5.1. The human genome diversity project

The Human Genome Diversity Project (HGDP) is the brainchild of a group of scientists headed by Luca Cavalli-Sforza who proposed in 1991 to create a global map of human genetic variation. The aim of the project is to take blood, tissue and hair samples from some 700 ethnic groups in order to produce detailed information on the origins and migration histories of human populations and the gene, tic basis of their differing susceptibilities to certain diseases.

Who are we?

Where do we come from?

Where are we going?

The aim of the HGDP, contends anthropologist Andre Langanay, is to help answer the first two of the questions that humans have always asked themselves. And so, it seems, genetic tinkering is going not only to cure world hunger and rid us of sickness and disease, but it is going to help us understand the meaning of life.

The cells of everybody alive today, regardless of where or how they live, contain the same 100 000 or so genes. Collectively known as the human genome', these genes contain all the information that distinguish us from other species. However, many human genes are described as polymorphic' because they exist in more than one form as different alleles (see p. 74). The physical differences (such as hair and eye colour) that help us to distinguish people are the results of genetic polymorphism. Each of us, apart from identical twins, is a unique individual, recognizably human but different from all other humans.

The genetic variation from one person to another reflects the evolution of our species, since it is the result, over many generations, of the survival or loss of different forms of genes or the natural introduction of new forms. The HGDP believes that 'studying this variation, which is the aim of the HGDP, can therefore provide a great deal of information about the development of our species which, integrated with findings from archaeology, linguistics, history and other disciplines, can lead to a much richer and more complete picture of our past than has previously been possible'. It goes on to say that it will also provide the scientific data to confirm and support what is already clear from population studies - that, in biological terms, there is no such thing as a clearly defined race and thus it will 'undermine the popular belief that there are clearly defined races, to contribute to the elimination of racism and to make a major contribution to the understanding of the nature of differences between individuals and between human populations'. Biologically, there is only a continual graduation from one population to another.

The third major contribution the HGDP is expected to make is to provide valuable information about the factors contributing to disease. The incidence of different diseases varies between populations and, while much of this variation can he explained by environmental factors such as diet, climate, the presence of parasites or pollutants, genetic factors are also known to have a predisposing effect in many cases. Scientists believe that studying the differences in the genetic composition of different communities will ultimately help to develop more effective ways of treating and preventing many diseases. Some of the areas on which the HGDP is expected to throw new light are the inheritance of disease, the development of cancer and the process of ageing.

The project was taken under the wing of the Human Genome Organization (HUGO) and the Human Genome Project (HGP), the European and US arms of the ambitious attempt to map the human genome using molecular genetic analysis. The HGDP can in some ways be seen as a natural extension of HUGO and the HGP, since it can complement the other two studies by helping to build up a more truly global picture of the genome. In Cavalli-Sforza's words, 'The "Book of Man" would be rather shallow if it were written without consideration of the well-known fact that everyone is different from everyone else.'

The HGDP is expected to cost between $23 and $35 million over five years, funding for which is largely to come from the HGP. Although funds are still not completely assured, sample collections have already begun. Cavalli-Sforza was very concerned that the project should get going as soon as possible because of the endangered nature of many of the indigenous groups.

Scope and strategy of the HGDP

More than 700 groups from all around the world were targeted for DNA sampling at the HGDP's Second Workshop meeting in 1992.4 The group comprises 165 from Africa, 212 from Asia, 114 from South America, 101 from Oceania, 107 from North America and 23 from Europe. Among them are the Yukaghir of Siberia (with about 100 people remaining in the group), the Alcaluf of Southern Chile (less than 50 remaining), the Amazon's Akuriyo (50 survivors) and the Tench of Micronesia (about 80 remaining).

Biological samples of blood, hair, and/or cheek scrapings will be collected anonymously from each group, along with socio-demographic data, such as sex, age, place of birth, place of residence, and further parental information. Between 25 and 150 people will be sampled from each population, depending on the size of the group; researchers are clear on how many samples are needed to ensure that the material deposited in the central HGDP repositories is representative of the population being sampled. It is intended that most of the initial collecting and handling of samples will be done by local investigators; regional collection centres will need to be established for sample storage and analysis.

The HGDP Summary Document notes that 'not all regions of the world are experienced in the techniques of molecular biology and genetics and that some countries will not, in the foreseeable future, acquire the "cutting edge" technology that is needed for the mapping and sequencing of the HGDP. However, it is feasible for the more limited technological demands of the HGDP to be met by most countries, given training of staff and help with techniques'. The HGDP team see this as one of the 'most exciting aspects of the project', in that it 'offers all countries a unique opportunity to become involved in . . . the global genome initiative'.

But according to critics of the project, there is a danger that the resources used for such capital-intensive initiatives could easily be diverted from more pressing public health projects in many countries. Some also question the justification of spending so much money on the HGDP, even if it isn't at the expense of other projects, when there are so many more immediate and pressing health needs for many communities. In defence of the HGDP, project organizer Ken Weiss points out, 'We are concerned about the wellbeing of these (indigenous) people. But a group of geneticists isn't going to save them. Stop clear cutting the Amazon rainforest. That will save them'.

Many of the scientists behind the diversity project, he points out, have been instrumental in publicizing the plight of the Yanomami people in Brazil, whose population has plummeted in recent years as the result of unrestrained mining for gold and tin, and the concomitant destruction of their environment and the introduction of disease.

Once the samples are placed in the central repository, DNA will be extracted and stored 'for long-term use'. In order to provide a back-up source of the DNA, a number of blood samples will be immortalized as cell lines (all descended from a single cell). In principle, DNA can be made to last indefinitely through the application of a group of techniques known as polymerase chain reaction (PCR), which can even make copies of DNA from single cells.

Human bioprospecting Newspeak

At the outset the project organizers recognized that their planned activities could cause dismay among indigenous people and the wider public. According to the report of the second workshop on the project, 'the establishment of permanent cell lines needs to be explained in terms that are understandable, but that do not mislead subjects in any population. English terms such as 'immortalization" of cell lines can be badly misunderstood . ..' Many indigenous groups, however, feel that the careful avoidance of using such terms is a convenient way of not allowing them to become aware of the full implications.

The same document also points out that there is 'no fully acceptable way to refer to populations that are in danger of physical extinction or of disruption as integral units (gene pools); some existing terms such as "endangered" populations can have various connotations . . . in this report we refer to such groups as "Isolates of Historical Interest" (IHI) because they represent groups that should be sampled before they disappear as integral units so that their role in human history can be preserved'. The logic and rationale behind this Newspeak is one of the aspects of the project that indigenous groups have reacted against most strongly (see pp. 145-8). More recent public documents on the HGDP have dropped the use of this term.

The importance of promoting the good image of the HGDP is made clear in the Summary Document. '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 the limits of their understanding. To scientists involved in the HGDP, such fears may not seem justified or even fully rational . . .' Nevertheless, it is seen as 'essential that a worldwide "public awareness" programme is included within the project to educate people about its aims, methods and results.'

Prior informed consent

Indigenous groups have strong ethical, religious and moral value systems, and it is critical that these are respected (see Chapter 5.2). HGDP documents recognize that sampled populations must 'be provided a full level of informed consent. Religious or other cultural concerns must be protected'. However, this statement is qualified in that there is only an expectation that the groups 'understand as fully as practical the implications of the study, and its purposes'. The vagueness of the language leaves it open to wide interpretation. In a recent TV programme broadcast in the UK, which followed HGDP researchers on their field work in Colombia, indigenous groups were given a very limited view of the project. Its implications were not made clear to the various communities and discussions of the wider objectives of the project were overshadowed by the carrots offered to the communities, such as opportunistic medical clinics set up to treat minor and immediate health concerns of the villagers and promises of the blood samples being used to test for diabetes in the population. By giving only half of the picture, the HGDP is not being true to its own principles, nor to the communities the researchers are dealing with.

Intellectual property rights

Earlier drafts of HGDP documents completely ignore the issue of intellectual property rights, and later versions only touch on it, stating that, 'Although very unlikely, it is nevertheless possible that the results of the HGDP may lead to the production of commercially beneficial pharmaceuticals or other products. Should a patent be granted on any specific product, the project must work to ensure that the sampled populations benefit from the financial return from sales'.

Some critics argue that the HGDP is greatly understating the potential economic returns from the project. According to RAFI, 'in the US, the patenting of human genetic material is well underway. Blood samples collected by the HGDP will be stored at the American Type Culture

Collection, near Washington D.C . . . In November, 1992, this respository held 1094 human cell line entries, more than one-third of which are the subject of patent applications'. RAFI goes on to point out that backing for the HGDP's primary funder, the HGP, comes from the US Govemment's National Institutes of Health (NIH), which has already made patent applications on human genetic material. Bioprospecting for human genes is very much a reality already, and many indigenous groups are already very concerned about being treated as commodities.

The involvement of industry in the HGDP is ambiguous. While project organizers are keen to stress that the project has no commercial ambitions, industry seems to be closely involved in the project. Researchers from Roche Molecular Systems accompanied HGDP researchers on their field work in Colombia and Ecuador, and the company has been involved in several other cases of human gene prospecting. Researchers have, for example, already made several attempts to gain access to the Aeta people in the Philippines, who are on the HGDP's list of suggested sampling populations.

References

1. Oral presentation by Andre Langanay of the University of Geneva at the 'Patents, Genes and Butterflies' Conference in Bern, Switzerland, October 1994. Langanay recently resigned as a committee member on the HGDP.

2. The Human Genome Diversity (HOD) Project - Summary Document (1994).

3. From an article in Genomics, as reported in the New Scientist, 29 May 1993.

4. Report of the Second Human Genome Diversity Workshop. Penn State University, 29 31 October 1992.

5. Lewin, R. (1993) Genes from a Disappearing World. New Scientist, May 29.

6. The Gene Hunters, Channel 4 Productions, 1994.

7. RAFI (1993). Patents, Indigenous People, and Human Genetic Diversity. RAFI Communique, May 1993.

8. Letter to Phillip Camara c/o the Makati Medical Centre from Elizabeth Trachtenherg of Roche Molecular Systems, 1 March 1993.

9. Letter to Dr. Elizabeth Trachtenberg of Roche Molecular Systems from Philip Camara of SASFI, 11 June 1994.

10. Reply to Philip Camara from Elizabeth Trachtenberg, 26 July 1994.