C.H. Waddington: Genesis of the Original Epigeneticist

Excerpt from my forthcoming book Epigenetics and Public Policy The Tangled Web of Science and Politics to be released February 2018 by Praeger

Conrad Hal Waddington, who initially proposed epigenetics in 1939, is one of the more eclectic and interesting personalities in the natural science of his time, not for any flamboyance or peculiar affectation on his part, but for the range of his interests and work, which beyond biology also included an especial interest in the arts and philosophy. For example, although Waddington was a widely respected laboratory experimentalist, writer, and lecturer in embryology and genetics, holding prestigious research and university positions throughout his career, he accomplished all this without being academically credentialed in genetics or even biology. This diverse background, including Waddington’s unorthodox politics, will be shown to have a significant influence in his ‘discovery’ of epigenetics, and also provides clues as to why epigenetics was as ignored it was until fairly recently.

Given the importance of geology in the unfolding of the science of evolution detailed over the past few chapters, perhaps the first most conspicuous biographical fact about Waddington is that he earned his bachelor’s degree at Cambridge with a specialization in geology in 1926. He then went to graduate school also at Cambridge to study paleontology, focusing on ammonites, an extinct group of marine mollusks, which again mirrors significant developments in the early history of the theory of evolution. In these details, at least, Waddington reflected the origins and development of evolutionary thought from the previous century.

As a graduate student, Waddington actually held two studentships: one in geology and another in philosophy,[1] neither of which seem to have much of a link to the geneticist and epigeneticist that Waddington would become. However, Waddington’s interests in philosophy can be shown to have direct connections with his eventual ‘discovery’ of epigenetics. In particular, Waddington’s philosophy of choice was the process philosophy of the mathematician and philosopher Alfred North Whitehead, and especially Whitehead’s “philosophy of organism.” According to this philosophy, the world is composed not of material objects with their own independent existences, but rather of deeply interdependent processes and events.[2] The impact on Waddington of process philosophy and Whitehead’s book Science and the Modern World as an undergraduate appears to have been so profound that it impelled his exit from geology and his entrance into the world of biology and genetics,[3] which culminated in his postulation of epigenetics.

Waddington and the philosophy of process

Process philosophy is famously distinct from the prevailing reductionist and analytic paradigm of Western philosophy and science since Plato, which identifies objects as independent entities which can be broken down into their constituent parts until the simplest components are revealed, which will then explain the entire object. Instead, in process philosophy, an object is just “an ingredient” in the character of some event, only having effects via its interactions with other objects in these “events.”[4] For Whitehead, the provisional successes of this reductionist approach in science rendered what was a useful heuristic into an unquestionable worldview—but one which reasoned in a circle by taking its stipulated assumptions about independent and reducible objects as evidence of their existence.[5] Instead, Whitehead proposed that all existing things were the organic product of the ongoing interactions of many different processes, existing only as “events,” or as the persistence of the product of these interactions.[6]

Process philosophy was a lifelong inspiration for Waddington in perceiving the organic world as composed not of individual and independent entities but as the product of ongoing interconnected processes. In the last year of his life, Waddington describes the enduring effects of this philosophy on his scientific work, remarking that this early exposure to Whitehead had “totally inoculated me against the present epidemic intellectual disease, which causes people to argue that the reality of anything is proportional to the precision with which it can be defined in molecular or atomic terms.”[7]

As a signal of what was to come, in the paper which won him his philosophy scholarship in 1929, Waddington focused on the implications for biology of the process philosophy of Whitehead. In this paper, Waddington suggests that if all things actually are the product of interacting processes, instead of independent entities, then the “scientific explanation of the process of evolution, as that it is brought about by natural selection acting on gene mutations,” would still not qualify as a complete general explanation of evolution until it even genes are conceived as events, or as the ongoing product of these other processes.[8]

After only three years of graduate school, Waddington left Cambridge without having completed his planned doctoral thesis in geology to pursue his burgeoning interests in biology. Through a close friend (the equally eclectic and iconoclastic anthropologist Gregory Bateson, son of the geneticist William Bateson who actually coined the term ‘genetics’ in 1905), Waddington was given the opportunity to work with the eminent horticulturist and geneticist Edith Saunders. Often referred to as The Mother of British Plant Genetics, Saunders is most known for her significant role in the rediscovery of Mendelian heredity. Waddington worked with Saunders on a longstanding problem in the genetics of maladaptive recessive traits in plants, writing a paper on his treatment of the problem which was published in the prestigious Journal of Genetics in 1929.[9] In 1931, Waddington published a highly technical statistics-based paper on inbreeding and genetic linkage in the equally prestigious journal Genetics,[10] which he wrote in collaboration with the respected population geneticist J.B.S. Haldane.[11]

The move from genetics to embryology (and back)

Even with these early successes, though, Waddington was dissatisfied with the emphasis on reduction that permeated the study of genetics. Through another close friend Waddington secured a job at the Strangeways lab at Cambridge to study embryology, which he felt better reflected his inclinations towards process and development. Within a year, Waddington was able to complete difficult experimental work on the development mechanics of embryos in vitro that the lab founders had been unable to figure out, and to publish the results in Nature.[12] Waddington was then able to parlay these successes into a six-month stint at one of the most prestigious laboratories of embryology in the world in Berlin (the lab of Hans Spemann and Otto Mangold). Upon his return to Cambridge, Waddington was offered a position teaching experimental zoology and a fellowship with the Medical Research Council. Also, with another of his closest friends (the biochemist and polymath Joseph Needham), Waddington was able to build up one of the most respected laboratories of embryology in Europe on a shoestring budget.[13]

In his laboratory work, Waddington focused for the most part on the ‘organizer,’ which is the cluster of cells in developing embryos which induces the development of the central nervous system.[14] The discovery of the organizer and its basic mechanisms in 1921 by Ph.D. student Hilde Mangold and her advisor Hans Spemann merited a Nobel Prize for Spemann in 1935, but not Mangold who died from severe burns suffered in a kitchen explosion in her apartment in 1924.[15] Through this lab work Waddington repeatedly observed firsthand how the processes of development depended on specific configurations of the results of prior developments, and how differences in these prior conditions altered the outcomes of development. These observations would be pivotal in his subsequent postulation of epigenetics.

However, during this period Waddington also spent time at the Drosophilia (fruit fly) labs in Caltech and at the labs in Cold Spring Harbor. These labs were the epicenters of the emergence of molecular genetics which established the conception of genes as atomistic units. At these labs Waddington worked with some of the foremost researchers in genetics, such as Theodosius Dobzhansky and Alfred Sturtevant, just as they were making the discoveries which would contribute so much to the gene-centric focus of the Modern Synthesis. From this work, Waddington published numerous papers on the genetic control of wing development in normal and mutant strains of drosophila in journals such as The Proceedings of the National Academy of Science of the U.S.A, the Journal of Genetics, and Nature.

After World War II, during which Waddington contributed to the Allied war effort via operational research with the Royal Air Force, Waddington accepted an offer to be the chair of animal genetics at the University of Edinburgh where he remained until his death in 1975. At the time, this was one of only three chairs of genetics in the United Kingdom.

Thus, although Waddington was at heart and in practice an embryologist, and had not earned a degree in genetics, he was deeply involved in the development of the genetics of his time, and was respected enough to be considered one of the top scientists in the field. As will be discussed elsewhere, though, Waddington’s identification as an embryologist was in many ways as politically charged as his controversial political associations, to be discussed next. This discussion will demonstrate the intimate connections between Waddington’s background, his scientific work, and his politics, culminating in his postulation of epigenetics.

[1] The majority of these biographical details are gathered from the excellent and highly detailed dissertation of Erik L. Peterson, 2010, Finding mind, form, organism, and person in a reductionist age: The challenge of Gregory Bateson and CH Waddington to biological and anthropological orthodoxy, 1924–1980. University of Notre Dame.

[2] Whitehead, A.N. (1929/2010). Process and Reality. New York: Simon and Schuster, p. 73.

[3] Peterson, E.L., 2011. The excluded philosophy of evo-devo? Revisiting CH Waddington’s failed attempt to embed Alfred North Whitehead’s” organicism” in evolutionary biology. History and philosophy of the life sciences, pp.301-320.

[4] Whitehead, A.N. (1920/2004). The Concept of Nature. Mineola, NY: Dover Publications, Inc., p. 143.

[5] Whitehead, A. N. (1925/2011). Science and the modern world. Cambridge University Press, pp. 50-51.

[6] Whitehead (1925/2011), pp. 151-152.

[7] C. H. Waddington, “Fifty Years On,” Nature 258 (1975): 20–21.

[8] Waddington 1929 [unpublished], p. 66 in Peterson, 2011.

[9] Waddington, C. H. (1929). Pollen germination in stocks and the possibility of applying a lethal factor hypothesis to the interpretation of their breeding. Journal of Genetics, 21(2), 193-206.

[10] Haldane, J. B. S., & Waddington, C. H. (1931). Inbreeding and linkage. Genetics, 16(4), 357.

[11] Waddington’s relationship with Haldane will come up again in regards to their politics, but it is important to note at this point that Waddington later recalled his experience with Haldane and the “thin gruel of mathematical formalism” as a rather joyless endeavor, and said of Haldane that “I never knew him well, and I don’t actually think very much of all the ‘mathematical theory of evolution’ stuff which he started [because] it is all ultimately based on the quite falacious [sic] notion that selection coefficients belong to genes, whereas actually they belong to phenotypes,” which for Waddington was a distinction with “profound consequences.”

[12] Waddington, C. H. (1930). Developmental mechanics of chicken and duck embryos. Nature, 125, 924-925.

[13] Peterson 2011, p. 307.

[14] Philbrick, S., O’Neil, E. (2012, January 12) Spemann-Mangold Organizer. Embryo Project Encyclopedia . ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/2330.

[15] Doty, M. (2011, May 9) Hilde Mangold (1898-1924). Embryo Project Encyclopedia. ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/1743.


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