Reflections on the Human Genome Diversity Project: a conversation with Marcus W. Feldman, Henry T. Greely, and Mary-Claire King

TL;DR

This paper reflects on the Human Genome Diversity Project's impact on understanding human genetic diversity and population genetics.

Contribution

The paper provides a historical and scientific reflection on the Human Genome Diversity Project's contributions and challenges.

Findings

The HGDP-CEPH panel has been a major resource for human population genetics research.

The project contributed to studies on human migrations and genetic diversity.

The conversation highlights the scientific and ethical challenges of launching the HGDP.

Abstract

The Human Genome Diversity Project (HGDP) began in 1991 as an initiative to study genetic variation from human populations worldwide. In 2002, the HGDP reported the HGDP-CEPH Human Genome Diversity Cell Line Panel, a global panel of 1064 cell lines that is maintained at the Centre d’Etude du Polymorphisme Humain (CEPH) and that has served as a major resource fundamental to the last 25 years of progress in human population genetics. HGDP-CEPH data have been central to research on topics such as human genetic diversity, human population structure, human migrations, the development of population-genetic statistics and software, and the potential value of inclusion of diverse sets of human populations in biomedical research. In this article, two researchers who participated in early analyses of genotypes from the HGDP-CEPH panel in the early 2000s speak with three researchers who played key roles in developing the Human Genome Diversity Project from its origin in 1991. The conversation reflects on the successes and challenges of the effort to launch the HGDP and on its scientific contributions.

Tables

Table 1.. Selected events in the history of the Human Genome Diversity Project.

Date	Event
1991	News story by Roberts (1991) describes the upcoming article of Cavalli-Sforza et al. (1991) (1991 June 21)
1991	Letter to the editor by Weiss (1991) in response to Roberts (1991) expresses interest by an NSF program officer in the ideas proposed by Cavalli-Sforza et al. (1991) (1991 September 27)
1991	Publication by Cavalli-Sforza, Wilson, Cantor, Cook-Deegan, and King (Cavalli-Sforza et al. 1991) proposes a human genome diversity project (1991 October)
1992	NSF grant of $178,178 to Stanford University begins, on “Human Genome Diversity” (1992 May 15)
1992	Workshop 1 on Human Genome Diversity is held at Stanford University (1992 July 16–18); of an estimated 5000 populations on the basis of distinct languages, a sample of 400 populations and 25 individuals per population is proposed
1992	Workshop 2 on Human Genome Diversity is held at Pennsylvania State University (1992 October 29–31)
1993	Workshop 3 on Human Genome Diversity is held at the National Institutes of Health campus (1993 February 16–18)
1993	HGDP hearing is held before the Committee on Governmental Affairs, United States Senate (1993 April 26)
1993	Workshop 4 on Human Genome Diversity is held at Alghero, Italy (1993 September 9–12)
1993	WCIP meeting is attended by Hank Greely in Quetzaltenango, Guatemala (1993 December 6–10)
1994	MacArthur Foundation grant of $170,000 is given to Stanford University, “to support the work of the Human Genome Diversity Project's ethics committee and the development of a communications plan”
1996	First International Conference on DNA Sampling & Human Genetic Research: Ethical, Legal and Policy Aspects takes place in Montreal, with chapters by Greely (1997) and Cavalli-Sforza (1997) in the proceedings (Knoppers et al. 1997) (1996 September 6–8)
1997	A National Research Council report on human genome diversity viewed by the HGDP as conditionally favorable provides recommendations for how HGDP can proceed (Committee on Human Genome Diversity 1997), but news stories differ on its conclusions (McIlwain 1997; Pennisi 1997) and lead to correspondence and clarifications (Cavalli-Sforza et al. 1997; Schull 1997, 1998) (1997 October)
1997	The model ethical protocol is published (North American Regional Committee of the Human Genome Diversity Project 1997)
1998	Cann (1998) discusses the plan to maintain HGDP cell lines at CEPH (1998 June)
2002	Cann et al. (2002) report the availability of DNA from 1064 HGDP cell lines (2002 April 12)

Table 2.. Timeline of non-HGDP events that indirectly relate to the conversation.

Date	Event
1938	Luca Cavalli-Sforza enrolls at the University of Turin as a medical student, later transferring to the University of Pavia
1948	Cavalli-Sforza goes to Cambridge to study with R. A. Fisher
1958	The Nobel Prize in Physiology or Medicine is awarded to Joshua Lederberg, along with George Beadle and Edward Tatum
1970	Curt Stern retires from the University of California, Berkeley
1971	Cavalli-Sforza joins the faculty of the Stanford Department of Genetics, having been recruited by Joshua Lederberg; Marc Feldman also joins the Stanford faculty (in the Department of Biological Sciences)
1972	Richard Lewontin publishes “The apportionment of human diversity” (Lewontin 1972)
1974	Ruth Kirschstein becomes Director of the National Institute for General Medical Sciences (until 1993)
1976	John Moore's spleen is removed at the University of California, Los Angeles
1980	The paper of Botstein et al. (1980) leads to intense interest in restriction fragment length polymorphisms (RFLPs)
1980	The Nobel Prize in Physiology or Medicine is awarded to Jean Dausset, along with Baruj Benacerraf and George Snell
1984	Mary-Claire King begins working with the Abuelas de Plaza de Mayo in Argentina to use genetics to link disappeared children with their grandparents and other relatives
1987	Cann et al. (1987) study the most recent common ancestor of 147 mitochondrial genomes, the so-called “mitochondrial Eve”
1988	Judith Greenberg becomes Director of the Division of Genetics and Developmental Biology at the National Institute for General Medical Sciences (until 2015)
1990	Mary-Claire King's lab demonstrates existence of a gene for early-onset breast cancer (Hall et al. 1990)
1990	The California Supreme Court rules that John Moore does not have rights to profits from the tissues removed from his body
1991	Stanford holds a Centennial Symposium on the Human Genome Project (January 11–13)
1991	Bernardine Healy becomes Director of the National Institutes of Health (1991 April 9 to 1993 June 30)
1991	Allan Wilson (1934–1991) dies of leukemia (1991 July 21)
1993	Francis Collins becomes Director of the National Center for Human Genome Research, which later becomes the National Human Genome Research Institute (1993 April 4 until 2008 August 1)
1994	Cavalli-Sforza et al. (1994) publish The History and Geography of Human Genes
1994	The legislation known as the “Clinton health care plan” fails to pass the United States Congress
1994	Myriad Genetics applies for patent protection for discovery of breast cancer genes
1995	A patent is awarded to the Department of Health and Human Services based on a cell line from the Hagahai population
1997	Collins et al. (1997) propose a major study of human genetic variation distinct from the HGDP
1998	Craig Venter announces a plan to compete with the Human Genome Project in sequencing the human genome
2000	The draft sequence of the human genome is reported
2002	The International Haplotype Map Project is launched as the project descended from the paper of Collins et al. (1997)
2018	Luca Cavalli-Sforza (1922–2018) dies after having retired to Italy in 2008 (2018 August 31)
2022	The Nobel Prize in Physiology or Medicine is awarded to Svante Pääbo, referencing the HGDP Melanesians and Papuans in the prize description documents

Full text

Introduction

Anyone seeking to understand the last 25 years of progress in human evolutionary genetics will quickly encounter findings obtained with the HGDP-CEPH Human Genome Diversity Cell Line Panel (see Appendix). Since 2002, this resource has been indispensable in studies of human genetic diversity, human evolutionary history, population structure, and the geographic distribution of genetic variation. It has been the basis for assessments of global patterns in numerous genes and in genetic marker sets of numerous types. It regularly supplies the data for developing and testing population-genetic statistics and software. Its data have helped motivate the importance of diverse worldwide populations in human biomedical genetics. It has inspired many new forms of visualization of the complexity of patterns of genetic variation. Its samples underlie various subsequent panels and data sets, and they have even been referenced in a Nobel Prize.

When the first genetic data emerged from the HGDP-CEPH panel beginning in 2002, we were among the junior scientists tasked with performing the early data analyses. One of us (N.A.R.) was a recent PhD graduate of Marc Feldman's laboratory with a research focus on statistical analysis of population-genetic data; the other (S.R.) was a Feldman Lab undergraduate, soon to be continuing in the lab as a PhD student.

As we understood during our training in the Feldman lab, the idea of an organized project for global sampling and analysis of human genome diversity had been proposed in 1991 by a team headed by Marc's close colleague, distinguished geneticist L. Luca Cavalli-Sforza, shortly after the official launch of the Human Genome Project in 1990. Although it was broadly supported by human population geneticists and by some anthropologists, the effort that came to be known as the Human Genome Diversity Project (HGDP) had attracted criticism, notably from activists, indigenous groups, bioethicists, and other anthropologists, and it never secured significant government funding. Nevertheless, dozens of researchers used funds from their own labs to create a unique collective resource, contributing to a lymphoblastoid cell line repository that would be made available for human population genetics research and data generation as genomic technologies advanced in the coming decades. The Centre d’Étude du Polymorphisme Humain (CEPH) provided crucial support for the project, agreeing to host the 1064 cell lines and to distribute DNA samples from the cells. Later, the resource became known as the “HGDP-CEPH Human Genome Diversity Cell Line Panel.”

During our scientific training and our early years as independent researchers, we experienced the early heyday of research activity based on the HGDP-CEPH Human Genome Diversity Cell Line Panel, beginning in 2002. At the time that it was introduced, the HGDP-CEPH panel was a rare human population-genetic resource that included many global regions, with multiple populations within regions, and it quickly became a touchstone to address questions of human evolutionary genetics, population-genetic theory, and statistical methods in population genetics more generally (summarized in the Appendix).

Having been too early in our careers to have followed the beginning of the HGDP in real time, we had limited knowledge of the deliberations and challenges of its early years, when the project was proposed and then scaled back from the original vision. We had, however, heard hints that the early events of the project had more dimensions than typical brief recountings of the project would suggest. Curious about the events that led to the development of an important resource for the field (and for our own research programs), we approached three leaders of the HGDP—Marc Feldman, Hank Greely, and Mary-Claire King—about the possibility of an oral history interview. In preparation for the interview, we examined the voluminous documents generated by the early years of the HGDP: among them, meeting reports and other writings from investigators working on the project, contemporaneous news articles, advocacy documents against the project, and scholarship in bioethics and science studies covering the project and the issues it raised. For synthetic accounts written from a variety of perspectives, see the news series by Salopek (1997a,b) that received a Pulitzer Prize for explanatory journalism, a bioethics discussion paper by Resnik (1999) and its 20 responses in Politics in the Life Sciences, a book-length treatment in the social studies of science by Reardon (2005) as well as an earlier article by Reardon (2001), a project-adjacent ethnography of human genetic diversity science by M’Charek (2005), perspectives from within the project by Greely (2001) and Cavalli-Sforza (2005), and the Cavalli-Sforza biography by Stone and Lurquin (2005); many additional documents are referenced from the endnotes in our Supplementary Material.

In the development of the HGDP, Marc, Hank, Mary-Claire, and the rest of the HGDP team were early in facing questions that we can now see as intrinsic to the field of human population genetics to this day. What does it mean to try to sample the world's human genetic diversity? What are the proper roles of individuals and populations in the design and analysis of human population-genetic studies? What are appropriate ways for researchers to interact with study subjects beyond formal regulatory requirements? What special considerations are important in genetic research involving indigenous populations? What is the role of human population genetics in contributing to biomedical advances? What types of responses from scientists and scientific institutions are appropriate when they are challenged in ways that do not follow the norms of scientific debate? These questions still resonate; as Hank said to us in relation to such topics, “no good problems ever get solved.” Marc, Hank, and Mary-Claire have long been renowned in the human population genetics field for their humanistic perspective and attention to ethical conduct of research; their efforts, and the successes, challenges, and approaches in the HGDP history more broadly, can serve as a case example through which today's human population geneticists can engage with difficult questions that they are likely to encounter. For the historical record of the HGDP, it is important to hear key project researchers reflect on it in their own words.

Last July, we sat down with Marc, Hank, and Mary-Claire on the Stanford campus to consider the long span of the HGDP, from the original ambitious effort beginning in 1991 to the report of the cell line panel in 2002 to the applications of the panel in subsequent decades and the lessons of the efforts to the launch the project—their thoughts about its early years, its contribution to science, and how they see the project now.

Our wide-ranging conversation traversed many of the central questions that the HGDP faced. The conversation also linked early events of the HGDP to the 1990s era in which they took place—for example, the science funding environment during the Clinton administration, and the elevated attention given at the time to the patenting of biological materials. The rapid rise in electronic communication was a backdrop to the period, facilitating the HGDP's international collaboration via email with coordinator Jean Doble at Stanford; however, it was also portentously noted in one news article (Taubes 1995) critical of HGDP's persistent antagonist, the activist group RAFI (Rural Advancement Foundation International), that the emerging internet could be used not only for rapid communication among scientists, but also for rapid dissemination of misinformation about their activities.

The early history of the HGDP has often been viewed through the lens of the interactions between the scientific world and indigenous populations and activists, and a reader examining the early HGDP documents in 2025 may well be taken aback by the statements that set the criticism of the project in motion, namely the project's references to vanishing populations and disappearing languages. In our conversation, Marc, Hank, and Mary-Claire argued that the HGDP—together with the criticisms it received—ultimately served to advance values that the project had originally sought to promote, such as inclusion of diverse populations, including indigenous populations, and respect for those populations, in human genetic studies.

A modern reader will also notice in early HGDP documents scientific statements that foreshadowed much of the agenda of subsequent research in human population genetics. For us, therefore, a poignant and previously underappreciated thread in the conversation was a sense in which Marc, Hank, and Mary-Claire viewed the fate of HGDP not solely in terms of interactions between scientists and indigenous populations, but also in terms of its unsuccessful effort to gain funding support from the National Center for Human Genome Research (NCHGR), later to become the National Human Genome Research Institute (NHGRI), which was running the Human Genome Project (HGP). The HGDP thus also serves as a case study for issues of the dynamics of the funding of science, the interaction between major projects developed by self-organized groups of scientists and those organized centrally by funders, and the relationship of basic research—in this case on human evolutionary history—to science that possesses an explicitly biomedical motivation.

One of the main events in the story of the federally funded HGP was the intense rivalry it experienced with Craig Venter and Celera Genomics when Venter duplicated the genome sequencing project with a parallel effort. However, when NHGRI, rather than supporting the genetic variation project that was already being developed by many of the leading population geneticists, designed its own separate major project on genetic variation, eventually to become the International Haplotype Map Project, it acted toward the HGDP in the same manner that had caused NHGRI such consternation when Craig Venter and Celera sought to supersede the HGP. Notably, although the HGDP was widely known at the time, the first call from NHGRI for a major study of human DNA variation did not acknowledge it (Collins et al. 1997).

Unlike Venter's genome project, HGDP was entirely noncommercial, and when NIH funds did not materialize, the scaled-down version of HGDP in the form of the HGDP-CEPH collaboration proceeded as a self-organized community project with contributions from many investigators, in contrast to funder-driven initiatives such as the HapMap project, 1000 Genomes Project, and Human Pangenome Project. The HGDP follows a pattern seen in studies of business innovation, in which the first effort to propose an idea can face the first-mover difficulties of uncovering the challenges inherent in the enterprise—but then serves to facilitate subsequent efforts (e.g. Lieberman and Montgomery 1988). The conversation revealed to us the sense of importance Marc, Hank, and Mary-Claire felt for the pioneering role of the project, their pride in the results that were achieved and the values that were advanced, and their admiration and respect for the colleagues who participated in the project, especially Luca.

An edited version of the conversation follows. A timeline of selected major events in the early history of the HGDP appears in Table 1. Other events mentioned in the conversation appear in Table 2.

The beginning of the HGDP

Ramachandran: Let's start with your involvement in the HGDP. The project begins with discussions among a small group of scientists, including Allan Wilson and Luca Cavalli-Sforza, in the late 1980s. We’d love to hear how you first became involved with the project that became the Human Genome Diversity Project.

Feldman: Luca was always interested in migration. He figured that when the Human Genome Project was going to be a reality, it would give a very good opportunity to study ancient migrations—to try to get as much data as he could from as many populations as he could, to study how the current population-genetic configuration of the world came about. As soon as it became obvious there was going to be a Human Genome Project, it was clear to Luca that that was missing a lot of the point—that you needed this other thing, too. Luca and I were meeting 3 to 4 nights a week for 35 years. He asked me to be involved because he thought that there would be great scope for modeling and data analysis when it eventuated.

King: It's a good guess that Luca had not thought about this idea for more than two minutes before he presented it to Marc.

In the late 1960s and early 1970s, I was a graduate student of Allan Wilson in Berkeley. My first introduction to genetics had been Curt Stern's course the last time he taught it, in 1967, before his retirement. I just loved it. As soon as he began speaking about population genetics, of course Luca's work was his focus. My dissertation project with Allan was evolutionary biology: the unexpected molecular similarity of human and chimpanzees.

By the mid-1980s, when I had my own lab in Berkeley, it was clear that restriction fragment length polymorphisms were going to revolutionize our capacity to work with human variation. I was still asking advice from Allan, and he suggested that I talk to Luca about coming to Stanford to learn “true population genetics.” So, I asked Luca if I could do an informal short sabbatical in his lab. He was extremely kind and said yes.

To Marc's point, he and Luca soon spoke with Allan about sampling people from all parts of the world. I wasn't present for their first conversations, but Allan and I talked a lot about the idea just after. He thought it was good but wondered about the design.

Greely: I was on the planning committee for a 3-day symposium Stanford put on about the then-new Human Genome Project. It was January of ‘91. The planning committee was chaired by Paul Berg, and it included Lucy Shapiro and David Botstein. They wanted a law professor. They told my dean, and since I was the only one at the law school who knew how to spell DNA, I was volunteered for it. I loved the planning committee. It was so much fun to see both Paul and especially Lucy constantly teasing David, and David's responses. I just enjoyed the people.

Until the Clinton Health Plan crashed and burned in ‘94, I still thought I was a health policy person. We ended up deciding that I would give a talk on health insurance and the implications of genetics for health insurance.

The talk was well received. It actually ultimately became a chapter in the Lee Hood/Dan Kevles Code of Codes book [Kevles and Hood (1992)]. Luca was introducing everybody on that panel, and he introduced me. I can't remember now the Latinate term he had for it, but as he was reading where I've been and gone, which really wasn't that many places, he decided I must have the genetic trait of nomadism, as part of his humorous introduction.

Well, I enjoyed the talk. In the summer of ‘92 Marc and Luca invited me to lunch. It was at the Faculty Club, to ask some questions about this project they were doing. I said I thought it sounded really interesting, and that is when I first got pulled in.

Rosenberg: Let's talk about the early arguments for why it was important to do a genome diversity project, and how these thoughts coalesced in an article in Genomics in 1991 [Cavalli-Sforza et al. (1991)].

King: Because we are not one genome! The evolutionary perspective on all of life requires that we recognize extraordinary diversity and the forces of evolution that are behind it.

My recollection is that Victor McKusick invited us to write a commentary for Genomics on this idea of a worldwide human variation project, with Luca and Allan as authors. They had not written together previously, and you can't imagine two more different people as the major contributors to our field. They were both progressive—but differently so. Allan was very left-wing, grew up on a New Zealand farm, and maintained a Bohemian kind of lifestyle his entire life. Luca, of course, had a very different background: urban and European. They were never close friends, but had huge respect for each other.

My goal was to help Allan and Luca to work together on this commentary. Also part of the story was Charles Cantor at the Department of Energy, which had a lot of capacity for sequencing. Charles was very interested in the project from the technical point of view: could one actually apply sequencing to the kinds of numbers of samples that Luca envisioned? It seemed important to bring DOE sequencing capacity to bear, and Charles was completely open to that. Another interested person was bioethicist Bob Cook-Deegan. The idea was to put some ideas down on paper so that the new genomics community would recognize its importance.

Rosenberg: We would like to know more about the interactions between Allan and Luca. In the lore of the project, there's a fair amount of weight placed on the somewhat competing visions of how to do the sampling, whether population-based sampling in Luca's view or a more geographic-based sampling in Allan's.

King: Allan thought in terms of sequence, which meant that every individual offered a data set, with the metric being numbers of DNA base pair differences between individuals. This was a different perspective than calculating allele frequencies and comparing frequencies between population clusters. Both perspectives are legitimate, but different.

Luca and Marc were thinking about sampling strategies. Allan felt strongly that the best way to sample was to represent the geography of the planet, so to sample either one or a very small number of people from as many different geographic regions as possible, always sampling people who had a depth of ancestry in that region. Luca thought of clusters of people defined by language groups, because he was thinking of allele frequencies. Allan was thinking of sequence.

Rosenberg: That's an interesting tension in the field that continues into the 21st century.

Looking back 35 years at what was most significant in human population genetics at the time, there's Mitochondrial Eve from Allan's group [Cann et al. (1987)], with this individual sequence-based perspective, and then there's Luca's more population-based book on history and geography of human genes [Cavalli-Sforza et al. (1994)].

Feldman: I think it's really important to emphasize that Luca was very influenced by linguistics. We would sit there with the Ethnologue, that big volume [Grimes (1992)]. And that's where this number 5,000 populations that you see in the first report of the project came from, because there were approximately 5,000 languages in the Ethnologue at that time.

King: Allan realized that he was ill only seven months before he died [of leukemia in July 1991]. He was thinking about this project all the time. It's what we talked about in my last visit with him. With his death, his “grid sampling” idea faded in the presence of the strong, coherent vision of Luca and Marc. Most of all, I think everyone felt that the main thing was to get it going…

Feldman: And also to utilize the resources that were already available that had been collected. I wanted to mention one other thing that was relevant to Luca's beginning there: the paper that [Richard] Lewontin did in 1972. Luca loved that paper, the one on apportionment of human diversity [Lewontin (1972)]. Luca was an analysis-of-variance person. That really was his cultural legacy from his time with [Sir Ronald] Fisher.

The planning workshops

Rosenberg: Let's talk about what happened after the 1991 Genomics article. The article attracted some attention, including a news story in Science [Roberts (1991)] and a letter to the editor from Mark Weiss, a program officer at the National Science Foundation [Weiss (1991)]. Mark Weiss's interest led to a proposal to NSF to run a series of workshops to develop the idea for a genome diversity project into a more concrete scientific project, and this proposal is funded for $178,178. We are wondering if you have any specific recollections from the workshops in 1992 and 1993 to develop the project.

Feldman: My recollection is at the first meeting at Stanford, we spent a huge amount of time talking about statistics and about sampling sizes. And I remember walking down what is now the pathway near Bytes Cafe, with [Joe] Felsenstein and Luca, and really going hammer and tongs on how many people you would need to sample.

At the second meeting, we talked about trying to write a proposal that would involve actually getting the samples. And the need to get people like Hank involved. How consents might be incorporated from tribes or peoples that had not had that sort of thing historically. Where the samples could go… people got down to the nitty gritty.

King: My memory is that the idea of community consent was real from the very beginning.

Greely: The third meeting was probably the first time I met anybody from NIH. Memories are flooding back, I’ve eaten the little madeleine. It was a really interesting and intense day, and I left thinking, “This is even more complicated than I thought it was going to be.”

Rosenberg: The project is estimating that it hopes to obtain $25 million, and there are program officers from NSF, NIH, and DOE at the meetings. We’d like to understand how the future funding plan for HGDP was developing.

Feldman: Irene Eckstrand from NIGMS [National Institute for General Medical Sciences] was really very nice. She was a card-carrying population geneticist, and when she became a program officer for genetics, a lot of what she saw was population genetics. I ended up chairing the genetics study section and had a lot to do with Irene, who was so sympathetic, and tried to move up the narrative and the conversation to Judith Greenberg [Director of NIGMS Division of Genetics and Developmental Biology] and the bosses.

King: Ruth Kirschstein [Director of NIGMS] was incredibly supportive of me and of my breast cancer work. She listened to her investigators and to her staff, young or established, and regardless of fields. When she heard about the HGDP from Irene, even though it wasn't her field at all, she believed in Irene's view of it.

Feldman: Mark Weiss at NSF was sympathetic, but NSF had pennies. NIH would have to be involved somehow.

A Senate hearing

Rosenberg: We’d like to talk about an interesting moment in the early development of the project, a hearing that took place at the US Senate Committee on Governmental Affairs on April 26, 1993. By this point, three planning workshops had already taken place, using the NSF funding. The most recent one was held at NIH in February of 1993 and had a significant presence of program officers, and a lot of discussion of ethical challenges such as sample collection, cell line management, how DNA would get distributed, databasing, and human subjects protections.

The Senate hearing was one of the first significant moments where the project was having a public conversation, beyond the scientific community. Luca and Mary-Claire represented the project at the hearing, and Francis Collins, who had just been appointed Director of the National Center for Human Genome Research (NCHGR), later the National Human Genome Research Institute (NHGRI), also testified.

Mary-Claire, your testimony spoke to the importance of the project, both the human evolution and biomedical dimensions, and you also mentioned your work using genetics to connect disappeared children in Argentina to their grandmothers, the Abuelas de Plaza de Mayo. Tell us about preparing for the hearing.

King: I felt that my assignment was to humanize the project and to link it to medical research; to clarify that we were not an island off in a sea of theory, and that human diversity was a good use of the new technology, just as medical research was. Judith Greenberg said to me (I'm paraphrasing here): you need to get this right… make sure that the connections between the Human Genome Diversity Project and Human Genome Project and biomedical research all make sense. I took her advice seriously.

Rosenberg: In retrospect, this hearing also appears to be the first moment when it looks like HGDP will have difficulty with funding from NIH. Is that your sense, looking at the transcript now?

Feldman: [examining the transcript] I think it's interesting, [Francis] Collins in his oral testimony raises more doubts about the informed consent than in his written testimony submitted in advance, and in particular, “will the Third World feel exploited?”

The points that he makes in person raise the difficulties that we'd already discussed. If you're going to sell something to the Senate, then you might not raise all the difficulties that the people who are doing the project already raised.

Greely: He was clearly for the Human Genome Project. That was the baby he was trying to protect. This was, as he notes, his first Congressional hearing as Director. He had just become Director a couple of weeks earlier in April.

During the Q&A in this transcript, you've got Collins saying he supports the Diversity Project, there are really interesting goals in common, but “it would be difficult for the Genome Project to expand its umbrella to take on other more diverse efforts, like the Diversity Project, without expanding its funding.” So he was already clearly distancing.

King: Bear in mind levels of funding at NIH in that year. This was early in the Clinton administration. NIH funding was going nowhere but up.

Ramachandran: Mary-Claire, at this time, you're in an incredible period of professional success after your major finding of linkage to an early-onset breast cancer gene in 1990 [Hall et al. (1990)]. It's interesting to us that of all things you could be doing in human genetics at this time—you’re working on identifying the breast cancer gene to which you had found linkage, your work on genetic identification of missing children is getting international attention, you’d been considered by NIH Director Bernardine Healy to direct the National Center for Human Genome Research and the Human Genome Project—you’re at this Senate hearing devoting a large part of your energy to HGDP. What was drawing you to HGDP?

King: It was the way to integrate evolution with human genetics, using technology that was coming online very, very fast. It seemed to me that biomedical questions and human diversity and evolution questions were absolutely integrable. We were saying, in effect, that people from populations that you all have never visited are just as important to understanding health and disease as the people whose DNA will be the first [human genome] sequence.

Supplementary Material

iyaf273_Supplementary_Data