Stem cell biology and systems biology are two prominent new approaches to studying cell development. In stem cell biology, the predominant method is experimental manipulation of concrete cells and tissues. Systems biology, in contrast, emphasizes mathematical modeling of cellular systems. For scientists and philosophers interested in development, an important question arises: how should the two approaches relate? This essay proposes an answer, using the model of Waddington’s landscape to triangulate between stem cell and systems approaches. This simple abstract model represents (...) development as an undulating surface of hills and valleys. Originally constructed by C. H. Waddington to visually explicate an integrated theory of genetics, development and evolution, the landscape model can play an updated unificatory role. I examine this model’s structure, representational assumptions, and uses in all three contexts, and argue that explanations of cell development require both mathematical models and concrete experiments. On this view, the two approaches are interdependent, with mathematical models playing a crucial but circumscribed role in explanations of cell development. (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)

If there is collective scientific knowledge, then at least some scientific groups have beliefs over and above the personal beliefs of their members. Gilbert's plural-subjects theory makes precise the notion of ‘over and above’ here. Some philosophers have used plural-subjects theory to argue that philosophical, historical and sociological studies of science should take account of collective beliefs of scientific groups. Their claims rest on the premise that our best explanations of scientific change include these collective beliefs. I argue that Gilbert's (...) account of collective scientific belief does not provide a better explanation of scientific change than a non-collective alternative. A different defence of collective scientific belief and knowledge is needed. (shrink)

Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases) ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the (...) lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial) characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells. (shrink)

This paper examines a case of failed interdisciplinary collaboration, between experimental stem cell research and theoretical systems biology. Recently, two groups of theoretical biologists have proposed dynamical systems models as a basis for understanding stem cells and their distinctive capacities. Experimental stem cell biologists, whose work focuses on manipulation of concrete cells, tissues and organisms, have largely ignored these proposals. I argue that ‘failure to communicate’ in this case is rooted in divergent views of explanation: the theoretically-inclined modelers are committed (...) to a version of the covering-law view, while experimental stem cell biologists aim at mechanistic explanations. I propose a way to reconcile these two explanatory approaches to cell development, and discuss the significance of this result for interdisciplinary collaboration in systems biology and beyond. (shrink)

This essay examines the role of social interactions in the search for blood stem cells, in a recent episode of biomedical research. Linked to mid-20th century cell biology, genetics and radiation research, the search for blood stem cells coalesced in the 1960s and took a developmental turn in the late 1980s, with significant ramifications for immunology, stem cell and cancer biology. Like much contemporary biomedical research, this line of inquiry exhibits a complex social structure and includes several prominent scientific successes, (...) recognized as such by participating researchers. I use personal interviews and the published record to trace the social interactions crucial for scientific success in this episode. All recognized successes in this episode have two aspects: improved models of blood cell development, and new interfaces with other lines of research. The narrative of the search for blood stem cells thus yields a robust account of scientific success in practice, which generalizes to other scientific episodes and lends itself to expansion to include wider social contexts. (shrink)

Epistemology of science is currently polarized. Descriptive accounts of the social aspects of science coexist uneasily with normative accounts of scientific knowledge. This tension leads students of science to privilege one of these important aspects over the other. I use an episode of recent immunology research to develop an integrative account of scientific inquiry that resolves the tension between sociality and epistemic success. The search for the hematopoietic stem cell by members of Irving Weissman’s laboratory at Stanford University Medical Center (...) exhibits both the goal-oriented character of contemporary immunology and the importance of social interactions in successful achievement of those goals. This episode includes three kinds of epistemic success: characterization of HSC, formation of new interdisciplinary interfaces, and reconciliation of apparently incompatible models. All three depend on coordinating the work of diverse participants via social interactions. Together, they reveal the crucial role of social interactions within and between research groups in producing epistemic success. These features of the search for the HSC generalize to immunology as a whole, and plausibly to other disciplines. This account thus resolves the polarizing tension in epistemology of science, and complements individualistic accounts of scientific knowledge and rationality. (shrink)

Ludwik Fleck’s theory of thought-styles has been hailed as a pioneer of constructivist science studies and sociology of scientific knowledge. But this consensus ignores an important feature of Fleck’s epistemology. At the core of his account is the ideal of ‘objective truth, clarity, and accuracy’. I begin with Fleck’s account of modern natural science, locating the ideal of scientific objectivity within his general social epistemology. I then draw on Fleck’s view of scientific objectivity to improve upon reflexive accounts of the (...) origin and development of the theory of thought-styles, and reply to objections that Fleck’s epistemological stance is self-undermining or inconsistent. Explicating the role of scientific objectivity in Fleck’s epistemology reveals his view to be an internally consistent alternative to recent social accounts of scientific objectivity by Harding, Daston and Galison. I use these contrasts to indicate the strengths and weaknesses of Fleck’s innovative social epistemology, and propose modifications to address the latter. The result is a renewed version of Fleck’s social epistemology, which reconciles commitment to scientific objectivity with integrated sociology, history and philosophy of science. (shrink)

What is a stem cell? The answer is seemingly obvious: a cell that is also a stem, or point of origin, for something else. Upon closer examination, however, this combination of ideas leads directly to fundamental questions about biological development. A cell is a basic category of living thing; a fundamental 'unit of life.' A stem is a site of growth; an active source that supports or gives rise to something else. Both concepts are deeply rooted in biological thought, with (...) rich and complex histories. The idea of a stem cell unites them, but the union is neither simple nor straightforward. This book traces the origins of the stem cell concept, its use in stem cell research today, and implications of the idea for stem cell experiments, their concrete results, and hoped-for clinical advances. (shrink)

Stem cells are defined as having capacities for both self-renewal and differentiation. Many different entities satisfy this working definition. I show that this general stem cell concept is relative to a cell lineage, temporal duration, and characters of interest. Experiments specify values for these variables. So claims about stem cells must be understood in terms of experimental methods used to identify them. Furthermore, the stem cell concept imposes evidential constraints on interpretation of experimental results. From these constraints, it follows that (...) claims about stem cell capacities are inherently uncertain. This result has important implications for stem cell research. (shrink)

This review surveys three central issues in philosophy of stem cell biology: the nature of stem cells, stem cell experiments, and explanations of stem cell capacities. First, I argue that the fundamental question ‘what is a stem cell?’ has no single substantive answer. Instead, the core idea is explicated via an abstract model, which accounts for many features of stem cell experiments. The second part of this essay examines several of these features: uncertainty, model organisms, and manipulability. The results shed (...) light on the form of our emerging knowledge of stem cells: mechanistic explanations. The third part of the essay sketches some key features of these explanations, which are constructed by a collaborative experimenting community. (shrink)

Epistemology of science is currently polarized. Descriptive accounts of the social aspects of science coexist uneasily with normative accounts of scientific knowledge. This tension leads students of science to privilege one of these important aspects over the other. I use an episode of recent immunology research to develop an integrative account of scientific inquiry that resolves the tension between sociality and epistemic success. The search for the hematopoietic stem cell (HSC) by members of Irving Weissman’s laboratory at Stanford University Medical (...) Center exhibits both the goal-oriented character of contemporary immunology and the importance of social interactions in successful achievement of those goals. This episode includes three kinds of epistemic success: characterization of HSC, formation of new interdisciplinary interfaces, and reconciliation of apparently incompatible models. All three depend on coordinating the work of diverse participants via social interactions. Together, they reveal the crucial role of social interactions within and between research groups in producing epistemic success. These features of the search for the HSC generalize to immunology as a whole, and plausibly to other disciplines. This account thus resolves the polarizing tension in epistemology of science, and complements individualistic accounts of scientific knowledge and rationality. (shrink)

Science is increasingly interdisciplinary, as evidenced by empirical measures, funding initiatives, and the rise of integrative fields such as systems biology and cognitive neuroscience. In this paper, I motivate and outline an account of explanation for interdisciplinary contexts, building on recent debates about scientific perspectivism. Insights from these debates yield an inclusive list of relations between models constructed from different perspectives, which I then refine and generalize into a simple taxonomy. Within this taxonomy of relations among models, I identify the (...) set of relations applicable to interdisciplinary contexts, discuss concepts of unification associated with each, and introduce three further constraints which furnish norms for this variety of explanation. Finally, I discuss implications of this account for a recent debate about understanding and explanation. One important consequence of my view is that explanation in interdisciplinary contexts and understanding of individual agents in those contexts are not equivalent. (shrink)

Philosophy of scientific practice aims to critically evaluate as well as describe scientific inquiry. Epistemic norms are required for such evaluation. Social constructivism is widely thought to oppose this critical project. I argue, however, that one variety of social constructivism, focused on epistemic justification, can be a basis for critical epistemology of scientific practice, while normative accounts that reject this variety of social constructivism cannot., idealized epistemic norms cannot ground effective critique of our practices. I propose a new approach, placing (...) SCj within a general framework of social action theory. This framework can be used to explicate epistemic norms implicit in our scientific practices. *Received July 2009; revised July 2009. †To contact the author, please write to: MS 14, P.O. Box 1892, Houston, TX 77251‐1892; e‐mail: [email protected]. (shrink)

Stem cell biology is driven by experiment. Its major achievements are striking experimental productions: "immortal" human cell lines from spare embryos (Thomson et al. 1998); embryo-like cells from "reprogrammed" adult skin cells (Takahashi and Yamanaka 2006); muscle, blood and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein). Well-confirmed theories are not so prominent, though stem cell biologists do propose and test hypotheses at a profligate rate. 1 This paper aims to characterize the role (...) of experiment in stem cell biology, so as to answer the following question: how do experiments contribute to our knowledge of stem cells and related phenomena? The .. (shrink)

It is widely assumed that mechanistic explanations are causal explanations. Many prominent new mechanists endorse interventionism as the correct analysis of explanatory causal models in biology and other fields. This article argues that interventionism is not entirely satisfactory in this regard. A case study of Jacob and Monod’s operon model shows that at least some important mechanistic explanations in biology present significant contrasts with the interventionist account. This result motivates a more inclusive approach to mechanistic explanation, allowing for noncausal aspects.

I have previously argued that stem cell experiments cannot demonstrate that a single cell is a stem cell (Fagan 2013a, b). Laplane and others dispute this claim, citing experiments that identify stem cells at the singlecell level. This paper rebuts the counterexample, arguing that the alleged ‘crucial stem cell experiments’ do not measure self-renewal for a single cell, do not establish a single cell’s differentiation potential, and, if interpreted as providing results about single cells, fall into epistemic circularity. I then (...) discuss the source of the dispute, locating it in differences between philosophical and experimental perspectives. (shrink)

I have previously argued that stem cell experiments cannot demonstrate that a single cell is a stem cell. Laplane and others dispute this claim, citing experiments that identify stem cells at the single-cell level. This paper rebuts the counterexample, arguing that the alleged ‘crucial stem cell experiments’ do not measure self-renewal for a single cell, do not establish a single cell’s differentiation potential, and, if interpreted as providing results about single cells, fall into epistemic circularity. I then discuss the source (...) of the dispute, locating it in differences between philosophical and experimental perspectives. (shrink)

Immunology is a notoriously complex field with distinct concepts and terminology. Yet immunologists regularly and effectively collaborate with other researchers, notably clinicians and experts in population health. How does such ‘collaboration without convergence’ work? This paper offers an answer. Immunology exhibits three features that support collaboration in the absence of major consensus on theories, methods, or concepts. These are: a multifaceted target of inquiry, therapeutic aspirations, and a clear interdisciplinary pathway. Building on these features, I sketch a general account of (...) “low-effort interdisciplinarity” and connect this result to recent work on population health. (shrink)

Sarah Franklin’s Biological relatives: IVF, stem cells, and the future of kinship and Charis Thompson’s Good science: the ethical choreography of stem cell research, examine recently normalized biotechnologies. Franklin’s monograph extends her previous work on in vitro fertilization , deconstructing the success of a technology that, she argues, has grown “curiouser and curiouser” while taking hold in scientific and social life. IVF in its diverse aspects becomes a lens for scrutinizing our ambivalence about new technology, which Franklin articulates by putting (...) disparate literatures into conversation: feminist science studies, political economy, fine art, and more. Thompson’s Good science focuses more concretely on the first decade of human pluripotent stem cell research, tracing the field from the innovation of cultured human embryonic stem cells through Bush-era policy debates, to current acceptance of stem cell research as a part of the scientific and policy landscape. Th .. (shrink)

There is a pervasive contrast in the early natural history writings of the co-discoverers of natural selection, Alfred Russel Wallace and Charles Darwin. In his writings from South America and the Malay Archipelago (1848-1852, 1854-1862). Wallace consistently emphasized species and genera, and separated these descriptions from his rarer and briefer discussions of individual organisms. In contrast, Darwin's writings during the Beagle voyage (1831-1836) emphasized individual organisms, and mingled descriptions of individuals and groups. The contrast is explained by the different practices (...) of the two naturalists in the field. Wallace and Darwin went to the field with different educational experiences and social connections, constrained by different responsibilities and theoretical interests. These in turn resulted in different natural history practices; i.e., different habits and working routines in the field. Wallace's intense collecting activities aimed at a complete inventory of different species and their distributions at many localities. Darwin's less intense collecting practice focused on detailed observations of individual organisms. These different practices resulted in different material, textual and conceptual products. Placing natural history practices at the center of analysis reveals connections among these diverse products, and throws light on Wallace and Darwin's respective treatment of individuals and groups in natural history. In particular, this approach clarifies the relation between individuals and groups in Wallace's theory of natural selection, and provides an integrative starting point for further investigations of the broader social factors that shaped Victorian natural history practices and their scientific products. (shrink)