The International HapMap Project: Ethical, Social, and Cultural Issues [Names and institutions of presenters]

Goal of the HapMap Project To develop a resource to facilitate future studies that relate human genetic variation to health and disease

The HapMap Will Facilitate Comparisons Among: Individuals Groups

Because the HapMap will facilitate comparisons among both individuals and groups, the ethical issues are especially challenging.

Populations Included Yoruba (Ibadan, Nigeria) 30 parent-child trios Han Chinese (Beijing, China) 45 unrelated individuals Japanese (Tokyo, Japan) 45 unrelated individuals CEPH (Utah residents with Northern & Western European ancestry) 30 parent-child trios

Inclusion Criteria for Populations Yoruba 4/4 Yoruba grandparents Han Chinese At least 3/4 Han Chinese grandparents Japanese “Japanese ancestry” CEPH Collected in 1980; inclusion criteria not specified

Inclusion Criteria for Individuals Adult age Competent to provide informed consent CEPH donors: Reconsent from living donors Local IRB gave permission to use samples from deceased donors

Individual Privacy Protections No names or other identifying information No medical information Only genotype information and sex (on Internet) More samples collected than used

Why Sample by Population?

Some Facts About Populations Any one population includes about 90% of the genetic variation that exists throughout the world. The most common haplotypes are expected to be found in all human populations. Thus, the HapMap could have been developed with samples from any one population.

But………… The frequencies of particular haplotypes vary among populations. Population differences in haplotype frequencies are important for discovering genes that influence health and disease.

So………… Studying samples from several populations with different ancestral geographies will make the HapMap most useful for studies in multiple populations (both those sampled and not sampled). A grid sampling strategy would have ignored population structure, making the HapMap less useful.

Why These Populations? Scientific reasons: * Recommendation to include samples from at least 3 Old World continents * Pilot data showing range of haplotype frequencies Ethical reasons: * No small, isolated populations * Inclusiveness (find some less common variation) Practical reasons: * Established relationships with communities * Funding agency interest

Plans to Study Other Populations NIH is organizing sample collection from several additional populations. These samples will initially be genotyped across a limited number of regions. The samples may be genotyped across the full genome and added to the HapMap if the haplotype patterns differ substantially and the tag SNPs for the already-studied populations are inadequate to describe them. Declining genotyping costs will make this feasible.

Scientific Rationale for Identifying Populations Enables researchers to choose the most efficient sets of tag SNPs in future association studies in particular populations Allows the accumulation of genetic and environmental data on any particular population

Ethical Rationale for Identifying Populations Prevented false sense of security among donors that not disclosing their population identities would have prevented those identities from being discovered Provided opportunity for proactive consideration of the scientific, ethical, and cultural factors relevant to the decision how to identify each population

Concerns Raised by Labeling Populations Group stigmatization, discrimination (if a higher frequency of a variant associated with a stigmatizing disease is found in one population and the results are improperly over- generalized) Population history studies (challenge to religious convictions, established legal or political claims) Reification of race (a mostly social construct) as a highly meaningful biological construct

Other Concerns Too much focus, money spent on genetic research, not enough on ensuring access to basic health care Too much focus on genetics, not enough on environment, as contributor to disease risk Intellectual property, commercialization (and no immediate benefit to participating communities)

Addressing Group Concerns Through Community Engagement Also called community consultation, public consultation, community review NOT community consent A chance for communities to share their views about the ethical, social, and cultural issues the Project raises, provide input on how their samples should be collected and described, and identify any other relevant community concerns

Methodologies Individual interviews Focus groups Community surveys Town meetings

International Guidelines Human Genome Organisation (HUGO), Statement on the Principled Conduct of Genetics Research (1996) Council for International Organizations of Medical Sciences (CIOMS), International Ethical Guidelines for Biomedical Research Involving Human Subjects (2002) United Nations Educational, Scientific and Cultural Organization (UNESCO), Universal Declaration on the Human Genome (1997) United Nations Educational, Scientific and Cultural Organization (UNESCO), International Declaration on Human Genetic Data (2003)

Policy on the Responsible Collection and Use of Samples from Identified Populations Coriell Institute for Medical Research National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository

Samples Stored at Non-Profit Coriell Institute for Future Studies Broad consent given for future studies of genetic variation Cell lines created Cell lines and DNA made available to academic, government, and commercial researchers around the world Protocols for all future studies must be approved by Coriell Institute’s IRB

Community Advisory Groups (CAGs) Way for participating communities to stay informed about how stored samples and HapMap are being used Quarterly reports and annual newsletter Periodic meetings Coriell Institute will provide up to US $1,000 per year to defray expenses

Withdrawal of Samples and Data Individuals cannot withdraw their samples or data because the samples do not have individual identifiers. A CAG can request withdrawal of a community’s samples after careful consideration, reflecting the views of a substantial portion of the community. Genotype data already in the HapMap database cannot be withdrawn because they will already have been widely distributed.

Commercialization Companies may develop drugs, diagnostic tests, and other commercial products from future research using HapMap data. However, no commercial products will be developed as part of the HapMap Project. The Coriell Institute prohibits commercialization of the stored samples.

Patents and Data Release Project participants will not seek patents on the data they generate for which they have not demonstrated a “specific utility”. Project participants will not use Project data for other projects in their laboratories before the data are released. An interim protective strategy has been adopted to try to ensure that no restrictive patents are filed by researchers who use HapMap data (click-wrap license).

Compensation and Profits Donors were compensated for their time, travel, and inconvenience. Donors will not share in profits resulting from future development of commercial products resulting from research based on HapMap data.

Benefits and Reciprocity The HapMap is expected eventually to benefit the health of all people. The health benefits will take a long time to materialize, especially in resource-poor countries. Donors receive no immediate health benefits from providing samples. An appropriate community benefit is being negotiated with the CAG in resource-poor Nigeria as a demonstration of reciprocity.

An Unanswered Question Is spending more than US $120 million to develop the HapMap ethically justified when so much of the world’s population lacks access to basic health care?