Waddington, Conrad Hal

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WADDINGTON, CONRAD HAL

(b. Evesham, United Kingdom, 8 November 1905;

d. Edinburgh, United Kingdom, 26 September 1975), embryology, developmental biology, evolutionary biology, genetic assimilation, canalization, epigenetics, epigenetic landscape.

The discovery in 1900 of Mendel’s experiments on genetics, coupled with a burst of research on genes and genetics in the ensuing several decades revolutionized the understanding of heredity but at the cost of divorcing embryos from genetics and from heredity. Conrad Hal Waddington was one of the first scientists to integrate genetics with embryology and evolution. He performed this remarkable feat (1) by formulating and providing experimental evidence for the mechanisms of genetic assimilation and canalization; and (2) by fostering— through direct experimentation and publication of seminal textbooks—an epigenetic (multi-process) rather than a genes-only basis of embryonic development and of evolutionary change in development and adult form. Waddington coined the term epigenetics for the causal analysis of embryonic development, by which he meant all the factors acting on a cell or embryo to allow it to develop, including genetic, and internal and external environmental factors. He saw phenotype as processes, not static structures and behaviors. A foundational member of the Theoretical Biology Club, Waddington was a pioneering theoretical biologist, especially in the application of the philosophy espoused by the philosopher and meta-physician Alfred North Whitehead: “Thus my particular slant on evolution—a most unfashionable emphasis on the importance of the developing phenotype—is a fairly direct derivative from Whiteheadian-type metaphysics” (Waddington, 1975, p. 597). Epigenetic and hierarchical approaches, which Waddington saw as metaphysical, stand in contrast to the reductionist approaches typical of most geneticists.

Origins and Early Interests. Waddington had the early life typical of so many of the children of British citizens who made their living in what were then the colonies. The first three years of his life were spent on a tea plantation in India with his parents Hal and Mary Ellen before being sent back to England to live with Quaker relatives, initially an uncle and aunt on a farm in Sedgeberrow, Worcestershire. Waddington did not see his father between his fifth and fifteenth birthday and was not reunited with his parents until he was a twenty-three-year-old married Cambridge graduate. As told by Barton Worthington to Alan Robertson, both undergraduate friends—“Waddington … became remarkably bald at about the age of twenty-one and in the early part of his career this, coupled with his erudition, caused many people to think that he was much older than he actually was” (Robertson, 1977, p. 578). He was known as Con to his relatives and childhood friends, Conway to his undergraduate friends, and as Wad to his wife and professional friends. His early fascination, acquired in Sedgeberrow, was with fossils, especially ammonites (a subclass of extinct cephalopods), which he collected from the gravel used to make paths and studied with a passion; he thought he could understand ammonite development by studying records of that development left in the forming and formed shell. His museum, a collection of biological, geological, and archaeological specimens, set the stage for a scholarship to Clifton, Sidney Sussex College, Cambridge, and a First Class Honours degree in geology. He married in the same year (1926), a marriage that produced a son, Jake, but which ended in divorce in 1936.

A well-rounded individual, Waddington was a capable runner, an enthusiastic walker and climber, and squire of the Cambridge Morris Men, which group he led on tours throughout the south and southwest of England, and for whom he collected Morris dances and folk tunes. Also a poet, he recalled,

More interested in poetry than in science as an undergraduate, I edited and printed a magazine of poetry that had the distinction of being the first vehicle in which Christopher Isherwood, the English novelist, appeared in print. (quoted in Robertson, 1977, p. 579)

Waddington’s scientific breadth and interests went beyond geology and natural history; he held an 1851 exhibition studentship in paleontology and an Arnold Gerstenberg studentship in philosophy, the latter won for an essay on the “Vitalist-Mechanist Controversy” that permeated much of the experimental embryology of the latter part of the nineteenth and first third of the twentieth centuries.

Waddington began graduate studies on the systematics of his boyhood passion, ammonites, with the intention of becoming an oil exploration geologist. However, he was diverted from paleontology into evolution and genetics, in part through a friendship with Gregory Bateson, the man who introduced genetics to England in 1900. Waddington never did finish his thesis, nor did he obtain any graduate degree, although he was awarded a Cambridge ScD in 1936 on the basis of his published work. His first four published papers illustrate the breadth of his interests as he sought a subject to devote himself to. In 1929, he published a method for recording the sizes of fossil ammonites and a paper on the genetics of germination in stocks of the genus Matthiola. His third paper (1930), a letter to Nature, was on the experimental embryology of avian embryos, and the fourth (1931)—coauthored with the polymath J. B. S. Haldane—was on genetic linkage.

Subsequently, Waddington became one of the great synthesizers of biology, although his prescience was only fully realized in the early 2000s. The British Society for Developmental Biology established the Waddington medal and Waddington Medal Lecture as its most prestigious award and the only national award in developmental biology within the United Kingdom. Most appropriately the obverse of the medal depicts an ammonite drawn by Waddington in his days as a budding paleontologist, and whose development he inferred from the fossilized remains of their shells.

Overview of His Career. Waddington spent six months of 1931 in Germany with Hans Spemann learning the techniques of experimental embryology, especially transplantation of small regions between amphibian embryos; a region of the early embryo named the organizer by Spe-mann and his student Hilda Mangold had been shown by them in 1924 to be responsible for inducing the formation of the nervous system and around it the entire embryonic axis. This seminal discovery demonstrated that a single region of frog embryos (the organizer) was responsible for “organizing” the entire embryo. Many of the worlds embryologists devoted themselves understanding the organizer, just as embryologists of the early twenty-first century (developmental biologists) pursue the genetic control of development. So, in the 1930s, genetics and experimental embryology replaced paleontology as Waddington began intensive investigation and experimental studies on the chemical nature of the primary organizer using amphibian embryos; Waddington received the first Albert Brachet Prize by the Royal Academy of Belgium, awarded for the best embryological research published in that year. Waddington extended his research to pioneering studies with avian and mammalian embryos at the Strangeways Research Laboratories in Cambridge, supporting himself, his first wife, and young family as a demonstrator in zoology at Cambridge and (from 1933 on) as a Fellow of Christ’s College. He was the first to use organ culture methods to culture whole chick embryos, which he used to study induction of the nervous system, the first to demonstrate the presence of an organizer in mammalian embryos, and the first to use radioactive tracers to analyze development.

A fruitful collaboration with Joseph and Dorothy Needham, development of the concepts central to embryonic induction, and of the founding of The Theoretical Biology Club (whose members included the Needhams, the biologist turned philosopher Joseph Woodger, the physicist John D. Bernal, cell biologist E. Neville Willmer, and future Nobel Laureate Peter B. Medawar) characterized this period of Waddington’s career.

During the 1930s, Waddington also began his close association with such emerging avant-garde painters, sculptors, and architects as Henry Moore, Barbara Hep-worth, Ben Nicholson, John Piper, Sandy Calder, and Walter Gropius. Waddington’s knowledge and appreciation of art was considerable; more than thirty years later he wrote his enormously ambitious analysis Behind Appearance: A Study of the Relations between Painting and the Natural Sciences in This Century (1969). In 1936, he married painter and architect Justin Blanco White. The two daughters from this marriage (Dusa and Caroline) and his son from his first marriage, all became academics, in mathematics, social anthropology, and physics respectively.

During World War II Waddington served in the Coastal Command. Thirty years later, based on his experience with anti-U-boat operations, he wrote Operational Research in World War II: O. R. against the U-boat (1973). In 1947, the year he was elected a Fellow of the Royal Society, Waddington extended his influence in genetics as chief geneticist and deputy director of an Agricultural Research Council Unit on Animal Breeding and Genetics Research, based in Edinburgh, coupled with his election to the Buchanan Chair of Genetics in the University of Edinburgh. By his fiftieth birthday in November 1955, Waddington had built the Edinburgh unit into the largest and strongest Genetics Department in the United Kingdom and one of the largest and strongest anywhere in the world.

During his career, Waddington was preoccupied with the integration of genetics, embryology (developmental biology), and evolution into an approach he called epigenetics. Unlike reductionism, which seeks all explanations at lower (often regarded as more fundamental) level, epigenetics takes a multi-causal approach to explanations of biological phenomena. Indeed, this is what distinguished biology from physics and chemistry— properties emerge at higher levels that could not be predicted from the properties of the lower level. Embryonic induction so long studied by Waddington is a classic example of emergent properties—the inductive influence of one region of an embryo on another region can neither be predicted from the properties of the inductive region nor from the properties of the responding region. Waddington’s epigenetic approach and philosophical/mathematical background provided a natural link to his efforts to seek a theoretical foundation for biology that went beyond reductionism. Epigenetics is Waddington’s most lasting legacy to development and evolution (see below). He also administered worldwide scientific activities through the International Biological Programme (IBP), as president of the International Union of Biological Sciences (IUBS), as a founding member of the Club of Rome, and by playing an instrumental role in starting journals such as Genetical Research. Waddington’s search for a theoretical biology, fostered in the Theoretical Biology Club, were manifested in his editorship of a four-volume series entitled Towards a Theoretical Biology (1968–1972), the proceedings of four IUBS meetings he organized in the late 1960s and early 1970s at the Villa Serbelloni in Bellagio, Italy; a chance attendance at the IUBS general assembly in Amsterdam in July 1961 resulted in Waddington being asked by the internationally renowned developmental biologist Paul Weiss to stand for president. Waddington saw an opportunity to further his aims for theoretical and integrative biology and so accepted the invitation, and proposed a series of IUBS symposia titled “Towards a Theoretical Biology.” The first biological application of catastrophe theory by René Thom appeared in this series. In all, Waddington wrote eighteen and edited nine books, published over a forty-two-year period, the last appearing posthumously in 1977. Robertson’s summary of these books is that “On the whole, his books are too stimulating, too wide-ranging and too speculative to be ideal textbooks” (1977, p. 595).

The combination of embryology and genetics provided a logical outlet for Waddington’s philosophical interests—embryology was emerging from the vitalistmechanist controversies of the late 1800s—and for which Waddington had received a studentship at Cambridge. The study of embryos embodied the search for causal links between ontogeny and phylogeny; genetics provided the basis through which development was manifest. In 1965, he established an epigenetics research group in Edinburgh funded by the Medical Research Council and then an Epigenetics Laboratory with its own building, funded by the Wellcome Foundation and the Distillers Company. Waddington now had the resources to investigate development within the broad context provided by his epigenetic approach. However, the time was not ripe for launching a major thrust into epigenetics; the mood of the biological world was molecular and reductionist, not developmental and integrative. In the service of promoting a synthesis of genetics, development, and evolution, Waddington wrote no fewer than eleven books, beginning with How Animals Develop(1935) and ending with New Patterns in Genetics and Development (1962). In addition there were books on theoretical biology and other matters.

Named a Commander of the British Empire (CBE) in 1958, Waddington was elected to foreign membership in the American Academy of Arts and Sciences and the Finnish Academy, to fellowship in the Deutsche Akademie der Naturforscher Leopoldina and received honorary degrees from Université de Montreal and from universities in Prague, Geneva, Cincinnati, Aberdeen, and Trinity College Dublin. Waddington spent the year 1970–1971 in an Albert Einstein Chair in Science at the State University of New York in Buffalo, where the first signs appeared of the heart condition that would kill him on 26 September 1975, two months short of his seventieth birthday.

Development and Evolution. In 1924, the German embryologists Hans Spemann and Hilda Mangold published their seminal paper on the initiation of the nervous system by interaction between two regions of the early amphibian embryo. The early 1930s saw Waddington pursuing the chemical nature of embryonic inducers in which he made the distinctions between induction and individuation, the latter as the formation of interdependent, spatially organized units such as tissues or organs, evoked by developmental processes such as induction and individuation, which he defined as the organizing effect of the organizer, the consequence of induction. His interests during this phase were virtually entirely developmental as he sought the chemical nature of induction.

Throughout his career, Waddington was concerned with integrating embryology (development) and genetics and with linking these two subfields of biology to evolution. His developmental studies were performed on the premise that gene activity lies at the heart of embryonic development. He came to this conclusion while a Rockefeller Fellow in Thomas Hunt Morgan’s laboratory at Columbia University in New York, where he initiated the first studies on organ formation in the fruit fly Drosophila using developmental mutants. His sensitivity to the genetic basis of development, coupled with the realization of the dynamic, organized, integrated, and channeled nature of embryonic development, led Waddington to develop the twin concepts of epigenetics and canalization, the latter being that development proceeds along channels, which once entered, are difficult to exit; cells stay on their path of differentiation. Spemann remained with experimental embryology for the rest of his career. Morgan switched from embryology to genetics and only returned to experimental embryology in post-retirement, Spemann was not concerned with evolution, Morgan placed his emphasis on the genes as the hereditary unit. Of the three only Waddington sought to integrate genes, development, and evolution.

Waddington’s position was initially articulated in Organisers and Genes (1940) and illustrated by the later well-known analogy of the epigenetic landscape, which was depicted initially as a bifurcating valley (representing channels of development) drawn by his friend, the artist John Piper, at Waddington’s fiftieth birthday party at the Genetics Institute in Edinburgh. The epigenetic landscape was represented as a pinball machine, with the ball running down valleys to produce wild type or mutant phenotypes.

His conviction that development was more than the working out of gene action led Waddington into evolutionary studies; the evolution of organisms reflects the evolution of developmental systems. Much of the motivation for Waddington’s approach to evolutionary studies lay in his persistent criticism of the adequacy of population genetics to provide a realistic model of how genes really operate in development and evolution; population geneticists treated gene frequencies in populations and ignoring any role for the embryos in which those genes nestled; they saw evolution as a property of populations; Waddington saw evolution as the working out of altered embryonic development, which only later would be reflected in changing gene frequencies in populations. The dual concepts of canalization and genetic assimilation were the platform from which Waddington launched his attacks on evolution as population genetics (Waddington, 1942).

Much of his boundless energies throughout the 1950s were devoted to documenting evidence for these two phenomena. Early twenty-first century conception of embryonic development as a highly integrated series of canalized pathways owes much to Waddington’s development of the concepts that embryos could buffer themselves against environmental influences, that development followed well-defined paths, and that genetic and non-genetic factors influenced development.

Waddington was a prodigious coiner of terms and neologisms. The metaphorical epigenetic landscape became the way that most developmental biologists “saw” the organization of embryonic development. As Thom (1989) noted, a person can never be considered as the owner of an idea but words that he creates follow him through life and hopefully outlive him. Some of the terms and concepts coined by Waddington—epigenetics, epigenetic landscape, genetic assimilation, canalization—have entered general usage in development, especially in analyses of development in relation to evolution. Others, such as epigenotype, individuation, chreod, evocation, and homeorhesis (the regular and regulatory pathways of development that canalization allows) have survived the test of time less well. The concept embryonic development as controlled by heritable and epigenetic factors is Waddington’s lasting legacy.

The Epigenetic Landscape and the Epigenotype. Waddington repeatedly stressed the role of the organization that links the genotype to the phenotype. With the term epigenotype Waddington (1939) sought to capture that linkage as the series of interrelated developmental pathways through which the genotype is manifest in the phenotype. The epigenotype encompasses all the interactions among genes and between genetic and environmental signals that produce the final phenotype, or epiphenotype. Interaction, integration, and heritability of these stable interactions are the essential elements of the epigenotype. Epigenetics and epigenotype are often used interchangeably in the early twenty-first century.

The epigenetic landscape is a visual analogy of the embryo, embryonic regions, or groups of cells progressing through ontogeny. In the epigenetic landscape, development is treated as a terrain with valleys serving as the developmental paths traversed by cells, which, moving through development down the valleys, may be moved up the slopes of the valley wall by potentially perturbing genetic or environmental influences but will, because of canalization, roll back down the valley wall to remain on the same developmental path or trajectory. If the influences are such that the zygote or embryonic region is pushed over the valley wall, it will come to lie within a new valley and develop along a new canalized path. Inductive and tissue interactions, altered timing of development or perturbations of growth take cells from one valley to another.

Epigenetics, by contrast, is a term and a concept that has been elusive and difficult to incorporate into models of evolutionary change, despite the perception of many that epigenetics represents an important missing element in evolutionary analyses. Waddington thought of epigenetics as the causal analysis of development and defined it as such in The Epigenetics of Birds (1952). While others were seeking developmental programmes based in instructions in the genome, Waddington developed a more multifactorial approach, and one of the few that attempted to provide a mechanism for how environmentally induced responses could be inherited. After that, biologists found more practical value in defining epigenetics as the sum of the genetic and non-genetic factors acting upon cells to control selectively the gene expression that produces increasing phenotypic complexity during development and evolution.

Canalization and Genetic Assimilation. Canalization was central to Waddington’s thinking; the collective action of groups of genes can isolate a developmental event from perturbations arising from the action of single or small numbers of genes. Such supragenomic organizational thinking is typically Waddington. Essentially similar concepts were developed by I. Michael Lerner (1954) as genetic homeostasis and Sewall Wright (1968) as universal pleiotropy.

Canalization produces canalized characters, i.e., phenotypes whose expression is restricted within narrow boundaries. Canalizing selection eliminates genotypes that would expose the organism to environmental fluctuations or genetic variability, i.e., there is selection for some independence from destabilizing influences. Canalization has resurfaced in evolutionary studies in the concept of developmental stability (Maynard Smith et al., 1985). Canalization allows the build-up of genetic variability within the genotype, even though that variability is not expressed phenotypically. Such hidden genetic variability can be brought to light and subjected to selection through genetic assimilation.

The essence of Waddington’s concept of genetic assimilation is that embryos possess the genetic capability to respond to environmental perturbations. By means of genetic assimilation, a phenotypic character initially produced only in response to some environmental influence, by responding to the operation of selection in subsequent generation is taken over by the genotype. The character then can form even in the absence of the environmental influence that evoked it in the initial generation. In a series of papers published between 1956 and 1961, Waddington provided experimental evidence for genetic assimilation by inducing phenotypic changes (crossveinless and bithorax) in Drosophila exposed to a heat or ether shock and then selected for the phenotype in the absence of the environmental stimulus (see Rendel (1968) and Hall (1992) for discussions).

Often, the features produced by genetic assimilation are an environmentally-evoked copy (a phenocopy) of a suite of features known to result following a mutation, evidence used by Waddington to argue for the genetic basis of assimilated phenotypes. The time of action of an environmental agent leading to assimilation often coincides with the known time of action of the mutant gene that results in the equivalent phenotype. But genetically assimilated phenotypes are not based on a mutation. They have a polygenic basis, often involving genes on several chromosomes (Waddington, 1957). The three processes—phenocopies, genetic assimilation, and canalization—demonstrate the considerable unexpressed genetic variability that can be evoked by selection following either a mutation or an environmental stimulus.

Waddington argued that genetic assimilation could produce adaptive change in nature (1956a), citing the experiments by Piaget on the European snail Limnaea as a prime example (Waddington, 1975), but had to argue strenuously that there is nothing Lamarckian about genetic assimilation. Its genetic basis lies in the genetic capability of organisms to respond to environmental changes, unexpressed genetic variability, and the ability of selection to increase the frequency of individuals expressing the previously hidden genetic potential. While the initial stimulus is environmental and the initial response is phenotypic, the transgenerational result is genetic. The identification of types of epigenetic interactions and their integration with zygotic and parental genomic control in producing phenotypic change in development and evolution (phenotypes as process and pattern) are the lasting legacy of Waddington’s conceptualization of the integration of genetics, development, and evolution through epigenetics.

BIBLIOGRAPHY

WORKS BY WADDINGTON

With Joseph Needham and Dorothy M. Needham. “Physico-Chemical Experiments on the Amphibian Organizer.”

Proceedings of the Royal Society of London, Series B, 114 (1934): 393–422. An early study on the chemical nature of embryonic induction.

How Animals Develop. London: Allen and Unwin, 1935.

With Dorothy M. Needham. “Studies on the Nature of Amphibian Organization Centre. II. Induction by Synthetic Polycyclic Hydrocarbons.” Proceedings of the Royal Society of London, Series B, 117 (1935): 310–317. The chemical nature of induction.

An Introduction to Modern Genetics. London: Allen and Unwin, 1939.

Organisers and Genes. Cambridge, U.K.: Cambridge University Press, 1940. The book in which the concept of epigenetics was first outlined.

“Canalization of Development and the Inheritance of Acquired Characters. “Nature (London) 150 (1942): 563.

The Epigenetics of Birds. New York: Cambridge University Press, 1952.

“Genetic Assimilation of the bithorax Phenotype.” Evolution 10 (1956a): 1–13. Pioneering study on genetic assimilation.

“The Genetic Basis of the ‘assimilated bithorax’ Stock.” Journal of Genetics 55 (1956b): 240–245.

The Strategy of the Genes. London: Allen and Unwin, 1957. The most complete development of Waddington’s ideas.

“Inheritance of Acquired Characters.” Proceedings of the Linnaean Society of London 169 (1958): 41–62.

“Canalisation of Development and Genetic Assimilation of Acquired Characters.” Nature (London) 183 (1959): 1654–1655.

“Genetic Assimilation.” Advances in Genetics 10 (1961): 257–293.

New Patterns in Genetics and Development. New York: Columbia University Press, 1962. A textbook that unified genetics and developmental biology.

ed. Towards a Theoretical Biology, vols. 1-4. Edinburgh: Edinburgh University Press, 1968–1972. An ambitious search for a theory for all of biology.

Behind Appearance: A Study of the Relations between Painting and the Natural Sciences in This Century. Edinburgh: Edinburgh University Press, 1969. Perhaps the best book on art by any scientist.

Operational Research in World War II: O. R. against the U-Boat. London: Elek Books, 1973. Autobiographical.

The Evolution of an Evolutionist. Ithaca and New York: Cornell University Press, 1975. What Waddington referred to as “an exposition with some autobiographical background.”

OTHER SOURCES

Bard, Jonathan “Waddington’s Legacy to Developmental and Theoretical Biology.” In Arriving at a Theoretical Biology: The Waddington Centennial, edited by Manfred Laubichler, Brian K. Hall, and Gerhard B. Müller. Cambridge, MA: MIT Press (forthcoming). An expert assessment by one who knew Waddington.

Gilbert, Scott F. “Diachronic Biology Meets Evo-Devo: C. H. Waddington’s Approach to Evolutionary Developmental Biology.” American Zoologist 40 (2000): 729–737.

Hall, Brian K. “Waddington’s Legacy in Development and Evolution.“American Zoologist 32 (1992): 113–122. An overview of Waddington’s contributions.

———. Evolutionary Developmental Biology. London: Chapman and Hall, 1992. 2nd ed., Dordrecht: Kluwer, 1999. Contains an analysis of Waddington’s views in the context of epigenetics and of interactions between development and evolution.

“Baldwin and Beyond: Organic Selection and Genetic Assimilation.” In Evolution and Learning: The Baldwin Effect Reconsidered, edited by Bruce H. Weber and David J. Depew. Cambridge, MA: MIT Press, 2003. An evaluation of genetic assimilation and the Baldwin Effect. Evaluates Waddington’s position on genetic assimilation in relation to organic selection.

Lerner, I. Michael. Genetic Homeostasis. Edinburgh: Oliver and Boyd, Edinburgh, 1954.

Maynard Smith, John; Richard Burian; Stuart Kauffman; et al. “Developmental Constraints and Evolution.” Quarterly Review of Biology 60 (1985): 265–287.

Palmer, A. Richard. “Symmetry Breaking and the Evolution of Development.” Science 306 (2004): 828–833. A ground breaking paper on how to identify genetic assimilation in nature.

Polikoff, D. “C. H. Waddington and Modern Evolutionary Theory.” Evolutionary Theory 5 (1981): 143–168. A clear and authoritative analysis.

Rendel, J. M. “Genetic Control of Developmental Processes.” In Population Biology and Evolution, edited by Richard C. Lewontin. Syracuse: Syracuse University Press, 1968. A comprehensive review of Waddington’s work.

Robertson, Alan. “Conrad Hal Waddington.” Biographical Memoirs of Fellows of the Royal Society 23 (1977): 575–622. A detailed biography, including a list of Waddington’s publications.

Saunders, P. T. “The Epigenetic Landscape and Evolution.” Biological Journal of the Linnaean Society 39 (1990): 125–134. An overview of the impact of Waddington’s metaphor on evolutionary theory.

Slack, Jonathan M. W. “C. H. Waddington—The Last Renaissance Biologist.” Nature Reviews Genetics 3 (2002): 889–895.

Spemann, Hans. Embryonic Development and Induction. New Haven, CT: Yale University Press, 1938. Reprinted New York: Hafner Publishing, 1962; and New York: Garland Publishing Inc., 1988.

Spemann, Hans, and Hilde P. Mangold. “Über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren.” Wilhelm Roux Archiv für Entwicklungsmechanik 100 (1924): 599–638.

Stern, Claudio D. “Conrad H. Waddington’s Contributions to Avian and Mammalian Development, 1930–1940.” In “Developmental Biology in Britain,” edited by James C. Smith. Special Issue, International Journal of Developmental Biology 44, no. 1 (2000): 15–22. Evaluation of Waddington’s experimental embryology by a leading authority.

Thom, R. “An Inventory of Waddingtonian Concepts.” In Theoretical Biology. Epigenetic and Evolutionary Order fromComplex Systems, edited by Brian Goodwin and Peter Saunders. Edinburgh: Edinburgh University Press, 1969. A thoughtful commentary from the then leading theoretical biologist.

Van Speybroeck, Linda. “From Epigenesis to Epigenetics: The Case of C. H. Waddington.” Annals of the New York Academy of Sciences 981 (2002): 61–81.

Wilkins, Adam S. “Canalization: A Molecular Genetic Perspective.” BioEssays 19 (1997): 257–262. An in-depth analysis of Waddington’s concept of canalization from the genetic point of view.

Wright, Sewall. Evolution and the Genetics of Populations, vol. 1. Chicago: The University of Chicago Press, 1968.

Yoxen, Edward. “Form and Strategy in Biology: Reflections on the Career of C. H. Waddington.” In A History of Embryology, edited by Tim J. Horder, Jan A. Witkowski, and Christopher C. Wylie. Cambridge, U.K.: Cambridge University Press, 1986.

Brian K. Hall