ELSI Publications and Products Database

The Mentored Scientist Development Award in Research Ethics will fulfill three main goals: 1) to obtain a broad and in-depth foundation in research ethics and to develop research skills in ethical reasoning and analysis in order to become a resource for those pursuing biomedical research; 2) to build a research program on the ethical implications of human genetic variation research for social distributive justice; and 3) to become an independent investigator in the field of research ethics upon the completion of this career development award. These goals will be accomplished through mentoring, formal coursework, faculty collaborations, and empirical research. The research plan focuses on social distributive justice in human genetic variation and pharmacogenomics research. The ethical principle of justice requires that medical research provide equitable distribution of benefits to human subjects. This project investigates whether pharmacogenomic research involving racially identified populations fulfills this principle in the fair, equitable and appropriate distribution of health benefits to all populations within the United States. The specific aims of the proposed project are: 1) to critically examine the assumptions and practice of human genetic variation research and its impact on current trajectories of pharmacogenomics research and to identify the major prospective recipients of these studies.; 2) to identify the meaning of justice for various stakeholders, including scientists, prospective human subjects, industry leaders, and policymakers, in pharmacogenomics research; 3) to examine the implications of pharmacogenomics research on the status of health disparities between racially identified populations; and 4) to develop an ethical framework in which to address social distributive justice in pharmacogenomics research that will lead to specific guidelines for those who apply this research to practice. The research will consist of an ethnographic study involving participant observation, in-depth interviews, and archival analysis.

This prospective, longitudinal study will examine decision-making about pre-surgery BRCA1/2 testing and the medical, psychosocial, and economic outcomes of testing among newly-diagnosed breast cancer patients who are at high risk for having a BRCA1/2 mutation. The theoretical framework for this investigation is derived from Expected Utility Theory. The specific aims are: 1) to establish rates of uptake of BRCA1/2 testing prior to surgical treatment for breast cancer, and to identify the determinants of the decision to be tested; 2) to evaluate the impact of BRCA1/2 testing on patients' surgical treatment choices; 2) to evaluate the impact of pre-surgery BRCA1 testing on psychosocial well-being; and 4) to develop a model to estimate the costs of BRCA1/2 testing for newly-diagnosed breast cancer patients per quality-adjusted life years saved.

An 8-part public television series on the scientific and technological advances transforming the practice of medicine, and the involvement of genetics in the issues medicine will have to deal with in the years ahead, including: the proliferation of genetic data and who controls it; medical intervention in conception and birth, aging and death; widespread expectation of rapid cures for all diseases; new surgical techniques; genes and mental illness; and ethical issues to be faced as the study of human genetics progresses.

Genomic literacy plays a critical role in informed decision-making for genomic testing, in the implementation of the test and the accurate interpretation of the results, and in our policy making process as a society. The National Human Genome Research Institute's 2011 vision for the future of genomic medicine specifically cites the need for both providers and consumers to achieve genomic literacy. Yet despite its importance, there is no effective tool for assessing genomic literacy. Deploying a common, rigorously validated measure will reduce duplicated effort among study groups, increase the quality of genomic literacy data, and enable comparison and meta-analysis. Existing literacy measures are focused on genetics as opposed to genomics, do not incorporate modern genomic technologies or are only informative over a limited range of examinee knowledge levels. In this pilot project, our aim is to define, test and preliminarily validate an item bank o genomics knowledge questions. First, we will assemble an up-to-date and comprehensive list of genetics and genomics concepts that will comprise the content domain and refine that list via focus groups with stakeholders. Then, we will assemble an item bank of 200 multiple-choice questions, and refine those items via individual cognitive interviews. We will test the item bank in a diverse cohort (500 examinees per item) drawn from the general public, students in genomics courses, participants in translational genomics studies and life-science professionals. Using those responses, we will perform a detailed psychometric analysis and calibration of the item bank using item response theory, preliminarily validate measure performance and perform simulations to test the suitability of computer adaptive testing in this domain. The item bank we develop and analyses we perform in this project will inform the development of a new, robust and valid genomics literacy measure to assess population genomic literacy and evaluate the pedagogical effectiveness of genomics educational interventions.

The long term objectives of this project are to develop an integrated package of public and professional education materials that would meet the pre-screening needs for education and informed consent of the public, and for the professional offering the testing. The materials would utilize innovative technology such as interactive computers, and would be developed for the average reader. Specific Phase I aims are to 1) assess pertinent content and innovative modes of delivery, 2) develop a preliminary design for the integrated package of materials, 3) complete a prototype of prescreening material for use with the general public, and 4) prepare a final design document for Phase II. Specific Phase II aims are: 1) to develop an integrated package of education materials that provides a thorough discussion of CF carrier screening which will allow the public to decide whether the test is appropriate for them, a companion video, and a professional education manual; 2) to conduct formative and outcome evaluation activities, with particular emphasis on validity, reliability and acceptability to potential users; evaluation activities will take place at a variety of clinical sites to allow for differences in setting, target population and testing modalities; and 3) to identify appropriate distribution modalities.

The objectives of this project are to determine the impact of the HGP on women, to examine whether this impact meets standards of fairness or gender justice, and to identify ways of avoiding or reducing the possibility of unfairness or gender injustice in the formulation of institution and social policies. The specific aims include the development of a common core of scientific, psychosocial, legal, and ethical knowledge regarding the impact, or probable impact, of the HGP on women; identification of criteria against which the possibility of gender justice may be measured; application of these criteria to three areas of research: cystic fibrosis, sickle cell disease, and breast cancer; determination of an agenda for future research; public education concerning impact of HGP on women; and recommendations for ways in which gender justice may be preserved or promoted by HGP research and its applications.

The goal of this project is the development of a casebook and compilation of related educational resources covering ethical issues encountered in the practice of genetic counseling. It will present educational materials for genetic counseling trainees and provide a resource for genetic counselors encountering difficult issues. The goals of the proposal are to: collect cases from certified genetic counselors in each of nineteen problem areas, and disguising each case to protect confidentiality; outlining an educational process for exploring each type of case; and compiling reading materials pertinent to each case type, to provide scientific details and additional information on social and legal ramifications of different counseling positions and decisions.

When the Human Genome Project was completed almost ten years ago it cost millions of dollars to sequence an individual's genome. Yet, the evolution of high-throughput sequencing and computational tools has been swift and it will soon be possible to genotype anyone for a nominal price. The ability to generate genomic data coincides with the adoption of electronic health records, setting the stage for large-scale personalized medicine research, the results of which can improve the efficiency, effectiveness, and safety of healthcare delivery. To ease barriers to population-based research, genomic and clinical data are often made available via a de- identified designation by various policies and regulations. However, there is a growing perception that de- identification is a fallacy and that biomedical data can be re-identified with relative ease. This argument, which is partially based on our own studies, forms the core of calls for legislative and regulatory modifications in the literature and court cases. Most notably, a recent Advanced Notice of Proposed Rule Making (ANPRM) inquires if biospecimens, as well as derived genomic data, should be redefined as inherently identifiable. Such labeling would require changes to the Common Rule and HIPAA Privacy Rule and could influence the availability of genomic data for research. It is clear that only a small amount of genomic data is necessary to uniquely distinguish an individual, even in the context of aggregated statistics. However, at the same time, it must be recognized that "distinguishable" is not equivalent to "identifiable" and though re-identification is possible it des not imply it is probable. Identifiability concerns should not be trivialized, but there is currentl no sound basis for reasoning about such risks, limiting the ability to make informed policy decisions. There are many factors associated with identifiability, including the information shared with genomic data (e.g., clinical, demographic), with whom it is shared, what other sources of data exist, and the relevant legal landscape. A limiting factor of prior studies in genomic identifiability is their consideration of these factors in isolation, which provides an incomplete picture. To fill this void, the overarching objective of our research is to engineer a foundation, rooted in ethical, legal, and computational formalisms, that provides a basis for reasoning about, and managing, genomic data identifiability risks. This foundation will be realized through specific aims: (1) build a protocol for modeling the extent to which sharing genomic data can substantiate re-identification concerns, (2) design and evaluate practical measures of genomic identifiability for risk assessment protocols, (3) develop a strategy that supplies options to mitigate genomic data identification risks. We envision several notable outcomes from this project. First, this work will yield guidelines and risk assessment strategies that can be employed by genomic data managers and policy makers to inform their decisions regarding identifiability. Second, we will perform an evaluation of our framework with a real, large de-identified database of clinical and genomic data to provide tangible and pragmatic results. PUBLIC HEALTH RELEVANCE: The protective nature of de-identification has been criticized and there are growing calls to relabel all genomic data as inherently identifiable. However, there are no reasoning tools to assist genomic data managers and policy makers to assess identifiability or determine which protections, technical or legal, should be invoked to mitigate risks. The goals of this research project are to develop an interdisciplinary framework to a) model genomic data re-identification risks, b) measure the risks given computational and socio-legal constraints, and c) assist in determining which data protection strategies are the most appropriate to specific data sharing scenarios.

The objective of this proposed research program is to evaluate the legal, ethical and policy implications of the application of genetic susceptibility data to environmental regulation. An enormous amount of data has been generated in recent years showing that individuals differ substantially in their susceptibility to environmental toxicants. While some research has addressed the legal and ethical implications of genetic research on environmental susceptibility or the use of such data in risk assessment, little if any work has examined how genetic susceptibility data could, and in some cases must, be applied within the existing environmental law framework in the United States. An extensive body of statutes, regulations, guidance documents, judicial decisions, and other legal materials exist that will largely govern how genetic susceptibility data will be incorporated into environmental regulatory decisions. Although most of these various legal materials were developed without specific recognition of the differences in genetic susceptibility, they nevertheless provide the relevant legal framework for the incorporation of new data on genetic susceptibility. For example, national ambient air quality standards promulgated under the Clean Air Act must be set at a level which protects the most susceptible subpopulations, and there is a large body of relevant rulemaking precedents, judicial decisions, and legislative history that will determine the appropriate role of genetic information under such a statutory provision. This project will evaluate how genetic susceptibility data can or in some cases must be incorporated under the existing regulatory framework and precedents. It will identify legal, ethical and scientific issues and challenges in the application of genetic susceptibility data under existing legal provisions, and recommend criteria and guidelines for incorporating genomic information into environmental regulatory decision-making. It will also evaluate potential improvements and alternatives to the existing legal framework to better accommodate genetic information, including greater reliance on individualized self-help or targeted measures, such as increased testing, warning and avoidance measures. This project will be undertaken by a consortium of three principal researchers with extensive experience and backgrounds in both environmental regulation and legal and ethical issues relating to genetics.

Personalized medicine (PM) has the potential to transform medicine and the health care system over the next decade. An overlooked variable that will play an important role in the implementation of PM is the potential for legal liability. Physicians, a key gatekeeper in the uptake of PM, are at the greatest risk of liability. Currently, there is great uncertainty, disagreement and rapid change with regard to the use of PM tests in clinical care. It is during this period of uncertainty and change where the potential for liabilityis at its greatest and thus the need for comprehensive legal research and analysis of the intersection of these issues is most pressing. This proposed project seeks to fill the gap in the understanding of PM liability risks by providing legal doctrinal, empirical, and policy research on the risks, impacts and possible policy approaches with regard to PM liability. The results of this project can help to better understand and predict the future course of PM and to identify the key legal and policy levers that may be available to ensure that liability plays a beneficial rather thn detrimental role in the implementation of PM. This project has five primary objectives. This project will provide a comprehensive investigation and analysis of potential liability to physicians, first by examining the applicable claims, defenses and doctrines that will, provide the legal framework for liability, and which themselves are currently undergoing important changes. Second, we will evaluate the potential risks of liability to physicians by integrating the doctrinal analysis with the fact patterns and evidence in four likely PM case studies, as well as by evaluating liability lessons from the uptake of previous medical technologies and practices. Third, we will examine the likely impact liability will have on physicians, patients, and the broader adoption, availability and implementation of PM. Fourth, we will identify and evaluate policy tools that can be used to better manage risks and uncertainties in the PM arena. Finally, we will communicate the findings and implications of our project through an outreach program targeting three key stakeholder groups: (i) physicians and medical educators; (ii) patient groups and advocates; and (iii) legal practitioners (including judges). At this critical juncture in the rollout of PM, before widespread liability has taken hold, it is very important and useful to comprehensively study and make widely available the best information and projections of the risks and relevant factors for physician liability relating to PM. PUBLIC HEALTH RELEVANCE: The advent of personalized medicine (PM) has the potential to greatly impact and improve patient care by providing the opportunity for better tests, better drugs, and overall better health outcomes. The increased risk of legal liability for physicians wil ultimately influence which technologies will be adopted and rejected in the PM space, shape the relevant standard of care, dictate public health outcomes, and affect access to PM technologies and the care that the ultimate beneficiary, the patient, receives. Better understanding, communication and policy interventions relating to PM liability risks can help to ensure that liability has a beneficial rather than detrimental impact on PM uptake and implementation.

The purpose of this project is to investigate the stigmatization of the sick as it applies to new developments in genetic testing, screening, and diagnostics. Using the methods of medical and social historiography, historical case studies of social alienation and isolation will be analyzed, compared, and contrasted to the potential social and ethical problems we face with the vast scientific knowledge to be gained from the HGP. A particularly useful historical paradigm for assessing the potential of stigmatization of carriers or sufferers of genetic diseases are the uses and abuses of quarantine in the United States over the past 150 years. This study intends on broadening the concept of quarantine to include any attempt society makes to place divisions between groups of people perceived to be 'diseased' be the reasons medical, moral, or social, and the mainstream society fearing contamination. These historical paradigms will be discussed in the context of society's responses to genetic screening programs during the 1970s in order to analyze the potential risks of a 'genetic quarantine' of people with 'undesirable' traits or characteristics.

As the scientific study of genetic variation between human groups gains momentum around the world, traditional questions of research ethics are being transformed in ways that challenge our conventional wisdom about the responsible conduct of research. Challenges associated with obtaining informed consent may be heightened because of difficulties explaining genetic concepts cross-culturally. In some cases, language barriers may diminish effective communication even when literal translation is not a problem. Genetic researchers conducting family studies may encounter notions of kinship and lineage that are inconsistent with genetic science and under which even the scientific depiction of a family 'pedigree' may be obscure. Questions pertaining to decisional authority are exacerbated when investigators view entire groups or populations as their 'subjects.' In this case, the issue of community representation and the delegation of authority to make decisions for participation in genetic research are socially and politically complex. In multi-national genetic studies, simply transferring standard methods from industrialized societies, which depend heavily on obtaining written consent, is inadequate, but no reasonable alternatives have yet been developed. A reformulation of the fundamental approach to informed consent for genetic epidemiological research is needed to accommodate the scientific need for information on sequence variation, to foster the development of effective clinical intervention, and to improve access to health care for all ethnic populations. Building on our current research (1 R01-HG-02207-01), the proposed study has four primary goals: 1) to develop, test, and implement a videotaped educational intervention to improve informed consent for genetic epidemiological research on hypertension and breast cancer being conducted with populations of African heritage in the U.S. and Nigeria; 2) to conduct a randomized trial to test the effect of the videotaped educational intervention on two specific outcomes: a) comprehension of research goals; and b) participation during the informed consent discussion, as measured by the number and quality of questions asked; 3) to examine beliefs about the implications of genetic research for personal health and individual and group identity, and determine their influence on individuals' willingness and motives to participate in genetic research; 4) to develop recommendations to improve informed consent procedures for genetic epidemiological research to ensure that they are culturally appropriate, maximally informative, and protective for ethnically diverse populations. The proposed study represents the first transnational attempt to evaluate a videotaped educational intervention for informed consent in genetic epidemiological research. Moreover, results of this study have the potential to contribute to the growing literature on the meaning of genetic research for individuals and communities of African heritage.

In its first five years, the CWRU Center for Genetic Research Ethics and Law (CGREAL) explored a range of ethical, legal, and policy issues in the design and conduct of genomic gene-discovery research. We now propose to follow the trajectory of genomics into its "translational" phase, where its expanded research needs and higher clinical aspirations are creating new ethical, legal, and policy challenges. Translational research is often simplified as a linear conversion of scientific discoveries into clinical applications, "from bench to bedside." In reality, it is complicated by interactions among a wide range of stakeholders. As translational genomic research moves increasingly into the "public square" of clinical, commercial, community, and public health settings in its search for data sources and practical applications, it must negotiate the competing interests and values of those settings in order to achieve its scientific goals. CGREAL's 5-year goal is to provide evidence and arguments that can help all parties in that negotiation work toward a just and responsible outcome. In its new incarnation, CGREAL will consist of three programs designed to help develop the policies and practices that should guide that process. Our Transdisciplinary Research Program will study translational genomic research by mapping and comparing stakeholder views on four value-sensitive features: driving hypotheses; instrumental strategies; social constraints; aspirational goals. Wherever divergent interests force decisions about these features, translational genomic research will encounter ethical, legal, and social challenges, triggering our normative and conceptual analyses of the arguments involved. Our Translation to Policy Program will develop our analyses into policy proposals for addressing the challenges our own research uncovers. In addition, we will monitor the field at large to steer our research agenda towards other emergent policy problems. This program will identify and communicate policy options at institutional, professional, regulatory, or legislative levels, in collaboration with other biomedical research policy development programs. Our Training Program will continue to expand its scope to bring a wider range of voices to ELSI research and policy development. PUBLIC HEALTH RELEVANCE: The translation of genomic research into health benefits for the public is a goal that is shared by many scientists, patients, public health agencies, and private enterprises. All these interested parties will need to work together to analyze large collections of DNA and clinical information. Our Center's goal is to help that process by providing the information that will be required to meet the ethical, legal, and social challenges.

Huntington's disease (HD) has for decades served as a model for how we think about genetic testing, and its benefits and risks for tested individuals and their families. In 1983, the gene for HD was mapped to chromosome 4, allowing linkage tests to be developed for use in presymptomatic genetic testing for HD. In 1986, Johns Hopkins launched one of the first two such testing programs in the United States. This work influenced guidelines for the provision of HD genetic test results, which have subsequently influenced contemporary guidance for other adult-onset neurodegenerative diseases. This early experience also arguably influenced our collective thinking about many issues related to genetic testing and the provision of genetic test results. Almost 30 years later, we are still in contact wth many members of this early cohort. As increasing numbers of genetic tests are being used to predict adult-onset neurodegenerative disease, and as large-scale genetic testing is increasingly integrated into clinical care, it is critical that we understand not only the implicatons of presymptomatic testing for the at-risk individual over several years, but also for the at-risk individual and her/his family over the course of their lives. Here, we have a unique opportunity to take a retrospective look over decades at how at-risk individuals and their families communicate about and cope with test results not months or years following testing, but decades following testing. We will do this through in-depth interviews with a subset of those at-risk individuals who were tested between 1986 and 1996, focus groups with a subset of family members of tested individuals, and a survey sent to all at-risk individuals who were tested from 1986 to 1996 and their family members. The outcomes of this research will improve our understanding of how the results of genetic testing for serious, currently incurable disease are communicated in and through families, how this information influences choices (e.g., career, participation in research, having children) and trajectories of at-risk individuals and their families over decades, and will help inform policies and procedures for communicating such results. Under Specific Aim 1, we will explore the impact of presymptomatic genetic testing for Huntington's disease (HD) on the lives and choices of at-risk individuals, 18-28 years after testing. Under Specific Aim 2, we will build on prior work with this cohort to determine longitudinal changes in individuals' feelings about and understanding of their testing experience as they have progressed through life's stages. Under Specific Aim 3, we will explore the impact of presymptomatic genetic testing for HD on family members (spouses, partners, children) of tested individuals, 18-28 years after testing. Under Specific Aim 4, we will build on the results of Aims 1-3 to explore how the views of individuals and their families comport with the current paradigms and policy for the conduct of clinical genetic and genomic testing. PUBLIC HEALTH RELEVANCE: This project is designed to improve our understanding of the impact of presymptomatic genetic testing for Huntington's disease on families over time. We will talk with individuals who received testing 15-25 years ago, along with spouses, partners, and children of those individuals to learn about the impact of the testing and the resulting informatio on the family. We hope this information will help inform current thinking and policy governing the return of results from genetic testing.

A major ethical and policy challenge facing genomics research stems from the existing mandate for rapid public release of all sequenced DNA data. It is now clear that an individual can be uniquely identified with access to a small number of SNPs from that person. Genome-wide association studies routinely use more than 100,000 SNPs to genotype individuals, creating privacy risks that are only going to increase as technology advances and electronic databases proliferate. Informed consent is not currently required for DNA data release because de-identified data are incorrectly assumed to be unidentifiable. We have argued for policy reform that mandates informed consent for data sharing. The goal of this proposal is to spearhead this effort by developing a consent process that will encourage data sharing while building public trust and fostering participation in genetic research. This project builds on a preliminary study of participants' attitudes toward DNA data release and has three specific aims: (1) conduct a randomized trial of three alternative types of consent for DNA data sharing (traditional, binary, and tiered) to compare their impact on enrollment and consent to data sharing, (2) evaluate subjects' judgments about data sharing and assessments of traditional, binary and tiered consent, focusing on calculations of risks and benefits, informational needs, and desired levels of control over decision making, and (3) develop clinically relevant policy recommendations for DNA data release. Participants in ongoing genomic studies of cancer and epilepsy at BCM will be invited to participate. Responses will be compared by type of consent (traditional, binary, tiered), subject population (patient, parent of affected minor, control), and disease type (epilepsy, cancer, healthy volunteer). It is our hypothesis that tiered consent will be best able to satisfy the range of participants' judgments, will yield the highest consent to data sharing, and will not negatively impact enrollment into genetic research. This project will culminate in a practical model consent process and form for data sharing that can be adapted by investigators and used as a guide by IRBs, and the results will help shape a broader conceptual model for ethical variation in types of consent for human subjects research. Moreover, it will increase our understanding of participants' judgments and attitudes toward data sharing, which will improve the overall conduct of biomedical research, build public trust, and foster research participation.

We propose an exploratory survey, parallel to the Human Microbiome Project (HMP), of the emergent ethical, legal, and social issues associated with human microbiome research. We will implement this study using in- depth interviews with key stakeholders in the HMP, including individuals who are recruited to the HMP but decline participation, study participants, and investigators and project leaders involved in planning for an conducting the first phases of the HMP. The overall goal of this project is to identify and analyze ethical, legal, and social issues related to human microbiome research and to develop ethically sound and empirically informed strategies for managing these issues in future research. This project has three Specific Aims: (1) Describe recruits and participants' ideas about the HMP (and participants' experiences of the HMP) as it relates to them physically, socially, and culturally and as it relates to their notions of health and disease, (2) Describe the ethical, legal, and social challenges of conducting the HMP from the perspective of study investigators and project leaders at the NIH, and (3) Provide a forum for interdisciplinary exchange with representative stakeholders (including study participants, members of the research team, and outside experts) to develop recommendations for the responsible management of ethical, legal, and social issues identified in Specific Aims 1 and 2. PUBLIC HEALTH RELEVANCE: The Human Microbiome Project (HMP) is a large study to learn more about the collections of bacteria, viruses and other tiny organisms that live in and on our bodies. We will interview three groups of people: (1) those who are asked to participate in the HMP but say no, in order find out why they said no, (2) those who decide to participate in the HMP, in order to explore their thoughts about the project and their experience with participating in the project, and (3) scientists who are conducting the HMP, in order to understand what ethical or social issues are related to this type of research. We will also host a workshop with members of our research team, study participants, and outside experts to discuss the issues that were identified in the interviews and develop recommendations for managing them.

Many national and international public and private initiatives are forming to collect and share data on a large scale for research and clinical use. Collectively, these efforts may lead to the creation of a medical information commons, a networked environment in which diverse sources of health, medical, and genomic data on large populations become widely shared resources. The success and value of such a commons will depend on development of policies and practices for effective governance that address barriers to data sharing and are developed with informed input from patients and members of the public whose data may populate it. In an NHGRI-funded study (McGuire R01HG006460), a diverse group of experts ranked reluctance of some institutions to share data as the most important, yet least politically tractable policy challenge among 17 posed in a modified Delphi process. The objective of this proposal is to engage expert stakeholders to inform policy decisions about effective governance for data sharing, while using deliberative methods to obtain informed public input to ensure that the values, rights and interests of individuals whose data may populate the information commons are represented. In Aim 1, we will work with a multi-disciplinary expert advisory committee and con- duct a systematic landscape analysis of existing and emerging data initiatives to summarize common approaches and identify alternative models. In Aim 2, we will conduct qualitative interviews with expert stake- holders to solicit feedback on existing models and alternative approaches to key policy challenges. In Aim 3, we will use intensive deliberative methods, Citizen Panels, to solicit informed input about key policy issues, and proposed models to address them, from patients and members of the general public. This contribution will be significant because it will provide critical stakeholder input to develop the necessary foundation for a sustainable ethical and legal framework for efforts to advance public and private sector data initiatives. The approach is innovative by engaging a diverse and representative group of stakeholders, including those involved with and potentially contributing to these data initiatives, to identify policy challenges and deliberate models for effective governance. The work is feasible in our hands because our team of established investigators have expertise in ethical and policy issues related to large-scale data sharing and a track record of success working together on large collaborative projects addressing ethical and policy issues in genomics.

Researchers and bioethicists have developed guidelines to protect human subjects in clinical experiments involving genetic technologies. However, these rules were developed for investigations of therapeutic interventions and do not address the risks involved in the potential use of genetic technologies for enhancement purposes. Society has reached a clear consensus against attempting germ-line genetic interventions in humans, but genetic knowledge could still be used for enhancement purposes in other ways, such as the somatic use of biosynthetic growth hormone to increase stature, or studies to identify genetic mutations associated with non-disease traits. In the absence of guidelines that explicitly address the special issues of enhancement research, subjects could be exposed to risks that would be acceptable in the case of therapeutic research but unacceptable in the case of enhancement research. Moreover, the absence of explicit enhancement research policy is likely to drive this type of research into the realm of 'underground' illicit or off-label use and self-experimentation, which could cause serious harm to research subjects and to society. To address this policy gap, this project will identify ethically relevant differences between therapeutic and enhancement genetic research and analyze these differences in terms of the ethical principles that govern human subjects research, in order to determine whether current rules and regulations adequately restrict enhancement research, and, if not, propose changes to existing rules and regulations so that society can respond effectively to possible future attempts to conduct genetic enhancement research using human subjects.

Advances in genomic science are attracting the interest of the U.S. military for their potential to improve medical care for members of the militay and to aid in military recruitment, training and specialization, and mission accomplishment. In addition, large DNA banks operated by the military could be a valuable resource for military and civilian researchers. While ELSI research projects have explored issues raised by the use of genomic science in a wide variety of contexts, there has been virtually no examination of the ethical, legal, and social issues raised by military genomics beyond those relating to forensic use of the Department of Defense (DoD) DNA Registry. This project will bring the insights from the ELSI program and the broader conversation on the ethical, legal, and social issues posed by genomic science in general to bear on the unique challenges presented by potential uses of genomic science by the military. Building on work now underway to develop a bioethical framework for military bioenhancement, this project will construct the first bioethical and legal framework for military genomics, and will employ this framework to analyze how ELSI issues might be resolved. PUBLIC HEALTH RELEVANCE: This project will construct an ethical and legal framework for military genomics and apply this framework would apply to uses of genomic science contemplated by the U.S. military. This will promote the public health by elucidating ethically and legally appropriate ways to construct and utilize a proposed new military/VA DNA biobank, and by offering suggestions for how to protect the health and well-being of members of the military and their families as the military increases its uses of genomics.

This project will examine the issue of affording access to the technologies that are expected to emerge from the Human Genome Project (HGP). The potential impact of these technologies on the fate of individuals, families, and ultimately, the species itself, will make the question of who is given access to them highly controversial. By matching the characteristics of these new technologies as closely as possible to technologies that currently exist, this study will project the degree of access to these genetic services that would result if access were governed by the principles of distributive justice currently embodied in major public health care programs. It will then compare this result with the patterns of access that would emerge from the application of alternate models of distributive justice. The study will conclude with recommendations for how access to these new technologies can best accomplish the goals of distributive justice.

The Human Genome Center at the University of Michigan is supporting projects designed to update and inspire secondary science teachers in the area of genome technology and its implications. The Education Coordinator will do rotations in each core lab of the center and then develop and distribute a Genome Information Brochure explaining the activities of each core lab. A quarterly Genome Center Newsletter for educators will be published which will describe the current status of the Genome Project, review a topic in genetics and its implications, and provide information on new educational resources and materials available nationwide. Lectures on the Genome Project and 'hands on' demonstrations will be presented to the lay public and at schools throughout the state. On-site tours of the Genome Center will be conducted. Biotechnology classroom demonstration kits for teachers will be developed to complement the curriculum guide provided by BSCS. The Center will also provide the biological sciences component for the Summer Science for Girls Program (7 &8th graders) at the University of Michigan. In addition, the center will host a summer workshop for high school teachers and another for community college instructors on genome technology and its implications. The Center will host a 'hands on' workshop for the media to educate them on the scientific and ethical issues in genome research. Finally, the center will conduct training workshops on the clinical and laboratory aspects of DNA diagnosis for providers who counsel patients about genetic testing.

The project focuses on the applied development of an effective informed consent form and process for donation of blood to a DNA Bank solely for research purposes. This form will be used for securing consent from patients in the General Clinical Research Center at the Hospital of the University of Pennsylvania, from whom a blood sample will be solicited. A short series of vignettes will also be developed to prompt cognitive processing of the information in the consent form. The effectiveness of these vignettes will be tested in actual clinical use as an informed consent intervention, randomly assigning patients from whom a blood donation is solicited to receive either just the consent form or the form and vignettes. Donors will also be asked to participate in a brief survey about the consent process. The questionnaire will examine understanding and perceptions of risks and benefits. The analyses of these questionnaires will help inform researchers about information needs and desires and how to facilitate meaningful choices of those asked to donate blood or other tissues for banking and research purposes.

The objective of this training and research project is to develop the candidate into an independent and interdisciplinary ELSI researcher, with the ability to intertwine qualitative empirical with normative approaches to issues in genetics and genomics. To accomplish this objective, I have proposed: (1) Training that builds upon my previous education and experience as a qualitative social scientist with additional training in genetics and bioethics; and (2) Research that takes a combined social scientific and bioethical approach to understanding and guiding the translational pathways of new genetic innovations. The proposed training includes coursework, directed readings, seminars and workshops, and the mentored development of an interdisciplinary ELSI research project. The long-term goal of the research project is to map out an ELSI-integrated translational pathway for genetic innovations: building a model of crucial points for, and types of, ELSI guidance throughout these translational processes. The specific Aims of this project are: (1) To follow the unfolding translational pathway of cffDNA testing technology, as a case study in translation processes for genetic innovations; and (2) To map crucial points for ELSI guidance along the translational pathway of genetic innovations. Through individual interviews with stakeholders and observations of meetings and conferences of stakeholders, this mapping project will examine the case of cell-free fetal DNA (cffDNA) testing and the actors and networks that influence its development toward potential clinical applications. Comparing features of this process with those of other translations of genetic innovations, it will identify critical moments, turning points, and intersections at which important decisions shape the unfolding translational pathway. Finally, through collaboration with key stakeholders in cffDNA and non-invasive prenatal testing, a model will be developed that proposes types of ethical and social guidance for these crucial points that would likely be most beneficial. PUBLIC HEALTH RELEVANCE: A significant part of the role of ELSI research is the identification and integration of ELSI considerations into translational research, promoting improved public health, health equity for underserved groups, concern for community values, and protection for vulnerable populations. Through detailed examination of the development of cell-free fetal DNA testing, this project will add complexity and contingency to existing models of the translational pathway. This, in turn, will lead to fuller and more situationally-responsive integration of ELSI guidance along the entire translational pathway for genetic innovations.