ELSI Publications and Products Database

Myocardial infarction (Ml) and peripheral arterial disease (PAD) pose an enormous public health burden and there is an urgent need to develop new strategies for their prevention and treatment. Both are manifestations of atherosclerotic vascular disease yet differ in risk factor profiles and clinical presentation. A major aim of this proposal is to identify novel genetic determinants of atherosclerotic vascular disease. Discovering such determinants will lead to new strategies for identifying high-risk subjects who would benefit from aggressive intervention to prevent Ml and PAD and uncover novel etiologic pathways that may serve as targets for new therapies. We will leverage a biorepository of blood samples in 750 Ml and 750 PAD cases and corresponding controls, genotyping performed by NHGRI, and phenotypes and environmental exposures extracted from Mayo's EMR and mapped to standard data formats such as HL7 and CHI standard vocabularies such as SNOMED and RxNorm; we will validate this process against humanly curated phenotype data on both cohorts. We will also serialize this data to facilitate conventional row-oriented analyses tools such as SAS or R. Since genomic data cannot be meaningfully de-identified or anonymized, we will engage extensively with research participants and the community regarding best practices to weigh the future benefits of genomic research to patients, families, and the society, against the potential risks. A systematic examination of patient consenting practices and patient understanding will inform our ethical conduct of research and foster community engagement with the genomic research agenda. We will develop and refine our consenting procedures in collaboration with Mayo's IRB on the basis of our findings, through an "Ethics Incubator" developed as part of Mayo's Clinical and Translational Science Award (CTSA). A combination of in-depth patient interviews, consenting "experiments", and community engagement using Deliberative Democracy methods will be employed. We will make anonymized phenotype annotations for consenting patients available for scientific access through methods to be defined by the NHGRI Cooperative Agreement steering committee. We will analyze whether genotypes at -500,000 SNP loci across the genome, supplied by NHGRI, are associated with two distinct phenotypes of atherosclerotic vascular disease: Ml and PAD. Further, we will investigate how environmental and lifestyle measures (e.g., smoking), identified from the Mayo EMR, modify the observed relationship between genotype and the atherosclerotic vascular disease phenotypes (i.e., gene-environment interactions). We will also investigate whether gene-gene interactions influence susceptibility to Ml and PAD.

This project represents a unique effort to give segments of the public an advance look at the emerging genetics technology, to learn from lay and professional communities how they feel about that technology, and to work with these communities in formulating laws, institutional policies, professional standards of practice, and applications to clinical decision-making. An instrument, to be called the Genetics Values History, will be developed for the use of health care professionals and their patients for making reproductive decisions. While input will be incorporated from ethics experts and law/policy makers, policy recommendations regarding the use of this emerging technology will be grounded in the wide and diverse views of the public and the health care delivery system. The project will focus on the increasing ability to predict traits and predisposition to disease at ever-earlier stages of pregnancy and prior to conception, and the use of the emerging technology in connection with reproductive decisions. The project proposes to develop a process for policy formulation including careful measurements of attitudes and values of the public and subgroups (patients, minorities, women, professionals, etc.) Dissemination activities will include a conference for policy-makers and the public, as well as involvement with various health, law, and medical ethics professional groups. Publications will be directed to both professional and policy making audiences through relevant journals.

This renewal project, conducted by a consortium of three universities (University of Michigan, Michigan State University and Tuskegee University) will develop a process for engaging minority populations of diverse socioeconomic levels in the process of rational democratic deliberation on moral and political issues relating to genome research and its resulting technology, and will develop recommendations for laws, professional standards and institutional policies regarding the use and application of genome research and technology. Fifteen African American and Latino community-based organizations will identify participants for focus groups and for a series of five dialogue sessions held in the 'home' communities. Focus groups will identify a menu of issues of concern, and dialogue sessions will discuss the issues and develop recommendations. Regional community policy meetings attended by all group participants will convert dialogue group output into specific policy recommendations. Both the recommendations and the process used in their development will be analyzed, with dissemination of recommendations and lessons learned to the public, policy-makers, health educators and practitioners. A Community Advisory Board, with representation from community-based organizations participating in the project, will provide input to all project phases. Qualitative and quantitative methods will be used to evaluate both process and outcome, with comparisons to the initial project.

The specific aim of this project is to determine what criteria should govern return of individual results of pediatric genomic research, using analysis of US law and international guidelines regarding decision making for and by minors as the foundation. This issue, which has received remarkably little attention, must be resolved if this research, which is vital to understanding the contributions of genetic variation to the health of children, is to proceed. In order to develop these criteria, it will be necessary to draw upon a host of ethical, legal, and sociocultural factors, using standard legal analytic tools. There is a long tradition within genetics, embodied in policy statements, such as those by the American Society of Human Genetics, the American College of Medical Genetics, and the American Academy of Pediatrics, of performing genetic tests on minors only when the results would alter the minor's immediate medical care. These limits are justified in part by the claim that, in the absence of need for immediate intervention, the minor should be allowed to decide about genetic testing upon reaching adulthood. More generally, decisions regarding the health care of children are treated differently from those of adults because children, as a matter of law, typically cannot make their own health care decisions. Procedurally, ethical and legal decision making authority, instead, is allocated among: 1) Parents who have broad authority to make choices among available options that affect their children. The scope of parental permission for their children's care, however, is not as broad as their discretion with regard to their own health care; 2) Clinicians who have an independent obligation to the welfare of the minor, which is bounded by the standards of clinical practice as well as legal requirements; 3) Minors who many hold have an increasingly important ethical and legal voice as they mature; and 4) In cases of abuse, neglect, or need to protect public health, the state. Substantively, defining the minor's best interest is often contested. One issue that is particularly challenging is deciding what weight should be given to various potential benefits from returning results, ranging from immediate benefit to the minor's health or reproductive information for the minor's later use to benefits that redound primarily to the family unit as a whole or exclusively to the parents or even to other minors of the same age or with the same condition. Research involving minors is subject to more legal and ethical requirements and limitations than apply to adults. This project brings together three internationally known lawyers, each of whom has written extensively about legal and policy issues in genomics research and in pediatrics, as well as an internationally known pediatrician-philosopher as a consultant, to define the applicable legal rules and to develop guidelines for returning results of genomic research involving minors. PUBLIC HEALTH RELEVANCE: Determining what criteria should govern the return of individual results of pediatric genomics research has to date received remarkably little attention. This issue must be resolved if this research, which is vital to understanding the contributions of genetic variation to the health of children, is to proceed. This project brings together three internationally known lawyers, each of whom has written extensively about legal and policy issues in genomics research and in pediatrics, as well as an internationally known pediatrician-philosopher as a consultant, to define the applicable legal rules and to develop guidelines for returning results of genomic research involving minors.

The grant will fund a working group of scholars in literature, film, and media studies to examine the representation of genetics in literary and popular culture. Throughout the twentieth century, numerous works of fiction, film, and popular culture have attempted to come to terms with advances in genetics. These diverse cultural works have had an enormous effect on the public perception of genetics. The misrepresentations of genetic science in many popular texts lead to mistaken assumptions and misguided pressures on policy makers. Just as important, thoughtful critiques of genetics are emerging in contemporary literature, critiques that could be of value to scientists, health care professionals, and other researchers exploring the ethical, legal, and social implications of the Human Genome Project. Using research methods traditional to the humanities, and particularly, to literary studies, the working group will (1) identify and classify this body of literary and popular texts; (2) compose critical assessments of these works; (3) gauge the accuracy of their representations of genetics; (4) discuss the social and ethical issues they raise; and (5) trace the history and nature of their influences on public understandings of genetics. The immediate outcome of this exploratory project is a volume of essays that will set the agenda for future research, as well as study aids for future literary scholars and teachers, including lists of primary texts in each category (literature, film, science fiction, etc.), sample syllabi, and bibliographies of secondary sources. In addition to publishing its work in scholarly venues, the working group will establish a web site for the dissemination of its study aids. The exploratory studies produced by the working group will establish the foundation for a new field of literary scholarship dedicated to examining genetics in literature, with the aim of extending the study of the ethical and social implications of genetics into literature departments in high schools, colleges, and graduate programs throughout the nation.

This project will explore the breadth of current efforts to structure public health practice to respond to advances in genetics, analyzing these efforts for their consistency with existing public health law and policy and for their responsiveness to the lessons of history. The roles of public health institutions in reproductive genetic testing, state-run newborn screening programs, and predictive genetic testing will receive particular emphasis. The results of this analysis will be used to determine whether the new policies being adopted in public health genetics optimally meet the needs of the public, and if not, to suggest areas for improvement. In March 2000, this project supported a meeting 'Public Dialogue on Gene Patenting,' to bring together consumers, researchers, and industry to discuss and coordinate a response to the Patent and Trademark Office's (PTO's) Revised Interim Utility Examination Guidelines insofar as they affect the patentability of genetic sequence data.

Individuals' religious beliefs and practices can be implicated and challenged as they deal with the consequences of advances in genomics. While many people can reconcile these two bodies of knowledge, others are made uneasy or distressed by this new science in ways that affect their personal and political choices. For the past two years with the support of the Center for the Study of Religion and Culture at Vanderbilt, faculty, staff, and graduate students at Vanderbilt University and Meharry Medical College, one of the nation's most distinguished historically black medical schools, have been working together to understand the role religion plays as clinicians - genetic counselors, nurses, and physicians, - clergy, and patients deal with learning about genetic contributions to disease in the clinical setting. Our work in this area has been both conceptual and empirical, with each inquiry informing and enriching the other. Other scholars around the country have been exploring this critical intersection as well. We seek funding in this application for a pre-conference meeting and an invited conference to bring our group together with investigators involved in transdisciplinary projects around the country as well as local participants from the clinic, the church, and the public. Our purpose is to identify: 1) What is currently understood about the role religion plays in individuals' response to genetic information; 2) What is currently understood about the role religion plays in shaping clinicians' and clergy's efforts to assist patients and parishioners when dealing with genetic information; and 3) What resources are needed to assist patients, clinicians, and clergy. We anticipate that the outcomes of our work together will be a richer understanding of these issues, a series of publications directed toward clinicians and clergy, and collaborations for future explorations.

The main goal of this proposal is to develop appropriate comprehensive counseling guidelines for predictive colon cancer gene testing by assessing perceptions and attitudes toward the gene tests, including their social and psychological determinants, and assessing the impact of the test on at-risk persons. Our specific aims are: (1) To characterize in at-risk individuals those psychosocial factors that predict willingness to undergo genetic testing for colon cancer, to determine projected uses that will be made of the gene test, and to determine the influence of social context, primarily family culture, in shaping at-risk individuals' attitudes toward and perceptions of the gene test. This will be accomplished by a mail survey of 1,000 adults at risk for colon cancer. (2) To compare attitudes toward and perceptions of genetic testing for colon cancer between white and African-American individuals (and a subsample of their families). This will be accomplished with the mail survey data and by qualitative telephone interviews with members of 50 families (25 white, 25 African-American) sampled from the mail survey. (3) To identify predictors of psychological distress associated with pre- and post-disclosure cancer risk perception based on: experiences with cancer, knowledge/beliefs/feelings about cancer, implicit models of illness regarding cancer, cancer risk perceptions, coping behaviors, and tolerance for ambiguity. 200 individuals at high risk for colon cancer, based on family history, will be offered MSH2 and MLH1 gene tests. Data will be collected by questionnaire and interviews before and after gene testing (at one month, six months, and one year post disclosure). The gene test will result in one of three possible outcomes: definite gene- positive, definite gene-negative, and inconclusive gene-negative. These will be stratified and compared using pre- and post disclosure measures of distress and attitudes. (4) To assess post disclosure prevention-oriented health behaviors among persons receiving gene positive, gene negative and inconclusive test results. Because screening recommendations may vary with age, we will stratify our analyses by age groups as well as gene test outcome.

The long-term objective of this project is to develop a comprehensive analysis of the emergence of a new technological regime in criminal identification constructed around genetic information. The project is interested in examining and understanding the implicit and explicit connections between archival, forensic, and diagnostic applications of genetic information in the criminal justice system. The project further seeks to elucidate the employment of predatory sex offenders as "poster criminals" for this new regime. The project seeks to explore the connection between genetic information, behavioral genetics, end the construction of the sexually violent predator as a medico-legal entity. The project seeks to draw connections between the application of genetic information to criminal justice and the construction of criminality as a problem of mobility and surveillance. The specific aims of the project are the gathering, analysis, and synthesis of data documenting this socio-legal phenomenon and the publication of peer-reviewed journal articles disseminating this documentation. These articles will then be assembled into a book manuscript to be published by a university or serious trade press. Data gathered will be drawn from legal, scientific, medical, and popular literatures. The project will employ the methods of science and technology studies, socio-legal studies, risk studies, history, and sociology.

This project explores the feasibility of producing messages about human genetic variation that are non-discriminatory in their impact on public attitudes. Toward this end it pursues three research objectives. First, the project employs focus groups to describe existing lay understandings of the relationships among genetics, race, and human characteristics (including disease). Second, building on the results of the focus groups, it will use a representative population survey and a message impact study to identify vocabularies and to generate sample messages for communicating about human variation in nondiscriminatory ways. Third, it will develop a reliable and appropriate measurement scale for assessing the discriminatory impact of messages about human genetic variation. The project will focus on the concerns of African Americans about discrimination and genetics and on attitudes about African Americans and genetics held by European Americans and the general population.

One of the projected health dividends of the Human Genome Project is the use of personalized multi-gene testing to identify individual susceptibilities, so that individuals can undertake preventive courses of action. Among other things, for this to be successful medical personnel must be able to convey this information without creating fatalism and in ways that are comprehensible and believable to lay people. To facilitate such health messages, this project will describe lay understandings of the interactions of genes with non- genetic factors (commonly referred to as "environmental" factors) in relationship to common complex diseases (adult onset diabetes, "heart" disease, depression, and lung cancer). It will compare these to the models employed in medical research and outreach, identifying areas of consonance and dissonance. It will then initiate studies to explore the effectiveness of use of particular models within health messages. Qualitative methods will be used to generate grounded, rich analyses of the models, and quantitative methods will be used to assess the frequency of distribution of various models. Medical research and clinical models will be assessed by examining published scientific journals and web-based clinical representations. Lay understandings will be assessed in a two stage process. In-depth, in-person interviews with lay people will be conducted. Then, these transcripts will be used to develop a closed question survey to be administered to a national random population sample to ascertain frequency and distributions of various models. After analysis of areas of commonalities in lay and expert models, preliminary "best message strategies" will be tested to assess 1) whether interactive models produce lower fatalism than non-interactive models, 2) whether use of consonant models increases belief, identity consonance, perceived efficacy, and intention to adhere to prescriptions and 3) whether some models are more effective than others at enhancing belief, identity consonance, perceived efficacy, and intention to adhere to prescriptions. This project will identify how lay people think about the role of genes in common diseases. It will develop ways of telling people the results of personalized genetic testing without increasing their fatalism. This will help recipients to adopt behaviors that will better stave off the risks identified by the tests.

This study employs a critical content analytic approach to ascertain the degree of perfectionist, essentialist and discriminatory social norms associated with the rise in public discourse about genetic medicine. It employs a coding protocol with demonstrated intercoder reliability. Using this protocol, coders will be able to produce a quantitative survey of a structured random sample of congressional discourse, newspapers, popular magazines, and television coverage from 1950 to 1995. The resulting comparative and proportional description of changes in public norms regarding human reproduction, health, and identity will enable more accurate forecasting of future uptake of genetic medicine and will help to highlight appropriate precautions and opportunities.

This sociological and historical study examines how the news media have presented information, findings and theories about genetics and behavior from 1945 to 1995. Specifically, it examines news reporting of findings related to 'behavioral genetics', focusing on the most frequently-reported genetic-behavior studies, alcoholism and mental illness. Other genetic-behavioral issues in the news, such as achievement (e.g., I.Q. and gender and math), hyperactivity, homosexuality, and criminal behavior, will also be investigated as a comparative case. By using a sociological framework, the study investigates how the news is selected, shaped and presented, and what frameworks, emphases, and 'biases' appear in the news stories. By examining these presentations over time and by comparing the various cases, key assumptions and factors used in presenting genetic findings in the news can be identified. Data for this study will come from a systematic examination of major newspapers and news magazines, televised national evening news, and wire service reports, supplemented by interviews with science and medicine journalists and editors of key scientific journals.

This qualitative study is designed to examine the ethical conduct of clinical research, including the conduct of clinical trials, in rural healthcare settings. This study is of great significance since more than half of the clinical research, including pharmacogenomic studies, conducted in the U.S. takes place in physicians' offices, clinics, and hospitals.(1-8) It is no longer unusual to encounter rural physicians, nurses, research coordinators, and hospital administrators who are engaged, in various capacities, in the clinical research enterprise. Many of the staff recruited in rural areas by pharmaceutical and other biotechnology companies have limited education, training, or experience in the responsible conduct of research, research ethics, and the protection of research participants. In addition, many rural institutions do not have their own Institutional Review Board (IRB) or policies in place to guide their research activities and so rely on oversight provided by central or independent IRBs. As rural healthcare professionals enter the research arena, it is important to ensure that adequate protocols and policies are in place so as to assure adequate protection of the human research participants who live in rural communities. Under the leadership of Multiple PIs Ann Cook, Ph.D., and Hoas, Ph.D., researchers at The University of Montana (UM) propose a qualitative study using key informant interviews to examine how four key stakeholder groups - physicians, nurses, research coordinators, and hospital administrators - who conduct or engage in clinical research in rural healthcare settings address these research ethics issues, especially the adequate protection of research participants. The study has two aims: Specific Aim 1: Identify the ethical issues that face four rural stakeholder groups who engage in clinical research in rural private practices, clinics, and hospitals. Specific Aim 2: Explore how features of the rural environment may influence stakeholders' abilities to maintain research integrity when engaging in clinical research activities. The three year study will be conducted in12 states with large rural populations; 11 of these states meet the criteria for the NIH Institutional Development Award (IDeA) program of the National Center for Research Resources (NCRR). The potential impact on science and the public's health and well-being is twofold. Findings from this proposed study will shed light on whether: (1) existing policies and guidance are sufficient to ensure optimal protection of rural research participants; (2) the safeguards are in place to assure adherence to the principles of research integrity when conducting clinical research in rural healthcare settings. PUBLIC HEALTH RELEVANCE: As rural clinicians, coordinators, nurses, and administrators increasingly participate in the clinical research enterprise, it is important to identify ethical issues that accompany such research when it is conducted in rural settings. The study's potential impact on science and the public's health and well-being is twofold. Findings from this proposed study will shed light on whether: (1) existing policies and guidance are sufficient to ensure optimal protection of rural research participants; (2) the safeguards are in place to assure adherence to the principles of research integrity when conducting clinical research in rural healthcare settings.

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