An ethical way forward for Indigenous microbiome research

For centuries, Indigenous communities have experienced the theft of their lands, their ancestors’ remains and, more recently, the unethical collection and use of their DNA without consent. “What we have seen is just an egregious abuse of power, an egregious culture of extraction,” says geneticist Keolu Fox, who is Kānaka Maoli (Native Hawaiian) and co-founder of the Indigenous Futures Institute at the University of California, San Diego.

Some Indigenous and non-Indigenous researchers are now working to draw up ethical frameworks for microbiome research with Indigenous communities. However, the rapid growth of the field has so far outpaced the formation of national or international agreements on the ethical collection, storage or use of microbiome data from Indigenous people, or on compensation for the people who provide them. “How rapidly we can sequence something and create data and commodify it — I don’t think that the policy has caught up,” says Fox.

He and many other researchers think that there is an ethical way forward, and most say that it will require placing research decisions and data in the hands of Indigenous communities — as well as ensuring that the people who participate in research are able to reap the benefits that might come from it.

“We have seen an egregious abuse of power, an egregious culture of extraction.”

The concern that the microbiomes of Indigenous people might not be around to study for much longer is a driving force behind the Microbiota Vault — a non-profit initiative founded in 2019 with the mission of preserving global microbial diversity, including the microbiomes of Indigenous people, to “conserve long-term health for humanity”.

“Within each country, there are likely to be teams of researchers and Indigenous peoples working together to collect these specimens and preserve them locally,” says Rob Knight, a microbiologist at the University of California, San Diego, and vice-president of the Microbiota Vault. The physical vault will keep back-up samples from local collections safe, “kind of like the seed bank in Svalbard”, Knight says, referencing the facility in the Arctic that stores more than one million seed samples from countries across the globe in an effort to secure the world’s food supply.

Samples held in the Microbiota Vault will only be accessible to the depositor. However, if depositors take up the organization’s offer of free sequencing of those samples, the terms require that the results be uploaded to an open-access database for anyone to use.

Fox is one of a number of researchers concerned that the Microbiota Vault is reminiscent of earlier efforts such as the Human Genome Diversity Project, which sought preferentially to collect biological samples such as blood and saliva from isolated populations at risk of disappearing to “study the genetic richness of the entire human species”. In 1993, the World Council of Indigenous Peoples dubbed it “the Vampire Project” owing to what it perceived as the use of Indigenous peoples’ genetic information for the benefit of others, with no consideration for the communities themselves.

For Fox, the Microbiota Vault’s goal of helping all of humanity is worryingly familiar. “The greater good argument is getting tired and old,” he says. “Whose greater good are we talking about here?”

Microbiota Vault president Maria Gloria Dominguez-Bello, a microbiologist at Rutgers University in New Brunswick, New Jersey, acknowledges that there has been “a history of exploitation and abuses and immorality” towards Indigenous peoples. However, she does not think that their samples should be excluded from the Microbiota Vault or from any other ethically conducted study that is aimed at improving human health. “I don’t think it’s ethical to exclude any human population,” she says.

“Whose greater good are we talking about here?”

The Microbiota Vault is still in its pilot phase, with various regions of the world being scouted to serve as its location. At the same time, says Knight, the team is evaluating the ethical models that it hopes to put in place before samples are deposited, including ensuring that researchers comply with religious and community expectations for interacting with participants and allowing providers of biological samples to retain control over those specimens. It is also discussing whether and how profits from any supplements or drugs that might be developed off the back of this research will be allocated. “We’re trying to avoid all of those categories of mistakes up front,” he says.

Ensuring that Indigenous communities benefit from their involvement in research is essential. The alternative is “biological theft,” says Crittenden — “going in and extracting biological materials from communities and profiteering off of those without any compensation back to the community.”

But the field’s current data-sharing structure makes this a challenge. Once a person’s microbiome data are uploaded to a public database, they are fair game. “You can’t prevent it from being used to make some sort of discovery that’s valuable,” says Knight.

If and when those data are used to develop microbiome-based therapeutics, the companies that are looking to sell the product typically won’t think of the Indigenous communities that made it possible, says Krystal Tsosie, an Indigenous geneticist and bioethicist at Arizona State University in Tempe. There is typically little thought to providing either financial compensation or access to the drugs to these communities. “They want to reintroduce a healthy or pre-industrial microbiome, into, frankly, wealthy patients who can afford these technologies,” she says.

“We’re trying to avoid all of those categories of mistakes upfront."

Concerns about unethical collection, storage and use of Indigenous data were a big motivator for the formation of the Native BioData Consortium. Founded in 2018, it is the first non-profit research institute in the United States run by Indigenous scientists and community members.

The group manages a biobank located on sovereign Native American land in Eagle Butte, South Dakota. The consortium stores a variety of biological and non-biological samples and data in partnership with collaborating Native American communities. “Having the biobank on sovereign Native land, where tribal laws and resolutions are in place, can afford additional protection for Indigenous communities who wish to engage in biomedical and other types of research,” says Tsosie, who is a co-founder and board member of the consortium. Fox and Anderson are also board members.

Unlike at the Microbiota Vault, none of the data generated from samples are uploaded to public data banks. The consortium also enforces dynamic consent, meaning that study participants can decide to remove their samples or data at any time through an online portal.

Investigators who want to work with the Native BioData Consortium need to have established a partnership with the Native American communities, says Tsosie. Approved investigators will then receive assistance in navigating the laws of Tribal Nations and policies to engage in ethical research.

Tsosie sees a way forward for microbiome research involving Indigenous communities only if there is a tangible benefit to the people who provide the potentially money-making data, such as investment in community health training or immediate access to any drug or other product that the research has helped to create. “I’m not talking a long-term promise a couple decades down the line,” she says. “Our peoples need health solutions that work for us now.”

In the United States, collecting human microbiome samples requires informed consent, as well as approval from an institutional review board (IRB) that provides regulatory oversight. Most researchers meet this bar; those who don’t are criticized by the community.

In 2014, for example, microbiome researcher Jeff Leach made waves when he used a turkey baster to give himself a faecal microbiota transplant (FMT) using faeces from a Hadza man. By 2015, some researchers who had previously collaborated with Leach, including Knight, had distanced themselves from him. As Knight recalls, he heard concerns from other researchers who worked with the Hadza that Leach was not obtaining the proper permits or consent from participants. His self-administered FMT, Knight says, was something that “our research-ethics group would certainly not have allowed”.

By this time, however, many of the samples Leach had collected had already been sequenced and the data made publicly available. Additional samples still sit in lab freezers; Knight has some of them. At one point, Knight hoped that there might be a way of retroactively obtaining approval and consent, but now he expects that the samples will be destroyed. “There is no ethical path forward to using them that I’m aware of,” he says.

Although most researchers obtain IRB clearance for their work, they could still aim higher. “We need to really separate what is legal versus what is ethical,” says Crittenden. IRBs are just a legal minimum, and can be inconsistent, she says. “You can be absolutely above board legally and be conducting unbelievably unethical research in a community.”

For this reason, the Native BioData Consortium requires that the researchers whom it works with adhere to a higher ethical standard. Projects must be approved not just by an IRB, but also by a council of Tribe officials to ensure that the people providing samples will benefit. Tsosie has received some push-back from scientists on this community consent process. “It’s often considered incongruent with the academic pathway of research,” Tsosie says. Researchers, who are under pressure to publish frequently, don’t think they have the time for it. “You get researchers who are like, ‘Oh, that’s too much work. And, you know, I technically don’t need to do it’,” she says.

When Crittenden decided to stop collecting biological samples from the Hadza, she embarked on a course of re-education. “I had to learn how to be a different scientist,” she says. “I had to learn different methods and methodologies. I had to learn different lines of enquiry. And honestly, I had to slow down.” For ethical standards to improve, she thinks that researchers need to be willing to move more slowly, despite incentives to do the opposite.

Funding agencies could be key to enabling researchers to take the time to do things properly. “As a scientific community, globally, we need to be thinking more about the fact that building relationships is part of the work,” says Anderson. Accounting for that time in the funding provided to researchers, he says, would make a big difference to the relationships between investigators and the communities that they study.

Although the field still has a way to go, Crittenden has seen improvements since she first decided to stop collecting biological samples from the Hadza ten years ago. At the time, when giving talks at various institutions, she remembers being asked to avoid talking about community-based research and ethics. “They invited me there for a scientific talk, not an ethics talk,” she says. But over the past few years, she has witnessed a change. Crittenden and other researchers, including Fox, Tsosie and Anderson, have published articles^5–7 relating to ethical research with Indigenous communities, and there has been an uptick in the frequency of conversations related to such research, she says.

“When you know better, you do better,” she says, referencing a quote from US author and civil-rights activist Maya Angelou. Helping researchers ‘know better’ is something Crittenden takes seriously. “The responsibility is on me to articulate why this is necessary, why this is a critical step forward and why your science is better for it.”

doi: https://doi.org/10.1038/d41586-024-02792-w

"We need to be thinking more about the fact that building relationships is part of the work.”