Today’s guest post was contributed by Miriam Bergeret, a scientific writer and editor. Miriam’s work can be found at pensandpipettes.com.

As the Human Genome Project started taking shape in 1990, celebrated scholar of human evolution, Luca Cavalli-Sforza was already envisioning a different kind of genomic map: one built from human populations around the world.

“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… how the current population-genetic configuration of the world came about,” recalled population geneticist Marc Feldman, Cavalli-Sforza’s long-time collaborator, with whom he co-founded the field of gene-culture coevolution. “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.”

At a time before large research consortia, the idea was unusually expansive: a coordinated effort to collect genetic data at a global scale, alongside the emerging reference genome.

Early discussions between Cavalli-Sforza and his colleagues laid the groundwork for what would become the Human Genome Diversity Project (HGDP)—a project built from samples contributed by many investigators, culminating in 2002 in a global panel of 1,064 cell lines maintained by the Centre d’Étude du Polymorphisme Humain (CEPH) in Paris and since used in thousands of research studies.

When Cavalli-Sforza passed in 2018, it sparked renewed reflection on the project. In their recent GENETICS paper, population geneticists Noah Rosenberg and Sohini Ramachandran, who had worked on HGDP early in their careers, speak with Feldman, Hank Greely, and Mary-Claire King, three of the project’s early leaders, reflecting on its beginnings, the challenges they faced, and its lasting influence on the field of human genetics.

“It solidified for me the importance of incorporating evolutionary thinking into biomedical research,” said human geneticist King, best known for finding the BRCA1 breast cancer gene. “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.”

However, the initial project faced criticism from multiple groups, including activists, Indigenous groups, bioethicists, and anthropologists, and never secured sustained funding from the National Human Genome Research Institute, ultimately moving forward as a community-organized effort. “It was frustrating for the project organizers to have support across the field of human population genetics but not see that support translate into funding. In the early years of genomics, it was an unexpected realization about how big science gets funded,” says Rosenberg. “The eventual scientific influence of the project was disproportionate to how much funding it received.”

The conversation also surfaced broader lessons about how research takes shape in a field. For Ramachandran, HGDP highlights the role of systems and institutions in shaping what becomes mainstream—and what does not. “It’s important to understand the structures that support research and how these structures influence which ideas get adopted,” she says.

At its core, HGDP was grappling with questions that extended far beyond data collection: How should the world’s genetic diversity be sampled and by whom? What responsibilities do researchers have to the communities they study? How should population genetics intersect with biomedicine? And what happens when scientific projects are challenged outside traditional academic norms?

“This project is an example of some of the most respected people in the field of human population genetics trying to address those difficult questions,” says Rosenberg. “And for researchers today who are facing many of the same challenges, those early efforts can serve as an important historical example.”

Many of the questions raised by HGDP are now reappearing in the context of large biobanks, says Ramachandran. Debates over sampling, representation, and interpretation echo those from the project’s earliest days. While sequencing ever-larger numbers of people can reveal vast genetic variation, she adds, understanding how that variation arose—and how history shaped it—still requires evolutionary thinking, and large datasets come with their own limitations.

“At the beginning, Luca was talking about sampling 5000 populations. There hasn’t been a coordinated project nearly that expansive,” says Rosenberg. “However, the emphasis on worldwide genetic variation in the HGDP’s original vision paved the way for the various human variation projects that were later implemented by others.”

Greely, a renowned scholar of the intersection of law and biosciences, noted the project’s role in moving the field toward better management of its inherent difficulties. Twenty-five years later, the scientific and organizational challenges that shaped HGDP remain deeply relevant for today’s researchers. By documenting these reflections, Rosenberg and Ramachandran hope to provide a resource for those navigating the same challenges today.

References

  • Reflections on the Human Genome Diversity Project: a conversation with Marcus W. Feldman, Henry T. Greely, and Mary-Claire King
    Sohini Ramachandran, Noah A. Rosenberg, GENETICS. March 2026;
    DOI: 10.1093/genetics/iyaf273

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