MEXICO CITY — Back in 2019, while she worked for the biotech Regeneron Pharmaceuticals, Claudia Gonzaga heard a rumor that thrilled her. The company would begin sequencing and analyzing the DNA of 150,000 people from Mexico City, thanks to a research collaboration with the University of Oxford.
As the only Mexican geneticist at Regeneron, Gonzaga saw this as a unique opportunity. She had previously tried to convince her colleagues to sequence the genomes of people from Mexico, where researchers have found a stunning amount of human genetic diversity, but to no avail. The new partnership meant she would be able to resume her plans. “I was so pleased,” she said.
She was similarly surprised when she later learned that Oxford researchers had very much tried to keep this a Mexican study. While Oxford, not a Mexican institution, had physical custody of all the samples, Mexican epidemiologists had actively participated in almost every step of the research, and once the genetic data were ready, the Oxford team would make them public and offer rapid, free, and preferential access to Mexican scientists.
It went against the long history of “parachute science” or “helicopter research” — when researchers from wealthier nations visit low- and middle-income countries to collect data and samples, analyze them back at home, and publish the results with little or no involvement of local scientists.
Gonzaga left the company for academia in 2020 and went back to Mexico. She hasn’t gotten her hands on the data yet, though she’s already planning what she’ll do with them, such as hunting for genetic variants closely linked to diseases like breast cancer and calculating how frequent they are in Mexicans. And she is pushing to have a physical copy of the genetic biobank hosted at her institution.
“I have many ideas of things we can do,” said Gonzaga, now a genomicist studying genetic disorders at the International Laboratory for Human Genome Research of the National Autonomous University of Mexico (UNAM) in Querétaro. “What I need now is having access to the data.”
The building and study of massive sets of genetic data from Mexicans is part of a global effort to make genetic collections and biobanks, which are still too white, representative of all humans. Though necessary to achieve that goal, international partnerships pose uncomfortable questions, such as who owns the data, whom to share it with, and what for.
Experts mostly laud the Mexico City project for avoiding the worst sins of parachute science and aiming to strengthen research capacity in the country, though Oxford controls access to the data and Mexican scientists like Gonzaga are still waiting for it. Some experts also warn that, when trying to promote fairer international collaborations and diversify the people they study, local researchers must be careful not to perpetuate the same discrimination they sometimes face, by excluding Mexico’s many Indigenous populations from participating actively in research involving their communities.
“Let’s not forget that exploitation, extractivism, and colonialism also exist [in our countries],” said Amaranta Manrique de Lara, a genomicist and bioethicist at the General Hospital of Mexico in Mexico City. “In our effort to combat old biases, we may be generating new ones.”
In the 1990s, a simple yet ambitious question arose: What is killing Mexicans?
“We knew an awful lot about what killed white middle-aged men and women,” said Jonathan Emberson, a statistical epidemiologist at the University of Oxford. But there was a real dearth of evidence for everyone else, he added.
To find that data, a group of epidemiologists from Oxford and Mexico’s Secretariat of Health teamed up. Between 1998 and 2004, they sent hundreds of trained nurses to the homes of more than 150,000 people in two contiguous districts in Mexico City — Iztapalapa and Coyoacán — to ask about their health history, measure their vitals, and draw a tube of blood from them. But their blood samples, and the DNA within them, remained largely untouched for about two decades at Oxford. Until 2019, that is, when the team approached Regeneron and the pharmaceutical companies AstraZeneca and AbbVie for help with sequencing and analyzing the genetic material.
It was then that Gonzaga first heard about the Mexico City Prospective Study, or MCPS — an ongoing project that has followed participants over the years to understand the social, lifestyle, physical, and genetic causes of complex diseases, such as diabetes and obesity. The study resurveyed 10,000 surviving participants between 2015 and 2019.
“It really is a waiting game,” said Emberson, who is the program leader for the MCPS. “You need to wait until, sadly, enough participants have had diseases of interest — and you don’t get that within just a few years.”
In fact, it was not until 2016 that the MCPS published its first major finding. After reviewing the death certificates of participants, the researchers found that those with diabetes had a strikingly worse prognosis than that seen in high-income nations. In Mexico City, it turns out, the rate of death from any cause was almost four times as high among people with diabetes as among those without the disease.
More recently, in a preprint published in late June, the team added to its extensive evidence the genetic sequences for MCPS participants, hoping to find new gene variants associated with diseases. They mostly focused on the exomes, regions that make up the 2% of the human genome that code for proteins, which drug hunters typically mine to uncover disease-linked changes.
With this, the MCPS has become the most extensive genetic study in people outside Europe, the U.K., or Iceland — which together account for over 72% of all participants in genome-wide association studies, known as GWAS, which scientists use to hunt for snippets of DNA that may be linked to a certain disease or trait. Latin Americans make up around 8% of all people on the planet, yet they constitute 0.25% of all these genetic studies, according to the online tracker GWAS Diversity Monitor.
The MCPS genetic sequences have already proven their worth. They were included in a paper, published in Science last year, that discovered rare mutations that inactivated a gene called GPR75, which was associated with protection against weight gain — people with these variants tended to weigh about 12 pounds less and face a 54% lower risk of obesity than those without the mutation. (Emberson noted that while MCPS data were “a worthwhile addition” to the GPR75 paper, the discovery didn’t ultimately depend on any of it. Regeneron spokesperson Ella Campbell, however, wrote in an email to STAT that they were needed to “ensure the discovery held true with different populations.”)
Regeneron and AstraZeneca have announced they are developing drug candidates directed against GPR75 to treat obesity. Should a medicine eventually reach market, Campbell wrote, Oxford and Regeneron would be able to share or generate their own intellectual property, according to their collaboration agreement.
As the only Mexican institution in the MCPS, UNAM equally shares any intellectual property rights with Oxford. “We both own the information,” said Jesús Alegre Díaz, a medical epidemiologist at UNAM’s Faculty of Medicine in Mexico City and one of the three Mexican principal investigators involved in the MCPS. “We’re Mexicans studying Mexicans.”
Elida Fernández, a lawyer at UNAM, said a research agreement between both universities was signed in early August with the purpose of resurveying surviving participants. Among other things, the contract, which STAT reviewed, dictates that both UNAM and Oxford can use the samples and data and that the results of the research – including all intellectual property rights, data, discoveries, and patents – will be shared between both institutions.
The vast amount of genetic data pouring out of the MCPS has some Mexican geneticists salivating to get their hands on it.
In 2016, Andrés Moreno Estrada, a human population geneticist at Mexico’s National Laboratory of Genomics for Biodiversity in Irapuato, and colleagues launched the MX Biobank project, which sequenced the DNA of about 6,000 people from across the country, including many from Indigenous communities and rural areas. Though the biobank also works in partnership with Oxford, Moreno Estrada said that they negotiated to keep the guts of the project in Mexico to build its research capacity — the samples are hosted in a Mexican institution, the bulk of the genomic analysis is led by the Mexican research team, and many of the project’s former students are continuing their careers studying the data they generated.
He recently approached the MCPS researchers in hopes to collaborate and share their respective datasets with each other. “We don’t have their numbers,” he said, referring to the size of the MCPS dataset. “They are discovering things that we can’t.”
He might need to wait a bit longer.
Regeneron has launched an online browser that includes the genetic variation found across all 150,000 participants, making it freely accessible to anyone. But the browser, for now, “is not very useful,” said Gonzaga. It lacks key information that makes it difficult to know whether a disease-linked variant is present in 100 or 10,000 people, for example.
So far, the MCPS research group at Oxford holds the custody of the study’s samples and data. “It happens to be that this process has been managed at Oxford at the moment,” Emberson said. “But, I mean, maybe in the future it will be done separately or jointly with UNAM.” The recently signed agreement may allow that.
Still, the MCPS has made important progress to support Mexican scientists and strengthen local research capacity. Oxford has trained staff in Mexico and paid for courses and short-term research placements, said Emberson. And as soon as the data are clean, Mexican researchers will have free and preferential access to it for a period of two years. Researchers based elsewhere in the world will need to pay up to £2,500 (about $3,000) to receive the data.
The policy feels like “a step in the right direction,” said Mashaal Sohail, an evolutionary geneticist at UNAM’s Center for Genomic Sciences in Cuernavaca. And one that’s not very common. “Even within Mexico,” she said, “people are generating data and not sharing it with other academic groups.”
Even if international partnerships move toward fairer conditions, some scientists warn that may not be enough.
“Stripping [genomic science] of its colonialism, hierarchy, and structural violence has to be an everyday task,” said Jocelyn Cheé Santiago, a Binnizá genomic scientist at UNAM in Mexico City (the Binnizá, also known as Zapotec, are one of Mexico’s 68 Indigenous groups.) “If we are not going to discuss the colonialism [aspect] of our research, then what’s the point?”
For decades, Mexico has tried to guard the genetic data of its citizens. In 2008, Congress passed a national law that embraced the idea of “genomic sovereignty,” a concept that aims to protect Mexican DNA — by itself absurdly difficult to define, critics say — from foreign interests. And many researchers saw it as a way to “break this relationship between us Mexicans as suppliers of samples, and foreign scientists as the ones who analyzed [them],” said Ernesto Schwartz-Marín, an ethnographer who probes the interaction between race and genomics at the University of Exeter, U.K.
But the law has made little difference. Genomic sovereignty “is a bulls— term,” Schwartz-Marín said. “It’s impossible to execute because there’s no way to say what the Mexican genome is” or looks like. And there’s no consensus about who is supposed to guard it.
In 2010, the state of Nayarit included a provision in its constitution on genomic sovereignty. Schwartz-Marín indirectly participated in its design, and suggested that the language enable Indigenous peoples to protect their own genetic data. “When we tried to get this into the draft,” he said, “that’s exactly what [legislators] erased.”
The incident is a window into a double standard in Mexico, said Manrique de Lara. When studying Indigenous populations or other groups, such as people who live with a disability or disease, Mexican scientists often “do a lot of this parachute research we so often criticize.” And rare is the case when study participants see any benefits from the science, she added.
The way to counter that is by creating fairer collaborations, Cheé Santiago said, where participants have an active role in the research — such as deciding what questions to ask, how to ask them, and who has custody over the data. “That we are no longer part of the menu,” she said, “but part of the table” where decisions are made.
It’s something that’s happening elsewhere. In Australia, the National Centre for Indigenous Genomics is governed by a majority-Indigenous board, and has approached communities to ask what they wish to do with their samples. In Chile, recent efforts to explain the uses and limitations of genetics led scientists and Indigenous people to come together in a three-day workshop. And in countries like the U.S. and Canada, the Summer Internship for Indigenous peoples in Genomics (also known as SING) have trained Indigenous participants in genomics and its ethical implications.
Such changes are coming slowly in Mexico. Manrique de Lara and colleagues who teach future geneticists at UNAM’s Center for Genomic Sciences have started to incorporate parachute science, scientific colonialism, and other bad practices into the syllabus of their classes.
“If we do our job right,” she said, “we’ll be seeing this internal change in the next generation of researchers.”