297
Orr, H. Allen, 239
Owen, Richard, 100
Paleobiology journal, 150
Paley, William, 38
parallel roads of Glen Roy, 22, 23fig
Parvancorina fossil, 89Pauling, Linus, 121, 122, 125
Peirce, C. S., 343

pentadactyl limb five-digit pattern, 99fig
People’s Daily (Chinese Communist party newspaper), 64
Perutz, Max, 187
Peterson, Kevin, 87, 109
Phacops rana, 136–37
phyla (animal groups). See animal phyla
phylogenetic classification: description of, 31, 33; phylogenetic inference
assumptions, 132–33; selection of incompatible phylogenetic trees, 131fig.
See also animal phyla
Pigliucci, Massimo, 330
PLoS Genetics journal, 220
Polanyi, Michael, 341
population genetics models: attempting to explain origin of complex
adaptations, 237–41; on chloroquine complexity cluster (CCC) coordinatedmutations, 247–49; co-option model of protein evolution, 249–54;
description and functions of, 233–34; the origin of genetic information and,
235–37; Powerball lottery game used to understand, 242–44fig; “waitingtimes” calculated using, 240–42
positivism scientific approach, 20
post-Darwinian models: evo-devo theory, 314–15; how new models deviate
from tenets of neo-Darwinism, 313fig, 314–35; natural genetic engineering,
332–35; neo-Lamarckism, 329–32; neutral or nonadaptive evolutionary
theory, 321–29; self-organizational theories, 293–310
Powerball lottery game, 242–44fig
Precambrian-Cambrian fossil record: Chengjiang discoveries (China), 62–64,
65fig, 71–76; Darwin’s Dilemma documentary challenging Darwin using
the, 77–79, 96; diagram showing representation of pattern of, 24fig;
examining possibility of tree of animal life from, 117–32; found at the
Burgess Shale site, 26, 27fig–28; looking for evidence of design in the, 371–
78; puzzling pattern of, 34; sponge fossils, 66–68, 81; statistical
paleontology failure to support Darwin’s tree of life in, 69–71; sudden
appearance and missing ancestors evidence in, 373, 375; top-down disparity
preceding diversity evidence in, 371–73, 374fig, 375. See also fossil record
Precambrian fossil record: animal phyla of, 81–92; debate over
Vernanimalcula as bilaterian ancestor, 89, 90, 91fig–96; Ediacaran Hills site,
79–80fig, 81–92; four main types of fossils found in, 80–81; primitive
mollusks, 81; sponge fossils, 66–68, 81; trace fossils, 81, 85–86
primordial germ cells (PGCs), 127, 129fig
The Principles of Geology (Lyell), 348
Proceedings of the Biological Society of Washington journal, 209, 384, 385

Proceedings of the National Academy of Sciences USA, 106, 192, 316–17
process control, 186–87
protein folds: Axe’s conclusion that natural selection preserves, 199–200,
202–8; importance in genetic information producing, 189–92; Long’s failure
to explain origin of new, 221–27; protein tertiary structure corresponding to,
189, 190fig; as smallest unit of structural innovation, 191
proteins: animal development and role of genes and, 258–59; argument thatmultiple improbable mutations are required for new, 244–47; Axe’s
experiments on natural selection and mutation of, 187–200, 202–8;
combinatorial inflation problem applied to amino-acid, 173–74fig, 181fig;
dynamical patterning modules (DPMs) and role of, 304; epigenetic
information in patterns of cell membrane, 279–81, 305; Hox genes role inproviding information for building, 320; LexA (DNA-binding protein), 333;
MAPs (microtubule associated proteins), 283–84; neo-Darwinian failure to
explain generation of new, 257; organismal and informational context
consideration of, 363–71; responses to Sauer’s experiment on amino-acid,180–84, 187–89, 192–94; TFs (transcription factors), 258–59; three levels of
structure of, 189, 190fig; TRs (transcriptional regulators), 258–59; underselection pressure, 197fig. See also amino-acid sequences
Prothero, Donald, 72, 73
Prud’homme, Benjamin, 317“punk eek.” See theory of punctuated equilibrium (“punk eek”)
Raff, Rudolf, 287, 312, 314
random variation: competition for survival driving, 10–11; description of, 10;
heritability of, 11; macromutations form of, 11
rank-free classification scheme, 31, 43
Raymond, Percy, 52“Reading the Entrails of Chickens: Molecular Timescales of Evolution andthe Illusion of Precision” (Graur and Martin), 107
Reidhaar-Olson, John, 192
Retallack, Gregory, 82
retro-positioning mRNA transcripts, 213fig, 217, 218, 219
reunion hypothesis, 134–35
RNA: complexity characterizing information in, 306–9; epigenetic
information role in function of, 279–80; often treated with DNA as sole
repositories of biological information, 275; retro-positioning mRNAtranscripts, 213fig, 217, 218, 219
Robinson, Mabel, 18
Rodin, A. S., 362

Rokas, Antonis, 120, 121
Salisbury, Frank, 238
Sam Noble Science Museum (University of Oklahoma), 77–78, 96–97
Sanger, Fred, 187
Sauer, Robert, 180–84, 187–89, 192–94
Schelling, Friedrich, 19, 320
Schindewolf, Otto, 311
Schmidt, Deena, 249, 253
Schopf, J. William, 58
Schuchert, Charles, 28, 48
Schützenberger, Marcel-Paul, 171–72, 176–77
Schwartz, Jeffrey H., 125, 314, 318
science: abductive inference basis for developing hypotheses in, 343–45;
causal adequacy in, 348–51; demarcation criteria issue of, 386–90; German
idealism and cosmic philosophy of, 18–19, 20; method of multiplecompeting hypotheses in, 346–49; methodological naturalism rule of, 19–20,
384–86; new objections to intelligent design as, 392–98; positivistic view of,
20; reasons to regard intelligent design as, 391–92; truth over “rules” of,398–400. See also evolutionary biology; vera causa (true cause) principle
Science journal, 41, 85, 120, 210, 220
Scientific American journal, 92
Scudder, Samuel, 20
Sedgwick, Adam, 13–14, 15
self-organizational models: on epigenetic information, 295–97; failure toprovide vera causa (true cause), 309–10; on genetic information, 297–99;
Kauffman proposal on the Cambrian explosion using, 299–300; Kauffman’ssystem of interconnected lights, 298–99; order vs. information dilemma of,
305–9; origin of body plans explained by, 300–302; overview of the, 293–
95; presupposing developmental genetic toolkit, 300–305
Sepkoski, David, 138, 150
Sepkoski, Jack, 41
sequence hypothesis, 159, 169, 177
Shannon, Claude, 164
Shannon information theory, 164–68, 274, 275
Shapiro, James, 332–35, 402
Shapiro, Leo H., 57, 103
Shu, D. G., 75
Signature in the Cell (Meyer), 359–60, 389, 391, 392, 402
Silurian period. See Cambrian period

Simpson, George Gaylord, 61
Slatkin, Montgomery, 149
Smith, Andrew, 109
Smith, William, 15
Smithsonian’s National Museum of Natural History (NMNH), 209–11, 384
Snoke, David, 240, 241, 244–47, 253
soft-bodied fossil representatives, 57–62, 105
species selection, eliminating less fit species, 147, 148
Spemann, Hans, 271, 273, 275
spliceosomes, 323–24
sponges: Chengjiang embryo fossils, 66–68, 67fig; Ediacaran mini-explosion
producing, 86–88; morphological studies on monophyletic nature of, 125
Spriggina fossil, 80fig, 81, 82–83, 88
St. Johnston, Daniel, 256
Stanley, Steven, 137, 141, 147, 314
statistical paleontology: casting more doubt on artifact hypothesis, 69–71,
105; Darwin’s tree of life inconsistency with findings of, 69–71; theory ofpunctuated equilibrium questions raised by, 145–46
Sternberg, Richard, 210, 384fig, 385, 402
stromatolite fossils, 58fig
Strongylocentrotus purpuratus (purple sea urchin), 266fig, 267–68
The Structure of Evolutionary Theory (Gould), 149, 150
sugar molecules, 280–81, 282–83
Syvanen, Michael, 120
Szathmáry, Eörs, 320, 362
TalkReason.org, 210–11
TFs (transcription factors), 258–59
Thaxton, Charles, 341fig–42
Theobald, Douglas, 122theory of blended inheritance, 155–57
theory of gene regulation for higher cells, 265–68
theory of punctuated equilibrium (“punk eek”): “allopatric speciation”
process used in, 139–42; Cambrian top-down pattern contradicting thebottom-up pattern of, 142–43; the fossil record problem for, 142–45; historyof life depicted by the, 141fig; initial interest and then decline of, 149–51;
origins and development of the, 137–39
Thomson, Keith Stewart, 259, 286
TIME magazine, 50
Todd, Scott, 402–3

top-down pattern: of Chengjiang fauna fossil, 74–76; found at Burgess Shalesite, 39–44; Precambrian-Cambrian fossil record, 371–73, 374fig, 375;
punctuated equilibrium history of life contradicted by Cambrian, 142–44fig.
See also bottom-up pattern
trace fossils (Ediacaran Hills site), 81, 85–86
traits: allopatric speciation allowing for rapid fixation of preexisting, 146–47;
analysis of anatomical, 125–32; “long periods of stasis” bringing about new,147; Mendel’s experiments with factors and genes for, 157; species selection
eliminating undesirable, 147, 148; theory of blended inheritance on, 155–57.
See also genetic mutationstransfer of mobile genetic units, 213fig, 217, 218–19
transistor (general purpose), 368fig
The Tree of Life, 110
tree of life. See animal tree of life
Trends in Ecology and Evolution journal, 119
Trends in Genetics journal, 107
Triassic period fossils, 14
trilobite fossils: anatomy, 9fig, 10; Burgess Shale site, 405fig
TRs (transcriptional regulators), 258–59
tubulin subunits, 277–78fig
Turing, Alan, 295–96“20+ Evidences for Macroevolution” (Theobald), 122
Ulam, Stanislaw, 171, 177
Ultrabithorax gene (fruit fly), 261–62
Understanding Bioinformatics, 110
uniformitarian principles, 391–92, 393
universal common ancestry: Burgess Shale’s failure to support, 36fig;
Cambrian explosion and tree of life of, 12–13; conflicting gene evidence on
the timing of, 105–6; convergent evolution invoked for, 133–34; Darwin’s
theory of evolution on pattern of, 3–5; deep-divergence hypothesis argumentfor, 100, 101–13; Long’s inferred common ancestral gene of, 214–15;
molecular clock analysis argument for, 102fig–3, 121; sequencing DNA toattempt to prove, 100–101; “shmoo-like” catch–22 of the assumption of,
111–13; similar anatomical structures evidence of, 99fig–100. See also
animal tree of life; degree of difference; intermediate animal life forms
universal metamorphism hypothesis, 57
Valentine, James, 41, 59, 69, 83–84, 90, 106, 107, 109, 110, 124, 143–44,
151, 162, 163, 292, 355–56
Vendian period, 79vera causa (true cause) principle: causal adequacy criteria of, 348; Darwin’s
argument using criterion of, 216–17; description of, 309; materialistic causes
compared to, 394; only known cause, 349–51; self-organization “natural
magic” versus, 309–10. See also hypotheses; science
Vernanimalcula fossil, 89, 90, 91fig–96
Waggoner, Benjamin, 81“Waiting for Two Mutations: With Applications to Regulatory Sequence
Evolution and the Limits of Darwinian Evolution” (Durrett and Schmidt),
249
waiting times: neutral or nonadaptive evolutionary theory on, 327–29;
population genetics models calculating, 240–42
Walcott, Charles Doolittle: Burgess Shale discovery of, 26, 26–29, 34, 40,
48–49, 52; lumping approach favored by, 47–48, 55; other versions ofartifact hypothesis by, 56–62, 105; Whittington’s analysis undercutting
solution offered by, 52–54. See also artifact hypothesis; Burgess Shale site
(Canada)“Walcott, the Burgess Shale and Rumours of a Post-Darwinian World”(Morris), 291
Wallace, Bruce, 260
Wall Street Journal, 385
Wang, Daniel, 106
Waptia arthropods, 60, 65fig
Ward, Peter, 11
Warrawoona Group fossils (Australia), 58
watch-to-watchmaker design argument, 37–38
Watson, James, 159, 160fig, 166, 187, 236
Wegener, Alfred, 346
Wells, Jonathan, 77, 92, 273fig, 370
Whittington, Harry, 52–54
Wieschaus, Eric, 255–56, 257fig, 260, 270, 315
Willmer, Pat, 132
Wistar Institute conference (1966), 170–77, 187
Wiwaxia fossils, 53, 62“word salad” explanations, 227–29
Wray, Gregory A., 57, 103
Yang, Ziheng, 106
Yockey, Hubert, 180–81, 308
Yunnanozoon lividum, 74–75

Zhou, Gui-Qing, 59, 61, 63
Zuckerkandl, Emile, 121, 122, 125

Acknowledgments
Though I am not a biologist, but a philosopher of biology, I have the good
fortune of overseeing an interdisciplinary scientific research effort that gives
me a bird’s-eye view on some cutting-edge discoveries and insights comingfrom some exceptional scientists. With that in mind, I would like to thank mycolleagues at the Discovery Institute and Biologic Institute, in particular Paul
Nelson, Douglas Axe, Jonathan Wells, Michael Behe, Ann Gauger, Richard
Sternberg, Paul Chien, and Casey Luskin—whose research has made theargument of this book possible. I would especially like to acknowledge Paul
Nelson for his assistance writing Chapters 6 and 13, expanded versions ofwhich we plan to publish jointly as technical articles. In addition, Casey
Luskin, Discovery research coordinator, has repeatedly gone above andbeyond the call of duty in his commitment to, and skillful work on, this book.
I’d also like to acknowledge the two anonymous biologists and two
paleontologists who gave such careful attention to improving the scientificrigor and accuracy of the manuscript during the peer-review process. I would
also like to express my thanks to Paul Chien, Marcus Ross, and Paul Nelson
for the research they did in support of our 2003 article “The Cambrian
Explosion: Biology’s Big Bang,” which provided a scaffolding for theargument developed here in a much expanded form.
In addition, I deeply appreciate the work of our Discovery Institute writersand editors—Jonathan Witt, David Klinghoffer, Bruce Chapman, and Elaine
Meyer—who have made this manuscript infinitely more readable. Jonathan
Witt deserves special mention for helping me to launch this project and for his
help developing story elements and ideas. I’d like to thank my assistantAndrew McDiarmid for his diligent work on the bibliography and managing
the flow of information. And Ray Braun cannot be thanked enough for his
beautiful artwork. Finally, I’d like to express my gratitude to the good people
at Harper: Lisa Zuniga for her exceptional coordination and skill in moving
the book through the production process; Ann Moru for her expert
copyediting; and to my senior editor Roger Freet for his vision, patience, anduncommon strategic guidance.

Photographic Insert

Plate 1. Mt. Maotian, near Chengjiang, China. The famous Chengjiang fossil
site was discovered near the top of this mountain. Courtesy Illustra Media(all).

Plate 2. The original discovery site of the first Chengjiang fossils. Today thisarea is a preserve.

Plate 3. Looking down from Mt. Maotian, with the large Fuxian Lake in the
distant foreground.

Plate 4. The opabinid Jianfengia multisegmentalis. Courtesy Paul Chien.
Unless otherwise noted, all fossils shown on this and subsequent color pages
are from the Maotianshan Shale near Chengjiang, China.

Plate 5. A fossilized comb jelly (a ctenophore). Species: Maotianoascus
octonarius. Courtesy J. Y. Chen.

Plates 6 & 7. Priapulid worms of the species Maotianshania cylindrica.
Courtesy Paul Chien and Illustra Media.

Plate 8. A lobopodian “worm with legs” of the genus Microdictyon.

Plate 9. Another lobopod worm. Species: Microdictyon sinicum.

Plate 10. Luolishania longicruris, a rare lobopod of the Maotianshan Shale.

Plate 11. The extinct and enigmatic Vetulicolia, thought to represent either anarthropod, a tunicate- like urochordate, or a distinct phylum. Courtesy Illustra
Media (all).

Plates 12 & 13. Two specimens of the arthropod Leanchoilia. The top
specimen shows its distinctive long frontal whiplike appendages.

Plate 14. Chengjiangocaris longiformis (below), a rare arthropod known only
from the Chengjiang biota. Courtesy Illustra Media (all).
Two fossils from the dark-colored Burgess Shale, near the town of Field in
British Columbia, Canada. Note the contrast in color to the fossils from thehoney-colored Maotianshan Shale depicted on the previous and subsequentpages.

Plate 15. A fossil of the arthropod Marrella from the Burgess Shale. Courtesy
Illustra Media.

Plate 16 (below). The shrimp-like arthropod Waptia. Courtesy Illustra Media.

Plate 17. The arthropod Fuxianhuia protensa. Note its exquisitely preserved
eyes, antennae, segmented body, and forked tail. Courtesy Illustra Media.

Plate 18. A fossil of the arthropod Waptia, from the honey- colored
Maotianshan Shale. Courtesy Paul Chien.

Plate 19. A fossil of an Anomalocaris, whose large eyes and jaws made it thefiercest predator in the Cambrian seas. Some reached a length of one meter.

Courtesy J. Y. Chen.

Plates 20–22. A montage of beautifully preserved trilo-bites from theMaotianshan Shale, including a specimen of Eoredlichia intermedia (left).
Courtesy Illustra Media (all).

Plate 23. A specimen of the trilobite Kuanyangia pustulosa from theMaotianshan Shale near Chengjiang, China. Courtesy Illustra Media.

Copyright
DARWIN’S DOUBT: The Explosive Origin of Animal Life and the Case forIntelligent Design. Copyright © 2013 by Stephen C. Meyer. All rights
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EPub Edition © APRIL 2013 ISBN: 9780062071491
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