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 Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice.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

To explain the phenomena in the world of our experience, to answer the question “why?” rather than only the question “what?”, is one of the foremost objectives of all rational inquiry; and especially, scientific research in its various branches strives to go beyond a mere description of its subject matter by providing an explanation of the phenomena it investigates. While there is rather general agreement about this chief objective of science, there exists considerable difference of opinion as to the function (...) and the essential characteristics of scientific explanation. In the present essay, an attempt will be made to shed some light on these issues by means of an elementary survey of the basic pattern of scientific explanation and a subsequent more rigorous analysis of the concept of law and of the logical structure of explanatory arguments. (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)

In summary, the creation and maintenance of the Wistar Rats as standardized animals can be attributed to the breeding work of Helen Dean King, coupled with the management and husbandry methods of Milton Greenman and Louise Duhring, and with supporting documentation provided by Henry Donaldson. The widespread use of the Wistar Rats, however, is a function of the ingenuity of Milton Greenman who saw in them a way for a small institution to provide service to science. Greenman's rhetoric, as captured (...) in his Director's Reports, prepared annually from 1905 until his death in 1937, shows that he was unusually sensitive to his times and to the economics of science and of society. In the era when biology was being defined, he recognized in the rat the potential to be a living analog to the pure chemicals that legitimated experimental science. From management literature he extracted the ideals of uniformity of product, standards of quality, and efficiency of production, applying them to scientific practice to generate an animal model that thrives as standard equipment in laboratories throughout the world today.I will close with a quote from Frederick W. Taylor that is a cogent statement of the contribution to science and scientific progress made by standardized tools and their creators. Equating the surgeon and the workman, Taylor wrote: [He is given] the finest implements, each one of which has been the subject of special study and development ... [and] the very best knowledge of his predecessors; and, provided with standard implements and methods which represent the best knowledge of the world up to date, he is able to use his own originality and ingenuity to make real additions to the world's knowledge, instead of reinventing things which are old.Standardized tools, whether surgeons' implements or laboratory-bred rats, are one of the vehicles for carrying scientific knowledge forward from generation to generation. In this sense, Greenman's Wistar Rats have done their job, in his words, of “providing service to science.”. (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.

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and representational target. We also examine (...) the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models.Keywords: Experimental organism; Genetics; Model organism; Modeling; Philosophy of biology; Representation. (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)

Through an examination of the actual research strategies and assumptions underlying the Human Genome Project, it is argued that the epistemic basis of the initial model organism programs is not best understood as reasoning via causal analog models. 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 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)