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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
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.
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.
114
BRIAN K. HALL
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
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
WADDINGTON'S LEGACY
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.
115
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
116
BRIAN K. HALL
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).
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.
WADDINGTON'S LEGACY
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.
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-
117
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
118
BRIAN K. HALL
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
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,
WADDINGTON'S LEGACY
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
119
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-
120
BRIAN K. HALL
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).
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
WADDINGTON'S LEGACY
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.
121
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.
122
BRIAN K. HALL
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
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.