Philosophy of Stem Cell Biology

Knowledge in Flesh and Blood

M. Fagan

• Publisher: Palgrave Macmillan
• Year: 2013
• ISBN:
  9781137296023
• Topic: Philosophy
• Subtopic: Philosophy & Ethics in Science

Thisexamination ofstem cell biology from a philosophy of science perspective clarifies the field's central concept, the stem cell, as well as its aims, methods, models, explanations and evidential challenges. Relations to systems biology and clinical medicine are also discussed.

1

Visceral Phenomena

1.1 Blood and guts

This book examines stem cell biology from a philosophy of science perspective. Philosophical ideas and arguments can illuminate significant features and prevailing trends in stem cell science, examining the field in a broadly accessible way. Stem cell research, in turn, offers valuable challenges and lessons for philosophers of science. Gaining insight into this experimental, clinically-oriented field requires some departure from the traditional focus on laws and theories. Stem cell biology offers new insights on scientific models, experimental evidence, causal explanations, and social epistemology, among other topics, So both philosophy of science and stem cell biology have something to gain from their interaction. This collaborative viewpoint is defended throughout the book.

The starting point for understanding in any field is the occurrence of phenomena. Ancient astronomical theories were tasked with ‘saving the phenomena’ – explaining and predicting the motions of celestial bodies observable from Earth, which have furnished the subject matter of astronomy for millennia. The phenomena of stem cell biology are quite unlike the grand, remote arcs of celestial bodies. They are, instead, the stuff of our bodies, the mundane motions of which track our development from birth to death. This first section introduces the visceral phenomena of stem cell biology and the questions that arise from them. The next section explains how philosophy of science can help answer these questions, and introduces the basic ideas and assumptions used to do so in the chapters that follow.

Stem cell phenomena are various. Some are so familiar as to seem beneath notice: hair grows, skin is shed and replaced, cells in our bodies gradually turn over. Other species’ regenerative capacities are more remarkable. Starfish and salamanders can replace severed limbs; worms and plants can re-grow an entire body from a fragment. Our own regenerative powers are demonstrated in wound-healing: bones knit, spilled blood is replaced, torn skin and muscle become smooth and whole. Most of these ‘self-renewing’ processes are internal and undetected. However, in the past century, innovations in ‘ex vivo’ cell culture have made many interior aspects of our embodied experience visible and accessible to experiment. Some of the most striking stem cell phenomena occur in transparent artificial bodies of liquid and glass. Blood, our most separable tissue, is the site of many stem cell phenomena. Blood is composed of fluid serum and cells, colloquially termed ‘red’ and ‘white.’ Red blood cells do the work of oxygen transport, while white blood cells, of which there are many types, mediate the immune response. Though these circulatory functions persist throughout life, individual blood cells do not. In humans, a single red blood cell typically circulates for a few months, then ‘dies,’ with its parts fragmenting to be reused or excreted. The lifespan of white blood cells is more variable, ranging from weeks to years, but the end is the same. The lifecycles of organisms and cells are not synchronized. For an organism to have a long and healthy life, new blood cells must continually develop to replace those that ‘die off.’

Blood cell development is extremely sensitive to the state of the organism, including its health. Cells lost because of injury can be replaced, while immune responses defend bodily integrity by selectively amplifying cells that target particular ‘invaders.’ The regular movement of circulating blood in the body is interwoven with slower, but equally orchestrated, developmental movements, which maintain the balance of this tissue throughout an animal’s life. The vital functions of blood require cell development and regeneration on a massive scale – about one trillion (1012) new blood cells per day in adult humans. Skin and hair are similarly regulated, being tissues at the boundary of organism and environment, continually shed and replaced. The gut, another boundary area, sloughs off cells at a staggering rate: about 250 per day from each of millions of threadlike protuberances that line the small intestine. New cells rise from evocatively-termed ‘crypts’ in the intestinal lining, developing as they migrate into place.¹ In other organs, such as brain and ovaries, cell turnover is slow or non-existent. The challenge of stem cell biology is to explain these phenomena of cell death and renewal; specifically, how they are coordinated within and among organs and tissues to constitute a healthy, fully-developed organism.

Because all organisms begin as a single cell, the entire developmental process can be construed as a stem cell phenomenon. A fertilized egg, given appropriate nutrients and environment, undergoes repeated cell division, growth, and specialization of parts to produce a multicellular organism.² Stages of embryonic development in many animal species are well characterized. But their causes are not. Robustness of developmental processes across environments and species suggests a common, pre-determined ‘program,’ which is often attributed to genes. ‘The genetic program for development’ cannot be the whole story, however. All the cells of an organism’s body (with minor exceptions) share the same genes. Yet, these cells exhibit different traits and perform disparate functions, both in the course of development and within a mature organism. The problem of explaining cellular diversity with invariant genes is termed the “developmental paradox” (Burian 2005). Stem cell biology approaches organismal development somewhat differently, as a cellular phenomenon. Processes by which an organism’s body is constructed are conceived as cellular activities – division, differentiation, and interaction with environment – with a single point of origin, the fertilized egg. The image of development that stem cell science seeks to explain is this branching ‘outward’ radiation, coordinated within, and constituting, a single healthy organism.

So conceived, stem cells are the active sources of organismal development. Understanding their abilities is the key to explaining the entire process. The explanations sought are of a particular kind, giving us control over developmental processes. This brings up another basic point: stem cell biology is not ‘pure science’ aimed at knowledge for its own sake. The field’s primary motive is to innovate new therapies for injury and disease, by harnessing cells’ regenerative capacities.³ The scope of these hoped-for therapies is very broad, precisely because the field’s explanatory aims comprehend the entirety of cell development within an organism. In principle, any disorder or injury involving any cell type in the body could be ameliorated by targeted manipulation of stem cells or their products. In practice, the main clinical targets are First World diseases: cancer, diabetes, heart attack, and neurodegenerative conditions. Proponents of stem cell research anticipate “an impending revolution” both in medicine and in our ideas about cell development (Trounson 2009, xix). Perhaps the grandest and most evocative prospect is healing spinal injuries and neurodegenerative conditions, restoring the ability to walk, think, and remember.

These hopes are extravagant, easily shading into hype. What is their scientific basis? And what more do we need to know in order to realize these regenerative scenarios? The following chapters offer answers to these questions, But they do so from a philosophical perspective, rather than a scientific one. An up-to-the-minute compendium of experimental results would soon be obsolete and merely summarize what scientists themselves have said elsewhere. Instead, I focus on more enduring features of scientific method: evidence, explanation, and experiment. These are core concepts of philosophy of science.

1.2 Aims and themes

Philosophy of science originated as a method for clear communication of ideas. Stem cell biology, a relatively new field that is the focus of continual hype, misunderstanding, and argument, stands to benefit from such a treatment. Though many ethical and political aspects of stem cell research have been examined philosophically, the science of stem cells has not yet been articulated in an accessible and philosophically-informed way. This book aims to fill the gap. To clarify this goal, a few caveats should be noted at the outset. First, the intent is neither to reiterate scientists’ own claims nor attempt to correct them. Rather, it is to provide an alternative, more general, perspective on stem cell research. This philosopher’s-eye-view of the field, while neither fully comprehensive nor exhaustive, captures a number of significant features that are not so clearly resolved from the standpoint of day-to-day experience. Stem cell scientists may find this perspective useful, as an engaged, but not fully immersed, alternative to their own viewpoints. But the main goal is to make stem cell science – its methods, technology, and results – accessible to a wider audience. Philosophy of science, with its traditional emphases on methodology and evidence, augmented by new accounts of explanation, causality, scientific models, and social epistemology, has the right tools for the job.⁴

Second, this work is intended as the start of a broader discussion of philosophical issues relating to stem cell science, not the final word on the subject. What follows does not exhaust the philosophical interest of stem cell biology nor every conceivable way philosophy of science may bear on that field. Though subsequent chapters explore a number of philosophy of science topics, there is space for much future work. Of particular interest are relations between philosophy of science and ethical, political, and historical accounts of stem cell research, on which a sizable scholarly literature exists.⁵ Emphasis on ethical controversies and the wider social context of stem cell science is understandable. In perhaps no other contemporary field have scientists had to be so conscious of the social context of their experimental practice, navigating a shifting landscape of political, bioethical, and financial constraints. Yet the political, economic, and cultural significance of stem cell biology is ultimately rooted in its biomedical potential. Clarifying the experimental field that inspires the welter of expectations, concerns, hopes, and plans surrounding stem cell research will also enrich ethical, political, cultural, and historical studies. However, in what follows there is little explicit discussion of these topics. Detailed engagements with history, sociology, political philosophy, and policy-making are left for future work.

Third, the connection between stem cell biology and philosophy of science goes both ways. Stem cell biology offers valuable lessons and insights for philosophers of science. Traditionally, the central task for philosophy of science is clarification of physical theories: their structure, meaning, and connection to reality or experience. However, stem cell biology has no obvious counterpart to physical theory and bears little resemblance to ‘canonical’ sciences, such as Newtonian mechanics or neo-Darwinian evolutionary theory. Instead, it is driven by experiment, motivated and guided by available technology and hoped-for applications. To engage with it on its own terms presents a challenge, and a departure from traditional focus on laws and theories. Other topics in philosophy of science come to the fore, including scientific models, experimental evidence, causal explanations, and interdisciplinarity. The past decade or so has yielded new accounts of all these, which can be productively applied to stem cell biology. So rather than focusing on a single problem or debate within philosophy of science, such as realism or induction, the following chapters discuss a variety of issues, using the case of stem cell biology to critique and extend general accounts of models, experiments, and explanation. This ‘topical’ approach allows multiple aspects of stem cell biology to emerge more clearly in philosophical perspective.

A final caveat follows from the previous: rather than defending a single philosophical thesis, this book presents a viewpoint from which a number of interrelated philosophical claims follow. This viewpoint concerns how knowledge emerges from interaction of different elements. Though its full articulation takes place over the course of the entire book, it can be briefly sketched in terms of three themes, which recur throughout the following chapters: interaction, pluralism, and unification. I discuss each briefly, then sketch the plan of the book.

First, interaction is crucial, both in representations of biological development (models) and in the scientific practices that produce them (experiments). The image of development that animates stem cell biology is not that of a solitary cell that develops autonomously to reveal its inner potential. Rather, development begins with a cell interacting with its environment, whether the latter is another organism, an artificial culture, or the outside world. In any of these environments, development proceeds by cell division. Interactions among cells therefore multiply and diversify as the process moves forward, all in continual responsiveness to the environment. Our explanatory models of development should reflect this dynamic complexity. Moreover, to inform new therapies, these explanations must also indicate ways we can influence development. Successful explanations in stem cell biology not only represent biological interactions, but enable new ones: clinical interventions. Knowledge of stem cells takes the form of therapeutically-useful explanations, constrained by both these interactive aspects. Furthermore, the experiments on which such explanations are based also involve interaction – of technologies and concepts from different biomedical fields. Progress in stem cell research, as well as validation of knowledge from particular experiments, depends on collaborative interaction.

Related to the theme of interaction is pluralism regarding scientific representations, or models. Pluralism and emphasis on models in science go hand-in-hand. Traditionally, philosophy of science distinguished only two key domains in scientific method: theory and observation. A seminal article, Saving the phenomena (Bogen and Woodward 1988), proposed a third domain, associated with models. Bogen and Woodward argue that theories, exemplified by classical mechanics, explain phenomena rather than data, while data provide evidential support for phenomena. This interposes a third ‘level’ between theories and observational data, mediating between them. The tripartite distinction – of phenomena, explanatory theories, and observational data – allows for more nuanced accounts of scientific practice than the traditional theory: observation dichotomy. Subsequent investigations of scientific practice further support the pivotal role of models in fields ranging from physics to economics. Models in biology run the gamut from abstract to concrete. Abstract models in stem cell biology include the stem cell concept itself, as well as images of development in the form of branching hierarchies. Concrete, or material models, are striking experimental productions: “immortal” cell lines with unlimited developmental abilities (Thomson et al. 1998); embryo-like cells from “reprogrammed” adult cells (Takahashi and Yamanaka 2006); muscle, blood, and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein).

Experiments in stem cell biology involve the interplay of diverse abstract and concrete models. The most controversial of stem cell models – embryonic stem cells – are the material realization of a simple, idealized abstract model of organismal development. Abstractions are implicit in experimental methods used to produce concrete experimental outcomes. Concrete model organisms and model systems mingle with abstract conceptions of development and ‘stemness’ to yield the basic epistemic standards, goals, and organization of stem cell biology today. An approach that privileges or prioritizes one kind of model over another can yield, at best, an impoverished, and, at worst, a perniciously distorted, view of the field. Pluralism about models is fundamental for understanding, as well as practice, of stem cell research. Furthermore, new stem cell phenomena are continually being created as technologies are applied to biological materials in new ways. The field is thus open-ended and continually in flux. Experimental systems multiply and diversify, generating new phenomena. In this respect, stem cell biology resembles its subject matter: cells differentiating in local environments. Stem cell experiments, and the evidential support they provide, are relative to local contexts, which maintain their specific arrangements of technology, biomaterials, concepts, and methods. The two themes are closely related: interaction among diverse models of stem cells is basic to both scientific and philosophical understanding of the field.

The third theme, unification, counterbalances the diversity of models and experiments. Unification is one outcome of interaction among diverse models, and, as argued in later chapters, the crux of explanation in stem cell biology. Many aspects of stem cell science are motivated by a demand for explanatory unification of different representations. As noted earlier, cell development is conceived in terms of responsiveness to features of the environment. This context-relativity raises a number of questions. Most pointedly, can any cell be a stem cell, given the appropriate environment? If so, then is the idea of a ‘stem cell’ misleading? If not, then what are the limits of context-relativity in cell development? Without a general ‘signature’ of traits shared by stem cells across different environments, the field of stem cell biology seems fragmented, unified only by a common label for disparate objects of study. Perhaps a successor concept, such as ‘stemness,’ would provide a better general characterization for stem cell biology today. Parallel concerns arise for experiments and their results. Claims about stem cell capacities, insofar as they are well-supported by experimental evidence, are relative to a specific context. What connects experimental results from different contexts? On what basis can they ...

Table of contents

• Cover
• Title
• Copyright
• Contents
• List of Figures and Tables
• Series Editor’s Foreword
• Acknowledgments
• 1 Visceral Phenomena
• Part I
• Part II
• Part III
• Notes
• Bibliography
• Index