The new mechanistic philosophy is divided into two largely disconnected projects. One deals with a metaphysical inquiry into how mechanisms relate to issues such as causation, capacities and levels of organization, while the other deals with epistemic issues related to the discovery of mechanisms and the intelligibility of mechanistic representations. Tudor Baetu explores and explains these projects, and shows how the gap between them can be bridged. His proposed account is compatible both with the assumptions and practices of experimental design (...) in biological research, and with scientifically accepted interpretations of experimental results. (shrink)

Biochemical kinds such as proteins pose interesting problems for philosophers of science, as they can be studied from the points of view of both biology and chemistry. The relationship between the biological functions of biochemical kinds and the microstructures that they are related to is the key question. This leads us to a more general discussion about ontological reductionism, microstructuralism, and multiple realization at the biology-chemistry interface. On the face of it, biochemical kinds seem to pose a challenge for ontological (...) reductionism and hence motivate a dual theory of chemical and biological kinds, a type of pluralism about natural kinds. But it will be argued that the challenge, which is based on multiple realization, can be addressed. The upshot is that there are reasonable prospects for ontological reductionism about biochemical kinds, which corroborates natural kind monism. (shrink)

Following Kripke and Putnam, the received view of chemical kinds has been a microstructuralist one. To be a microstructuralist about chemical kinds is to think that membership in said kinds is conferred by microstructural properties. Recently, the received microstructuralist view has been elaborated and defended, but it has also been attacked on the basis of complexities, both chemical and ontological. Here, I look at which complexities really challenge the microstructuralist view; at how the view itself might be made more complicated (...) in order to accommodate such challenges; and finally, at what this increasingly complicated picture implies for our standard assessment of chemical kindhood—primarily, for the widespread assumption that chemical kinds in general are more neat and tidy than those messy biological ones. _1_ The Received View _2_ A Taxonomy of Chemical Kinds _3_ Atomic Number _4_ H2O, H3O+, OH−, and More _5_ Complicating the Microstructuralist Picture _6_ Concrete and Other Mixtures _7_ Macromolecules, Especially Proteins _8_ Abandoning Sameness of Elemental Composition _9_ Not So Different after All. (shrink)

What are the conditions under which one biological object is a part of another biological object? This paper answers this question by developing a general, systematic account of biological parthood. I specify two criteria for biological parthood. Substantial Spatial Inclusionrequires biological parts to be spatially located inside or in the region that the natural boundary of t he biological whole occupies. Compositional Relevance captures the fact that a biological part engages in a biological process that must make a necessary contribution (...) to a condition that is minimally sufficient to one or more of the characteristic behaviors of the biological whole. Instead of emphasizing the diversity of part-whole relations in the biological world, this paper asks what biological part-whole relations have in common and what constrains their existence, in general. After presenting the two criteria for biological parthood I discuss in how far my account can cope with hard cases (e.g., redundant parts) and I reveal the merits and limits of monism. (shrink)

Chemical kinds are generally treated as having timelessly fixed identities. Biological kinds are generally treated as evolved and/or evolving entities. So what kind of kind is a biochemical kind? This article defends the thesis that biochemical molecules are clustered chemical kinds, some of which—namely, evolutionarily conserved units—are also biological kinds. On this thesis, a number of difficulties that have recently occupied philosophers concerned with proteins and kinds are shown to be either resolved or dissolved. 1 Introduction2 Conflicting Intuitions about Kinds (...) of Proteins3 Against Permissive Pluralism4 Against Nominalism, Toward a Duality of Kinds5 Biological Kinds, Chemical Kinds, and Their Relations6 Implications for Biological Individuals7 Implications for Monism and Scientific Practice. (shrink)

A scientific explanatory project, part-whole explanation, and a kind of science, part-whole science are premised on identifying, investigating, and using parts and wholes. In the biological sciences, mechanistic, structuralist, and historical explanations are part-whole explanations. Each expresses different norms, explananda, and aims. Each is associated with a distinct partitioning frame for abstracting kinds of parts. These three explanatory projects can be complemented in order to provide an integrative vision of the whole system, as is shown for a detailed case study: (...) the tetrapod limb. My diagnosis of part-whole explanation in the biological sciences as well as in other domains exploring evolved, complex, and integrated systems (e.g., psychology and cognitive science) cross-cuts standard philosophical categories of explanation: causal explanation and explanation as unification. Part-whole explanation is itself one essential aspect of part-whole science. (shrink)

This fine collection of essays by a leading philosopher of science presents a defence of integrative pluralism as the best description for the complexity of scientific inquiry today. The tendency of some scientists to unify science by reducing all theories to a few fundamental laws of the most basic particles that populate our universe is ill-suited to the biological sciences, which study multi-component, multi-level, evolved complex systems. This integrative pluralism is the most efficient way to understand the different and complex (...) processes - historical and interactive - that generate biological phenomena. This book will be of interest to students and professionals in the philosophy of science. (shrink)

Robustness is often presented as a guideline for distinguishing the true or real from mere appearances or artifacts. Most of recent discussions of robustness have focused on the kind of derivational robustness analysis introduced by Levins, while the related but distinct idea of robustness as multiple accessibility, defended by Wimsatt, has received less attention. In this paper, I argue that the latter kind of robustness, when properly understood, can provide justification for ontological commitments. The idea is that we are justified (...) in believing that things studied by science are real insofar as we have robust evidence for them. I develop and analyze this idea in detail, and based on concrete examples show that it plays an important role in science. Finally, I demonstrate how robustness can be used to clarify the debate on scientific realism and to formulate new arguments. (shrink)

In this powerful work of conceptual and analytical originality, the author argues for the primacy of the material arrangements of the laboratory in the dynamics of modern molecular biology. In a post-Kuhnian move away from the hegemony of theory, he develops a new epistemology of experimentation in which research is treated as a process for producing epistemic things. A central concern of the book is the basic question of how novelty is generated in the empirical sciences. In addressing this question, (...) the author brings French poststructuralist thinking—notably Jacques Derrida’s concepts of “différance” and “historiality”—to bear on the construction of epistemic things. Historiographical perspective shifts from the actors’ minds to their objects of manipulation. These epistemological and historical issues are illuminated in a detailed case study of a particular laboratory, that of the oncologist and biochemist Paul C. Zamecnik and his colleagues, located in a specific setting—the Collis P. Huntington Memorial Hospital of Harvard University at the Massachusetts General Hospital of Boston. The author traces how, between 1945 and 1965, this group developed an experimental system for synthesizing proteins in the test tube that put Zamecnik’s research team at the forefront of those who led biochemistry into the era of molecular biology. (shrink)

Featuring contributions from the world’s leading experts on the subject and based partly on several detailed case studies, this volume is the first comprehensive analysis of the scientific notion of robustness as well as of the general ...

The practical criteria by which developmental biologists choose their model systems have evolutionary correlates. The result is a sample that is not merely small, but biased in particular ways, for example towards species with rapid, highly canalized development. These biases influence both data collection and interpretation, and our views of how development works and which aspects of it are important.

There are two facets to the central dogma proposed by Francis Crick in 1957. One concerns the relation between the sequence of nucleotides and the sequence of amino acids, the second is devoted to the relation between the sequence of amino acids and the native three-dimensional structure of proteins. 'Folding is simply a function of the order of the amino acids,' i.e. no information is required for the proper folding of a protein other than the information contained in its sequence. (...) This protein side of the central dogma was elaborated in a scientific context in which the characteristics and functions of proteins, and the mechanisms of protein folding, were seen very differently. This context, which made the folding problem a simple one, supported the bold proposition of Francis Crick. The protein side of the central dogma was not challenged by the discovery of prions if one adopts the definition of information given by Francis Crick. It might have been challenged by the discovery that regulatory enzymes exist in different conformations, and the evidence for the existence of chaperones assisting protein folding. But it was not, and folding remains what it was for Francis Crick, 'simply a function of the order of amino acids'. But the meaning of 'function' has dramatically changed. It is no longer the result of simple physicochemical laws, but that of a long evolutionary process which has optimized protein folding. Molecular mechanistic explanations have to be allied with evolutionary explanations, in a way characteristic of present biology. (shrink)

In the contemporary life sciences more and more researchers emphasize the “limits of reductionism” (e.g. Ahn et al. 2006a, 709; Mazzocchi 2008, 10) or they call for a move “beyond reductionism” (Gallagher/Appenzeller 1999, 79). However, it is far from clear what exactly they argue for and what the envisioned limits of reductionism are. In this paper I claim that the current discussions about reductionism in the life sciences, which focus on methodological and explanatory issues, leave the concepts of a reductive (...) method and a reductive explanation too unspecified. In order to fill this gap and to clarify what the limits of reductionism are I identify three reductive methods that are crucial in the current practice of the life sciences: decomposition, focusing on internal factors, and studying parts in isolation. Furthermore, I argue that reductive explanations in the life sciences exhibit three characteristics: first, they refer only to factors at a lower level than the phenomenon at issue, second, they focus on internal factors and thus ignore or simplify the environment of a system, and, third, they cite only the parts of a system in isolation. (shrink)

Douglas proposes a new ideal in which values serve an essential function throughout scientific inquiry, but where the role values play is constrained at key points, protecting the integrity and objectivity of science.

Microstructuralism in the philosophy of chemistry is the thesis that chemical kinds can be individuated in terms of their microstructural properties (Hendry in Philos Sci 73:864–875, 2006 ). Elements provide paradigmatic examples, since the atomic number should suffice to individuate the kind. In theory, Microstructuralism should also characterise higher-level chemical kinds such as molecules, compounds, and macromolecules based on their constituent atomic properties. In this paper, several microstructural theses are distinguished. An analysis of macromolecules such as moonlighting proteins suggests that (...) all the forms of microstructuralism cannot accommodate them. (shrink)

Introduction: Science and Common Sense Long before the beginnings of modern civilization, men ac- quired vast funds of information about their environment. ...

Inferences like these are known as extrapolations.

This fascinating study in the sociology of science explores the way scientists conduct, and draw conclusions from, their experiments. The book is organized around three case studies: replication of the TEA-laser, detecting gravitational rotation, and some experiments in the paranormal. "In his superb book, Collins shows why the quest for certainty is disappointed. He shows that standards of replication are, of course, social, and that there is consequently no outside standard, no Archimedean point beyond society from which we can lever (...) the intellects of our fellows. "- -Donald M. McCloskey, Journal of Economic Psychology "Collins is one of the genuine innovators of the sociology of scientific knowledge.... Changing Order is a rich and entertaining book. "- - Isis "The book gives a vivid sense of the contingent nature of research and is generally a good read. "- -Augustine Brannigan, Nature "This provocative book is a review of [Collins's] work, and an attempt to explain how scientists fit experimental results into pictures of the world.... A promising start for new explorations of our image of science, too often presented as infallibly authoritative. "- -Jon Turney, New Scientist. (shrink)

Different chemical species are often cited as paradigm examples of structurally delimited natural kinds. While classificatory monism may thus seem plausible for simple molecules, it looks less attractive for complex biological macromolecules. I focus on the case of proteins that are most plausibly individuated by their functions. Is there a single, objective count of proteins? I argue that the vagaries of function individuation infect protein classification. We should be pluralists about macromolecular classification.

Although epistemic values have become widely accepted as part of scientific reasoning, non-epistemic values have been largely relegated to the "external" parts of science (the selection of hypotheses, restrictions on methodologies, and the use of scientific technologies). I argue that because of inductive risk, or the risk of error, non-epistemic values are required in science wherever non-epistemic consequences of error should be considered. I use examples from dioxin studies to illustrate how non-epistemic consequences of error can and should be considered (...) in the internal stages of science: choice of methodology, characterization of data, and interpretation of results. (shrink)

"Theoretical pluralism" obtains when there are good evidential reasons for accommodating multiple theories of the same domain. Issues of "relative significance" often arise in connection with the investigation of such domains. In this paper, I describe and give examples of theoretical pluralism and relative significance issues. Then I explain why theoretical pluralism so often obtains in biology--and why issues of relative significance arise--in terms of evolutionary contingencies and the paucity or lack of laws of biology. Finally, I turn from explanation (...) to justification, and raise questions about the purpose and value of concerns and disagreements about relative significance. (shrink)

A classification of models of reduction into three categories — theory reductionism, explanatory reductionism, and constitutive reductionism — is presented. It is shown that this classification helps clarify the relations between various explications of reduction that have been offered in the past, especially if a distinction is maintained between the various epistemological and ontological issues that arise. A relatively new model of explanatory reduction, one that emphasizes that reduction is the explanation of a whole in terms of its parts is (...) also presented in detail. Finally, the classification is used to clarify the debate over reductionism in molecular biology. It is argued there that while no model from the category of theory reduction might be applicable in that case, models of explanatory reduction might yet capture the structure of the relevant explanations. (shrink)

Philosophers’ traditional emphasis on theories, theoretical modeling, and explanation misguides research in philosophy of science. Articulating and applying core theories is part of scientific practice, but it is not the essence of scientific practice. Insofar as science has an essence, it is to systematically investigate and learn about what is not yet understood. This lecture analyzes genetics to articulate a broad-practice-centered approach to philosophy of science. It concludes by arguing that this approach can lead to richer, deeper, and more useful (...) philosophies of science, philosophies that can better inform science policy and the public’s understanding of science. (shrink)

Biologists studying complex causal systems typically identify some factors as causes and treat other factors as background conditions. For example, when geneticists explain biological phenomena, they often foreground genes and relegate the cellular milieu to the background. But factors in the milieu are as causally necessary as genes for the production of phenotypic traits, even traits at the molecular level such as amino acid sequences. Gene-centered biology has been criticized on the grounds that because there is parity among causes, the (...) “privileging” of genes reflects a reductionist bias, not an ontological difference. The idea that there is an ontological parity among causes is related to a philosophical puzzle identified by John Stuart Mill: what, other than our interests or biases, could possibly justify identifying some causes as the actual or operative ones, and other causes as mere background? The aim of this paper is to solve this conceptual puzzle and to explain why there is not an ontological parity among genes and the other factors. It turns out that solving this puzzle helps answer a seemingly unrelated philosophical question: what kind of causal generality matters in biology? (shrink)

Scientific practices have been changed by the increasing use of computer simulations. A central question for philosophers is how to characterize computer simulations. In this paper, we address this question by analyzing simulations in biochemistry. We propose that simulations have been used in biochemistry long before computers arrived. Simulation can be described as a surrogate relationship between models. Moreover, a simulative aspect is implicit in the classical dichotomy between in vivo–in vitro conditions. Based on a discussion about how to characterize (...) a simulative aspect in this dichotomy, we will argue that an adequate understanding of computer simulations in biochemistry requires a previous understanding of simulations in experimental contexts. (shrink)

According to the "experimenter's regress", disputes about the validity of experimental results cannot be closed by objective facts because no conclusive criteria other than the outcome of the experiment itself exist for deciding whether the experimental apparatus was functioning properly or not. Given the frequent characterization of simulations as "computer experiments", one might worry that an analogous regress arises for computer simulations. The present paper analyzes the most likely scenarios where one might expect such a "simulationist's regress" to surface, and, (...) in doing so, discusses analogies and disanalogies between simulation and experimentation. I conclude that, on a properly broadened understanding of robustness, the practice of simulating mathematical models can be seen to have sufficient internal structure to avoid any special susceptibility to regress-like situations. (shrink)

I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims about (...) causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity. (shrink)

This paper considers two recent arguments that structure should not be regarded as the fundamental individuating property of proteins. By clarifying both what it might mean for certain properties to play a fundamental role in a classification scheme and the extent to which structure plays such a role in protein classification, I argue that both arguments are unsound. Because of its robustness, its importance in laboratory practice, and its explanatory centrality, primary structure should be regarded as the fundamental distinguishing characteristic (...) of protein taxonomy. (shrink)

Scientific development influences philosophical thought, and vice versa. If philosophy is to be of any use to the production, evaluation or application of biochemical knowledge, biochemistry will have to explicate its needs. This paper concentrates on the need for a philosophical analysis of methodological challenges in biochemistry, above all the problematic relation between in vitro experiments and the desire for in vivo knowledge. This problem receives much attention within biochemistry, but the focus is on practical detail. It is discussed how (...) a theoretical analysis can go beyond a naïve understanding of scientific success and failure in such cases. Several examples are presented to elucidate this issue, including the methodological implications of the precautionary principle, the possible interplay between theoretical methodology of biochemistry and the science studies, and the methodological complexities related to experimental protocol standardisation and use of instruments and kits. (shrink)

Biological macromolecules, considered as the items of the biochemical domain, are typically conceived under the ontological category of substantial individuals. In this paper, I will argue that the philosophical framework of process ontology, according to which the living world is not populated by individuals but by a dynamic hierarchy of processes, is more adequate to account for the structure and functioning of macromolecules. In particular, I will analyze its application to the phenomenon of cell signaling and to one of its (...) key concepts, cell receptors. Current knowledge in biochemistry allows us to conceive receptors as processual and dynamic entities, relationally stabilized and not separated from the biochemical phenomenon of which they are part. (shrink)

Both clinical research and basic science rely on the epistemic practice of extrapolation from surrogate models, to the point that explanatory accounts presented in review papers and biology textbooks are in fact composite pictures reconstituted from data gathered in a variety of distinct experimental setups. This raises two new challenges to previously proposed mechanistic-similarity solutions to the problem of extrapolation: one pertaining to the absence of mechanistic knowledge in the early stages of research and the second to the large number (...) of extrapolations underpinning explanatory accounts. An analysis of the strategies deployed in experimental research supports the conclusion that while results from validated surrogate models are treated as a legitimate line of evidence supporting claims about target systems, the overall structure of research projects also demonstrates that extrapolative inferences are not considered definitive or sufficient evidence, but only partially justified hypotheses subjected to further testing. 1 Introduction2 Surrogate Models2.1 What exactly is a surrogate model?2.2 Why use surrogate models?3 Prior Validation of Surrogate Models3.1 The validation and ranking of surrogate models in the early stages of basic research3.2 The validation of surrogate models in later stages of basic research and in clinical research4 ‘Big Picture’ Accounts and the Extrapolations Underpinning Them4.1 The mosaic nature of mechanistic descriptions in basic science4.2 Challenges for mechanistic-similarity-based validation protocols5 Retrospective Testing of Extrapolated Knowledge5.1 Holistic confirmation5.2 Fallback strategies6 Conclusions. (shrink)

Prediction is more than testing established theory by examining whether the prediction matches the data. To show this, I examine the practices of a community of scientists, known as threaders, who are attempting to predict the final, folded structure of a protein from its primary structure, i.e., its amino acid sequence. These scientists employ a careful and deliberate methodology of prediction. A key feature of the methodology is calibration. They calibrate in order to construct better models. The construction leads to (...) knowledge of how to construct or build an object. Thus, prediction serves a cognitive goal of model construction and not just model or theory testing. The kind of knowledge that results is relevantly different than theoretical knowledge. (shrink)