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 ChineseAt 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 forIdentifying 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 forIdentifying 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

http://locus.umdnj.edu/nigms/comm/submit/collpolicy.html

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?