Stem cell biology and systems biology are two prominent new approaches to studying cell development. In stem cell biology, the predominant method is experimental manipulation of concrete cells and tissues. Systems biology, in contrast, emphasizes mathematical modeling of cellular systems. For scientists and philosophers interested in development, an important question arises: how should the two approaches relate? This essay proposes an answer, using the model of Waddington’s landscape to triangulate between stem cell and systems approaches. This simple abstract model (...) represents development as an undulating surface of hills and valleys. Originally constructed by C. H. Waddington to visually explicate an integrated theory of genetics, development and evolution, the landscape model can play an updated unificatory role. I examine this model’s structure, representational assumptions, and uses in all three contexts, and argue that explanations of cell development require both mathematical models and concrete experiments. On this view, the two approaches are interdependent, with mathematical models playing a crucial but circumscribed role in explanations of cell development. (shrink)

C.H. Waddington is today remembered chiefly as a Drosophila developmental geneticist who developed the concepts of “canalization” and “the epigenetic landscape.” In his lifetime, however, he was widely perceived primarily as a critic of Neo-Darwinian evolutionary theory. His criticisms of Neo-Darwinian evolutionary theory were focused on what he saw as unrealistic, “atomistic” models of both gene selection and trait evolution. In particular, he felt that the Neo-Darwinians badly neglected the phenomenon of extensive gene interactions and that the “randomness” of (...) mutational effects, posited in the theory, was a false postulate. This last criticism dealt with the phenomenon known today as “developmental constraints.” Although population genetics itself has evolved considerably from its form at mid-20th century, much of Waddington’s critique, it is argued here, retains cogency. Yet, he did not attempt to develop a full-fledged alternative theory himself. Perhaps most surprisingly, in retrospect, is that he did not try to marry his work on gene interactions in development with his evolutionary interests, to create a theory of “genetic networks” and their evolution. Whether evolutionary genetics today will incorporate “network thinking” as a central element or whether there will be a general retreat to the more atomistic approach offered by genomics, remains an open question. (shrink)

In an interesting work ‘The Ethical Animal’ Professor C. H. Waddington valiantly attempts to bridge the gap between ‘ought’ and ‘is’ without, it seems, succeeding in doing so. Notwithstanding his erudition, honesty of purpose and charm in exposition, the gulf remains unbridged. Indeed there are passages where it is difficult to be certain whether the author considers that he has bridged it or even what standpoint he finally adopts.

In 1956, in his Principles of Embryology, Conrad Hal Waddington explained that the word “epigenetics” should be used to translate and update Wilhelm Roux’ German notion of “Entwicklungsmechanik” to qualify the studies focusing on the mechanisms of development. When Waddington mentioned it in 1956, the notion of epigenetics was not yet popular, as it would become from the 1980s. However, Waddington referred first to the notion in the late 1930s. While his late allusion clearly reveals that (...) class='Hi'>Waddington readily associated the notion of epigenetics with the developmental process, in the contemporary uses of the notion this developmental connotation seems to have disappeared. The advent and success of molecular biology have probably contributed to focusing biologists’ attention on the “genetic” or the “non-genetic” over the “developmental”. In the present paper, I first examine the links that exist, in Waddington’s work, between the classical notion of epigenesis in embryology and those of epigenetics that Waddington proposed to connect, and even synthesize, data both from embryology and genetics. Second, I show that Waddington’s own view of epigenetics has changed over time and I analyze how these changes appear through his many representations of the relationships between genetic signals and developmental processes. (shrink)

Conrad Hal Waddington was a British developmental biologist who mainly worked in Cambridge and Edinburgh, but spent the late 1930s with Morgan in California learning about Drosophila. He was the first person to realize that development depended on the then unknown activities of genes, and he needed an appropriate model organism. His major experimental contributions were to show how mutation analysis could be used to investigate developmental mechanisms in Drosophila, and to explore how developmental mutation could drive evolution, his (...) other deep interest. Waddington was, however, predominantly a thinker, and set out to provide a coherent framework for understanding the genetic bases of embryogenesis and evolution, developing his ideas in many books. Perhaps his best-known concept is the epigenetic landscape: here a ball rolls down a complex valley, making path choices. The rolling ball represents a cell’s development over time, while the topography represents the changing regulatory environment that controls these choices. In its later forms, the role of each feature in the landscape was controlled by the effects of sets of interacting genes, an idea underpinning contemporary approaches to systems biology. Waddington was the first developmental geneticist and probably the most important developmental biologist of the pre-molecular age. (shrink)

C .H. Waddington was one of the founders of the Theoretical Biology Club at Cambridge in the 1930s whose members advanced a philosophy of biology, “organicism,” that would offer an alternative to the reductionism of mechanistic materialism and the obscurity of vitalism in coming to terms with the dynamic, interdependent, and purposeful character of life. This view was embraced in one form or another by E. S. Russell, John Scott Haldane, C. Lloyd Morgan, Lawrence J. Henderson, C. D. Broad, (...) and Alfred North Whitehead. Waddington, in particular, was devoted to the integration of genetics, development, and evolution within the context of theoretical biology. This article explains the influence of Alfred North Whitehead's philosophy of organism on C. H. Waddington's work. (shrink)

In an interesting work ‘The Ethical Animal’ Professor C. H. Waddington valiantly attempts to bridge the gap between ‘ought’ and ‘is’ without, it seems, succeeding in doing so. Notwithstanding his erudition, honesty of purpose and charm in exposition, the gulf remains unbridged. Indeed there are passages where it is difficult to be certain whether the author considers that he has bridged it or even what standpoint he finally adopts.

From the 1930s through the 1970s, C. H. Waddington attempted to reunite genetics, embryology, and evolution. One of the means to effect this synthesis was his model of the epigenetic landscape. This image originally recast genetic data in terms of embryological diagrams and was used to show the identity of genes and inducers and to suggest the similarities between embryological and genetic approaches to development. Later, the image became more complex and integrated gene activity and mutations. These revised epigenetic (...) landscapes presented an image of how mutations could alter developmental pathways to yield larger phenotypic changes. These diagrams became less important as the operon became used to model differential gene regulation. (shrink)

The Neo‐Darwinian concept of natural selection is plausible when one assumes a straightforward causation of phenotype by genotype. However, such simple 1:1 mapping must now give place to the modern concepts of gene regulatory networks and gene expression noise. Both can, in the absence of genetic mutations, jointly generate a diversity of inheritable randomly occupied phenotypic states that could also serve as a substrate for natural selection. This form of epigenetic dynamics challenges Neo‐Darwinism. It needs to incorporate the non‐linear, stochastic (...) dynamics of gene networks. A first step is to consider the mathematical correspondence between gene regulatory networks and Waddington's metaphoric ‘epigenetic landscape’, which actually represents the quasi‐potential function of global network dynamics. It explains the coexistence of multiple stable phenotypes within one genotype. The landscape's topography with its attractors is shaped by evolution through mutational re‐wiring of regulatory interactions – offering a link between genetic mutation and sudden, broad evolutionary changes. (shrink)

In 2011, Peterson suggested that the main reason why C.H. Waddington was essentially ignored by the framers of the modern evolutionary synthesis in the 1950s was because they were Cartesian reductionists and mathematical population geneticists while he was a Whiteheadian organicist and experimental geneticist who worked with Drosophila. This paper suggests a further reason that can only be seen now. The former defined genes and their alleles by their selectable phenotypes, essentially the Mendelian view, while Waddington defined a (...) gene through its functional role as determined by genetic analysis, a view that foresaw the modern view that a gene is a DNA sequence with some function. The former were interested in selection, while Waddington focused on variation. The differences between the two views of a gene are briefly considered in the context of systems biology. (shrink)

It seems that the reception of Conrad Hal Waddington’s work never really gathered speed in mainstream biology. This paper, offering a transdisciplinary survey of approaches using his epigenetic landscape images, argues that (i) Waddington’s legacy is much broader than is usually recognized—it is widespread across the life sciences (e.g. stem cell biology, developmental psychology and cultural anthropology). In addition, I will show that (ii) there exist as yet unrecognized heuristic roles, especially in model building and theory formation, which (...) Waddington’s images play within his work. These different methodological facets envisioned by Waddington are used as a natural framework to analyze and classify the manners of usage of epigenetic landscape images in post-Waddingtonian ‘landscape approaches’. This evaluation of Waddington’s pictorial legacy reveals that there are highly diverse lines of traditions in the life sciences, which are deeply rooted in Waddington’s methodological work. (shrink)

It was C.H. Waddington's contention that the Neo-Darwinian Theory of Evolution ought to be amended by imbedding it in a broader theoretical framework which takes the role of the phenotype into account. Waddington's theory alleges the existence of two interlocking feedback circuits between environment and phenotype on the one hand and genotype and phenotype on the other. The resulting dynamical model of evolutionary change gives new meaning to the notion of progress in evolution. In this model natural selection (...) acts directly on the phenotype, thereby influencing the feedback relationships. Better tuning of the feedback relations, however, leads to progress in adaptability which in Waddington's theory replaces the cumbersome concept of progress in adaptation.This paper expounds Waddington's theory and places it into a broader philosophical perspective. (shrink)

Conrad Hal Waddington integrated genetics with embryology and evolution by formulating and providing experimental evidence for the mechanisms of canalization and genetic assimilation in the context of stabilizing selection, and by fostering an epigenetic rather than the prevailing gene-centered view of embryonic development and of evolutionary change in development and adult form. Waddington saw phenotypes as processes, not static structures and behaviors. Trained in geology at Cambridge, Waddington turned to experimental studies on the chemical nature of the (...) primary organizer and developed the concepts of evocation and individuation as separable components of embryonic induction. A move after WW II to Edinburgh provided Waddington with his professional home for the rest of his career, during which he integrated 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 integrated, heritable, epigenetic organization of embryonic development is Waddington’s lasting legacy to development. He demonstrated organismal response to environmental change and hidden genetic variation, integrated environmental responsiveness into heritable change in response to selection, and coupled development, environment, and evolution. (shrink)

Studies performed in absence of gravitational constraint show that a living system is unable to choose between two different phenotypes, thus leading cells to segregate into different, alternative stable states. This finding demonstrates that the genotype does not determine by itself the phenotype but requires additional, physical constraints to finalize cell differentiation. Constraints belong to two classes: holonomic (independent of the system's dynamical states, as being established by the space‐time geometry of the field) and non‐holonomic (modified during those biological processes (...) to which they contribute in shaping). This latter kind of “constraints”, in which dynamics works on the constraint to recreate them, have emerged as critical determinants of self‐organizing systems, by manifesting a “closure of constraints.” Overall, the constraints act by harnessing the “randomness” represented by the simultaneous presence of equiprobable events restraining the system within one attractor. These results cast doubt on the mainstream scientific concept and call for a better understanding of causation in cell biology. (shrink)

This article develops a media philosophical framework for addressing the intersection of epigenetics and complex dynamical systems in theoretical biology. In particular, it argues that the theoretical humanities need to think critically about the computability of epigenomic regulation, as well as speculatively about the possibility of an epigenomics beyond complexity. The fact that such a conceptual framework does not exist suggests not only a failure to engage with the mathematics of complexity, but also a failure to engage with its history. (...) Both epigenetics and the application of complex dynamical systems to biology originate in the mid-twentieth-century work of Conrad Hal Waddington. The article demonstrates how this genealogy of epigenetic complexity reveals the need for a speculative conception of epigenomic mediation beyond mathematical complexity. Using Whitehead’s philosophy as a conceptual anchor, the “epimedial landscape” serves as a first pass at a media philosophical revision of the complex dynamical systems view of the epigenetic landscape. (shrink)

This article develops a media philosophical framework for addressing the intersection of epigenetics and complex dynamical systems in theoretical biology. In particular, it argues that the theoretical humanities need to think critically about the computability of epigenomic regulation, as well as speculatively about the possibility of an epigenomics beyond complexity. The fact that such a conceptual framework does not exist suggests not only a failure to engage with the mathematics of complexity, but also a failure to engage with its history. (...) Both epigenetics and the application of complex dynamical systems to biology originate in the mid-twentieth-century work of Conrad Hal Waddington. The article demonstrates how this genealogy of epigenetic complexity reveals the need for a speculative conception of epigenomic mediation beyond mathematical complexity. Using Whitehead’s philosophy as a conceptual anchor, the “epimedial landscape” serves as a first pass at a media philosophical revision of the complex dynamical systems view of the epigenetic landscape. (shrink)

Lorenz proposed in his (1935) articulation of a theory of behavioral instincts that the objective of ethology is to distinguish behaviors that are “innate” from behaviors that are “learned” (or “acquired”). Lorenz’s motive was to open the investigation of certain “adaptive” behaviors to evolutionary theorizing. Accordingly, since innate behaviors are “genetic”, they are open to such investigation. By Lorenz’s light an innate/acquired or learned dichotomy rested on a familiar Darwinian distinction between genes and environments. Ever since Lorenz, ascriptions of innateness (...) have become widespread in the cognitive, behavioral, and biological sciences. The trend continues despite decades of strong arguments that show, in particular, the dichotomy that Lorenz invoked in his theory of behavioral instincts is literally false: no biological trait is the product of genes alone. Some critics suggest that the failure of Lorenz’s account shows that innateness is not well-defined in biology and the practice of ascribing innateness to various biological traits should be dropped from respectable science. Elsewhere (Ariew 1996) I argued that despite the arguments of critics, there really is a biological phenomenon underlying the concept of innateness. On my view, innateness is best understood in terms of C.H. Waddington’s concept of “canalization”, i.e. the degree to which a trait is innate is the degree to which its developmental outcome is canalized. The degree to which a developmental outcome is canalized is the degree to which the developmental process is bound to produce a particular endstate despite environmental fluctuations both in the development’s initial state and during the course of development. The canalization account differs in many ways to the traditional ways that ethologists such as Konrad Lorenz originally understood the concept of innateness. Most importantly, on the canalization account the distinction between innate and acquired is not a dichotomy, as Konrad Lorenz had it, but rather a matter of degree difference that lies along a spectrum with highly canalized development outcomes on the one end and highly environmentally sensitive development outcomes on the other end. Nevertheless, I justified the canalization account on the basis of a set of desiderata or criteria that I suggested falls-out of what seemed uncontroversial about Lorenz’s account of innateness (briefly): innateness is a property of a developing individual, innateness denotes environmental stability, and innate-ascriptions are useful in certain natural selection explanations (more below). From that same set of desiderata I argued (in my 1996) that neither the concept of heritability nor of norms of reactions—two concepts from population genetics—suffice to ground innateness. In this essay, I wish to provide further support of the canalization account in two ways. First, I wish to better motivate the desiderata by revisiting a debate between Konrad Lorenz and Daniel Lehrman over the meaning and explanatory usefulness of innate ascriptions in ethology. Second, I wish to compare my canalization account of innateness with accounts proposed by contemporary philosophers, one by Stephen Stich (1975), another by Elliott Sober (forthcoming), and a third by William Wimsatt (1986). (shrink)

In Insight, Bernard Lonergan provides, albeit schematically, a unique philosophy of biology which he takes as having “profound differences” with the world view presented by Darwin. These turn on Lonergan's idea of “schemes of recurrence” and of organisms as “solutions to the problem of living in an environment.” His lapidary prose requires some deciphering. I present the broad lines of his philosophy of biology and argue that Jean Piaget's structuralism can shed light on Lonergan's intentions in virtue of his use (...) of cybernetics and the isomorphism between biology and knowledge. In turn, Piaget draws on Waddington's restatement of epigenesis and I suggest that the result, “process structuralism,” is a viable alternative to the modern Darwinian synthesis. (shrink)

The discovery by Hans Spemann of the “organizer” tissue and its ability to induce the formation of the amphibian embryo's neural tube inspired leading embryologists to attempt to elucidate embryonic inductions’ underlying mechanism. Joseph Needham, who during the 1930s conducted research in biochemical embryology, proposed that embryonic induction is mediated by a specific chemical entity embedded in the inducing tissue, surmising that chemical to be a hormone of sterol-like structure. Along with embryologist Conrad H. Waddington, they conducted research aimed (...) at the isolation and functional characterization of the underlying agent. As historians clearly pointed out, embryologists came to question Needham's biochemical approach; he failed to locate the hormone he sought and eventually abandoned his quest. Yet, this study finds that the difficulties he ran into resulted primarily from the limited conditions for conducting his experiments at his institute. In addition, Needham's research reflected the interests of leading biochemists in hormone and cancer research, because it offered novel theoretical models and experimental methods for engaging with the function of the hormones and carcinogens they isolated. Needham and Waddington were deterred neither by the mounting challenges nor by the limited experimental infrastructure. Like their colleagues in hormone and cancer research, they anticipated difficulties in attempting to establish causal links between complex biological phenomena and simple chemical triggering. (shrink)