Reduction in Genetics

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)

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)

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)

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)

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.

Though the realm of biology has long been under the philosophical rule of the mechanistic magisterium, recent years have seen a surprisingly steady rise in the usurping prowess of process ontology. According to its proponents, theoretical advances in the contemporary science of evo-devo have afforded that ontology a particularly powerful claim to the throne: in that increasingly empirically confirmed discipline, emergently autonomous, higher-order entities are the reigning explanantia. If we are to accept the election of evo-devo as our best conceptualisation (...) of the biological realm with metaphysical rigour, must we depose our mechanistic ontology for failing to properly “carve at the joints” of organisms? In this paper, I challenge the legitimacy of that claim: not only can the theoretical benefits offered by a process ontology be had without it, they cannot be sufficiently grounded without the metaphysical underpinning of the very mechanisms which processes purport to replace. The biological realm, I argue, remains one best understood as under the governance of mechanistic principles. (shrink)

This article describes how empirical discoveries in the 1930s–1950s regarding population variation for chromosomal inversions affected Theodosius Dobzhansky and Richard Goldschmidt. A significant fraction of the empirical work I discuss was done by Dobzhansky and his coworkers; Goldschmidt was an astute interpreter, with strong and unusual commitments. I argue that both belong to a mechanistic tradition in genetics, concerned with the effects of chromosomal organization and systems on the inheritance patterns of species. Their different trajectories illustrate how scientists’ commitments affect (...) how they interpret new evidence and adjust to it. Dobzhansky was moved to revised views about selection, while Goldschmidt moved his attention to different genetic phenomena. However different, there are significant connections between the two that enrich our understanding of their views. I focus on two: the role of developmental considerations in Dobzhansky’s thought and the role of neutrality and drift in Goldschmidt’s evolutionary account. Dobzhansky’s struggle with chromosomal variation is not solely about competing schools of thought within the selectionist camp, as insightfully articulated by John Beatty, but also a story of competition between selectionist thinking and developmental perspectives. In contraposition, Goldschmidt emphasized the role of low penetrance mutations that spread neutrally and pointed out that drift could result from developmental canalization. This account adds to the dominant story about Goldschmidt’s resistance to the splitting of development from genetics, as told by Garland Allen and Michael Dietrich. The story I tell illustrates how developmental thinking and genetic thinking conflicted and influenced researchers with different convictions about the significance of chromosomal organization. (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)

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)

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 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 ...

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: rgw@ucsc.edu. (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)

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.