Rachel Allyson Ankeny

The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project. They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the “community” of C. elegans researchers, and were introduced and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner’s proposal for a nematode research program at the Laboratory of Molecular Biology at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology.

Prior to the genomic sequencing era, the bible for those working in clinical genetics was McKusick’s Mendelian Inheritance in Man, which appeared in multiple editions between the 1960s and the late 1990s. This catalogue was organized according to general patterns of inheritance and focused on phenotypes. Beginning in the mid-1980s, it was replaced by Online Mendelian Inheritance in Man, a continuously updated catalogue documenting molecular relationships between genetic variation and phenotypic expression. This paper explores this resource’s evolution with attention to how disease is distinguished from clinically irrelevant variation and how phenotypic similarities are captured in cases where there is no obvious genotypic association. It is argued that hybrid compromises are encoded into OMIM®; in addition to serving its key original purpose of being a diagnostic catalogue, it also began to record detectable variations in the genome even if they were not known to be associated with phenotypically visible disorders or even phenotypic variations. Although the impacts of geneticization have been well recognized, particularly in popular media, this example allows exploration of some of the historic, epistemic, and methodological causes that underlie tendencies toward disease geneticization in contemporary medicine, while highlighting that such gene-focused strategies may in fact be warranted in some contexts.

Is inheritable genetic modification the new dividing line in gene therapy? The editors of this searching investigation, representing clinical medicine, public health and biomedical ethics, have established a distinguished team of scientists and scholars to address the issues from the perspectives of biological and social science, law and ethics, including an intriguing Foreword from Peter Singer. Their purpose is to consider how society might deal with the ethical concerns raised by inheritable genetic modification, and to re-examine prevailing views about whether these procedures will ever be ethically and socially justifiable. The book also provides background to define the field, and discusses the biological and technological potential for inheritable genetic modification, its limitations, and its connection with gene therapy, cloning, and other reproductive interventions. For scientists, bioethicists, clinicians, counsellors and public commentators, this is an essential contribution to one of the critical debates in current genetics.

The moral importance of the ‘intention–foresight’ distinction has long been a matter of philosophical controversy, particularly in the context of end-of-life care. Previous empirical research in Australia has suggested that general physicians and surgeons may use analgesic or sedative infusions with ambiguous intentions, their actions sometimes approximating ‘slow euthanasia’. In this paper, we report findings from a qualitative study of 18 Australian palliative care medical specialists, using in-depth interviews to address the use of sedation at the end of life. The majority of subjects were agnostic or atheistic. In contrast to their colleagues in acute medical practice, these Australian palliative care specialists were almost unanimously committed to distinguishing their actions from euthanasia. This commitment appeared to arise principally from the need to maintain a clear professional role, and not obviously from an ideological opposition to euthanasia. While some respondents acknowledged that there are difficult cases that require considered reflection upon one's intention, and where there may be some ‘mental gymnastics,’ the nearly unanimous view was that it is important, even in these difficult cases, to cultivate an intention that focuses exclusively on the relief of symptoms. We present four narratives of ‘terminal’ sedation – cases where sedation was administered in significant doses just before death, and may well have hastened death. Considerable ambiguities of intention were evident in some instances, but the discussion around these clearly exceptional cases illustrates the importance of intention to palliative care specialists in maintaining their professional roles

I’m sick of being treated like a dumb Mum who doesn’t understand the science. As far as I’m concerned, my family’s health is just too important. … If the government can’t protect the safety of my family, then I will.Recent Greenpeace activism in Australia resulted in the destruction of a field trial of a line of wheat “designed” to improve human nutrition. This incident demonstrates that, while there is significant ongoing public and private investment in genetically modified crop research and development in Australia, many people continue to oppose GM foods strongly. We noted with interest that Greenpeace described this activism with language that explicitly connected the actions to the gender..

The past year in bioethics in Australia has been relatively predictable. We continue to struggle with rising healthcare costs, though thankfully not on par with numerous other countries due to a relatively positive economic outlook. We are still fighting difficulties associated with higher medical indemnity costs, which have again caused many physicians to leave private practice, particularly in high-risk and specialty practice areas. In response, the federal government delayed the imposition of the medical indemnity levy for physicians until mid 2005. In May, the Australian Law Reform Commission and the Australian Health Ethics Commission issued their final joint report on genetic testing entitled “Essentially Yours” and endorsed use of genetic tests by insurance companies, despite the concerns of some geneticists and many members of the public about their scientific reliability. However, they also advocated the establishment of the Human Genetics Commission of Australia to oversee such uses of genetic tests in terms of both scientific and actuarial reliability, and debates continue over the implementation of this and a number of their other recommendations. And state governments continue to phase in smoking bans in public places, with most implementing full bans in enclosed restaurants and cafes and planning to require provision of nonsmoking areas in all pubs within the next year. a

Although cases are central to the epistemic practices utilized within clinical medicine, they appear to be limited in their ability to provide evidence about causal relations because they provide detailed accounts of particular patients without explicit filtering of those attributes most likely to be relevant for explaining the phenomena observed. This paper uses a series of recent case reports to explore the role of cases in casual attribution in medical diagnosis. It is argued that cases are brought together by practitioners to generate causal attributions and testable predictions using a manipulability view of causation

Human embryonic stem cell research has generated considerable discussion and debate in bioethics. Bioethical discourse tends to focus on the moral status of the embryo as the central issue, however, and it is unclear how much this reflects broader community values and beliefs related to stem cell research. This paper presents the results of a study which aims to identify and classify the issues and arguments that have arisen in public discourse associated with one prominent policy episode in the United States: the 2004 Californian Stem Cell Research and Cures Initiative. The findings show that public discourse about Proposition 71 is characterised by a broader range of issues than those usually addressed in scholarly publications and public policy documents. While attention to the moral status of the embryo is an important issue in stem cell research, making it the main focus of public discourse has a polarising effect. This also limits opportunities to identify shared values, understand how political alliances are forged, and develop social consensus. Implications for future research and policy are discussed

The so-called "biometric-Mendelian controversy" has received much attention from science studies scholars. This paper focuses on one scientist involved in this debate, Arthur Dukinfield Darbishire, who performed a series of hybridization experiments with mice beginning in 1901. Previous historical work on Darbishire's experiments and his later attempt to reconcile Mendelian and biometric views describe Darbishire as eventually being "converted" to Mendelism. I provide a new analysis of this episode in the context of Darbishire's experimental results, his underlying epistemology, and his influence on the broader debate surrounding the rediscovery and acceptance of Mendelism. I investigate various historiographical issues raised by this episode in order to reflect on the idea of "conversion" to a scientific theory. Darbishire was an influential figure who resisted strong forces compelling him to convert prematurely due to his requirements that the new theory account for particularly important anomalous facts and answer the most pressing questions in the field.

This article unpacks a particular use of ‘cases’ within developmental biology, namely as a means of describing the typical or canonical patterns of phenomena. The article explores how certain cases have come to be established within the field and argues that although they were initially selected for reasons of convenience or ease of experimental manipulation, these cases come to serve as key reference points within the field because of the epistemological structures imposed on them by the scientists using them and, hence, become usable in a wider variety of circumstances including future theory development.

Debates continue to surround the system in the United States for allocating transplantable cadaveric organs, due in large part to the scarcity of such organs in relation to the number of individuals waiting to undergo transplantation. Candidates awaiting transplantation gain access to cadaveric organs by being placed by individual transplant programs on the national list of the Organ Procurement and Transplantation Network, overseen by the United Network for Organ Sharing. In recent years, the UNOS board has visited the issue of multiple listing, that is, allowing one candidate to be registered on the waiting lists of two or more transplant programs, and has continued to permit multiple listing

In an article somewhat ironically entitled “Disambiguating Clinical Intentions,” Lynn Jansen promotes an idea that should be bewildering to anyone familiar with the literature on the intention/foresight distinction. According to Jansen, “intention” has two commonsense meanings, one of which is equivalent to “foresight.” Consequently, questions about intention are “infected” with ambiguity—people cannot tell what they mean and do not know how to answer them. This hypothesis is unsupported by evidence, but Jansen states it as if it were accepted fact. In this reply, we make explicit the multiple misrepresentations she has employed to make her hypothesis seem plausible. We also point out the ways in which it defies common sense. In particular, Jansen applies her thesis only to recent empirical research on the intentions of doctors, totally ignoring the widespread confusion that her assertion would imply in everyday life, in law, and indeed in religious and philosophical writings concerning the intention/foresight distinction and the Principle of Double Effect

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