Stem-cell nomenclature is in a muddle! So-called stem cells may be self-renewing or emergent, oligopotent (uni- and multipotent) or pluri- and totipotent, cells with perpetual embryonic features or cells that have changed irreversibly. Ambiguity probably seeped into stem cells from common usage, flukes in biology's history beginning with Weismann's divide between germ and soma and Haeckel's biogenic law and ending with contemporary issues over the therapeutic efficacy of adult versus embryonic cells. Confusion centers on tissue dynamics, whether stem cells are (...) properly members of emerging or steady-state populations. Clarity might yet be achieved by codifying differences between cells in emergent populations, including embryonic stem and embryonic germ (ES and EG) cells in tissue culture as opposed to self-renewing (SR) cells in steady-state populations. BioEssays 28: 301–308, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

This paper explores how current United States policies for funding nonreproductive cloning are justified and argues against that justification. I show that a common conceptual framework underlies the national prohibition on the use of public funds for cloning research, which I call the simple argument. This argument rests on two premises: that research harming human embryos is unethical and that embryos produced via fertilization are identical to those produced via cloning. In response to the simple argument, I challenge the latter (...) premise. I demonstrate there are important ontological differences between human embryos (produced via fertilization) and clone embryos (produced via cloning). After considering the implications my argument has for the morality of publicly funding cloning for potential therapeutic purposes and potential responses to my position, I conclude that such funding is not only ethically permissible, but also humane national policy. (shrink)

Calls for the “translation” of research from bench to bedside are increasingly demanding. What is translation, and why does it matter? We sketch the recent history of outcome-oriented translational research in the United States, with a particular focus on the Roadmap Initiative of the National Institutes of Health. Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice. We explore the nature of and obstacles to translational research and assess (...) the ethical and biomedical challenges of embracing a translational ethos. (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)

Calls for the “translation” of research from bench to bedside are increasingly demanding. What is translation, and why does it matter? We sketch the recent history of outcome-oriented translational research in the United States, with a particular focus on the Roadmap Initiative of the National Institutes of Health (Bethesda, MD). Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice. We explore the nature of and obstacles to translational research (...) and assess the ethical and biomedical challenges of embracing a translational ethos. (shrink)

The complexities of modern science are not adequately reflected in many bioethical discussions. This is especially problematic in highly contested cases where there is significant pressure to generate clinical applications fast, as in stem cell research. In those cases a more integrated approach to bioethics, which we call systems bioethics, can provide a useful framework to address ethical and policy issues. Much as systems biology brings together different experimental and methodological approaches in an integrative way, systems bioethics integrates aspects of (...) the history and philosophy of science, social and political theory, and normative analysis with the science in question. In this paper we outline how a careful analysis of the science of stem cell research can help to refocus the discussions related to the clinical applications of stem cells. We show how inaccurate or inadequate scientific assumptions help to create a set of unrealistic expectations and badly inform ethical deliberations and policy development. Systems bioethics offers resources for moving beyond the current impasse. (shrink)

This article explores the collaborative research of the Nobel laureate Hans Spemann (1869–1941) and the Swiss zoologist Fritz Baltzer (1884–1974) on problems at the intersection of development and heredity and raises more general questions concerning science and politics in Germany in the interwar period. It argues that Spemann and Baltzer’s collaborative work made a significant contribution to the then ongoing debates about the relation between developmental physiology and hereditary studies, although Spemann distanced himself from _Drosophila_ genetics because of his anti-reductionist (...) position. The article analyzes how Spemann framed the issues of heredity in terms of an epigenetic principle in the context of his work on the “organizer,” and it explores the experimental dynamics of research on newt merogones carried out by Baltzer in a methodological development of Spemann’s constriction experiments. Finally, these research attempts are discussed as part of a broader “prehistory” of the mid-twentieth century cell nuclear transplantation experiments, which provided the basis for later animal cloning. (shrink)

ABSTRACT. This paper contemplates Organicism and its relation with molecular and evolutionary biology. We explore whether twentieth-first century biology is returning to positions held at the beginning of the twentieth century and then abandoned. The guiding line is a history of theoretical biology in which we distinguish three periods: 1. The 20s-30s, and the Theoretical Biology Club (Needham, Woodger, and Waddington, among others); 2. An intermediate period in the 60s-70s, in which, in spite of the eclosion of the molecular and (...) evolutionary biologies, there is some recovery of organicist positions, and 3. The present post-genomic situation, which is demanding a systemic approach. (shrink)

The technique of nuclear transplantation – popularly known as cloning – has been integrated into several different histories of twentieth century biology. Historians and science scholars have situated nuclear transplantation within narratives of scientific practice, biotechnology, bioethics, biomedicine, and changing views of life. However, nuclear transplantation has never been the focus of analysis. In this article, I examine the development of nuclear transplantation techniques, focusing on the people, motivations, and institutions associated with the first successful nuclear transfer in metazoans in (...) 1952. The conflict between embryologists and geneticists over the mechanisms of differentiation motivated Robert Briggs to pursue nuclear transplantation experiments as a way to resolve the debate. Briggs worked at the Lankenau Hospital Research Institute, a research facility devoted to the study of cancer. The goal of understanding cancer would play a role in the development of the technique, and the story of nuclear transplantation sheds light on the role that biomedical contexts play in biological research in the second half of the twentieth century. (shrink)

“Incarnate reason” names, in Peter Dabrock's essay, both the task of utilizing natural reason in ethical and political discourse, and an answer to the ontological question about human persons, “What are we?” In this essay, I investigate the significance of this construal for questions about the metaphysical, moral, and political status of the human embryo.

Philosophers of science have often favoured reductive approaches to how-possibly explanation. This article identifies three alternative conceptions making how-possibly explanation an interesting phenomenon in its own right. The first variety approaches “how possibly X?” by showing that X is not epistemically impossible. This can sometimes be achieved by removing misunderstandings concerning the implications of one’s current belief system but involves characteristically a modification of this belief system so that acceptance of X does not result in contradiction. The second variety offers (...) a potential how-explanation of X. It is usually followed by a range of further potential how-explanations of the same phenomenon. In recent literature the factual claims implied by the second variety have been downplayed whereas the heuristic role of mapping the space of conceptual possibilities has been emphasized. I will focus especially on this truth-bracketing sense of potentiality when looking closer at the second variety in the paper. The third variety has attracted less interest. It presents a partial how-explanation of X. Typically it aims to establish the existence of a mechanism by which X could be and was generated. The third conception stands out as the natural alternative for the advocate of ontic how-possibly explanations. This article transfers Salmon’s view that explanation-concepts can be broadly divided into epistemic, modal, and ontic to the context of how-possibly explanations. Moreover, it is argued that each of the three above-mentioned varieties of how-possibly explanation occurs in science. To recognize this may be especially relevant for philosophers. We are often misled by the promises of various why-explanation accounts, and seem to have forgotten nearly everything about the diversity of how-possibly explanations. (shrink)

The phrase “regenerative medicine” is used so often and for so many different things, with such enthusiasm or worry, and often with a sense that this is something radically new. This paper places studies of regeneration and applications in regenerative medicine into historical perspective. In fact, the first stem cell experiment was carried out in 1907, and many important lines of research have contributed since. This paper explores both what we can learn about the history and what we can learn (...) from the history of regenerative medicine research. (shrink)

Biological development is about history, the history of an individual through time. Historically, the dominant epigenetic tradition has seen the developmental process as an unfolding of potential or in terms of the emergence of new organization that becomes an individual organism over time. The concept of development has included differentiation, growth, and morphogenesis; since the mid-nineteenth century, it has been seen in terms of cell division. Along the way have come explorations of such issues as the extent to which development (...) is driven by hereditary determination rather than flexible regulation in response to changing conditions. Some researchers have focused specifically on examining the capacity for regeneration in response to injury or loss, or on the extent to which parts are self-organizing individually rather than determined segments of a whole. This paper introduces the historical study of development. (shrink)

Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational (...) research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may—together with financial and organizational problems—be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the “translational imperative.”. (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)

In this chapter I investigate the prospects of integrated history and philosophy of science, by examining how philosophical issues raised by “hidden entities”, entities that are not accessible to unmediated observation, can enrich the historical investigation of their careers. Conversely, I suggest that the history of those entities has important lessons to teach to the philosophy of science. Hidden entities have played a crucial role in the development of the natural sciences. Despite their centrality to past scientific practice, however, several (...) of them (e.g., phlogiston, caloric, and the ether) turned out to be fictitious. For this reason, they have figured prominently in recent debates on scientific realism. The issues I explore in this paper are entangled with those debates. I argue that our understanding of hidden entities and their role in experimental practice can be enhanced by adopting an integrated historical-cum-philosophical approach. On the one hand, philosophical reflection on the reality of those entities has a lot to gain by examining historically how they were ntroduced and investigated. On the other hand, the historical reconstruction of the careers of those entities may profit from philosophical reflection on their existence. (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)

The case of embryo research provides insight into the challenges for historians and philosophers of science who want to engage social issues, and even more challenges in engaging society. Yet there are opportunities in doing so. History and philosophy of science research demonstrates that the public impression of embryos does not fit with our scientific understanding. In cases where there are competing understandings of the phenomena and public impacts, we have to negotiate social responses. Historians and philosophers of science can (...) both inform and learn from engaging in the process, by helping to recognize underlying assumptions and by demonstrating changing ideas over time and what factors have caused the changes. (shrink)

Making nuts-and-bolts public policy is not—and never has been—the long suit of professional historians, but general historical work, whatever its durée, has done a good deal to shape discourse on public issues. Jo Guldi and David Armitage neglect that fact, as well as the opinion-shaping influence of history conveyed via nonprint media. They also ignore the large body of scholarship produced in all media during recent decades in the history of science, technology, and science-related medicine (SciTech), even though SciTech itself (...) looms enormously large in the modern era as an instrument of national and international security, a driver of the economy, and a transformer of medicine, public health, and the environment. Much of this scholarship, even though of short durée, can illuminate salient contemporary issues, including innovation; patronage and practice; government and policy; imperialism and globalization; intellectual property; science and religion; and human rights, environment, energy, and disasters. (shrink)

Biophysics has been either an independent discipline or an element of another discipline in the United States, but it has always been recognized as a stand-alone discipline in the People’s Republic of China since 1949. To inquire into this apparent divergence, this paper investigates the formational history of biophysics in China by examining the early institutional history of one of the best-known and prestigious science and technology universities in the PRC, the University of Science and Technology of China. By showing (...) how the university and its biophysics program co-evolved with national priorities from the school’s founding in 1958 to the eve of the Cultural Revolution in 1966, the purpose of this paper is to assess the development of a scientific discipline in the context of national demands and institutional politics. Specific materials for analysis include the school’s admission policies, curricula, students’ dissertations, and research program. To further contextualize the institutional setting of Chinese biophysics, this paper begins with a general history of proto-biophysical institutions in China during the Nationalist-Communist transitional years. This paper could be of interest to historians wanting to know more about the origin of the biophysics profession in China, and in particular how research areas that constitute biophysics changed in tandem with socio-political contingencies. (shrink)

This paper explores how current United States policies for funding nonreproductive cloning are justified and argues against that justification. I show that a common conceptual framework underlies the national prohibition on the use of public funds for cloning research, which I call the simple argument. This argument rests on two premises: that research harming human embryos is unethical and that embryos produced via fertilization are identical to those produced via cloning. In response to the simple argument, I challenge the latter (...) premise. I demonstrate there are important ontological differences between human embryos (produced via fertilization) and clone embryos (produced via cloning). After considering the implications my argument has for the morality of publicly funding cloning for potential therapeutic purposes and potential responses to my position, I conclude that such funding is not only ethically permissible, but also humane national policy. (shrink)

DNA methylation is a quintessential epigenetic mechanism. Widely considered a stable regulator of gene silencing, it represents a form of “molecular braille,” chemically printed on DNA to regulate its structure and the expression of genetic information. However, there was a time when methyl groups simply existed in cells, mysteriously speckled across the cytosine building blocks of DNA. Why was the code of life chemically modified, apparently by “no accident of enzyme action” (Wyatt 1951 )? If all cells in a body (...) share the same genome sequence, how do they adopt unique functions and maintain stable developmental states? Do cells remember? In this historical perspective, I review epigenetic history and principles and the tools, key scientists, and concepts that brought us the synthesis and discovery of prokaryotic and eukaryotic methylated DNA. Drawing heavily on Gerard Wyatt’s observation of asymmetric levels of methylated DNA across species, as well as to a pair of visionary 1975 DNA methylation papers, 5-methylcytosine is connected to DNA methylating enzymes in bacteria, the maintenance of stable cellular states over development, and to the regulation of gene expression through protein-DNA binding. These works have not only shaped our views on heritability and gene regulation but also remind us that core epigenetic concepts emerged from the intrinsic requirement for epigenetic mechanisms to exist. Driven by observations across prokaryotic and eukaryotic worlds, epigenetic systems function to access and interpret genetic information across all forms of life. Collectively, these works offer many guiding principles for our epigenetic understanding for today, and for the next generation of epigenetic inquiry in a postgenomics world. (shrink)

In his 1987 book "Controlling Life: Jacques Loeb and the Engineering Ideal in Biology", Philip Pauly presented his readers with the biologist Jacques Loeb and his role in developing an emphasis on control of life processes. Loeb's work on artificial parthenogenesis, for example, provided an example of bioengineering at work. This paper revisits Pauly's study of Loeb and explores the way current research in regenerative medicine reflects the same tradition. A history of regeneration research reveals patterns of thinking and research (...) methods that both echo Loeb's ideology and point the way to modern studies. Pauly's work revealed far more than we readers realized at the time of its publication. (shrink)

These preprints were automatically compiled into a PDF from the collection of papers deposited in PhilSci-Archive in conjunction with the PSA 2012.

Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration. In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of regeneration (...) studies by looking in depth at Regeneration and evaluating Morgan’s contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan’s earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research. (shrink)

In the history of life sciences, it has often been argued that the individual organism emerged, around 1800, as a four-dimensional entity—a temporalized entity. Against this backdrop, the article asks how research on development contributed to structuring the time of the organism in terms of a historical process, that is, by understanding a given phenomenon as brought forth by what preceded it and as establishing conditions for what will follow, thus relating the past, the present and the future in a (...) specific way. To shed light on this conceptualization, we must take into account not only embryological research on morphogenesis but also physiological research on the genesis of vital functions and the causation of congenital anomalies. Three layers of structuring time in such research may be discerned: the making of a trans-natal continuity of the developing organism; a conceptualization of birth as a threshold of past and future that paradigmatically reveals the historical understanding of such developmental continuity; and an approach to intergenerational transmission that confronts developmental continuity with historical contingency. My contribution focuses on the work of William T. Preyer and Charles Féré but, in a genealogical vein, situates their work in the larger context of nineteenth-century research on development. (shrink)

It is useful on the occasion of the 21st anniversary of the ‘Cyborg Manifesto’ not only to reconsider its lessons in the context of what is frequently described as the re-engineering of ‘life itself’, but to look at Haraway’s earlier work on embryos. In this article I begin with Haraway’s analysis of embryology in the 1970s to suggest her cyborg embryo was already there, and has, if anything, gained relevance in today’s embryo-strewn society. I argue further, as the title suggests, (...) that the cyborg embryo has been crucial in defining our path to what I am calling here, building on Haraway’s notion of trans from Modest_Witness, ‘transbiology’ - broadly meaning stem cell research, cloning, tissue engineering and regenerative medicine. To illustrate this argument I draw on recent ethnographic fieldwork in a new stem cell derivation facility in the UK built adjacent to an IVF surgery. Using this example, I explore the important and paradoxical role of IVF in the emergence of stem cell science, cloning and transbiology, suggesting that Haraway’s analysis remains crucial to understanding the ironic and contradictory, and unexpectedly generative, circumstances through which the IVF-stem cell interface - the door to transbiology - came into being. (shrink)

This paper aims to bring the epistemic dimensions of stem cell experiments out of the background, and show that they can be critically evaluated. After introducing some basic concepts of stem cell biology, I set out the current “gold standard” for experimental success in that field (§2). I then trace the origin of this standard to a 1988 controversy over blood stem cells (§3). Understanding the outcome of this controversy requires attention to the details of experimental techniques, the organization of (...) epistemic communities, and relations between the two (§4). With its resolution, a standard for experimental success was established for HSC research, which in turn serves as an exemplar for studies of other stem cells. This historical case study reveals a robust standard for experimental success in stem cell biology: to trace processes of development at the single-cell level, in the form of cell lineage hierarchies. Experiments conforming to this standard can be further critically assessed as means to the therapeutic end of stem cell research: use of stem cells to repair human organs and tissues. (shrink)