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 Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice.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)

Two decades of critique have sensitized historians and philosophers of science to the inadequacies of conventional dichotomies between theory and practice, thereby prompting the search for new ways of writing about science that are less beholden than the old ways to the epistemological mores of theoretical physics, and more faithful to the actual practices not only of physics but of all the natural sciences. The need for alternative descriptions seems particularly urgent if one is to understand the place of theory (...) (and, in parallel, the role of modeling) in contemporary molecular biology, a science where, until now, no division between theory and experiment has obtained, and where distinctions between representing and intervening, and more generally, between basic and applied science, are daily becoming more blurred. Indeed, the very division between theory and experiment threatens to slight the extensive and sophisticated theoretical analyses (and even modeling) on which experimental work in contemporary molecular biology so often depends. My aim in this paper is to find a way of talking about theoretical practices in biology that is directly rooted in the mix of conceptual and material work that biologists do. As an example of such theoretical practices, I choose for the focus of my analysis the development of a model for gene regulation out of the experimental work of Eric Davidson and his colleagues at Cal Tech. (shrink)

Stem cell scientists and ethicists have focused intently on questions relevant to the developmental stage and developmental capacities of stem cells. Comparably less attention has been paid to an equally important set of questions about the nature of stem cells, their common characteristics, their non‐negligible differences and their possible developmental species specificity. Answers to these questions are essential to the project of justly inferring anything about human stem cell biology from studies in non‐human model systems—and so to the possibility of (...) eventually developing human therapies based on stem cell biology. After introducing and discussing these questions, I conclude with a brief discussion of the creation of novel model systems in stem cell biology: human‐to‐animal embryonic chimeras. Such novel model systems may help to overcome obstacles to extrapolation, but they are also scientifically and ethically contentious. BioEssays 26:1005‐1012, 2004. © 2004 Wiley Periodicals, Inc. (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)

The biological sciences have become increasingly reliant on so-called 'model organisms'. I argue that in this domain, the concept of a descriptive model is essential for understanding scientific practice. Using a case study, I show how such a model was formulated in a preexplanatory context for subsequent use as a prototype from which explanations ultimately may be generated both within the immediate domain of the original model and in additional, related domains. To develop this concept of a descriptive model, I (...) focus on use of the nematode worm Caenorhabditis elegans and the wiring diagrams that were developed as models of its neural structure. In addition, implications of the concept of a descriptive model, particularly its relevance for the data-phenomena distinction as well as its relation to long-standing debates on realism, are briefly examined. (shrink)

Genesis: The Evolution of Biology presents a history of the past two centuries of biology, suitable for use in courses, but of interest more broadly to evolutionary biologists, geneticists, and biomedical scientists, as well as general readers interested in the history of science. The book covers the early evolutionary biologists-Lamarck, Cuvier, Darwin and Wallace through Mayr and the neodarwinian synthesis, in much the same way as other histories of evolution have done, bringing in also the social implications, the struggles with (...) our religious understanding, and the interweaving of genetics into evolutionary theory. What is novel about Sapp's account is a real integration of the cytological tradition, from Schwann, Boveri, and the other early cell biologists and embryologists, and the coverage of symbiosis, microbial evolutionary phylogenies, and the new understanding of the diversification of life coming from comparative analyses of complete microbial genomes. The book is a history of theories about evolution, genes and organisms from Lamarck and Darwin to the present day. This is the first book on the general history of evolutionary biology to include the history of research and theories about symbiosis in evolution, and first to include research on microbial evolution which were excluded from the classical neo-Darwinian synthesis. Bacterial evolution, and symbiosis in evolution are also excluded from virtually every book on the history of biology. (shrink)

This paper emphasizes the crucial role of variation, at several different levels, for a detailed historical understanding of the development of the biomedical sciences. Going beyond valuable recent studies that focus on model organisms, experimental systems and instruments, we argue that all of these categories can be accommodated within our approach, which pays special attention to organismal and cultural variation. Our empirical examples are drawn in particular from recent historical studies of nineteenth- and early twentieth-century genetics and physiology. Based on (...) the quasi-paradoxical conclusion that biological and cultural variation both constrains and enables innovation in the biomedical sciences, we argue that more attention should be paid to variation as an analytical category in the historiography of the life sciences. (shrink)

Through an examination of the actual research strategies and assumptions underlying the Human Genome Project (HGP), it is argued that the epistemic basis of the initial model organism programs is not best understood as reasoning via causal analog models (CAMs). In order to answer a series of questions about what is being modeled and what claims about the models are warranted, a descriptive epistemological method is employed that uses historical techniques to develop detailed accounts which, in turn, help to reveal (...) forms of reasoning that are explicit, or more often implicit, in the practice of a particular field of scientific study. It is suggested that a more valid characterization of the reasoning structure at work here is a form of case-based reasoning. This conceptualization of the role of model organisms can guide our understanding and assessment of these research programs, their knowledge claims and progress, and their limitations, as well as how we educate the public about this type of biomedical research. (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)

In this paper we argue that an operational organism concept can help to overcome the structural deficiency of mathematical models in biology. In our opinion, the structural deficiency of mathematical models lies mainly in our inability to identify functionally relevant biological characters in biological systems, and not so much in a lack of adequate mathematical representations of biological processes. We argue that the problem of character identification in biological systems is linked to the question of a properly formulated organism concept. (...) Lastly, we demonstrate how a decomposition of an organism into independent characters in the context of a specific biological process--such as adaptation by means of natural selection--depends on the dynamical properties and invariance conditions of the equations that describe this process. (shrink)

The practical criteria by which developmental biologists choose their model systems have evolutionary correlates. The result is a sample that is not merely small, but biased in particular ways, for example towards species with rapid, highly canalized development. These biases influence both data collection and interpretation, and our views of how development works and which aspects of it are important.

A case-study of the interaction between philosophical context and observational data in the practice of Science.