Before Tomorrow- Epigenesis and Rationality

by Catherine Malabou

  20. Genova, “Kant’s Epigenesis of Pure Reason,” p. 267.

  21. Boltzmann, Principien der Naturfilosofi, p. 222. Cited by Bouveresse in “Le problème de l’a priori,” p. 364.

  22. “Le problème de l’a priori,” p. 357.

  23. Gottlob Frege, Posthumous Writings, trans. Peter Long and Roger M. White, Chicago: University of Chicago Press, 1979, p. 4.

  24. Gottlob Frege, The Foundations of Arithmetic: A Logico-Mathematical Inquiry into the Concept of Number, trans. J.L. Austin, second revised edition, Evanston, IL: Northwestern University Press, 1980, p. vi.

  25. Frege, The Foundations of Arithmetic, p. vi.

  26. The Foundations of Arithmetic, p. vi.

  27. The Foundations of Arithmetic, p. 6.

  28. Cited by Bouveresse in “Le problème de l’a priori,” p. 361. Frege, 17 Key Sentences on Logic, in Posthumous Writings, p. 174.

  29. Bouveresse, “Le problème de l’a priori,” p. 366. On this point, it is impossible not to refer to the polemic between Frege and Husserl on the topic of transcendental idealism. Bouveresse reminds us that for Husserl, only an exploration of transcendental interiority could allow for situating the source of truth. In Formal and Transcendental Logic, Husserl actually states: “Only by virtue of a fundamental clarification, penetrating the depths of the inwardness that produces cognition and theory, the transcendental inwardness, does what is produced as genuine theory and genuine science become understandable. Only by virtue of such a clarification, moreover, does the true sense of that being become understandable, which science has labored to bring out in its theories as true being, as true Nature, as the true cultural world.” Edmund Husserl, Formal and Transcendental Logic, trans. Dorion Cairns, The Hague: Martinus Nijhoff, 1969, pp. 15–16. Cited by Bouveresse, in “Le problème de l’a priori,” p. 366. For a full and detailed study of the problem, see Jacques Derrida’s major study in his work The Problem of Genesis in Husserl’s Philosophy, trans. Marian Hobson, Chicago: University of Chicago Press, 2003, “The Polemic with Frege,” pp. 23–4.

  30. Bouveresse, “Le problème de l’a priori,” p. 366.

  31. “Le problème de l’a priori,” p. 368. In arguing for this position, Bouveresse counters Hans D. Sluga’s interpretation developed in his work Gottlob Frege, London: Routledge & Kegan Paul, 1980. He explains this position on p. 368.

  32. “Le problème de l’a priori,” p. 354.

  33. CPR, p. 263, B164.

  7

  FROM EPIGENESIS TO EPIGENETICS

  This last conclusion is all the more powerful given that contemporary mental evolutionism, or mental Darwinism, puts the concept of brain epigenesis to work and thus presents itself as the most contemporary version of the neo-skeptical thesis.

  Mental or neural Darwinism is based on a theory known as the epigenesis of neuronal networks by selective stabilization of synapses.It is striking that even in this theory it is again a matter of describing the agreement process between cognitive categories and the objects of experience. However, in mental Darwinism, epigenesis sheds its role as analogy and appears instead as a physiological reality. The systematic alignment of cognitive structures and the constitution of mental objects develop through epigenesis on the basis of a natural, biologically determined dynamic.

  In what respect is neural Darwinism a radicalization of the neo-skeptical argument, and to what extent does it cut epigenesis off still further from its transcendental moorings? How does it construe the relation between the focus and epicenter of the agreement? And how do we measure the distance that separates it from the Kantian position?

  Defining Epigenetics

  Let’s start by explaining that the contemporary understanding of epigenesis draws on the meaning of “epigenetics,” to which it is closely linked. The neologism “epigenetics” was created in 1940 by British biologist Conrad Waddington. The noun “epigenetics” refers to the branch of molecular biology that studies relations between genes and the individual features they produce, that is, the relation between genotype and phenotype. Reflecting with hindsight on the creation of this term, in 1968 Waddington commented: “Some years ago [. . .] I introduced the word ‘epigenetics,’ derived from the Aristotelian word ‘epigenesis’, which had more or less passed into disuse, as a suitable name for the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being.”1 The adjective “epigenetic” thus refers to everything to do with this interaction and is concerned with the mechanisms of expression and transcription of the genetic code.

  These mechanisms are largely determinant for the activation or inhibition of genes in the process of constituting the phenotype. Take, for example, cellular differentiation. In 1935, in his acceptance speech for the Nobel Prize, Thomas Morgan was already asking: “[I]f the characters of the individual are determined by the genes, then why are not all the cells of the body exactly alike?”2 How can the difference between a neuron and a hepatic cell, for example, be explained, given that their starting point is one and the same, since all the cells of a single organism share an identical genetic heritage? Differentiated cellular development depends on the selective use of certain genes via activation and silencing. Epigenetic mechanisms structure the self-differentiation of the living being.

  One essential aspect of the meaning of “traditional” epigenesis is thus also found in contemporary “epigenetics.” It is still a matter of defining ontogenesis, or individual development, as an autonomous, self-formed, and formative growth, also known as “epigenetic history.”

  The prefix “epi” is illuminated in an entirely remarkable manner at this point since epigenetics studies the mechanisms that modify the function of genes by activating or deactivating them. Insofar as these modifications never alter the DNA sequence itself, epigenetics is said to work on the “surface” (epi) of the molecule.

  So what kinds of changes take place on the “surface”? Three main epigenetic actors are currently known: RNA, the nucleosome, and the methylation of DNA. The function of RNA as messenger and transmitter of information between DNA and proteins situated outside the cell is familiar. It has a major role, particularly since the discovery of RNA interference. The nucleosome is a structure that represents the first level of compression of DNA in the cell’s nucleus. By controlling the accessibility of the double strand of DNA, it is directly involved in the regulation of nuclear processes such as the transcription, regulation, or repairing of DNA. It is formed from four histones (proteins) and is the basic unit of the chromatin (the chromosome substance) for eukaryotes.3 Modifications and variations in these histones impact the degree of openness or closure of the chromatin. The third epigenetic mechanism is the methylation of DNA. DNA has four nucleobases: thymine, adenine, guanine, and cytosine. The methylation of DNA modifies these bases and also plays a key role in the activation and inactivation of genes.4

  To be Done, Once and for All, with “Everything’s Genetic”

  Again, changes implemented by epigenetic factors do not affect the DNA sequence. While epigenetics has a wide field of action, it does not have any impact on the code. It is striking that the complex relation between the genetic and the epigenetic – a relation that is one of the fundamental questions of contemporary biology – is a renewed version of the debate between preformationism and epigenesis that gave rise to just as many polemics. In the second half of the twentieth century, the concept of “program” dominated genetics. This phenomenon was often described as the symptom of a “resurgence of preformationism.”5 But the idea of a program is precisely that which is in question today as a result of the importance of epigenetic factors in debates on heredity. In his “critique of the notion of genetic program,” Changeux even proposes that we “relinquish” it, just like the transcendental!6

  This new orientation in the “logic of life” derives largely from the results of the sequencing of the human genome. On February 15, 2001, the American scientific journal Nature pu
blished the virtually complete sequence of the three billion bases of this genome.7 The result was surprising: the human genome is made up of only 30,000 genes, in other words, just 13,000 more than Drosophila (commonly known as fruit flies). Furthermore, it appears that genes make up only 5 percent of the genome. Assembled in bunches and clusters, they are separated by vast expanses of so-called “gene deserts,” made up of “junk” or “repetitive” – that is, non-coding – DNA. According to studies, this “non-coding” DNA accounts for a quarter or a third of the totality of the genome. Consequently, within chromosomes there are long DNA sequences which, according to current understanding, do not appear to match genes and cannot be given any particular function.8 The sequencing of the genome did not, therefore, offer the expected revelations.

  Nor did the sequencing of the genome show the all-powerful effect of genetic determinism; instead, it indicated its weakening. In his book eloquently entitled La Fin du “tout génétique”? Vers de nouveaux paradigmes en biologie, Henri Atlan notes the challenge to the “genetic paradigm.” He writes: “The idea that ‘everything is genetic’ is starting to be seriously unsettled.”9 More recently, he wrote:

  During the last forty or fifty years, the classical ideal that seeks to explain very complex observations by reducing them to laws or simple mechanisms appeared to have been attained in biology thanks to the discovery of the genetic code and its universality. This was truly an extraordinary discovery that ought to have led to the invariable law underlying all biological processes. As such, a genetic reductionism crowned with success appeared to be in sight and it was assumed that the achievement of the sequencing of the human genome would conform to this expectation. In fact, the completion of this project showed that everything was not written in DNA sequences, even at the molecular and cellular level.10

  From that point on, a new model was established, “which renews interest in molecules that vector information that is not reducible to the information contained in the DNA structures alone.” Atlan subsequently wrote:

  [T]he idea that the totality or essential aspects of the development and functioning of living organisms is determined by a genetic program tends to be gradually replaced by a more complex model that is based on notions of interaction, reciprocal effects between the genetic, whose central role is not denied, and the epigenetic, whose importance we are gradually discovering.11

  We have thus entered the biological “post-genomic” era.12 François Jacob had already anticipated this when he wrote:

  [T]he genetic programme is not rigidly laid down. Very often it only sets the limits of action by environment, or merely gives the organism the ability to react, the power to acquire some extra information which is not inborn. Phenomena such as regeneration or modifications produced in the individual by environment certainly indicate some degree of flexibility in the expression of the programme.13

  This “flexibility” is precisely the object of epigenetics today.

  The Importance of Environment

  Epigenetic modifications have the particularity of being inheritable from one generation of a cell to the next. Unlike genetic heredity, this heredity is reversible. Nevertheless, it causes increased complexity in the evolutionary process. Let me explain this point. Epigenetic modifications depend on two types of causes: internal and structural, on the one hand, and environmental, on the other. First, it is a matter of the physical and chemical mechanisms described earlier (RNA, nucleosome, methylation). Secondly, epigenetics also supplies genetic material with a means of reacting to the evolution of environmental conditions. For example, while plants do not have a nervous system, they have the ability to memorize seasonal changes at the cellular level.14 Among animals, reactions to environmental conditions are even greater. Laboratory studies of consanguine mice have recently shown that a change of diet has an influence on offspring. The fur color of the young – brown, yellow, or dappled gray – depends strictly on this change. When pregnant females are given certain food supplements,15 the majority of their young develop brown fur. The young mice born of the control mice that did not receive these supplements have yellow or dappled fur. There is, therefore, a transmissible memory of changes linked to environment. Many geneticists now think that the behavior of genes can thus be modified by life experiences.16

  Let’s return to our initial question. I said that the debate between preformationism and epigenetism has shifted and now occurs between genetic determinism and epigenetic shaping. The fundamental question of the biology of development is to determine whether genes contain all the information necessary for the formation of the embryo and the adult organism. An increasing number of scientists support the idea that, more than a program that simply unfolds (the thesis held by biologists from 1970 to 1990), “it is the system constituted by the organism and its environment that in fact develops.”17

  The quarrels between the two parties (genetic/epigenetic) are reminiscent of the debates that raged during Kant’s era.18 Despite it all, contemporary epigenetics seems not to serve the Kantian thesis insofar as it does appear to present a greater contradiction with the idea of a priori epigenesis! An important element in epigenetic factors in fact derives from the environment, the outside, and, as we shall see with brain epigenesis, learning, the milieu, habit, in a word, experience. The definition of phenotypical malleability proposed by the American biologist Mary-Jane West-Eberhard is eloquent in this respect. She says that it is a matter of the “ability of an organism to react to an environmental input with a change in form, state, movement, or rate of activity.”19 The a posteriori thus plays an essential role in the “formative drive” of epigenetics!

  “Neural Darwinism” and Brain Epigenesis

  The example of brain epigenesis appears to confirm these conclusions once and for all. In Neuronal Man, Jean-Pierre Changeux revealed to the general public for the first time the theory initially presented in 1976 in an article entitled “A Theory of Epigenesis of Neuronal Networks by Selective Stabilization of Synapses,” which was the result of his collaboration with Philippe Courrèges and Antoine Danchin.20 A later version of this theory appeared under the title: “Selective Stabilization of Developing Synapses as a Mechanism for the Specification of Neural Networks.”21

  To speak of mental or neural Darwinism might initially appear contradictory. Indeed, for Darwin, epigenesis, as a theory of individual development, was relegated and subordinated to the concept of the evolution of the species. Yet contemporary epigenetics reintroduces precisely the development of the individual into the heart of evolution, opening a new theoretical space called “evo-devo” – “evolutionary developmental biology.” Philosopher of biology Thomas Pradeu confirms this innovation when he writes: “There is a virtual consensus that in the years to come evo-devo will be one of the most dynamic fields of biology and one of the most fascinating objects for the philosophy of biology.”22

  The genetics’ claim that development does not influence the passage from the genotype to the phenotype is no longer tenable today. For this reason, it is now impossible to separate embryology, developmental biology, and evolutionary biology. Without going into the lively debates that this new understanding of evolutionism provokes, I should mention that the adaptive factors of organisms other than natural selection are now recognized as playing a prime role in evolutionary processes. The evolutionary dynamic is enriched by the contribution of epigenetics.23

  Synaptic Mechanisms

  Let us return to synaptic epigenesis. During the life of the fetus, most of the 100 billion neurons at work in the brain are formed, as are the innumerable synaptic connections that link them. Under the influence of experiences lived in utero and later on during the first years of life, many of these so-called “irrelevant” or “redundant” connections are eliminated, while others are consolidated. This is the work of epigenesis by selection–stabilization. This process does not only take place during the “critical” periods of development, for throughout life the brain undergoes synap
tic modifications imposed on it by experience.

  In fact, brain development continues long after birth and depends to a large extent on environmental and cultural factors. As Changeux constantly reminds us, the theory of epigenesis by synaptic stabilization is thus the opposite of innatism. This results in a widened definition of epigenesis: epigenesis now concerns everything “that is not preformed.” As Changeux also points out, we observe “an evolutionary paradox” that marks the discontinuity between brain complexity and genetic complexity, with brain complexity being far greater than genetic complexity.24 This discontinuity, or non-linear evolution, between the increasing complexity of brain organization, on the one hand, and the apparent invariability of the DNA content in the cellular nucleus at the level of living beings, on the other, prevents us from calling on innatism or any other version of preformationism. Here again the brain has its own life and development, which do not depend entirely on genetic information. Neurobiologists agree that “the brain is more than a reflection of our genes.”25

  Selection Levels

  How do epigenetic brain mechanisms function? During the development of the nervous system, the networks’ activity leads either to stabilization or to the elimination of the synapses of which they are formed. Among all the possible neuronal pathways that exist between two areas of the brain, the most efficient will be chosen and consolidated with a view to subsequent solicitations.