Paradigm shifts in biology of the 19th century- "Theory of natural selection" by Darwin and "Negation of spontaneous
generation theory" by Pasteur

Here I will briefly describe the history of the theory on the origin of species. Until
recently, the majority of naturalists believed that all species were invariable andcreated separately. This view has been maintained eloquently by many writers.
However, only a small number of naturalists believed that species were subject totransformation, and the existing life forms are the true descendants of preceding
generations of preceding forms of life.
(Charles Darwin “The Origin of Species” p. 1)

As you go down the chain of animals from the most complete to the most incomplete,
we are faced with the singular situation of the gradual degradation in the configurationof the system - it is natural that I should think that the various life forms produced bylife are born in sequence, developing from the simplest form to the most structured
form.
(Jean Baptiste Lamarck, “Animal Philosophy”, p. 8)

How could a material transform to a living organism by itself. In other words, could aliving form come into existence without parent and without ancestors? That is the
problem that requires a solution. Actually it must be said that the belief in spontaneous
generation has been the belief of many eras. It was believed in ancient times and it isdebated more and more in modern times. What I am rebutting is this belief.
(Louis Pasteur, “Consideration of Spontaneous Generation Theory”)

1This chapter will describe the outline of the paradigm shift experienced by 20th century
physics and 19th century biology. The intention is to reach the understanding that 20th
century biology also faces the need for a new paradigm shift. Next we shall give an
overview of the achievements of molecular biology soon after its birth, and discuss
about the “theory of natural selection” proposed by Darwin and the negation of“spontaneous generation” proved by Pasteur. Then, after pointing out the issue of originof life as the limit of applicability of the natural laws that they discovered, I will
describe the state of research on the origin of life and my views on its issues.
Paradigm shift in physics and biology – creative development of science
Physics in the 20th century, faced with a succession of unexpected experimental
results, was confronted with the need to try to entirely re-examine theoreticalfoundations that had been believed for more than 200 years. Relativity theory denied theconcepts of absolute space and absolute time that classical theory had consideredobvious. Quantum mechanics required that the two concepts of “wave” and “particle”,
which had been inconsistent concepts in classical theory, be recognized as different
attributes of the same object. However, when one tries to unify these two new theories
of relativity and quantum mechanics, one faces a logical contradiction that does nothave a mathematical solution. It was not possible to avoid this contradiction just bymathematical generalization. New conceptual changes due to Shinichiro Tomonaga’s“kurikomi” (renormalization) theory were necessary.
Through repeated paradigm changes, we have learnt valuable lessons.
Firstly, the construction of a new theory is not just a problem of mathematicalformulation. It must be accompanied by a fundamental conceptual change. Needless tosay, in order to fundamentally change a concept, inspiration is more important thancomputational power.
Secondly, it is not possible to take a theory obtained by observing one aspect of nature
and apply it to other phenomena in the same form. Different theories obtained byobserving different phenomena may appear to be mutually contradictory. However, bymaking clear the limits of applicability of theories, it is possible for theories that appear
to contradict to coexist.

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Hence, whatever the theory, the validity, at every opportunity, should be checkedagainst the most recent experimental results, and the range of applicability should beclearly limited *.
* According to Godel’s “incompleteness theorem”, it can be said that “Any powerfulformal theory, by itself cannot guarantee the determinability of its theorems or theabsence of self-contradiction”. Such limits, although they may decrease with thedevelopment of the theory, will continue to exist. Thus, we can only approach subjects
approximately. For just this reason, we must forever repeat the constructive process andcontinue to endeavor to get closer to the subject, one step after another.
Thirdly, when we learn a theory, we must correctly understand the assumptions uponwith which the theory was obtained. When a theory becomes widely accepted, often thevery assumptions upon which it is based are forgotten*. Then the form of nature will be
more and more distorted to fit the theory. However, if we correctly understand theunderlying assumptions, it should be possible, to some extent, for us to prevent thetheory from “running away”.
It must be remembered that, in the development of a theory, in addition to theaccumulated history of human thought over many generations, in other words, inaddition to the phylogenetic history, there is the additive history of thought of eachsingle person, in other words the ontogenetic history of the theory. It is not possible tocorrectly understand the limits of applicability of a theory without unraveling thishistorical context of the establishment of a theory.
As did physics, 19th century biology also experienced paradigm shifts. The “Creation
theory”, according to which man and other higher beasts were created separately by
God and are immutable throughout life, and the “Spontaneous generation theory”,
according to which microorganisms and other lower life forms were generated
spontaneously from septic waste, that were believed up to that time, were each negated,by Darwin and Pasteur.
It was a time when the concept of genes was not yet established, and the significanceof the discovery of natural laws that are still valid today was unmeasurable. However,speaking in analogy with physics, it was just “classical” theory. Just like 20th century
physics, biology faces the need to continue to shift its paradigms.

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In the words of Ukichiro Nakaya in “Methods of Science”, “The truth of science is thejoint product of man and nature, and science forever evolves and changes” (Iwanami
Shinsho, p. 197). In other words, science is not the digging up of something that alreadyhas a shape, as in treasure hunting.
The scholars Hadamard (“The psychology of invention in the mathematical field”) andPiaget (“Genetic epistemology”) cite the historical fact of the discovery of America by
Columbus in the context of “treasure hunting” in the sense of Ukichiro Nakaya.
Ukichiro Nakaya, Methods of Science (“Kagaku no hoohoo”, Iwanami Shinsho, p. 197)
Jacques Hadamard, The psychology of invention in the mathematical field (“Sugaku ni
okeru hatsumei no shinri”, Misuzu Shobo, p. 7)
Jean Piaget, Genetic epistemology (“Hasseiteki ninshikiron,” Hakusuisha, p. 104)
With regard to the complex subject of nature, the choice of what and how to study, andhow to describe the results, always deeply involves human factors. Moreover, against
the background that science forever evolves and transfigures, and is tied with “creativity”
and “historicity”, we cannot ignore the “internal observation” problem that we are notthinking about nature from outside of nature - our thinking selves are also part of nature.
It can be said that this has a commonality with the ontogenetic issue of the developmentof our body and mind through repeated divisions starting from a single fertilized egg,
and the phylogenetic issue of our evolution from a single original species. Cognition isforever in parallel with genesis and evolution. Hence, science, like life, forever evolves
in a creative way.
Here, I think there is a reason why the “conflictual coexistence of self and non-self”
that is the essence of life, as described in the previous chapter, is essentially the same as
the essence of science, which is the product of human cognition. Hence, we cannot
expect the healthy advancement of science if we do not allow the coexistence of
conflicting concepts, and emphasize only phenomena that can be treated with a single
concept.
It is just as, so long as you do not consider abnormal developments such as disease andcancer, you cannot understand the normal development of an organism, and you cannot
expect to understand the whole process of life if you ignore regularity and only4

emphasize irregularity.
In regard to the problem of cognition too, I think that studying not just the brains andneural systems of higher organisms, but also apparently unrelated living phenomena,such as the agents of infection - germs, virus, prions, and studying not just animals, butalso plants and fungi, will give a more essential understanding of cognition.
Now, the number of wonders of life that confront us, or the number of mysteries of lifethat we must solve, are extremely numerous.
For example, there is no shortage of topics, the origin of life made possible by changes
of material states, the origin of mind brought about through the long evolution of livingorganisms, the allergies known as modern diseases, the AIDS virus which causes
immunodeficiency, the infectious agent prion which does not have genes, the E. coli
bacteria O-157 with Shigella verotoxin gene, the environmental “hormones” that are
attracting attention as endocrine disruptors, and so on.
And, for example, even manipulating advanced mathematics such as accessible only tomathematicians, or, conversely, introduce an easily solvable “toy model”, a method
often used by physicists, as long as researchers are obsessed with “classical theory”, it is
not possible to understand living phenomena *.
The expression “toy model” is used, for example, by Dyson (“Origins of life”) and
Shin-ichiroTomonaga (“Quantum mechanics and I”). What it means is a model that
does not exist but is mathematically easy to solve. Just like a child’s toy, it might not be
useful, but it is suitable for children to play with and might even be educational.
Freeman Dyson, “Seimei no kigen”, Kyoritsu Shuppan, p. 55
Shin-ichiroTomonaga, “Ryoshi rikigaku to watashi”, Iwnami Bunko, p. 218
Just as Darwin and Pasteur were not constrained by the preceding old paradigms, now,
we have to seek a road to liberation from the spells of Darwin and Pasteur. For thispurpose, it is necessary to correctly understand the assumptions and achievements of the“classical” theories, and their limits, and perhaps doubt the assumptions themselves, andeven re-lay the fundamental concepts of genes, evolution, origins and essence of life. I
5would like to give an overview of the achievements of molecular biology soon after its
birth, within the context of this chapter.
The achievement of molecular biology in describing the single origin of life – therise of reductionism
The spectacular advancement of molecular biology from the 1950s through the 1960s,
saw many new discoveries, one after the other, with such momentum that one could
think that the mystery of life would be completely solved. It was also the success ofthorough reductionism, which sought essence in “simplicity”, rather than “complexity”,
of living phenomena.
* Piaget says “The opposition to reductionism had to appeal to structuralism. Between
two structures at different levels, there does not exist reduction in one direction, rather
the exists mutual assimilation” (“Genetic epistemology,” Hakusuisha, p. 145)
Be that as it may, let us list here some of the glorious successes of molecular biology
at that time.
- All living things have genes consisting basically of a nucleic acid DNA, and that
substance has a splendid spiral structure.
- The genetic code of DNA, consisting of three nucleotide sequences that specify aminoacids, is basically common in all forms of life
- Even though there are hundreds of amino acids that have been artificially synthesized,
there are only 20 types of amino acid in the protein actually used in living organisms.
- The same amino acids are common, regardless of the form of life.
And so on.
Let us synthesize these facts. It can be very clearly seen that the various forms of life
living and breathing on the earth – from the fish living in the deepest seas, to the birds
flying high in the sky, towering trees and microorganisms that can only be seen with amicroscope – have common ancestry.
However, long before these results of molecular biology became apparent, even before
the “laws of inheritance” were discovered by Mendel, there was a person who
theoretically argued that the various living forms transformed progressively from asingle original species. He was Charles Darwin *.
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* Alfred Wallace (“The Malay Archipelago”) also independently arrived at the sameconclusion as Darwin. That Darwin even considered withholding from publication after
reading an essay sent to him from Wallace is well-known as an episode that calls tomind his character.
Darwin’s “Law of Natural Selection” – thinking from “models” of domestic
animals and cultivated plants
Darwin synthesized the theories of the time, collected as many observational facts as
possible, and published “The Origin of Species” in the form of a compilation. It was
1859. That Darwin was able to have sharp insights about the origin of the variety oflife forms at a time when “Divine creation” was widely believed, is encouraging for us
in our research, as we run this way and that way observing complex living phenomena.
Here I wish to touch a little on the history of Darwin’s reasoning.
Darwin was interested in the fact that organisms placed in an artificial environment,such as cultivated plants and domestic animals, are full of a lot of variants that cannot
be seen in the field. He focused on traits that human mutations appear by chance inindividuals, and considered that it was the result of repeating "artificial selection" using
a genetic predisposition for similar things to produce similar things.
Namely, it was realized that it is not that humans directly did something to suddenly
create a new variant, but rather that by simply accumulating “genetic mutations”
through generations, they indirectly selected a variant. Hence, it was thought that
mutations that are not inherited are not important even if they are large, and mutations
that are inherited, even if they are small, can have large cumulative effect due to“human selection”. Thus, Darwin, by first considering the origin of domesticatedspecies, discovered “the law of variation of species” that comes from “genetic mutation”
and “human selection”.
Next, Darwin considered that this law, which was discovered in an artificial
environment, could hold similarly also in natural environments. It just so happens,Darwin, who was reading Malthus’ “An Essay on the Principle of Population”, wasdeeply sympathetic with claims such as “Conflict is selection, and also creation”.

7For this reason, if we assume that all living creatures in the natural world were to leave
more offspring than is necessary, we can imagine that a tough “struggle for existence”
would unfold. Actually, the fact that imported animals spread quickly because they havefew natural competitors, vividly speaks of the “struggle for existence” that is always
going in every place.
And Darwin thought that in the “struggle for existence”, if an individual happens to beborn with a feature that is even a little advantageous in the struggle, then that individual
would be naturally selected. This is “natural selection”. Further, if such an advantageous
feature were passed to the next generation, then the offspring of the individuals who
survived due to natural selection would increase in number more and more. During thisproliferation process, “genetic mutation”, “struggle for existence”, and “natural
selection” continues relentlessly, and eventually no doubt a new species could appear.
In this case, the origin of a new species in the natural world can be explained by the lawof transformation consisting of genetic mutation, struggle for existence, and natural
selection.
So then, with this law in hand, let us look back at the history of the variety of species
that exist today. Then, the many species can be aggregated into a few ancestral species.
This small number of ancestral species can be reduced to an even smaller number ofprimitive species. Finally, we reach a single primitive species. In this way, it was shownthat the variety of species that exist today can be derived progressively through theaccumulation of random mutations starting from a single primitive species. At the sametime it meant a negation of the “divine creation theory”. This is the logical process of
Darwin.
In Darwin’s research method, it is possible to point out two aspects that are useful forpursuing our research. The first aspect is that he used a “model” to probe living
phenomena, and checked the validity of the insights obtained the model by observing
the living phenomena in the natural world. The specific “model” in his case was
breeding animals and cultivated plants. The second aspect is that, by the most naïve
method, observation, he explored simple laws from complex living phenomena.
Of course, the two aspects pointed out here were indispensable for the discovery of the“law of natural selection”. But at the same time we must not forget that it also
demonstrates the limit of applicability of the “law of natural selection”. First, we should8be careful of the point that the “model” of breeding animals and plants has an implicit
hidden assumption that breeding animals and plants essentially do not differ from wild
animals and plants. Incidentally, this assumption is not necessarily obvious. That is
because living organisms in high stress states of breeding environments exhibit higher
mutation, and cooperative rather than competitive relations are often observed in wild
animals. Hence, that there are differences between the conclusions of the “segregation
theory” of Kinji Imanishi who focused on the social behavior of wild life, and “thenatural selection theory” of Darwin who considered breeding animals, does not meanthat we should think one is correct and the other is incorrect.
The issue here is not which theory is right and which theory is wrong. Rather, theproblem is that it has not been made clear which theory is applicable to which domain,and not applicable to which domain. For Kenji Imanishi’s “segregation theory” see“Seibutsu shakai no ronri” (Heibonsha). And comparison with Darwin’s “natural
selection” is described in “Dauin ron” (ChukoShinsho). The sprouts of Imanishi-stylenatural science can be seen in “Seibustu no sekai” (Kodansha).
Kinji Imanishi,“The world of living things” (Translation Pamela J. Asquith, Routledge
2002)
However, the “natural selection theory” of Darwin should not be regarded as aprinciple of “from unity to diversity”. Certainly, there is no doubt that a single original
species was transformed into a variety of species. However, for this, there is a premisethat before the single original species began to speciate the individuals belonging to thespecies already had variety. Each individual, each in its own way, adapts to various
environments. This is how new species are formed. In other words, the origin of thevariety of the species is the variety of the environment and the variety intrinsic in livingorganisms that could respond and realize transformation. This is what I would like totreat as a principle of “diversity from diversity”.
Once Darwin’s “natural selection” theory was accepted, it soon came to be called“Darwin’s evolution theory”, and spread to more and more people. However, here there
is a puzzle. Actually, in “The Origin of Species” the word “evolution” cannot be found.
Instead, the words “genetic transformation” and “change” are frequently used. Why isthat? We can point to one possible reason that in the biological science of the time theconcept of “evolution” was not established.
9This may be just the reason why “The Origin of Species” caused such a great reaction.
However, the concept of “evolution” was well-known in social science and philosophy,
politics and natural science, and we shouldn’t forget that before the publication of “TheOrigin of Species”, it was already introduced to biology by Herbert Spencer (forexample, recorded in “Sekai no meicho 36”, Chuokoronsha), who is also known forproposing using the term “survival of the fittest” in place of “natural selection”,* Daisetz Suzuki (D.T. Suzuki), says that "Evolution is development toward the outside.
… We are destined to involution, i.e., proceeding toward the inside” (“Toyo no kokoro”,
Shunjusha, p. 144). These words resonate with the observation of Hideki Yukawa, citedin the introduction, “observation from the inner side”.
It seems simply because there was such a foreshadowing, that the concept of evolution
rapidly became established as popular knowledge in the 10 years after the publication of"The Origin of Species". This can also be perceived from the fact that in the preface of"Origin of human race" that Darwin published in 1871 (for example, "“Sekai no meicho39", Chuokoronsha) he uses the word “evolution” without hesitation when citing "The
Origin of Species". However, even in the sixth edition of the "The Origin of Species"
published the following year, the word “evolution” is still not used. There must be an
important reason. The reason will become apparent by consideration of the "Origin oflife" in the following.
Darwin in the conclusions of “The Origin of Species” writes “life was imbued withbreath by the creator”. From this expression it should not be simply concluded that “inregard to the origin of life, there is a divine domain where the scientific scalpel cannot
enter, even for Darwin”. In a letter to friend Hooker in 1871, there is mention of “there
exists ammonia, phosphate, light, heat, electricity, …”, intimating that the origin of life
was “evolution” of living phenomena from chemical phenomena.
Here we finally solve the mystery of why Darwin did not use the word `evolution' in
the "The Origin of Species". As we know from the observation by Thomas Huxley,
Darwin grasped his own theory in this way. “It is a theory which assumes that living
things first existed, and clarifies the mechanism for their changing”. Since it assumes
that life existed, it is clear that it cannot be used to explain the origin of life.

10* The achievement of Darwin is that he revealed the law of transformation exhibited by
species that already exist. From this “law of transformation” it is impossible tofundamentally argue about “What is life?” - in other words “What does it mean for life
to exist?” In order to have a fundamental debate, I think it is necessary to mention
about “How is life born?” and “How is consciousness born?” However, if the origin oflife is considered as the evolution from chemical phenomena to living phenomena, thelaw of evolution must be a law that also explains the origin of life. Perhaps it was
because Darwin was aware of the limitations of his theory, that he did not use the word
evolution.
Here, I want to consider a little bit about the context of the scientific revolution leading
to the paradigm shift of the negation of the Creation Theory. While for better or forworse Darwin’s “The Origin of Species” was causing a stir, the “Law of inheritance”
discovered by Mendel (1866) had been forgotten for 30 years. I think that this factteaches us a valuable lesson.
First, it can be said that for a scientific revolution to take place, it is important that a
number of scientists independently acquire awareness of the same issue as thediscoverer. In the case of Darwin, Wallace’s existence was valuable. Also, it was certainthat there was a mutual effect from Spencer bringing the idea of “evolution” to biology.
Moreover, we shouldn’t overlook the fact that Huxley, as “Darwin’s bulldog”, not only
advocated the claims of Darwin, but he also made speeches and obtained theunderstanding of the masses. However, unfortunately in the case of Mendel, he was notblessed with (the support of) such intellectuals*.
Hideki Yukawa in “My reason for living” (Kagaku bunmei to sōzōsei, Yukawa Hideki
Chosakushū 4, Iwanami Shoten, p. 265), makes the following point. “In the beginningwhen I have a new idea, it is absolutely a minority view. It is creative because I think of
it by myself. This original idea might later become recognized by others. Then it is truth.
However, it might not be recognized by others. In some cases, it is possible that the idea
might never be recognized in one’s lifetime. I realized that even then it is very importantto keep trying.” There are many things that make us think about how original was the“Laws of inheritance” discovered by Mendel (see Chapter 5, pp. 123-137).
However, more important than anything, we should remember, as Huxley said, “thework of Darwin is the greatest compilation of biological knowledge that could be made11

by one man". It is full of the vigor of Darwin as a pioneer. Taking the opposite view,
already many intellectuals were becoming aware of the “transformation of species”.
However, the reason why we have the impression that Darwin’s achievements stand out,
is because he doesn’t just emphasize the conclusion of “transformation of species”, but
he collected and presented encyclopedic evidence, and showed the derivation of theconclusion, “transformation of species”, in “The Origin of Species”. For this reason,
readers of “The Origin of Species”, as they read, can reconstruct the logical process of
Darwin, each in his own way. This process of constructing from separate elements isessential for understanding new concepts.
Now, here a dilemma occurs. The reason for the success of Darwin in changing theparadigm was his work exhibited a high degree of completion for the time. However,
because it was so complete, 20th century biology faces the dilemma that it cannot take a
step toward a new paradigm change. The only way to overcome this difficulty is to takemore time than Darwin took, take an original voyage into a “new world” that he did notknow, and make a compilation of it.
Lamark’s “Use and disuse theory” – fluid motion theory with the model of simple
lifeform amoeba
Exactly a half century before Darwin’s “The Origin of Species”, in 1809, Frenchnaturalist Lamarck published "Animal Philosophy". In it, he proposed the “use anddisuse theory” (organs that are used develop, and organs that are not used degenerate)
based on the assumption that the individual adapts to the environment. And he claimed
that the adaptive changes of the individual to the environment were inherited – in otherwords, there was inheritance of acquired characteristics, and so any individual could
uniformly achieve adaptive transformations. In regard to explaining the variety of
species, while Darwin considered the variety of individuals as important, Lamarck
considered that the variety of the environment was more important than the variety of
the individuals.
* A complete translation of "Animal Philosophy" was published in 1988 from Asahi
Press series Phase II "Great Books of Science", Series II, Volume 5. The subtitle of thischapter only mentions Pasteur and Darwin. Actually, when I started to write this book a
few years ago now, I myself was within the flow of modern biology, and I was unable
to incorporate a conflicting concept in my “concept construction”. Hence I had a12negative view of Lamarck. What gave me the motivation to read “Animal Philosophy”
and an opportunity to have an interest in Lamarck was one book that I found by chancein the English books section of a bookstore, (E. Jablonka, and M. J. Lamb, “Epigenetic
Inheritance and Evolution-The Lamarkian Dimension”, Oxford University Press, 1995).
** Lamarck theory stands on the assumption that “individuals are homogenous” andclaims that the whole species transforms simultaneously together, as if the individuals
are the species and the species is the individuals”. I wish to point out the point that thisclaim is consistent with what Kinji Imanishi claimed (“Dauin ron”, Chukoshinsho, p.
43) based on the “truth” obtained from observations of living creatures in the wild, that“the species and the individuals are one and the same, when a species changes the eachindividual must change in the same way”. In contrast, Darwin, since he was assuming
the variety of the individual, he was for the first time able to explain the “truth”
obtained from observations of breeding animals and plants. My intention is not toemphasize the conflict between incompatible theories, but to re-emphasize that theconflict occurs because the observation subjects differ – in other words, “conflicting
coexistence” is the true essence.
The word “evolution” is not in Lamarck’s "Animal Philosophy" either of course,
Instead, “progression” is used *. This is because, as motivation for writing this book,while observing various animals, he realized that there was no absolute constancy in theconcept of “species” – it is always relative with even an artificial ambiguity. Then there
arose the irresistible question of why the concept of “species” is such a relative one. Asa question to that question, he thought that the variety of animal and plant structures
could be always “progressing” in the direction of increasing complexity. Moreover, heclaimed that the origin of the advanced complexity of body and sophisticatedintelligence exhibited by humans, can both be found in the “fluid motion” of life forms
with extremely simple structures, such as amoeba. Although the “fluid motion theory”
of Lamarck would be discarded, this approach, that is a constructive approach based on
phylogenetic history, would be useful for understanding not only the bodies andintelligence of we humans, but various living phenomena, including health and diseasephenomena such as immune systems and cancer.
* In order to distinguish between animals and plants that continue to “progress” withever increasing variety, and substances that do not exhibit such “progress”, Lamarckinvented the word “biology”.
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As Lamarck himself emphasized, the reason for writing "Animal Philosophy" was notjust to present a conclusion, but to rely on the descriptions there to re-constructconclusions that the readers would judge to be reasonable. Actually, in the preface of“Animal Philosophy”, he writes “As is well known, one inference can always be met byanother inference… So, the truth that can be clearly trusted is in practice only the factsof observation. Not the conclusion that is drawn from them.” (Asahi Shuppansha, p.
15).
Despite the care to add annotations to caution against over-emphasizing theconclusions that he derived, ironically, his conclusions have continued to be
misunderstood to this day. One of the possible reasons, is that in the English translation
which was published in 1814, five years after the publication of “Animal Philosophy",
the word “besoin” was translated as “will” or ”wish” instead of “need”, giving thewrong impression to many intellectuals, including Darwin.
In regard to Lamark’s annotations, I completely agree. However, in regard to whether
or not Larmak’s theory is logically and scientifically constructed, or whether it requires
modification in the light of the new facts known today, some discussion is necessary. So
next I will point out problems in Lamark’s theory.
The first problem, is the point that in the “use-disuse theory”, he assumes from the
beginning that “an individual adapts to its environment throughout its life”. Thus, forexample, the claim that the adaptive changes of an individual are accumulated in later
generations through the inheritance of acquired characteristics, leading consequently toadaptive transformation, falls into circular reasoning. In order to avoid this circularreasoning, it is necessary to clarify the mechanisms and laws underlying the initialassumption that “individuals adapt to the environment”, without relying on the concept
of “adaptation”. Actually, the concept of “adaptation” can be explained by the law oftransformation involving genetic mutation, survival struggle, and natural selection, as
discovered by Darwin.
The second problem is that he invokes two assumptions that cannot be accepted today.
One is the assumption that spontaneous generation of simple living species occurs
continually, in the past and today. (As we show in the next section, this spontaneous
generation theory was brilliantly negated by the experiments of Pasteur). The other is14the assumption that in nature, species do not become extinct. These assumptions induce
complete inconsistency with the facts.
The third problem is, in regard to inheritance of “acquired characteristics”, Lamarck
does not make clear a concrete mechanism. Incidentally, the concept of “inheritance ofacquired attributes” was widely accepted as “common knowledge” at the time.
Therefore, Darwin also had accepted this concept. In his publication “The Variation ofAnimals and Plants under Domestication” (1868) he endeavored to explain how
acquired characteristics were inherited by the next generation. This is the “pangenesis”
hypothesis. However, today Lamark’s theory of “inheritance of acquired characteristics”
and is often used as if synonymous with “adaptive evolution” (or “directed evolution”).
Just as genetic information changes as it gets successively copied, concepts and theories
become completely transformed when they leave their original text and get copied frombook to book. For this reason, it is important as much as possible to return to theoriginal text and understand it correctly.
Anyway, while Darwin’s theory of natural selection spread widely, Lamarckism was
hidden in the shadows. However, as will be discussed in Chapters 5 and 6, the facts
prompt the rise not only of neo-Darwinism but also of neo-Lamarckism.
Pasteur’s “negation of spontaneous generation” - Consequences from the ideal“model” of fermentation phenomenon
In England, Darwin wrote the "The Origin of Species", and negated "creation theory''.
Then just two years later, in France now, Louis Pasteur authored "Study of the Theoryof Spontaneous Generation” and negated the "theory of spontaneous generation".
The theory of spontaneous generation, supported also by philosopher Aristotle ofancient Greece, was widely believed until the late Middle Ages. According to it, forexample, "a frog may occur from the mud of the swamp, and an eel is generated fromthe water of the river". Of course, needless to say, such “beliefs” were destroyed one by
one by facts. Finally, spontaneous generation was negated and the issue was settled withthe proof that maggots, which were believed to generate from rotting flesh, actuallycame from the eggs of flies. It looked like spontaneous generation theory was gone andforgotten. However, from around the beginning of the 18th century, observation withmicroscopes became widespread, and the world of microorganisms could not only be
15

seen with marvel, but also exaggerated and dramatized by imagination, and thespontaneous generation theory reappeared. Doubtless such circumstances of this age
were also behind Lamarck’s assumption of spontaneous generation of life forms withsimple structures.
In such an era, Pasteur, without heeding the warnings of his friends, headed toward“An examination of the doctrine of spontaneous generation”. It is perhaps more correct
to view that it was due to the fact that the fermentation that Pasteur had studied to thenwas a suitable model for examination of spontaneous generation, rather than due to thefact that examination of spontaneous generation was the subject of a prize sponsored by
the Paris Scientific Academy.
In the fermentation theory of the time, one could not deny the possibility that “whentwo substances are mixed together, a change occurs and as a result the organic
substance yeast is spontaneously generated”. The two substances are a fermentable
substance such as sugar and a proteinaceous substance that acts on it. It was thought thatwhen the proteinaceous substance comes into contact with air, the characteristic of yeast– namely the tendency to act on the fermentable substance - was acquired.
Pasteur was particularly interested in the origin of yeast. It had already been
established in 1836 that beer yeast was organic. The issue was “Was an organic
substance generated from a non-organic substance, or was it already mixed in with thenon-organic substances?” As a result of investigating various fermentation phenomena,
including lactic acid fermentation, butyric acid fermentation, and malic acidfermentation, Pasteur arrived at the conclusion that in all cases “organic material
already existed with the non-organic substances”.
In this way, because Pasteur was able to use the “model” of fermentation as his basis,
it was possible for him to scientifically advance the study of spontaneous generation,
which till then was considered the touchstone of wisdom of naturalists. He decided touse an even simpler experimental system to study the crux of the problem of the originof yeast in fermentation. It was an experiment that would see if life was spontaneously
generated by sealing a substance like milk that changes easily in a glass container andbringing it into contact with air. The experimental results were very clear. They showedthat if the air was treated with strong heating, no change was observed in the milk, andif the milk is placed in an atmosphere that is not heat-treated then mold and bacteria
16breed quickly. Obviously, the origin of the mold and bacteria was in the air. Thus thelaw that “only life begets life” was established.
By careful observation, Pasteur was able to show that when the growth of mold was
rapid, the growth of bacteria was very small. He explains the reason as “the things thatfirst multiply inhibit others” (L. Pasteur, in “Consideration of Spontaneous Generation
Theory” (“Shizenhassei setsu no kento”, Iwanamibunko, p. 72)). It can be said that thisobservation by Pasteur graphically shows that the “struggle for survival” also occurs in
the world of microorganisms. In other words, the pattern that Darwin was observing in
the world of animals, Pasteur was also observing in the world of microorganisms.
Thus, it became definite that all species, from lower organisms to higher organisms,
have been transformed from a single original species, in accordance with ''natural
selection theory "of Darwin. Of course, needless to say, the law discovered by Pasteur at
this time, that “only life begets life” became the basis for the subsequent developmentof medical and biological sciences. Actually, the first application of this law can be seenin the success of rabies vaccine by Pasteur himself. He saved the life of a boy called
Meister who had been bitten by a rabid dog, by using an inactive vaccine in which thepathogen had been killed and the ability to infect had been lost. The reason he was able
to use the vaccine was because he was confident that once the pathogen was killed it
would not reappear. The simple method for long term preservation of foods in cans andbottles is possible because once germs are killed, they do not re-generate. The law
discovered by Pasteur saw one application after enough. However, even this law, which
is now common knowledge, has a counter-example. That is the “origin of life”, whenlife appeared from non-living substances for the first time.
In the 18th century, Tenner developed attenuated live vaccine using cow pox instead ofhuman pox. However, in live vaccine, the pathogen is not dead, and in this respect ismore dangerous. The name vaccine came from “vacca” meaning cow.
It may be thought that after the important discoveries in biology, of “natural selection”
by Darwin and “negation of spontaneous generation” by Pasteur, that the discovery of anatural law concerning the origin of life would be achieved in just a few more steps.
However, to this day, 140 years since the publication of “The Origin of Species”, thelaw of the origin of life has not been found.

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So next, we will give an overview of what modern molecular biology has made clear
about the problem of the origin of life.
The achievements and limits of molecular biology in regard to the origin of life –the outlook for reduction to elemental “processes”
In 1983, an RNA nucleic acid called “ribozyme” that had genetic information andcatalytic function was independently discovered by Cech and Altman (Cech, 1990). The
reason why this discovery aroused interest was because it was thought that the “chicken
and egg” paradox that had continued for many years would be immediately resolved.
The “chicken and egg” paradox refers to the ongoing debate about whether the firstmolecule to appear is the nucleic acid (the egg) or the functional protein (the chicken),since nucleic acid (the egg) cannot be copied without protein (the chicken), but protein(the chicken) cannot be synthesized without the corresponding nuclei acid (the egg).
However, so far, RNA that can catalyze its own self-replication or catalyze thereplication of other RNA has not been found in the natural world. The discovered
ribozyme function just catalyzes the splicing and linking of RNA. Nevertheless, it isclear that the discovery that one type of molecule RNA can have both information andfunction overturned the common sense that “there is an absolute distinction between
information molecules and functional molecules and there is no cross-over between
them”. Thus it came to be thought that the first domain of life is RNA – as named by
Gilbert, “the RNA world” (W. Gilbert, 1986)
However, here we face the next paradox. Let us try to imagine the origin of the single
species of RNA molecule. Certainly, if we adopt the assumption that self-replicating
RNA modules exist, natural selection will lead to the selection of an optimal RNA
molecule species. However, the situation is not promising. If RNA was “spontaneously
generated”, such a species would not have self-replicating ability. Then we would haveto consider how the process of evolution could be driven. We can think of two
possibilities. One is the viewpoint focusing on the “self-organizing function” within
RNA itself. The other possibility is the viewpoint that considers an evolutionary process
different from RNA.
The situation became confused again with multiple claims about the “domain for theorigin of life” - crystals of clay by the English chemist Cairns-Smith (Cairns-Smith,
1985, 1987), metallic-surface of pyrite by the German lawyer and amateur researcher,18

Wachtershauser (Wachtershauser, 1988, 1990), and sulfur compound called thioester by
the Belgian biochemist De Duve (De Duve, 1991). It is still not yet clear what laws
govern the evolution from materials to life. In other words, the original living species
has been just been replaced by the molecular species of RNA, and the problem of theorigin of the “RNA world” has not been fundamentally solved.
In 1993, the book “The RNA World” (eds. R. F. Gesteland and J. F. Atkins, 1993) was
published from Cold Spring Harbor Research Laboratories. Crick and Watson eachseparately wrote prefaces, and many famous researchers contributed papers. In the
beginning is a paper by Joyce and Orgel. The conclusion of their paper commences withthe following sober phrase. "After dreaming of self-replicating ribozymes..., and having
nightmares about the difficulties …, we awaken to the cold light of day ...” (Joyce andOrgel, 1993, p.22) *.
Following after the well-received first edition, a second edition with recent findings
was published in 1999 (eds. R. F. Gesteland, T. R. Cech, and J. F. Atkins, 1999).
However, the conclusion of Joyce and Orgel, that a fundamental solution to the problem
was a long way off, was the same as in the first edition.
Moreover, Stanley Miller, who in 1953 shocked scientists throughout the world by
succeeding in synthesizing amino acid in a primitive atmosphere experiment, severely
assessed the situation with the comment “At this time, no-one has said anything
conclusive” (Hogan, 1991).
Thus, so far, research about the origin of life has run aground. What is the reason forthis? Perhaps it is because the strong adherence to the reductionist research method has
resulted in too much focus on searching for the molecules that are directly linked to theorigin. Reduced to molecules, the essence of life will be lost. I do not think thatmolecules that are missing the essence of life can be used to grasp the origin of life. It isnecessary to not adhere to old paradigms, and take up new viewpoints. I think that inorder to discover the law of the origin of life, it is necessary to clarify the origin of the“process” of “evolution”. This is where “process” reduction theory can be used.
Here I wish to raise a problem. In the experimental research concerning the origin of life,
as in the research of artificial life, moral discussions are necessary *.

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* Moral issues are described for example in the postscript of theoretical biologist
Maturana ‘s “Biology of Cognition” (“Autopoesis”, Kokubunsha, pp. 161-241)
H. R. Maturana, “Biology of Cognition” in “Autopoiesis and Cognition: The
Realization of the Living”, Dordecht: D. Reidel Publishing Co., 1980, pp. 5-58.
http://www.enolagaia.com/M70-80BoC.html
In each case, assuming the experiment is successful, in Pasteur’s law that “only life
begets life”, another exception will be added in addition to the origin of life. That is not
the only problem. It is conceivable that at that time we will lose the basis for medical
and biological sciences that we have built up starting with the rabies vaccine. That
will bring on a very serious situation. I think of “life” as a system that can exchange allof structure, function, information, and energy. Hence, undoubtedly, such “life” after
being created would immediately negate our own existence.
Finally, I would like to finish the chapter by summarizing my views about the essenceof paradigm change, comparing “development of cognition” and “advancement of
biology”.
The essence of paradigm change – development process of cognition anddevelopment process of biology
Just as in embryology, there was a paradigm shift from “preformation theory”, inwhich the structure of the individual exists before development, to “postformation
theory”, in which the structure is composed, in the field of natural history there was aparadigm shift from “divine creation theory”, in which animal species forever remain
the way that they were created by God, to “species transformation theory”, in whichanimal species forever transform. Thus, a “Copernican revolution”, so to speak, from`static' existence to `dynamic' existence is a common criterion for realizing scientificrevolution, in any field of study.
For example, consider we thoroughly analyze the embryo and adult organism of ananimal. Most likely, we would discover a set of properties of the subject. However,since such `intra-subject` analysis only grasps the `static` existence, the description is no
more than local. As the next stage of cognition, we shift our focus from the embryo tothe adult, and from the embryo and adult of one species to the embryo and adult of20

another species. From this `inter-subject` comparative analysis it is possible to see themutual relations between subjects. By linking up the inter-subject relations it is possible
to see the embryonic process and evolutionary process as `dynamic' processes. This iswhat was referred to earlier as the Copernican revolution in the history of biology.
Of course, cognition proceeds to the next stage. Once the mutual relations between
objects are seen by `inter-subject' analysis, then `inter-relation' analysis is possible. In
the example described above, this corresponds to the `embryonic process' from embryo
to adult derived through `inter-subject' analysis, and then the `evolutionary process'from one animal species to another animal species. At this time, our interest is not in the
animal embryo and adult which were the original subject of analysis, but in aiming for alarger unification that allows us to grasp the whole of life while exploring the dynamic
processes common to genesis and development. In that case, through the changing
processes, it will become possible to construct new concepts with which we can explain
the existence of life. As an example, we can give the comparative study of `antigen
recognition by the immune system' and `the onset of cancer in a healthy cell' as
unfolded in the next chapter. These two seemingly completely different processes wereperceived by Barnett as `natural selection' processes at the molecular level *. Thus 20th
century biology transcended the Copernican revolution of the 19th century, and headed
toward an even larger unification.
* As we describe in the next chapter, according to Burnett, the concept of ‘evolution’and Darwin’s concept of ‘natural selection’ have almost the same meaning. However, as
will become clear as we proceed through Chapters 5 and 6, it is necessary to reconsider
the concept of ‘evolution’. The reason is that ‘evolution’ has aspects that can be reduced
to the transformation process based on Darwin’s ‘natural selection’, but there areaspects that cannot be understood in this way – for example, aspects linked with the‘origins’ of new structures with leaps. In other words, it is necessary to redefine‘evolution’ as a wider concept that can incorporate continuous transformation processesand ‘origins’ with non-continuous leaps
In this way, our interest transcends the original subjects (in this case, the subjects
embryo and adult organism introduced at the beginning), and aims for a larger
integration of genesis, evolution, immune system, and cancer – which can be expressedas ‘super subject’. By continuing this operation further, from the phase of change that is‘process’ it becomes possible provide an explanation about the ‘reality’ that is life. Here,21

another revolution (opposite to a Copernican-like revolution) occurs, from ‘dynamic’process to ‘static’ existence (here we aim for a systematic explanation of life).
We note that the terms ‘intra-', `inter-' and `trans-' used here are due to the work of
Piaget and Garcia (“Psychogenesis and the History of Science”). I think that one of thegreatest achievements left by Piaget is, comparing children and scientists from the pointof view of development of cognition, and found the general process of development ofcognition from ‘intra-‘ to ‘inter-’ and then to ‘trans-’ as a characteristic of thedevelopment of cognition. However, in the case of Piaget, the scientists that hecompared with children were mainly mathematicians and physicists. I constructed thehistory of biology introduced here by including biologists in the comparison, and inregard to biological phenomena, I considered not only normal processes but also
abnormal processes.
I wish to add one additional explanation. In Chapter 1, I pointed out that, whether it
was nucleic acid or protein, new diseases evolve with historical development fromintra-species propagation to inter-species propagation. Such transition from “intra” to“inter” has been taking place commonly not only in the development of our cognition,
but also in the world of living organisms.
Summary of this chapter
With the theme that it is essential that, like living organisms, the study of livingorganisms that is biology, changes continually, we gave an overview of 19th century
biology, focusing on Darwin’s “theory of natural selection” and Pasteur’s “negation of
spontaneous generation”. As history shows, these theories caused a paradigm shift in
19th century biology. However, there remain many problems that are not solved by these
theories. One is the problem of the “origin of life”. Despite the spectacularadvancements of the molecular biology that was born in the mid-20th century, it is thetruth that we are still troubled by the fact that there is not even an outlook toward
solving the problem.
In the second part, the reason that I propose “Self-non-self circulation theory” is, by
focusing on the elemental process, we throw a light on such unsolved problems.

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In the next chapter, I wish to discourse about how we came to be able re-grasp bothantigen cognition by immune system, which is representative of “health”, and cancer,
which is representative of “disease”, in the context of “theory of natural selection at thecell level”.

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