Leading animal models are powerful tools for translational research, but they also present obstacles. Poorly conducted preclinical research in animals is a common cause of translational failure, but even when such research is well-designed and carefully executed, challenges remain. In particular, dominant models may bias research directions, elide essential aspects of human disease, omit important context, or subtly shift research targets. Recognizing these stumbling blocks can help us find ways to avoid them: employing a wider range of models, incorporating more (...) realistic environmental conditions, better aligning studies between animals and patients, and focusing on human biology and therapeutic goals. Such changes are costly; but insisting it would be impractical or unrealistic to change strategies offers no way out of the current impasse. Rather, we must acknowledge the obstacles as well as the advantages presented by core models, and direct some of our investments in translational research toward getting around them. The dominance of biomedical research by a handful of animal models introduces subtle but significant obstacles to translation. Recognizing these obstacles is a critical first step toward finding ways around them; this paper describes how dominant models can create roadblocks, and suggests strategies to improve the efficiency of translation from animal models to humans. (shrink)

The Hodgkin–Huxley (HH) model of the action potential is a theoretical pillar of modern neurobiology. In a number of recent publications, Carl Craver ([2006], [2007], [2008]) has argued that the model is explanatorily deficient because it does not reveal enough about underlying molecular mechanisms. I offer an alternative picture of the HH model, according to which it deliberately abstracts from molecular specifics. By doing so, the model explains whole-cell behaviour as the product of a mass of underlying low-level events. The (...) issue goes beyond cellular neurobiology, for the strategy of abstraction exhibited in the HH case is found in a range of biological contexts. I discuss why it has been largely neglected by advocates of the mechanist approach to explanation. 1 Introduction2 A Primer on the HH Model2.1 The basic qualitative picture2.2 The quantitative model3 Interlude: What Did Hodgkin and Huxley Think?4 Craver’s View4.1 Mechanistic explanation4.2 Sketches4.3 Craver's view: The HH model as a mechanism sketch5 An Alternative View of the HH Model5.1 Another look at the equations5.2 The discrete-gating picture5.3 The road paved by Hodgkin and Huxley5.4 Summary and comparison to Craver6 Conclusion: The HH Model and Mechanistic Explanation6.1 Sketches and abstractions6.2 Why has aggregative abstraction been overlooked? (shrink)

How do we go about weighing evidence, testing hypotheses, and making inferences? According to the model of _Inference to the Best Explanation_, we work out what to infer from the evidence by thinking about what would actually explain that evidence, and we take the ability of a hypothesis to explain the evidence as a sign that the hypothesis is correct. In _Inference to the Best Explanation_, Peter Lipton gives this important and influential idea the development and assessment it deserves. The (...) second edition has been substantially enlarged and reworked, with a new chapter on the relationship between explanation and Bayesianism, and an extension and defence of the account of contrastive explanation. It also includes an expanded defence of the claims that our inferences really are guided by diverse explanatory considerations, and that this pattern of inference can take us towards the truth. This edition of _Inference to the Best Explanation_ has also been updated throughout and includes a new bibliography. (shrink)

Microbes and microbiology are seldom encountered in philosophical accounts of the life sciences. Although microbiology is a well-established science and microbes the basis of life on this planet, neither the organisms nor the science have been seen as philosophically significant. This book will change that. It fills a major gap in the philosophy of biology by examining central philosophical issues in microbiology. Topics are drawn from evolutionary microbiology, microbial ecology, and microbial classification. These discussions are aimed at philosophers and scientists (...) who wish to gain insight into the basic philosophical issues of microbiology. (shrink)

A common method for warranting the historical adequacy of philosophical claims is that of relying on historical case studies. This paper addresses the question as to what evidential support historical case studies can provide to philosophical claims and doctrines. It argues that in order to assess the evidential functions of historical case studies, we first need to understand the methodology involved in producing them. To this end, an account of historical reconstruction that emphasizes the narrative character of historical accounts and (...) the theory-laden character of historical facts is introduced. The main conclusion of this paper is that historical case studies are able to provide philosophical claims with some evidential support, but that, due to theory-ladenness, their evidential import is restricted. (shrink)

Many biological investigations are organized around a small group of species, often referred to as ‘model organisms’, such as the fruit fly Drosophila melanogaster. The terms ‘model’ and ‘modelling’ also occur in biology in association with mathematical and mechanistic theorizing, as in the Lotka–Volterra model of predator-prey dynamics. What is the relation between theoretical models and model organisms? Are these models in the same sense? We offer an account on which the two practices are shown to have different epistemic characters. (...) Theoretical modelling is grounded in explicit and known analogies between model and target. By contrast, inferences from model organisms are empirical extrapolations. Often such extrapolation is based on shared ancestry, sometimes in conjunction with other empirical information. One implication is that such inferences are unique to biology, whereas theoretical models are common across many disciplines. We close by discussing the diversity of uses to which model organisms are put, suggesting how these relate to our overall account. 1 Introduction2 Volterra and Theoretical Modelling3 Drosophila as a Model Organism4 Generalizing from Work on Model Organisms5 Phylogenetic Inference and Model Organisms6 Further Roles of Model Organisms6.1 Preparative experimentation6.2 Model organisms as paradigms6.3 Model organisms as theoretical models6.4 Inspiration for engineers6.5 Anchoring a research community7 Conclusion. (shrink)

In this article I argue that a methodological challenge to an integrated history and philosophy of science approach put forth by Ronald Giere almost forty years ago can be met by what I call the Kuhnian mode of History and Philosophy of Science (HPS). Although in the Kuhnian mode of HPS norms about science are motivated by historical facts about scientific practice, the justifiers of the constructed norms are not historical facts. The Kuhnian mode of HPS therefore evades the naturalistic (...) fallacy which Giere’s challenge is a version of. Against the backdrop of a discussion of Laudan’s normative naturalism I argue that the Kuhnian mode of HPS is a superior form of naturalism: it establishes contact to the practice of science without making itself dependent on its contingencies. (shrink)

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and representational target. We also examine (...) the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models.Keywords: Experimental organism; Genetics; Model organism; Modeling; Philosophy of biology; Representation. (shrink)

Imre Lakatos' philosophical and scientific papers are published here in two volumes. Volume I brings together his very influential but scattered papers on the philosophy of the physical sciences, and includes one important unpublished essay on the effect of Newton's scientific achievement. Volume II presents his work on the philosophy of mathematics (much of it unpublished), together with some critical essays on contemporary philosophers of science and some famous polemical writings on political and educational issues. Imre Lakatos had an influence (...) out of all proportion to the length of his philosophical career. This collection exhibits and confirms the originality, range and the essential unity of his work. It demonstrates too the force and spirit he brought to every issue with which he engaged, from his most abstract mathematical work to his passionate 'Letter to the director of the LSE'. Lakatos' ideas are now the focus of widespread and increasing interest, and these volumes should make possible for the first time their study as a whole and their proper assessment. (shrink)

This article examines the role of experimental generalizations and physical laws in neuroscientific explanations, using Hodgkin and Huxley’s electrophysiological model from 1952 as a test case. I show that the fact that the model was partly fitted to experimental data did not affect its explanatory status, nor did the false mechanistic assumptions made by Hodgkin and Huxley. The model satisfies two important criteria of explanatory status: it contains invariant generalizations and it is modular (both in James Woodward’s sense). Further, I (...) argue that there is a sense in which the explanatory heteronomy thesis holds true for this case. †To contact the author, please write to: SNF‐Professorship for Philosophy of Science, University of Basel, Missionsstrasse 21, 4003 Basel, Switzerland; e‐mail: [email protected]. (shrink)

What can we conclude from a mere handful of case studies? The field of HPS has witnessed too many hasty philosophical generalizations based on a small number of conveniently chosen case studies. One might even speculate that dissatisfaction with such methodological shoddiness contributed decisively to a widespread disillusionment with the whole HPS enterprise. Without specifying clear mechanisms for history-philosophy interaction, we are condemned to either making unwarranted generalizations from history, or writing entirely "local" histories with no bearing on an overall (...) understanding of the scientific process. I propose a move away from the habit of viewing historical cases as an inductive evidence-base for general philosophical theses. The relation between historical and philosophical studies should not be seen as one between the particular and the general, but as a relation between the concrete and the abstract. An abstract framework is necessary for telling any concrete story at all. In this paper I explore how doing concrete history can help our abstract philosophizing. In the absence of ready-made philosophical concepts appropriate for understanding a given historical episode, the historian is compelled to craft new abstract philosophical concepts. Therefore, history-writing can be a very effective method of philosophical discovery. I will illustrate these claims through a discussion of two investigations in HPS from my own recent and current work: (1) temperature measurement and epistemic iteration; (2)constitution and laboratory practices in the Chemical Revolution. (This will also raise, and solve, a problem of reflexivity: how can we use case studies to show how to go beyond case studies?). (shrink)

Normative naturalism is a view about the status of epistemology and philosophy of science; it is a meta-epistemology. It maintains that epistemology can both discharge its traditional normative role and nonetheless claim a sensitivity to empirical evidence. The first sections of this essay set out the central tenets of normative naturalism, both in its epistemic and its axiological dimensions; later sections respond to criticisms of that species of naturalism from Gerald Doppelt, Jarrett Leplin and Alex Rosenberg.

This essay contains a partial exploration of some key concepts associated with the epistemology of realist philosophies of science. It shows that neither reference nor approximate truth will do the explanatory jobs that realists expect of them. Equally, several widely-held realist theses about the nature of inter-theoretic relations and scientific progress are scrutinized and found wanting. Finally, it is argued that the history of science, far from confirming scientific realism, decisively confutes several extant versions of avowedly 'naturalistic' forms of scientific (...) realism. (shrink)

The drive to describe cultural history as an evolutionary process has two sources. One from within social theory is part of the impetus to convert social studies into "social sciences" providing them with the status accorded to the natural sciences. The other comes from within biology and biological anthropology in the belief that the theory of evolution must be universal in its application to all functions of all living organisms. The social scientific theory of cultural evolution is pre-Darwinian, employing a (...) developmental model of unfolding characterized by intrinsic directionality, by definable stages that succeed each other and by some criterion of progress. It is arbitrary in its definitions of progress and has had the political problem that a diachronic claim of cultural progress implies a synchronic differential valuation of present-day cultures. The biological scheme creates an isomorphism between the Darwinian mechanism of evolution and cultural history, postulating rules of cultural "mutation", cultural inheritance and some mechanism of natural selection among cultural alternatives. It uses simplistic ad hoc notions of individual acculturation and of the differential survival and reproduction of cultural elements. It is unclear what useful work is done by substituting the metaphor of evolution for history. (shrink)

What are the features of a good scientific theory? Samuel Schindler's book revisits this classical question in the philosophy of science and develops new answers to it. Theoretical virtues matter not only for choosing theories 'to work with', but also for what we are justified in believing: only if the theories we possess are good ones can we be confident that our theories' claims about nature are actually correct. Recent debates have focussed rather narrowly on a theory's capacity to predict (...) new phenomena successfully, but Schindler argues that the justification for this focus is thin. He discusses several other theory properties such as testability, accuracy, and consistency, and highlights the importance of simplicity and coherence. Using detailed historical case studies and careful philosophical analysis, Schindler challenges the received view of theoretical virtues and advances arguments for the view that science uncovers reality through theory. (shrink)

Peter Lipton argues that inference to the best explanation involves the selection of a hypothesis on the basis of its loveliness. I argue that in optimal cases of IBE we may be able to eliminate all but one of the hypotheses. In such cases we have a form of eliminative induction takes place, which I call ‘Holmesian inference’. I argue that Lipton’s example in which Ignaz Semmelweis identified a cause of puerperal fever better illustrates Holmesian inference than Liptonian IBE. I (...) consider in detail the conditions under which Holmesian inference is possible and conclude by considering the epistemological relations between Holmesian inference and Liptonian IBE.Keywords: Inference to the best explanation; Peter Lipton; Abduction; Holmesian inference; Eliminative induction. (shrink)

Semmelweis’s investigations of puerperal fever are some of the most interesting in the history of medicine. This paper considers Hempel’s analysis of the Semmelweis case. It argues that this analysis is inadequate and needs to be supplemented by some Kuhnian ideas. Kuhn’s notion of paradigm needs to be modified to apply to medicine in order to take account of the classification schemes involved in medical theorising. However with a suitable modification it provides an explanation of Semmelweis’s failure which is argued (...) to be superior to some of the external reasons often given. Despite this success in applying Kuhn’s ideas to medicine, it is argued that these ideas must be further modified to take account of the fact that medicine is not a natural science but primarily a practice designed to prevent and cure diseases. (shrink)

The case of Semmelweis has been well known since Hempel. More recently, it has been revived by Peter Lipton, Donald Gillies, Alexander Bird, Alex Broadbent, and Raphael Scholl. While these accounts differ on what exactly the case of Semmelweis shows, they all agree that Semmelweis was an excellent reasoner. This widespread agreement has also given rise to a puzzle: why Semmelweis’s views were rejected for so long. I aim to dissolve both this puzzle and the standard view of Semmelweis by (...) showing that, contrary to prevailing opinion, Semmelweis was not the excellent reasoner he has been assumed to be. (shrink)

This essay offers some reflections on the recent history of the disputes about the relation between history and philosophy of science (HPS) and the merits and prospects of HPS as an intellectual endeavor. As everyone knows, the issue was hotly debated in the 1960s and 1970s. That was the hey-day of the slogan "history without philosophy of science is blind, philosophy without history of science is empty" as well as of the many variations on the theme of HPS as a (...) "marriage of convenience," "intimate relation," or "marriage for the sake of reason." There was a flurry of interest in the early 1990s, as evidenced by sections in the 1992 and 1994 issues of PSA, entitled: "Do the History of Science and the Philosophy of .. (shrink)

Thomas S. Kuhn's classic book is now available with a new index.

In arguing a "role for history," Kuhn was proposing a naturalized philosophy of science. That, I argue, is the only viable approach to the philosophy of science. I begin by exhibiting the main general objections to a naturalistic approach. These objections, I suggest, are equally powerful against nonnaturalistic accounts. I review the failure of two nonnaturalistic approaches, methodological foundationism (Carnap, Reichenbach, and Popper) and metamethodology (Lakatos and Laudan). The correct response, I suggest, is to adopt an "evolutionary perspective." This perspective (...) is defended against one recent critic (Putnam). To argue the plausibility of a naturalistic approach, I next sketch a naturalistic account of theories and of theory choice. This account is then illustrated by the recent revolution in geology. In conclusion I return to Kuhn's question about the role of history in developing a naturalistic theory of science. (shrink)

In his seminal Inference to the Best Explanation, Peter Lipton adopted a causal view of explanation and a broadly Millian view of how causal knowledge is obtained. This made his account vulnerable to critics who charged that Inference to the Best Explanation is merely a dressed-up version of Mill’s methods, which in the critics’ view do the real inductive work. Lipton advanced two arguments to protect Inference to the Best Explanation against this line of criticism: the problem of multiple differences (...) and the problem of inferred differences. Lipton claimed that these two problems show Mill’s method of difference to be largely unworkable unless it is embedded in an explanationist framework. Here I consider both arguments as well as the best Millian defense against them. Since the existing Millian defense is only partially successful, I will develop a new and improved account. As an integral part of the argument, I show that my solutions to the problems of multiple and inferred differences offer new insight into Lipton’s main case study: Ignaz Semmelweis’s discovery of the cause of childbed fever. I conclude that the method of difference can overcome Lipton’s challenges outside an explanationist framework. (shrink)

Kuhn closed the Introduction to The Structure of Scientific Revolutions with what was clearly intended as a rhetorical question: How could history of science fail to be a source of phenomena to which theories about knowledge may legitimately be asked to apply? (Kuhn 1970, 9) This paper argues that there is a more fruitful way of conceiving the relationship between a historical and philosophical study of science, which is dubbed the 'phylogenetic' approach. I sketch an example of this approach, and (...) take a first pass at an abstract characterization of the method. (shrink)

What do appeals to case studies accomplish? Consider the dilemma: On the one hand, if the case is selected because it exemplifies the philosophical point, then it is not clear that the historical data hasn't been manipulated to fit the point. On the other hand, if one starts with a case study, it is not clear where to go from there—for it is unreasonable to generalize from one case or even two or three.

Philosophy of Experimental Biology explores some central philosophical issues concerning scientific research in experimental biology, including genetics, biochemistry, molecular biology, developmental biology, neurobiology, and microbiology. It seeks to make sense of the explanatory strategies, concepts, ways of reasoning, approaches to discovery and problem solving, tools, models and experimental systems deployed by scientific life science researchers and also integrates developments in historical scholarship, in particular the New Experimentalism. It concludes that historical explanations of scientific change that are based on local laboratory (...) practice need to be supplemented with an account of the epistemic norms and standards that are operative in science. This book should be of interest to philosophers and historians of science as well as to scientists. (shrink)

Semmelweis’s discovery of the cause of puerperal fever around the middle of the 19th century counts among the paradigm cases of scientific discovery. For several decades, philosophers of science have used the episode to illustrate, appraise and compare views of proper scientific methodology.Here I argue that the episode can be profitably reexamined in light of two cognate notions: causal reasoning and mechanisms. Semmelweis used several causal reasoning strategies both to support his own and to reject competing hypotheses. However, these strategies (...) have gone unappreciated in the existing literature. I show that a causal reasoning approach makes sense of the multitude of tables in Semmelweis’s main text, which in later editions were often abridged because they appeared redundant.Moreover, the existing literature tends to focus on Semmelweis’s clinical intervention and on the extent to which it alone confirms his theoretical conclusions. This neglects Semmelweis’s efforts to show by animal experiments that his clinical results are in agreement with a demonstrable mechanism of puerperal fever pathogenesis. I argue that the full evidential force of Semmelweis’s argument can only be appreciated if both his clinical and his laboratory investigations are taken into account. (shrink)

The claim that conceptual systems change is a platitude. That our conceptual systems are theory-laden is no less platitudinous. Given evolutionary theory, biologists are led to divide up the living world into genes, organisms, species, etc. in a particular way. No theory-neutral individuation of individuals or partitioning of these individuals into natural kinds is possible. Parallel observations should hold for philosophical theories about scientific theories. In this paper I summarize a theory of scientific change which I set out in considerable (...) detail in a book that I shall publish in the near future. Just as few scientists were willing to entertain the view that species evolve in the absence of a mechanism capable of explaining this change, so philosophers should be just as reticent about accepting a parallel view of conceptual systems in science evolving in the absence of a mechanism to explain this evolution. In this paper I set out such a mechanism. One reason that this task has seemed so formidable in the past is that we have all construed conceptual systems inappropriately. If we are to understand the evolution of conceptual systems in science, we must interpret them as forming lineages related by descent. In my theory, the notion of a family resemblance is taken literally, not metaphorically. In my book, I set out data to show that the mechanism which I propose is actually operative. In this paper, such data is assumed. (shrink)

Tim Lewens aims to understand what it means to take an evolutionary approach to cultural change, and why it is that these approaches are sometimes treated with suspicion. While making a case for the value of evolutionary thinking for students of culture, he shows why the concerns of sceptics should not dismissed as mere prejudice, confusion, or ignorance. Indeed, confusions about what evolutionary approaches entail are propagated by their proponents, as well as by their detractors. By taking seriously the problems (...) faced by these approaches to culture, he shows how such approaches can be better formulated, where their most significant limitations lie, and how the tools of cultural evolutionary thinking might become more widely accepted. (shrink)

For many years—and with some energy since Laudan’s “Confutation of Convergent Realism” —the scientific realist has sought to accommodate examples of false-yet-successful theories in the history of science. One of the most prominent strategies is to identify ‘success fueling’ components of false theories that themselves are at least approximately true. In this article I develop both sides of the debate, introducing new challenges from the history of science as well as suggesting adjustments to the divide et impera realist strategy. A (...) new ‘recipe’ for the prospective identification of working/idle posits is considered. (shrink)

In many domains of biology, explanation takes the form of characterizing the mechanism responsible for a particular phenomenon in a specific biological system. How are such explanations generalized? One important strategy assumes conservation of mechanisms through evolutionary descent. But conservation is seldom complete. In the case discussed, the central mechanism for circadian rhythms in animals was first identified in Drosophila and then extended to mammals. Scientists' working assumption that the clock mechanisms would be conserved both yielded important generalizations and served (...) as a heuristic for discovery, especially when significant differences between the insect and mammalian mechanism were identified. †To contact the author, please write to: Department of Philosophy and Interdisciplinary Programs in Science Studies and Cognitive Science, 0119, University of California, San Diego, La Jolla, CA 92093‐0119; e‐mail: [email protected]. (shrink)

Current debates about “Darwinizing culture” have typically focused on the validity of memetics. In this article we argue that meme-like inheritance is not a necessary requirement for descent with modification. We suggest that an alternative and more productive way of Darwinizing culture can be found in the application of phylogenetic methods. We review recent work on cultural phylogenetics and outline six fundamental questions that can be answered using the power and precision of quantitative phylogenetic methods. However, cultural evolution, like biological (...) evolution, is often far from treelike. We discuss the problems reticulate evolution can cause for phylogenetic analyses and suggest ways in which these problems can be overcome. Our solutions involve a combination of new methods for the study of cultural evolution , and the triangulation of different lines of historical evidence. Throughout we emphasize that most debates about cultural phylogenies can only be settled by empirical research rather than armchair speculation. (shrink)

Hodgkin and Huxley’s model of the action potential is an apparent dream case of covering‐law explanation in biology. The model includes laws of physics and chemistry that, coupled with details about antecedent and background conditions, can be used to derive features of the action potential. Hodgkin and Huxley insist that their model is not an explanation. This suggests either that subsuming a phenomenon under physical laws is insufficient to explain it or that Hodgkin and Huxley were wrong. I defend Hodgkin (...) and Huxley against Weber’s heteronomy thesis and argue that explanations are descriptions of mechanisms. †To contact the author, please write to: Department of Philosophy, Philosophy‐Neuroscience‐Psychology Program, Washington University in St. Louis, One Brookings Drive, Wilson Hall, St. Louis, MO 63130; e‐mail: [email protected]. (shrink)