AAAS Scientific Responsibility, Human Rights and Law Program

THE HUMAN GENOME DIVERSITY PROJECT

The Model Ethical Protocol as a Guide to Researchers

Report of a Symposium and Workshop
Annual Meeting of the American Association for the Advancement of Science
February 15, 1998 Philadelphia, Pennsylvania

EXECUTIVE SUMMARY*

Introduction

In 1991, a project was proposed by an international group of scientists to collect and store DNA information from indigenous populations from around the world. This Human Genome Diversity Project (HGDP) was intended to provide insight into the evolutionary history of the human race and certain populations' susceptibilities to diseases. What the project planners did not expect was an onslaught of criticism from the indigenous groups. Just as the HGDP was getting underway, tribes from around the world issued statements summarily denouncing the project and declaring their refusal to participate. In response to these criticisms, members of the North American Regional Committee of the HGDP organized a working group to assess the ethical and legal issues of the project. The group produced a Model Ethical Protocol (MEP) to guide discussions of ethical and legal issues implicated in sample collection and to serve as a frame of reference for investigators, Institutional Review Boards (IRBs), and potential funders.

The American Association for the Advancement of Science (AAAS) organized a special one-day event at its February 1998 Annual Meeting in Philadelphia, PA to address the cross-cultural ethical, legal, and social issues associated with implementation of the proposed Human Genome Diversity Project (HGDP). The event consisted of a morning symposium, which included five formal presentations covering the nature and goals of the HGDP, the issues it raises, and the role of the Model Ethical Protocol in guiding and evaluating the research that would be carried out under the banner of the HGDP. This was followed by a three-hour afternoon workshop convened to address the controversies raised by the HGDP and to explore in an open forum whether the provisions of the MEP adequately addresses those concerns. The workshop participants included members of potentially affected populations, members of the scientific community, journalists, and other interested persons attending the AAAS Annual Meeting, which typically attracts a diverse, multidisciplinary audience. In addition, four people representing the target research populations of the HGDP were invited to attend this one-day event and contribute their own perspectives to the proceedings. The workshop dialogue was able to bring together differing points of view and, though no final consensus was reached or intended, inferences can be made from the participants' reactions to both the HGDP and the MEP.

The concerns raised by the indigenous groups can be categorized into three main types of issues. First, concerns related to the procedures for the collection and retention of DNA samples from the study populations. Second, those pertaining to the intellectual property of the communities sampled and the commercial exploitation of products developed from the HGDP. And third, a concern about the potential uses and abuses of the knowledge produced by the project, with fears that genetic information could be used to foster prejudices or otherwise threaten the well-being of the sampled populations. Failure to resolve the issues that have surfaced during the early planning stages of the HGDP has created tension between scientists and those they wish to study. It is important for the HGDP in particular, and for science in general, to improve everyone's understanding of those issues, to identify where differences exist, and to seek collaborative responses to them. The sessions at the AAAS Annual Meeting were intended to be a step in this direction.

The Model Ethical Protocol

In response to the heavy criticism and to meet head on the ethical challenges posed by the HGDP, the North American Regional Committee prepared a Protocol for collecting DNA samples. (For the most recent draft see http://www.stanford.edu/group/morrinst/Protocol.html) The proposed Protocol deals with the ethical and legal issues that are raised when DNA is collected from populations, not individuals, especially when those populations may be scientifically illiterate and politically vulnerable. Although the MEP is primarily intended to guide HGDP research conducted in North America, it is likely to influence research practices in other parts of the world as well. The current version has been formulated over the course of two years and has not been adopted by either the North American Regional Committee (NARC), the other regional committees of the HGDP, or the HGDP's international executive committee; comments are still being sought.

The MEP is aimed at several audiences. First, for scientists involved in the HGDP, the MEP presents "important principles and rules, to show researchers non-obvious issues that may arise, and to discuss usefully the complexities that may confront them in the field." Second, for populations participating in the project, it should help them understand some of the possible implications of participating, and give them more of a voice in the project's implementation. Third, the MEP should be useful to IRBs or other groups that review human subjects research in judging whether proposed research projects have given sufficient consideration to the ethical issues their work may raise, and whether their plans for informed consent are appropriate. And fourth, the MEP is meant to guide the work of the NARC, such that activities within North America or sponsored by North American institutions will not be accepted as part of the HGDP unless they comply with these guidelines. The NARC offers to provide assistance to scientists participating in the project needing help in implementing the procedures set forth in the Protocol. The three fundamental principles embedded in the MEP are: (1) informed consent; (2) respect for the participating population's culture; and (3) adherence to international standards of human rights. Considerable emphasis is placed on explaining the nature and goals of the project to the potentially involved communities, in the language appropriate for the population and in terms that are relevant to its culture, and engaging them as partners in planning and carrying out the research and not just as research subjects.

Other matters covered in the MEP include: the selection of populations for inclusion in the project, including procedures for contacting them; informed consent at both the individual and community levels; concerns related to providing benefits, including medical services produced by the project for use by the participating populations, and the need to be sensitive to the fine line between an appropriate return for the community's participation and inappropriate inducement that can vitiate the community's informed consent; challenges to privacy and confidentiality for both individuals and the community; education aimed at preempting efforts to use the findings of the HGDP to promote prejudices related to race, ethnicity, or religion; matters relating to ownership and control over the data collected by the project; the partnering relationship that researchers should strive to create between themselves and the communities that they study, which should provide for the populations' involvement in the planning and conduct of the research and include a plan for apprising them of the research results.

Symposium

The five speakers in the morning session addressed different aspects of the HGDP and MEP. The symposium began with Kenneth K. Kidd, Professor of Genetics, Psychiatry and Biology at Yale University School of Medicine. He addressed the need for a HGDP, the scientific goals and possible health benefits that could be derived from such a project, and some scientific data and theories originating from current and past investigations of HGDP-type research. He was followed by Frank C. Dukepoo, a Native American Geneticist of Hope and Launa heritage in the Department of Biological Sciences at Northern Arizona University. His talk offered a cultural context for assessing the various arguments in support of and in opposition to the HGDP as expressed by indigenous populations. The third speaker, Henry T. Greely, Professor of Law at Stanford University Law School, who chaired the North American Regional Committee of the HGDP, gave a presentation on the Model Ethical Protocol. He reviewed some of the history behind its development, described the process by which it has evolved, and highlighted its main provisions. A summary of the assessment by the National Research Council of the National Academy of Sciences of the type of research proposed by the HGDP was then presented by the Chair of its Committee on Human Genome Diversity, William J. Schull, who is Director of the Human Genetics Center at the University of Texas Health Science Center, Houston. In the concluding presentation, Charles E. Riggs, Jr., Associate Professor in the Department of Internal Medicine, University of Iowa, addressed the issues related to the HGDP that would most likely be scrutinized by an IRB.

Workshop

With the symposium as background, the afternoon workshop examined more closely the ethical and social issues surrounding the HGDP, the MEP as a source of ethical guidance to HGDP researchers and funders, and the participation of study populations and scientists in the Protocol's development and implementation. The workshop included three speakers from the morning symposium as panelists (Frank C. Dukepoo, Henry T. Greely, and Charles E. Riggs, Jr.) along with a moderator from AAAS. There were no formal presentations; instead, an open exchange of views between the participants and panelists was encouraged.

During the three-hour workshop many topics were touched upon concerning both the ethics of HGDP research and whether the MEP adequately addresses the issues that have arisen. Though the discussions followed a path that ran freely from one question to the next, several main themes emerged. These included: the expected or hoped for effect of the MEP; the difficulties in obtaining informed consent; the benefits versus risks for populations and individuals; potential involvement of the pharmaceuticals and biotech industry; the compliance with and enforceability of the Protocol's provisions; and the assessment and future status of the MEP.

It appears that the MEP has to a limited extent already helped raise the standards of research practices in population genomic studies, and has the potential to have a far greater impact in the future if the HGDP goes forward or if it becomes more widely known and applied to community research on its own merits. Nevertheless, whether the MEP goes far enough, at least in the view of the target populations, remains uncertain, and many groups continue to say that it does not. Some groups feel that the members of the HGDP are making a sincere effort to address their concerns, but the lack of basic enforcement mechanisms still remains a serious issue. As reflected in the comments during the workshop, for certain groups there may simply never be an acceptable research protocol. One of the main points made during both the course of the morning and afternoon sessions was that, whatever the decision of the population may be, it must be respected and accepted. The scientific interests at stake always come secondary to those of the populations. If a population does not wish to participate in the research then it must be left alone.

It was pointed out during the workshop that perhaps one of the greatest barriers to indigenous populations' involvement in the HGDP is their complete lack of interest in the stated goals of the project. Their understandable priority continues to be basic human rights, such as access to improved health care, to better guarantee their own well-being and survival. As stated in the Declaration of Indigenous Peoples of the Western Hemisphere Regarding the HGDP (1995), "we demand that scientific endeavors and resources be prioritized to support and improve social, economic and environmental conditions of indigenous peoples in their environments, thereby improving health conditions and raising the overall quality of life." Indeed, what benefits might arise from the HGDP appear to be far removed from these priorities.

The HGDP's interest in evolution and history is likely to often run contrary to some peoples differing perspectives of their own histories and evolutions. Groups want to protect their own understanding of who they are. They do not welcome the prospect of having their origin stories corrected through genetic reductionism. It can already be predicted that the outcomes of many studies will suggest that the received mythological charters for some groups' identities are mistaken, and such findings could have a serious impact on their sense of self worth and identity. Indigenous populations believe that their origins are their own concept, which can be difficult for Western scientists to understand.

Frank Dukepoo informed participants that the Akwesasne Task Force on the Environment had written its own Protocol for Review of Environmental and Scientific Research Proposals. This document was created because the number of research projects being proposed by scientists was increasing and the Akwesasne community wanted to protect itself and its future generations. The protocol states that the review process for research projects "should not be viewed in a negative way or be seen as an impediment to research. It has been developed to serve as a guide to improve relations between the community of Akwesasne and the scientists/researchers and to promote collaboration within a framework of mutual trust and cooperation." This language is reminiscent of the partnership concept in the MEP. The difference between the two is that the Akwesasne Protocol goes one step further than the MEP in its required level of community involvement and in the population's control of the research and its results. Many scientists will find these guidelines to be a significant departure from how they have conducted their investigations in the past. Whether researchers will be willing to abide by such strict requirements remains to be determined.

One of the greatest weaknesses of the MEP identified during the workshop discussion is the lack of any mechanisms for assessment, compliance and enforcement. Although regulations on research practices currently exist, reported transgressions against research subjects continue to occur. For investigations based in research institutions, as would most likely be the case for the HGDP, it was pointed out by Charles Riggs during the symposium, that much depends upon the tenor of the institution and the tenacity of the chair and other members of the IRB. This creates some concern, since the IRB system is currently under criticism for gaps in its capacity for protecting subjects. And although the education of IRBs and funding agencies, as well as new regulations, were suggested as necessary steps, no clear resolution to this problem appears to be on the horizon.

The future of both the HGDP and the MEP in North America is uncertain at this stage. As Henry Greely noted during the workshop, the project is at a critical point as to whether it will proceed. The objections of the indigenous populations appear to be as strong as ever despite attempts by the NARC to address their concerns in the MEP. In the end, however, the fate of the HGDP as a coordinated, systematic effort will likely be determined by the funding agencies. Even if it does not come to fruition in its current manifestation, it has brought serious ethical issues associated with population genomic research to the attention of scientists, funding agencies, and the public. Its legacy may well be that it has helped raise the consciousness and sensitivity of scientists to the implications of their research on indigenous populations.

Conclusion

The primary focus of the AAAS symposium and workshop was on the MEP and its promise for addressing the ethical concerns that have arisen as a response to the proposed HGDP. Although the MEP would only guide investigations conducted in North America, it might also influence researchers elsewhere around the world and eventually be adopted by other HGDP regional committees. Its fate in North America, therefore, bears watching elsewhere by those with a stake in the fortunes of the HGDP.