The Human Genome Diversity Project (the "HGD Project") is an international project that seeks to understand the diversity and unity of the entire human species. The HGD Project is still largely in its planning stages, seeking the best ways to reach its goals. We hope this document will provide important background information to help people gain a better understanding of this evolving initiative. It was written by the North American Committee of the HGD Project in late 1993 and early 1994 to respond to questions committee members were frequently asked. It represents the views of that Committee at that time.
At this point, the HGD Project is still in its planning stages. Researchers have been collecting genetic data throughout this century from populations around the world, and these data still exist in the scientific literature and individual researchers are continuing such studies. Although its organizers had discussed the Project since 1991, the Project was formally organized only in mid-September 1993. Its North American Committee has not collected any samples under HGD project auspices. That collection will not occur until the Project's structure, including its ethical guarantees, is fully in place.
All human groups seem to be interested in their origins; many are interested in scientific evidence about those origins. The information this Project gathers may help clarify the history of specific human populations and of our species as a whole. The frequencies of different variations in different populations can reveal how recently they shared a large pool of common ancestors. Those frequencies can be used to see if, for example, the Irish are more closely related to the Spaniards or to the Swedes.
The kinds of genetic variation useful for these studies are often common forms of variation such as the genetic differences among individuals that are responsible for different blood types or the (as yet unidentified) genes that lead to some people having narrow noses and others wide noses; some having dark hair and others light hair. Many other times, the small differences in DNA that the Project will study may make absolutely no difference in what the individual is like. These differences, apparent only at the genetic level, can still be used to help understand relationships between different populations.
That kind of information will help clarify the major human migrations. It can help tell us, for example, whether different migrations brought Native Americans to the Western Hemisphere from Asia or whether a single group is ancestral to all modern Native Americans. Because migrating peoples carry their languages with them, and because these are rarely abandoned, it may be possible to learn how people speaking Bantu languages expanded through much of sub-Saharan Africa in the last two millennia or how the Indo-European languages spread through Europe and Asia. It may tell us who are the closest relatives to the Euskadi (also known as Basque) people of northern Spain and southern France, whose language seems unrelated to any other. And it may settle the continuing debate about whether Homo sapiens evolved to modern humans in Africa or over the whole world.
The Project will also provide increased knowledge about the factors that lead to disease or to health, both in the United States and throughout the world. People vary in their susceptibility to different diseases, and while much of the explanation will be due to environmental factors like diet, genetic predispositions play a role in many cases. The collection and analysis of DNA samples may, in conjunction with epidemiological evidence, help lead to the identification of genetic factors in some human diseases and eventually to ways to treat or prevent those diseases.
These samples can also help resolve some fundamental scientific issues about how genetic change takes place in humans. How quickly do humans adapt to changed environments and how is the response made? Such questions may be answered by the HGD Project.
Without this Project, science will characterize “the” human genome, with its historical and medical implications, largely in terms of what is known from a small sample of people of European origin, where most research in this field is being done. And if sampling is too long delayed, some human groups may disappear as discrete populations, usually through urbanization or other forces leading to the loss of their language or the other characteristics that identify them as a separate group. At a time when we are increasingly concerned with preserving information about the diversity of the many species with which we share the Earth, surely we cannot ignore the diversity of our own species.
These questions are all interesting to scientists. Many of them are likely to interest non-scientists. One goal of the Project is to find out what the people sampled would like to learn from the genetic data, and then try to answer those questions as well.
Several months earlier, a first draft of more-detailed organizational plans for the HGD Project were developed at an international meeting of those interested in the Project. A formal statement of the Project structure and objectives is in preparation and soon to be released. The HGD Project has an international executive committee that currently has 13 members, all with limited terms, from North America, Europe, Africa, India, and Japan. The HGD Project executive committee has two standing subcommittees, one on ethical issues and one on informatics (the computerized storage and use of large amounts of data the Project will generate). The HGD Project executive committee will hold an annual forum, made up of representatives from international organizations, regional HGD Project committees, non-governmental organizations, sampled populations, and others concerned with the Project. That forum eventually will nominate new members to the HGD Project executive committee.
The HGD Project executive committee has encouraged each region of the world to create its own regional HGD Project committee. Those regional committees will be responsible for raising funds in their region and for overseeing collection efforts in that region. This will allow local control over the Project and greater sensitivity to local concerns. Regional committees have been formed for Europe and for North America, with others in the process of formation in Eastern and Southeastern Asia, Australia and the Pacific, India, Central and South America, Africa, and other areas.
The structure of the various committees may vary. As an example, the North American Committee currently has 13 members, including anthropologists, geneticists, a lawyer, a law professor, and a sociologist. Two members of the North American Committee are Native Americans; one is African-American. The North American Committee is also creating its own ethics subcommittee. That subcommittee will have about 4 members from the Committee and 5–7 members who are not associated with the Committee. The members of the ethics subcommittee, like members of the Committee, will come from diverse ethnic and professional backgrounds.
The definition of a separate human "population" is not precise, but, using language as the primary criterion, there are between 4,000 and 8,000 distinct human populations around the world. As an interim goal, the HGD Project would like to collect DNA samples from about 500 of those populations within five years. In some large linguistic or geographic populations, which cannot be adequately represented by a single sample, many samples will be taken from different parts of the population. The DNA samples can be taken from small and harmless blood samples, from hair roots, from cells scraped off the inside of a cheek with a tongue depressor, and from sputum and other biological materials.
The Project will preserve these samples in both central and regional repositories around the world. Most of the samples will be frozen; some of the blood samples will be changed into cell lines, which are capable of producing a large amount of duplicate DNA for study. For only the cost of making and shipping the duplicate samples, they will be made available to qualified scientists interested in doing research on them. Such availability or use of such samples may be limited by contracts between the HGD Project and researchers, in order to protect the interests of the sampled populations.
The Project itself plans to carry out some basic, preliminary analyses of the DNA samples. It might subject all samples to the same set of tests on variation at the DNA level to provide some uniform data across the collection.
Once the samples have been analyzed, either as part of the standard battery funded by the Project or by researchers who have received samples from the Project, the results of those analyses will be put into a computerized data base. Information in the data base will be broadly available to those who want to use the results for legitimate research, again subject to contractual limitations.
In almost all humans, almost all genes are almost identical. These genes have to be very similar or else the bodies they build wouldn't work and their owners would die. Some DNA bases and sequences can differ from person to person without changing anything, as they don't seem to have any effect on how the body functions. Other variants produce such effects as variation in our height, eye color, fingerprints, blood groups, and whether we can roll our tongues. Sometimes, particular genetic variants can lead to susceptibility to disease or to unusual resistance to disease. Genes of these types exist in all human populations and are of great interest to medical researchers trying to improve human health and welfare. And even where the variations are of little, if any, functional significance, they can tell us something about the human past.
These various kinds of variations — those in portions of the genome that do not code for proteins, those changes in the genes that don't change the resulting proteins, and those that do make some differences in the body's structure or performance — are not distributed randomly. The more closely related two people are, the more likely they are to share the same variant genes, or alleles. Siblings have a 50 percent chance of sharing any one allele; less closely related family members have a smaller chance. To the extent that people who live in a particular area, or who make up an ethnic group, a nation, or a "population" share common ancestors, they are more likely to share these kinds of genetic variants than people who do not share common ancestors. Of course, ultimately, we all share the same ancestors, but in the tens of thousands of years during which, for example, the ancestors of Native Americans did not live in the same region as (and hence did not have children with) the ancestors of Europeans, those two population groups developed separately. New genetic variants appeared in each group, and ancestral shared genes are present in different frequencies. Any one Native American may have the same alleles as any one European. When one looks at a number of alleles in a number of Native Americans and Europeans, however, it becomes clear that the two groups of people often differ in their variant genes. Thus, for example, the blood groups O, A, B, and AB, all genetically determined, may appear in all human populations, but often in very different proportions reflecting the frequencies of the underlying alleles.
Scientists already know at least one interesting thing about these kinds of genetic variation. Although there are genetic differences between groups, the extent of such difference is small compared with the amount of difference found within a group. People within "ethnic groups" are genetically more different from each other than their group is from other groups.
These knowledgeable people, from inside or outside the population, can act as cultural interpreters, translating the lifeways, goals, and hopes of each for the other to help ensure that the population and the Project understand each other. This is important to guarantee that the population has really understood the sampling process and the purposes for which the Project will use their samples and has truly consented to be involved. It could also help investigators determine what questions interest the population and to try to sample in ways that may help answer those questions. No samples will be collected without explicit informed consent from surveyed subjects, obtained in a way that is culturally appropriate to that population. This expert involvement also lets the Project maintain continued communication with the population, in part to give them a chance to learn any findings from the research of interest to them.
Different numbers and types of samples will be obtained depending on the circumstances. For some research questions, samples as small as 25 unrelated individuals may be sufficient; to study other problems, larger samples will be needed.
In all populations that wish to participate, we expect that, after the Project has been fully explained and has been approved, some blood samples will be taken. This will involve drawing about 15 to 20 milliliters (less than an ounce) of blood from each donor. Blood will be drawn only by trained personnel — usually by health-care personnel. Some people will give hair-root samples, with DNA taken from the roots of a few hairs, pulled out of the scalp as is often done with a simple brushing. Others will give cheek scrapings, where the DNA can be taken from the cells that are scraped onto a tongue depressor when it is run across the inside of a person's cheek. Often, sputum is enough. None of the collection methods is dangerous and only drawing blood involves even minor pain. For scientific purposes, some personal information will have to be collected about the donors, such as age, sex, languages spoken, and birthplace, but the Project will keep the identities of individual donors confidential. Indeed, such confidentiality is a condition of funding of the Project by all national and international foundations.
The application should also indicate what, if anything, is of particular interest in studying that population. Some of the things that might make a population of particular interest include an unusual language, culture, or history; an indication of susceptibility to or immunity from particular diseases; or a possible relationship to another interesting population. This Project is not an effort to collect samples from isolated populations in danger of disappearing. It intends to take a representative sample of all human populations, including those in Europe and North America. No group is necessarily excluded. In the long run, if time and money permit, the Project would like to include samples from all human populations worldwide. But none will be included who do not want to participate.
In planning workshops, groups of knowledgeable scholars have discussed the major issues that might be of importance in various regions of the world. This was done to develop a clearer idea of the potential scope and nature of the samples that might be needed for the HGD Project to be successful. Working lists of hundreds of examples of populations that might be included to answer various specific questions were developed, as a way of accomplishing the objective of specifying objectives for the Project. These lists were obtained by various people not involved in the workshops, some of whom misunderstood their purpose and used them in a way that incorrectly misrepresents the Project, as if it had already decided what populations it would include, and indeed, some claims were made in the news media that the Project had already been collecting such samples. This was not correct. The Project cannot collect samples from any population without its prior consent, and since no such consent had been obtained prior to the sampling workshops, the lists discussed there were always intended as examples to help focus the discussions.
Some people may object to outsiders studying local indigenous populations as if this implies they were somehow "unusual" forms of human. The HGD Project objects to such a notion too! Scientists involved with the HGD Project are concerned that most human genome research concentrates only on persons from the major ethnic groups in the industrialized countries. Indigenous groups are not being served — and this deliberately ignores their importance as members of the human species. Not knowing enough about the genetics of such populations may also have medical ramifications. What is going on now is ethnic exploitation by neglect.
The Project wants to encourage researchers to provide useful feedback to individuals and populations that provide samples. Individuals who want information about their samples should be given the chance to request that it be sent to them. Populations should receive timely information about the Project's findings concerning them, in a way that gives them a chance to ask further questions. After collection, as well as during it, the Project's goal is a partnership with the sampled populations.
The Project also hopes to provide some direct medical services as part of the collection process when it can do so. Health-care workers participating in the collection process could provide, if requested, some screening, immunization, diagnosis, or treatment of medical conditions while working with the population. For example, one of the founders of the Project, Dr. Cavalli-Sforza, worked for many years with populations in central Africa. He quickly discovered that many of the people he saw suffered from yaws, a rare but terrible skin disease. On subsequent trips, he brought large amounts of antibiotics that cured this affliction. Although the HGD Project cannot solve the health problems of the populations it samples, when feasible, and authorized by the appropriate governmental authorities, it would like to provide some medical services as part of its collection efforts.
The developing world believes that the seed and drug companies from the developed world have long exploited their plant genetic resources. These companies, they believe, freely gathered plants from the developing world — often variants that had been domesticated, developed, and maintained by generations of indigenous farmers. Without paying anything to the farmers or their country, the companies used those resources to create patented products that were then sold back to the developing world at high prices for large profits — with none of the profits returning to the plants' original users. Some in the developed world would dispute whether this belief is entirely accurate, but all agree it has some validity. This concern about the developed world's exploitation of the plant and animal genetic resources of the developing world played a major role in the 1992 Biodiversity Treaty.
Some advocates for indigenous peoples or the developing world have been concerned that the Project will be a human version of these plant- collecting expeditions. It will not be.
First, it is not clear whether any commercial products are likely to emerge from its samples or data. More important, even if commercial products were created using the Project's samples, the HGD Project is committed to two propositions: (1) that financial benefits should not go to the Project and (2) that an adequate part of the financial gains, if any, must go back to the sampled populations. The best ways to implement those commitments are not yet entirely clear. Implementation depends on some complex issues of patent and contract law that have not been entirely resolved, as well as on some decisions by the sampled populations or their representatives on how best to proceed. The Project plans to make those implementation decisions after consultation with such representatives. But, whatever method ends up being chosen to implement the Project's commitments, the commitments themselves are firm. The HGD Project will not profit from the samples and it will do its best to make sure that financial profits, if any, return to the sampled populations.
No population should take part in the Project because it expects to earn royalties from pharmaceuticals. We do not know whether any commercial products will come from the Project, let alone whether samples from any one population will lead to valuable products. But the Project can promise to share with the sampled population the information derived from the samples — about history, medicine, or other topics. And, in many cases, the Project may attract useful outside attention to populations that are struggling with abuse or exploitation.
Each region is seeking funding independently. The North American Committee hopes for substantial governmental funding, but neither Canada nor the United States has yet decided whether to support the Project. In the United States, the Project is particularly interested in funding from the National Science Foundation and the National Institutes of Health. The North American Committee also plans to seek some funding from private foundations, but it does not intend to seek funding from commercial sources. Thus far, the North American Committee has received only small planning grants from several United States agencies. Those planning grants were used to hold four planning meetings in 1992 and 1993. Those grants are now nearly exhausted. The North American Committee has just received a grant from the MacArthur Foundation for preliminary work on ethical issues, communications, and other foundational efforts.
Within Europe, funding of about $500,000 over two years has been received from the European Community's Human Capital and Mobility Program to establish a network of laboratories interested in the Human Genome Diversity project. Other regions will also be seeking money from other governmental or private sources.
Back to the Human Genome Diversity Project.Revised October 6, 1994