Joseph Yracheta knows the value of genomics-based medicine. As a master's student, Yracheta, who is of Mexican Indigenous ancestry, studied genetic variants that influence how Native Americans respond to medications. But when it comes to a massive U.S. effort to identify correlations between DNA and health, called All of Us, Yracheta is a skeptic.
"I just don't think tribes should participate in All of Us" because of the lack of clear benefit and a history of mistreatment by researchers and the U.S. government, says Yracheta, who is now studying health disparities among Native Americans as a doctoral student at Johns Hopkins University in Baltimore, Maryland. "I don't think there's a correct way to do this." Many tribal leaders and researchers are also hesitant, creating an unexpected obstacle for the ambitious study.
Earlier this month, leaders of the National Institutes of Health (NIH) in Bethesda, Maryland, celebrated the 1-year anniversary of the effort, which aims to gather DNA and health records for 1 million volunteers by the end of 2024. They pointed with pride to the study's diversity: More than 50% of the 143,000 volunteers fully enrolled so far belong to minority groups. They did not mention that Native Americans, who make up 1.7% of the U.S. population, are not formally on board.
"I'm very excited and supportive of the research," says Aaron Payment, tribal chairman for the Sault Ste. Marie Tribe of Chippewa Indians in Michigan and chair of NIH's Tribal Advisory Committee. But, he adds, "There is a level of frustration and anger and skepticism." Formal meetings with tribal nations began this month, and NIH staff members say the discussions will lead to an action plan before the project's data are released to researchers next winter. But tribal leaders are unhappy that these discussions did not begin sooner, and that Native Americans are informally enrolling in the study in the meantime.
Announced by then-President Barack Obama 4 years ago, the All of Us study will make anonymized data widely available so the scientific community can use them again and again in open-ended studies. A similar project in the United Kingdom has had remarkable success.
All of Us has partnered with Latino and African American organizations, but efforts to engage the Native American community have faltered. With some 600 tribes to consult and a limited budget, "obviously, this is very complicated," says Gwynne Jenkins, chief of staff for the All of Us Research Program. But Payment says NIH officials, including NIH Director Francis Collins, seemed "naïve" about past problems that make tribes cautious about participating in research studies.
One prominent case involved the Havasupai tribe in Arizona, which sued researchers in 2004 after their DNA samples, gathered for diabetes research, were allegedly used to study schizophrenia and inbreeding without permission from the tribe. "Indian communities were treated as specimens in the past. The research was not done in a culturally appropriate way," Payment says. The Navajo Nation banned all genetic studies in 2002.
Meanwhile, All of Us launched nationwide in May 2018, including in cities such as Phoenix that have large populations of Native Americans. As of mid-February, the study already had DNA samples and health records for more than 1600 volunteers who self-identified as American Indian or Alaska Native and were able to indicate their tribe. That's 1.5% of participants, close to proportional representation of Native Americans.
That worries tribal leaders. In August 2018, a report from an All of Us working group of tribal leaders, health experts, and NIH officials said that data from individual volunteers could lead to findings with implications for an entire tribe. The report also suggested an individual participant from a small tribe might be identifiable in spite of data safeguards. Yracheta and some other indigenous scientists add that participation should enable tribes, not just companies, to benefit if data from Native Americans lead to a promising test or treatment.
Some tribes believe they should be able to decide whether their members take part in research. "Not all tribes agree. But it raises questions about whether or not it is appropriate to recruit tribal members off reservation when the tribe is not aware that type of recruitment is going on," says Nanibaa' Garrison, a Navajo and a geneticist and bioethicist at the University of Washington in Seattle.
The working group noted that tribes should have the power to approve publications on their group, a clear explanation of the role of companies in the study, and an opportunity to bless biological samples before disposal. Native Americans should also be part of a special committee that approves research projects focused on this group, the report concluded.
Acting on recommendations from the working group, All of Us plans to add a Native American to its research advisory panel. After gathering more input, NIH will decide later this year whether to include already-gathered Native American data in the database.
Formal consultations with tribes will ramp up in June in Reno, Nevada, at the midyear meeting of the National Congress of American Indians, which represents many tribes. By September, NIH expects to release a report that describes "things we can do and things that we can't do," Jenkins says. She hopes some tribes will eventually invite All of Us to recruit on their reservations. "My aspiration would be that we're able to develop those kinds of rich, trusting partnerships."