How Latin America’s genomics revolution began — and why the field is under threat

Date:03-23-2023

By Carrie Arnold

Daniela Robles-Espinoza was a first-year undergraduate at the National Autonomous University of Mexico’s (UNAM’s) newly established Center for Genomic Sciences in Cuernavaca when she got a front-row seat to the dawn of genomics in her country.

The year was 2005. Scientists in Cuernavaca, nestled in the highlands 50 kilometres southwest of Mexico City, led a government-funded project to sequence the genome of Rhizobium etli, a bacterium that lives on the roots of some bean plants, helping them to fix nitrogen. Mirroring a Brazilian effort at the University of São Paulo to sequence the bacterial plant pathogen Xylella fastidiosa five years earlier, the project was an ambitious attempt to build up the country’s biotechnology infrastructure, providing Robles-Espinoza and her fellow students with an opportunity to watch cutting-edge genomics at first hand.

Citrus trees can be infected with the bacterium Xylella fastidiosa. Its genome was sequenced by a Brazilian team in 2000.Credit: Courtesy of Fundo de Defesa da Citricultura - FUNDECITRUS

″I had this perception that if you want to do good science, you have to go abroad,″ says Robles-Espinoza, who is now a group leader at UNAM’s International Laboratory for Human Genome Research in Querétaro, 200 km northwest of Mexico City. ″It was kind of in the air that people want to leave. But I would say, not any more.″

Two decades later, the sequencing of a bacterium no longer sounds like much of a milestone, but with a US$11.6-million grant from the São Paulo government, the project’s leaders say the X. fastidiosa research received more state funding than any other single piece of Brazilian science. The Mexican project received $2 million, also a major investment. To scientists across South and Central America, these projects represented more than just a loosening of governmental purse strings. By funding Mexican and Brazilian scientists to sequence agriculturally important bacteria, which were significant to their own economies, the projects have helped to spark the region’s biotech revolution.

The X. fastidiosa work ″created a network and a buzz within the São Paulo community. That was really important″, says Lygia da Veiga Pereira, director of the National Laboratory for Embryonic Stem Cell Research at the University of São Paulo. ″The greatest impact was in making these tools more available — not just sequencing but also molecular biology.″

Both Mexico and Brazil’s initial, time-limited sequencing projects also helped to train a new generation of genomics researchers, says Rafael Palacios, one of the directors of the R. etli sequencing effort and coordinator of UNAM’s International Laboratory for Human Genome Research. Mexico created a specialized undergraduate programme for future geneticists. And, in Brazil, the number of students earning master’s- and doctoral-level degrees in science doubled between 2000 and 2008 (see go.nature.com/3rfim1e).

Yet without greater investment, those gains are in danger. Although some large institutes have secured sustainable funding, not all researchers are so lucky. Brazil’s former president Jair Bolsonaro repeatedly cut science funding during his administration; in 2021, Brazil’s science budget was 4.4 billion reais (US$852 million), compared with 14 billion reais in 2015, the country’s peak. Researchers hope that Brazil’s newly elected president, Luiz Inácio Lula da Silva, who took office on 1 January, will reverse this trend. Mexico invests less than 1% of its gross domestic product in scientific research (compared with more than 3% in the United States and nearly 5% in Israel), and according to the World Bank, Mexico has just 327 scientists for every one million people (compared with 4,821 per million in the United States). Still, both Brazil and Mexico host small but vibrant biotech communities, says Palacios.

″There are very good scientists doing very good genomics in Mexico,″ says Palacios. ″They are the ones that will change the image of Mexican genomics.″

International sprint

From his office in sprawling São Paulo, Fernando Reinach watched a revolution unfold.

By the mid-1990s, US and European researchers had begun making huge strides in genome sequencing — first the laboratory bacterium Escherichia coli, then the nematode worm, the fruit fly and a flowering plant. At the same time, two international teams were racing to complete the human genome. As the biochemistry coordinator at the São Paulo Research Foundation (FAPESP), the scientific funding agency for the state of São Paulo, Reinach wanted to spark a revolution of his own. But this one would be completely Brazilian.

″In these new areas where fields were booming, it was clear that Brazil was being left behind,″ says Reinach. ″There were just two to three people in Brazil who were able to sequence a genome.″

The country had geneticists and bioinformaticians, but most of them trained abroad and in many cases stayed there. Those who returned often collaborated on European or US projects rather than leading their own. Fuelled by optimism and a desire to prove his country’s scientific mettle on the global stage, in 1997 Reinach invited 191 scientists from across São Paulo to participate in the sequencing and analysis of the bacterium X. fastidiosa.

The bacterium causes citrus variegated chlorosis, a disease that has infected more than 100 million citrus trees in Brazil since 1987. Yet, although scientists had begun to tackle human-associated bacteria, no one had yet sequenced a plant pathogen. Previous work had shown that X. fastidiosa had a genome of 2.7 million base pairs. That placed it in the genomics Goldilocks zone: enough DNA to challenge scientists but small enough to be manageable.

Steven Lindow, a microbiologist at the University of California, Berkeley, recalls wondering about the project’s expense. ″I knew it could be worthwhile, but it was also hideously expensive,″ he says. But in less than two years, the Brazilian team had sequenced, annotated and analysed the X. fastidiosa genome, on time and under budget. (It took a team of researchers five-and-a-half years to sequence E. coli.) The resulting paper was published on 13 July 2000, just months after the human genome, and made the cover of Nature. João Carlos Setubal, a bioinformatics researcher at the University of São Paulo who co-led the project, says this might have been a first for Brazilian scientists.

″The simple fact that a group of Brazilian scientists were able to organize a project, carry it out according to plan, and publish their results in one of the best scientific journals in the world — those are things that back then almost never happened,″ Setubal says.

João Carlos Setubal is a bioinformatics researcher at the University of São Paulo, Brazil.Credit: Aldrey Olegario

Lindow says the project ″changed the field″ by providing key insights into the complex genomics and metabolism of pathogens such as X. fastidiosa, which have to survive both their plant host and an insect vector. The fact that such a discovery came from Brazilian scientists was a bonus, he says.

″Before that genome, there were very few research papers from Brazil,″ adds Leonardo De La Fuente, a plant pathologist at Auburn University in Alabama, who was born in Uruguay. ″That motivated a lot of people to work more in biology.″

Continue reading at https://www.nature.com/articles/d41586-023-00794-8