Recent work on gene concepts has been influenced by recognition of the extent to which RNA transcripts from a given DNA sequence yield different products in different cellular environments. These transcripts are altered in many ways and yield many products based, somehow, on the sequence of nucleotides in the DNA. I focus on alternative splicing of RNA transcripts (which often yields distinct proteins from the same raw transcript) and on 'gene sharing', in which a single gene produces distinct proteins with (...) the exact same amino acid sequence. These are instances of molecular pleiotropy, in which distinct molecules are derived from a single putative gene. In such cases the cellular and external environments play major roles in determining which protein is produced. Where there is molecular pleiotropy, alternative gene concepts are naturally deployed; molecular epigenesis (revision of sequence-based information by altering molecular conformations or by action of non-informational molecules) plays a major role in orderly development. These results show that gene concepts in molecular biology do, and should, have both structural and functional components. They also show the need for a plurality of gene concepts and reveal fundamental difficulties in stabilizing gene concepts solely by reference to nucleotide sequence. (shrink)

Philosophers of science turned to historical case studies in part in response to Thomas Kuhn's insistence that such studies can transform the philosophy of science. In this issue Joseph Pitt argues that the power of case studies to instruct us about scientific methodology and epistemology depends on prior philosophical commitments, without which case studies are not philosophically useful. Here I reply to Pitt, demonstrating that case studies, properly deployed, illustrate styles of scientific work and modes of argumentation that are not (...) well handled by currently standard philosophical analyses. I illustrate these claims with exemplary findings from case studies dealing with exploratory experimentation and with interdisciplinary cooperation across sciences to yield multiple independent means of access to theoretical entities. The latter cases provide examples of ways that scientists support claims about theoretical entities that are not available in work performed within a single discipline. They also illustrate means of correcting systematic biases that stem from the commitments of each discipline taken separately. These findings illustrate the transformative power of case study methods, allow us to escape from the horns of Pitt's "dilemma of case studies," and vindicate some of the post-Kuhn uses to which case studies have been put. (shrink)

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

Collected for the first time in a single volume are essays which examine the developments in three fundamental biological disciplines - embryology, evolutionary biology, and genetics. These disciplines were in conflict for much of the twentieth century and the essays in this collection examine key methodological problems within these disciplines and the difficulties faced in overcoming the conflicts between them. Burian skilfully weaves together historical appreciation of the settings within which scientists work, substantial knowledge of the biological problems at (...) stake and the methodological and philosophical issues faced in integrating biological knowledge drawn from disparate sources. The final chapter describes what recent findings in development biology and genetics can tell us about the history and development of animals. Written in a clear, accessible style this collection should appeal to students and professionals in philosophy of science, and the philosophy and history of biology. (shrink)

History of science, it has been argued, has benefited philosophers of science primarily by forcing them into greater contact with "real science." In this paper I argue that additional major benefits arise from the importance of specifically historical considerations within philosophy of science. Loci for specifically historical investigations include: (1) making and evaluating rational reconstructions of particular theories and explanations, (2) estimating the degree of support earned by particular theories and theoretical claims, and (3) evaluating proposed philosophical norms for the (...) evaluation of the degree of support for theories and the worth of explanations. More generally, I argue that theories develop and change structure with time, that (like biological species) they are historical entities. Accordingly, both the identification and the evaluation of theories are essentially historical in character. (shrink)

This article shows how Lamarckism was essential in the birth of the French school of molecular biology. We argue that the concept of inheritance of acquired characters positively shaped debates surrounding bacteriophagy and lysogeny in the Pasteurian tradition during the interwar period. During this period the typical Lamarckian account of heredity treated it as the continuation of protoplasmic physiology in daughter cells. Félix d’Hérelle applied this conception to argue that there was only one species of bacteriophage and Jules Bordet applied (...) it to develop an account of bacteriophagy as a transmissible form of autolysis and to analyze the new phenomenon of lysogeny. In a long-standing controversy with Bordet, Eugène Wollman deployed a more morphological understanding of the inheritance of acquired characters, yielding a particulate, but still Lamarckian, account of lysogeny. We then turn to André Lwoff who, with several colleagues, completed Wollman’s research program from 1949 to 1953. We examine how he gradually set aside the Lamarckian background, finally removing inheritance of acquired characters from the resulting account of bacteriophagy and lysogeny. In the conclusion, we emphasize the complex dual role of Lamarckism as it moved from an assumed explanatory framework to a challenge that the nascent molecular biology had to overcome. (shrink)

In this study we have examined the reception of Mendelism in France from 1900 to 1940, and the place of some of the extra-Mendelian traditions of research that contributed to the development of genetics in France after World War II.

The essays in this collection examine developments in three fundamental biological disciplines--embryology, evolutionary biology, and genetics--in conflict with each other for much of the twentieth century. They consider key methodological problems and the difficulty of overcoming them. Richard Burian interweaves historical appreciation of the settings within which scientists work, substantial knowledge of the biological problems at stake and the methodological and philosophical issues faced in integrating biological knowledge drawn from disparate sources.

In this paper I respond to Wim van der Steen''s arguments against the supposed current overemphasis on norms ofcoherence andinterdisciplinary integration in biology. On the normative level, I argue that these aremiddle-range norms which, although they may be misapplied in short-term attempts to solve (temporarily?) intractable problems, play a guiding role in the longer-term treatment of biological problems. This stance is supported by a case study of apartial success story, the development of the one gene — one enzyme hypothesis. As (...) that case shows, thegoal of coherent interdisciplinary integration not only provides guidance for research, but also provides the standard for recognizingfailed integrations of the sort that van der Steen criticizes. (shrink)

In biology proteins are uniquely important. They are not to be classed with polysaccharides, for example, which by comparison play a very minor role. Their nearest rivals are the nucleic acids....The main function of proteins is to act as enzymes....In the protein molecule Nature has devised a unique instrument in which an underlying simplicity is used to express great subtlety and versatility; it is impossible to see molecular biology in proper perspective until this peculiar combination of virtues has been clearly (...) grasped. (shrink)

Recently improved understanding of evolutionary processes suggests that tree-based phylogenetic analyses of evolutionary change cannot adequately explain the divergent evolutionary histories of a great many genes and gene complexes. In particular, genetic diversity in the genomes of prokaryotes, phages, and plasmids cannot be fit into classic tree-like models of evolution. These findings entail the need for fundamental reform of our understanding of molecular evolution and the need to devise alternative apparatus for integrated analysis of these genomes. We advocate the development (...) of integrative phylogenomics for analyzing these genomes and their histories, with tools suited to analyzing the importance of lateral gene transfer (LGT) and of DNA evolution in extra-cellular mobile genetic elements (e.g., viruses, plasmids). These phenomena greatly increase the complexity of relationships among interacting genetic partners, as they exchange functional genetic units. We examine the ontology of functional genetic units, interacting genetic partners, and emergent genetic associations, argue that these three categories of entities are required for a successful integrated phylogenomics. We conclude with arguments to suggest that the proposed new perspective and associated tools are suitable, and perhaps required, as a replacement for the bifurcating trees that have dominated evolutionary thinking for the last 150 years. (shrink)

Biology deals, notoriously, with complex systems. In discussing biological methodology, all three papers in this symposium honor the complexity of biological subject matter by preferring models and theories built to reflect the details of complex systems to models based on broad general principles or laws. Rheinberger's paper, the most programmatic of the three, provides a framework for the epistemology of discovery in complex systems. A fundamental problem is raised for Rheinberger's epistemology, namely, how to understand the referential continuity of the (...) theoretical terms and concepts employed in typical case studies involving complex systems. (shrink)

The formal framework of Kauffman (1991) depicts the constraints of self-organization on the evolution of complex systems and the relation of self-organization to selection. We discuss his treatment of 'generic constraints' as sources of order (section 2) and the relation between adaptation and organization (section 3). We then raise a number of issues, including the role of adaptation in explaining order (section 4) and the limitations of formal approaches in explaining the distinctively biological (section 5). The principal question we pose (...) is the relation of generic constraints on evolution to more specific local constraints, imposed, for example, by the characteristic materials out of which organisms are constructed, the accidental features characteristic of the Bauplan of a lineage, and the local vicissitudes of adaptation. We offer no answer to this large question. (shrink)

Introduces a series of articles which deals with the relationship between history of science and philosophy of science.; Introduces a series of articles which deals with the relationship between history of science and philosophy of science.

This last result leads, rather naturally, to some concluding observations and a series of questions for further investigation. These case studies show that in all of the sites examined, the institutionalization of molecular biology as a “discipline” was primarily driven by the need to separate groups of practitioners with divergent but overlapping interests within the local context. Thus molecular biology was contingently separated from agricultural or medical biochemistry, virology, work on the physiology of nucleic acids, and so forth for contingent (...) local institutional reasons. This makes it even more pressing to try to understand how molecular biology came to be delimited on a larger scale. How did it come to be a discipline with specific intellectual content (or did it?), including some problems, tools, and practices and excluding others? How did it gain authority as the forefront biological science by the mid-1960s? We need to understand the ways in which the tensions between different practices, projects, aims, understandings of the goals of molecular biology, and so on were resolved, on what scale and in what venues, so that something approximating the political character of a discipline, rather than a federation, was achieved. If these case studies provide a sound starting point, it will nevertheless prove difficult to answer the interconnected questions implicit here satisfactorily.One means of getting at such questions that should prove of considerable interest is to examine carefully the work of those who were widely cited in the papers of the late fifties through the mid-seventies by the people now considered major founders of molecular biology. By studying the contributions of those who are now omitted in the standard histories and recollections, we will gain a clearer sense of the possibilities that were open as molecular biology took shape. It is already widely recognized that the contributions of a number of biochemists have been given short shrift, but (as the example of Ernest Gale in Rheinberger's study illustrates) there are a great many more figures whose line of work were then crucial but who are now overlooked.6 To understand both what molecular biology was at the time of its early institutionalization and what is has become, it will be enormously helpful to understand at what point the definition or ideology “hardened” and the grounds for inclusion and exclusion of individuals and lines of work were reformed. Studies of this sort are appropriate in many other areas as well, of course; in general, they should different histories, political standing, and institutional bases of those disciplines in their national cultures. It is likely (but a matter for investigation!) that such differences influenced the opportunities for introducing new bench practices, if in no other way than by delimiting the niches within which certain practices could be initiated.7 And since new practices can fail to achieve their objectives, can transform the direction of work and disciplinary allegiances of their practitioners, can lead to only routine results, or can open up important new vistas, the character of the available niches from which to work can prove to have a strong influence on the direction that new work takes if and when it starts to flourish. A key aspect of this problematic (not yet adequately studied, I believe) is the problem of drawing boundaries between different kinds of work and determining where each should fit among established disciplines and/or within some new construct. To the extent that an “international” solution is ultimately achieved to such problems, it must surely be achieved in light of initially different ways of dealing with it in different countries.Underlying work of the sort we have been exploring is the thorny problem of how best to contextualize the work being studied. This, I believe, is one of the major historiographic problems that we must face in the history of science. It is by no means a new problem, of course, but a particularization of the age-old problem of the (seeming) overdetermination of historical events. If we deal with local cultures, to understand how they develop and their fate we need to understand their location within larger cultures. But it is utterly unclear how to draw appropriate boundaries on the relevant larger culture(s). As even this brief discussion has shown, institutional cultures, the cultures of sponsoring agencies, “the” culture of science (or of biological science, physical science, etc., as appropriate), and national cultures all can provide relevant contexts, all can occasionally determine the fate of work undertaken in a particular local context. The potentially intractable problem of delimiting the boundaries of investigation looms large here, but it is one that must be faced explicity if we are to profit fully from the enormously stimulating investigations of local cultures exemplified in the four papers published in this symposium. My own view is that we have no abstract standard available for determining which boundaries are appropriate to a given study, and, indeed, that no single contextualization is adequate to the examination of any given case, but that, nonetheless, we can (at least sometimes) distinguish useful and explanatory delimitations of the larger context from others that prove to be misleading.Against this background, I hope that the four papers published in this special issue will stimulate the readers of the JHB to carry out similar studies—that is, studies that seek to characterize and contextualize local experimental cultures —over a wide range of cases. I also hope that some of those who take up this challenge will deal with the larger questions raised by the need to find a way of balancing different, sometimes competing, contextualizations of such studies. The fact that any given case requires multiple contextualizations, resulting in multifaceted representations no one of which is alone adequate, will surely land us in fascinating, hopefully fruitful and productive, controversies. (shrink)

The Greater Philadelphia Philosophy Consortium was launched in the early eighties. It began during a particularly lean period in the American economy.

This chapter offers a review of standard views about the requirements for natural selection to shape evolution and for the sorts of ‘units’ on which selection might operate. It then summarizes traditional arguments for genic selectionism, i.e., the view that selection operates primarily on genes (e.g., those of G. C. Williams, Richard Dawkins, and David Hull) and traditional counterarguments (e.g., those of William Wimsatt, Richard Lewontin, and Elliott Sober, and a diffuse group based on life history strategies). It (...) then offers a series of responses to the arguments, based on more contemporary considerations from molecular genetics, offered by Carmen Sapienza. A key issue raised by Sapienza concerns the degree to which a small number of genes might be able to control much of the variation relevant to selection operating on such selectively critical organs as hearts. The response to these arguments suggests that selection acts on many levels at once and that sporadic selection, acting with strong effects, can act successively on different key traits (and genes) while maintaining a balance among many potentially conflicting demands faced by organisms within an evolving lineage. (shrink)

This anthology collects some of the most important papers on what is believed to be the major force in evolution, natural selection. An issue of great consequence in the philosophy of biology concerns the levels at which, and the units upon which selection acts. In recent years, biologists and philosophers have published a large number of papers bearing on this subject. The papers selected for inclusion in this book are divided into three main sections covering the history of the subject, (...) explaining its conceptual foundations, and focusing on kin and group selection and higher levels of selection.One of the book's interesting features is that it draws together material from the biological and philosophical literatures. The philosophical literature, having thoroughly absorbed the biological material, now offers conceptual tools suitable for the reworking of the biological arguments. Although a full symbiosis has yet to develop, this anthology offers a unique resource for students in both biology and philosophy.Robert N. Brandon is Professor in the Philosophy Department, Duke University. Richard M. Burian is Professor of Philosophy and Department Chairman, Virginia Polytechnic Institute and State University.A Bradford Book. (shrink)

In the grand tradition, philosophical ontology was considered logically and epistemologically prior to scientific ontology. Like many contemporary philosophers of science, we consider this to be a mistake. There is two-way traffic between philosophical and scientific ontologies; the more we learn about what there actually is, the more we learn about what can be and what must be, and vice versa. But that is not the present topic; here we focus on the ontology or ontologies of science, not traditional philosophical (...) ontologies or the traffic between scientific and philosophical ontologies. (shrink)

Stuart Kauffman’s forthcoming book, The Origins of Order: Self Organization and Selection in Evolution (1991), is a large and ambitious attempt to bring about a major reorientation in theoretical biology and to provide a fundamental reinterpretation of the place of selection in evolutionary theory. Kauffman offers a formal framework which allows one to pose precise and well-defined questions about the constraints that self-organization imposes on the evolution of complex systems, and the relation of self-organization and selection. He says at the (...) outset that he wants to “delineate the spontaneous sources of order, the self organized properties of simple and complex systems” and to understand how they “permit, enable and limit the efficacy of natural selection” (Introduction, p. 2).2 As he says somewhat later, the central theme running through his book is that “the order in organisms may largely reflect spontaneous order in complex systems” (ch. 6, p. 224). (shrink)