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Evaluating Human Genetic Diversity 6 Organizational and Other Issues The complexity of the proposed global research on the extent of human genetic variation leads to many administrative and organizational problems heretofore seldom encountered in human biologic research, or at least not encountered on a commensurate scale. The problems relevant to the choice of a sampling strategy and sample sizes have been set out in chapter 3, those related to the management of specimen and database repositories derived from international research on human genetic variation have been detailed in chapter 4, and those involving ethical issues have been described in chapter 5. Equitable solutions to those problems clearly are central to the success of any international effort to define better the extent of human genetic variation, and they are essential if funding agencies—such as the National Science Foundation and the National Institutes of Health—are to consider properly the scientific merits and limitations of this research. It is also important that these agencies recognize the humanitarian concerns voiced by people who are alarmed by the ethical and social ramifications that they believe are inherent in the research. However, other vexing and potentially contentious administrative and organizational issues must also be addressed. They vary from the establishment of an effective, flexible, and transparent method of governance that acknowledges the international nature of the enterprise to scientifically mundane considerations, such as sharing of indirect costs when multiple sources of funds are available to support a specific endeavor or when more than one institution is involved in the research, as seems likely in many instances. The importance attached to those individual matters will vary from investigator to investigator, institution to institution, nation to nation, circumstance to circumstance, and time to time.
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Evaluating Human Genetic Diversity We are concerned here not with the particulars of those matters, but with their overall effect on the success of the research. For example, it is the committee's impression, which is based on a modest number of interviews and scrutiny of the results of a questionnaire, that the 2 most-important considerations that determine the willingness of many investigators to be involved are the degree of centralization of the global effort and the openness of, the accessibility to, and their possible involvement in whatever process of governance is established to manage the program. Younger investigators in industrialized countries and those of whatever age in developing nations express the concern that any international research effort, such as the one contemplated, will be quickly captured by established groups in the developed nations or be captive to them from the outset. They are not reassured by the experience of the Human Genome Project as it is known to them, particularly with respect to their own nations or nations in which they have been trained. They appear to fear that they will be relegated to a secondary role in the research, which will not allow them the opportunity to grow in skill or to equip their laboratories better, and that their contributions will go unrecognized and hence unrewarded. The committee cannot evaluate the merits or legitimacy of their concern, nor are we properly constituted to do so. However, we note that such perceptions, whether based on fact or not, are powerful determinants of human conduct. We recognize that any sense of exclusion of younger investigators or those from developing nations, or both, from the governance process undoubtedly would seriously compromise the contemplated research, particularly if no clear provision were made for the appeal of judgments that they see as capricious or self-serving, such as those related to access to the specimen and data repositories or the transfer of technologies. It is of paramount importance that the process of governance be seen as inclusive, not exclusive. However, effective governance cannot be totally democratic, encompassing all potential investigators; some delegation of authority and responsibility is inevitable. It is how the latter occurs that is potentially contentious and where governance needs to be flexible and transparent. Similarly, it is the committee's impression that much of the concern of lay groups, as presented by their spokespersons, involves the belief that they will not participate in the selection of the groups to be studied, in the design of the studies, or in possible financial and public-health benefits that stem from the projected research. In chapter 5, we have set out steps that we believe meet some, although possibly not all, of their concerns and apprehensions. However, we believe that early and continued consultation with the groups selected for study not only is mandatory, but is the only assurance of group as well as individual participation. Moreover, provision needs to be made for some tangible and immediate return to the individuals and communities as an outgrowth of their cooperation. Some of the general administrative and organizational problems have been confronted by the Human Genome Project and in the context of the proposed Human Genome Diversity Project by the regional committees, such as the North
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Evaluating Human Genetic Diversity American one, that have been formed to stimulate regional and global interest in an international study of human genetic variation, to identify the problems posed by such research, and ultimately to monitor its conduct. The composition of these committees has been seen by some individuals and groups as at best elitist and at worst constituting a self-serving cabal. As a result, the actions of the committees have been endorsed by some but challenged by others, predominantly spokespersons for the historically disadvantaged. Nevertheless, the solutions offered by these committees to the ethical, political, and scientific issues posed by collaborative international research warrant careful consideration as possible paradigms. We believe these to constitute a conscientious effort to identify the issues and to offer possible solutions, but we note that the relevance of some of the solutions to the research currently projected, when viewed globally, might be debatable. This opinion rests largely on the geographic focus of the regional committees and the disparate levels of activity of the various committees. Some have been exceptionally active; others seem still to be in the formative stage, and the issues that they might identify as important in the successful conduct of the research in their regions are unknown to us. Nonetheless, those committees or something akin to them could play a fundamental role in the administration of the research. If the regional bodies are to serve their purposes as monitors and managers of the contemplated research, means must be found to support their activities and to permit active interaction between them. If that does not occur, the research will continue to be opportunistic and poorly integrated and will fail to serve the stated purposes of the international effort. Support might occur in several ways. Possibly the simplest would be through the early establishment of an international mechanism of governance that is representative of all the regional groups, both scientific and lay, and the allocation of funds to this group to support regional administrative needs. We note that continued support will be required for the specimen and data repositories and that their support and administration could be a function of the international body established to govern the enterprise. The cost of these core activities is difficult to project and will depend much on the degree of centralization of effort that emerges. However, it should be noted that support must be seen as extending over the long term, possibly decades, if the goal of establishing a resource for future use is to be achieved. We recognize that neither the National Science Foundation nor the National Institutes of Health is prepared or even able to fund a global survey like that contemplated, and we recommend that they seek advice on the role that they should play. Accordingly, these agencies should focus their financial support, at least initially, on projects originating in the US and expand their support to the international scene only after activities in the US are successfully launched. This recommendation might seem parochial to some, but the following arguments can be adduced in its support. Some of the organizational difficulties we envisaged in a global study could
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Evaluating Human Genetic Diversity be avoided or at least mitigated by initially focusing on an area of the world rich in the human resources and experience that the survey will require. There already exists in the US a formidable infrastructure: experienced investigators; well-equipped laboratories with members knowledgeable in the design and implementation of tissue repositories and in the management of large, computer-based data sets; and a means, through the existing system of institutional review boards, to protect the ethical and legal rights of individual participants and the privacy and confidentiality of the information that would be collected. The committee recognizes that a similar richness exists in Europe and encourages parallel activities there. Second, as a result of centuries of immigration, the United States does have a diverse representation of the people of the world. Thus, a well-designed survey of human genetic variability there could shed some light on the extent of human genetic variation globally. It can be argued that migrants rarely constitute a random sample of the populations from which they came and that not all parts of the world are well-represented in the United States; this is certainly true with respect to a variety of cultural, social, and even physical measures. It is less well-established, however, whether these differences translate into a grossly biased sample of the genetic variability in their countries of origin, and this argument should not be used as a basis not to conduct a survey of human genetic variability in the United States. Third, the establishment of an international effort will require defining the roles of interested investigators, on the one hand, and national and international agencies, on the other. Without defining such roles, any global survey would be correctly criticized for substituting a self-appointed set of administrators without official standing in any country for the recognized national and international agencies of governance, and it would be unlikely to succeed. It is not immediately obvious how the discussions of roles should be initiated. The funding agencies, specifically the National Science Foundation and the National Institutes of Health, should initiate such discussions through their international offices. These discussions will take time to bring to fruition; until a consensus is achieved, the US effort would be generating information of substantial moment relevant to the feasibility and urgency of an international study and would be identifying administrative barriers that would have to be surmounted. Finally, the committee found its deliberations on the value, design, and implementation of tissue repositories, whether central or regional, constantly thwarted by the absence of information on what is actually available and accessible now. A number of repositories are of potential utility to many investigators, particularly in the US, such as the collections of the National Marrow Donor Program; the Center for Health Statistics through its periodic survey of the population of the United States; numerous multi-institutional programs, including the study of atherosclerotic risks in communities (ARIC); the Lipid Research Clinics; and the specimens assembled by individual investigators sponsored by the National Insti-
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Evaluating Human Genetic Diversity tutes of Health or the National Science Foundation. However, the information at our disposal was largely anecdotal and we could identify no complete enumeration of such collections. The committee recommends that the National Institutes of Health or the National Science Foundation identify all such repositories, as well as the availability of the specimens to the scientific community in the US and elsewhere. We believe it to be inappropriate for us, as a committee, to intrude on the prerogatives of the funding agencies by suggesting a detailed mechanism for reviewing applications for support in this sphere of research. Those agencies are better informed on the options available to them than this committee and can therefore establish a more-flexible program of support and peer review. However, we do recommend that, whatever mechanism is chosen, the primary criterion for support be the scientific merit of the individual request for support. We also suggest that in the assessment of merit the recommendations of this committee with regard to sampling strategy, sample size, and the collection of specimens and data be taken into account.
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