3. Ethics in genetic research and practice

3.6 The Human Genome Diversity Project
The Human Genome Diversity Project (HGDP) is a collaborative research project that is being developed on a global basis under the auspices of the Human Genome Organisation (HUGO). The overall goal of the project is to arrive at a much more precise definition of the origins of different world populations by integrating genetic knowledge, derived by applying the new techniques for studying genes, with knowledge of history, anthropology and language.

The cells of every human being contain the same l00,000 or so genes. Collectively known as 'the human genome', these genes contain all the information that makes us appear and function as humans rather than as members of some other species. However, many human genes exist in more than one form (or 'allele') and not all of us carry exactly the same forms of every variable ('polymorphic') gene. Each of us, apart from identical twins, is thus a unique individual, recognisably human but different from all other humans. The genetic variation from one person to another reflects the evolution of our species, because it is the result, over many generations, of the survival or loss of different forms of genes or the natural introduction of new forms. Studying this variation among people from around the world provides a great deal of information about the development of our species which, integrated with findings from archaeology, linguistics, history and other disciplines, may lead to a much richer and more complete picture of our past than has previously been possible.

The specific aims of the HGDP are:

1. to investigate the variation occurring in the human genome by studying samples collected from populations that are representative of all of the world's peoples; and
2. ultimately, to create a resource for the benefit of all humanity and for the scientific community world-wide.

The resource is intended to exist as a collection of biological samples representing the genetic variation in human populations world-wide. It is also an open, long-term, genetic and statistical database on variation in the human species that will accumulate as the biological samples are studied by scientists from around the world.

The founders of the project intended the main value of the HGDP to lie in its enormous potential for illuminating our understanding of human history and identity. The resource created by the HGDP also provides valuable information on the role played by genetic factors in predisposition or resistance to disease. Considerable effort has been devoted to reviewing the ethical issues involved in the proposed project. The areas of concern range from the preservation of individual rights within indigenous communities, where the presumption of 'informed consent' and adherence to 'Western ethics' are likely to be at variance with common practice, to a concern with the preservation of intellectual property rights. The two major areas of ethical concern relate to collection and storage issues, and intellectual property rights to products derived from the collected samples.

3.6.1 Collection issues
It is clearly set out in the HGDP guidelines^r that respect for individuals and their cultural integrity must be the foundation on which all collection efforts are based. This necessitates the informed consent of all those participating in the HGDP. Regardless of the varying legal requirements that may need to be met, true informed consent requires that people agreeing to participate understand:

1. that the actual collection of the sample involves some (specified) risks although these are very small;
2. that the sample collection will cause a little discomfort; and
3. that DNA from the sample will be stored in a repository and may be used by many investigators for a long period (for many subjects this also requires that they understand that cell-lines will be established; see 5.3 Book 1).

Further, the issue of testing for disease is not only a very important aspect of collection, but is also many faceted. For example, there are obligations to resolve with regard to testing for infectious disease, which raises issues of protecting laboratory workers and investigators, as well as issues of protecting the individuals from whom samples are collected.

The disclosure of the infectious disease diagnosis to the community or participants must be closely considered. There are also obligations to resolve with regard to testing for non-infectious disease. In all cases, there are many questions to be addressed. For example, is it ethical to test for any disease without providing pre- testing counselling or evaluation of the test? (For example, in South Africa people may be tested for HIV only with proper pre- and post-test counselling.) Who is to be informed of results? If disease is tested for, what is the obligation to provide treatment?

Finally, the anonymity of all participants must be preserved, to provide protection against possible abuse or adverse effects arising from the consequences of the study. However, the HGDP is based on the fundamental principle that the resulting data may be accessed by any scientist. The primary concern regarding access to the database is the prospect of military access. Population-targeted biotech weapons are not an impossibility. In fact, the World Medical Association has expressed concern about the potential development of genetically targeted weapons, a topic of debate in the US Department of Defence, as possibilities in future combat scenarios.⁴⁴

3.6.2 Intellectual property rights
The guidelines state that patenting products derived from the samples contributed to the HGDP should include provision for the financial return on sales to benefit the sampled population or individual. However, there are many precedents where this principle has not been applied. In many areas of the world, such abuses have made people aware of this problem. While the HGDP asserts that it has no financial or commercial interest in the collection and analysis of the samples, it must be noted that the HGDP operates under the auspices of the Human Genome Organisation, and that major funding for the HGDP has been obtained from the US National Institutes of Health, while the National Science Foundation supports individual researchers. Further, the US Government is very interested in the commercial prospects of biotech products. On this basis, it would be desirable to put the management of the database into the hands of a respected and independent international organisation.

The guidelines do not touch on the issue of patenting cell-lines derived from the genes or cell-lines of participants. Such patents by the US Government of the cell-lines of indigenous communities have elicited an outcry among indigenous peoples. Seventeen native groups have criticised the HGDP, calling for a halt to the project and asserting their entitlement to the recognition of full ownership, control and protection of their property. The potential for profit from indigenous genes is demonstrated by just one example - the isolation of genes which code against cardiovascular disease, found in an isolated community in Italy.⁴⁵

The following ethics guidelines produced for researchers of the HGDP, were proposed as a measure of protection against potential abuses of the samples and donor communities.

1. The HGDP and its participating researchers must always respect the humanity of the sampled individuals and the cultural integrity of the sampled populations. This respect demands that collections proceed only with the informed consent of both the population and individual members. It also demands that the project observes the primary responsibility to avoid harming sampled individuals or their communities. Wherever possible, studies should be carried out by local investigators known to and trusted by the population to be sampled.
2. Informed consent is both an ethical imperative and a legal requirement. The HGDP must satisfy both conditions. To do so, the question of obtaining informed consent from participating individuals cannot be considered a mere formality but must be obtained in a culturally appropriate manner. This may differ from country to country. In addition, when scientists are funded to collect samples abroad, they must be sensitive to differences of protocol in obtaining informed consent. Funding agencies should respect these differences and not seek to impose their own cultural procedures. The requirement in all cases is for people to be informed both of the collection procedure and of the overall goals, and possible financial benefits, of the HGDP in ways they understand and that are appropriate to their culture. All participation should be voluntary. The objective should be to have the individual participants and the entire community become partners in the scientific effort. The idea of informed consent should also include an appropriate form of feedback of the results of the study to the sampled population.
3. Researchers should actively seek ways in which participation in the HGDP might bring benefits to the sampled individuals and their communities. Examples of such benefits include health screening, medical treatment or educational resources.
4. One way to avoid harming the sampled individuals or their communities is to protect the identity of those sampled and, in some cases, of the entire community - the latter to prevent possible group stigmatisation.
5. Although very unlikely, it is nevertheless possible that the results of the HGDP may lead to the production of commercially beneficial phamaceuticals or other products. Should a patent be granted on any specific product, the investigators and sponsors must ensure that the sampled populations benefit from the financial return.
6. Human history - and the human present - is full of racism, xenophobia, hypernationalism and other tragedies stemming from beliefs about human populations. In the past, some of those tragedies have been perpetrated by, or aided by, the misuse of scientific information. All those involved in the HGDP must accept a responsibility to strive, in every way possible, to avoid misuse of the project data.
7. Many people in the world have, at best, a limited understanding of human genetics. Some fear the consequences of human genetic research, in part because of their limited knowledge. To scientists involved in the HGDP, their fears may not seem justified or even, in some cases, fully rational, but the concerns are very real to the people involved and they must be addressed. It is essential that a world-wide 'public awareness' programme be included in the project to educate people about its aims, methods and results.
8. Inevitably, the ethical issues faced by the HGDP will evolve over time. They must therefore be kept under continual review. The widest possible consideration of the issues should be encouraged.
9. The transfer of technology to developing regions of the world, which is an integral part of the proposed project, should contribute positively to the development of self-sufficiency in these regions. The help given should not be superficial or of only short-term usefulness.
10. There should be a feedback of information to populations that participate in the HGDP, most especially about any aspect of the project in which a particular interest was expressed.

In summary, although the stated intent of the HGDP is laudable, the evidence indicates that, in carrying out its intent, the HGDP has thus far failed in its primary goal of bringing together the peoples of the world in an effort to eliminate prejudice, racism and xenophobia. The above guidelines should be adhered to, in order to improve collaborative research.