First Community Consultation on the Responsible Collection and Use of Samples for Genetic Research

Location

Bethesda, Maryland

Start Date
End Date

September 25-26, 2000

Executive Summary

The First Community Consultation on the Responsible Collection and Use of Samples for Genetic Research was held in Bethesda, Maryland, on September 25-26, 2000. The consultation was convened by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH), in cooperation with and with financial support from the National Science Foundation, the Department of Energy, and eight other NIH components (National Human Genome Research Institute, Fogarty International Center, National Institute of Environmental Health Sciences, National Institute on Deafness and Other Communication Disorders, National Institute on Aging, National Eye Institute, National Institute of Neurological Disorders and Stroke, and Office of the Director). Approximately 120 individuals participated in the consultation, half from a broad range of communities and populations, and half from government. The participants shared their views and concerns about population- and community-based genetic research, expanding the focus of the meeting from the collection and use of blood or other tissue samples for genetic research to broader issues and concerns about the conduct of genetic research in general with populations and communities.

With completion of the first draft of the human genome sequence in June 2000, scientists have unprecedented opportunities for further research that will help them develop methods to understand, treat, and prevent human diseases. Through genetic research, scientists now know that individuals and populations are more alike than they are different and that most genetic variation occurs within all ethnic and racial groups, resulting from their common origin. Only about 200,000 sites among the 3 billion bases of human DNA account for functionally significant, common variants in the world's population, while 99.9 percent of the genome is the same between any two individuals. Genetic research that involves populations and communities, particularly those with a higher frequency of a particular disease, is important for identifying genetic variants that may be associated with a disease. The promise of this research has already been shown, with the discovery of gene variants associated with a number of diseases, including cystic fibrosis, diabetes, Tay-Sachs disease, and colon cancer.

The participation of populations and communities in genetic research presents some concerns, however, and every effort must be made to ensure that the research proceeds fairly. The potential for discrimination, stigmatization, and breaches of privacy is a major concern for individuals and communities who may wish to participate in the research. Other concerns relate to the definition of communities, the perceived benefits and risks of the research for these communities and their members, and the full participation of communities in the entire research process. Different communities and community members will have different needs and interests in the proposed research and may want to participate in various ways.

Several overriding themes for NIH-supported genetic research involving populations and communities arose during the discussions:

  • Involving communities in the planning, conduct, and reporting of research can be a "win-win" situation for both NIH and the communities participating in genetic research.
  • The ethical principles of beneficence, justice, and respect for persons should be upheld in all community-based research. The primary message to researchers is: "do no harm."
  • NIH must consider community aspects and risks and benefits to the community as significant, and as important, as the risks and benefits for individuals.
  • NIH should implement systemic changes in its extramural grants program to advance biomedical and behavioral research in a responsible way by including the community at every stage of the research.

Ten major recommendations for genetic research involving populations and communities are, in brief:

  1. Define "Community" in Appropriate and Meaningful Ways. "Community," a social construct, can be defined in many different ways, and individuals may consider themselves members of multiple, fluid communities. Reliable criteria are needed for defining communities for genetic research, and all potential stakeholders should be included in the definition of community for a particular research study.
  2. Understand the Potential Benefits and Risks for Communities and Community Members. As much as possible, all benefits and risks should be identified and understood in consultation with the community during the planning, conduct, and followup of a research study. Special efforts may be needed to maximize the benefits and to minimize the risks or harms to communities and their members.
  3. Obtain Broad Community Input for All Phases of Research. Communities participating in genetic research may have a strong desire to be involved in all aspects and stages of the research. Researchers should give special attention to soliciting broad input throughout the community, and NIH should establish criteria, goals, and mechanisms for obtaining input from communities.
  4. Respect Communities as Full Partners in Research. Lack of reciprocity between communities and researchers undermines the research process. Effective research depends on the full participation of communities and on mutual respect and a continuing, interactive dialogue between researchers and communities. Researchers should be encouraged to be sensitive to communities' perspectives and needs.
  5. Resolve All Issues Pertaining to Tissue Samples. Continued efforts are needed to clarify the legal status of tissue samples; establish criteria for the collection, use, and storage of samples; understand the potential risks and benefits for individuals and communities providing samples; and assure appropriate procedures for obtaining informed consent regarding samples. Communities should participate fully in these efforts.
  6. Establish Appropriate Review Mechanisms and Procedures. Researchers are, and should be, held accountable for any research involving communities. NIH should ensure the transparency of this research to communities and foster the participation of communities, public advisory groups, and institutional review boards in initial and ongoing reviews of community-based research studies.
  7. Facilitate the Return of Benefits to Communities. Communities participating in research often do not believe that they receive any benefits, or returns, from their participation. Researchers should make an effort to provide these benefits, and NIH should extend support for follow-up studies of the benefits of research for communities and their members. The ownership of research results and data needs to be clarified.
  8. Foster Education and Training in Community-Based Research. To enhance researchers' understanding and skills for conducting community-based genetic research, support is needed for education and training of predoctoral investigators and for continuing education for established investigators and research reviewers. Curricula should include community issues; ethical, legal, and social implications of genetic research; and model programs.
  9. Ensure Dissemination of Accurate Information to the Media and Public. NIH should disseminate widely the results of genetic research which shows that genetic variation within populations is greater than that between populations; foster education of health professionals about these findings; and promote dialogue with the public about the ethical, legal, and social implications of genetic research.
  10. Provide Sufficient Funding and Encourage Partnerships. NIH should provide sufficient funding to ensure that meritorious community-based genetic research can be conducted adequately. Specifically, NIH should expand funding to foster community involvement and participation in this research and encourage partnerships among government, industry, and academia.

Introduction

The First Community Consultation on the Responsible Collection and Use of Samples for Genetic Research, held September 25-26, 2000, was one of the first large NIH meetings to bring together diverse communities to address ways of involving these communities in genetic research. Genetic issues affecting individuals (e.g., genetic screening and privacy of genetic information) have been, and continue to be, addressed in many meetings and discussions. The consultation provided a forum for members of identified populations in the United States to exchange views formally and informally with research administrators. For one and a half days, educators, social scientists, biologists, lawyers, ethicists, clergy, doctors, nurses, and community leaders from diverse communities engaged in lively and thoughtful discussions.

The consultation included five presentations from researchers and research administrators; two panels, which focused on potential benefits and risks to populations participating in genetic research and on lessons from international experiences; five breakout groups, which were asked to address a series of questions about issues affecting communities; and a plenary session for reports from each breakout group and a general discussion.

Welcome and Opening Remarks

The meeting organizer, Dr. Judith H. Greenberg, Director, Division of Genetics and Developmental Biology, NIGMS, NIH, welcomed the participants to the First Community Consultation. She reviewed the purpose of the meeting and emphasized NIH's interest in hearing the participants' views on the collection and use of tissue samples for genetic research and in beginning a process to develop ways to involve communities in research that affects them. She noted that "community" and "population" are used interchangeably at NIH and can be defined variously, reflecting different contexts.

Dr. Greenberg provided background on NIGMS's cell repository and noted that members of some populations, researchers, and bioethicists have raised concerns about possible negative consequences to a community resulting from storage and use of tissue samples from that community. The participants at an NIGMS workshop in 1999 endorsed the scientific value of the continued collection of samples from identified populations, but only if members of the community are appropriately involved in decisions about the use of these samples. The First Community Consultation was convened to hear a wide range of views on how best to involve U.S. communities in research that uses tissue samples. Dr. Greenberg thanked the planning committee, external advisors, and sponsors of the meeting for making the consultation possible.

Opening Remarks

Dr. Ruth L. Kirschstein, Principal Deputy Director, NIH, described the importance and value of genetic research and of the public's involvement in decision-making and planning for this research. She noted, in particular, the value of NIGMS's and other tissue repositories and the need to ensure that these samples are responsibly collected, stored, and used. Dr. Kirschstein highlighted the success of genetic research, for example, in identifying the single-gene defects for Huntington's disease and cystic fibrosis and in explaining the effects of some single-gene variants on individuals' response to drugs. She also noted that most common diseases are more complex and are associated with a variety of genetic and environmental factors. The completion of the first draft of the human genome sequence in June, 2000 will help researchers untangle the complexity of genetic variations and gene-environment interactions within and across population groups.

Dr. Kirschstein anticipated that considerable progress will be made in treating genetic diseases, and she noted that much progress has been made possible by the availability of tissue samples. The opportunities for research are unique and exciting; yet, the process of conducting genetic research with populations and communities is still largely unexplored and a considerable challenge for the future. Dr. Kirschstein noted that NIH and the scientific community must move forward with great caution, to protect individuals and identified groups and to avoid dissemination of mis-information. Current regulations, providing for the protection of individuals, must be expanded to also protect communities and groups participating in research.

Dr. Kirschstein encouraged the communities of the participants to become partners with NIH at the beginning of this process of collaboration to ensure that the research proceeds fairly. She invited the participants to share their insights and experience for the benefit of NIH.

Genetic Research and the Role of the Community: A Case Study of Jewish Attitudes

Prof. Karen Rothenberg, University of Maryland School of Law, Baltimore, presented an overview of the historical context, current issues, perceived value, and discrimination and stigma associated with genetic research in the Jewish community; the potential role of the Jewish community in genetic research; and the results of a pilot study of attitudes about this research in the Jewish community. She highlighted the media's role in communicating and formulating perspectives within, and outside, the Jewish community.

Historically, Jewish attitudes about genetic research have passed through three phases. Beginning in the 1920s, the eugenics movement precipitated a belief in the "genetic inferiority" of Jews, resulting in restrictive quotas on immigration to the United States and with the Holocaust. By the mid-1970s, the community viewed genetic research positively and participated successfully in genetic testing for Tay-Sachs disease. More recently, this community has expressed concern about the use of tissue samples stored from this earlier period for genetic research on breast cancer and colon cancer affecting the Jewish population. While the community places strong value on testing for genetic diseases and the knowledge, medical benefits, and social justice gained from genetic research, fears about the misuse of genetic information and potential discrimination and stigma are being expressed and are being fueled by the media. In response to the rising tension between these fears and the concern that an overreaction may halt research that could benefit the community, some Jewish scientists have called for a group debate on gene studies which would include professional groups, NIH, and national advisory committees.

Prof. Rothenberg noted that findings of a recent pilot telephone survey of 287 Jews from a diverse community in the Baltimore/Washington, DC, metropolitan area are informative. Among the respondents, 82.1 percent noted that genetic research was very important to "help society"; 62.4 percent were very concerned about potential discrimination and anti-Semitism in the United States; 74.0 percent and 62.4 percent said that conveying the benefits of research through the informed consent process was very important to the family and the Jewish community, respectively; 71.0 percent said that conveying the risks of research through this process also was very important to the Jewish community; and more than 77.0 percent noted that community consultations were very (41.0 percent) or somewhat (36.0 percent) important, but only 55.0 percent said that community approval was very (21.0 percent) or somewhat (34.0 percent) important.

Prof. Rothenberg suggested that the Jewish community could contribute positively to considerations of the appropriate roles of institutional review boards (IRBs), informed consent, community consultations, tissue bank panels, and community consent. Critical issues for community consultations include how the community is defined and who speaks for the community.

The Culture of Science: The Biomedical Outcomes of Genome Research

Dr. Francis Collins, Director, National Human Genome Research Institute, NIH, presented a scientist's perspective on the genetics of human disease. He noted that the First Community Consultation was timely and important and that the Human Genome Project includes attention to the ethical, legal, and social implications of genetic research. Quoting John Dewey as saying, "Every great advance in science has issued from a new audacity of imagination," Dr. Collins said that the major scientific motivation for genetic research is to understand the disease process and to predict individuals' risk of disease and to use the information gained to design more effective interventions. Driving the Human Genome Project is a desire to understand the genetic contributions to all diseases. Some diseases have large genetic components, such as single-gene disorders (e.g., cystic fibrosis); some diseases are affected by multiple genes and environmental factors (e.g., adult-onset diabetes); and some diseases arise largely from environmental factors (e.g., Acquired Immunodeficiency Syndrome, or AIDS), but have some genetic influences.

Dr. Collins noted that 99.9 percent of the genome is the same between any two individuals and that only about 200,000 sites in the DNA account for functionally significant, common variants in the world's population. He noted further that the world's population has evolved from a single population in Africa and that the "branching tree" of relatedness, commonly used to depict the connections between different populations, should really be a "trellis" consisting of many connected branches. Most genetic variation occurs within all ethnic and racial groups, which results from our common origin. The large overlap among groups in the genetic variation they contain, as well as the large amount of historical mixing among groups, mean that the separation of human populations into precisely defined racial categories is scientifically unjustifiable.

Dr. Collins stated that most genetic variants of functional significance are differences at single DNA sites, single-nucleotide polymorphisms (SNPs). By cataloging the variants in individuals with and without a particular disease, scientists can potentially identify genetic variations that correlate with risk of the disease, which will help to identify genes affecting that disease. Finding the genes helps scientists to understand the process that leads to the disease, with the hope of then developing interventions to prevent or treat the disease. When a small number of individuals start a new population, they may happen to have a higher frequency of a particular genetic variant that contributes to a disease. The population may then have a more uniform genetic basis for the disease and a higher frequency of the disease than the parent population or populations with more heterogeneous backgrounds. This "founder effect" means that such populations are useful for finding genes affecting diseases that their members have. Similarly, some variants have arisen in certain populations and have not spread much to other populations. Scientists have been able to find particular variations associated with an increased frequency of disease among certain populations. Examples of diseases associated with this founder effect include cystic fibrosis in northern Europeans, sickle cell disease in African and Mediterranean populations, and Tay-Sachs disease and colon cancer in Ashkenazi Jews.

Dr. Collins emphasized that the founder effect is "real" and can be successfully explored within population groups. A major concern is how to balance the potential medical benefits of this research with the potential risks of stigmatization. He agreed that a continuing dialogue is needed between communities and researchers.

Discussion

The participants expressed strong concern about potential discrimination, stigmatization, and breaches of privacy for individuals and communities participating in genetic research. Dr. Collins noted that the Administration and the Congress are taking steps to establish effective legal protections against such outcomes for individuals in the workplace and by insurance carriers and that protections for communities still need to be addressed. Prof. Rothenberg emphasized that the dialogue between researchers and communities must be maintained over the continuum of a study--before, during, and after. For example, communities must participate in discussions of whether a study is even worth doing.

Commenting on the participation of communities in genetic screening, Prof. Rothenberg noted differences in participation and trust among African American communities (e.g., in genetic screening for sickle cell disease) compared with Jewish communities (e.g., for Tay-Sachs disease). She emphasized the need for community involvement, participation of researchers from the community, and legal protections against potential discrimination.

A participant remarked about the tremendous overload of information on genetics that is being disseminated to the public and suggested that better ways to communicate and disseminate information need to be explored before focusing on the participation of communities in research. Dr. Collins agreed and noted that a poll conducted by Time Magazine and CNN in June, 2000 demonstrated a "disconnect" among the public: 46 percent of those surveyed responded that they thought the Human Genome Project, when completed, would likely be generally harmful, but 61 percent said that if they could gain information about their genetic code or DNA, they would want to know what diseases they were predisposed to get. He suggested that a long, detailed process of listening and sharing of information through community consultations will be needed to "sift through" individuals' complex assumptions about genetic research.

Scientific Basis of Conducting Genetic Studies on Identified Populations

Dr. Aravinda Chakravarti, McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, expanded on the scientific rationale for conducting genetic studies in identified populations. He noted that: (a) the genetic variation in the human genome is largely observable within any population and is widespread worldwide; (b) the pattern of variation worldwide is shaped by human history and ecology; and (c) geneticists and biologists choose a specific population to study because a genetic disorder or trait occurs with fairly high frequency in that population or previous research indicates that the study would help the understanding of a genetic disease.

Dr. Chakravarti noted that the first known genetic difference in humans was established in the 1930s with identification of the ABO blood groups. Subsequent findings of variability in human DNA sequences (e.g., for DMD1, the dystrophin gene associated with muscular dystrophy) show that the frequency of genetic variants may vary among populations but most variants are found in most populations; variants restricted to a specific population group are extremely rare. He agreed with Dr. Collins that the "branching tree" does not convey the complexity of human relatedness. He noted further that the commonality of genetic variation in large regions of the world is the basis for hypotheses of the origin and migration of human populations from Africa. Dr. Chakravarti agreed further with Dr. Collins on the importance of the founder effect and the potential for understanding certain genetic diseases by studying variants in specific population groups. For example, by focusing on a Finnish population and on the Old Order Mennonites, scientists have been able to identify the single-gene variants responsible for two rare disorders and an intestinal defect. And, as shown by the distribution of sickle cell disease and malaria, some variants may provide a health advantage in some regions of the world, but not in others, which contributes to differences in the frequency of the genetic variant among populations.

Dr. Chakravarti noted that completion of the first draft of the human genome sequence also helps scientists to explore genetic diseases with a complex mode of inheritance. He suggested that 60 percent of genetic diseases arise in adults and are multifactorial. To elucidate the causes of these diseases, scientists will have to study both genetic and environmental factors and gene-gene and gene-environment interactions. This research will initially require a systematic search and cataloging of variations, especially SNPs, in the sequence of DNA. He emphasized that tissue samples are an extremely valuable resource for cataloging genetic variants. Once these variants are discovered, researchers can compare the frequency of specific variants in individuals with the disease to controls without disease, in order to find genes contributing to the disease. Studies are under way to explore these differences in insulin-dependent diabetes mellitus, Alzheimer's disease, venous thrombosis, osteoporosis, and resistance to AIDS.

Discussion

The participants again noted the need to educate the public about the genetics of human disease and the implications of studies of the human genome. The concepts of inheritance within families, the founder effect, "genetic drift," and the uniqueness of individual susceptibility to disease within populations need to be communicated better to the general public and to specific communities invited to participate in genetic research. For many communities (e.g., Native Americans), the value of genetic research has not been communicated effectively.

Dr. Chakravarti noted that studies of genetic variants and of human migration patterns are both important for understanding human disease. He said that population-based research has been important for establishing the frequency of genetic variants within and among populations and that the definition of a population depends on the nature of the research to be conducted. By studying the variation in the human genome, scientists will be able ultimately to address the genetics of disease in families and populations and the prevention of disease in individuals.

Culture of Communities that Participate in Research

Dr. Nancy Press, Department of Public Health and Preventive Medicine, Oregon Health Sciences University, Portland, addressed the "culture of communities," as a counterpoint to Dr. Collins' remarks on the "culture of science." She noted five major points: (a) communities are defined by social and ethnic group boundaries; (b) boundaries between groups are highly permeable; (c) social and ethnic identities and boundaries are fluid and purposeful; (d) few individuals reside fully in one group over time and place; and (e) social challenges to group barriers and the responsiveness of groups to these challenges precede genetics.

Dr. Press emphasized the difficulty of defining "community" as a social or biological unit with boundaries. Barriers used to identify and isolate groups are highly permeable, e.g., the transfer of genes among interacting groups (e.g., along trade routes). Social barriers are not only permeable, but also can be socially constructed, redefined, and manipulated to reform a group or community. Drawing on the sociological theories of Frederick Barth and Max Weber, Dr. Press noted that ethnicity represents a social boundary and is fluid and purposeful. For example, individuals who have immigrated to the United States may have multiple social and ethnic identities (e.g., as a Mayan Indian, a Guatemalan, or a North American). Similarly, the reaction and response of individuals or populations to group identities (e.g., Hispanic, or American) depends on time and place. Dr. Press also noted that challenges to group identity (barriers) are based on social definitions, not genetics. Referring to a contemporary elite group in Charleston, South Carolina, she noted that a genetic connection existed among members of this group and was supposed to be necessary and sufficient for group membership, but that, actually, some individuals were subtly excluded despite their genetic connection, in order to preserve the links of wealth and status to the group.

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