Anya Plutynski

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer.

The variable “p” is characterized as a single dimension of risk for psychopathology. The aim of this paper is to critically assess debates over “p” in the scientific literature, and their larger philosophical import. What uses – practical, or theoretical – does such a measure serve? What reasons might one have to be skeptical of p? Drawing upon methodological and empirical critiques of p in the scientific literature, this paper argues that p is not itself explanatory. However, the controversy over p is informative in at least three ways: First, it is illustrative of a larger divide surrounding the value and import of factor analysis in psychiatric research. Second, it provides insight into debates over p and other “open” partial operational definitions or “wide operational” concepts. Third, debates over p shed light on competing research programs in psychiatry that place greater emphasis on dimensional as opposed to categorical approaches to psychopathology (and in particular HiTOP, the hierarchical taxonomy of psychopathology). The debate over p, in other words, is not best understood as a debate over the “reality” of a single common cause of psychopathology; rather, it is a debate over how best to organize research into the mechanisms underlying psychopathology.

There are a variety of trade-offs involved in biomedical research on cancer. This chapter focuses on reductive heuristics (Wimsatt, 1994, Canadian Journal of Philosophy Supplementary, 20, 207–274, 1997, Philosophy of Science, 64(S4), S372–S384, 2007, Re-engineering philosophy for limited beings: Piecewise approximations to reality. Harvard University Press), and their role in the cancer genomes projects. The advantage of reductive heuristics is that they yield “solvable” problems and can scaffold future research; the disadvantage is that they can lead to relative conservativism. I consider this picture viz. Lakatos’s picture of progress in science and argue that the import of enterprises such as TCGA needs to be assessed viz. a larger set of heuristics than the ones Lakatos imagined, including attention to practical applications, and questions of value or social aims, as well as potential future import for scientific inquiry.

_A COMPANION TO THE PHILOSOPHY OF BIOLOGY_ “Sarkar is to be congratulated for assembling this talented team of philosophers, who are themselves to be congratulated for writing these interesting essays on so many fascinating areas in philosophy of biology. This book will be a wonderful resource for future work.” _Elliot Sober,_ University of Wisconsin-Madison “Many of the discussions here start with a definition of terms and a historical context of the subject before delving into the deeper philosophical issues, making it a useful reference for students of biology as well as philosophy.” _Northeastern Naturalist_ “The topics that are addressed are done so well. This book will appeal to the advanced student and knowledgeable amateur and may prove useful catalyst for discussion among research teams or those engaged in cross-disciplinary studies.” _Reference Reviews_ _A Companion to the Philosophy of Biology_ offers concise overviews of philosophical issues raised by all areas of biology. Addressing both traditional and emerging areas of philosophical interest, the volume focuses on the philosophical implications of evolutionary theory as well as key topics such as molecular biology, immunology, and ecology Comprising essays by top scholars in the field, this volume is an authoritative guide for professional philosophers, historians, sociologists and biologists, as well as an accessible reference work for students seeking to learn about this rapidly-changing field.

_A COMPANION TO THE PHILOSOPHY OF BIOLOGY_ “Sarkar is to be congratulated for assembling this talented team of philosophers, who are themselves to be congratulated for writing these interesting essays on so many fascinating areas in philosophy of biology. This book will be a wonderful resource for future work.” _Elliot Sober,_ University of Wisconsin-Madison “Many of the discussions here start with a definition of terms and a historical context of the subject before delving into the deeper philosophical issues, making it a useful reference for students of biology as well as philosophy.” _Northeastern Naturalist_ “The topics that are addressed are done so well. This book will appeal to the advanced student and knowledgeable amateur and may prove useful catalyst for discussion among research teams or those engaged in cross-disciplinary studies.” _Reference Reviews_ _A Companion to the Philosophy of Biology_ offers concise overviews of philosophical issues raised by all areas of biology. Addressing both traditional and emerging areas of philosophical interest, the volume focuses on the philosophical implications of evolutionary theory as well as key topics such as molecular biology, immunology, and ecology Comprising essays by top scholars in the field, this volume is an authoritative guide for professional philosophers, historians, sociologists and biologists, as well as an accessible reference work for students seeking to learn about this rapidly-changing field.

While there have been forty years of active debate among philosophers of psychiatry about how to define mental disorder, there has been relatively little discussion of mental health. This is starting to change. A new literature is emerging about what it means to have mental health. While some define mental health as simply as the absence of mental disorder, others argue to the contrary that mental health is distinct from, and not reducible to, the presence or absence of mental illness. In this paper we review competing accounts and develop our own account. We characterize a diverse set of dispositions, skills, habits, and capacities, associated with aspects of personality structure. These are some of the same capacities developed across many psychotherapies. Attention to the literature on personality, and clinical psychotherapy, can, in our view, illuminate one (of several) dimensions of positive mental health.

“Actionability” is a key concept in precision oncology. Its precise definition, however, remains contested. This article undertakes a philosophical analysis of “actionability” to aid in conceptual clarification. We map distinct concepts of actionability, arguing that each is best understood as a contextually objective category articulated to mitigate risk of “conceptual slippage.” We defend “interactive pluralism,” acknowledging the need for distinct concepts but also for conceptual interaction in practice. This article thus offers insights for both practitioners and philosophers, clarifying approaches to actionability for scientists and clinicians and serving as a case study to test competing views on scientific pluralism.

This paper argues that the process of modeling in science and the process of encountering and working with a client in clinical psychotherapy overlap. In briefer terms: what makes a good therapist is much like what makes a good scientific modeler. Both modeling and psychotherapy are iterative processes, requiring careful observation, generation and testing of hypotheses. Both processes also face similar epistemic and pragmatic trade-offs. Heuristics and biases can shape both practices, for better and worse. Implications are considered for both training in clinical psychotherapy, and for larger debates concerning evidence-based methods in assessment of mental health care, and categorical v. dimensional approaches to diagnosis.

This paper argues that the process of modeling in science and the process of encountering and working with a client in clinical psychotherapy overlap. In briefer terms: what makes a good therapist is much like what makes a good scientific modeler. Both modeling and psychotherapy are iterative processes, requiring careful observation, generation and testing of hypotheses. Both processes also face similar epistemic and pragmatic trade-offs. Heuristics and biases can shape both practices, for better and worse. Implications are considered for both training in clinical psychotherapy, and for larger debates concerning evidence-based methods in assessment of mental health care, and categorical v. dimensional approaches to diagnosis.

Mitchell’s philosophical contributions are part of an ongoing conversation among philosophers and scientists about laws and unification in biology, going back at least to Darwin. This article situates Mitchell in this conversation, explains why and how she has correctly guided us away from false idols, and engages several difficult questions she leaves open. I argue that there are different epistemic roles laws (or models describing lawlike regularities) play in biological inquiry. First, they play the role of “how possibly” explanations, akin to Herschel’s characterization of Whewell’s “a priori Pegasus,” and second, they provide descriptions of empirical regularities, akin to the “plain matter of fact roadster.”

Abstract:In this paper, I distinguish four ways in which aspects or features of mental illness may be said to be functional. I contend that discussion of teleological perspectives on mental illness has unfortunately tended to conflate these senses. The latter two senses have played important practical roles both in predicting and explaining patterns of behavior, cognition, and affective response, atnd relatedly, in developing successful interventions. I further argue that functional talk in this context is neither inconsistent with viewing some disorders as dysfunctional in one of several senses, nor inappropriately adaptationist, provided we keep these senses of function distinct, and are precise about which is in play in a given context.

Biodiversity conservation as a practical discipline has been significantly transformed over the past twenty years. Given the extent to which humans influence not only biodiversity loss, but also geographical distribution, and ecological dynamics, there has been a shift in the study of conservation as a scientific discipline from a concern strictly with ecological and biological diversity measures to an interdisciplinary field, drawing upon the human sciences. We draw upon several case studies to argue for the importance of attention to local stakeholders, culture, and community values, in conservation practice.

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.

The focus of this chapter will be on the epistemic and normative questions at issue in debates about cancer screening, with a special focus on mammography as a case study. Such questions include: How do we know who needs to be screened? What are the benefits and harms of cancer screening, and what is the quality of evidence for each? How ought we to measure and compare these benefits and harms? What are the sources of uncertainty about our estimates of benefit and harm? Why are such issues so contested? What are the major drivers of dissent and consensus on the data and their interpretation? How, if at all, do values play a role in debates surrounding mammography screening? In sum: In what ways does inductive risk, broadly conceived, 1 come into play in the science behind cancer screening, and mammography screening in particular?

Cancer—and scientific research on cancer—raises a variety of compelling philosophical questions. This entry will focus on four topics, which philosophers of science have begun to explore and debate. First, scientific classifications of cancer have as yet failed to yield a unified taxonomy. There is a diversity of classificatory schemes for cancer, and while some are hierarchical, others appear to be “cross-cutting,” or non-nested. This literature thus raises a variety of questions about the nature of the disease and disease classification. Second, philosophers of science have historically taken the aim of science to be arriving at true theories. However, scientists studying cancer come from a variety of disciplines, with different scientific as well as practical aims. Perhaps it is not surprising, then, that historians and philosophers of science do not seem to agree on how best to characterize the aim and structure of cancer research; it is far from clear whether the appropriate characterization of the aim is arriving at true theories, or even whether the proper units of analysis are “theories”, or instead, “models”, “explanatory frameworks”, “research programs”, “paradigms”, or perhaps, “experimental traditions”. With the rise of “big data” science—such as the Cancer Genome Atlas Project (or TCGA)—and “systems” approaches to the study of disease, both philosophers and historians of science are rethinking how best to describe and explain these distinctive kinds of scientific inquiry. Third, cancer is in part a byproduct of our developmental and life history, as well as our evolutionary history. Cancer progression can be compared to a reversion of development, or, to the evolution of multicellularity. Thus, cancer raises intriguing questions about how we conceive of “functions”, “development”, and the role of our evolutionary history and particularly, selective trade-offs, in vulnerability to disease. Last but not least, cancer research provides a case study for consideration of the roles of values at the science-policy interface. Epidemiological and toxicological research on cancer’s causes informs toxics law and regulatory policy, which raises a variety of questions about the nature of evidence and inductive risk in such contexts.

This chapter discusses Mina Bissell's pathbreaking research on cancer. Along with her colleagues and students, Bissell focused her attention on how the causal pathways regulating cell behavior were a two way street. Healthy cells’ and cancer cells’ behavior are both highly context-dependent. The pathway to this insight was not direct. Bissell’s work began with research into cellular metabolism. As a result of this early research, she found that cells can “change their fate” – revert to, or activate, functions not typical of cells in the differentiated state. This had important implications for our understanding of cancer's etiology and treatment. Bissell - among others - emphasized in her research that it was not simply cell intrinsic properties – such as mutations to “oncogenes” and “tumor suppressor” genes – that determine the typical behaviors of cancer cells, but also a variety of extrinsic properties in the surrounding environment: metabolic and other signaling molecules, the extracellular matrix, and tissue architecture.

November 2009’s announcement of the USPSTF’s recommendations for screening for breast cancer raised a firestorm of objections. Chief among them were that the panel had insufficiently valued patients’ lives or allowed cost considerations to influence recommendations. The publicity about the recommendations, however, often either simplified the actual content of the recommendations or bypassed significant methodological issues, which a philosophical examination of both the science behind screening recommendations and their import reveals. In this article, I discuss two of the leading ethical considerations at issue in screening recommendations: respect for patient autonomy and beneficence and then turn to the most significant methodological issues raised by cancer screening: the potential biases that may infect a trial of screening effectiveness, the problem of base rates in communicating risk, and the trade-offs involved in a judgment of screening effectiveness. These issues reach more broadly, into the use of “evidence-based” medicine generally, and have important implications for informed consent.

One of the major developments in cancer research in recent years has been the construction of models that treat cancer as a cellular population subject to natural selection. We expand on this idea, drawing upon multilevel selection theory. Cancer is best understood in our view from a multilevel perspective, as both a by-product of selection at other levels of organization, and as subject to selection at several levels of organization. Cancer is a by-product in two senses. First, cancer cells co-opt signaling pathways that are otherwise adaptive at the organismic level. Second, cancer is also a by-product of features distinctive to the metazoan lineage: cellular plasticity and modularity. Applying the multilevel perspective in this way permits one to explain transitions in complexity and individuality in cancer progression. Our argument is a reply to Germain’s scepticism towards the explanatory relevance of natural selection for cancer. The extent to which cancer fulfills the conditions for being a paradigmatic Darwinian population depends on the scale of analysis, and the details of the purported selective scenario. Taking a multilevel perspective clarifies some of the complexities surrounding how to best understand the relevance of evolutionary thinking in cancer progression

In 2015, Tomasetti and Vogelstein published a paper in Science containing the following provocative statement: “… only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells.” The paper—and perhaps especially this rather coy reference to “bad luck”—became a flash point for a series of letters and reviews, followed by replies and yet further counterpoints. In this paper, I critically assess Tomasetti and Vogelstein's argument, discuss the meaning of “luck” (or, better: “chance”) in the context of the debate, and use this case study to address larger questions about methodological criteria for causal explanations of population level patterns in biomedicine.

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.