Waddington's Legacy in Development and Evolution1

AMER. ZOOL., 32:113-122 (1992)

Waddington's Legacy in Development and Evolution1 BRIAN K. HALL

Department of Biology, Dalhousie University, Halifax, Nova Scotia B3H 4J1, Canada

back to England to live with an aunt and then with his grandmother. Waddington's early life was moulded by Quaker traditions and female relatives; he did not see his father between hisfifthandfifteenthbirthdays and was not reunited with his parents until 1928, by which time he was 23 years old and a recently married Cambridge graduate. His early fascination was with fossils, especially ammonites which he collected and studied with a passion. Known as "Con" to his relatives and friends, he established at an early age what was known as Con's museum; a collection of biological, geological and archaeological specimens. An avid interest and ability in natural C. H. WADDINGTON sciences took him to Cambridge University Waddington had the early life typical of where he obtained a First Class Honours so many of the children of British citizens degree in Geology. Already his interests were who made their living in what were then the broad; he held a prestigious 1851 Exhibition colonies. His first three years were spent on in palaeontology as well as a studentship in a tea plantation in India, before being sent philosophy, won for an essay on the "Vitalist-Mechanist Controversy," a controversy that permeated much of the experimental 1 From the Symposium on Development and Macembryology of the latter part of the nineroevolution sponsored by the Division of the History teenth century and that still preoccupied and Philosophy of Biology of the American Society of embryologists in the 1920s and 1930s. Later Zoologists and presented at the Annual Meeting of the he was preoccupied with the integration of American Society of Zoologists, 27-30 December 1990, at San Antonio, Texas. disciplines, notably genetics and develop113 INTRODUCTION

I begin with a summary of the major features of the life and career of Conrad Hal Waddington, born in Evesham in 1905, died in 1975 in Edinburgh, his professional home for most of his career; a detailed biographical memoir may be found in Robertson (1977) with additional information in Yoxen (1986). Then I go on to discuss the major research interests that preoccupied Waddington throughout his career. Finally, I discuss the legacy of Waddingtonian terms and concepts, especially genetic assimilation and epigenetics.

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SYNOPSIS. This paper provides an overview of the life and works of Conrad Hal Waddington (1905-1975). After an early life spent apart from his parents pursuing ammonites, natural history, geology and archaeology, Waddington took a degree in Geology at Cambridge (1926). Genetics and experimental embryology soon replaced palaeontology as he began his experimental studies on the chemical nature of the primary organizer discovered by Spemann and Mangold in 1924. It was during this period of collaboration with Joseph and Dorothy Needham that Waddington developed the concepts of evocation and individuation. The establishment of a Unit on Animal Breeding and Genetics in Edinburgh after the second World War provided Waddington with his professional home for the rest of his career as he sought to integrate genetics and development into an evolutionarily relevant discipline. Our conception of embryonic development as a highly integrated series of canalized pathways owes much to Waddington's development of the concepts of canalization, chreods, epigenetics and the epigenotype. The metaphorical epigenetic landscape became the way that most developmental biologists "saw" the organization of embryonic development. The concept of supragenomic, integrated, heritable, epigenetic organization of embryonic development is arguably Waddington's lasting legacy to development and evolution. The integration of his epigenetic legacy into a quantitative developmental genetics model of the developmental and evolutionary origin of phenotypes is now being undertaken. It has still to be proven whether genetic assimilation, which Waddington demonstrated to be a real phenomenon in laboratory experiments, has been a force in evolutionary adaptation.

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Spemann was actively investigating primary embryonic induction in amphibians (Spemann 1931a, b; Spemann and Geinitz, 1927; Spemann and Schotte, 1932; Mangold, 1933), led Waddington to begin his experimental studies using amphibian embryos, studies which he extended to avian and mammalian embryos at the Strangeway's Research Laboratories in Cambridge. At this time Waddington was supporting himself and his family as a Demonstrator in Zoology at Cambridge and from 1933 onwards as a Fellow of Christ Church College. An extensive collaboration began with Joseph and Dorothy Needham, the first papers appearing in 1933 (Waddington et al., 1933a, b, c) and continuing for several years (Waddington^ al., 1934, 1935, 1936; Waddington and D. M. Needham, 1935; Waddington and J. Needham, 1936; Needham et al, 1934). Both Waddington and the Needhams would move from experimental embryology into other spheres, Joseph Needham into the production of the multivolume series Science and Civilization in China and to the Mastership of Gonville and Caius College of Cambridge University, and Waddington into the integration of genetics, development, and evolution; theoretical biology, and administration of world-wide scientific activities through the International Biological Programme and the International Union of Biological Sciences (I.U.B.S.; see below). He was also an active member of the Theoretical Biology Club during this time, a group that included Woodger, Bernal, Willmer, Medawar and the Needhams. During the 1930s Waddington was closely associated with emerging avant-garde painters and sculptors such as Henry Moore, Barbara Hepworth and Sandy Calder. In 1936 he married for the second time, this time to the painter and architect Justin Blaco White. Over thirty years later he would publish Behind Appearances, his enormously ambitious analysis of the relations between painting and the natural sciences in the twentieth century (Waddington, 1969a). During the second World War Waddington served in the Coastal Command. Thirty years later he published a book based on his


ment, and to a lesser degree, evolution and paleontology, and with establishment of a theoretical biology based on the principles enunciated by the British philosopher, Whitehead. Waddington's interests were not only cerebral. He was a very capable runner, an enthusiastic walker and climber in the best British traditions, a poet and editor of an undergraduate poetry magazine, and, much to my surprise, given the impressions one has of the man from his writings, Squire of the Cambridge Morris Men, a Morris dancing team which he led on tours throughout the south and southwest of England. Waddington began a graduate degree intent on becoming a geologist and began studies on a thesis on the systematics of ammonites, his boyhood passion. However, he was diverted from palaeontology into evolution and genetics, in part through a friendship with Gregory, son of William Bateson, who introduced genetics to England. Waddington never did finish his thesis, nor did he complete any graduate degree, although he was awarded a Cambridge Sc.D. in 1936 on the basis of his published work. Waddington's first four papers illustrate both the breadth of his interests and his search for a subject to devote himself to. In 1929 he published a method for recording the sizes of fossil ammonites (Waddington, 1929a), and a paper on the genetics of germination in stocks of the genus Matthiola (19296). His third paper, a letter to nature, was on the experimental embryology of avian embryos (Waddington, 1930), and the fourth (1931) coauthored with J. B. S. Haldane, was on genetic linkage. The early 1930s marked Waddington's period of intensive investigation into experimental embryology, especially a search for the chemical nature of induction. Spemann and Mangold had published their seminal paper on induction of the nervous system from ectoderm by the dorsal lip of the amphibian blastopore in 1924. This followed studies on qualitatively similar interactions on lens formation in amphibians (Spemann, 1901; Lewis, 1904; see reviews in Spemann, 1938 and Hamburger, 1988). A six month period spent in Germany, when

WADDINGTON'S LEGACY

WADDINGTON'S RESEARCH INTERESTS

In this section I provide an overview of the major areas of Biology that preoccupied Waddington through his career. As already indicated, Waddington's early desire to become a palaeontologist and to make a career in oil exploration geology was diverted by his introduction to genetics and experimental embryology. The latter provided a logical outlet for his philosophical interests—embryology was only just emerging from the vitalist-mechanist controversies of the late 1800s, and the embryo embodied the philosophical search for causal links between ontogeny and phylogeny; genetics provided the basis through which development was manifest. The early 1930s saw Waddington pursuing the chemical nature of embryonic inducers in which he made the distinction between induction and individuation (see below). His interests during this phase were virtually entirely developmental and not evolutionary. In fact, throughout his career, it was primarily development and genetics and not development and evolution that Waddington effectively integrated. The concentration on development was also for very practical reasons; Waddington did not feel that a living could be earned as a geneticist; development provided better prospects. Waddington's developmental studies were performed on the premise that the activities of genes lay at the heart of embryonic development. This 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 concept of epigenetics and canalization, initially articulated in his 1940 book Organisers and Genes, and illustrated by the analogy of the epigenetic landscapes and the chreod (see following section). The epigenetic viewpoint adopted by Waddington led him into evolutionary studies. His conviction was that the evolution of organisms was really the evolution of developmental systems. According to PolikofFs (1981) analysis much of the motivation for Waddington's approach to evolutionary studies lay in his persistent criticism of the adequacy of population genetics


experience with anti-U-boat operations (Waddington, 1973). It was after the war that Waddington began his extensive foray into genetics as Chief Geneticist and Deputy Director of an Agricultural Research Council Unit on Animal Breeding and Genetics Research, based in Edinburgh, coupled with a Chair in Genetics at the University of Edinburgh. As Robertson (1977) recounts, in the early days of the Institute, all the staff lived essentially in a "commune," although admittedly the commune was a country house, an arrangement that lasted from 1947 to 1953. By his fiftieth birthday in 1955, Waddington had built in Edinburgh the largest and perhaps the strongest Genetics Department in the United Kingdom and one of the largest and strongest anywhere in the world. So identified was he by then with the twin themes of canalization and the epigenetic landscape (see below) that these featured very prominently at the birthday celebrations. In fact, ten years later an "Epigenetics Laboratory" was established in Edinburgh. 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. However, epigenetics may be Waddington's most lasting legacy to development and evolution (see last section). In the service of promoting a synthesis of genetics, development and evolution Waddington produced no fewer than eleven books, beginning with How Animals Develop in 1935 and ending with New Patterns in Genetics and Development in 1962. In addition there were books on Theoretical Biology and other matters; see Robertson (1977) for a complete list. Waddington played a leading role in the international biological scene and an instrumental and perhaps pivotal role in the establishment of the International Biological Programme (IBP) of the I.U.B.S., serving as President of I.U.B.S. in the late 1960s. (Another eminent experimental embryologist, Sven Horstadius, had earlier served as I.U.B.S. president [1953-1958].) Waddington was also a founding member of the Club of Rome and instrumental in starting several journals such as Genetical Research.

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WADDINGTONIAN TERMS AND CONCEPTS

Waddington was a prodigious coiner of terms and neologisms. As Thorn (1989) noted, you can never be considered as the owner of an idea but words that you create follow you through life and hopefully outlive you. 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

Chreod (Waddington, 1961) Canalization necessitates fixed, or at least predictable, paths in development. A chreod is the necessary or obligatory path of a canalized developmental sequence; a developmental trajectory. Chreods cannot exist without canalization and as the term carries no mechanistic explanation other than canalization it has not been adopted into general usage.


to provide a realistic model of how genes development in relation to evolution. Othreally operate in development and evolu- ers, such as epigenotype, individuation, tion. The dual concepts of canalization and chreod, evocation and homeorhesis, have genetic assimilation were the platform from lasted the test of time less well. I consider which Waddington launched his attacks on each of these in turn to provide a lexicon prevailing evolutionary theory (Wadding- of Waddington's legacy. ton, 1942). Much of his energies throughout the 1950s were devoted to documenting Canalization (Waddington, 1940) evidence for these two phenomena (see Canalization is the property of developbelow). mental pathways to produce standard pheWaddington's early interests in theoreti- notypes despite environmental or genetic cal biology, fostered in the Theoretical Biol- influences that would otherwise disrupt ogy Club, were manifested in his editorship development. It is the buffering of develof a four volume series entitled Towards a opment against perturbations, whether of Theoretical Biology (1968, 19696, 1971, environmental or genetic origin. The latter 1972), the proceedings of four I.U.B.S. is especially significant and was central to meetings which he organized in the late Waddington's thinking; the collective action 1960s. The first biological application of of groups of genes can isolate a developcatastrophe theory by Rene Thorn appeared mental event from perturbations arising from the action of single or small numbers in this series. In all Waddington wrote 18 and edited 9 of genes. Such supragenomic organizational books, published over a forty two year thinking is typically Waddingtonian. Essenperiod, the last appearing posthumously in tially similar concepts were developed by 1977. Robertson's summary of these books Lerner (1954) as genetic homeostasis and is that "On the whole, his (Waddington's) Wright (1968) as universal pleiotropy. books are too stimulating, too wide ranging Canalization allows the build-up of genetic and too speculative to be ideal textbooks" variability within the genotype, even though (Robertson, 1977, p. 595). My own expe- that variability is not expressed phenotyprience as an undergraduate accords with this ically. Such hidden genetic variability can analysis. I was introduced to Waddington's be brought to light and subjected to selecbooks by P. D. F. Murray who had shared tion through genetic assimilation (see below). a laboratory with Waddington at the Canalization produces canalized characters, Strangeway's Laboratory in the early 1930s. i.e., phenotypes whose expression is Murray, a great admirer of Waddington's, restricted within narrow boundaries; see the opined that reading Waddington's books was discussion of the epigenetic landscape below. like "wading through mud up to the arm- Canalizing selection eliminates genotypes pits" but worth the effort required to make that would expose the organism to environit to the other side. mental fluctuations or genetic variability, Only one of his books remains in print i.e., there is selection for some indepenalthough his work is still frequently cited in dence from destabilising influences. Canathe primary scientific literature; an average lization has resurfaced in evolutionary studof 110 citations/year between 1987-1989. ies in the concept of developmental stability (Maynard Smith et ai, 1985).

WADDINGTON'S LEGACY

Individuation (Waddington and Schmidt, 1933) Waddington proposed individuation as the formation of interdependent, spatially organized units such as tissues or organs evoked by developmental processes such as induction. Individuation represented the organizing effect of the organizer, the consequence of induction. The difficulties with both evocation and individuation are that non-specific stimuli can act as "organizers" and evoke responses indistinguishable from those evoked by the normal inducer. This creates considerable difficulties with evocation but few problems with individuation, provided that individuation is seen as a property of the responding tissue that is independent of the particular inductive stimulus that evokes it. Homeorhesis (Waddington, 1957a) Waddington coined the term homeorhesis for the regular and regulatory path-

ways of development that canalization allows. Homeostasis or equilibrium exists because many genes are organized and orchestrated through the integrated, epigenetic nature of developmental processes. Genetic assimilation (Waddington, 1942) Waddington proposes genetic assimilation as a mechanism to relate genetics, development, adaptation and environmental changes. Its essence is that embryos possess the genetic capability of responding to environmental perturbations. Genetic assimilation has been defined as "the process by which a phenotypic character initially produced only in response to some environmental influence becomes, through a process of selection, taken over by the genotype, so that it is formed even in the absence of the environmental influence that at first had been necessary" (King and Stansfield, 1985). Experimental evidence supporting genetic assimilation was provided by a series of experiments inducing phenotypic changes in Drosophila exposed to a heat or ether shock, but then selected for the phenotype in the absence of the environmental stimulus. The production of crossveinless and bithorax flies is the paradigmatic example (Waddington, 1956a, b, 19576, 1958,1959, 1961; see Bateman, 1959a, b; Rendel, 1968; CapdevilaandGarcia-Bellido, 1974; Thompson and Thoday, 1975; and Ho et al, 1983 for other studies using Drosophila, and Matsuda, 1982, 1987 and Hall, 1992 for recent discussions). The phenotypes produced by genetic assimilation are phenocopies of phenotypes produced by mutations, major evidence used by Waddington to argue for the genetic basis of" assimilated phenotypes. The time of action of environmental agents leading to assimilation also often coincided with the known time of action of the mutant gene that produced the equivalent phenotype, a piece of evidence interpreted as indicating that both phenotypes were produced by activation of equivalent developmental processes (Hadorn, 1961). Genetically assimilated phenotypes have a polygenic basis, involving genes on several chromosomes (Waddington, 19576). Phenocopies


Evocation (Needham et al., 1934) Waddington's initial studies concentrated on the organizing properties of embryonic inducers. He coined the term evocation for the induction of differentiation. King and Stansfield (1985) define evocation as "the morphogenetic effect produced by an evocator," an evocator as "the morphogenetically active chemical emitted by an organizer," the organizer being "a part of an embryo which exerts a morphogenetic stimulus upon another part, bringing about its determination and morphological differentiation." Clearly, this sequence of terms has a substantial element of circularity. This coupled with the discovery that artificial organizers (inducers) could organize or evocate just as readily as naturally occurring inducers and the transition to an emphasis on properties of the responding cells as critical for the morphogenetic responses has rendered the evocation concept as dated and possibly outmoded. However, the current active interest in morphogens as molecules which evoke morphogenetic specificity indicates that interest in the biological problem addressed by evocation remains.

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as it is based on unexpressed but available genetic variability, canalization of development, a genetic capability to respond to environmental changes and selection for new gene combinations. However, there is a fundamental problem with detecting evidence of genetic assimilation in nature. Its only distinctive feature is the environmental stimulus that initiated the genetic and selectional processes that produced the new phenotype, and if the phenotype, having been assimilated, is expressed in the absence of the environmental signal that originally evoked it, then distinguishing a genetically assimilated character from one that arose through selection of a mutation rather than through selection for preexisting genetic variability would not be possible. We could only detect genetic assimilation when it was occurring and through a multigenerational study that included the generation exposed to the originating environmental perturbation. Effectively, genetic assimilation could only be verified under experimental conditions. We may never be able to tell how many genetically fixed, dimorphic and environmentally adaptive characters arose through genetic assimilation. Epigenotype (Waddington, 1939) Waddington repeatedly stressed the role of the organization that links the genotype to the phenotype. With the term epigenotype he sought to capture that linkage as the series of interrelated developmental pathways through which the genotype is manifest in the phenotype. It 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. Epigenetics and the epigenetic landscape (Waddington, 1940) Development is hierarchical and structured as a succession of epigenetic events— a hierarchy of epigenetic cascades (Hall and Horstadius, 1988; Hall, 1990a; Herring,


and genetic assimilation, along with canalization, document considerable hidden genetic variability that can be evoked either through a mutation or through selection following exposure to an environmental stimulus, i.e., there are genes present but below the threshold required for their activation. The environmental stimulus alters the threshold of activation allowing their expression. Genetic assimilation is thus the expression of previously hidden genetic variability in response to selection following an environmental stimulus. 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. We should not confuse the initial stimulus which is environmental (but which can be mutational in other circumstances) with response which is genetic. Genetic polymorphism for the phenotype, an environmental signal, and selection to alter gene frequency in the population are the essential elements of genetic assimilation (Stern, 1958, 1959). A conceptually similar situation exists with the maintenance of balanced or seasonal polymorphisms or cyclomorphosis where environmental cues elicit the developmental program for one morphological type or another (Gilbert, 1966,1980; Greene, 1989; Dodson, 1989a, b; Stearns, 1989; Harvell, 1990; Hall, 1992). Selective shifts in gene expression in response to different environments are shared as basic mechanisms by genetic assimilation, seasonal polymorphism and cyclomorphosis; see Dun and Fraser (1959) and Fraser and Kindred (1960) for experimental evidence, and Grant (1963), Arthur (1984), Thomson (1988), and Hall (1992) for discussions. Waddington argued that genetic assimilation could produce adaptive change in nature (Waddington, 1956a) and cited the experiments by Piaget on the European snail Limnaea as a prime example (Waddington, 1975). Whether genetic assimilation does occur in nature is controversial (Matsuda, 1987; Hall, 1992). It is certainly plausible

WADDINGTON'S LEGACY

because of exposure to the primary organizer. Switching later in development produces differences that are less extreme (e.g., adrenergic or cholinergic neurons, cartilage or bone) but the differences are none the less real for the end points being individual cell types rather than major embryonic regions or germ layers. The epigenetic landscape can be readily visualized as an analogy of the embryo or embryonic regions progressing through ontogeny. Epigenetics on the other hand, 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 (Atchley and Hall, 1991; Hall, 1992). Waddington thought of epigenetics as simply the causal analysis of development and defined it so in The Epigenetics of Birds in 1952. Such a definition is not incorrect but is too broad to be of practical value. Similarly broad is the following "In the modern usage 'epigenesis' stands for all the processes that go into implementation of the genetic instructions contained within the fertilized egg. 'Genetics proposes: epigenetics disposes'" (Medawar and Medawar, 1983, p. 114). Geneticists associate epigenetics only with gene action. Thus King and Stansfield defined epigenetics as "the study of the mechanisms by which genes bring about their phenotypic effects" (King and Stansfield, 1985). However, to place epigenetics solely within the realm of gene activation/ repression is to omit the integrative nature of epigenetic processes.

Henderson's Dictionary of Biological Terms on the other hand isolates epigenetics from initial gene action as "the chain of processes linking genotype and phenotype other than the initial gene action" (Lawrence, 1989). This view of epigenetics establishes an artificial dichotomy between gene activity and subsequent processes as ifevents after initial gene activity were qualitatively different from primary gene activity. I endeavoured to provide a definition of epigenetics that would encompass what I saw as the four essential elements of epi-


1990). Each step in the cascade both depends upon a prior step(s) and initiates a subsequent step(s), i.e., cascades are causal temporal and/or spatial sequences. Epigenetic events create new microenvironments that both influence the future behaviour of cells and create future cells, resulting in increasing integration, specification, and complexity during development (Wessells, 1982; Hall, 1983, 1990a, 1982). This summary reflects Waddington's vision of the organization of embryonic development, a vision that he encapsulated in the epigenetic landscape in his 1940 book Organisers and Genes. The visualization was completed by the inclusion of a painting of an "epigenetic landscape" as a frontispiece. The landscape celebrated its fiftieth birthday in 1990. At Waddington's fiftieth birthday party at the Genetics Institute in Edinburgh the epigenetic landscape was represented as a pinball machine. The epigenetic landscape refers to divergent paths (chreods) of canalized development taken by cells. In the epigenetic landscape development is treated as a terrain with valleys serving as the developmental paths traversed by cells. Cells 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. Induction and tissue interactions take cells from one valley to another as can altered timing or position in development (heterochrony, heterotopy) or perturbations in growth (Hall, 1983, 19906, 1992; Brylski and Hall, 1988a, b). Switching from one path to another early in development when embryonic potential is high and cell determination labile brings about major changes in embryonic cell fate as when marginal ectoderm becomes mesoderm because of exposure to growth factors emanating from the endoderm, or when epidermal ectoderm becomes neural ectoderm

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The consequences of canalization, thresholds, bipotentiality and epigenetic cascades both for developmental and for evolutionary change in morphology are great. They rest on the threefold properties of discrete end points of differentiation or morphogenesis, the existence of few, stable canalized developmental pathways, and the ability of embryonic cells to switch from one developmental pathway to another. All three were major themes of Waddington's work and writing. They point to a directing or constraining role of development that needs to be incorporated into evolutionary theory (Arthur, 1984; Thomson, 1988; Hall, 1992). Waddington's legacy is now manifest in attempts to integrate epigenetics into quantitative developmental genetics models of the origin of complex morphologies (Atchley, 1990; Atchley and Hall, 1991; Hall, 1992). The precise identification of types of

epigenetic interactions and their integration with zygotic and parental genomic control in producing phenotypic change in development and evolution are a direct legacy of Waddington's conceptualization of the integration of genetics, development and evolution through epigenetics. ACKNOWLEDGMENTS

I thank Bill Atchley, Annie Burke, Paula Mabee, Tom Miyake and Gerd Miiller for discussions on development and evolution and NSERC of Canada for financial support. REFERENCES Arthur, W. 1984. Mechanisms of morphological evolution: A combined genetic, developmental and ecological approach. John Wiley & Sons, Chichester. Atchley, W. R. 1990. Heterochrony and morphological change: A quantitative genetic perspective. Sem. Devel. Biol. 1:289-297. Atchley, W. R. and B. K. Hall. 1991. A model for development and evolution of complex morphological structures. Biol. Rev. 66:101-157. Bateman, K. G. 1959a. The genetic assimilation of the dumpy phenotype. J. Genetics 56:341-351. Bateman, K. G. 19596. The genetic assimilation of four venation phenocopies. J. Genetics 56:443474. Brylski, P. and B. K. Hall. 1988a. Ontogeny of a macroevolutionary phenotype: The external cheek pouches of geomyoid rodents. Evolution 42:391— 395. Brylski, P. and B. K. Hall. 19886. Epithelial behavior and threshold effects in the development of external and internal cheek pouches in rodents. Z. Zool. Syst. Evolforsch. 26:144-154. Capdevila, M. P. and A. Garcia-Bellido. 1974. Development and genetic analysis of bithorax phenocopies in Drosophila. Nature (London) 250: 500-502. Dodson, S. 1989a. Predator-induced reaction norms: Cyclic changes in shape and size can be protective. Bioscience 39:447-452. Dodson, S. 19896. The ecological role of chemical stimuli for the zooplankton predator-induced morphology in Daphnia. Oecologia (Berlin) 78: 361-367. Dun, R. B. and A. S. Fraser. 1959. Selection for an invariant character, vibrissa number, in the house mouse. Aust. J. Biol. Sci. 21:506-523. Fraser, A. S. and D. M. Kindred. 1960. Selection for an invariant character, vibrissa number, in the house mouse. II. Limits to variability. Aust. J. Biol. Sci. 13:48-58. Gilbert, J.J. 1966. Rotifer ecology and embryological induction. Science 151:1234-1237. Gilbert, J.J. 1980. Female polymorphism and sexual reproduction in the rotifer Asplanchna: Evolution


genetic control of development; (a) that epigenetic control can be genetic or non-genetic, (b) that cells are the embryonic unit of epigenetic action, (c) that it is gene expression that is controlled epigenetically, and (d) that epigenetics results in the development of increasing phenotypic complexity (Hall, 1992). Thus, in a definition taken from that study, epigenetics is "the sum of the genetic and non-genetic factors acting upon cells to selectively control the gene expression that produces increasing phenotypic complexity during development." It is clear that the concept of the epigenetic landscape and the factors just outlined apply irrespective of the mechanism that evokes the developmental event, whether that mechanism be (a) the differential segregation of cytoplasmic constituents in oocytes and blastulae as in the determination of germ cells or mesoderm in anurans, or in the determination of most cell lines in C. elegans, (b) gradients of gene activity as in specification of basic body plan in Drosophila, or (c) in the embryonic inductions and tissue interactions that characterise the differentiation and morphogenesis of most vertebrate organ systems. For explicit discussions of epigenetic cascades in development see Saxen and Karkinen-Jaaskelainen (1981); in relation to evolution see Hall (1983, 1990a, b, 1992) and Saunders (1990).

WADDINGTON'S LEGACY

1934. Physico-chemical experiments on the amphibian organizer. Proc. R. Soc. London B 114: 393-422. Polikoff, D. 1981. C. H. Waddington and modem evolutionary theory. Evol. Theory 5:143-168. Rendel, J. M. 1968. Genetic control of developmental processes. In R. C. Lewinton (ed.), Population biology and evolution, pp. 47-68. Syracuse University Press, Syracuse, New York. Robertson, A. 1977. Conrad Hal Waddington. Biog. Mem. Fellows R. Soc. 23:575-622. Saunders, P. T. 1990. The epigenetic landscape and evolution. Biol. J. Linnean Soc. 39:125-134. Saxen, L. and M. Karkinen-Jaaskelainen. 1981. Biology and pathology of embryonic induction. In T. G. Connelly, L. L. Brinkley, and B. M. Carlson (eds.), Morphogenesis and pattern formation, pp. 21-48. Raven Press, New York. Spemann, H. 1901. Uber Correlationen in der Entwicklung des Auges. Verhandl. Anat. Ges. 15: 61-79. Spemann, H. 1931a. Uber den Anteil von Implantat und Wirtskeim an der Orientierung und Beschaffenheit der induzierten Embryonalanlage. Wilhelm Roux Arch. Entwickl. 123:389-517. Spemann, H. 19316. Das Verhalten von Organisatoren nach Zertstorung ihrer Struktur. Verhandl. Deutschen Zool. Ges., pp. 129-132. Spemann, H. 1938. Embryonic development and induction. Yale University Press, New Haven. (Reprinted in 1962 by Hafner Publishing Co., New York, and in 1988 by Garland Publishing Inc., New York and London.) Spemann, H. and B. Geinitz. 1927. Uber Weckung organisatorischer Fahigkeiten durch Verpflanzung in organisatorische Umgebung. Wilhelm Roux Arch. Entwickl. 109:129-175. Spemann, H. and H. P. Mangold. 1924. Uberinduktion von Embryonalanlagen durch Implantation artfremder Organisatoren. Wilhelm Roux Arch. Entwickl. 100:599-638. Spemann, H. and O. Schotte. 1932. Uber xenoplastische Transplantation als Mittel zur Analyse der embryonalen Induktion. Naturwissenschaften 20: 463-467. Stearns, S. C. 1989. The evolutionary significance of phenotypic plasticity. Bioscience 37:436-445. Stem, C. 1958. Selection for subthreshold differences and the origin of pseudoexogenous adaptations. Amer. Nat. 92:313-316. Stem, C. 1959. Variation and heredity transmission. Proc. Amer. Phil. Soc. 103:183-189. Thorn, R. 1989. An inventory of Waddingtonian concepts. In B. Goodwin and P. Saunders (eds.), Theoretical biology. Epigenetic and evolutionary order from complex systems, pp. 1-7. Edinburgh University Press, Edinburgh. Thompson, J. N. and J. M. Thoday. 1975. Genetic assimilation of part of a mutant phenotype. Genet. Res. 26:149-162. Thomson, K. S. 1988. Morphogenesis and evolution. Oxford University Press, Oxford. Waddington, C. H. 1929a. Notes on graphical methods of recording the dimensions of ammonites. Geol. Mag. 66:180-186.


of their relationship and control by dietary tocopherol. Amer. Nat. 116:409-431. Grant, V. 1963. The origin of adaptations. Columbia University Press, New York. Greene, E. 1989. A diet-induced developmental polymorphism in a caterpillar. Science 243:643-646. Hadom.E. 1961. Developmental physiology and lethal factors. John Wiley & Sons, New York. Hall, B. K. 1983. Epigenetic control in development and evolution. In B. C. Goodwin, N. Holder, and C. C. Wylie (eds.), Development and evolution, The Sixth Symposium of the British Society for Developmental Biology, pp. 353-380. Cambridge University Press, Cambridge. Hall, B. K. 1990a. Genetic and epigenetic control of vertebrate development. Neth. J. Zool. 40:352361. Hall, B. K. 19906. Heterochrony in vertebrate development. Sem. Devel. Biol. 1:237-243. Hall, B. K. 1992. Evolutionary developmental biology. Chapman and Hall, London. Hall, B. K. and S. Horstadius. 1988. The neural crest. Oxford University Press, Oxford. Hamburger, V. 1988. The heritage of experimental embryology. Hans Spemann and the organizer. Oxford University Press, New York. Harvell, C. D. 1990. The ecology and evolution of inducible defenses. Q. Rev. Biol. 65:323-340. Herring, S. W. 1990. Concluding remarks: Trends in vertebrate morphology. Neth. J. Zool. 40:403-408. Ho, M-W., E. Bolton, and P. T. Saunders. 1983. The bithorax phenocopy and pattern formation. 1. Spatiotemporal characteristics of the phenocopy response. Exp. Cell Biol. 51:282-290. King, R. C. and W. D. Stansfield. 1985. A dictionary of genetics. Third Edition. Oxford University Press, New York and Oxford. Lawrence, I. 1989. Henderson's dictionary of biological terms. 10th ed. Longman Scientific and Technical, Harlow, Essex. Lerner, I. M. 1954. Genetic homeostasis. Oliver and Boyd, Edinburgh. Lewis, W. H. 1904. Experimental studies on the development of the eye in Amphibia. I. On the origin of the lens in Rana patustris. Amer. J. Anat. 3:505-536. Mangold, O. 1933. Uber die induktionsfahigkeitdem verschiedenen Bezirke der Neurula von Urodelen. Naturwissenschaften 21:761-766. Matsuda, R. 1982. The evolutionary process in talitrid amphipods and salamanders in changing environments, with a discussion of "genetic assimilation" and some other evolutionary concepts. Can. J. Zool. 60:733-749. Matsuda, R. 1987. Animal evolution in changing environments with special reference to abnormal metamorphosis. John Wiley & Sons, New York. Maynard Smith, J., R. Burian, S. Kauffman, P. Alberch, J. Campbell, B. Goodwin, R. Lande, D. Raup, and L. Wolpert. 1985. Developmental constraints and evolution. Q. Rev. Biol. 60:265-287. Medawar, P. B. and J. S. Medawar. 1983. Aristotle to zoos. A philosophical dictionary ofbiology. Harvard University Press, Cambridge, Massachusetts. Needham, J., C. H. Waddington, and D. M. Needham.

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BRIAN K. HALL World War II: O. R. against the U-boat. Elek Books, London. Waddington, C. H. 1975. The evolution of an evolutionist. Cornell University Press, Ithaca and New York. Waddington, C. H. and J. B. S. Haldane. 1931. Inbreeding and linkage. Genetics 16:357-374. Waddington, C. H. andD. M. Needham. 1935. Studies on the nature of emphibian organization centre. II. Induction by synthetic polycyclic hydrocarbons. Proc. R. Soc. London B 117:310-317. Waddington, C. H. and J. Needham. 1936. Evocation, individuation, and competence in amphibian organiser action. Proc. Kon. Akad. Wetens. Amsterdam 39:3-6. Waddington, C. H., J. Needham, and J. Brachet. 1936. Studies on the nature of the amphibian organisation centre. III. The activation of the evocator. Proc. R. Soc. London B 120:173-198. Waddington, C. H., J. Needham, and D. M. Needham. 1933a. Physico-chemical experiments on the amphibian organizer. Proc. R. Soc. London B 114: 394. Waddington, C. H., J. Needham, and D. M. Needham. 19336. Physico-chemical experiments on the amphibian organizer. Nature (London) 132:219. Waddington, C. H., J. Needham, and D. M. Needham. 1933c. Beo bachtungen tiber die physikalischchemische Natur des Organisators. Naturwissenschaften 21:771-772. Waddington, C. H., J. Needham, and D. M. Needham. 1934. Physico-chemical experiments on the amphibian organizer. Arch. Exp. Cell 15:307-309. Waddington, C. H., J. Needham, and D. M. Needham. 1935. Studies on the nature of the amphibian organization centre. I. Chemical properties of the evocator. Proc. R. Soc. London B 117:289-310. Waddington, C. H. and D. A. Schmidt. 1933. Induction by heteroplastic grafts of the primitive streak in birds. Wilhelm Roux Arch. Entwickl. 128:522563. Wessells, N. K. 1982. A catalogue of processes responsible for metazoan morphogenesis. In J.T. Bonner (ed.), Evolution and development. Report of the Dahlem Workshop on Evolution and Development, Berlin 1981, May 10-15, pp. 115-154. Springer-Verlag, Berlin, and Heidelberg. Wright, S. 1968. Evolution and the genetics of populations, Vol. I. The University of Chicago Press, Chicago. Yoxen, E. 1986. Form and strategy in biology: Reflections on the career of C. H. Waddington. In T. J. Horder, J. A. Witkowski, and C. C. Wylie (eds.), A history of embryology, pp. 309-329. Cambridge University Press, Cambridge.


Waddington, C. H. 1929*. Pollen germination in stocks and the possibility of applying lethal factor hypothesis to the interpretation of their breeding. J. Genetics 21:193-206. Waddington, C. H. 1930. Developmental mechanics of chicken and duck embryos. Nature (London) 125:924. Waddington, C. H. 1935. How animals develop. Allen and Unwin, London. Waddington, C. H. 1939. An introduction to modern genetics. Allen and Unwin, London. Waddington, C. H. 1940. Organisers and genes. Cambridge University Press. Waddington, C. H. 1942. Canalization of development and the inheritance of acquired characters. Nature (London) 150:563. Waddington, C. H. 1952. The epigenesis of birds. Cambridge University Press, Cambridge. Waddington, C. H. 1956a. Genetic assimilation of the bithorax phenotype. Evolution 10:1-13. Waddington, C. H. 1956ft. The genetic basis of the 'assimilated bithorax' stock. J. Genetics 55:241245. Waddington, C. H. 1957a. The strategy of the genes. Allen and Unwin, London. Waddington, C. H. 19576. The genetic basis of the assimilated bithorax stock. J. Genetics 55:240245. Waddington, C. H. 1958. Inheritance of acquired characters. Proc. Linnean Soc. London 169:4162. Waddington, C. H. 1959. Canalisation of development and genetic assimilation of acquired characters. Nature (London) 183:1654-1655. Waddington, C. H. 1961. Genetic assimilation. Adv. Genetics 10:257-293. Waddington, C. H. 1962. New patterns in genetics and development. Columbia University Press, New York. Waddington, C. H. 1968. Towards a theoretical biology, Vol. I, Prolegomena. Edinburgh University Press, Edinburgh. Waddington, C. H. 1969a. Behind appearances. A study of the relations between painting and the natural sciences in this century. Edinburgh University Press, Edinburgh. Waddington, C. H. 19696. Towards a theoretical biology, Vol. II, Sketches. Edinburgh University Press, Edinburgh. Waddington, C. H. 1971. Towards a theoretical biology, Vol. Ill, Drafts. Edinburgh University Press, Edinburgh. Waddington, C. H. 1972. Towards a theoretical biology, Vol. IV, Essays. Edinburgh University Press, Edinburgh. Waddington, C. H. 1973. Operational research in