Conrad Hal Waddington

Conrad Hal Waddington (born November 8, 1905 in Evesham , † September 26, 1975 in Edinburgh ) was a British developmental biologist , paleontologist, geneticist, embryologist and philosopher. He delivered fundamental work on developmental biology and epigenetics . Waddington is considered to be an important precursor of today's evolutionary developmental biology (EvoDevo) and has been experiencing a "kind of renaissance" since the 1990s.

The terms “epigenetic landscape”, “ channeling ” and “ genetic assimilation ” introduced by Waddington are now common in EvoDevo research.

Life

Waddington was born to colonial British parents and grew up with his parents on a tea plantation in India for the first three years of his early childhood. At the age of three he was sent back to England, where he grew up with a related Quaker family in Sedgeberrow, Worcestershire. It was only when he was married at 23 that Waddington found a connection with his parents. Even as a child, Waddington was fascinated by fossils, especially ammonites , which he looked for and collected himself. Even in his youth he believed that the evolutionary development of ammonites could be explained by their patterns and shapes.

Waddington had a variety of interests since his youth, including poetry. As a student he edited and published his own poetry magazine. He was also a good athlete and loved hiking and climbing. As an adult he found great interest in the fine arts, sculpture and architecture and in 1969 even published a book ("Behind Appearance") on the relationship between art and science. He maintained close ties to famous artists, including the British sculptor Henry Moore and the German Bauhaus founder Walter Gropius .

In 1926 he married. His first marriage lasted until 1936. A son Jake was born from the marriage. Waddington studied at Cambridge University , where he became a lecturer in zoology and in 1936 a fellow at Christ's College.

During his studies he met Gregory Bateson (son of William Bateson ), with whom he was friends. Until 1936 Waddington had no scientific degree, but since 1929 he published several scientific papers on ammonites (1929), experimental embryology in avian embryos (1930), and together with JBS Haldane on genetic linkages (1931). Based on these early publications, Waddington was awarded a Cambridge ScD (Doctor of Science) degree in 1935.

In the course of his scientific career, Waddington dealt primarily but not only with developmental biology. In contrast to genetics and molecular biology research in his day , Waddington recognized that epigenetic mechanisms play a role in heredity, development, and evolution. He received decisive impulses from his six-month stay in Germany in 1931 with the developmental biologist Hans Spemann in Freiburg, the discoverer of the organizing region ( Spemann organizer ). In 1936 he worked in Thomas Hunt Morgan's laboratory in California. In the following years Waddington deepened experimental embryonic studies, examined the chemical nature of organizer regions on amphibious embryos. For the best embryonic research work of the year he received the highest award of the Royal Academy of Belgium, the Albert Brachet Prize for Embryology, in 1936. He was the first scientist to use organic culture methods to cultivate chicken embryos , which he used to analyze the induction of the nervous system. He was also the first to show the existence of an organizer in mammalian embryos and was the first to use radioactive tracer methods to analyze development.

Waddington's first book was published in 1939 on genetics, his second in 1940 on "Organizers and Genes", in which he brought together the findings of Spemann and Morgan.

In 1936 Waddington married the painter and architect Margaret Justin Blanco White (1911-2001), with whom he had two daughters, including the mathematician Dusa McDuff, born in 1945 as Margaret Dusa Waddington in London. During the war, Waddington worked for the Coast Guard.

In 1947 he was elected a Fellow of the Royal Society and was from 1947 Professor and Head of the Institute for Animal Genetics at the University of Edinburgh . By his 50th birthday in 1955, he built this institute into the largest genetic department in Great Britain and one of the most respected worldwide at the time. At this institute Waddington worked consistently after the war on the concept of epigenetics he founded for the causal research of development. He understood epigenetics as the sum of the factors that act at the cell, cell group or embryonic level to enable development, including genetic as well as internal and external environmental factors. Epigenetics understood in this way was multi-causal for him (as opposed to genocentric). It was also of an emergent nature ( emergence ) in the sense that the manifestations of higher levels in the embryo cannot be explained by the analysis of underlying levels alone, and likewise the properties of certain regions on one level of development cannot be explained without knowledge of the properties of other regions can be answered at the same level.

At the same time, Waddington conducted research in the field of theoretical biologists and took on the editing of a four-volume series entitled: "Towards a Theoretical Biology" (1968–1972) and organized four symposia of the International Union of Biological Sciences (IUBS), of which he became president .

Since 1948 he was a member of the Royal Society of Edinburgh . In 1958 he was appointed Commander of the British Empire (CBE). The American Academy of Arts and Sciences elected him a member in 1960, as did the German Academy of Sciences Leopoldina in 1974 . He received honorary doctorates from the Universities of Montreal, Prague, Geneva, Cincinnati, Aberdeen and Trinity College Dublin. 1970-71 he worked at the State University of New York Buffalo, where the first signs of a heart condition made themselves felt. He died of it two months before his seventieth birthday.

In total, Waddington published 18 books and edited 9 works in his 42 year career. During his lifetime and until long afterwards he did not find the recognition that science pays him today. The science of his time was focused on genetics and molecular biology. It was not until the 1990s that new epigenetic approaches gradually emerged in evolutionary developmental biology, which is still heavily based on the findings of Waddington today. Against this background, Waddington can be seen as one of the great integrators who brought the disciplines of genetics, epigenetics, development and evolution closer together.

Scientific positions

The environmental impact of evolution

Waddington demonstrated that a genetic and epigenetic interaction is possible in such a way that, despite certain mutations, the same phenotype characteristic is developed or retained. In development, several paths are usually laid out in order to produce the phenotype or to produce a certain phenotypic characteristic. The large number of genetic alternatives is due to the fact that a large number of genes are always combined to form a phenotypic trait. The selection affects the entire system of existing and alternative development paths.

Waddington used the ostrich as an example of epigenetic developmental processes and, as a special feature, the evolutionary origin of which he intended to explain, the conspicuous skin calluses on the bird's chest, where it has no feathers. (The calluses protected the animal when it crouched on the hot, rough desert floor.) Waddington assumed that at some point the calluses did not exist in the ostrich. The species may have contracted the calluses over generations during its youthful growth through stress on the corresponding body parts. For example, an environmental factor that Waddington does not specify could be very hot and / or stony sandy soil that was previously absent. This may have been the reason that the developmental course is changed and it is now based on the diverse gene combinations and expressions described above and also the capabilities of the developmental system that produce the calluses. This happens initially with the help of the persistent environmental stressor that has occurred, which affects not only a single animal but the entire population.

In a first phase, the trait is assumed to have been formed by straining the body part in question while crouching and has not yet been genetically inherited. Then in development what Waddington calls channeling took place , which in this case is a change in the course of development. Contrary to all views of the (then) Darwinian theory of evolution, it cannot be genetically inherited, but first of all it needs the external stressor.

Waddington's understanding of epigenetics

The term epigenetics was first used by Waddington. Epigenetics, as he understood it, can be seen in today's terms as the transmission of certain properties to the offspring that are not or not exclusively due to changes in gene regulation and gene expression in development . Waddington presented this graphically for the first time in his essay "The Strategy of the Genes" (1957). You can see hills and valleys through which a ball is rolling. The ball represents the course of development. At the highest point of the plateau is the fertilized egg cell, the zygote . The ball follows existing development paths (channeling). Because of the valley walls between the individual paths, the course cannot be easily changed (buffering). However, an induction from outside can be strong enough to overcome a valley wall in the epigenetic landscape. The ball then reaches a neighboring valley, or the development is channeled differently.

Channeling

Once the path is channeled in a valley, the phenotypic output (e.g. calluses) does not change despite persistent genetic mutations, because the entire system reacts in such a way that the channeling established is retained with the same output "calluses". The genotype is buffered, it has precautions ready which, together with development and the environment, lead to the "desired" output "calluses".

Genetic assimilation

→ Main article : Genetic assimilation

As a result, the stimulus may become unnecessary or only necessary in a weakened manner. The response of the whole system to the exogenous stimulus (e.g. hot sand) is such that it is relatively easily overwritten by existing redundant, internal, genetic / epigenetic mechanisms and the system is thus genetically fixed. Waddington later said: The developmental change triggered by the stressor can be genetically assimilated (genetic assimilation). The system then “works” without any external impetus. It is directed towards the same phenotype . As at the beginning of the variation, this is ensured by gene combinations and expression patterns that can cause similar variation and that are always present in various ways in the organism, as well as the emergent epigenetic abilities of the entire development system. The processes leading up to genetic assimilation are always subject to selection. Since selection already favors the phenotype exhibiting environmentally induced calluses, it stands to reason that it also selects the type in the population that will produce genetic assimilation.

If an environmental factor continues to act long enough on the development process, it can influence the course of development in such a way that the ball not only overcomes a ridge and reaches another valley, but as a result the epigenetic landscape itself changes in such a way that the inhibiting hill between the old and the new valley is dismantled by the development apparatus and the ball naturally follows the new valley. Genetic assimilation has taken place.

Channeling thus allows genetic diversity or variability to develop even though it does not appear in the phenotype. Such hidden, genetic variability or hidden developmental paths (the different valleys) are only revealed through genetic assimilation.

Genotype buffering

Waddington describes the diverse gene combinations and epigenetic developmental pathways present in the organism during development that lead to the same or very similar phenotypic result as buffering the genotype. In his words, he says: “The genotype can absorb (or buffer) a certain amount of its own mutation ), without allowing a change in development. ”This buffering of the genotype is nothing other than the constancy (robustness) of the wild type of species in their natural environment. Because of their greater genetic diversity, species there are known to be more immune to phenotypic variation than is the case with breeding animals.

Buffering and channeling are two sides of the same coin. They are the result of natural selection. The whole process doesn’t take nearly as long as it would alternatively be assumed that the organism with purely genetic (random) mutations will arrive at the same result. Channeling is an evolutionary path that enables species to react more flexibly and faster to environmental changes, and to take a quasi “holding position” until the genome brings about the fixation. "Some aspects of the phenotype appear to be remarkably invariant despite genetic and environmental differences." By this is meant what Waddington describes by channeling.

Empirical evidence

In 1953, Waddington provided empirical evidence for his theses in the essay Genetic Assimilation of an Acquired Character and shows how the veins in fly wings disappear, triggered by short heat shocks of the fly eggs repeated over several generations, and how the veins in some animals also without them the heat shocks stay away. The change is assimilated in the development of the flies. A similar experiment is repeated for the first time 50 years later by Fred Nijhout, USA, on tobacco hawks. The very short-term evolution of the beak forms of Darwin's finches , as described by Peter and Rosemary Grant, is also associated with changes in development, especially with changes in the protein Hsp90 . Likewise, the decades-long attempt by the Russian geneticist Dmitry Belyaev to tame silver foxes shows many changes in development that are now interpreted in the sense of Waddington.

Waddington thus proved theoretically and empirically his doubts, which he had already expressed in 1942, "that the purely statistical, natural selection, which does nothing other than sort out random mutations, can be completely satisfactory even for the most convinced, statistically trained geneticist."

Coordination of development, evolution and the environment

Overall, Waddington's study shows “how the genotype of an evolving organism can respond to the environment in a coordinated way.” Development and evolution can be coordinated with environmental influences and deal with them in a directed manner (in relation to the retention of the phenotype). "Channeling is an ability of the system that was brought about by natural selection." "The existence of an adaptive response to an environmental stimulus depends on the selection of the coordinated and genetically controlled responsiveness in the organism."

Waddington and the synthetic theory of evolution

Waddington has been very committed to ensuring that ontogeny is recognized by the synthetic theory of evolution . He did not succeed in doing this during his lifetime. In his time, genetic centrism and molecular biology were the driving forces, not epigenetics and development. Waddington found attention in Ernst Mayr's 1966 book Animal Species and Evolution . Mayr wrote there: "Our ideas about the relationship between genotype and phenotype have been fundamentally reconsidered and the phenotype is no longer seen as a mosaic of individually controlled gene characteristics as the combined product of a complex interactive system, the 'epigenotype'." However, Mayr did not remain with this view and appreciation, who later relativized Waddington's contributions to the effect that he evaluated his arguments as "the basis for individual selection versus genetic selection but not as the basis for seeing development as relevant to the theory of evolution." In the 1970s the number of voices who saw development as important for evolution increased, Mayr remained on the side of synthesis and viewed Waddington more skeptically. During this time, Waddington was repeatedly brought closer to Lamarckism , as his 1953 essay "Genetic Assimilation of an Acquired Character" expresses this closeness. In fact, however, Waddington's thinking is not related to Lamarck's thinking. Only the extended synthesis in evolution takes up important ideas of Waddington for an opening of the theory of evolution.

Waddington's importance as a forefather of EvoDevo

Only with the advancement of evolutionary developmental biology ( EvoDevo ) does Waddington come to honor again. To this day he is on a path of increasing recognition. In their 2005 book Evolution in Four Dimensions , Eva Jablonka and Marion Lamb paid tribute to Waddington several times. “Long before we knew about the intricate pathways of gene regulation and the interaction of genes, and long before concepts about gene networks became fashionable, geneticists recognized that the development of any trait from a web of interactions between genes, their products, and the environment depends. A visible representation of these ideas that is still relevant and helpful was developed by the British embryologist and geneticist Conrad Waddington in the 1940s and 50s. ” Scott F. Gilbert and David Epel, in their 2009 work“ Ecological Devolopment Biology - Integrating Epigenetics, Medicine and Evolution ”also highlights Waddington's achievements and contrasts them with the achievements of the Russian researcher Ivan I. Schmalhausen , who came to similar findings at the same time as Waddington. In his essay Evo-Devo as a discipline, Gerd Müller names both the (genetic) assimilation of Waddington and the entire field of epigenetics in the Waddingtonian sense as the conceptual roots of EvoDevo. Finally, the Altenberg-16 group, which published their work Evolution The Extended Synthesis in 2010 (Ed. Massimo Pigliucci and Gerd B. Müller ), referred to Waddington. In a speech at the Konrad Lorenz Institute for Evolution and Cognition Research in Altenberg in 2008, Manfred Laubichler calls Waddington the forefather of theoretical evolutionary developmental biology.

Writings and works

items

• The genetic control of wing development in Drosophila. In: J. Genet. Volume 39, 1940, pp. 75-139.
• Evolution of developmental systems. In: Nature. Volume 147, 1941, pp. 108-110.
• Canalization of development and the inheritance of acquired characters. In: Nature. Volume 150, 1942, pp. 563-564.
• Selection of the genetic basis for an acquired character. In: Nature. Volume 169, 1952, p. 278.
• Genetic assimilation of an acquired character. In: evolution. Volume 7, 1953, pp. 118-126.
• Genetic assimilation of the bithorax phenotype. In: evolution. Volume 10, 1956, pp. 1-13.
• Canalisation of development and genetic assimilation of acquired characters. In: Nature. Volume 183, 1959, pp. 1654-1655.
• Experiments on channeling selection. In: Genet. Res. Vol. 1, 1960, pp. 140-150.
• Genetic assimilation. In: Adv. Genet. Volume 10, 1961, pp. 257-293.

Books

• The Scientific Attitude . Pelican Books, 1941.
• How animals develop . George Allen & Unwin, London 1946.
• Organizers & genes . Cambridge University Press, Cambridge 1947.
• Principles of Embryology . George Allen & Unwin, London 1956.
• The Strategy of The Genes . Allan and Unwin, London 1957.
• Biological organization cellular and subcellular. proceedings of a symposium . Pergamon Press, London 1959.
• The ethical animal . George Allen & Unwin, London 1960.
• The human evolutionary system. In: Michael Banton (Ed.): Darwinism and the Study of Society . Tavistock, London 1961.
• Principles of development and differentiation . Macmillan Company, New York 1966.
• New patterns in genetics and development . Columbia University Press, New York 1966.
• as editor: Towards a Theoretical Biology. 4 volumes. Edinburgh University Press, Edinburgh 1968-1972.

Web links

• Literature by and about Conrad Hal Waddington in the catalog of the German National Library

Individual evidence

1. ^ Eva Jablonka, Marion J. Lamb: Evolution in four dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life . MIT Press, Cambridge, Mass. 2005, ISBN 0-262-10107-6 .
2. ↑ Académie royale des Sciences, des Lettres et des Beaux-Arts de Belgique: Conrad Hal Waddington - Prix Albert Brachet 1934 ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. 
3. ^ Fellows Directory. Biographical Index: Former RSE Fellows 1783–2002. (PDF file) Royal Society of Edinburgh, accessed April 19, 2020 . 
4. ^ List of members Leopoldina, Conrad Hal Waddington
5. ^ ^{A b} C. H. Waddington: Canalization of development and the inheritance of acquired characters. 1942, p. 564.
6. ↑ CH Waddington: Canalisation of development and the inheritance of acquired characters. 1942, p. 563f.
7. ↑ CH Waddington: Canalisation of development and the inheritance of acquired characters. 1942, p. 564f.
8. ↑ Waddington's term epigenetics has to be clearly distinguished from epigenetics .
9. ↑ The graphic can be found e.g. B. on http://www.pep-web.org/document.php?id=joap.049.0250.jpg
10. ^ Eva Jablonka, Marion J. Lamb: Evolution in four dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. MIT Press, 2005, p. 63.
11. ↑ ^{a b c d e} C. H. Waddington: Canalization of development and the inheritance of acquired characters. 1942, p. 563.
12. ↑ CH Waddington: Canalisation of development and the inheritance of acquired characters. 1942, p. 564.
13. ^ Eva Jablonka, Marion J. Lamb: Evolution in four dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. MIT Press, 2005, p. 275.
14. ^ Eva Jablonka, Marion J. Lamb: Evolution in four dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. MIT Press, 2005, p. 62.
15. ↑ Yuichiro Suzuki, H. Federic Nihjout: Genetic basis of adaptive evolution of a polyphenism by genetic accommodation . In: Journal of Evolutionary Biology. 21, No. 1, 2008, pp. 57-66. doi: 10.1111 / j.1420-9101.2007.01464.x
16. ↑ Peter R. Grant, B. Rosemary Grant: Genetics and the origin of bird species. In: Proceedings of the National Academy of Sciences. Volume 94, No. 15, July 1997, pp. 7768-7775. (PDF)
17. ↑ Ludmila N. Trut: Early Canid Domestication: The Farm-Fox Experiment. In: American Scientist. Vol. 87, 1999.
18. ↑ CH Waddington: Canalisation of development and the inheritance of acquired characters. 1942, p. 563f.
19. ↑ CH Waddington: Canalisation of development and the inheritance of acquired characters. 1942, p. 565.
20. ^ Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought. 2005, p. 194.
21. ^ Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought. 2005, p. 195.
22. ^ Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought. 2005, p. 210.
23. ^ Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought. 2005, p. 210, with reference to Ernst Mayr 1966, p. 6 u. 148, 185.
24. ^ ^{A b} Ron Amundson: The Changing Role of the Embryo in Evolutionary Thought. 2005, p. 211.
25. ^ Eva Jablonka, Marion J. Lamb: Evolution in four dimensions. Genetic, Epigenetic, Behavioral and Symbolic Variation in the History of Life. 2005, pp. 62f and 261–266.
26. ^ Scott F. Gilbert, David Epel: Ecological Devolopment Biology - Integrating Epigenetics, Medicine and Evolution. Sinauer, 2009, p. 375f, genetic assimilation p. 443, 427, plasticity p. 455f.
27. ^ Gerd Müller: Evo-Devo as a Discipline. In: A. Minelli, G. Fusco: Evolving Pathways - Key Themes in Evolutionary Development Biology. Cambridge University Press, 2008, p. 7.
28. ^ M. Pigliucci: Phenotypic Plasticity. In: Massimo Pigliucci , Gerd B. Müller : Evolution - the Extended Synthesis. MIT Press, 2010, p. 367.
29. ↑ Manfred D. Laubichler: Conrad Hal Waddington, Forefather of Theoretical EvoDevo. Guest editorial at a conference of the Konrad Lorenz Institute for Evolution and Cognition Research in Altenberg b. Vienna