Rachel Allyson Ankeny

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 Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice.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

This study focuses on the concept of a 'model organism' in the biomedical sciences through an historical and philosophical examination of research with the nematode Caenorhabditis elegans. I explore the choice of C. elegans in the mid-1960s, showing a rich context existed within which the organism was selected as the focus for a molecular biological research program, including an experimental life prior to Sydney Brenner's work. I argue that this choice can be seen as an obvious outcome of what was a complex search procedure, and that the success of the 'worm project' depended not only on organismal choice but also on the conceptual and institutional framework at the Laboratory of Molecular Biology in Cambridge within which it was pursued. Examination of C. elegans work in the late 1960s through the early 1980s illuminates several additional theses. Although development and behavior were the general areas of interest for the project, the original goals and proposed methodology were extremely vague. As the project evolved, which investigations proved to be tractable using the worm depended not only on which methodologies were fruitful but also on the interests and skills of early workers. Much of the power of C. elegans as a model organism can be traced historically to the investment of resources which resulted in an unprecedented, complete description of the organism, and represented a return to a more naturalistic biological tradition. In light of the historical study, I develop a philosophical analysis of C. elegans as a model organism through exploration of the three kinds of modeling with the worm: modeling of structures, processes, and information. I expand the notion of a descriptive model, arguing that C. elegans is best understood as a prototype of the metazoa, and that C. elegans as a model organism has been not only heuristically valuable, but also essential to this research project particularly in its pre-explanatory stages. I conclude by suggesting that more investigation of descriptive prototypes such as those in the worm project must be done to capture important aspects of the biomedical sciences that will be neglected if explanatory models are the sole focus in the philosophy of science

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

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

Bioethics has entered a new era: as many commentators have noted, the familiar mantra of autonomy, beneficence, nonmaleficence, and justice has proven to be an overly simplistic framework for understanding problems that arise in modern medicine, particularly at the intersection of public policy and individual preferences. A tradition of liberal pluralism grounds respect for individual preferences and affirmation of competing conceptions of the good. But we struggle to maintain (or at times explicitly reject) this tradition in the face of individual preferences that we find distasteful, suspect, or even repugnant, especially where the broader social good or respect for equality is at stake. Directed donation presents us with such a dilemma: can we uphold the right of self-determination through respect of individual preferences regarding disposition of transplantable organs while at the same time maintaining an allocation system that reflects values of equity and justice claimed to underlie the socially negotiated practice of transplantation? Or are some preferences simply to be deemed unethical and not respected, even if that leads to a reduction in the number of transplantable organs available and to an apparent disregard for the autonomous decisions of the recently deceased?

There has been much debate regarding the 'double-effect' of sedatives and analgesics administered at the end-of-life, and the possibility that health professionals using these drugs are performing 'slow euthanasia.' On the one hand analgesics and sedatives can do much to relieve suffering in the terminally ill. On the other hand, they can hasten death. According to a standard view, the administration of analgesics and sedatives amounts to euthanasia when the drugs are given with an intention to hasten death. In this paper we report a small qualitative study based on interviews with 8 Australian general physicians regarding their understanding of intention in the context of questions about voluntary euthanasia, assisted suicide and particularly the use of analgesic and sedative infusions (including the possibility of voluntary or non-voluntary 'slow euthanasia'). We found a striking ambiguity and uncertainty regarding intentions amongst doctors interviewed. Some were explicit in describing a 'grey' area between palliation and euthanasia, or a continuum between the two. Not one of the respondents was consistent in distinguishing between a foreseen death and an intended death. A major theme was that 'slow euthanasia' may be more psychologically acceptable to doctors than active voluntary euthanasia by bolus injection, partly because the former would usually only result in a small loss of 'time' for patients already very close to death, but also because of the desirable ambiguities surrounding causation and intention when an infusion of analgesics and sedatives is used. The empirical and philosophical implications of these findings are discussed.