ELSI Publications and Products Database

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

This project will develop a nine-week module to be used in the biology curriculum for high school students, as part of the NIH/ADAMHA Science Education Partnership awards. The module, 'Molecular Genetics and Human Affairs' will teach the structure of DNA and include activities focused on the organization, replication, and utilization of the information of DNA, using humans as a model system. Students will learn how to clone a gene and how to analyze a gene at the molecular level. Problems in human genetics will be discussed in molecular terms, and the new techniques being used to map the human genome will be described. Laboratory exercises will involve DNA isolation, transformation and restriction analysis and the uses of PCR. Our ability to create new genes and to transform bacteria, plant cells, and animal cells will be described, including a discussion of the prospects for human gene therapy. The module will be developed at four levels: for honors, main-stream, and low achieving high school students, and also for adult students in the Washington University continuing education program. This module will also provide material for a summer workshop for high school teachers. A second module in environmental chemistry is also being developed.

This workshop will bring together 22 distinguished individuals including experts in the fields of ethics, law and the social sciences as well as investigators playing key roles in the human genome initiative and related biomedical research. The purpose of this workshop is to attempt to reach consensus on the most important ethical and legal issues raised by the human genome initiative and to suggest mechanisms that can deal with these issues in the most effective and efficient manner. The aim is to identify those ethical and legal issues on which there is consensus, and to crystallize that consensus into a strategy for dealing with the issues. On issues on which consensus cannot be reached, the issues will be identified, and the competing views on them summarized, together with a suggested prioritization and strategy as to how to continue to work toward consensus on them in the future. The written products from this workshop will be both a summary article prepared by the co-investigators, as well as a set of proceedings.

The primary goal of this pilot project is to examine the relationship between BRCA1 genetic counseling communication patterns and cancer-related health behaviors and psychosocial adjustment of an ethnically and culturally diverse sample. Audio-taped genetic counseling sessions of a Utah-based Caucasian kindred (K2082) and a large African American kindred (K2099) will be analyzed using a widely used provider-patient communication analysis system, Roter Interaction Analysis System (RIAS) adapted for this study. Trained coders will analyze 180 audio tapes (90 from each kindred) of BRAC1 pre-test genetic counseling sessions using the adapted version of RIAS. These communication variables will be merged within the larger data sets of baseline and outcome measures on health behaviors (e.g., clinical and breast self-exam, prophylactic surgery, etc.) and psychosocial adjustment (e.g., cancer-specific distress) for one week and four months post-testing. Predicator variables of participant adjustment include: sociodemographics, communication factors (e.g., medical information), kindred, pre-test distress levels, and carrier status. The two studies used as data sources provide extensive psychosocial and behavioral data on participants' pre and post testing. These data will allow the investigators to examine the relationship between BRCA1 genetic counseling communication patterns and longitudinal outcomes. Specifically, it will examine individuals who are at risk for adverse psychosocial effects of genetic testing and how their communication process varies according to their level of distress.

This project will bring together an interdisciplinary working group of scholars to explore these questions. During a three year period, it will meet to develop the language, criteria, and conceptual framework for exploring issues related to genetic variation research and social identity. Specifically the project will address ways in which the information emerging from research into human genetic variation may affect three overlapping domains: concepts of identity and authenticity; concepts of identity and community; and concepts of identity, family, and kinship. The multidisciplinary working group that will explore these complex and novel issues includes scholars from genetics, philosophy, religious studies, sociology, cultural anthropology, and history, as well as scholars whose work is intimately tied to questions of race and ethnicity, such as those working in African-American studies, Jewish Studies, and Native American Studies. At the end of the project, we will be prepared to both publish the scholarly discourse to the academic community and to disseminate the results of our reflections to a wider audience via the Internet.

Ethical and Cultural Implications of Specimen Banking among Alaska Native People is proposed by Principal Investigator Ruth A. Etzel, M.D., Ph.D. The aims of this project are to: 1) determine the feasibility of obtaining current addresses for Native persons with tissue stored in the Specimen Bank; 2) determine whether adequate informed consent was obtained from individuals whose specimens are stored in the specimen bank; 3) determine specific past uses of each participants? specimens and assess whether uses were consistent with participants? consent, if any; 4) conduct a pre- and post-survey among a sample of Alaska Native and American Indian people to find out their knowledge of and attitudes towards use of stored tissue specimens; 5) convene a small group of researchers with experience in community-based participatory research to learn from one another about strategies for success; 6) begin a dialogue with Alaska Native communities about the specimen bank, including its benefits and risks; 7) develop by consensus a guideline document on the operation and management of Alaska Native specimens in the specimen bank; 8) develop a model comprehensive consent form for the specimen bank; and 9) develop a method for periodic communications with identifiable participants in order to provide them with information about specimen bank activities and opportunities to consent. The project is significantly relevant to Southcentral Foundation?s mission of "working together with the Native community to achieve wellness through health and related services," and will help Alaska Native people to ensure that the specimen bank is ultimately used to answer their questions about their health. The project is relevant to NARCH purposes and objectives of increasing partnership capacity to reduce distrust by Alaska Native /American Indian communities and people toward research, and of encouraging competitive research linked to the health priorities of the applicant organization in reducing health disparities. Alaska Native people have been subjected to unethical and dangerous research activities in the past, creating a communal sense of wariness about research and researchers. An estimated 84,500 persons have blood or tissue stored in the specimen bank, but many do not know or remember that they have samples stored there. Public health relevance: This project enhances future public health efforts by building trust and demonstrating that research using stored specimens will not be conducted without the informed consent of those who gave the specimens that are stored in the Alaska Area Specimen Bank. The project will build a longterm research partnership between Alaska Native American Indian people and health researchers.

This conference was a collaboration of the Mid-Atlantic Regional Human Genetics Network (MARHGN) and the Alliance of Genetic Support Groups. Represented groups included consumers, genetics and other health professionals, industrial representatives, and ethicists. The purpose was to increase understanding of the process and expected outcome of the Human Genome Project among genetics professionals and consumers, to provide a forum in which the potential ethical, legal, and social implications of the HGP can be identified and discussed, and to serve as a demonstration model for future educational efforts and public discussion about the HGP. The format consisted of plenary sessions, discussion sessions, and a summary of conference conclusions and recommendations.

The purpose of this project is to contribute empirical data concerning the values, beliefs, and experiences of persons (or family members of persons) with genetic conditions regarding informational privacy and access to health insurance in the context of health care reform. These data then will be analyzed for their normative and legal implications for public policy. Using a cross-sectional design, data will be obtained by personal interviews with 450 persons affected by genetic conditions or their family members. As a comparison, 150 persons affected by HIV, 150 persons with diabetes, and 150 persons with a mental illness or their family members also will be interviewed. Participants will be asked questions concerning their beliefs about who has access to medical information under what circumstances, their experiences concerning medical disclosure, their fears concerning potentially harmful disclosure, and the value they place on restricting access to medical information and on having the government protect them against unwanted losses of privacy with respect to such information. Questions also will be asked concerning specific experiences regarding access to health insurance and the relationship between their employment choices and securing or maintaining health insurance benefits. Data obtained from this project should materially assist policy makers in effecting the necessary balance between the privacy interests of the individual and the interest of the public in the health benefits likely to emerge from the Human Genome Project.

Student Pugwash, an international organization for undergraduate science students interested in science and society interactions, developed and implemented a working group within the 7th biennial Student Pugwash USA Conference on 'Ethics and the Use of Genetic Information on June 14-20, 1992. They will follow up the conference with related activities at campus chapters. The working group on Ethics and the Use of Genetic Information was one of the dedicated groups that met every day of the six-day conference to explore specific issues in depth. The working group was composed of four senior professionals and 15 undergraduate college students competitively selected on the basis of original research papers written on ELSI issues, which will subsequently be published. Follow up activities include a chapter organizing workshop, and two regional chapter meetings dedicated to fostering the discussion of HGP and ELSI issues in local Student Pugwash chapters and organizing HGP-related events on their campuses.

This project seeks to delineate problems to be addressed in testing programs in this study of perception of carrier status by CF siblings. By interviewing the adult siblings of CF patients and the CF siblings' spouses, the study will identify factors motivating or interfering with the pursuit of CF carrier testing in siblings, and assess the spouses' level of interest in testing. In addition to examining interest in testing, this study aims to assess the levels of understanding of test results and knowledge of medical aspects of CF by the interviewees, as well as to assess psychological functioning of CF siblings and spouses following testing.

Although cystic fibrosis (CF) is the most common, life threatening autosomal recessive genetic disorder of the white population, there are often delays in diagnosis and hence initiation of treatment. Advances of the past two decades have made CF screening feasible using routinely collected neonatal blood specimens and determining trypsinogen levels and CF mutations by DNA analyses. Our overall goal is to address the following hypothesis: Early diagnosis of CF through neonatal screening will be medically beneficial without major risks. 'Medically beneficial' refers to better nutritional and/or pulmonary status, whereas 'risks' include laboratory errors, potential iatrogenic medical sequelae, miscommunication or misunderstanding and adverse psychosocial consequences. Specific aims include assessment of the benefits, risks, costs, quality of life, and cognitive function associated with CF neonatal screening and delineation of the characteristic epidemiologic features of CF. A comprehensive, randomized clinical trial emphasizing early diagnosis as the key variable has been underway since 1985. Nutritional status has been assessed by anthropometric and biochemical methods, and the results have demonstrated significant benefits in the screened group. Answering the important questions about pulmonary outcome will require five more years of follow-up evaluation focused on lung function measures and quantitative chest radiology, including high resolution computerized tomography. If the questions underlying this study are answered favorably, it is likely that neonatal screening using a combination of trypsinogen and DNA tests will become the routine method for identifying new cases of CF and that diagnosis in early infancy will allow prevention of many clinically significant problems such as malnutrition. If CF neonatal screening is implemented nationally, however, several epidemiologic gaps must be closed, and this will require more precise data on the course of this disease and determination of risk factors for pulmonary infections with Pseudomonas aeruginosa. This project will generate that important information, as well as essential data on the quality of life and cognitive function of children with CF who experience early or delayed diagnosis. We will also clarify the risks of screening and delineate for the first time the costs of diagnosis and treatment of CF throughout childhood as well as the cost-effectiveness of screening.

As a part of their work on the U.S. Human Genome Project, NHGRI has produced a multimedia educational kit, The Human Genome Project: Exploring our Molecular Selves. The kit (which could only be ordered online) is intended to reach a wide variety of audiences including high school biology teachers and students as well as other educators, scientists, healthcare professionals, and college students. Long-term goals of this resource are to increase access to current information about the Human Genome Project, to enhance science education, and to enhance presentations and discussions about the Human Genome Project, genetics, and genomics. The proposed research is an outcome evaluation of this multimedia education kit, to: (a) measure the effects of this resource on the community, including both users of the materials and those who will benefit from its use (e.g., students), and (b) assess its effectiveness in meeting the above mentioned project goals. Specific evaluation objectives include: 1) identifying who ordered the kit to establish a picture of its reach, 2) exploring the extent to which recipients perceive their access to the latest information about the Human Genome Project to be improved, 3) examining use of kit and determining factors that predict extent of use among recipients (e.g., grade and subject taught, place of employment, level of supervisor support), 4) assessing its perceived effectiveness among teachers and students in enhancing high school science education, and 5) assessing its perceived effectiveness among the range of users in enhancing presentations and discussions about the Human Genome Project, genetics, and genomics. Using a sample of kit recipients, the evaluation will employ both online and mail surveys and phone interviews in the collection of quantitative and qualitative data. Post only data will be collected from recipients during the school year to assess plans for use, actual use, and perceived outcomes of use regarding the specific areas of interest to NHGRI, as described above.

This project will utilize the expertise of genetic counselors in developing, implementing and evaluating education programs for health professionals which focus on the clinical applications of human genome research. After the development of the curriculum and communication materials, the courses will be piloted for a group of local health professionals. Following evaluation and revision, a 'train the trainer' model will be used whereby selected genetic counselors will be trained to conduct courses in their area using the developed curriculum and communication materials as well as local resources to ensure a referral network. These trained genetic counselors will then be asked to train other genetic counselors to conduct courses for health professionals in their catchment areas. In addition, research on needs, attitudes, perceptions and knowledge of human genome/genetic counseling and testing issues will be conducted.

The specific aims of this project are: to identify the ethical, legal, and social implications of the HGP from the perspectives of two Native American communities, with particular emphasis on Native conceptions of privacy issues; to describe the decision making process in each community, with particular emphasis on collective decision making and the extent of communal authority over individual members; to compare the results of ELSI research conducted with the two Native populations; and to use this comparison to construct a model for ELSI research and possible HGP participation with non-Western communities that will be generally applicable while still culturally sensitive. Project researchers will use qualitative, ethnographic approaches including genealogical, oral historical, political anthropological, and discourse analysis methodologies to work with participants from the Plains Apache and Euchee communities. Study participants in each community will be organized into working groups which will discuss ELSI issues in three general areas: biological substance and genealogical relationship; conceptions of history and identity; and community decision making and authority. Based on these discussions, which will make use of empirical case studies to consider HGP implications from the Native community's point of view, project researchers will identify, describe, and compare community perspectives and construct the general model.

This is a qualitative, ethnographic study that is designed to generate a number of empirical examples of community review in action. Project investigators have established a working relationship with three diverse African American populations in Oklahoma: 1) rural all-Black towns that were initially established in the 1890s; 2) rural populations of Freedmen who were initially brought to Oklahoma in the 1830s by slave-owning members of the Five Civilized Tribes; and 3) the urban African American population of Oklahoma City, which is comprised of complex, heterogeneous, and overlapping local social networks and communities. A collaborative study of variation in haplotypes associated with prostate cancer will be proposed in each of these populations. A process of community review will be undertaken in each local community as well as in higher-order, nested communities to identify appropriate social units and networks to engage in discussions about research questions and design as well as human subjects issues and protections. Community members will assist in developing culturally appropriate informed consent protocols. The combined ethnographic and genetic study will provide a crucial context for understanding the population-specific implications of research on human genetic variation. It is anticipated that different levels of community review will be applicable to different kinds of local and nested communities.

The relevance of racial and ethnic identities for biomedical research and patient care increasingly is at issue, particularly in the emerging contexts of post-genomic research and genetic medicine. The relationship between biological relatedness and social construction of identity is not a direct one. Mistaken uses of social identity as a proxy for biological relatedness can harm entire categories of people by implying that they are biologically different from others. At the same time, though, some socially defined populations do have higher incidences of some diseases and higher frequencies of some polymorphisms and haplotypes, suggesting that there is some value in using social identity as an indicator for participant recruitment in research studies as well as for clinical diagnoses. One way of resolving the imperfect fit between biological relatedness and social identity, at least in the case of genetic research and medicine, is to develop approaches for rigorously specifying social identity (i.e., by constructing extended pedigrees with health history information that go beyond the family health history information typically collected in clinical situations). Thus, we will conduct an empirical study of two questions: 1) Does a rigorous investigation of study participants' social identities (i.e.. families, extended pedigrees, and racial and ethnic groups and subgroups) add scientific and clinical value compared with the standard use of self-reported family health histories and racial and ethnic identifies? 2) How do existing familial, group and subgroup social dynamics affect study participants' perceptions and concerns about the collection and use of third-party information for clinical and research purposes? We will adapt an approach we developed for historically stable Native North American populations to rigorously specify social identity in historically mobile, geographically dispersed African-American and Euro-American populations. Doing so will allow us to construct extended pedigrees and population subgroups that we will then use to investigate the scientific and clinical value of more rigorously specified social identities compared with currently standard practices. Finally, we will examine the implications of third-party information from the perspectives of study participants. We will conduct this project in the contexts of actual clinical populations.

The proposed project explores how researchers in the new and growing arena of gene- environment interaction (GxE) research operationalize the concept of "a human population." The proposed project will add critical information about how traditional epidemiologists and genetic epidemiologists, using different kinds of data, work together to operationalize groups in their biomedical studies of disease. This phase of our research will investigate the challenges and complexities faced by researchers during a) the design of populations when environmental variables are integrated into genetics studies, and b) when research centers pool samples along "similarities" in genetics or environmental exposures. The project will examine the social and ethical dimensions of analyses and results generated by GxE research. This is particularly important as these GxE studies aim to integrate genetic data with environmental variables that may be connected to socio-cultural categories like race and ethnicity, including diet and lifestyle. The GxE research sites to be studied have longitudinal information on environmental exposures from about 70,000 individuals of mostly under-represented racial and ethnic backgrounds, and have recently added DNA and tissue materials. This combination of GxE variables, diverse populations, and the large size of the cohort makes their repository one of the most desirable in the US for samples for GxE studies. The research methodology for the proposed study involves primarily ethnographic observation of work processes in these laboratories, interviews with scientists, and documentary analyses. This project will provide a broader base of empirical information from which the scientific community, bioethicists and policy makers can understand the potential impact of using different frameworks for grouping people and defining populations in biomedicine. Its findings will be useful to scientists in efforts to recognize and deliberate about their usage of concepts of population in future studies. PUBLIC HEALTH RELEVANCE: The proposed project will investigate the conceptualization and operationalization of concepts of population in studies of gene-environment interactions in human genetic epidemiology research. The project will analyze the practices and problems faced by researchers as they work to compare genomic data with information on environmental factors to understand gene-environment interactions. Some of the challenges faced involve analyzing pooled data collected using different categories. The aim of the proposed project is to provide information and analyses about different uses and notions of population in biomedicine, which will be useful for improving the reliability and relevance of public health-related gene-environment interaction studies for different individuals and groups.

With the recent 'completion' of the human genome sequence, geneticists have turned their attention to a detailed consideration of variation, both as it occurs in the genome and as it relates to the etiology of common complex traits. The main objective of the research training proposed here is to place the uses and understandings of human variation in a multidisciplinary perspective, both to identify the processes by which scientific understanding is negotiated and constructed, and to consider the ways in which scientific choices determine ethical outcomes. Specifically, the proposed research will 1) identify the historical antecedents of current ideas regarding the genetic basis of complex disease, in particular the Common Disease/Common Variant hypothesis, 2) explore the ways in which 'knowledge' about the genetic basis of complex disease is currently constructed, aiming to identify the forces (scientific, commercial, and political) that have led to the success of the CD/CV model, and 3) use this historical and sociological analysis to inform a detailed look at the ethical and epistemological implications of the current research consensus. To the extent that nonscientific forces and vested interests direct the development of a dominant research paradigm like the CD/CV, epistemological issues may be overlooked or downplayed, with potentially important ethical consequences. Research methods will include extensive archival research (of both primary data reports and related press coverage) as well as semi-structured interviews with human geneticists.

The purpose of this study is to explore the interplay of parents' beliefs and behaviors in order to identify information management styles used by families in which there is a child with a genetic condition. In addition, the role that health care professionals play in helping families manage genetic information will be explored. Specific aims: 1) identify family information management styles by a) describing the parents' knowledge, beliefs and behavioral strategies for interpreting and using genetic information; b) describing the family and health care context in which information management occurs; and c) further refining the styles using family context variables of life satisfaction, family functioning, and child functional status; 2) identify factors that facilitate or impede the parents' ability to access, interpret, convey, and use information; 3) describe health professionals' beliefs and strategies for helping parents use genetic information; and 4) examine the linkages between the views and strategies of parents and health care professionals. Using a noncategorical approach, 75 to 100 families (N=182 parents) of a school- aged child with a genetic condition will comprise the sample. Parents will be invited to participate in a tape recorded semi-structured interview, and complete three structured instruments measuring life satisfaction, family functioning, and child's functional status. Twenty-seven health care professionals from clinics the child with a genetic conditions attends will also be invited to be interviewed about their role in information management. Qualitative analysis of the interview data will focus on identifying major themes and overarching patterns (styles) of information management of parents and health care professionals. Cluster analysis will be used to refine the family information management styles. The results will inform professionals working with families, and contribute to the development of expert clinical judgment as a basis for addressing families' questions and concerns about a child's genetic condition.

This pilot project will invite adult members of classic and variant Li-Fraumeni families at 50% risk of carrying an altered p53 gene to participate in a program in which they could be made aware of their p53 status. We will assess the expectations and motivations of at-risk adults and their partners for participation in a program of predictive testing. We will explore their psychological preparedness to participate, and, after disclosure of results, will evaluate the impact of the knowledge of their p53 status on their psychological well-being and family relationships. We will assess their understanding of genetic information, and will provide extensive genetic counseling regarding relevant choices and their implications through the process. We will explore with them the readiness of subjects who are parents and prospective parents to enter their at-risk children into a predictive testing program were it to exist, and what features of such a program might be important to families. We will also assess the receptiveness of the population to advice regarding disease surveillance and risk avoidance. We will conduct this program with full cognizance of the complex ethical and social issues which are inextricable from this work.