Karola Stotz

(1963 - 2019)

The paper argues against the central dogma and its interpretation by C. Kenneth Waters and Alex Rosenberg. I argue that certain phenomena in the regulation of gene expression provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. My thesis of 'molecular epigenesis' with its three classes of phenomena, sequence 'activation', 'selection', and 'creation', is exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA editing. It argues that other molecular resources share the causal role of genes; the sequence specificity for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (thesis of distributed causal specificity). I conclude that the central dogma has unnecessarily restricted genetic research to the sequencing of protein-coding genes, unilinear pathway analyses, and the focus on exclusive specificity

In this chapter we examine the relationship between biological information, the key biological concept of specificity, and recent philosophical work on causation. We begin by showing how talk of information in the molecular biosciences grew out of efforts to understand the sources of biological specificity. We then introduce the idea of ‘causal specificity’ from recent work on causation in philosophy, and our own, information theoretic measure of causal specificity. Biological specificity, we argue, is simple the causal specificity of certain biological processes. This, we suggest, means that causal relationships in biology are ‘informational’ relationships simply when they are highly specific relationships. Biological information can be identified with the storage, transmission and exercise of biological specificity. It has been argued that causal relationships should not be regarded as informational relationship unless they are ‘arbitrary’. We argue that, whilst arbitrariness is an important feature of many causal relationships in living systems, it should not be used in this way to delimit biological information. Finally, we argue that biological specificity, and hence biological information, is not confined to nucleic acids but distributed among a wide range of entities and processes.

The paper describes the change from molecular genetics to postgenomic biology. It focuses on phenomena in the regulation of gene expression that provide a break with the central dogma, according to which sequence specificity for a gene product must be template derived. In its place we find what is called here ‘constitutive molecular epigenesis’. Its three classes of phenomena, which I call sequence ‘activation’, ‘selection’ and ‘creation’, are exemplified by processes such as transcriptional activation, alternative cis- and trans-splicing, and RNA editing. These phenomena support the following main theses of the paper: 1. Other molecular resources share the causal role of ‘genes’: the ‘causal specificity’ for the linear sequence of any gene product is distributed between the coding sequence, cis-acting sequences, trans-acting factors, environmental signals, and the contingent history of the cell (the cellular code) (thesis of distributed causal specificity). 2. These multiple and overlapping processing and targeting mechanisms amplify the repertoire of RNA and protein products specified through the eukaryotic genome, expanding the possibilities specified by the literal code of DNA (thesis of genetic underdeterminism). 3. These mechanisms of gene expression change the focus of postgenomic research from single molecules and their molecular, biochemical and intrinsic function to their cellular, constituent, component or contextual function due to their recruitment and organization in complex cellular networks. In other words, all agents involved in the regulation of gene expression, including DNA, must interact with other agents to achieve full specificity, which is imposed by regulated recruitment and combinatorial control (theses of regulated recruitment and of system analysis). I conclude from these three main theses that the complexity of higher organisms lies not in its number of genes but in the flexibility, versatility and reactivity of its whole genome.

Recent theories in cognitive science have begun to focus on the active role of organisms in shaping their own environment, and the role of these environmental resources for cognition. Approaches such as situated, embedded, ecological, distributed and particularly extended cognition look beyond ‘what is inside your head’ to the old Gibsonian question of ‘what your head is inside of’ and with which it forms a wider whole—its internal and external cognitive niche. Since these views have been treated as a radical departure from the received view of cognition, their proponents have looked for support to similar extended views within (the philosophy of) biology, most notably the theory of niche construction. This paper argues that there is an even closer and more fruitful parallel with developmental systems theory and developmental niche construction. These ask not ‘what is inside the genes you inherited’, but ‘what the inherited genes are inside of’ and with which they form a wider whole—their internal and external ontogenetic niche, understood as the set of epigenetic, social, ecological, epistemic and symbolic legacies inherited by the organism as necessary developmental resources. To the cognizing agent, the epistemic niche presents itself not just as a partially self-engineered selective niche, as the niche construction paradigm will have it, but even more so as a partially self-engineered ontogenetic niche, a problem-solving resource and scaffold for individual development and learning. This move should be beneficial for coming to grips with our own (including cognitive) nature: what is most distinctive about humans is their developmentally plastic brains immersed into a well-engineered, cumulatively constructed cognitive–developmental niche

What kind mechanisms one deems central for the evolutionary process deeply influences one's understanding of the nature of organisms, including cognition. Reversely, adopting a certain approach to the nature of life and cognition and the relationship between them or between the organism and its environment should affect one's view of evolutionary theory. This paper explores this reciprocal relationship in more detail. In particular it argues that the view of living and cognitive systems, especially humans, as deeply integrated beings embedded in and transformed by their genetic, epigenetic, behavioral, ecological, socio-cultural and cognitive-symbolic legacies calls for an extended evolutionary synthesis that goes beyond either a theory of genes juxtaposed against a theory of cultural evolution and or even more sophisticated theories of gene-culture coevolution and niche construction. Environments, particularly in the form of developmental environments, do not just select for variation, they also create new variation by influencing development through the reliable transmission of non-genetic but heritable information. This paper stresses particularly views of embodied, embedded, enacted and extended cognition, and their relationship to those aspects of extended inheritance that lie between genetic and cultural inheritance, the still gray area of epigenetic and behavioral inheritance systems that play a role in parental effect. These are the processes that can be regarded as transgenerational developmental plasticity and that I think can most fruitfully contribute to, and be investigated by, developmental psychology.

We outline three very different concepts of the gene—instrumental, nominal, and postgenomic. The instrumental gene has a critical role in the construction and interpretation of experiments in which the relationship between genotype and phenotype is explored via hybridization between organisms or directly between nucleic acid molecules. It also plays an important theoretical role in the foundations of disciplines such as quantitative genetics and population genetics. The nominal gene is a critical practical tool, allowing stable communication between bioscientists in a wide range of fields grounded in well-defined sequences of nucleotides, but this concept does not embody major theoretical insights into genome structure or function. The post-genomic gene embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit. This final concept of the gene poses a significant challenge to conventional assumptions about the relationship between genome structure and function, and between genotype and phenotype.

Keller explains the persistence of the nature/nurture debate by a chronic ambiguity in language derived from classical and behavioral genetics. She suggests that the more precise vocabulary of modern molecular genetics may be used to rephrase the underlying questions and hence provide a way out of this controversy. I show that her proposal fits into a long tradition in which other authors have wrestled with the same problem and come to similar conclusions. - Review of 'The mirage of a space between nature and nurture' by Evelyn Fox Keller, Duke University Press, 2010, ISBN 9780822347316

This paper serves as an introduction to the special issue on “Reconciling Nature and Nurture in Behavior and Cognition Research” and sets its agenda to resolve the 'interactionist' dichotomy of nature as the genetic, and stable, factors of development, and nurture as the environmental, and plastic influences. In contrast to this received view it promotes the idea that all traits, no matter how developmentally fixed or universal they seem, contingently develop out of a single-cell state through the interaction of a multitude of developmental resources that defies any easy, dichotomous separation. It goes on to analyze the necessary ingredients for such a radical, epigenetic account of development, heredity and evolution: 1. A detailed understanding of the epigenetic nature of the regulatory mechanisms of gene expression; 2. The systematical questioning of preconceptions of 'explanatory' categories of behavior, such as 'innate' or 'programmed'; 3. Especially in psychological research the integration of the concepts of 'development' and 'learning', and a richer classification of the concept of 'environment' in the production of behavior; 4. A fuller understanding of the nature of inheritance that transcends the restriction to the genetic material as the sole hereditary unit, and the study of the process of developmental niche construction; and last 5. Taking serious the role of ecology in development and evolution. I hope that an accomplishment of the above task will then lead to a 'postgenomic' synthesis of nature and nurture that conceptualizes 'nature' as the natural phenotypic outcome 'nurtured' by the natural developmental process leading to it.

This paper understands reductionism as a relation between explanations, not theories. It argues that knowledge of the micro-level behavior of the components of systems is necessary, but only combined with a full specification of the contingent context sufficient for a full explanation of systems phenomena. The paper takes seriously fundamental principles independent and transcendent of the laws of quantum mechanics that govern most of real-world phenomena. It will conclude in showing how the recent postgenomic revolution, taking seriously the physical principle of organization and collective behavior, can be understood as attempting to complement a reductionist investigative strategy with an antireductionist explanatory strategy.

The 'developmental systems' perspective in biology is intended to replace the idea of a genetic program. This new perspective is strongly convergent with recent work in psychology on situated/embodied cognition and on the role of external 'scaffolding' in cognitive development. Cognitive processes, including those which can be explained in evolutionary terms, are not 'inherited' or produced in accordance with an inherited program. Instead, they are constructed in each generation through the interaction of a range of developmental resources. The attractors which emerge during development and explain robust and/or widespread outcomes are themselves constructed during the process. At no stage is there an explanatory stopping point where some resources control or program the rest of the developmental cascade. 'Human nature' is a description of how things generally turn out, not an explanation of why they turn out that way. Finally, we suggest that what is distinctive about human development is its degree of reliance on external scaffolding.

Recent years have seen the development of an approach both to general philosophy and philosophy of science often referred to as ‘experimental philosophy’ or just ‘X-Phi’. Philosophers often make or presuppose empirical claims about how people would react to hypothetical cases, but their evidence for claims about what ‘we’ would say is usually very limited indeed. Philosophers of science have largely relied on their more or less intimate knowledge of their field of study to draw hypothetical conclusions about the state of scientific concepts and the nature of conceptual change in science. What they are lacking is some more objective quantitative data supporting their hypotheses. A growing number of philosophers , along with a few psychologists and anthropologists, have tried to remedy this situation by designing experiments aimed at systematically exploring people’s reactions to philosophically important thought experiments or scientists’ use of their scientific concepts. Many of the results have been surprising and some of the conclusions drawn from them have been more than a bit provocative. This symposium attempts to provide a window into this new field of philosophical inquiry and to show how experimental philosophy provides crucial tools for the philosopher and encourages two-way interactions between scientists and philosophers.Keywords: Experimental philosophy; Naturalism; Continuity thesis; Philosophy of science; Quantitative data