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A Brief Conceptual History of Epigenetics, and More Besides

Arnaud POCHEVILLE

CRBE, Université de Toulouse, France

1.1. Introduction

Epigenetics concerns the expression of genetic information - or, more generally, non-genetic (biological) information altogether.

A polymorphous concept with multiple origins, sometimes used very liberally or absent where it is expected, epigenetics is deeply rooted in understanding "generation", in other words, the way in which living beings are formed.

There are two main groups of answers to the question of generation: either the form is already there, pre-existing its manifestation in the organized being; or it is created as it grows.

The history of epigenetics is the history of a dialectic between these two groups, always in tension, always on the verge of resolution, always in transformation.

Figure 1.1. Epigenetics has many faces. Its definition depends on the context in which we find ourselves, and it may yet evolve. Follow us in Chapter 1 to find out why. Illustration by Annette Köhn

1.2. The birth of the term: from epigenesis to pangenesis

The term "epigenetics"appeared in the 17th century as a noun, "epigenesis", in a treatise by the English physician and anatomist William Harvey (1651, Exercitatio 45). In it, Harvey outlined his work on the causes of animal generation, responding in particular to Aristotle (330-322 BCE) (Aristotle 1887) and his own master, Fabricius (1621). Harvey distinguishes two possible modes of generation: either the material of the future animal is already present and receives its form like wax imprinted by a seal, all parts being formed simultaneously, which he calls metamorphosis; or the material is added as the form is born, like a potter's pot, the parts of the animal coming into being from one another, which he calls epigenesis. For Harvey, the generation of the chick from the egg is clearly the result of epigenesis, not metamorphosis. It is an idea that is tempting to see already discussed, albeit ambiguously, by Aristotle; however, it is important to bear in mind the differences in frameworks and debates between eras (Lennox 2006; Goy 2018; Bolduc 2021).

In the 18th century, another vision of generation gained ground: mechanistic preformationism (Bowler 2001, pp. 26-28). Preformationism assumes that form pre-exists generation. From an empirical point of view, the idea is justified by the observation (thanks to the use of the microscope) of microscopic organs and organisms, which suggest the possible existence in the living world of structures of infinitesimal size and therefore undetectable to our senses (Malpighi 1666; Malebranche 1674, pp. 41-42; see Gasking 1967, pp. 45-46, quoted by Roe 1981, pp. 83-87). From a philosophical point of view, preformation allows the formation of a living being to be reduced to simple growth, a mechanism set in motion at conception, at a time when the mechanistic vision is gaining traction (Bowler 2001, pp. 26-28; Wolfe 2016, 2017). The most extreme form of this vision (known as pre-existing germs) assumes that all living beings pre-exist their generation, nested like nesting dolls within each other since Creation, such as aphids whose parthenogenesis and nested generations are demonstrated by a proponent of preformation (Bonnet 1745, 1762, Chapter 1, 1770, pp. 190-191). This vision resonates with a Christian point of view, which in turn justifies the comprehensibility of the world (God lays down natural laws) (Roe 1981, p. 111; Bowler 2001, pp. 29-31). Conversely, preformationists see epigenesis as synonymous with chance, chaos and indeterminacy (and hence incomprehensibility). Advocates of atheism favor epigenetic theories, as well as those of spontaneous generation, which dispense with the idea of Creation (Buffon 1749; see Roe 1981, pp. 16-18; Spallanzani 1765; d'Holbach 1770; Bowler 2001, pp. 29-36).

Mechanistic preformationism fell into disfavor at the turn of the 18th and 19th centuries (Roe 1981, p. 150; Bowler 2001, p. 32; Wolfe 2016, 2017). We would prefer an epigenesis whose mechanistic vision is supplemented by the idea of forces specific to living organisms, which organize them (e.g. Maupertuis 1745, Chapter XI-XII, 1756a, Chapter LXV-LXVII; see Ibrahim 2019; Wolff 1759, 1768; Blumenbach 1780; see Bowler 2001, pp. 40-42; Dupont 2007; Wolfe 2019; Schmitt 2021). This vision gives rise to mystical trends (Naturphilosophie: Schelling 1797; Oken 1809; Bowler 2001, pp. 41-42), as well as to so-called teleomechanist trends, which aim to naturalize the notion of finality in living organisms, embryogenesis appearing to be such a process oriented towards a finality, the formed organism (Kant 1790; Lenoir 1982; Bowler 2001, p. 42; Huneman 2006; Moreno and Mossio 2015). The vision that emerges is that of a homology between the individual and the lineage, with parents shaping their children in the same way a craftsman produces an artifact, in a process akin to copying the parent, part by part - there is therefore, said in today's terms, inheritance of acquired traits (Bowler 2001, p. 23, 38).

This is a vision carried forward by Jean-Baptiste de Lamarck (1809a, Chapter II)in particular, who produced a veritable physicalist theory of the transformation of living beings (and of their spontaneous generation). For him, living beings become organized and complex throughout life and across generations by virtue of movements of fluids, caused by the use of certain parts of the organism whose needs, according to circumstances, are felt (Lamarck 1809b, Chapter VI). The use of a part strengthens it, and the acquired form is transmitted to descendants: this is a law that Lamarck considers empirically evident - the same one that posterity has associated with the neck of the giraffe (Lamarck 1809a, Chapter VII, p. 235). This posterity, sometimes simplifying and very unfaithful, remained influential until the middle of the 20th century, particularly in France, where it resonated with nationalist impulses that were sporadically reactivated by the international context (Boesiger 1980; Limoges 1980; Sapp 1987, pp. 124-128). However, we must be wary of reducing Lamarck to transformism through the inheritance of acquired traits (Bowler 2001, p. 37; Corsi 2001): his intuitions on the self-organization of what we would today call open systems are more reminiscent of the physics of out-of-equilibrium systems (Nicolis and Prigogine 1977; Bejan and Lorente 2004), and, in biology, organizational approaches to viability (Moreno and Mossio 2015).

In the Germanic world, teleomechanism underwent influential developments, culminating in the formulation of the law of parallelism - in the course of its development, the embryo passed through the hierarchy of animal forms, from fish to reptile to mammal, with man at the top (Meckel 1821, 1828 contra Von Baer 1828; Russell 1916; Temkin 1950; Oppenheimer 1967; Bowler 2001, pp. 42-44); a law which, when interpreted as the product of evolutionary history, forms the basis of recapitulation theory - the developing embryo recapitulates its evolutionary history (Haeckel 1866). Recapitulation theory, such as Lamarck's transformism, invites us to understand the transmission of traits between generations as analogous to memory (Haeckel 1876; Gould 1977; Robinson 1979; Bowler 2001, p. 52). However, teleomechanist embryologists are not so much interested in trait transmission as in how the "potentialities" of a fertilized egg develop (Lenoir 1982, Chapter 3; Bowler 2001, p. 44).

Meanwhile, heredity was emerging as a subject of study in its own right, particularly in the medical field, with the study of hereditary diseases (Lopez-Beltran 2007)1. In the 18th century, the notion of heredity could be prefigured by the study of noble diseases (such as gout), supposedly acquired through lifestyle (delicious food) and transmissible diseases, which resonated with the pressure put on the aristocratic family (Pomata 2003, p. 150; Müller-Wille and Rheinberger 2007, p. 11, 19). Mendelian-looking studies, such as that by Pierre Louis Moreau de Maupertuis (1756b, letter xiv, pp. 275-278) on the prevalence of polydactyly in a Berlin family, were in fact interpreted within a framework of epigenesis with the transmission of acquired traits (Bowler 2001, pp. 33-35; Terrall 2007, pp. 265-268). In the 19th century, the social tropism for the study of hereditary diseases changed (Müller-Wille and Rheinberger 2007, p. 19). Among other things, the aim was to improve hygiene: the poorer classes and their share of diseases, supposedly caused by the environment and being more or less hereditary, were perceived as the new threat to social order (Pomata 2003; Cartron 2007; Müller-Wille and Rheinberger 2007, p. 19). Other fields of...