Reduction in Genetics

I attempt to characterize the relationship of classical experimental embryology (CEE) and molecular developmental biology and compare it to the much-discussed case of classical genetics. These sciences are treated here as discovery practices rather than as definitive forms of knowledge. I first show that CEE had some causal knowledge and hence was able to answer specific why?-questions. A paradigm was provided by the case of eye induction, perhaps CEE’s greatest success. The case of the famous Spemann-Mangold organizer is more difficult. (...) I argue that before the advent of molecular biology, knowledge of its causal role in development was very limited. As a result, there was no functional definition of the concept of organizer. I argue that, like the classical gene concept, it is best viewed as an operational concept. This means that an account of reduction such as Kim’s functional reduction, which is still a mainstay in scientific metaphysics, cannot work in these cases. Nonetheless, again like in the classical gene case, the operational concepts of CEE played an important heuristic role in the discovery of molecules involved in morphogenesis and cell differentiation. This was made possible by what I call inter-level investigative practices. These are practices that combine experimental manipulations targeting two (or more) different levels. I conclude that the two sciences are more closely related via their experimental practices than by any inter-level explanatory relations. (shrink)

Since the ENCODE project published its final results in a series of articles in 2012, there is no consensus on what its implications are. ENCODE’s central and most controversial claim was that there is essentially no junk DNA: most sections of the human genome believed to be «junk» are functional. This claim was met with many reservations. If researchers disagree about whether there is junk DNA, they have first to agree on a concept of function and how function, given a (...) particular definition, can be discovered. The ENCODE debate centered on a notion of function that assumes a strong dichotomy between evolutionary and non-evolutionary function and causes, prevalent in the Modern Evolutionary Synthesis. In contrast to how the debate is typically portrayed, both sides share a commitment to this distinction. This distinction is, however, much debated in alternative approaches to evolutionary theory, such as the EES. We show that because the ENCODE debate is grounded in a particular notion of function, it is unclear how it connects to broader debates about what is the correct evolutionary frame- work. Furthermore, we show how arguments brought forward in the controversy, particularly arguments from mathematical population genetics, are deeply embedded in their particular disciplinary contexts, and reflect substantive assumptions about the evolution of genomes. With this article, we aim to provide an anatomy of the ENCODE debate that offers a new perspective on the notions of function both sides employed, as well as to situate the ENCODE debate within wider debates regarding the forces operating in evolution. (shrink)

The “Encyclopedia of DNA Elements” (ENCODE) project was launched by the US National Human Genome Research Institute in the aftermath of the Human Genome Project (HGP). It aimed to systematically map the human transcriptome, and held the promise that identifying potential regulatory regions and transcription factor binding sites would help address some of the perplexing results of the HGP. Its initial results published in 2012 produced a flurry of high-impact publications as well as criticisms. Here we put the results of (...) ENCODE and the work on epigenomics that followed in a broad theoretical and historical context, focusing on three strands of research. The first is the history of thinking about the organization of genomes, both physical and regulatory. The second is the history of ideas about gene regulation, primarily in eukaryotes. Finally, and connecting these two issues, we suggest how to think about the role of genetic material in physiology and development. (shrink)

Reductionism is an old doctrine desperate for new direction. With nomologically constructed theories commanding less attention in the life sciences, concern for the twentieth-century tradition of a...

Causation has multiple distinct meanings in genetics. One reason for this is meaning slippage between two concepts of the gene: Mendelian and molecular. Another reason is that a variety of genetic methods address different kinds of causal relationships. Some genetic studies address causes of traits in individuals, which can only be assessed when single genes follow predictable inheritance patterns that reliably cause a trait. A second sense concerns the causes of trait differences within a population. Whereas some single genes can (...) be said to cause population-level differences, most often these claims concern the effects of many genes. Polygenic traits can be understood using heritability estimates, which estimate the relative influences of genetic and environmental differences to trait differences within a population. Attempts to understand the molecular mechanisms underlying polygenic traits have been developed, although causal inference based on these results remains controversial. Genetic variation has also recently been leveraged as a randomizing factor to identify environmental causes of trait differences. This technique—Mendelian randomization—offers some solutions to traditional epidemiological challenges, although it is limited to the study of environments with known genetic influences. (shrink)

Dies ist eine ausgezeichnete Überprüfung der Gen-/Umgebungsinteraktionen auf das Verhalten und ist, obwohl sie etwas veraltet ist, eine einfache und lohnende Lektüre. Sie beginnen mit Zwillingsstudien, die den überwältigenden Einfluss der Genetik auf das Verhalten zeigen. Sie stellen die immer bekannter werdenden Studien von Judith Harris fest, die die Fakten erweitern und zusammenfassen, dass die gemeinsame häusliche Umgebung fast keinen Einfluss auf das Verhalten hat und dass adoptierte Kinder so anders wachsen als ihre Stiefbrüder und -schwestern wie zufällig ausgewählte Menschen. (...) Ein grundlegender Punkt, den sie (und fast alle, die über Verhaltensgenetik diskutieren) nicht zur Kenntnis nehmen, ist, dass die Hunderte (Tausende je nach Standpunkt) menschlicher Verhaltensuniversalen, einschließlich aller Grundlagen unserer Persönlichkeiten, zu 100% von unseren Genen bestimmt werden, ohne Variation in normalen Werten. Jeder sieht einen Baum als Baum und nicht als Stein, sucht und isst Nahrung, wird wütend und eifersüchtig usw. Worüber sie hier also meistens sprechen, ist, wie viel Umwelt (Kultur) das Ausmaß beeinflussen kann, in dem verschiedene Merkmale gezeigt werden, und nicht ihr Aussehen. Schließlich diskutieren sie die Eugenik in der üblichen politisch korrekten Weise, ohne festzustellen, dass wir und alle Organismen die Produkte der Eugenik der Natur sind und dass Versuche, die natürliche Selektion mit Medizin, Landwirtschaft und Zivilisation als Ganzes zu besiegen, für jede Gesellschaft, die dies weiterhin tut,katastrophalsind. Bis zu 50 % aller Empfängnisse oder etwa 100 Millionen pro Jahr enden in einer frühen spontanen Abtreibung, fast alle ohne Dassmund die Mutter. Diese natürliche Keulung defekter Gene treibt die Evolution an, hält uns relativ genetisch gesund und macht die Gesellschaft möglich. Dysgenös ist ausreichend, um die Zivilisation zu zerstören, aber Überbevölkerung wirdd o eszuerst. Wer aus der modernen zweisystems-Sichteinen umfassenden, aktuellen Rahmen für menschliches Verhalten wünscht, kann mein Buch "The Logical Structure of Philosophy, Psychology, Mindand Language in Ludwig Wittgenstein and John Searle' 2nd ed (2019) konsultieren. Diejenigen,die sich für mehr meiner Schriften interessieren, können 'Talking Monkeys--Philosophie, Psychologie, Wissenschaft, Religion und Politik auf einem verdammten Planeten --Artikel und Rezensionen 2006-2017' 3rd ed (2019) und andere sehen. (shrink)

Contemporary philosophy of science has seen a growing trend towards a focus on scientific practice over the epistemic outputs that such practices produce. This practice-oriented approach has yielded a clearer understanding of how reductive research strategies play a central role in contemporary scientific inquiry. In parallel, a growing body of work has sought to explore the role of non-reductive, or systems-level, research strategies. As a result, the relationship between reductive and non-reductive scientific practices is becoming of increased importance. In this (...) paper, I provide a framework within which research strategies can be compared. I argue that no strategy is reductive or non-reductive simpliciter, rather strategies are more, or are less, reductive than one another according to a frame of reference. That frame of reference is provided by a continuum of possible ways in which the target system might be conceptualised. I illustrate the utility of the framework by deploying it to analyse a recent debate in cancer research. When set within the framework, a prominent reductive strategy—the somatic mutation theory—and a prominent non-reductive strategy—the tissue organisational field theory—do not stand opposed to one another. Rather, they serve as boundary markers to chart the territory of approaches to carcinogenesis within which most strategies in the field fall. (shrink)

Roughly, the Central Dogma of molecular biology states that DNA codes for protein, not the other way around. This principle, which is still heralded as an important element of contemporary biological theory, has received much critical attention since its original formulation by Francis Crick in 1958. Some have argued that the principle should be rejected, on the grounds that it fails to fully capture the ins-and-outs of protein synthesis, while others have argued that the Dogma is predicated on notions of (...) information that are simply implausible. Yet, despite all this criticism, there is much about the Dogma that has not been said. Existing discussions, for example, gloss over the many distinct, logically independent readings of the Central Dogma that have been defended in the philosophical and biological literature, making it difficult to see which dogma is being criticized. Additionally, this oversight makes it unclear what the overall upshot of these discussions should be taken to be. My aim in this paper is to fix this. (shrink)

Ongoing empirical discoveries in molecular biology have generated novel conceptual challenges and perspectives. Philosophers of biology have reacted to these trends when investigating the practice of molecular biology and contributed to scientific debates on methodological and conceptual matters. This article reviews some major philosophical issues in molecular biology. First, philosophical accounts of mechanistic explanation yield a notion of explanation in the context of molecular biology that does not have to rely on laws of nature and comports well with molecular discovery. (...) Second, reductionism continues to be debated and increasingly be rejected by scientists. Philosophers have likewise moved away from reduction toward integration across fields or integrative explanations covering several levels of organization. Third, although the gene concept has undergone substantial transformation and even fragmentation, it still enjoys widespread use by molecular biologists, which has prompted philosophers to understand the empirical reasons for this. At the same time, it has been argued the notion of ‘genetic information’ is largely an empty metaphor, which generates the illusion of explanatory understanding without offering an adequate explanation of molecular and developmental mechanisms. (shrink)

Much of the book is aimed at persuading the reader that genes are not ‘the prime movers in all biological processes’ and that ‘postgenomic genes’ are better understood in a functional sense, as ‘things an organism can do with its genome.' With the main argument in place, the authors examine its impact on a number of philosophical debates. I will discuss three of them: causation, information, and reduction.

In 1809--the year of Charles Darwin's birth--Jean-Baptiste Lamarck published Philosophie zoologique, the first comprehensive and systematic theory of biological evolution. The Lamarckian approach emphasizes the generation of developmental variations; Darwinism stresses selection. Lamarck's ideas were eventually eclipsed by Darwinian concepts, especially after the emergence of the Modern Synthesis in the twentieth century. The different approaches--which can be seen as complementary rather than mutually exclusive--have important implications for the kinds of questions biologists ask and for the type of research they conduct. (...) Lamarckism has been evolving--or, in Lamarckian terminology, transforming--since Philosophie zoologique's description of biological processes mediated by "subtle fluids." Essays in this book focus on new developments in biology that make Lamarck's ideas relevant not only to modern empirical and theoretical research but also to problems in the philosophy of biology. Contributors discuss the historical transformations of Lamarckism from the 1820s to the 1940s, and the different understandings of Lamarck and Lamarckism; the Modern Synthesis and its emphasis on Mendelian genetics; theoretical and experimental research on such "Lamarckian" topics as plasticity, soft (epigenetic) inheritance, and individuality; and the importance of a developmental approach to evolution in the philosophy of biology. The book shows the advantages of a "Lamarckian" perspective on evolution. Indeed, the development-oriented approach it presents is becoming central to current evolutionary studies--as can be seen in the burgeoning field of Evo-Devo. Transformations of Lamarckism makes a unique contribution to this research. (shrink)

This article is arranged around two general claims and a thought experiment. I begin by suggesting that the genome should be studied as a developmental system, and that genes supervene on genomes (rather than the other way around). I move on to present a thought experiment that illustrates the implications a dynamic view of the genome has for central concepts in biology, in particular the information content of the genome, and the notion of responses to stress.

Advancing the reductionist conviction that biology must be in agreement with the assumptions of reductive physicalism (the upward hierarchy of causal powers, the upward fixing of facts concerning biological levels) A. Rosenberg argues that downward causation is ontologically incoherent and that it comes into play only when we are ignorant of the details of biological phenomena. Moreover, in his view, a careful look at relevant details of biological explanations will reveal the basic molecular level that characterizes biological systems, defined by (...) wholly physical properties, e.g., geometrical structures of molecular aggregates (cells). In response, we argue that contrary to his expectations one cannot infer reductionist assumptions even from detailed biological explanations that invoke the molecular level, as interlevel causal reciprocity is essential to these explanations. Recent very detailed explanations that concern the structure and function of chromatin—the intricacies of supposedly basic molecular level—demonstrate this. They show that what seem to be basic physical parameters extend into a more general biological context, thus rendering elusive the concepts of the basic level and causal hierarchy postulated by the reductionists. In fact, relevant phenomena are defined across levels by entangled, extended parameters. Nor can the biological context be explained away by basic physical parameters defining molecular level shaped by evolution as a physical process. Reductionists claim otherwise only because they overlook the evolutionary significance of initial conditions best defined in terms of extended biological parameters. Perhaps the reductionist assumptions (as well as assumptions that postulate any particular levels as causally fundamental) cannot be inferred from biological explanations because biology aims at manipulating organisms rather than producing explanations that meet the coherence requirements of general ontological models. Or possibly the assumptions of an ontology not based on the concept of causal powers stratified across levels can be inferred from biological explanations. The incoherence of downward causation is inevitable, given reductionist assumptions, but an ontological alternative might avoid this. We outline desiderata for the treatment of levels and properties that realize interlevel causation in such an ontology. (shrink)

The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology ‘revolutionizes’ molecular biology and ‘transcends’ its (...) assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology’s use of modelling and bioinformatics, and by its scale enlargement. (shrink)

Although molecular biology has meant different things at different times, the term is often associated with a tendency to view cellular causation as conforming to simple linear schemas in which macro-scale effects are specified by micro-scale structures. The early achievements of molecular biologists were important for the formation of such an outlook, one to which the discovery of recombinant DNA techniques, and a number of other findings, gave new life even after the complexity of genotype–phenotype
relations had become apparent. Against this (...) background we outline how a range of scientific developments and conceptual considerations can be regarded as enabling and perhaps necessitating contemporary systems approaches. We suggest that philosophical ideas have a valuable part to play in making sense of complex scientific and disciplinary issues. (shrink)

Schaffner’s model of theory reduction has played an important role in philosophy of science and philosophy of biology. Here, the model is found to be problematic because of an internal tension. Indeed, standard antireductionist external criticisms concerning reduction functions and laws in biology do not provide a full picture of the limits of Schaffner’s model. However, despite the internal tension, his model usefully highlights the importance of regulative ideals associated with the search for derivational, and embedding, deductive relations among mathematical (...) structures in theoretical biology. A reconstructed Schaffnerian model could therefore shed light on mathematical theory development in the biological sciences and on the epistemology of mathematical practices more generally. *Received November 2006; revised March 2009. †To contact the author, please write to: Philosophy Department, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064; e‐mail: [email protected]. (shrink)

After the discovery of the structure of DNA in 1953, scientists working in molecular biology embraced reductionism—the theory that all complex systems can be understood in terms of their components. Reductionism, however, has been widely resisted by both nonmolecular biologists and scientists working outside the field of biology. Many of these antireductionists, nevertheless, embrace the notion of physicalism—the idea that all biological processes are physical in nature. How, Alexander Rosenberg asks, can these self-proclaimed physicalists also be antireductionists? With clarity and (...) wit, Darwinian Reductionism navigates this difficult and seemingly intractable dualism with convincing analysis and timely evidence. In the spirit of the few distinguished biologists who accept reductionism—E. O. Wilson, Francis Crick, Jacques Monod, James Watson, and Richard Dawkins—Rosenberg provides a philosophically sophisticated defense of reductionism and applies it to molecular developmental biology and the theory of natural selection, ultimately proving that the physicalist must also be a reductionist. (shrink)

Although epistasis is at the center of the Fisher-Wright debate, biologists not involved in the controversy are often unaware that there are actually two different formal definitions of epistasis. We compare concepts of genetic independence in the two theoretical traditions of evolutionary genetics, population genetics and quantitative genetics, and show how independence of gene action (represented by the multiplicative model of population genetics) can be different from the absence of gene interaction (represented by the linear additive model of quantitative genetics). (...) The two formulations converge with weak selection but not with strong selection or, for multiple loci, when the aggregated interaction terms are not negligible. As a result of the different formulations of gene interaction, the presence or absence of linkage disequilibrium,/D/, does not necessarily indicate the presence or absence of fitness epistasis. Indeed, linkage disequilibrium is generated in ‘additive’ models in quantitative genetics whenever two (or more) loci experience simultaneous selection. As a research strategy, it is often practical, for theoretical or experimental reasons, to minimize gene interaction by assuming independence of gene action in regard to fitness, or by assuming linear additive effects of multiple loci on a phenotype. However, minimizing the role of epistasis in theoretical investigations hinders our understanding of the origins of diversity and the evolution of complex phenotypes. (shrink)

The study of mental illness by the methods of molecular genetics is still in its infancy, but the use of genetic markers in psychiatry may potentially lead to a Virchowian revolution in the conception of mental illness. Genetic markers may define novel clusters of patients having diverse clinical presentations but sharing a common genetic and mechanistic basis. Such clusters may differ radically from the conventional classification schemes of psychiatric illness. However, the reduction of even relatively simple Mendelian phenomena to molecular (...) genetics has been shown to be a surprisingly complex and problematic enterprise. Mental illnesses exist at many levels of including social, environmental, and developmental interactions. Reductionistic shifts in the classification of such a disease entity will have to address the interlevel dynamics that take place within the structure of theories of mental illness. The question of how molecular analysis of psychiatric disease will impact on the structure of existing theories and classification systems is the central topic of this paper. (shrink)

The discussion of theory reduction in genetics threatens to become more and more confused. The position taken is that before one tries to work out complicated reduction principles which might be applicable to broad areas of biology in their relationships to chemistry and physics, it would be better to attempt first to elucidate the internal structure of some limited biological theories in a formal way and to consider simple constructs for reduction between them. This proposal is elaborated with respect to (...) the original Mendelian genetics, linkage genetics and fine-structure genetics, and their relationship to non-formalized molecular genetics. (shrink)

Taking reduction in the traditional deductive sense, the programmatic claim that most of genetics can be reduced by molecular genetics is defended as feasible and significant. Arguments by Ruse and Hull that either the relationship is replacement or at best a weaker form of reduction are shown to rest on a mixture of historical and logical confusions about the nature of the theories involved.

. Introductory Remarks THEODOSIUS DOBZHANSKY The problems of reduction in biology are currently of considerable theoretical interest and practical ...

I have not attempted to provide here an analysis of the methodology of molecular biology or molecular genetics which would demonstrate at what specific points a more reductionist aim would make sense as a research strategy. This, I believe, would require a much deeper analysis of scientific growth than philosophy of science has been able to provide thus far. What I have tried to show is that a straightforward reductionist strategy cannot be said to be follwed in important cases of (...) theory development in molecular biology, and that in at least one important case, the Jacob-Monod operon theory, the methodology followed was more biological than chemical. It should be noted in closing, however, that since biological systems are thought by molecular biologists to be nothing but chemical systems, in the long run detailed investigations of such systems will be in full accord with the dictates suggested by the general reduction model. (shrink)