Vol. 100, No. 715        The American Naturalist   September-October, 1966

EXPERIMENTALGENETICSANDHUMANEVOLUTION

JOSHUA LEDERBERG

Department of Genetics, Stanford University School of Medicine,
            Palo Alto, California

Planning based on informed foresight is the hallmark of organized human
intelligence, in every theater from the personal decisions of domestic life to
school bond elections to the world industrial economy. One sphere where it
is hardly ever observed is the prediction and modification of human nature.
The hazards of monolithic sophistocratic rationalization of fundamental hu-
man policy should not be overlooked, and medicine is wisely dedicated to
the welfare of individual patients one at a time.  However, though lacking
machinery for global oversight, we must still find ways to cope with the
population explosion, environmental pollution, clinical experimentation, the
allocation of scarce resources like kidneys (transplant or artificial), even a
convention on when life begins and ends, which confounds discussion of
abortion and euthanasia. Concern for the biological substratum of posterity,
I.e., eugenics, is divided by the same cross-purposes. Nevertheless, whether
or not he dares to advocate concrete action, every student of evolution must
be intrigued by what is happening to his own species (what else matters?),
and especially the new evolutionary theory needed to model a self-modifying
system that makes imperfect plans for its own nature.

Repeated rediscovery notwithstanding, the eugenic controversy started in
the infancy of genetic science. More recently, the integration of experimen-
tal genetics and biochemistry has provoked a new line of speculation about
more powerful techniques than the gradual shift of gene frequencies by se-
lective breeding for the modification of man. This article will first reca-
pitulate a widely held skepticism about the criteria for the "good man" who
is the aim of eugenic policy. The strategic impasse will not deter tactical
assaults, but favors those with the most obvious, short-run payoff. I will
then show how this points to an impending revision of the experimental de-
sign of human evolution, based on precedents already established in other
species of animals and plants.

The debate needed to ventilate these issues has started in a few con-
ferences: Man and his /uture (G. Wolstenholme, ed.) Ciba Foundation Sym-
posium, 1962; Control of human heredity and evolution (T. M. Sonneborn,
ed.) MacMillan, 1965; and Biological aspects of social problems (Meade 8r
Parkes, eds.) Plenum Press, 1965, which document many other ideas and
references to primary literature.  I would refer especially to Dobzhansky
(1962) and Harris (1964) for outlines of the philosophical and technical foun-
dations of the discussion.

Despite every intention of generality, the outlook of this article is un-
avoidably culture-bound; many of my allusions pertain to academic life in

517


520                THE AMERICAN NATURALIST

the United States and might seem utterly absurd to the vast majority of the
world's population, of which we are hardly an unbiased sample. The futility
of discussing the patterns of human evolution without fairer representation
of its actual components is the most cogent criticism of any simplicistic
definition of eugenic goals.

1) Human culture has grown so rapidly that the biological evolution of
the species during the last hundred generations has only begun to adjust to
it. Microscopic processes of human evolution go on, but the instability of
the historical milieu obscures any coherent pattern of biological adaptation
since the Paleolithic.  Cultural cohesion tends to mute strident biological
innovation, by the exclusion of deviants (whether "positive" or "negative").
But of course it generates its own biases, with many short-term fluctuations
in the selective value of different genotypes and the long term-cancellation
of many advantages irrelevant to civilized life.

2) Even on the time scale of the cultural revolution, we must acknowledge
a singularity in the history and evolution of the planet: the emergence of
scientific insight and technological power in the present era.  In one life-
time, the parish has become the solar system.

3) The historical examples of the application of technology such as ar-
maments and the population explosion are premonitions of the future. The
hazards of imbalance as between technical power and social wisdom are well
advertised, but technology itself is out-of-balance. For example, the tech-
nology of arms control has only recently attracted a fraction of the scientific
attention devoted to its politics.

4) There has been considerable discussion of the supposed hazard to the
human gene pool from the sheltering of the tacitly "unfit" by medicine or
social welfare. Not so widely understood is the futility of negative-eugenic
programs: most deleterious genes are represented and maintained in the pop-
ulation mainly by normal (conceivably sometimes supernormal?) heterozy-
gotes.  If we attack the heterozygotes as well as overtly afflicted homozy-
gotes, almost no human being will qualify. In addition, many well-established
institutions, such as the comfort of the automobile, and of heated shelters,
war, and inheritance of unearned wealth or power, are equally suspect as
dysgenic. It is very difficult to see how we can reconcile any aggressive
negative eugenic program with humanistic aspirations for individual self-
expression and the approbation of diversity. Positive eugenic programs can
be defended roughly in proportion to their ineffectiveness: applied on a really
effective scale they would state the same dilemmas.  At present the main
hazard of these proposals is the oblique even if unintended weight they may
appear to give to the enforcement of negative eugenics on outcast groups.

Genetic counseling can nevertheless play an important role within the
framework of personal decision and foresight for the immediate family. It
can offer grave negative cautions about inbreeding and recurrence of genetic
disease; it might also encourage optimists to look for compatibility or com-
plementarity of positive attainments as a factor in mating preference. How-
ever, the public advertisement of "superior germ plasm" (sperm banks) is


EXPERIMENTAL GENETICS AND HUMAN EVOLUTION       521

open to so many distortions-like most manipulations of mass taste-that
its implementation would probably run very differently from its sponsors'
hopes.  As in adoption proceedings, the anonymity of third parties can be
set aside only at great risk to the stability of family life.

5) The cultural revolution has begun its most critical impact on human
evolution, having generated technical power which now feeds back to bio-
logical nature. The last decade of molecular biology has given us a mecha-
nistic understanding of heredity, and an entry to the same for development.
These are just as applicable to human nature as they are to microbial physi-
ology. Some themes of biological engineering are already an inevitable ac-
companiment of scientific and medical progress over the next five to 20
years.

The sharpest challenges to our pretensions about human nature are already
in view-and may be overlooked by too farsighted focussing on more so-
phisticated possibilities, like "chemical control of genotype".  (To save
repeating a phrase, let me call this genetic alchemy, or algeny). Algeny is
diversionary, not because I doubt its eventual realization, but because the
obvious difficulties provide a too convenient refuge for evading sooner anx-
ieties. Perhaps I might point to some analogous history. Some years ago,
I suggested that the genetics of somatic cells of mammals could be worked
out most directly by exploiting precedented interactions of cells in fusion,
coalescence of karyotypes, and segregation.  This was already being bril-
liantly realized, but much more energy has still been spent in vain pursuit
of DNA- and virus-mediated transfer of genes in mammalian cells. These
algenical visions still dominate the imagination of most of my colleagues,
and may of course ultimately succeed.

The realization of applied biology is, simply, medicine; a more effective
slogan on which to focus an alternative to eugenics is "euphenics," whose
meaning should be transparent to readers of this journal.  Euphenics then
means all the ameliorations of genotypic maladjustment, including liability
to any disease, that could be brought about by treatment of the affected in-
dividual, more efficaciously, the earlier in his development. Disease is any
deficit relative to a desired norm, and with its shots to accelerate brain
growth, the next generation or two will surely have an even more dismal
clinical appreciation of our intellectual capacity than we as students did for
our professors.

The eventual impact of molecular biology on medicine should be self-
evident. An immediate point of application follows from the clarification of
' immunity.  It is now certain that the next few years will see the develop-
ment of tissue and organ transplantation on a large scale.  It would be a
mistake to think of this as merely the repair of catastrophic defects in kid-
ney or heart. Many more of us have slighter imbalance in our homeostats,
muscles, teeth, stomachs or scalps, whose amenability to exchange will
add up more weightily for standards of human performance. These implants
will compete with their mechanical counterparts, which already prove the
eminence of the trivial. The automobile is evolving into an all-purpose exo-


522                THE AMERICAN NATURALIST

skeleton now augmented not only with locomotors but also a variety of sen-
sors, effecters, and communicators. As it can also be equipped with auxil-
iary blood-pumps, gas-bubblers, and a laundry (kidney), much of the effort
that goes into making these medical devices implantable may be already
irrelevant to contemporary man.

Embedded in molecular biology are the crucial answers to grave and basic
questions about aging, the major degenerative diseases, and cancer; and it
seems an easy gamble that very consequential changes in life-span and the
whole pattern of life are in the offing, provided only that the momentum of
existing scientific effort is sustained. Quite apart from the glimpses of the
bizarre that mechanical and transplanted organs may offer, this is a general
issue of the utmost importance to the fabric of human relationships; we have
hardly begun to face it.

It is already a very heavy burden on the conscience of our physicians
that the ebbing of life is a gradual process; that the spontaneous beating of
the heart is no longer the uncontrollable axiom of human life; indeed that
many a "person" could be maintained indefinitely as an organ culture if
there were any motive for it. Biological science already has a great deal to
say and more questions to ask about the foundations of personality and its
temporal continuity, which we have not begun to apply to the disposition of
our own lives. The whole issue of self-identification needs scientific reex-
amination before we apply infinite effort to preserve a material body, many
of whose molecules are transient anyhow. Inevitably, biological knowledge
weighs many human beings with personal responsibility for decisions that
were once relegated to divine Providence. In mythical terms, human nature
began with the eating of the fruit of the Tree of Knowledge. Curiously,
Genesis correlates this with the pain of childbirth, an insight that the growth
of man's brain has gone beyond the safe and comfortable.  However, the ex-
pulsion from Eden only postponed our access to the Tree of Life.

  If the limit to a brain volume of 1500 ml is dictated by the proportions of
the female pelvis-and obstetrics testifies how marginal the adaptation
is-the simple practice of cesarean section could set us on a new evolu-
tionary track. Very little is now known of the embryological homeostat for
size and complexity of the brain. However, the few hints from early effects
of some hormones, and the "NGF" regulator of the sympathetic ganglia war-
rant the expectation of prophylactic control of the development of the grow-
\  ing brain. As such techniques become available, the responsibility for their
administration can no more be evaded than for sending a child to school.
Unfortunately, there are bound to be serious risks on both sides of the
equation.

The elaboration of euphenics is, however, not the main purpose of a dis-
cussion of human evolution, except for the one point-the added difficulties
it creates for any measure of human value.  If this subject were not at the
heart of the eugenic controversy, it would be arrogant to insist on the dis-
cussion of it.

Reconsider how we must reevaluate the cumulative score of a human geno-


EXPERIMENTAL GENETICS AND HUMAN EVOLUTION      523

type regarded over a lifetime, and for its contribution to the human future.
Besides present perplexities, look to future perturbations:
1) Durability. The mere extension of lifespan alters the scores. Perform-

ance must be measured over the whole term of life, not based only on youth-
ful precocity.

2) The euthenic context. Educational opportunity and practice are changing
rapidly. Consider

  a) Recognition of individual diversity. Educators have begun to learn,
and exercise the knowledge, that children vary widely in the details of their
information-processing machinery, e.g., the relative acuity of their sensory
modalities. Many "dull" children must be reclassified as over-specialized;
we might well make virtue out of necessity in enabling each child to exploit
his inherent skills. This can be accomplished realistically by
  b) Computer-assisted teaching. The computer display is perhaps just

an extension of the printed book, but we need a much more versatile adjust-
ment of the information channels to the subtle requirements and performance
of each child.  This can hardly be achieved where each teacher must deal
with any number of children simultaneously. In fact, the apparent value of a
genotype will fluctuate according to the current status and the availability
of the teaching programs and their relevance to the values of the community!
Human teachers remain indispensable for developing and guiding these pro-
grams and for their insights into motivational and social sides of their stu-
dents behavior. In the long run, the individuation of the euthenic environ-
ment can only accentuate the importance of genotypic variation.

  c) Within the United States and in other ways throughout the world, we
observe an unprecedented experiment in equality of opportunity without re-
gard to race. The uncontrollability of environments has left no room for the
scientist to embrace any conclusions whatever about the genetic basis of
differences in racial performance. Community attitudes have made genes for
dark skin handicaps to academic achievement, often overriding superior
brains.  Many other genes play on the interaction of child and community,
and ultimate human performance, just as deviously. As our knowledge of,
and more to the point, the community's response to, these idiosyncrasies
evolves, there will be a corresponding revision of the value equation.

  d) Job skills change.  Neat handwriting and mental arithmetic once
crucial for white collar work are now obsolete. Tolerance for assembly line
tedium is following muscular power onto the wasteheap of redundant skills.
Social skills, leadership, and esthetic breadth are becoming the criteria of
job success in many fields as machines take over the more routine tasks,
in which logical rigor may soon be encompassed.

  e) Western culture and its limited population is being succeeded by a
much broader world culture.  Is there much point in setting eugenic stand-
ards relevant only to a small minority of the world's population even as we
watch the unprecedented breakdown of intercultural barriers?  The jet air-
plane has already had an incalculably greater effect on human population
genetics than any conceivable program of calculated eugenics.


524                THE AMERICAN NATURALIST

3) The world situation.  The central problem for the species must bias
any momentary evaluation.  Until recently, this was perceived as agricul-
tural efficiency. Hunger still haunts the earth, but we might just manage to
marshal the technical resources to assuage it.  The specter of the indus-
trialized world is suddenly nuclear suicide, and this has already led to some
concern as to the biological adaptation of the species most appropriate to
an age dominated by nuclear power. Political institutions are likely to change
course much more rapidly than any biological response. As has been pointed
out repeatedly, adaptability is man's unique adaptation.

This begs the question how to anticipate future needs, how far adapta-
bility can be generalized, and how well it can compete, in any well-defined
microniche, with more rigorous specialization.  To put it another way, how
do we identify the most adaptable genotypes now living and what is the
price, to the detriment in special skills, of this adaptability?

4) Response to euphenics.  The medico-technological context of human
performance is more predictable than the socio-political. We are already
committed to the attempted eradication of infectious agents like malaria,
tuberculosis, cholera, variola, and poliovirus.  In consequence, any break-
down of public health services can be catastrophic by exposing large, im-
perfectly immunized populations to these parasites. If the interplay of He-
moglobin S and malaria is a useful model, genetic adaptations to a germ-free
environment are taking place too; chemical pollution might replace germs as
a major selective factor except that its cumulative impact on adults is less
cogent than acute infanticide.  The context of modern man, in fact, includes
steadily increasing reliance on medicine, i.e., euphenics, from ovulation on-
wards.  It makes as little sense to decry genetic adaptations to this as to
other components of civilized life. The quality of a genotype cannot now be
evaluated in terms of a hypothetical state of nature (wherein we would quickly
grunt in chilly displeasure at our unfurred skins), but must match the prag-
matic expectations of the milieu of the individual and his descendants. In
fact selection is so slow, especially for rare genes, as to make this a theo-
retical issue for some time. It would be a tour-de-force to demonstrate any
change in the frequency of a specific deleterious gene in a human popula-
tion that could be unambiguously traced to a relaxation of natural selection
against it. In comparison to the pace of medical progress, these exigencies
are trivial.

As medical practice evolves so does the evaluation of health and vigor.
What has happened to pancreatic diabetes is happening to phenylketonuria,
and is bound to happen to many other biochemical and developmental dis-
eases. Indeed, it would be no surprise to find compensating advantages, in
certain contexts, for some of these genotypes.
The availability of transplants and prosthetics is an extension of the so-
cial process which relaxes the demands placed on a single genotype. We
can imagine the systematic use of chimerism as another way of merging the
best that each of a variety of genotypes can offer.
Recall that the most successful exercises in plant breeding have not es-


EXPERIMENTAL GENETICS AND HUMAN EVOLUTION      525

tablished pure lines of vigorous individuals.  Instead, somewhat over-spe-
cialized strains are nurtured and the latent resources of individually un-
promising parents are merged in vigorous hybrid offspring. (A good farmer
has learned how common sense conflicts with reality when he tries to use
ears of hybrid corn as seed for another generation.)

5) Social adjustment.  We are on the shakiest ground trying to sort out
the genetic basis of such social diseases as crime and delinquency. In any
case we have a long way to go in elucidating how nature and nurture inter-
act in this field; e.g., what penalty the species would suffer by extirpating
every gene that might in some environment contribute to crime and rebellious
behavior.'  Instability of family life, the estrangement of the generations,
and the shallowness of human communication are more prevalent and cumu-
latively more serious diseases than violent crime, and must be given equal
account in any effort to define the "good man," or in any lament of human
deterioration.

Who will toss the first stone?
6) The sexual dimorphism.  Most eugenic discussions have been over-
whelmingly male-oriented, as is academic life.  Western culture is more
paradoxical than ever in its assignment of roles to women, and thereby in
the design of their education and the advertised criteria of feminine suc-
cess, stressed by conflicting demands for decoration and utility, dependence
and initiative.  The lack of useful occupation for many older women is a
premonition oft the leisure society where "work may become the prerogative
of a chosen elite." Half the beneficiaries of eugenic design will be women.
Will their creativity and happiness be augmented in a genotype that recom-
bines XX and a set of male-oriented autosomes?  Or shall we bypass the
dimorphism and evolve a race where this does not matter? To shout "Vive
la difference" and then ignore it is hypocrisy.
Occupational discrimination by sex has been outlawed as a byproduct of

the civil rights movement in the United States, which raises nice biological
questions.  The sexual dimorphism is one of the most primitive of genetic
differentials.  Yet, in forthcoming attempts to enforce and evade the law,
we shall see how thin the scientific groundwork is to answer how far the
statistics of female performance in industrial society are biologically vs.
socioculturally determined. In some ways this may be even harder to answer
objectively than for the racial counterpart, since we are even less able to
perform a meaningful experiment. What finesse it will take to design geno-
types optimized for both sexes, i.e., properly rechanneled by the develop-
mental switch with respect to the full set of desiderata, besides the primary
sex characteristics!

7) The leisure society. This discussion has been dominated by criteria
of performance at work.  The whole framework may be obsolescent on the
time scale of a few generations.  As machines come to do almost all of the
work, and this must include managerial and inventive tasks as well as cleri-
cal and manual, what are the relevant human values?  Will not boredom be

`P f
  ro essor Walter Bodmer proposes labelling this concept "the social load."


526                THE AMERICAN NATURALIST

the most pernicious disease, and a zest for life without the compulsion of
labor the rare essential for the species. 7  Play rather than work will be the
substratum of human activity, and the transmutation of play into cultural
progress will replace the underpinning by industrial and military technology
of its superstructure of basic science.

Perhaps the scientist who works for his joy in it is the most nearly pre-
adapted for that topsy-turvy world, obviously an impeccable criterion for
eugenic choice.

This leads us finally to algeny. Man is indeed on the brink of a major
evolutionary perturbation, but this is not algeny, but vegetative propagation.
(No one will be surprised that Haldane had anticipated this reasoning years
ago.)

For the sake of argument, suppose we could mimic with human cells what
we know in bacteria, the useful transfer of DNA extracted from one cell line
to the chromosomes of another cell.  Suppose we could even go one step
further and sprinkle some specified changes of genotype over that DNA.
What use could we make of this technology in the production as opposed to
the experimental phase?

Repair genetic-metabolic disease. 7  Indeed, if a diffusibie hormone or en-
zyme were involved; but the same virtues are more readily available by
transplantation. The advantage is consequential only if some nondiffusible
product or irreversible developmental commitment (like a neuronal pattern;
were involved. However, it is utterly unreasonable to anticipate the correct
reprogramming of every treated cell.  Then we must perform the algeny on
gamete or zygote, but in so doing we face the difficulty of testing the con-
sequences of the intervention ! If the purpose is a better human being, by
any standard, we would need 20 years to prove that the developmental per-
turbation was the intended, or in any way a desirable one. And if it were,
we would face the same hazards generatron after generation.  The premise
of this argument is that the inherent complexity of the system precludes any
merely prospective experiment in algeny.  It is bound to fail a large part of
the time, and possibly with disastrous consequences if we slip even a single
nucleotide.

To recapitulate, if the desired effect is achieved by modifying some so-
matic cells, the same end is available by transplanting cells already known
to have these properties. In general this should be much easier than sys-
tematically changing the existing ones. If the zygote or a gamete needs to
be altered, the operation is bound to have an uncertain outcome, and needs
some kind of retrospective test.  This ability to manipulate zygote nuclei
should depend on prior capacity for nuclear transplantation and vegetative
proliferation of the involved cells-both as part of the operation, and for the
experimental calibration of the results.

If we have efficacious methods for testing and selecting new genotypes,
do we have much need for algeny?  Would not recombination and mutation
give ample material for test? Perhaps for some time. But I would credit
the possibility of designing a useful protein from first premises, replacing


        EXPERIMENTAL GENETICS AND HUMAN EVOLUTION      527

evolution by art. It would then be requisite to implant a specified nucleotide
sequence into a chromosome. This would still be useless without retrospec-
tive inspection and approval of the result, e.g., in a clone of somatic cells.
What to do with the mishaps needs to be answered before we can believe
that these risks will be undertaken in the fabrication of humans. But, during
an experimental phase, algeny may be as useful for the generation of de-
signed genotypes, especially if they can be verified in cell culture, as other
combinatorial tricks in the geneticists' repertoire.
Vegetative reproduction, once we are reminded that it is an indispensable
facet of experimental technique in the microbial analogy, cannot be so readily
dismissed.  In fact there is ample precedent for it, and not only throughout
the plant and microbial kingdoms, but in many lower animals. Monozygotic
twins in man are accidental examples. Experimentally, we know of success-
ful nucIear transplantation from diploid somatic as well as germline cells
into enucleated amphibian eggs. There is nothing to suggest any particular
difficulty about accomplishing this in mammals or man, though it will rightly
be admired as a technical tour-de-force when it is first implemented (or will
this sentence be an anachronism before it is published?) Indeed I am more
puzzled by the rigor with which apogamous reproduction has been excluded
from the vertebrate as compared to the plant world, where its short-run ad-
vantages are widely exercised.  If the restriction is accidental from the
standpoint of cell biology, nevertheless a phylum that was able to fall into
this trap might be greatly impeded in its evolutionary experimentation to-
wards creaiive innovation.
Vegetative or clonal reproduction has a certain interest as a investigative
tool in human biology, and as an indispensable basis for any systematic
algenics; but other arguments suggest that there will be little delay between
demonstration and use. Clonality outweighs algeny at a much earlier stage
of scientific sophistication, primarily because it answers the technical speci-
fications of the eugenicists in a way that Mendelian breeding does not. If a
superior individual (and presumably then genotype) is identified, why not
copy it directly, rather than suffer all the risks of recombinational disrup-
tion, including those of sex.  The same solace is accorded the carrier of
genetic disease: why not be sure of an exact copy of yourself rather than
risk a homozygous segregant; or at worst copy your spouse and allow some
degree of biological parenthood.  Parental disappointment in their recom-
binant offspring is rather more prevalent than overt disease. Less grandiose
is the assurance of sex-control; nuclear transplantation is the one method
now verified.
Indeed, horticultural practice verifies that a mix of sexual and clonal re-
production makes good sense for genetic design. Leave sexual reproduc-
tion for experimental purposes; when a suitable type is ascertained, take
care to maintain it by clonal propagation.  The Plant Patent Act already
gives legal recognition to the process, and the rights of the developer are
advertised "Asexual Reproduction Forbidden."
Clonality will be available to and have significant consequences from


528                THE AMERICAN NATURALIST

acts of individual decision-Medawar's piecemeal social engineering-
given only community acquiescence or indifference to its practice. But here
this simply allows the exercise of a minority attitude, possibly long before
its implications for the *hole community can be understood. Most of us pre-
tend to abhor the narcissistic motives that would impel a clonist, but he (or
she) will pass just that predisposing genotype intact to the clone. Wherever
and for whatever motives close endogamy has prevailed before, clonism and
clonishness will prevail.
Apogamy as a way of life in the plant world is well understood as an evo-
lutionary cul-de-sac, often associated with hybrid luxuriance. It can be an
unexcelled means of multiplying a rigidly well-adapted genotype to fill a
stationary niche. So long as the environment remains static, the members of
the clone might congratulate themselves that they had outwitted the genetic
load; and they have indeed won a short-term advantage. In the human con-
text, it is at least debatable whether sufficient latent variability to allow for
any future contingency were preserved if the population were distributed
among some millions of clones. From a strictly biological standpoint, tem-
pered clonality could allow the best of both worlds-w; would at least en-
joy being able to observe the experiment of discovering whether a second
Einstein would outdo the first one.  How to temper the process and the ac-
companying social frictions is another problem.
The internal properties of the clone open up new possibilities, e.g., the
free exchange of organ transplants with no concern for graft rejection. More
uniquely human is the diversity of brains.  How much of the difficulty of
intimate communication between one human and another, despite the func-
tion of common Iearned language, arises from the discrepancy in their ge-
netically determined neurological hardware? Monozygotic twins are notori-
ously sympathetic, easily able to interpret one another's minima1 gestures
and brief words; I know, however, of no objective studies of their economy
of communication. For further argument, I will assume that genetic identity
confers neurological similarity, and that this eases communication.  This
has never been systematically exploited as between twins, though it might
be singularly useful in stressed occupations-say a pair of astronauts, or a
deep-sea diver and his pump-tender, or a surgical team. Ic would be rela-
tively more important in the discourse between generations, where an older
clonont would teach his infant copy.  A systematic division of intellectual
labor would allow efficient communicants to have something useful to say to
one another.
The burden of this argument is that the cultural process `poses contra-
dictory requirements of uniformity (for communication) and heterogeneity
(for innovation). We have no idea where we stand on this scale. At least
in certain areas -say soldiery-it is almost certain that clones would have
a self-contained advantage, partly independent of, partly accentuated by the
special characteristics of the genotype which is replicated.  This intro-
verted and potentially narrow-minded advantage of a clonish group may be
the chief threat to a pluralistically dedicated species.


         EXPERIMENTAL GENETICS AND HUMAN EVOLUTION      529

Even when nuclear transplantation has succeeded in the mouse, there
would remain formidable restraints on the way to human application, and
one might even doubt the further investment of experimental effort. However
several lines are likely to become active. Animal husbandry, for prize cattle
and racehorses, could not ignore the opportunity, just as it bore the brunt
of the enterprises of artificial insemination and oval transplantation.  The
dormant storage of human germ plasm as sperm will be replaced by the freez-
ing of somatic tissues to save potential donor nuclei.  Experiments on the
efficacy of human nuclear transplantation will continue on a somatic basis,
and these tissue clones used progressively in chimeras. Human nuclei, and
individual chromosomes and genes of the karyotype, will also be recombined
with cells of other animal species-these experiments now well under way
in cell culture.  Before long we are bound to hear of tests of the effect of
dosage of the human 21st chromosome on the development of the brain of the
mouse or the gorilla.  Extracorporeal gestation would merely accelerate
these experiments. As bizarre as they seem, they are direct translations to
man of classical work in experimental cytogenetics in Drosophila and in
many plants. They need no further advance in algeny, just a small step in
cell biology.
My colleagues differ widely in their reaction to the idea that anyone could
conscientiously risk the crucial experiment, the first attempt to clone a man.
Perhaps this will not be attempted until gestation can be monitored closely
to be sure the fetus meets expectations.  The mingling of individual human
chromosomes `with other mammals assures a gradualistic enlargement of the
field and lowers the threshold of optimism or arrogance, particularly if clon-
ing in other mammals gives incompletely predictable results.
What are the practical aims of this discussion? It might help to redirect
energies now wasted on naive eugenics and to protect the community from a
misapplication of genetic policy. It may sensitize students to recognize the
significance of the fruition of experiments like nuclear transplantation. Most
important, it may help to provoke more critical use of the lessons of history
for the direction of our future. This will need a much wider participation in
these concerns. It is hard enough to approach verifiable truth in experimen-
tal work; surely much wider criticism is needed for speculations whose sci-
entific verifiability falls in inverse proportion to their human relevance.
Scientists are by no means the best qualified architects of social policy,
but there are two functions no one can do for them: the apprehension and in-
terpretation of technical challenges to expose them for political action, and
forethought for the balance of scientific effort that may be needed to manage
such challenges.  Popular trends in scientific work towards effective re-
sponses to human needs move just as slowly as other social institutions,
and good work will come only from a widespread identification of scientists
with these needs.
The foundations of any policy must rest on some deliberation of purpose.
One test that may appeal to skeptical scientists is to ask what they admire
in the trend of human history.  Few will leave out the growing richness of


530                THE AMERICAN NATURALIST

man's inquiry about nature, about himself and his purpose.  As long as we
insist that this inquiry remain open, we have a pragmatic basis for a humble
apprecration of the value of innumerable different approaches to life and its
questions, of respect for the dignity of human life and of individuality, and
we decry the arrogance that insists on an irrevocable answer to any of these
questions of value. The same humility will keep open the options for human
nature until their consequences to the legacy momentarily entrusted to us
are fully understood. These concerns are entirely consistent with the rig-
orously mechanistic formulation of life which has been the systematic basis
of recent progress in biological science.
Humanistic culture rests on a definition of man which we already know to
be biologically vulnerable. Nevertheless the goals of our culture rest on a
credo of the sanctity of human individuality. But how do we assay for man
to demarcate him from his isolated or scrambled tissues and organs, on one
side, from experimental karyotypic hybrids on another.  Pragmatically, the
legal privileges of humanity will remain with objects that look enough like
men to grip their consciences, and whose nurture does not cost too much.
Rather than superficial appearance of face or chromosomes, a more rational
criterion' of human identity might be the potential for communication with
the species, which is the foundation on which the unique glory of man is
built.
Coda. Recent discussions of controlled human evolution have focussed
on two techniques: selective breeding (eugenics) and genetic alchemy (algeny).
The implementation will doubtless proceed even without an adequate basis
of understanding of human values, not to mention vast gaps in human genetics.
Eugenics is relatively inefficacious since its reasonable aims are a nec-
essarily slow shift in the populatio,n frequencies of favorable genes. Segre-
gation and recombination vitiate most short-range utilities. Its proponents
are therefore led to advocate not only individual attention to but the wide-
spread adoption of its techniques, and a minority of them would seek the
sanction of law to enforce the doctrine. Most geneticists would insist on a
deeper knowledge of human genetics before considering statutory intrusion
on personal liberties in this sphere.  Meanwhile there is grave danger that
the minority view will lead to a confusion of the economic and social aims
of rational population policy with genocide.  The defensive reaction to such
a confusion could be a disastrous impediment to the adoption of family plan-
ning by just those groups whose economic and educational progress most
urgently demands it.
Algeny presupposes a number of scientific advances that have yet to be
perfected; and its immediate application to human biology is, probably un-
realistically, discounted as purely spectulative.  In this paper, I infer that
the path to algeny already opens up two major diversions of human evolu-
tion : clonal reproduction and introgression of genetic material from other
*On further reflection I would attack any insistence on this suggestion (which I
have made before) as another example of the intellectual arrogance that I decry a
few sentences before--a human foible by no means egregious.


        EXPERIMENTAL GENETICS AND HUMAN EVOLUTION      531

species.  Indeed, the essential features of these techniques have already
been demonstrated in vertebrates, namely nuclear transplantation in amphibia,
and somatic hybridization of a variety of cells in culture, including human.
Paradoxically, the issue of "subhuman" hybrids may arise first, just be-
cause of the touchiness of experimentation on obviously human material.
Tissue and organ cultures and transplants are already in wide experimental
or therapeutic use, but there would be widespread inhibitions about risky
experiments leading to an object that could be labelled as a human or para-
human infant.  However, there is enormous scientific interest in organisms
whose karyotype is augmented by fragments of the human chromosome set,
especially as we know so little in detail of man's biological and genetic
homology with other primates. This is being and will be pushed in steps as
far as biology will allow, to larger and larger proportions of human genome
in intact animals, and to organ combinations and chimeras with varying pro-
portions of human, subhuman, and hybrid tissue (note actual efforts to trans-
plant primate organs to man). The h y rr r
                        b `d'z ation is likely to be somatic, and
the elaboration of these steps to make full use of nuclear transplantation to
test how well these assorted genotypes will support the full development of
a zygote.
Other techniques may well be discovered as shortcuts, especially how to
induce the differentiation of a competent egg from somatic tissue, bypassing
meiosis. This process has no experimental foundation at present, but plenty
of precedent in natural history.
These are not the most congenial subjects for friendly conversation, es-
pecially if the conversants mistake comment for advocacy. If I differ from
the consensus of my colleagues it may be only in suggesting a time scale of
a few years rather than decades.  Indeed, we will then face two risks, (1)
that our scientific position is extremely unbalanced from the standpoint of
its human impact, and (2) that precedents affecting the long-term rationale of
social policy will be set, not on the basis of well-debated principles, but on
the accidents of the first advertised examples.  The accidentals might be
as capricious as the nationality, batting average, or publicesteem of a clonont,
the handsomeness of a parahuman progeny, the private morality of the experi-
menters, or public awareness that man is part of the continuum of life.


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Harris, M. 1964. Cell culture and somatic variation.  Holt, Rinehart and
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Meade, J. E., and A. S. Parkes (eds.). 1965. Biological aspects of social
    problems.  Plenum Press, New York.
Sonneborn, T. M. (ed.). 1965. Control of human heredity and evolution. The
     MacMillan Co., New York.
Wolstenholme, G. (ed.). 1962. Man and his future. Ciba Foundation Sym-
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