microbiome collecting art

Gut Week

The “disappearing” human microbiome — and the fraught push to preserve it

Competing ideas on how to collect and study our microbiota raise a vital question: Who benefits?

Sam Dean Lynn

Jutting out the side of an icy mountain in remote Svalbard, Norway is a heavily secured collection of seeds from all over the world. This strange library is one of our best preparations for the apocalypse. If the world’s supply of wheat dries up, you'll be able to find the seeds in Norway.

But by 2028, the Svalbard Global Seed Vault may have a neighboring bank built to conserve genetic diversity of a different sort — poop. The Microbiota Vault is intended to house the diverse microbiomes of the world’s human population. It is an idea rich in potential for treating diseases and safeguarding future generations.

Scientists are worried we’re at risk of losing certain microbial species which may prove to be the most helpful for treating disease — specifically, the microbiomes of people who are less affected by industrial living, and often belong to rural and Indigenous communities. Competing efforts are underway to collect and preserve samples of these microbiomes, found within feces, in banks like the Microbiota Vault.

But this is not a “break in case of emergency” situation. If the Seed Vault is insurance for the future, scientists say we should have already started to collect microbiomes. The emergency, chronic disease, is happening now. Because the microbiome interacts with so many aspects of the body, scientists say there’s therapeutic potential.

The entrance to the international gene bank Svalbard Global Seed Vault.picture alliance/picture alliance/Getty Images

Martin Blaser, co-founder of the Microbiota Vault, a Rutgers University professor, and one of the first scientists to connect a loss of variety within “industrialized” microbiomes to “post-modern conditions” like asthma or diabetes, offers this hypothetical:

“Let's say we find that there are some bacteria, there are some microbes that really help humans avoid becoming obese, but they have disappeared from us,” he tells Inverse. “Maybe we would start giving them back to people. Maybe we would give them back to young children so they can start their life the way their ancestors started their life.”

But engaging in this effort incites questions that have long plagued genetic research. In collecting, preserving, and studying material that comes from people’s bodies — while scientists search for “ancestral” samples — will the people whose samples are taken from them really benefit? Who will control, and in turn profit from, the genetic data they generate?

“That colonialistic way of doing science is not valid anymore.”

As Blaser and others race to preserve microbes, there’s impassioned debate within this scientific community about science in service of colonialism, one of the medical research community’s most destructive features.

Some microbiome-collectors tell Inverse they’re striving to do better than their forebears. But others say this isn’t good enough, rejecting the notion that Indigenous people can really be served by academic projects relying on Indigenous people’s biological material.

Disappearing microbiome

Original illustration bySam Dean Lynn

The human microbiome is so complex, some call it the “second genome.”

An ecosystem of bacteria, protozoa, fungi, and viruses, the genetic material within these mostly intestinal microbes influences everything from the immune system to our emotional state. Fecal specimens, while imperfect, are proxies for gut microbiota because they contain these microbes.

A deeper understanding of the human microbiome, scientists hope, will lead to treatments or cures for chronic disease. The microbiome makeup of those with psoriasis, asthma, colitis, and even colorectal cancer and obesity are distinct, leading researchers to seek treatments that target this microbial imbalance.

The central premise of the “disappearing microbiome” theory is that a sweeping change in our external environments has led to similarly sweeping changes in our internal environments.

As societies begin to “industrialize,” beneficial microbes die off. This process is marked by changes that include but aren’t limited to:

  • Taking antibiotics
  • Using antibacterial soap
  • Having fewer vaginal births (which transfer microbiota)

Studies suggest that remote and traditional communities, with less exposure to these forces, have more diverse gut microbiomes.

Microbiota, some scientists argue, are a limited resource worth preserving before it dies out completely.

Microbiota, some scientists argue, are a limited resource worth preserving before it dies out completely.Shutterstock

Microbiota Vault co-founder Martin Blaser likens the situation to another disaster:

“Climate change is a change in human macro-ecology. This is a change in human micro-ecology,” he says. “I think the scale is about the same and is probably happening faster.”

Blaser is also one of the first scientists to connect a loss of variety within “industrialized” microbiomes to “post-modern conditions” like asthma or diabetes.

Leaders in this movement, including Blaser, Maria Gloria Dominguez-Bello of Rutgers’s Center for Advanced Biotechnology and Medicine, and Eric Alm at the Massachusetts Institute of Technology, say microbiomes are rapidly becoming less diverse, a result of more people living in increasingly industrialized societies. The richest microbiomes, they say, and in turn, the most valuable, remain in communities who live in remote or “non-industrialized” areas.

These scientists are putting into practice measures to right the wrongs of past researchers — those who profited off marginalized communities by mining their biological material. Yet microbiome researchers are now turning to similar groups of people and asking for samples.

Leaders of another new, localized biobanking effort, the Native BioData Consortium, say this kind of effort still evokes colonialism. Even the framing of the problem as a “disappearing microbiome” plays into the idea that Indigenous people practicing ancestral ways of life are almost gone, or are “non-modern” or “pre-industrial”, says Krystal Tsosie, co-founder of the Native BioData Consortium, an Indigenous-led biobank. Tsosie is a Ph.D. candidate in genomics and health disparities at Vanderbilt University.

“Scientists tend to over-dichotomize things,” she tells Inverse, “It’s frustrating.”

Tsosie and others are building their own biobank — one that begins and ends with the donors of biological data and prioritizes projects which use the microbiome to tackle health problems affecting their communities in the here and now.

Conserving and biobanking

Around the world, dozens of other efforts to gather and sequence human microbiomes have taken place in one-off studies or stool banks for fecal transplants.The Global Microbiome Conservancy

Plans for the Microbiota Vault are still underway, but a 2020 feasibility study paints a picture: Ten cryopreservation tanks in a building lined with 200 meters of piping and outfitted with an oxygen alarm (exposure to oxygen destroys microbiota samples). It would be located in Norway as part of the Seed Vault facility, or in Switzerland, for its political neutrality and connections to international policy.

Alongside this main vault (or biobank) would be “local working collections” — smaller storage facilities in nations like Angola, Tanzania, Bolivia, and Venezuela where samples are extracted and researchers have an established connection with other scientists.

It is a far-reaching endeavor to store and preserve microbiome samples from around the world. Like Noah’s Ark, there will be two copies of every sample, and local communities can choose whether or not they’d like to deposit one copy to be stored in the Vault and genetically sequenced.

Ideally, Dominguez-Bello says, local researchers can co-author papers alongside international researchers who access data on samples from local collections.

“The days in which people from Europe or the U.S. went to Africa or South America and got samples, and then publish without a single local author? Those days are gone,” Dominguez-Bello, who is originally from Venezuela, says. “That colonialistic way of doing science is not valid anymore.”

“We want to give back.”

Around the world, dozens of other efforts to gather and sequence human microbiomes have taken place in one-off studies or stool banks for fecal transplants, although only about a handful have a stated goal as lofty as preserving microbiota diversity, like the Global Microbiome Conservancy; making a “global microbial map,” like the Earth Microbiome Project; or the largest human microbiome database, like the Million Microbiomes of Humans Project.

There’s no consensus on how research on the microbiome should be done and the legal status of microbiota samples is also unclear. It’s something scientists say mostly hinges on informed consent.

“We train the people so they can also do the microbiome work in their university or labs.”
Photos courtesy of the Global Microbiome Conservancy

The Global Microbiome Conservancy has already started collecting samples. Based out of the Massachusetts Institute of Technology, the endeavor is led by founders and scientific directors Mathilde Poyet and Mathieu Groussin. Scientists associated with the Conservancy typically accompany local partners into communities before collecting samples, with a scientific objective in mind.

In 2017, they went to southeastern Cameroon through a connection to researchers at the French National Research Institute for Sustainable Development and collected samples from the BaAka people. On trips like these, a translator helps them sign consent forms saying they agree to share their biological material. Then, they collect stool samples, freeze them in liquid nitrogen on-location, and ship them back to MIT.

Depending on the collaboration, the Conservancy scientists sometimes also leave Helicos, a kind of gene-sequencing equipment, in the country. “We train the people so they can also do the microbiome work in their university or labs,” Poyet tells Inverse.

People who participate in the project own their samples and can withdraw them at any time.

Poyet and colleagues have collected over 1,000 samples, sequencing and isolating over 9,000 strains of bacteria in the MIT labs and trying out new methods, and multiplying individual kinds of microbes. They’ve already succeeded in multiplying bacteria that were considered “unculturable” before, expanding practical scientific understanding of the tiny organisms and ostensibly, building toward a future where microbiota could be used in targeted treatments.

“Bioprospecting”

The Global Microbiome Conservancy

While the steps in the conservancy project seem straightforward, ethical questions come up at every step in the biobanking process: how data is collected, what to do with the samples, who has access to the genetic data, and who the resulting research ultimately benefits.

Researchers behind the Microbiota Vault and the Global Microbiome Conservancy both tell Inverse their intent is to change a legacy of exploitation in conducting research with biological material. But exactly how is not yet known.

“We don't want to follow the traditional model of science, or bioprospecting,” Katya Moniz, the executive director of the Global Microbiome Conservancy, tells Inverse. “We want to give back.”

The Conservancy does this, she explains, by “supporting local collaborators and scientists so that they can do the work that serves their local populations and their health concerns.”

Bioprospecting, in this context, refers to the history of academics from wealthy nations using biological material and data from non-white and Indigenous communities without consent or approval in ways that align with belief systems and cultural values.

The Conservancy in Coronel Juan Solá, Argentina.The Global Microbiome Conservancy

Although Moniz emphasizes this point, there doesn’t seem to be a standardized approach yet, at least when it comes to monetary gain. Legal safeguards would, at a minimum, prevent companies from turning a profit off the biological data of people who gave it up for free.

What would they do to ensure that if the genetic data is used by a company to develop a profitable therapeutic, for example, the benefits would be shared with the donor communities? Monez’ response suggests the answer isn’t as far along as you might think.

“We are building a benefit-sharing strategy in communication with other nonprofits who already do this,” she says. “And we're seeking guidance from them on the best way to do this because it's a very complicated thing to do.”

“It's possible, down the line, we might have an arrangement in place that would allow the knowledge taken from this to then be commercialized,” Moniz adds.

Until then, Moniz reasons, letting donors own their own samples will help protect their interests.

The legacy of Henrietta Lacks

A photo of Henrietta Lacks.The Washington Post/The Washington Post/Getty Images

In 1951, Henrietta Lacks visited the Johns Hopkins Hospital (the only hospital in the area treating poor Black Americans at the time). Lacks died later that year, but cells removed from her tumor were used for years without her or her family’s consent or knowledge. And although the case has helped bring about changes in privacy laws around the use of human tissue or cells, the same cell line is still used in medical research.

In Arizona, a more recent case illustrates the issue of “informed consent.” In 2003, members of the Havasupai tribe learned that blood samples they had given to researchers at the Arizona State University, which they believed would be used for research on diabetes, were used in several other unrelated studies. Members of the tribe said they would not have consented had they been informed of the other research, and the next year filed a lawsuit against the Arizona Board of Regents and Arizona State University.

Supai Charlie, a Havasupai man, standing in front of his ha-wa, a structure made of sticks and grass.Historical/Corbis Historical/Getty Images

In these cases, and many others, biological material and data extracted from people in vulnerable situations ended up benefiting researchers, institutions, and even companies who use medical research to develop medical treatments — and not the people from whom they were taken.

These also include biological data on an individual level, like in the case of a patent filed by the U.S. government on cell lines of a Panamanian-Guyami woman and a Haghai man from Papua New Guinea, which became high-profile examples of the exploitation of indigenous peoples during scientific research.

Larger-scale projects like the Human Genome Diversity Project were also opposed by groups like the Indigenous Peoples Council on Biocolonialism and the Rural Advancement Foundation International for ethical reasons, like the participant’s lack of control over who accesses data after it is taken and the assumption that indigenous peoples are “vanishing.”

“If we're looking to Indigenous populations to provide this supposed, ‘ancestral’ narrative, then that is creating a whole layer of suppositions about Indigenous peoples as being non-modern, which is not correct,” says Native BioData co-founder Krystal Tsosie, Consortium. “It's a false characterization.”

While there are protocols in place all over the world to ensure ethical use of biological material, some argue they aren’t enough. And while well-meaning, efforts at “inclusion” and “partnership” with donor communities have their limits.

“There's always been a rush in the inclusion of indigenous peoples in data sets — that's not new. I'm tired of it being stated as this brand new thing,” Tsosie says. “What should be different is providing greater agency and authority for Indigenous peoples to direct the data decisions that affect them.”

Competing approaches to biobanking

A child looks out of the window of his home, in Bandipur, Nepal, a hilltop settlement on the Mahabharat mountain saddle.Majority World/Universal Images Group/Getty Images

In Nepal, the Global Microbiome Conservancy (the MIT biobank) partners with Dibesh Karmacharya to collect samples from the Chepang community, a semi-nomadic group that primarily lives in central Nepal’s Mahabharat mountain range.

The Conservancy sends participants their microbiome profiles and works with an ethical committee to tailor informed consent forms to specific communities.

Karmacharya, the chairman and executive director of the Center for Molecular Dynamics Nepal, says the Conservancy has also provided conservation education and hired local residents to do other kinds of fieldwork.

“We would do the health camps,” Karmacharya says. “So we provide them with access to doctors and nurses and basic medicines so they feel that they have gained something out of it.”

But Tsosie argues that the problems associated with this type of biomedical work aren’t limited to community relationships.

In the communities she’s connected to and works with, focusing on this aspect perpetuates “this unfortunate narrative that as long as we build trust relations, or as long as we atone for problems in the past, that Native Americans, Indigenous peoples will hop on board with genetics,” she says.

“That's not true,” she adds. “These discussions are ongoing. They have a lot to do with where the data is being collected and stored and how it's being used or misused to tell stories about us, and that is something that's a continual process in research.”

The Global Microbiome Conservancy, for example, shares sequenced genomes of the samples to a large repository of genetic data called dbGap.

This allows other researchers all over the world to use their research. The data they’d share would be anonymized, but include demographic information on the donor's diet and lifestyle. Representatives from any institution planning to use it would file a request and send it to the National Institute of Health’s Data Access Committee representative, who approves or denies their access to the data.

The Conservancy sends participants their microbiome profiles and works with an ethical committee to tailor informed consent forms to specific communities.The Global Microbiome Conservancy

The Microbiota Vault proposes a slightly different model. Communities that participate in sample collection can keep a copy of their microbiota locally for their experts to conduct research on. But they also donate another copy to the Vault. Ultimately, Dominguez-Bello and colleagues want to provide free Rutgers classes online to donating communities, teaching the genetic science behind their samples.

The Native BioData Consortium (NBDC), run by scientists and researchers who are members of Indigenous communities in the United States and Mexico, takes a different approach.

Based in South Dakota, the NBDC wants Indigenous data to be protected, which means not sharing it publicly — period.

“If the people on that land see themselves as caretakers or stewards of their environment... they could see the open-access nature of that data as a violation of that trust and that relationship that they have with the land,” Matthew Anderson tells Inverse. He sits on the board of the NBDC and is an assistant professor at Ohio State University.

“The data that we're collecting as part of this project will not be open access,” Anderson says. “It will not be freely available to whoever wants it.”

And while they don’t speak for other communities who have worked with various global microbiome biobanking efforts, their work within an Indigenous framework offers a new model for microbiome research and banking.

Instead of preserving microbiomes with the aim of using the material to make future therapeutics, the Native Biodata Consortium is using the data to tackle pressing health issues that are happening now.

Who should science serve?

A group portrait of Big Foot's Miniconjou Sioux band at a Grass Dance on the Cheyenne River, South Dakota. Historical/Corbis Historical/Getty Images

Rheumatoid arthritis is five times more prevalent among the Cheyenne River Sioux tribe than the rest of the U.S. population, and scientists from the Native BioData Consortium think they can use microbiomes to work toward better treatment.

The Cheyenne River Indian Reservation covers counties in South Dakota, and several chronic health conditions there are linked to mercury emitted by coal power plants and other pollutants from extractive industries in the region.

Native BioData Consortium board member Matthew Anderson says a better understanding of this community’s microbiome could add a more precise layer of needed information, especially because its contents may reflect highly specific differences in environmental exposures.

“It's not just where you live in a general sense,” Anderson says. “It's a more specific response to what you are eating there, where are you living on the rez, our traditional food sources, as well as commodity foods or grocery store foods. Where are you encountering the environment in different ways? This is not just an ethereal concept. This is life or death, or the quality of life and death, for different people.”

“Tribes no longer have to be reliant on outside entities to do the work.”

Their approach to health equity goes beyond social indicators like income or access to health care.

“It's actually collecting biological data types and then using those data types to get a better understanding of what somebody's genetic determinants are,” Anderson says. “Or what some of the environmental determinants are that could be causing greater incidences of disease.”

The samples will be stored with the Cheyenne River Sioux Tribe, which the NBDC website states, “will provide additional protections for the participants’ samples from exploitation.”

“I think this is the beginning of a movement toward tribes taking ownership of performing the work themselves, instead of those in academia, or government, or private industry,” Anderson says. It’s a step away from what he describes as the “worst-case scenario” — Indigenous donors becoming “victims of bio-colonial efforts.”

And while the arthritis microbiome project is being done in collaboration with Mike Snyder, the director of the Center of Genomics and Personalized Medicine at Stanford’s University School of Medicine Department of Genetics, Anderson says that in the near future, relying on outside entities won’t be necessary to do science that serves Indigenous communities.

With more and more Indigenous people in science and in positions of power in recent years, “tribes no longer have to be reliant on outside entities to do the work,” Anderson says. “That is the future.”

Inverse celebrates your wonderous gut. Read more.

Related Tags
Share: