The Human Genome Diversity Project (1991–2002)

The Human Genome Diversity Project, or HGDP, was an effort led by US-based scientists to collect DNA from members of Indigenous communities living around the world for the purpose of understanding human history, migration, and evolution. Launched in 1991, and led by Luca Cavalli-Sforza, a scientist at Stanford University in Stanford, California, the HGDP initially had the support of US funding agencies. However, the project eventually lost that support when representatives of Indigenous groups protested the project as being exploitative and fellow scientists accused it of racism. Though the project ultimately failed to collect most of the samples it had originally planned, the HGDP was one of the first attempts by scientists to catalogue worldwide human genetic variation, and the DNA samples it did collect formed the basis of many subsequent research studies concerned with understanding human genetic variation and migration patterns.

1. Background and Context of the HGDP
2. Start of the HGDP
3. Controversies Surrounding the HGDP
4. The HGDP Responds to Criticism
5. The HGDP Cell Line Panel
6. Scientific and Social Legacies of the HGDP

Background and Context of the HGDP

The HGDP emerged out of scientific discussions over the utility of the then-ongoing Human Genome Project that began in 1990. The goals of the Human Genome Project, or HGP, included sequencing the entire three billion base pairs of DNA in one human genome, defined as the total amount of DNA found within one complete set of the twenty-three human chromosomes. HGP leaders argued that the knowledge gained would contribute to improvements in health by pinpointing the genetic causes of diseases. Evolutionary studies would also benefit, HGP leaders claimed, by showing how humans relate to other organisms, whose genomes the scientists also planned to sequence as a part of the project. In the early 1990s, Cavalli-Sforza, who was not affiliated with the HGP, argued that however useful it would be to have a complete sequence of one human genome, many questions related to understanding human disease and human evolution would require information about genetic variation among individuals. For that reason, Cavalli-Sforza put forward the idea of the HGDP to further understand human genetic variation.

Cavalli-Sforza and several colleagues who researched human genetics, namely Allan Wilson, Charles Cantor, Robert Cook-Deegan, and Mary-Claire King, laid out their proposal in a 1991 article published in the journal Genomics. They urged national and international funding agencies to support a coordinated effort to collect blood, hair, or skin cells from what they termed isolated Indigenous populations located around the world. From those cells, the scientists would extract and sequence DNA. They further urged that the collected blood cells be preserved in cell lines, which are populations of cells that can reproduce indefinitely in the lab. Preserving the cells as cell lines, they argued, would enable future researchers to continue studying the genetic information within them for years to come. Because many of the Indigenous populations lived far from airports and modern laboratories, the researchers proposed setting up regional laboratories to turn perishable blood samples into stable cell lines within hours after collection. Cavalli-Sforza estimated that an initial five-year stint of the project would cost between $23 and $35 million. They initially planned to collect biological samples from between 10,000 and 100,000 people from roughly 500 populations. The emphasis of the proposed project was on using such samples to understand prehistoric human migrations and evolution. Through the data, researchers could also acquire knowledge about inherited diseases and disease risk in different populations.

Cavalli-Sforza and colleagues explained that their rationale for focusing on isolated Indigenous world populations was twofold. First, they argued that the DNA from members of groups that had remained relatively isolated from other human groups through linguistic or geographic barriers would be more useful than DNA from more recently assembled urban populations for reconstructing prehistoric human migrations. Second, they stated that those isolated human populations were in the process of merging with others due to improvements in communication and transportation, with the result that their DNA would soon no longer preserve the record of that history. In their 1991 article, Cavalli-Sforza and colleagues refer to their project as time sensitive, indeed a vanishing opportunity.

Cavalli-Sforza, the HGDP’s main proponent, had a long history of using genetic information to study human migration and evolution. In the mid twentieth century, he had begun using measures of ABO blood group frequencies to analyze genetic variation. All humans have an ABO blood type. They are either blood type A, B, AB, or O, depending on what specific markers on their red blood cells they have inherited. For any given population of people, say people living in a small town in the Italian countryside, scientists can calculate the frequency of the A, B, and O alleles in that population, provided they have a representative sampling of blood from individuals living in that population. By comparing the frequencies of blood type alleles in neighboring populations, Cavalli-Sforza drew conclusions about how the populations in Italy were related to each other. In the 1960s, along with a colleague, Cavalli-Sforza developed a new statistical method to compare and create evolutionary trees from such data. In the 1960s, Cavalli-Sforza began using data on genetic changes on the Y-chromosome to trace back male lineages and draw conclusions about the routes that humans took as they began migrating out of Africa 50,000 to 70,000 years ago. By the late twentieth century, new methods for assessing human population genetics became available, namely DNA sequencing. In 1984, Cavalli-Sforza and his colleague Kenneth Kidd from Yale University in New Haven, Connecticut, began collecting blood samples from Indigenous populations in Africa to obtain DNA for population genetic studies. Seven years later, in 1991, Cavalli-Sforza and colleagues proposed the HGDP.

Start of the HGDP

US funding agencies were initially receptive to the idea of conducting a study of worldwide genetic variation as Cavalli-Sforza and colleagues proposed. In 1991, Walter Bodmer, then president of the Human Genome Organization, which coordinated efforts of the Human Genome Project, asked Cavalli-Sforza to chair a committee to study the feasibility of the HGDP. The US National Science Foundation, the National Human Genome Research Center, the National Institutes of Health, and the US Department of Energy provided funds for four meetings to plan the project.

The first meeting, which Cavalli-Sforza and his colleague Marcus Feldman organized at Stanford University in Palo Alto, California, in July 1992 brought together forty anthropologists and population geneticists to develop a sampling strategy, or a strategy for how to go about deciding which individuals or groups from which to collect DNA, and how. The second meeting, held at Pennsylvania State University in State College, Pennsylvania, in October 1992 included fifty anthropologists, archeologists, and linguists and concerned which of the 5,000 or so distinct human populations around the globe the scientists would decide to study. They decided, at that meeting, to choose groups based on scarcity of native language speakers, isolation, and those groups they argued would be most useful for understanding specific anthropological questions, such as when and how humans first began to inhibit the Americas. The third meeting, held in Bethesda, Maryland, in March 1993 concerned molecular details of the project as well as issues of ethics and informed consent. The fourth was an international meeting held in Sardinia, Italy, in September 1993 and devoted to forming organizational structures and executive committees.

An early point of contention that held off agreement emerged during the first meeting in 1992 concerning the ideal sampling method for the HGDP. Allan Wilson, who studied biochemistry and evolutionary biology at the University of California in Berkeley, California, had been a proponent of collecting DNA from individuals at set geographic intervals along a grid, arguing that such an approach would best limit researchers’ bias in choosing which people to study. Wilson died just prior to the first planning meeting for the HGDP, but several of his former students attended, including Mary-Claire King and Mark Stoneking. In opposition to Wilson, Cavalli-Sforza argued for collecting DNA from populations defined principally by markers such as shared language or culture. But according to the Wilson camp, Cavalli-Sforza’s population approach was predicated on too many assumptions that could bias the conclusions. It assumed, for example, that biological populations and linguistic groups were synonymous, which others argued may not be accurate.

By the end of the July 1992 meeting, Cavalli-Sforza had reached a compromise with the Wilson camp. Instead of making cell lines from the blood of fifty individuals in each of 200 populations, they planned to create cell lines from twenty-five people in each of 400 populations and take additional blood samples from people between populations. Increasing the number of populations studied and the additional blood samples solved some of King’s and Stoneking’s concerns, because it would allow researchers to determine whether the HGDP’s definition of a particular population was real or imaginary. At a follow-up meeting in October 1992, the scientists discussed exactly which populations to sample.

Controversies Surrounding the HGDP

In 1993, the HGDP became embroiled in controversy when representatives of Indigenous groups around the world began to protest the project, claiming it was a form of biopiracy. By biopiracy, they meant taking biological samples and profiting off them without sharing those profits with the donors of the samples. Starting April 1993, the Rural Advancement Foundation International, or RAFI, an advocacy group focused on issues of biodiversity and intellectual property, published an article stating the concerns it had about the possibility that the HGDP would bring harm to vulnerable groups by seeking to profit off their genetic information. RAFI situated its concerns about the HGDP in the context of past efforts on the part of scientists from wealthy nations to collect and store valuable plant genetic material from developing countries. The HGDP had never expressed interest in patenting cell lines and stressed the importance of open access to the information since the program’s inception, but that did not stop criticism. RAFI’s 1993 article demanded answers to questions such as whether profits would be shared with the Indigenous people whose physical survival is in question, and where the genetic material would be stored. RAFI called for an immediate halt to any collecting of blood or skin samples from Indigenous people. RAFI also called for more communication with Indigenous leaders and confirm a community’s ability to veto any part of the project.

Other groups raised additional concerns about the HGDP. Also in 1993, the World Council of Indigenous Peoples, an international group based in Canada focused on supporting Indigenous rights, dubbed the HGDP a vampire project. The term conjures up the image of scientists sucking up valuable biological materials from vulnerable groups and then leaving them to die. In 1995, several Indigenous organizations issued a joint declaration condemning the HGDP. They homed in on certain language as particularly threatening and offensive. For example, the HGDP called its sample groups “isolates of historical interest,” which Indigenous groups argued was offensive because it suggested they were valuable to the scientists mainly as evolutionary curiosities rather than as living, breathing members of the present.

Critics also cited a remark of Cavalli-Sforza’s––that one scientist can bleed fifty people and get to the airport in one day––as particularly offensive because it seemed to support the notion of the HGDP as a vampire project. Other groups expressed concerns that the evolutionary findings of the HGDP might conflict with traditional origin stories of Indigenous people or might challenge Indigenous claims to territories or land rights.

Criticism of the project also came from fellow scientists who argued that its premises were flawed, and possibly even racist. Jonathan Marks, who studied biological anthropology in the US, was especially critical of the project, arguing that it was premised on archaic notions about homogeneous, or pure, racial groups that differ qualitatively from each other. Marks argued that genetic variation in the human species is largely clinal, changing gradually over geographic distance, and so choosing where to divide the species into groups is subjective. Alan Swedlund, who studied anthropology at the University of Massachusetts, in Amherst, Massachusetts, pointed out that the mix of nineteenth-century anthropological ideas intertwined with then modern technology was a bad blend.

The HGDP Responds to Criticism

HGDP leaders took several measures to address the barrage of concerns that emerged. In response to the charge that the project was racist, they argued that their project would contribute evidence showing why race is a meaningless category in humans. In a 1994 speech before the United Nations Educational, Scientific and Cultural Organization in Paris, France, Cavalli-Sforza himself pointed out that population genetics shows that there are no genetically pure or homogenous races in humans, that there is more genetic variation within so-called racial groups than there is between them, and that physical features like skin color that distinguish individuals living on different continents are trivial from a genetic standpoint.

In response to concerns about biopiracy, HGDP leaders pointed out that the HGDP was not a commercial venture, but agreed that if profits did accrue, the Indigenous groups themselves would benefit. They also made plans to involve Indigenous groups and their representatives in the planning process and in the collection and handling of samples. Finally, they developed a notion of group consent that would in theory address some of the ethical concerns.

In 1993, HGDP project organizers formed a North American Regional Committee, or NAmC, to address ethical issues and appointed Stanford lawyer and professor Henry Greely as chair of its ethics subcommittee. The HGDP and NAmC developed what they called a Model Ethical Protocol, which eventually included the notion of obtaining consent not just from individuals, as is required by the principles of the standard for biomedical ethical behavior known as the Belmont Report, but also from the larger group of which those individuals were a part, or group consent. The NAmC’s protocol was one of the first of any research protocol to include the idea of group consent. Because the research involved populations, populations as a whole should therefore be allowed to refuse to participate, according to the NAmC’s protocol. The ethics committee developed group consent as a way to recognize Indigenous groups as subjects and not just objects of research. But when several Native American groups reviewed the Model Ethical Protocol, they challenged the notion that outside experts such as anthropologists or ethicists could define what counted as an appropriate group and who belonged to it. Other commentators pointed out that what a population geneticist might think of as a biological population might not correspond to a culturally defined group that ethicists could approach to ask permission.

Faced with all those questions and concerns, in 1994, agencies that had financed the HGDP meetings asked the US National Research Council, or NRC, of the National Academy of Sciences to study the ethics and feasibility of the HGDP. While that review took place, the HGDP took no major action to pursue its goals. In 1997, the NRC released its report, concluding that that the HGDP could proceed. However, funding agencies declined to continue funding the project and the HGDP never was able to collect the vast majority of samples it had initially planned.

The HGDP Cell Line Panel

Although institutional and financial support for the HGDP’s plan dried up, Cavalli-Sforza continued to pursue the idea of a stored collection of worldwide genetic information. At a meeting on human evolution held in October 1997 at Cold Spring Harbor Laboratories in Cold Spring Harbor, New York, Cavalli-Sforza asked the participants, many of whom were anthropologists, to contribute cell lines that they had made over previous years to the HGDP collection. The participants unanimously agreed, and over the new few years, they sent Cavalli-Sforza cell lines containing genetic information from populations from around the world. Those samples provided the bulk of what became the HDGP-CEPH cell lines.

HGDP leaders announced the creation and availability of the cell lines in the journal Science in 2002. The collection consists of 1,063 cell lines from 1,050 individuals from fifty-two populations. As of 2025, it is housed at the Centre d'Étude du Polymorphisme Humain, or CEPH, at the Foundation Jean Dausset, in Paris, France. The cell lines are anonymous. The only identifying features listed for each are sex, population, and geographic origin. Labs requesting access to HGDP-CEPH DNA must be non-profit-making. CEPH will not distribute the cell lines themselves, only the DNA.

Scientific and Social Legacies of the HGDP

The Human Genome Project, whose draft results scientists announced in 2000, confirmed previous estimates that all humans are 99.9 percent identical to one another in their DNA. But even before the Human Genome Project was finished, scientists like Cavalli-Sforza began to wonder about the 0.1 percent of DNA that differs between people. As he and colleagues pointed out in 1991, those variations are part of the reason why different individuals have different traits, including different susceptibility to disease.

The HGDP was supposed to fill in that intellectual gap by assembling a catalogue of worldwide human genetic diversity, but it failed to surmount political hurdles thrown up by representatives of the groups it planned to study and the substantive criticisms made by fellow scientists. According to many observers, including Marks, the biological anthropologist who criticized the project, it was naïve of the HGDP researchers to think they could conduct their study without involving the Indigenous groups themselves from the very beginning. Though HGDP leaders tried to address the various criticisms of their project, they were unable to quell controversy.

The HGDP has become something of a cautionary tale for researchers studying human genetic variation. It showed that when interacting with Indigenous groups, scientists must understand the relevant histories of colonialism and biopiracy, as well as the way the scientists’ goals may conflict with those of the groups, especially with concerns of group identity and self-governance. It also showed that the language scientists use to describe their project can have unintended consequences, as was the case with the HGDP’s references to living human communities as isolates of historical interest.

Several efforts to catalogue human genetic variation have followed the HGDP, such as the International HapMap Project and the 1,000 Genomes project. In terms of accessing funding and avoiding controversy, they appear to have succeeded where the HGDP failed. However, scientists still face challenges in communicating the results of such studies in ways that do not mislead the public about the nature of human genetic variation. As a 2023 National Academies of Sciences, Engineering, and Medicine report entitled Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field points out, scientific researchers often use population descriptors inconsistently or inappropriately to capture the complex patterns of continuous human genetic variation. The report aims to provide researchers with guidance about the appropriate population descriptors to use in the hopes of preventing misunderstanding and perpetuating inaccurate notions of human genetic variation.

Though the HGDP proved controversial and did not ultimately collect all the samples it had intended to, the HGDP cell line panel that Cavalli-Sforza assembled has entered the research domain. Since 2002, over 1,600 scientific papers have relied on the HGDP-CEPH cell lines according to Google Scholar as of 2025. According to the authors of the textbook Human Evolutionary Genetics, 2^nd edition, published in 2014, the importance of the HGDP collection has been immense, transforming the field of evolutionary human genetics and providing the best evidence scientists have for human migration, including the serial founder model for the spread of humans out of Africa. The serial founder model holds that modern humans migrated out of Africa about 60,000 years ago and populated the rest of the world in a stepwise fashion. A prediction of the model is that more genetic variation will be found in African populations than in non-African populations, and that levels of genetic variation found in human populations will decrease steadily the further away from Africa they are located, which is what the HGDP panel shows.

Nevertheless, human genetic diversity projects like the HGDP and those that came after it continue to occupy a charged space between science and politics, a legacy of the history of scientific racism that has marred studies of many studies of human variation.

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