This introduction to the special section on integration in biology provides an overview of the different contributions. In addition to motivating the philosophical significance of analyzing integration and interdisciplinary research, I lay out common themes and novel insights found among the special section contributions, and indicate how they exhibit current trends in the philosophical study of integration. One upshot of the contributed papers is that there are different aspects to and kinds of integration, so that rather than attempting to offer (...) a universal construal of what integrations is, philosophers have to analyze in concrete cases in what respects particular aspects of scientific theorizing and/or practice are ‘integrative’ and how this instance of integration works and was achieved. (shrink)

Research on diseases such as cancer reveals that primary mechanisms, which have been the focus of study by the new mechanists in philosophy of science, are often subject to control by other mechanisms. Cancer cells employ the same primary mechanisms as healthy cells but control them differently. I use cancer research to highlight just how widespread control is in individual cells. To provide a framework for understanding control, I reconceptualize mechanisms as imposing constraints on flows of free energy, with control (...) mechanisms operating on flexible constraints in primary mechanisms. I argue that control mechanisms themselves often form complex, integrated networks. (shrink)

Examining stem cell biology from a philosophy of science perspective, this book clarifies the field's central concept, the stem cell, as well as its aims, methods, models, explanations and evidential challenges. The first chapters discuss what stem cells are, how experiments identify them, and why these two issues cannot be completely separated. The basic concepts, methods and structure of the field are set out, as well as key limitations and challenges. The second part of the book shows how rigorous explanations (...) emerge from stem cell experiments, and compares these to other kinds of scientific explanation. Model organisms, the role of genes, and the significance of collaboration are also discussed. The last part of the book considers relations to systems biology and clinical medicine, arguing that both the mathematical models of the former, and ethical principles of the latter, are necessary for stem cell biology to deliver on its promises. (shrink)

Cancer is a paradigmatic case of a complex causal process; causes of cancer operate at a variety of temporal and spatial scales, and the respects in which these causes act and interact are diverse. There are, for instance, temporal order effects, organizational effects, structural effects, and dynamic relationships between causes operating at different temporal and spatial scales. Because of this complexity, models of cancer initiation and progression often involve deliberate choices to focus on one time scale, one causal pathway, or (...) one aspect of cancer’s dynamics. As in most of biology, modeling cancer involves simplification and idealization. At the same time, theoretical perspectives inform the construction of these models. Such perspectives might involve viewing cancer ‘as’ a genetic disease, metabolic disease, stem cell disease, an infectious disease, or a disease of tissue disorganization. This paper will argue that purportedly competing theoretical views of cancer are not at odds, but can be viewed as mutually informative. Models are most often developed in the service of asking very specific questions, and this requires limiting our view of the phenomena to a specific temporal or spatial scale, a particular cause, or a particular outcome, dynamic, or pattern. Thus, while some models may seem at odds, often they are simply concerned with different questions, or, they are complementary and mutually informative. I hope to bring this case to bear on debates among philosophers of science over perspectivism and realism, as well pluralism about the aims and scope of scientific theory. (shrink)

In this paper, I defend an empiricist account of modality that keeps a substantive account of modal commitment, but throws out the metaphysics. I suggest that if we pair a deflationary attitude toward representation with a substantive account of how scientific models are constructed and put to use, the result is an account that deflates the metaphysics of modal commitment without deflating the content of modal claims.

This book explores a variety of conceptual and methodological questions about cancer and cancer research: Is cancer one disease, or many? If many, how many exactly? How is cancer classified? What does it mean, exactly, to say that cancer is “genetic,” or “familial”? What exactly are the causes of cancer, and how do scientists come to know about them? When do we have good reason to believe that this or that is a risk factor for cancer? How is cancer a (...) product or byproduct of multilevel evolution? Is cancer research unified? What sort of models, or theories, govern cancer research? This book takes a close look at these philosophical questions, by examining work in disciplines as diverse as cell and molecular biology, epidemiology, clinical medicine, and evolutionary biology. (shrink)

This Element has two main aims. The first one is an historically informed review of the philosophy of probability. It describes recent historiography, lays out the distinction between subjective and objective notions, and concludes by applying the historical lessons to the main interpretations of probability. The second aim focuses entirely on objective probability, and advances a number of novel theses regarding its role in scientific practice. A distinction is drawn between traditional attempts to interpret chance, and a novel methodological study (...) of its application. A radical form of pluralism is then introduced, advocating a tripartite distinction between propensities, probabilities and frequencies. Finally, a distinction is drawn between two different applications of chance in statistical modelling which, it is argued, vindicates the overall methodological approach. The ensuing conception of objective probability in practice is the 'complex nexus of chance'. (shrink)

This paper responds to recent criticisms of the idea that true causal claims, satisfying a minimal “interventionist” criterion for causation, can differ in the extent to which they satisfy other conditions—called stability and proportionality—that are relevant to their use in explanatory theorizing. It reformulates the notion of proportionality so as to avoid problems with previous formulations. It also introduces the notion of conditional independence or irrelevance, which I claim is central to understanding the respects and the extent to which upper (...) level explanations can be “autonomous”. (shrink)

This paper attempts to elucidate three characteristics of causal relationships that are important in biological contexts. Stability has to do with whether a causal relationship continues to hold under changes in background conditions. Proportionality has to do with whether changes in the state of the cause “line up” in the right way with changes in the state of the effect and with whether the cause and effect are characterized in a way that contains irrelevant detail. Specificity is connected both to (...) David Lewis’ notion of “influence” and also with the extent to which a causal relation approximates to the ideal of one cause–one effect. Interrelations among these notions and their possible biological significance are also discussed. (shrink)

If counterfactual dependence is sufficient for causation and if omissions can be causes, then all events have many more causes than common sense tends to recognize. This problem is standardly addressed by appeal to pragmatics. However, Carolina Sartorio [2010] has recently raised what I shall argue is a more interesting problem concerning omissions for counterfactual theories of causation—more interesting because it demands a more subtle pragmatic solution. I discuss the relationship between the idea that causes are proportional to their effects, (...) the idea that causation is contrastive, and the question of the dimensions along which causal explanations should be evaluated with respect to one another. (shrink)

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

A statement of the form ‘C caused E’ obeys the requirement of proportionality precisely when C says no more than what is necessary to bring about E. The thesis that causal statements must obey this requirement might be given a semantic or a pragmatic justification. We use the idea that causal claims are contrastive to criticize both.

Two approaches to evidential reasoning compete in the biomedical and social sciences: the experimental and the pragmatist. Whereas experimentalism has received considerable philosophical analysis and support since the times of Bacon and Mill, pragmatism about evidence has been neither articulated nor defended. The overall aim is to fill this gap and develop a theory that articulates the latter. The main ideas of the theory will be illustrated and supported by a case study on the smoking/lung cancer controversy in the 1950s.

Debates concerning the character, scope, and warrant of abductive inference have been active since Peirce first proposed that there was a third form of inference, distinct from induction and deduction. Abductive reasoning has been dubbed weak, incoherent, and even nonexistent. Part, at least, of the problem of articulating a clear sense of abductive inference is due to difficulty in interpreting Peirce. Part of the fault must lie with his critics, however. While this article will argue that Peirce indeed left a (...) number of puzzles for interpreters, it will also contend that interpreters should be careful to distinguish discussion of the formal and strictly epistemic question of whether and how abduction is a sound form of inference from discussions of the practical goals of abduction, as Peirce understood them. This article will trace a history of critics and defenders of Peirce’s notion of abduction and discuss how Peirce both fueled the confusion and in fact anticipated and responded to several recurring objections. (shrink)

Meeting grand challenges requires responses that constructively combine multiple forms of expertise, both academic and non-academic; that is, it requires cross-disciplinary integration. But just what is cross-disciplinary integration? In this paper, we supply a preliminary answer by reviewing prominent accounts of cross-disciplinary integration from two literatures that are rarely brought together: cross-disciplinarity and philosophy of biology. Reflecting on similarities and differences in these accounts, we develop a framework that integrates their insights—integration as a generic combination process the details of which (...) are determined by the specific contexts in which particular integrations occur. One such context is cross-disciplinary research, which yields cross-disciplinary integration. We close by reflecting on the potential applicability of this framework to research efforts aimed at meeting grand challenges. (shrink)

In recent cancer research, strong and apparently conflicting epistemological stances have been advocated by different research teams in a mist of an ever-growing body of knowledge ignited by ever-more perplexing and non-conclusive experimental facts: in the past few years, an 'organicist' approach investigating cancer development at the tissue level has challenged the established and so-called 'reductionist' approach focusing on disentangling the genetic and molecular circuitry of carcinogenesis. This article reviews the ways in which 'organicism' and 'reductionism' are used and opposed (...) in this context, with an aim at clarifying the debate. Methodological, epistemological and ontological implications of both approaches are discussed. We argue that the 'organicist/reductionist' opposition in the present case of carcinogenesis is more a matter of diverging heuristics than a claim about theoretical or ontological (ir)reducibility. As a matter of fact, except for the downward causation claim, which we question, we argue that the organicist arguments are compatible with the reductionist approach. Moreover, we speculate that both approaches, which currently focus on specific entities i.e., genes versus tissues, will need to shift their conceptual frameworks to studying complex arrays of relationships potentially ranging over several levels of entities, as is the case with 'systems biology'. (shrink)

The interventionist account of causal explanation, in the version presented by Jim Woodward, has been recently claimed capable of buttressing the widely felt—though poorly understood—hunch that high-level, relatively abstract explanations, of the sort provided by sciences like biology, psychology and economics, are in some cases explanatorily optimal. It is the aim of this paper to show that this is mistaken. Due to a lack of effective constraints on the causal variables at the heart of the interventionist causal-explanatory scheme, as presently (...) formulated it is either unable to prefer high-level explanations to low, or systematically overshoots, recommending explanations at so high of a level as to be virtually vacuous. (shrink)

In 1687 Isaac Newton ushered in a new scientific era in which laws of nature could be used to predict the movements of matter with almost perfect precision. Newton's physics also posed a profound challenge to our self-understanding, however, for the very same laws that keep airplanes in the air and rivers flowing downhill tell us that it is in principle possible to predict what each of us will do every second of our entire lives, given the early conditions of (...) the universe. Can it really be that even while you toss and turn late at night in the throes of an important decision and it seems like the scales of fate hang in the balance, that your decision is a foregone conclusion? Can it really be that everything you have done and everything you ever will do is determined by facts that were in place long before you were born? This problem is one of the staples of philosophical discussion. It is discussed by everyone from freshman in their first philosophy class, to theoretical physicists in bars after conferences. And yet there is no topic that remains more unsettling, and less well understood. If you want to get behind the façade, past the bare statement of determinism, and really try to understand what physics is telling us in its own terms, read this book. The problem of free will raises all kinds of questions. What does it mean to make a decision, and what does it mean to say that our actions are determined? What are laws of nature? What are causes? What sorts of things are we, when viewed through the lenses of physics, and how do we fit into the natural order? Ismael provides a deeply informed account of what physics tells us about ourselves. The result is a vision that is abstract, alien, illuminating, and-Ismael argues-affirmative of most of what we all believe about our own freedom. Written in a jargon-free style, How Physics Makes Us Free provides an accessible and innovative take on a central question of human existence. (shrink)

Comprehensive evaluation and study of man's theories and knowledge of genetical characteristics and the evolutionary processes.

This chapter explores the idea that causal inference is warranted if and only if the mechanism underlying the inferred causal association is identified. This mechanistic stance is discernible in the epidemiological literature, and in the strategies adopted by epidemiologists seeking to establish causal hypotheses. But the exact opposite methodology is also discernible, the black box stance, which asserts that epidemiologists can and should make causal inferences on the basis of their evidence, without worrying about the mechanisms that might underlie their (...) hypotheses. I argue that the mechanistic stance is indeed a bad methodology for causal inference. However, I detach and defend a mechanistic interpretation of causal generalisations in epidemiology as existence claims about underlying mechanisms. (shrink)

Despite decades of focused philosophical investigation, Inference to the Best Explanation still lacks a precise articulation and compelling defense. The primary reason for this is that it is not at all clear what it means for a hypothesis to be the best available explanation of the evidence. This paper first seeks to rectify this problem by developing a formal explication of the explanatory virtue of power. A resulting account of IBE is then evaluated as a form of uncertain inference. Overall, (...) this paper offers a precise account and novel defense of one important version of IBE. (shrink)

I defend a three-fold form of pluralism about chance, involving a tripartite distinction between propensities, probabilities, and frequencies. The argument has a negative and a positive part. Negatively, I argue against the identity thesis that informs current propensity theories, which already suggests the need for a tripartite distinction. Positively, I argue that that a tripartite distinction is implicit in much statistical practice. Finally, I apply a well-known framework in the modelling literature in order to characterize these three separate concepts functionally (...) in terms of their roles in modelling practice. (shrink)

Evolutionary theory is awash with probabilities. For example, natural selection is said to occur when there is variation in fitness, and fitness is standardly decomposed into two components, viability and fertility, each of which is understood probabilistically. With respect to viability, a fertilized egg is said to have a certain chance of surviving to reproductive age; with respect to fertility, an adult is said to have an expected number of offspring.1 There is more to evolutionary theory than the theory of (...) natural selection, and here too one finds probabilistic concepts aplenty. When there is no selection, the theory of neutral evolution says that a gene’s chance of eventually reaching fixation is 1/(2N), where N is the number of organisms in the generation of the diploid population to which the gene belongs. The evolutionary consequences of mutation are likewise conceptualized in terms of the probability per unit time a gene has of changing from one state to another. The examples just mentioned are all “forwarddirected” probabilities; they describe the probability of later events, conditional on earlier events. However, evolutionary theory also uses “backwards probabilities” that describe the probability of a cause conditional on its effects; for example, coalescence theory allows one to calculate the expected number of generations in the past that the genes in the present generation find their most recent common ancestor. (shrink)

This paper examines a fundamental problem in applied mathematics. How can one model the behavior of materials that display radically different, dominant behaviors at different length scales. Although we have good models for material behaviors at small and large scales, it is often hard to relate these scale-based models to one another. Macroscale models represent the integrated effects of very subtle factors that are practically invisible at the smallest, atomic, scales. For this reason it has been notoriously difficult to model (...) realistic materials with a simple bottom-up-from-the-atoms strategy. The widespread failure of that strategy forced physicists interested in overall macro-behavior of materials toward completely top-down modeling strategies familiar from traditional continuum mechanics. The problem of the ``tyranny of scales'' asks whether we can exploit our rather rich knowledge of intermediate micro- scale behaviors in a manner that would allow us to bridge between these two dominant methodologies. Macroscopic scale behaviors often fall into large common classes of behaviors such as the class of isotropic elastic solids, characterized by two phenomenological parameters---so-called elastic coefficients. Can we employ knowledge of lower scale behaviors to understand this universality---to determine the coefficients and to group the systems into classes exhibiting similar behavior? (shrink)