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)

Is knowledge in the natural sciences discovered or constructed? For objectivists, scientific knowledge is discovered through investigations into a mind-independent, natural world. For constructivists, such knowledge is produced through negotiations among members of a professional guild. I examine the clash between the two positions and propose that scientific knowledge is the concurrent outcome from investigations into a natural world and from consensus reached through negotiations of a professional guild. Specifically, I introduce the general methodological notion, instituting science, which incorporates both (...) the discovery and the construction processes in the generation of scientific knowledge. To that end, I use a case study from the biomedical sciences to illustrate the notion. I conclude with a discussion of how this methodological notion helps to address the debate between objectivists and constructivists over the generation of scientific knowledge, and of how it compares with others who have also attempted to address the debate. (shrink)

In the past decades, an enormous amount of precious information has been collected about molecular and genetic characteristics of cancer. This knowledge is mainly based on a reductionistic approach, meanwhile cancer is widely recognized to be a ‘system biology disease’. The behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. There is not solely a matter how to integrate all available knowledge in such a way that we can still deal with complexity, (...) but we must be aware that a deeply transformation of the currently accepted oncologic paradigm is urgently needed. We have to think in terms of biological networks: understanding of complex functions may in fact be impossible without taking into consideration influences outside of the genome. Systems Biology involves connecting experimental unsupervised multivariate data to mathematical and computational approach than can simulate biologic systems for hypothesis testing or that can account for what it is not known from high-throughput data sets. Metabolomics could establish the requested link between genotype and phenotype, providing informations that ensure an integrated understanding of pathogenic mechanisms and metabolic phenotypes and provide a screening tool for new targeted drug. (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)

Contrary to empiricist hopes, Chakravartty claims that science cannot escape metaphysics. According to him, in line with the theory-ladenness thesis, science necessarily includes metaphysical presuppositions and metaphysical inferences. He contends that strong empiricism provides an implausible description of what scientists do. Furthermore, he claims, empiricists should recognize that in fact they entertain metaphysical beliefs. I analyze Chakravartty’s arguments and point out some significant weaknesses. Drawing on recent experimental results in the field of experimental psychology, I question the use of an (...) exaggerated theory-ladenness thesis and conclude that Chakravartty’s view concerning the relationship between science and metaphysics is far of successfully rebutting the empiricist proposals. (shrink)

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. (shrink)

Some strongly empiricist views of scientific knowledge advocate a rejection of metaphysics. On such views, scientific knowledge is described strictly in terms of knowledge of the observable world, demarcated by human sensory abilities, and no metaphysical considerations need arise. This paper argues that even these views require some recourse to metaphysics in order to derive knowledge from experience. Central here is the notion of metaphysical inference, which admits of different “magnitudes”, thus generating a spectrum of putative knowledge with more substantially (...) empirical beliefs at one end, and more metaphysically imbued beliefs at the other. Given that metaphysical inference is required even concerning knowledge of the observable, the empiricist hope of avoiding metaphysics altogether is futile: knowledge of the observable simply involves metaphysical inferences that are of smaller magnitudes than others. Metaphysical inferences are required not only to distinguish veridical from non-veridical experience and to determine the quality of empirical information, but also in order to explain how we construct experience (through categorizations and classifications of objects, events, processes, and properties), how we extrapolate from empirical evidence to generalize about observable phenomena, and how we use this evidence to test and confirm hypotheses and theories. (shrink)

Are the small and indolent cancers found in abundance in cancer screening normal variations, risk factors, or disease? Naturalists in philosophy of medicine turn to pathophysiological findings to decide such questions objectively. To understand the role of pathophysiological findings in disease definition, we must understand how they mislead in diagnostic reasoning. Participants on all sides of the definition of disease debate attempt to secure objectivity via reductionism. These reductivist routes to objectivity are inconsistent with the Bayesian nature of clinical reasoning; (...) when they appeal to the sciences, they are inconsistent with what philosophy of biology tells us about its natural kinds. Proposals that we narrow the scope of our claims in the disease definition debates are useful, but paradigms can still distort our reasoning in particular cases, even when we are self-conscious about their status. (shrink)