ELSI Publications and Products Database

Harvesting the benefits of genomics requires a new kind of transdisciplinary cooperation. Over the next three years, we will create the Center for Transdisciplinary ELSI Research in Translational Genomics (CT2G) to address key ELSI questions in translational research. The proposed Center brings together the unique resources of Kaiser Permanente Northern California (KPNC), including its Division of Research, and the University of California, San Francisco (UCSF), including the Hastings College of the Law Consortium on Law, Science & Health Policy. A key CT2G resource for training, research, deliberation, and policy analysis is the Kaiser Permanente "Research Program on Genes, Environment, and Health" (RPGEH), designed to foster epidemiological studies. The RPGEH links together participants' data from electronic medical records, biospecimens, health surveys and geographic information systems. The RPGEH includes genome-wide genetic data and measures of telomere length from a sample of over 110,000 men and women, who constitute the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort. Deepening the existing collaborations between scientists and clinicians at KPNC and UCSF, and utilizing the unique structure of KPNC's integrated health care delivery system, we aim to: 1) Create CT2G and nurture its development as a novel resource for ELSl research in translational genomics. * Implement a management plan and form a Steering Committee and External Advisory Panel * Develop a strong intellectual community through a website, seminar series, and annual conferences * Fund small pilot projects to elucidate barriers to effective genomics translation 2) Convene joint KPNC/UCSF working groups to address critical issues in translational genomics. Focusing on projects with tangible outcomes, we will bring together scholars who have not yet collaborated, creating a blueprint for long-term transdisciplinary work that joins empirical and normative approaches. 3) Plan and initiate a program in ELSI education focused on pre-doctoral students and clinicians. * To expand the pool of under-represented minority ELSI scholars, we will plan and gain approval for a pre-doctoral fellowship program for students from a range of disciplines. * To enhance transdisciplinary collaboration, we will develop a one year ELSI fellowship for clinicians from multiple fields, including nursing, pharmacy, genetic counseling, and clinical medicine. PUBLIC HEALTH RELEVANCE: To facilitate the translation of genetic discoveries into improvements in prevention, clinical care, and public health, we will create a Center to encourage collaboration among scholars from many fields, and to train clinicians. The CT2G will develop better ways to protect research subjects and create strategies for inclusion of public voices in the management of genomic data. Our goal is to ensure that society benefits from genomic discoveries in a manner that diminishes, rather than exacerbates, health disparities.

This study compares two CF carrier screening arrangements: a 'local screen' with pre-screening education provided by a pamphlet and a blood sample drawn by a private physician or public health professional; and a genetic center screen, with pre-screening education by a genetic counselor and a blood sample drawn by a clinic technician. Secondly, this study assesses the effectiveness and cost-effectiveness of a pre-genetic counseling video for CF carrier clients to improve learning in counseling and to increase the utility of counseling information. The study focuses on close relatives of CF patients. Both before and after receiving the results of CF carrier testing, subjects will be assessed to determine genetic and medical knowledge, psychological status, and selected health behaviors.

This study will (a) describe the medical, genetic, and carrier knowledge and beliefs in a population of female relatives of individuals with severe type A hemophilia before and after the relatives accept or decline direct mutation carrier testing; (b) identify the percent of these women who accept the offer of free pre test counseling, testing, and follow up genetic counseling and note their choice of one of three formats for pre test counseling - individually, with a spouse/partner, or in a group; and (c) describe their one and six months reactions to knowledge of personal carrier status and pre test counseling format on selected personal health behaviors and psychosocial variables. The study will also describe nuclear and extended family communication patterns about hemophilia and carrier status. This longitudinally designed study will enroll 480 female relatives of individuals with severe hemophilia A who have been or are currently being followed at the UNC Comprehensive Hemophilia Diagnostic and Treatment Center who have a factor VIII gene mutation that can be detected by currently available methods. Study participants will be interviewed before the pre test counseling and will complete self administered questionnaires (a) immediately after the pre test counseling and (b) at one and twelve months after receiving their test results and accepting or declining follow up genetic counseling. The information to be collected in this study will help to close gaps in the research literature and will be useful in the development of more empirically informed clinical and public health policies on direct mutation carrier testing for hemophilia A in particular and for carrier testing for X-linked disorders in general.

The specific aims of this research are to develop, implement, and assess the effectiveness of a decision balance risk-benefit component as part of the informed consent process for women deciding to accept or reject free hemophilia A Carrier testing. To accomplish this, this project will randomly assign 414 women, by family membership, to receive either a standard or experimental informed consent statement. One month after their decision, all women, both those who chose testing and those who did not, will complete a self administered questionnaire and six and twelve months later they will complete telephone interviews. Major outcome variables include —> satisfaction with the testing decision; —> level of post decision regret; —> post decision assessments of the adequacy of pre decision risk/benefit considerations; —> stability and change in assessed risks and benefits from before to 6 and 12 months post decision; and —> similarities and differences between black/white, as well as in carrier/non carrier risk and benefit assessments at each data collections point as well as over the period of the study. <p+R498> The study will employ both quantitative methods (SUUDAN cluster analyses) and qualitative methods (in depth interviews, theme and cases analyses.) If demonstrated to be effective, the decision balance risk/benefit procedure could be widely used in research involving human subjects.

The goal of this project is to explore the range of ethical, legal, and social implications of genetic research and health services with Indian and Native peoples. These issues have proven to be intensely controversial in some quarters and the intent in this proposal is to explore areas of common ground and possibility for compromise between Indian and Native communities and genetic researchers. Beginning with a conference of national experts and representatives from diverse Indian and Native communities to set the agenda for this research, the project then moves to community consultations in five Indian and Native communities (three rural and two urban). This community work will then be followed by a survey of the Institutional Review Boards (IRBs) that review research in Indian and Native communities, including tribal and Indian Health Service bodies. The project has three specific aims: —> to articulate the possibilities and problems that accompany emerging genetic knowledge about Indian and native people; —> to consult members of diverse urban and rural Indian and Native communities about the ethical, legal, and social implications of possible developments in genetic research and health services, and —> to formulate guidelines for the conduct of genetic research and the delivery of genetic health services in Indian and Native communities.

This proposal seeks to build on 4 years of funded work on the ethical, legal, and social implications (ELSI) of genetic research in American Indian and Alaska Native (AI/AN) communities. In the course of that work, questions of trust have emerged with unique salience as American Indian and Alaska Native community members have expressed concerns with abusive treatment by researchers whom they characterize as primarily interested in self advancement and who, it is argued, have returned little of value to these communities that suffer so disproportionately from health disparities. These concerns have been raised with particular acuity in the context of genetic research on complex disorders such as diabetes and alcohol dependence  problems for which genetic contributions have proven to be much more difficult to discern than originally hoped and for which environmental and behavioral interventions continue to show the best promise. As we have surveyed the extant ELSI literature for other populations, we have been struck by the degree to which many of the concerns we have heard in AI/AN communities are raised elsewhere. We focus, here, on cancer genetics instead of the more easily critiqued work in diabetes and alcohol dependence because it is in this area that the promise of personalized medicine may first be realized. Cancer genetics thus provides us with what is arguably a much stronger basis for exploring the possible benefits and risks of genetic knowledge in biomedical research and health care. We have three specific aims: 1. to explore attitudes toward genetic knowledge, research, and health care for cancer in four urban cultural communities; 2. building on these discussions, to articulate the sources of both trust and mistrust toward research in these communities; and 3. to work collaboratively with community members and organizations to identify policies and procedures that can address sources of mistrust and strengthen trust in possible future genetic research and health care.

This project is an investigation of the implications of research on ancient and contemporary human microbiomes for the social and ancestral identities of indigenous people. It will engage indigenous communities on the U.S. Southern Plains (Apache, Caddo, and Kiowa nations) and in the Andean region of Peru (Aymara, Quechua and Uros-descended communities). Community members will take part in focus groups, individual survey interviews, and public meetings to discuss the ways in which local variations in human microbiomes related to differences in environment, lifestyle and culture may have implications for health disparities, population histories, and social and ancestral identities. Local communities also will be engaged in discussions about how to conduct ethically and culturally appropriate microbiome research using contemporary samples from some members. PUBLIC HEALTH RELEVANCE: This project will advance our understanding of the relationship between social and ancestral identities and biology as well as develop a model for engaging indigenous communities in human microbiome studies. Both those goals will contribute to reducing health disparities in populations with histories of exploitation and economic and political disadvantages.

From the passage of the country's first sterilization law in Indiana in 1907 until the 1960s approximately 60,000 people were sterilized based on eugenic criteria that sought to regulate the reproduction of the "unfit" and mentally deficient. California performed about 20,000, or one-third, of all documented sterilizations nationwide. Few empirical historical analyses of this practice are available. In 2007, while conducting historical research at the Department of Mental Health (now Department of State Hospitals) in Sacramento, Dr. Stern located 19 microfilm reels from this era that contain 15,000 sterilization recommendations along with supplemental letters and forms from nine state hospitals (in total, over 30,000 individual documents). Over the past two years Dr. Stern and her team have created a de-identified HIPAA-compliant data set of these recommendations, which date from 1921 to 1952. We now propose to conduct quantitative analyses with the eugenic sterilization dataset, which contains 212 coded variables, to describe trends in sterilization over time and to describe patterns of sterilization according to gender, age, ethnicity, nationality, diagnosis, institutional home, and many other variables. We propose to link the eugenic sterilization dataset to individual-level census microdata and tract-level census reports, which will allow us to calculate population-based estimates of sterilization rates and test hypotheses about the associations of gender, age, ethnicity, nationality, and diagnosis with the risk of sterilization. or example, we hypothesize that teenagers and Spanish-surnamed patients were disproportionately sterilized in California institutions. In addition, we will analyze qualitative patterns in the data with respect to familial resistance to sterilization, patient refusal, and experiences of institutionalization and sterilization. This study is relevant to contemporary ethical, legal, and social issues in human genomics, as it will provide an empirically-based, richer understanding of how medical paternalism and a particular variant of genetic determinism operated during the eugenics era in the United States, and how eugenic stereotypes about ethnicity, gender, sexual behavior, and intellectual disability influenced the state's intervention into the reproductive lives of institutionalized persons. Furthermore, our findings can inform contemporary conversations about the extent to which societal values of "fitness" and "unfitness," abnormality and normality, can insinuate themselves into the norms of disease prevention and human improvement that guide some genetic technologies and tests.

The Human Genome Project (HGP) is a source of hope and a cause for concern for people with disabilities and their families. Few researchers have solicited the input of the disability community about the HGP or reviewed possible responses to their concerns and expectations. In particular, little is known about the 'grassroots' disability perspectives and, within the grassroots perspective, the views of underrepresented subgroups including women, minorities, and low-income families. To address these issues, this research will identify the concerns and expectations of selected segments of the disability community, examine possible responses in policy and health care practice to address those concerns and expectations, and test a conceptual framework for creating and evaluating disability policy and practice, created in prior research, for its applicability to human genome issues affecting individuals with disabilities, their families, and their representatives. The study will address four key research questions. Question 1: What are the concerns and expectations of persons with disabilities, their families, and their representatives about human genetic research and technologies? Question 2: What are the sources, situations, timing, contexts, and potential impacts for each expectation and concern? Question 3: What ethical, legal/policy, and social responses, educational initiatives, and health-care delivery practices, whether theoretical, proposed, or currently available, might address these expectations and concerns? Question 4: To what extent is the Core Concepts of Disability Policy and Practice Conceptual Framework valid for the purpose of facilitating the creation and evaluation of ethical, legal/policy, and social responses, educational initiatives, and health-care delivery practices that respond to the expectations and concerns of members of the disability community about human genetic research and technologies.

This project explores whether the current regulations for protecting research subjects will provide adequate protections and guidance for future research involving human prenatal gene therapy. It seeks to determine whether additions or other revisions to the regulations are needed to deal with the ethical issues that will be raised in protecting human subjects in such research. Examples of issues that will need to be addressed include the following: 1) The current regulations do not specify how risks and benefits should be balanced between the fetus and pregnant woman. Is there a need for new rules concerning weighing risks and benefits? 2) For certain types of research, the current regulations give children stronger protections than fetuses. Are these relatively weaker protections for fetuses appropriate in the context of gene transfer research, or should stronger protections be extended to them? 3) The fetuses who might be considered for prenatal gene transfer research will have serious genetic diseases. One of the options for women who are informed about such diagnoses will be termination of pregnancy. Should an offer to participate in prenatal gene transfer research be made before, or should it be made after, the woman has made a decision about termination of pregnancy? Alternatively, should this vary, depending on the nature of the particular research? 4) In what situations should the informed consent of the father be obtained for fetal gene transfer research, in addition to the informed consent of the mother? 5) How should the definition of "minimal risk" in the current regulations, which includes the concept of "risks ordinarily encountered in daily life", be interpreted when applied to fetal research subjects? These and other questions will be addressed by carrying out literature research and conceptual and ethical analysis. For each issue, the project will identify main alternative views and the pros and cons of each view. Proposals concerning how the regulations should be worded will be presented. The results of this research will be disseminated by publication of peer-reviewed journal articles and by distribution to research oversight bodies. PUBLIC HEALTH RELEVANCE: Gene therapy research seeks treatments for serious genetic diseases, and it promises to have a significant health impact for society. In the future, it is anticipated that research into human prenatal gene therapy will be feasible and important. This project seeks to improve the protections that will be provided to subjects of prenatal gene therapy research, thereby contributing to the ethical standards for such research.

The long-term objective of this Pathway to Independence Award (K99/ROO) is to train to become an independent researcher in bioethics with a strong interdisciplinary foundation in genetics and epidemiology. My research plan is to characterize ethical and social issues in genetic studies of complex traits and evaluate how and whether they differ from those in genetic studies of Mendelian traits. This research will enable current and future complex disease researchers and policy makers to understand and address these issues proactively. The specific aims of the Mentored Phase (K99) of this award are: 1) to obtain training in qualitative research methods, such as those used in cultural anthropology and oral history research, 2) to expand my training in ethics and my expertise in genetics, specifically current issues in genetics and ELSI issues from the genetics researcher perspective. These training goals will be accomplished through formal coursework and directed readings, participation in seminars and activities at the Stanford Center for Biomedical Ethics and the Department of Genetics, teaching activities and consultation with members of a multi-disciplinary advisory board. During the training period, I also will conduct pilot studies to ensure the successful transition to the Independent Investigator Phase of the award (ROD). The specific aims of the Independent Investigator Phase (ROD) of this proposal are: —> Through semi structured interviews, characterize and analyze the perspectives of genetics and epidemiology researchers and research advocacy group leaders on ethical issues in conducting complex disease research and on the construction of the meaning of genetic data for complex disease risk and identity; —> Through analysis of data from pilot studies, focus groups and surveys, characterize and analyze the perspectives of participants in large studies of Parkinson's Disease and autism about ethical and social concerns, including consent, return of results, sharing of samples and data, the meaning of genetic data, and potential benefits and harms; —> Develop, implement and evaluate a protocol for an "embedded ethicist" to work collaboratively with a team of researchers at the Veterans Affairs Cooperative Studies Program to proactively identify and address ethical and social issues in ongoing complex disease research.

Exome sequencing and whole genome sequencing (ES/WGS) are rapidly emerging as important tools in human genetics research. Unlike conventional approaches, ES/WGS can putatively identify all functional variation in the entire coding sequence of a research participant. As a result, both the number and scope of findings with clinical utility are substantially greater than anticipated by existing guidelines and traditional approaches to return of results. Our objective is to investigate: (1) the best ways to communicate with research participants about what kinds of ES/WGS results could be returned to them; (2) the most effective way to return different kinds of ES/WGS results to participants across a range of study populations; and (3) the impact on study participants of receiving results from ES/WGS studies. We will take advantage of an existing collaboration between genome scientists and ethicists who together are using ES/WGS to discover variants/genes underlying Mendelian and complex diseases in both pediatric and adult populations. Together with experts in clinical genetics, genomics, genetic counseling, and biomedical informatics we will compare the use of traditional approaches for the return of results to the use of an innovative web-based tool that enables longitudinal personalized management of ES results and dynamic engagement of research participants. The proposal has four specific aims: (1) assess and describe participant preferences about return and management of ES results across a broad range of study populations; (2) assess annotated variants in ten candidate genes from participant ES data (annotated exome data are already available on all participants to be studied herein) to identify mutations of potential clinical utility and make recommendations about which results to offer for return; (3) compare the effectiveness of an innovative web-based tool for results management to return of results from a single face-to-face session with a genetic counselor; and (4) assess the psychological, social and health-related impact of the return of ES results using validated survey tools and interviews, and by a comparison of outcomes and satisfaction. We will use our results to develop a comprehensive framework and a set of guidelines and policies for return of results from ES/WGS studies. PUBLIC HEALTH RELEVANCE: Exome sequencing and whole genome sequencing (ES/WGS) are rapidly becoming important tools for the discovery of alleles underlying both Mendelian and complex health-related traits. The scope of the potential results generated by ES/WGS is unprecedented and challenges many of the existing guidelines and policies about return of results from human genetics studies. We propose to develop, optimize and share protocols and innovative tools for return of ES/WGS results across a broad range of study populations.

This project will examine the ethical, legal and policy issues that arise in using emerging genetic testing technologies in four areas: medical research and practice; the workplace; insurance; and law enforcement. The aims of this project are to: focus ethical and legal deliberations by providing an appropriate context with a solid foundation in science; conduct an examination of the key values and ethical issues that must be considered; and address specific legal problems that require resolution. To accomplish this, a series of three interdisciplinary, invitational conferences that will build upon one another will be held. Thirty-five participants--scientists, health care professionals, legal experts, policymakers, ethicists, industry representatives, and others--will be invited to each conference. The first conference will detail the scientific base of genetic testing and the potential capabilities enhanced by the HGP. The second conference will explore the values and ethical con-cerns that underlie assessment of the social implications of genetic testing as well as the develop-ment of professional standards and public policy. The third conference will address key legal problems and develop recommendations for consideration by lawyers, policymakers and other professional and industry groups. Dissemination strategies for conference findings will include wide distribution of conference reports and final project report, symposia and panels at profes-sional or trade association meetings, and seminars for journalists and policymakers.

One of the primary motivations for parents to participate in BRCAI/2 testing is to find out about their minor children's risk of developing cancer. However, parents often report feeling distressed and conflicted about sharing this information with their youngsters once it is available. As few parents receive professional guidance in evaluating the potential risks and benefits of disclosure to children, parents may be prone to make ineffective decisions about communication that could lead to adverse psychosocial outcomes. As clinical genetic testing becomes increasingly more common, this presents an ethical challenge that needs to be better understood so that interventions to promote positive outcomes can be implemented. The investigators propose a prospective, longitudinal study to examine decision-making about disclosing a maternal BRCAI/2 test result to children and the psychosocial outcomes of parents' communication choices among tested mothers and non-tested fathers. The theoretical framework for this investigation is the Conflict Theory of Decision Making and data will be collected using qualitative and quantitative interview procedures. The specific aims are to: —> establish rates of mothers' disclosure of a BRCA1/2 test result to minor children and to identify the determinants of the decision to disclose or not disclose; —> evaluate the impact of BRCA1/2 test result and mother-father shared decision making on parents' communication choices; and —> evaluate the impact of BRCA1/2 test result communication decisions on psychosocial well-being. The subjects in this study are 250 intact mother-father parenting dyads with children ages 8-17 years, where mothers participate in a BRCA1/2 testing program and fathers are not tested. A subset of 20 of these dyads will also complete qualitative interviews to allow us to describe motivation, parental decision making, and emotional impact in greater detail and to heifer define the role of these factors in communication and psychosocial outcomes. A baseline assessment will be conducted with both parents after mothers have attended pre-test education and genetic counseling, but prior to mothers' receipt of their test result, to collect information on background/controlling variables (sociodemographics, medical and family factors, communication history), decision making predictor variables (intentions to disclose, vigilance, decisional balance, decisional conflict), and baseline levels of psychosocial predictor/outcome variables (motivations, appraisals, general and genetic testing distress, parenting alliance, parent-child communication). Follow-up interviews will be conducted 1- and 6-months after post-test counseling/receipt of test result to collect outcome data (disclosure of test result to child, decision satisfaction, psychosocial well-being). The primary group comparisons in multiple regression models will be between mothers who disclose and those who do not disclose.

The MCET and a community of academics, researchers and practitioners have designed an interdisciplinary educational program about the ethical, social and legal implications of the HGP. Using multiple telecommunications networks and manipulatives of print materials, MCET will provide a comprehensive series of programs for the general public, including students, their families, teachers, and health care providers. The cornerstone of this project is a one-semester, bi-weekly elective biology telecourse for senior high students on The Human Genome: Exploring the Human and Scientific Dimensions. The course, to be offered in the fall of 1992 and 1993, will be developed from MCET's prototype course piloted in 1991. Through its satellite and computer networks, MCET is currently linked to 120 school districts in New England. This number is expected to grow, potentially reaching 34,000 teachers and one million students overall. The project design also includes laboratory placements for students, two week-long summer institutes for teachers, public fora and family teleconferences, field trips to laboratories, research sites, and counseling centers, and national teleconferences featuring leaders in the field of genetics research, counseling, bioethics, jurisprudence, and public policy.

Most discussion of the ethical challenges raised by the growth of research biobanks relies on the assumption that the only ethically relevant interests are those that concern risks to subjects' welfare or well-being. Once materials have been collected, and any further risks have been reduced to near-zero by de-identification, it follows that no further protection of the interests of research subjects is required. For this reason, the Office of Human Research Protections has determined that research on de-identified material in biobanks is exempt from the authority of US Federal research regulations. Ethically, this is a highly questionable assumption, since people have a variety of other interests or concerns about the kinds of research that might use their material. These "non-welfare" interests have been the subject of very little empirical research or ethical analysis. The proposed study will remedy this by developing, implementing, and evaluating methods to answer these questions: 1. What is the nature, frequency, distribution, and strength of public attitudes toward non-welfare interests that might be affected by uses of de-identified archived biological samples? 2. What is the ethical weight of those interests in designing policies for the collection and use of biological samples for future research? 3. What is the appropriateness of various models for protecting or accommodating such interests? Methods will include a factorial survey designed to evaluate the effect of selected non-welfare interests on subjects' willingness to give a blanket consent to future uses of biological materials; evaluation of the ethical weight of such interests using various ethical frameworks, such as theories of complicity and group harm; and a systematic evaluation of the suitability of various methods for protecting or accommodating the non-welfare interests of research subjects, which will extend well beyond reliance on informed consent as the primary form of ethical protection. PUBLIC HEALTH RELEVANCE: Research using archived biological samples collected in "biobanks," especially when these are anonymized or de-identified, may often pose no risks to the welfare of those who contributed their samples -- but welfare interests are not the only kind of stake that individuals may have in the uses of their samples. Too little is known about the "non-welfare interests" contributors might have, and how they should shape the ethical protections appropriate to research using biological samples. This study will determine how much these sorts of interests matter to people, and how such interests should be accommodated by biobank policies.

This project investigates the area of newborn genetic screening programs and policies governing state sponsorship of genetic screening. Legal aspects of confidentiality and informed consent will be analyzed in the context of genetic science and medicine. A detailed analysis of state-by state statutory schemes will be undertaken in order to identify potential discriminatory policies and mechanisms for protecting privacy and for obtaining informed consent. The study will include an analysis of situations in which a third party's right to know may prevail over individual privacy interests. Decision-making policies on how genetic conditions are entered into or excluded from a state's genetic screening program will also be studied. Minority populations access to and use of genetic medical and counseling services will be examined, including the nature of services available to rural populations. This project will examine the social and legal aspects of genetic counseling in terms of expertise and cultural sensitivity elements of counseling and the impact of counseling on medical practice liability. Initial phases of the research will study Florida and Georgia's policies and systems in depth.

As we learn more and more about the genetic causal factors for various diseases, there will in many cases be a shift to explaining these diseases in terms of genetics. First, this project will trace the conceptual connections underlying these shifts and to assess their justifications. Second, the project will examine some of the ethical and policy consequences of these shifts. Specifically, the project team will —> examine the impact of the new genetic information on our understanding of health, normality, disease causation, and explanation; —> articulate assumptions in medical genetics about disease causation, explanation, and normality, especially in diagnoses of genetic susceptibility, and compare them with the assumptions about causation and normality embodied in legal theory, case law, and statutes; —> analyze the legal and practical consequences associated with greater awareness of genetic susceptibilities, assess the related policy options, and formulate model legislation; and —> examine the impact of changes in medical diagnoses and medical explanation arising from the HGP on the traditional conception of confidentiality.

The U.S. civil rights movement took place nearly a half century ago, yet significant racial disparities persist in health and justice. The elimination of these disparities is a goal shared by many, including biomedical researchers, medical practitioners, legal scholars, and attorneys. The way in which Americans conceptualize race is more nuanced than the categorical perspective that dominated the early 20th Century. Racial discrimination is itself a health risk factor and known to vary by appearance (e.g. skin pigmentation). A growing number of Americans do not fall within the clear confines of one racial category, an issue that plagues researchers (biomedical and sociological alike) and hinders our efforts to understand the genetic and environmental factors and gene-environment interactions that contribute to the disparities. Despite this, policy mechanisms implemented to resolve the disparities and promote equality continue to rely on concepts of categorical race. How we perceive race, appearance, and ancestry may have important implications for today's manifestations of explicit and implicit racism and understanding these relationships may improve our ability to develop effective policies and educational tools to eliminate disparities in health and justice. I have devoted my career and training to the study of race as a bio-cultural phenomenon and to the ultimate goal of eliminating racial disparities in health and justice. The proposed career development plan is tailored to my multidisciplinary background and is designed to help me secure a full-time faculty position in a multidisciplinary institute or a dual-departmental appointment at a premiere university. With mentor support from accomplished scholars from diverse disciplines - including primary mentor and race/ethnicity/ancestry expert, Dr. Charmaine Royal; ELSI scholar, Dr. Robert Cook-Deegan; and Law Professor Guy-Uriel Charles), I will enhance my prior training in anthropology, genetics, and law and prepare myself for professional independence by (1) gaining additional training in social science research design and analysis and multivariate statistical analysis; (2) gaining experience with research involving DNA ancestry testing, racial identity issues, and minority populations; (3) developing effective teaching techniques for courses with interdisciplinary audiences; (4) improving my grantsmanship; (5) publishing additional law review articles in my area of expertise; and (6) building collaborative, multidisciplinary relationships. The career development plan consists of formal training, informal workshops, regular seminars, and attendance at national professional meetings to maintain a current understanding of anthropology, genetics, and ELSI topics while building my legal publication record and the foundation for my independent research agenda. This proposed research seeks to address racial disparities in health and justice using a multidisciplinary approach. First, this project will involve biological anthropology research to explore the relationships between categorical race, physical appearance, genealogical ancestry, perceived ancestry, and genomic ancestry. Second, this project will involve legal research to explore whether racial disparities in criminal and civil legal contexts are more appropriately attributable to appearance or perceived ancestry as opposed to categorical race and how the existing legal framework can address more nuanced forms of racial discrimination. Third, this project will involve cultural anthropology research to explore the perceptions of race, appearance, and ancestry and the implicit racial prejudices of future legal and medical practitioners. Together, the research aims of this project will have broad implications for biomedical research, medical practice, and legal practice and will help us come closer to eliminating racial disparities in health and justice. PUBLIC HEALTH RELEVANCE: This study will provide important preliminary information on how future medical practitioners (that is, current medical students) view race, appearance, and ancestry. This will assist policymakers and medical institutions in understanding the implications of "racially profiling" doctors and race-indicated pharmaceuticals such as BiDil or carbamazepine. The study's focus on the relationship between race, appearance, and ancestry generally will assist biomedical researchers in research design as well as medical practice.

Forensic DNA profiling is increasingly becoming a standard tool in the search for missing people in the aftermath of mass violence and mass disaster. Yet, there has been very little systematic effort to identify and analyze the major ethical and policy challenges associated with this new use of genetic technology. Thus, stakeholders involved in post-conflict and post-disaster investigations have had to develop their own ad hoc rules and ethical principles for the identification process. This project seeks to identify and analyze the ethical and policy challenges associated with post-conflict and post-disaster DNA identification. There are three sets of specific aims. The first is to determine the extent to which scientists and relatives of the missing share a common understanding of capacities and limitations of the DNA identification process. The second relates to ethical issues associated with the use of DNA identification, including: how to deal with incidental findings (e.g., misattributed paternity); the extent to which for-profit biotechnology companies have unique ethical obligations to victims and human rights organizations that contract their services; and issues of privacy, anonymity, trust, data ownership, informed consent, and illicit use associated with the creation of large genetic databases in countries emerging from conflict or disaster. The third set of aims seeks to elucidate why DNA identification is used enthusiastically in some cases (e.g. Bosnia and post-9/11 New York City), reluctantly in others (e.g., post-Hurricane Katrina Louisiana), and not at all, or under extremely limited circumstances, in others (e.g., Rwanda). It also examines the expanding mandates of the organizations involved in post-conflict and post-disaster DNA identification. The project will begin with a workshop in which post-conflict and post-disaster DNA identification stakeholders from around the world will discuss the ethical and policy challenges they face in their daily work. This workshop will enable the research team to determine what information will be most useful to stakeholders and will guide their subsequent research. In the second phase of the project, the research team will conduct interviews, oral histories, and ethnographic and archival research in various post-conflict and post-disaster settings, including: post-9/11 New York City, post-Katrina Louisiana, Argentina, Bosnia and Herzegovina, Chile, Guatemala, Iraq, Peru, South Africa, and post-tsunami Thailand. This phase will also examine the U.S. military's efforts to recover and identify missing soldiers from the Vietnam War. In addition to writing case studies and comparative analyses to be published in academic journals and online, the research team, in collaboration with the bioethics advisory board, will also produce a white paper that highlights the major ethical challenges associated with post-conflict and post-disaster DNA identification and provides examples of best practices, model policies, and analytical tools for thinking through dilemmas at all stages of the identification process. Finally, the research team will publish a collection of oral histories documenting the family and community perspective on missing persons in a book series for lay readers called Voice of Witness. PUBLIC HEALTH RELEVANCE: A major cause of anger, despair, and hostility in post-conflict and post-disaster settings around the world is the uncertainty and lack of closure felt by families and communities whose loved ones disappeared without a trace. DNA identification of the missing has the potential to ameliorate these situations, but use of the technology is fraught with ethical dilemmas and policy challenges that can severely limit its potential benefits. This research will identify and analyze these issues and challenges, and inform the development of concrete policy recommendations by relevant stakeholders.

The primary objective of this study, first begun in 1999, is to compare newborn identification by expanded screening to clinical identification in children with biochemical genetic disorders in terms of the health and development of affected children and psychosocial consequences for families. The study also assesses the impact of a false positive screen compared to a normal screen in terms of parental response and interactions with the healthcare system. Continuation of this study increases the sample size of children with similar disorders and permits comparisons of children at similar ages, since clinically diagnosed children generally come to attention later than newborn-screened children. The longer-term implications for families can also be assessed. As a supplement to the earlier study, cost effectiveness analyses will be incorporated to quantify the projected health benefits, health risks and costs of expanded newborn screening, including quality of life measures associated with false positive test results. Mothers and fathers of infants diagnosed with metabolic disorders through expanded newborn screening in Massachusetts, Maine and Pennsylvania and parents of children diagnosed with the same set of metabolic disorders in New England States, where expanded newborn screening has not been authorized, will participate in the study. Six months after the diagnosis is confirmed, parents are interviewed and children are administered a medical and neurodevelopmental evaluation. Follow-up interviews and child assessments are administered annually. Mothers and fathers of infants screened false positive (due to an initial specimen in which an abnormality is found but which does not ultimately indicate a disorder) and a control group (parents randomly selected form the public birth registry) are interviewed over the phone when their infants are 6 months old. Primary data from parent interviews and the New England Newborn Screening Program, as well as secondary data from published reports and a panel of experts will be used as inputs to the cost-effectiveness model.

The goal of this project is to collect, and disseminate information on the ethical, legal, and social implications of human genetics. 'Human genetics' includes the HGP, genetic testing and screening, genetic therapy or enhancement, and eugenics. For published materials, the products will be: —> a collection of print and non-print materials on the ethical and policy aspects of human genetics; —> an on-line bibliographic database; —> quarterly and annual printed bibliographies; —> periodic review essays; and —> a full-text database for selected articles. For unpublished/archival materials, the products will be: —> an aid for locating materials in the US and abroad; —> an on-line directory of archival materials; and —> collections of materials on ethics and human genetics.

The overall goal is to study the licensing policies and practices of 24 academic institutions regarding their DNA-based patents. The proposed project is conceived as a pilot study that will test the feasibility of conducting a more comprehensive follow-up study of such policies and practices. Specific aims are as follows: —> provide a clear, concise definition of the phrase 'DNA-based patents'; —> analyze DNA-based patents into subtypes, using categories that are useful for understanding the policies and practices under which they are commercialized; —> gather and publish precise, up-to-date information on the number of U.S. DNA-based patents held by all U.S. and Canadian academic institutions; —> invite the technology transfer offices of all institutions holding at least 25 such patents to participate in a pilot study of their patenting and licensing policies regarding DNA-based patents; —> with the aid of a project advisory board, select a representative group of 24 positive respondents for more detailed study of their licensing policies; —> provide the technology transfer offices of the 24 participating institutions with categorized lists of their DNA-based patents, and to solicit input on categories; —> gather detailed information about the licensing of DNA-based patents at these institutions through a questionnaire and follow-up interviews; —> analyze and publish the data that have been gathered, paying special attention to policies and practices regarding the licensing of DNA-based patents that were based, at least in part, on research supported by federal funding; —> during the second year of the project, to select 10 patents or clusters of patents and to develop case studies that illustrate technology transfer based on DNA-based patents. At least one of these case studies will be focused on a research tool. —> In light of the results from the pilot study, consider the feasibility and utility of conducting a more comprehensive follow-up study of licensing policies and practices regarding DNA-based patents at U.S. and Canadian academic institutions.