Rebecca L. Walker

Looking for Trouble: Preventive Genomic Sequencing in the General Population and the Role of Patient Choice

Advances in genomics have led to calls for developing population-based preventive genomic sequencing (PGS) programs with the goal of identifying genetic health risks in adults without known risk factors. One critical issue for minimizing the harms and maximizing the benefits of PGS is determining the kind and degree of control individuals should have over the generation, use, and handling of their genomic information. In this article we examine whether PGS programs should offer individuals the opportunity to selectively opt out of the sequencing or analysis of specific genomic conditions (the menu approach) or whether PGS should be implemented using an all-or-nothing panel approach. We conclude that any responsible scale-up of PGS will require a menu approach that may seem impractical to some, but that draws its justification from a rich mix of normative, legal, and practical considerations.

Bioethics Methods in the Ethical, Legal, and Social Implications of the Human Genome Project Literature

While bioethics as a field has concerned itself with methodological issues since the early years, there has been no systematic examination of how ethics is incorporated into research on the Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. Yet ELSI research may bear a particular burden of investigating and substantiating its methods given public funding, an explicitly cross-disciplinary approach, and the perceived significance of adequate responsiveness to advances in genomics. We undertook a qualitative content analysis of a sample of ELSI publications appearing between 2003 and 2008 with the aim of better understanding the methods, aims, and approaches to ethics that ELSI researchers employ. We found that the aims of ethics within ELSI are largely prescriptive and address multiple groups. We also found that the bioethics methods used in the ELSI literature are both diverse between publications and multiple within publications, but are usually not themselves discussed or employed as suggested by bioethics method proponents. Ethics in ELSI is also sometimes undistinguished from related inquiries (such as social, legal, or political investigations).

Charting ELSI's future course: lessons from the recent past

Purpose:We sought to examine the ethical, legal, and social implications (ELSI) literature research and scholarship types, topics, and contributing community fields of training as a first step to charting the broader ELSI community’s future priorities and goals.Methods:We categorized 642 articles and book chapters meeting inclusion criteria for content in both human genetics or genomics and ethics or ELSI during a 5-year period (2003–2008) according to research and scholarship types, topics, and the area of advanced training of the first-listed author. Research and scholarship type categories were developed and characterized through in-depth review of 95 randomly sampled publications from the larger group.Results:There is a single dominant approach to ELSI, which focuses on ethical and other social issues “downstream” of advances in genomics, the contributors to which predominately have advanced training in medicine or science fields other than social science. A comparatively low percentage of publications primarily offer policy recommendations, and these are much more likely to be written by those with advanced training in law than is the case for the literature as a whole. Social science studies predominately employ qualitative methods and vary significantly with respect to the extent and types of recommendations offered. Two further types of ELSI research and scholarship offer alternative models for so-called “normative” work in this field.Conclusion:Considering topics, training, and types of ELSI research and scholarship from the most recent past allows for a baseline perspective that is sorely needed in charting this field’s future course.Genet Med 2012:14(2):259–267

Funding and Forums for ELSI Research: Who (or What) Is Setting the Agenda?

Background: Discussion of the influence of money on bioethics research seems particularly salient in the context of research on the ethical, legal, and social implications (ELSI) of human genomics, as this research may be financially supported by the ELSI Research Program. Empirical evidence regarding the funding of ELSI research and where such research is disseminated, in relation to the specific topics of the research and methods used, can help to further discussions regarding the appropriate influence of specific institutions and institutional contexts on ELSI and other bioethics research agendas. Methods: We reviewed 642 ELSI publications (appearing between 2003 and 2008) for reported sources of funding, forum for dissemination, empirical and nonempirical methods, and topics of investigation. Results: Most ELSI research is independent of direct grant-based funding sources; 66% reported no such sources of funding. The National Human Genome Research Institute (NHGRI) is the most dominant source of funding; 16% of publications acknowledged at least one source of NHGRI grant funding. Funding is acknowledged more frequently in empirical than nonempirical publications and more frequently in publications in public health journals than in any other ELSI research dissemination forums. Dominant research topics vary by publication forum and by reported funding. Conclusions: ELSI research is surprisingly independent of direct grant-based funding, yet correlations are apparent between this type of funding and publication placement, topics addressed, and methods used, implying a not insignificant influence on ELSI research agenda setting. However, given the relatively low percentage of publications acknowledging external grant-based funding, as well as other significant correlations between publication placement and topics addressed, additional institutional contexts, perhaps related to professional advancement or valuation, may shape research agendas in ways that potentially exceed the direct influences of grant-based funding in this area. In some cases, grant-based funding may actually counter other potentially problematic institutional influences.

Respect for rational autonomy.

The standard notion of autonomy in medical ethics does not require that autonomous choices not be irrational. The paper gives three examples of seemingly irrational patient choices and discusses how a rational autonomy analysis differs from the standard view. It then considers whether a switch to the rational autonomy view would lead to overriding more patient decisions but concludes that this should not be the case. Rather, a determination of whether individual patient decisions are autonomous is much less relevant than usually considered in determining whether health care providers must abide by these decisions. Furthermore, respect for rational autonomy entails strong positive requirements of respect for the autonomy of the person as a rational decision maker. The rationality view of autonomy is conceptually stronger than the standard view, allows for a more nuanced understanding of the practical moral calculus involved in respecting patient autonomy, and promotes positive respect for patient autonomy.

Serial Participation and the Ethics of Phase 1 Healthy Volunteer Research

Phase 1 healthy volunteer clinical trials-which financially compensate subjects in tests of drug toxicity levels and side effects-appear to place pressure on each joint of the moral framework justifying research. In this article, we review concerns about phase 1 trials as they have been framed in the bioethics literature, including undue inducement and coercion, unjust exploitation, and worries about compromised data validity. We then revisit these concerns in light of the lived experiences of serial participants who are income-dependent on phase 1 trials. We show how participant experiences shift attention from discrete exchanges, behaviors, and events in the research enterprise to the ongoing and dynamic patterns of serial participation in which individual decision-making is embedded in collective social and economic conditions and shaped by institutional policies. We argue in particular for the ethical significance of structurally diminished voluntariness, routine powerlessness in setting the terms of exchange, and incentive structures that may promote pharmaceutical interests but encourage phase 1 healthy volunteers to skirt important rules.

Genomic Research with the Newly Dead: A Crossroads for Ethics and Policy

Recent advances in next generation sequencing along with high hopes for genomic medicine have inspired interest in genomic research with the newly dead. However, applicable law does not adequately determine ethical or policy responses to such research. In this paper we propose that such research stands at a crossroads between other more established biomedical clinical and research practices. In addressing the ethical and policy issues raised by a particular research project within our institution comparatively with these other practices, we illustrate the moral significance of paying careful heed to where one looks for guidance in responding to ethical questions raised by a novel endeavor.

The Ethics of General Population Preventive Genomic Sequencing: Rights and Social Justice

Advances in DNA sequencing technology open new possibilities for public health genomics, especially in the form of general population preventive genomic sequencing (PGS). Such screening programs would sit at the intersection of public health and preventive health care, and thereby at once invite and resist the use of clinical ethics and public health ethics frameworks. Despite their differences, these ethics frameworks traditionally share a central concern for individual rights. We examine two putative individual rights-the right not to know, and the childs right to an open future-frequently invoked in discussions of predictive genetic testing, in order to explore their potential contribution to evaluating this new practice. Ultimately, we conclude that traditional clinical and public health ethics frameworks, and these two rights in particular, should be complemented by a social justice perspective in order adequately to characterize the ethical dimensions of general population PGS programs.

Professionalism and ethics in animal research

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Confidentiality: Concealing “Things Shameful to be Spoken About”

A requirement to uphold the confidentiality of information shared in the physician-patient relationship is a central tenet of medical professionalism that, while at risk and undermined in various ways in modern medicine, has been consistently endorsed from the time of Hippocrates.