ELSI Publications and Products Database

Duke's Center for the Study of Public Genomics will gather and analyze information about the role of publication, data sharing, materials-sharing, patenting, database protection, and other practices that affect information flow in genomics research and development. Managing intellectual property and ensuring the preservation of a robust "scientific commons" could prove as difficult as or more so than the science and technology, and could have as large of an impact on what results are produced, who has access to them, and how fairly they are distributed. These are deeply ethical questions, highly dependent on policy decisions in government and the private sector. Intellectual property is new to the ELSI scene, but it is here to stay. The Center will combine qualitative and quantitative research and analysis involving Duke Arts & Sciences, the Medical School, Law School, Fuqua Business School, Sanford Institute for Public Policy, as well as the DNA Patent Database at Georgetown University. The Center builds on structures designed to enable collaborative research at Duke and with external organizations. The Center will bring together economists, legal scholars, molecular biologists, computational biologists, philosophers, English professors, and others. It will combine research training with Center research activity. The pervasiveness, importance, complexity, uncertainty, and persistence of concerns about the role of intellectual property will be addressed in four research projects, supported by four cores. The projects are: —> case histories, including intellectual property landscapes of seminal genomic technologies and data sharing practices (DNA sequencing and microarray technologies, data-release and data-sharing practices); —> models of open and collaborative production in genomics research and development; —> intellectual property protection of databases and alternative regimes to reconcile public science with the commercialization of research results; and —> empirical analysis of information flow in genomics based on a pilot survey.

The proposed study, Project LeARN (Learning About Research in North Carolina), will build on a series of well established population based studies of the genetic, environmental and behavioral predictors of colorectal cancer among African American and white cases and controls, the North Carolina Colorectal Cancer Study (NCCCS), to understand participants' views of genetic variation research. Project LEARN contains both a longitudinal component to assess change in beliefs about causality as a result of participation in NCCCS, and a cross-sectional component to examine NCCCS participants' motivations, assessment of positives and negatives and understanding of genetic variation research. The proposed study will survey 832 NCCCS study participants with the following specific aims, to describe: 1) NCCCS participants' perceptions of causality of colorectal cancer and how perceptions of causality of colorectal cancer change after participation in the NCCCS determinants of colorectal cancer interview; 2) what motivates research participants to participate in the NCCCS study; 3) NCCCS participants' perceptions of positives and negatives related to collecting genetic data in epidemiologic research; and 4) how NCCCS research participants understand the purpose of the NCCCS research. All aims will be examined for differences by disease status and race/ethnicity.

This project involves the research and writing of a history of modern prenatal diagnosis. Recent scholarly work in the history of science, technology, and medicine will provide the conceptual perspectives for the work. Resources to be used include the professional literatures of medicine, genetic counseling, bioethics, genetics, and medical administration; the popular literature of medical advice to the general public; the literature of the women's health movement; published legal records; archival records; and the secondary literature on the abortion controversy and on the women's movement since 1950. The book which will result from this research will be intended for a general audience of intelligent readers -- and will, hopefully, demonstrate the way in which historical research and analysis can be fruitfully brought to bear in making social and moral decisions.

The policies of academic health centers (AHCs) for human subjects protection in the collection, storage, use, and sharing of biospecimens and associated data (i.e., biobanking) will have significant effects on the country's capacity to advance genetic science through collaborative multi-institutional research. Variation in policies for core issues such as informed consent to obtain biospecimens and sharing biospecimens and/or data across institutions can impede or prevent collaborative research. Our preliminary data suggest that this is already occurring. These issues are particularly timely for the NIH's Clinical and Translational Science Awards (CTSA) program, in which AHCs are expected to act as a consortium and collaborate on research. Despite their importance, systematic information on institutional policies is lacking, as is an understanding of the views of key AHC stakeholders about these issues. To address these deficiencies, we propose to: (1) Define the range and variation of policies and practices among CTSA institutions for human subjects protection in biobanking - with emphasis on informed consent and biospecimen/data sharing; (2) Deter- mine the attitudes of stakeholder groups at CTSA institutions (including IRB chairs, CTSA Ethics Directors, investigators) about specific feasible policy options to address barriers to collaboration; and (3) Analyze, through an interdisciplinary process, the ethical and regulatory issues that frame policies on informed consent and sharing biospecimens/datasets across institutions, as well as develop a set of policy recommendations. To accomplish these goals, we will use rigorous analyses of written policies, surveys with structured questionnaires, semi-structured interviews, and an established consensus development process to address specific policy issues on consent and biospecimen/data sharing. Our multidisciplinary research team has complementary strengths. We have an outstanding expert advisory group and robust linkages with CTSA institutions. The preliminary data strongly support the feasibility of our plans; moreover, they suggest substantial inter-institutional policy differences that stakeholders see as barriers to collaboration. The results will be disseminated broadly and include:1) empirically and conceptually based analyses in scholarly journals and 2) practical policy recommendations (developed with the advisory group, CTSA stakeholders, and other authorities) that facilitate ethically sound, collaborative, multi-institutional genetic research. We believe this project will have high impact. It directly addresses an important problem and barrier to progress toward the ultimate goal of using genomic information to improve human health. It responds directly to ELSI priorities and NIH roadmap goals. Moreover, the findings will provide knowledge that improves our capacity to advance multi-institutional studies, and the results are likely to influence concepts and methods in clinical and translational genetic research. PUBLIC HEALTH RELEVANCE: Collaborative multi-institutional genetic research is pivotal to advancing genetic science, and often involves use of biospecimens contributed by human subjects and stored in repositories (biobanks) - but variation in institutions' policies for human subjects protection in biobanking can impede or prevent such research. This project will provide new knowledge on institutional policies and attitudes of key stakeholders, and will provide policy recommendations that facilitate ethically sound advancement of collaborative genetic research. The project therefore addresses an important problem and barrier to progress toward the goal of using genomic information to improve human health.

Project Summary The breakneck pace of development towards potential uses of germline gene editing (GGE) in medicine raises some very crucial ethical questions. Though much research still needs to be done before GGE will be safe for use on humans, the technology has progressed very rapidly over the past few years. Among the most pressing of the ethical issues raised by GGE are those concerning human subjects research. Future clinical trials will confront novel ethical conundrums that are difficult to resolve given current guidelines. The most difficult of these conundrums are those concerning intergenerational monitoring “ long-term follow-up study not just of the original subjects, but also of their children and grandchildren. Numerous scientists, advisory panels, and professional associations have stated that such study will be necessary. There is currently little precedent in research ethics for the kind of intergenerational monitoring required here, and no precedent for the specific challenges posed by GGE. If future clinical trials are going to meet requirements of ethical research, the difficult issues raised by intergenerational monitoring must be resolved. This project will make an initial start on designing intergenerational monitoring protocols for future clinical trials of GGE. Drawing on prior work in clinical research ethics and the broader literature on the ethical, social, legal, and philosophical dimensions of GGE, the project will examine this unique set of ethical issues and apply these insights to the design of future clinical trials. The ultimate aim of the project will be to help advance research into the uses of GGE in medicine by dealing with a set of crucial barriers to future applications. In so doing, this project will contribute to the role of NHGRI and the ELSI program in providing leadership and guidance on the ethics of GGE in medicine, and on the potential use of this technology for the treatment of disease and improvement of human life.

This study will examine the efficacy of brief, nurse-delivered counseling intervention, Stress Inoculation Therapy (SIT), on the enhancement of psychological adjustment to the receipt of genetic cancer risk information, on the improvement of comprehension of genetic risk, and on the promotion of adherence to follow-up prevention recommendations. In addition, we will assess how coping style disposition moderates the effects of the intervention. Outcome measures will include both general psychological adjustment as well as risk-specific distress. The availability of DNA markers for the BRCA1 gene will allow us to compare risk assignment based on clinical parameter with that provided by genetic testing to determine if family history can serve as a tool to select appropriate candidates for genetic screening in the future. The proposed study provides a unique opportunity to develop and test among women of different socioeconomic and ethnic groups a relatively brief psychoeducational counseling intervention which could have a significant public health impact on cancer control.

The objective of this proposed historical and analytical study is to identify the major ethical concerns of Evangelical ('Born Again') Protestant Christians in the United States relative to genetic research and the Human Genome Project during the time period 1956 to the present. The method employed will be a content analysis of books and articles published by Evangelical authors, at both the scholarly and popular levels, with special concern for keywords such as 'genetics', 'genetic engineering' 'genetic testing/screening', 'gene/genetic therapy', 'cloning', and 'Human Genome Project.' The scope of the data set to be examined will be defined by the indexing of the books and periodicals in question by the ATLA (American Theological Library Association) Religion Database on CD-ROM, including Religion Index One: Periodicals. The value and health relatedness of this study will be to assist scientific researchers to more effectively interpret and communicate new findings in genetics to Evangelical Protestants and other religious communities, so as to maintain and enhance public support for research in these areas.

With the growing importance of biobank research, concerns have been raised about how to protect the interests of donors. The current ethics framework mainly focuses on protecting against risks to donors' welfare and to their privacy. However, there has been little systematic empirical, normative, or policy focus on the non-welfare interests of donors, i.e., concerns about the moral, societal, or religious implications of research using their donation that may affect their willingness to donate. Although important theoretical discussions, mentions in commission reports, and insights from several qualitative studies have drawn attention to the serious nature of these interests, we lack important data for policy development: (1) systematic data on the nature and extent of potential impact of non-welfare interests and (2) high quality (i.e., informed and considered) policy preferences of the public addressing how to balance these non-welfare interests with the promise of biobank research. Our project will fill these gaps with two complementary projects. First, a national survey will assess the contours of the potential impact of non-welfare interests on biobank research, by addressing: what kinds of non-welfare interests substantially affect willingness to donate biological materials?; how common are these interests?; how much do donors want to know about the potential involvement of such non-welfare interests when donating?; how are non-welfare interests affected by such factors as race or ethnicity, socioeconomic status, trust in medical research, religious beliefs and practice, or political orientation? Second, we will obtain considered, informed judgments of the public regarding how to handle the tension between the public good of biobanks and the conflicting non-welfare interests of potential donors, using a democratic deliberation method in which subjects will attend an all-day education and peer deliberation session. The impact of the deliberation will be validated using a randomized, experimental design. In summary, despite the ethical significance of non-welfare interests for biobank research, there is a paucity of systematic data regarding both their potential impact and the potential policy solutions. This project will provide a highly generalizable assessment of the potential impact of non-welfare interests as well as policy recommendations based on informed, deliberative opinions of the general public. PUBLIC HEALTH RELEVANCE: The ethical discussions surrounding how to protect the donors of biobank research have focused mostly on reducing harms and respecting privacy interests of donors. There has been little focus on the ethical and policy significance of the non-welfare related interests of individual donors, i.e., individual concerns about the moral, societal or religious implications of research using their donation. This project will provide a systematic, generalizable assessment of the potential impact of non-welfare interests as well as policy recommendations based on informed, deliberative preferences of the general public.

The objective of this research is to conduct and evaluate a pilot program for the simultaneous screening of carriers for CF, Tay Sachs Disease (TSD) and Gaucher's Disease (GD) in the Ashkenazi Jewish population. This ethnic group is unique since 95 percent of CF and GD carriers can be detected, providing the rationale to introduce CF and GD screening in conjunction with TSD carrier screening programs. This pilot study will address issues of education, improved and cost effective test methods, effective counseling and potential psychologic harm, as well as ethical and health policy considerations. 10,000 Ashkenazi Jewish participants (about 5,000 couples) will be recruited for the study. Comparison of screening for these diseases will permit identification of screening issues related to differences in disease severity, availability of treatment, and detection accuracy for carrier couples.

Developments in transgenic animal research, together with the limited success of gene transfers targeting human somatic cells, have triggered renewed interest in research on germ line interventions in humans. Debates over modifying the human germ line tend to focus on the long-term consequences to society. Comparatively little attention is paid to the human research that will be necessary to establish that genetic interventions are safe and effective. The aim of this project is to apply U.S. policies governing research involving human participants - and the ethical principles underlying such policies - to studies of germ line interventions. In the project, a Core Group of experts in genetics and research ethics and policy will consider how policy provisions and ethical principles would bear on research proposals to alter the genome of a human embryo when the goal is to allow that embryo to develop into a child. The Core Group will receive information and guidance from scientific consultants with expertise in human and animal genetics. Project participants will prepare materials to inform investigators, local and national oversight bodies, and the interested public about the ethical and policy complexities of conducting research altering the genotype of human embryos. Project participants will also: (1) develop guidelines for applying federal policy governing research involving human subjects to germ line studies; and (2) consider additional rules and procedures that may be warranted to ensure that subjects are adequately protected in the research process. The project will yield two manuscripts, one aimed at a general audience and a more detailed monograph for groups asked to evaluate the ethical and regulatory acceptability of proposals to conduct germ line research in humans.

The purpose of this project is to illuminate the processes by which genetic screening and genetic concepts of health and illness penetrate two contrasting communities and become integrated into the health concerns of high-risk families. The goal is to clarify the cultural frames used to process new genetic information and to explore both barriers and bridges to successful genetic interventions. High risk young men and women in their reproductive years will be studied. Those who have used genetic services will be compared with those who have not. The social networks and extended family members of those whose lives have been touched by the targeted genetic disorders will be examined. The project will also focus on issues of privacy, stigma, and discrimination identified in earlier research and their management within family and institutional networks. The understandings, interest, and responses will be analyzed in two cultural contexts; one in which the disorder is generally recognized as race-linked, and the other in which this association is not part of the popular consciousness. This will contribute to culturally sensitive genetic screening and counseling.