A Geneticist’s Dilemma

A growing number of scientists believe that the cure for disease can be found in our DNA. But that poses a unique problem for some Native Americans.
Navajo researcher and geneticist Rene Begay at Cherry Creek State Park in Aurora, Colo.

On a clear and icy morning in February of this year, I picked up Rene Begay from the Albuquerque airport. We headed west toward the Navajo Nation reservation, the largest tribal land base in the United States, spanning 27,500 square miles between Arizona, Utah and New Mexico. Begay, a 31-year-old Navajo scientist with a background in genetic research, spent her childhood in various towns throughout the reservation. She’d just flown in from Denver, where she works as a research assistant at the Centers for American Indian and Alaska Native Health at the University of Colorado Anschutz Medical Campus. She wore a blue velveteen blouse — a garment customarily worn by Navajo women — and jeans. “Something traditional and something modern,” she said.

Our first stop would be Chinle, Ariz., a town of about 5,000 people, where Begay’s mother lives. The two are very close, and Begay flies down from Denver as often as possible to visit. As we exited the Albuquerque city limits, Begay told me I could turn off the GPS; she’d direct me the rest of the way. The landscape grew flatter and redder as we approached the border of the Navajo Nation. “It always feels good to be coming home,” she said.

After investigating the causes of hereditary heart disease for her master’s project, Begay dreamed of using genetic insights to better understand cardiovascular health in her community. Given that Native American adults are 50 percent more likely to be affected by obesity than non-Hispanic whites, and twice as likely to be diabetic, this would be valuable work. But it would also contravene tribal law. In 2002, the Navajo Nation government instituted a tribal-wide moratorium on genetic research. This decision, which had both medical and religious motivations, put a stop to any genetic research taking place on the reservation and holds to this day.

The moratorium stands at odds with a much-hyped and well-funded national health initiative, called the All of Us Research Program, launched by the Obama administration in 2015. Led by the National Institutes of Health (NIH), the program aims to collect medical and genetic data from 1 million Americans by around 2025, at a cost of about $1.5 billion. The purpose is to advance “precision medicine,” a medical paradigm that postulates that the determinants of disease often lie in glitches in our biology.

To ensure that the benefits of this research go to every American, All of Us has been actively recruiting participants from racial and ethnic minorities. At NIH, this diverse recruitment drive is seen as part of a progressive, trailblazing vision that will bring medical insight to communities that have historically been overlooked and underfunded, including Native American tribal nations.

Yet providing DNA samples to a federal study as a member of a sovereign tribal nation is not a matter of opting in as an individual; participants would be representing a nation within a nation. And for Navajo living on tribal land, participating in All of Us directly contradicts the 2002 moratorium. Since 2015 officials at All of Us have devoted time and funds toward engaging with Native American communities to ensure that recruitment accords with these unique circumstances. But last year, after it became clear that All of Us had recruited some tribal members — albeit off tribal lands — without first completing a consultation process with tribal leaders, concerns were raised about the program’s policies by some Native American scientists.

To some precision-medicine evangelists, the Navajo moratorium appears to be an outdated policy, holding the community back from participating in valuable research, possibly exacerbating current health disparities. Others, however, feel that the Navajo Nation’s moratorium is a prudent policy — that precision medicine is simply a high-tech medical panacea destined to fail the Americans who need it most. Amid the coronavirus crisis — which has disproportionately affected the Navajo Nation — more are joining the chorus questioning this gene-centric approach to medicine.

As a scientist, Begay comprehends the potential of programs like All of Us, which could bring new medical insight for underserved communities. But as a Navajo woman, steeped in the traditions and history of her people, she discerns the wisdom of the moratorium’s precautionary logic. “Many things have been taken from us and we have seen nothing in return,” she said as she directed me down the highway toward her ancestral homelands. “We want to make sure that it won’t be the same with our DNA. That if we give it up, we will see the benefits.”

Begay in a lab at the University of Colorado Anschutz Medical Campus in Aurora. (Jay Dickman)

After a 3½-hour drive west, Begay and I arrived in Chinle, a town that lies a few miles from the perimeter of Canyon de Chelly, a great cascading national monument of red sandstone. Eons before Europeans arrived in the region, the Diné — which translates as “the people” and is how the Navajo refer to themselves — had established a highly organized way of life along the river that flows through the canyon, building houses of packed mud and wood called hogans; hunting deer and antelope; and sowing crops of corn, beans and squash.

In the 1840s, U.S. troops initiated a scorched-earth campaign against the Navajo, burning settlements and slaughtering livestock. In 1864, more than 10,000 tribespeople were captured and forcibly marched to a reservation 300 miles away in modern-day New Mexico. This deportation, known as the Long Walk, ended in four years of exile in a dysentery- and smallpox-infested camp, where thousands perished. In 1868, the U.S. government signed a treaty with the Navajo that allowed them to return to their homelands.

Over the decades, the Navajo rebuilt. Now the Nation is the second-largest tribe in America, with more than 300,000 members, about half living on the reservation. For the Navajo, as for other Native Americans, the oppression of colonialism persists in health disparities. Today, a resident of Chinle is, on average, more likely to suffer from tuberculosis, diabetes, alcoholism and heart disease than a resident in most other American towns.

Begay grew up on the reservation among a family of healers, nurses and medical workers. From a young age, she was keenly aware of her people’s condition. Her mother’s maternal grandfather was a medicine man who performed healing ceremonies up until his 104th year. Begay never met him, but she spent every summer under the care of his daughter, her grandmother, who oversaw the ritual and communal life of the family.

“Many things have been taken from us and we have seen nothing in return,” Rene Begay said. “We want to make sure that it won’t be the same with our DNA.”

When Begay was 12, she underwent her coming-of-age ceremonies at the family’s hogan at their property in Salina Springs, a small settlement 31 miles southwest of Chinle. Over four days, relatives and friends visited to present her with jewelry and belts. Laden with these ornaments, she ran three times a day, toward the rising, midday and setting sun — each journey a little bit farther than the one before. This ceremony provided strength to help Begay move on to the next stage of life with the support of her community. A sense of belonging and peoplehood, Begay explained to me, is central to Navajo health. “It was at my grandmother’s that I learned that health is tied to tradition; it is a community effort,” she said.

She learned about Western medicine from her mother, a nurse for the U.S. Department of Health and Human Services’ Indian Health Service who worked in hospitals around the Southwest. Begay absorbed everything her mother told her about work at the hospital. “When she was only a little girl Rene got sick, so I took her to the pediatrician,” her mother told me. “The doctor asked me what medication she’d been taking, but before I could get a word out, Rene answered, ‘acetaminophen.’ ”

Begay studied science at the University of Arizona in Tucson, then moved to Denver after graduation to take a post-baccalaureate research position at the University of Colorado Anschutz Medical Campus. She joined a team investigating the causes of cardiomyopathy, a disease that weakens the heart muscle and restricts movement of blood around the body. Mostly, this is caused by aging and lifestyle, but in some cases the disease is heritable. Begay worked in a lab analyzing the genetic profile of an intergenerational Italian family that suffered from the hereditary form of this disease.

During her days in the lab, Begay often thought about how she might apply her new skills on the reservation. She knew that heart disease was chronic among her people, but now she began to consider whether there might be a genetic explanation. Perhaps, she thought, she could continue her family’s legacy of health work — this time at a molecular level.

Such is the promise of precision medicine: that deciphering the genetic code of disease will allow scientists to fix our biological glitches. This medical paradigm has its origins in the 1980s, when scientists began identifying specific genetic mutations associated with rare inherited diseases, like cystic fibrosis. In the 1990s, an international consortium set about mapping the full human genome to better understand this genetic basis of disease, a task that was completed, at an expense of $3 billion, by 2003.

This was a significant achievement. But the full genome map also revealed a more complicated genetic structure for disease than previously imagined. Unlike cystic fibrosis, where there is a neat correlation between a single DNA error and sickness, the maladies that are responsible for the vast majority of human morbidity — heart disease, diabetes, cancer — implicated a web of mutations too numerous and complex to plot. For some, this suggested that there was a limit to the medical insight to be gained from studying the genome. Others maintained that by gathering more genomic data, scientists would eventually understand the biological cause of disease and from there would be able to tailor treatments to individual bodies.

Begay, like many others, became enthralled by the promise of precision medicine. Toward the end of her first year at the lab outside Denver, her supervisor encouraged her to start formulating a master’s project. Begay wanted to conduct research within the Navajo community, but she soon found that there was little existing genetic data to work with. If she was going to investigate the genetic cause of heart disease among the Navajo, she would have to collect the samples herself.

But this would not be possible. Twelve years earlier, when the Navajo Nation had asserted its sovereign right to suspend all genetic research involving tribal members who live on the reservation, the decision was, in part, justified on religious grounds. In the Navajo belief system, every small part of the body contains the essence of the whole. For some, even fingernails and hair must be disposed of correctly, lest fragments fall into the wrong hands.

To find a way through this impasse, Begay met with a medicine man at her uncle’s house for a ceremony. She had been oblivious to the moratorium when she started working in genetics; now she was finding it difficult to reconcile her chosen science with her inherited traditions. The medicine man told Begay that even though she could not conduct research on the reservation, she could continue working with non-Navajo populations. “He wanted to make sure that before handling samples I’d ask the holy people for permission, that I keep up my prayers and continue to ask the creator to do this kind of work,” she told me.

In 2014, Begay started her master’s project at the University of Colorado medical campus, sequencing gene mutations associated with cardiomyopathy in zebrafish. She had received permission from her elders to work with non-Navajo DNA but still felt uncertain about her future. Seeking guidance, she reached out to Náníbaaʼ Garrison, a Navajo scientist with a PhD in genetics. Garrison told Begay about the Summer Internship for Indigenous Peoples in Genomics (known as SING), an annual, week-long course about genetics taught by mostly Native academics.

That summer, Begay traveled to Austin for the workshop, where she met other Indigenous geneticists from around the world. Opposition to genetic research was not unique to the Navajo, Begay learned, but was a position taken by many communities, responding directly to a history of medical exploitation. In America, this stretched back to the days when the remains of Native American people were exhumed, measured, analyzed and displayed in vast medical exhibitions known as bone rooms.

The same colonial attitude echoed throughout the genetic era, beginning toward the end of the past century. In the 1990s, for instance, researchers from Arizona State University drew blood from members of the Havasupai, a tribal nation of fewer than 1,000 people. The stated purpose was to investigate the genetic cause of diabetes, an illness that affects the Havasupai in high numbers. Blood was given on the premise that the tribe would see some medical insight in return for their contribution. In the years that followed, however, the diabetes research program stalled while the blood samples were shared with other researchers to investigate subjects to which the tribe had not consented.

The Havasupai only learned of this in 2003, when Carletta Tilousi, a tribal member and an ASU undergraduate student, attended a lecture by a doctoral student whose project involved using Havasupai DNA to trace the tribe’s migration history. For many Native American tribes, this type of population genetics is threatening, as it can undermine creation stories or complicate the principles of tribal membership. At the end of the presentation, Tilousi raised her hand and asked the doctoral student if he had been given permission from any tribal member to handle their blood. He had not. (The Havasupai took the university to court, where they settled in 2010. ASU paid $700,000 to the tribe and returned the blood samples.)

The story of the Havasupai was not an isolated incident. Similar events transpired when genetic researchers took blood from the Pima Indians of Arizona and the Nuu-chah-nulth people of the Canadian Pacific Northwest: Promises were made about what the samples would be used for, and were later broken. This history troubled Begay, but she felt grateful to have learned about it from other Indigenous researchers. “The people I met saw their role not just as scientists, but as a kind of barrier between their communities and non-native biomedical researchers,” Begay told me. “It was the first time I realized that scientists could advocate for their people.”

Begay works as a research assistant at the Centers for American Indian and Alaska Native Health at the University of Colorado Anschutz Medical Campus. In 2002, the Navajo Nation government instituted a tribal-wide moratorium on genetic research.

In January 2015, when Begay was a year through her master’s program, President Barack Obama unveiled the Precision Medicine Initiative (later renamed All of Us), an ambitious plan to build one of the largest and most diverse genetic databases in the world. Until that point, the vast majority of global medical genetic studies had been conducted on people of European ancestry.

If the genetic determinants of common disease were the same across different populations, this sampling bias would have been inconsequential. But this is not the case. Type 2 diabetes, for example, might be associated with a different DNA variant in a person of native South American ancestry than someone of European or African ancestry. By leaving non-European populations out, the potential benefits of precision medicine would go only to a small, White subset of humanity.

The project attempted to correct for this by recruiting a population that adequately represented the country’s population. “We knew we couldn’t exclude people in this endeavor that was really meant to be a national resource,” Stephanie Devaney, the chief operating officer for All of Us, told me. To this end, a fleet of blue minibuses were sent from state to state to do community outreach and enroll participants.

In the summer of 2017, a delegation from All of Us gave a lecture at the annual SING workshop, held that year at the University of Arizona. The representative explained how Native American communities had been underrepresented in genetic databases and that All of Us was trying to rectify this through active recruitment. Begay, who now had her master’s degree and a research position at the Centers for American Indian and Alaska Native Health, heard little about the program again until June 2019, when delegates from All of Us started a nationwide tribal consultation tour.

By this stage, however, the study had already enrolled more than 1,600 people who self-identified as American Indian or Alaskan Natives with tribal affiliation. This recruitment occurred off tribal lands, meaning the program did not technically contravene sovereignty. But All of Us had targeted research institutions in cities with a high percentage of Native American residents.

As news of this recruitment made its way to members of SING, some became increasingly critical of the program. Two of the most outspoken voices were Krystal Tsosie, a Navajo geneticist, and Joseph Yracheta, a research scientist of Mexican Indigenous ancestry. Both questioned whether this drive for “diversity” was motivated by a colonial impulse to collect rare genetic data. “The whole reason people want to sample us is because our genome doesn’t look like anybody else,” Yracheta told me. “Is there a cure for HIV or hepatitis in some variant that only we have? The danger is that we give this data up and it doesn’t benefit the people it comes from.”

In July 2019, Tsosie and Yracheta published an article in Nature Reviews Genetics questioning All of Us’s consent procedures. The individual-based informed consent model that was used to recruit tribal members who lived off tribal land, they argued, failed to acknowledge that the individual genomic information of a person from a small tribe can be used as a representative sample to make statistical inferences about the whole community. The tribal consultations were, for Tsosie and Yracheta, too little, too late. “If respecting tribal sovereignty were so important,” Tsosie wrote to me in an email, “one would think this type of consultation would have occurred prior to recruiting Indigenous individuals.”

That August, Begay, who followed the conversation around All of Us with interest, attended one of the tribal consultation sessions at a federal office building in downtown Denver. Tribal leaders from nearby regions sat around a rectangular desk in the middle of the room, while Devaney, who oversaw the tribal consultation process, went through slides that explained the benefits of precision medicine for minority communities.

In the previous months, Devaney had visited several tribal communities across the country to listen to tribal leaders’ key concerns about participating. In one consultation, a tribal leader told Devaney of an experience where a local environmental agency had come onto his land and taken blood samples from children to test for lead poisoning after apparent contamination. He had allowed this to happen because he was assured that the research would benefit his people and that the samples would one day be returned. Yet they were never given back. “He was talking about his community in a very emotional way,” Devaney told me. “From his perspective, his samples were part of the children in his community.”

Devaney understood that part of her job would be building trust that had understandably eroded. After her presentation in Denver, leaders were invited to ask questions. The most pressing concern, Begay told me, was what was going to be done to the collected DNA. Some worried that it would be used to study taboo or stigmatizing topics, such as inbreeding and alcoholism. Others worried it might be used to disprove Native American creation stories. Devaney listened patiently, then explained that the All of Us program was not using the data to conduct any studies of their own, but were more like custodians. Researchers would be able to approach them and request access to the data to do their own studies.

Begay felt the atmosphere in the room turn. “The idea of taking DNA, not knowing what it is going to be used for, touched upon a lot of the fears that we have as Native Americans,” she said. “Like our blood is going to be mined for someone else’s benefit and that we will have no say in it.”

Still, while she understood the suspicion toward the federal study, she also acknowledged that it could lead to significant medical insight. “I’m all for protecting our sovereignty,” Begay said. “But at the same time, we have so many people who need help, and this type of research might one day be a tool to help make life better.”

A view of Fish Point on the Navajo Nation in Arizona. The area is commonly known as Tselani (Salina Springs, Ariz.). (Courtesy of Rene Begay)

In the coming years, Begay might play an important role in assisting the Navajo Nation with formulating research policy around genetics that would allow them to reconsider the moratorium. She currently sits on a working group that is tasked with advising tribal agencies on the matter. At the beginning of our road trip, she requested that I not ask her questions relating directly to the moratorium. The details are confidential, she said, and the conversation evolving. But she did invite me to speak to her family members.

Opinions were varied. Begay’s cousin, who served in the Marines, saw participation in genetic research as a type of civic duty. “To serve and contribute has always been in our culture and is part of our social belief,” he said. Her uncle held a similar perspective.

Her mother’s position was different. During her 30 years as a nurse, she said, the most effective interventions in Navajo health that she’s seen are those that find a balance between traditional healing and modern medicine. Large-scale genetic studies like All of Us, she believes, are too alien from the culture. “Navajo believe that you are made in a holy way. Whatever parts that you’re born with, so you should be put in the ground,” she said. “The resistance to genetic testing comes from this.”

What united Begay’s family was the question of benefit: Since the very first interactions between the Navajo and the U.S. government, the tribe has made sacrifices for the country based on the promise of mutual benefit, which has not been forthcoming. They all wondered, at some level, whether genetic research would be the same.

“I’m all for protecting our sovereignty,” Begay said. “But at the same time, we have so many people who need help, and this type of research might one day be a tool to help make life better.”

The spectacular ranges of Navajo sandstone that Begay and I drove through together stand as a constant reminder of why this question remains so sensitive. Between 1944 and 1986, millions of tons of uranium ore were mined from this multicolored earth. Families from across the reservation flocked to mine sites and open pits, often on horseback, where the men toiled in poorly ventilated mines for as little as 81 cents an hour.

The endless extraction was sold to the tribe as an economic opportunity. Yet, while mine owners grew rich, the new industry was killing the Navajo. By the 1980s, the long-term health effects of uranium mining were undeniable. Lung cancer was contracted by miners at a rate 56 times higher than the national average. Rates for liver cancer were more than 200 times the national average. Mining families had higher rates of diabetes, kidney disease and, perhaps most disturbing, a rare neuropathic disease that caused liver damage, dimmed vision, deformations of the hands and feet, and a life expectancy of around 10 years.

In the 1990s, when the Indian Health Service studied the cause of Navajo neuropathy, they prioritized searching for a genetic cause. Without screening patients for exposure to uranium, the epidemiologist leading the study concluded that the most probable cause of the disease was a DNA change unique to the Navajo — an “inborn error” of the metabolism.

Some studies conducted since suggest that the neuropathy is, at least in part, genetic. But by offering this genetic explanation without also examining the particular environmental history, blame shifted from the mine owners, the Environmental Protection Agency and Congress — all of whom had failed to clean up the mess the uranium extraction left behind — and ended up in the DNA of the Navajo people. The memory of this injury, which is inscribed in the land and the bodies of the Navajo, lingers. “This is why we have the moratorium,” Begay says. “Over time, we have learned that we need to look after ourselves.”

Begay at Cherry Creek State Park in Aurora. The Navajo Nation is the second-largest tribe in America.

While the Navajo Nation’s debate about the potential benefit of genetic medicine is tied to its particular history, it is a conversation that is taking place more broadly, too. In recent years, a coalition of medical dissenters has cast doubts on precision medicine’s ability to deliver better health across the board. The primary concern is that this approach pursues a narrow, genetic hypothesis for disease, meaning social and environmental causes are overlooked.

“What we’ve learned over the past 20 or so years is that the vast source of risk for common disease has nothing whatsoever to do with genetic predisposition and everything to do with what you eat and smoke and where you’re born,” Richard S. Cooper, chair of the department of public health sciences at Loyola University, told me. “If you have a rare familial syndrome, genetics is important. But for the 99 percent garden-variety diseases that affect most of us, it’s just not relevant.”

According to Devaney, All of Us acknowledges that the causes of disease do not lie entirely in our genome, which is why the initiative is seeking to collect not just biospecimens, but also in-depth lifestyle data, and it hopes to get access to electronic health records. “While the genome is really important to us, we do our best to emphasize all of the other data types,” she says.

Nevertheless, All of Us’s underlying motivation is still to improve personalized care — to collect and analyze data in order to tailor treatments that target our individual differences. While this is a compelling vision, Sandro Galea, dean at the Boston University School of Public Health, told me that it has led to divestment from public health initiatives that seek to prevent disease by addressing broader social causes rather than individual biology. Indeed, as genome research has expanded, NIH-funded projects with the words “public” or “population” have dropped by 90 percent. “This shift in medical priorities has been a disaster,” Galea says. “The underlying cause of these diseases that are affecting the population — addiction, suicide, heart disease, diabetes, obesity — have nothing to do with a person’s biology.”

In the weeks after my trip with Begay, as a novel coronavirus tore across the country, this idea was highlighted with alarming clarity. The pandemic, which was initially framed as a great equalizer, ended up accentuating pre-existing health disparities. The disproportionate disease burden was, and continues to be, borne by racial and ethnic minorities, none more so than the Navajo. By the middle of June, the Navajo Nation had 322 confirmed deaths, a rate of 177 deaths per 100,000 people, higher than any other state.

Amid the pandemic, All of Us paused in-person enrollment and postponed releasing its findings from the tribal consultations carried out in 2019. It expects to release the final consultation report early next year. Devaney acknowledges that the program made some initial missteps with tribal outreach and regrets recruiting before the tribal consultation was concluded. For now, the program has committed to not releasing any data about self-identified Native American participants to researchers without agreement from specific tribal nations. “What I’m hoping is that by doing this in a really thoughtful way now, and being really true to process and being really transparent, that we can rebuild some of that trust,” Devaney says.

She remains optimistic about the role All of Us can play in engaging underserved communities and eventually in making sense of the uneven spread of the virus. This is a view shared by the NIH director, Francis Collins, who published a blog post on the NIH website titled “Genes, Blood Type Tied to Risk of Severe COVID-19.” In it, Collins proposes that part of why covid affects people so differently “may be found in the genes that each one of us carries.”

Genetics has a role to play during the pandemic, of course: It helps scientists understand the biology of the virus, which is crucial for developing antibody testing and vaccines. But genes likely have little to do with why the Navajo have been many times more likely to be infected and die because of the virus than those in neighboring states. Much more obvious explanations are incomplete plumbing, electricity and Internet access on the reservation, which are critical to defending against spread, and high rates of underlying conditions like diabetes and obesity, which have been ignored because of decades of insufficient Indian Health Service budgets.

Begay and her husband, Donovan, who also grew up on the reservation, have watched the virus spread across the Navajo Nation from Denver, where they live with their two dogs. In late April, Begay’s aunt and uncle tested positive and were hospitalized with complications from the infection. They recovered, but then almost immediately after, Begay’s mother, who has been working on the front lines as a nurse at Chinle Comprehensive Health Care Facility, woke up one morning with aches and a fever. “She called me and told me that she had been diagnosed,” Begay told me over the phone in June. “I am doing my best to support her, but it is difficult to be so far away.” (Her mother has recovered.)

Begay and her husband plan to move back to the reservation eventually, but first they have to finish their studies. Donovan is nearing the end of his veterinary science program, and Begay was recently accepted into a master of public health program at Johns Hopkins University on a full scholarship. Next year, she will apply for medical school. Her dream is to open a clinic on the reservation that combines biomedical research, public health and traditional approaches to medicine.

Since the initial outbreak, the Navajo Nation has managed to bring the virus under control on its sovereign lands. Public health guidelines issued by the Navajo government have been assiduously followed. At a virtual town hall in September, Anthony Fauci congratulated the Navajo Nation. “You have done things extraordinarily well, and when I go out and plead with the rest of the nation, I will actually bring up the example of the success of what the Navajo Nation has been able to do,” he said.

For Begay, this is further evidence of Navajo courage and tenacity. “I feel proud, but it has been hard to be so far away,” she says. Begay and her husband say prayers together in the morning, facing the white line on the horizon at dawn where the sun rises, the direction toward which she ran as a young girl. “It reminds us,” she says, “that we’re still connected.”

Oscar Schwartz is a writer in New York.

Designed by Twila Waddy. Photo editing by Dudley M. Brooks.

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