SÃO PAULO, Brazil - It has no laboratories or research teams of its own, only a modest administrative staff working out of a nondescript building in a residential neighborhood here. But through canny management and careful choices, the Research Support Foundation of the State of São Paulo is rapidly becoming a powerhouse in genomics and a model for scientific investigation in the third world.
Last July, a Brazilian consortium organized and financed by the foundation became the first anywhere to decode the genome of a plant pathogen, Xylella fastidiosa, an insect-borne bacterium that infests oranges. A few months later, the foundation, known as Fapesp, announced that the consortium had completed the genetic sequence of a second pest that plagues this country's thriving fruit export industry, Xanthomonas citri, or citrus canker.
"From the moment we began, our objective has always been the same: to work on the frontiers of science while addressing issues of social and economic relevance," Dr. José Fernando Pérez, the foundation's scientific director, said in an interview here. "The genome project has served that purpose and created an image of leadership for us."
Indeed, Fapesp's twin successes have not only established its international reputation but also led to important collaborations, including one with a group that is sequencing human cancer genes, financed in part by the Ludwig Institute in Switzerland. In another unusual turnabout, the United States Department of Agriculture recently contracted Fapesp to sequence the gene of a bacterium that afflicts vineyards in California. "What they are doing is science of the highest quality, comparable to anything that is being done at the largest sequencing centers in the United States or Europe," Dr. Claire Fraser, president of the Institute for Genomic Research in Rockville, Md., said in a telephone interview. "As a result, they have really become recognized as an important player in the field, making a major contribution to the international genome effort."
Increasingly, Fapesp's accomplishments are also making it the standard for scientific research in the third world. In an editorial last year, the magazine Nature called the genome work here "a political as well as a scientific achievement" that refutes the "common misconception that only advanced industrialized nations have the wherewithal and skilled human resources needed to achieve cutting edge science." The foundation's rise to prominence is just one of several recent signs of the advance of Brazilian science, in which the government, through a cabinet-level Ministry of Science and Technology, and the private sector have begun to invest. In March, for instance, Brazil became the first country in the developing world to clone an animal, a calf named Vitória, or Victory.
Brazil has the largest commercial cattle herd in the world, more than 160 million animals, and Marcus Vinicius Pratini de Moraes, the minister of agriculture, said Brazilian research into cloning intended to "improve animal and plant health and technology," including the eventual development of cattle resistant to foot-and-mouth and mad cow disease. "This is the first step to gaining complete mastery of this technology," he said. Brazil's progress can also be measured in the increase in the number and variety of papers its scientists publish in international journals.
Brazil now accounts for 1.2 percent of scientific papers produced around the world, three times its rate of just 15 years ago, according to the Institute for Scientific Information, which tracks the number of papers produced around the world. Even more notably, since 1996 "the number of citations of Brazilian scientists has grown three times faster than the worldwide level," Ronaldo Sardenberg, the minister of science and technology, said in an interview in Brasília last year. "We are determined to do everything we can to encourage that process to continue because we realize that research is good business." A large part of Brazil's success, however, can be attributed directly to Fapesp, which has a degree of institutional autonomy rare in this part of the world.
Since the foundation began operations in 1962, state law has guaranteed it a fixed share, now 1 percent, of all the tax revenues collected in São Paulo, Brazil's richest and most populous state, with 37 million people. Along with federal contributions, that allows Fapesp to pump $270 million a year into research projects as diverse as a catalog of biodiversity and the syntax correction software used in the Portuguese-language version of Microsoft Word. Fapesp's charter states that it can spend no more than 5 percent of its budget on administration, preventing the political featherbedding so common in government agencies in developing countries.
The same statute also prohibits Fapesp from assembling its own corps of scientists, requiring it to work through some 50 university laboratories and research departments around the state. "I guess you would have to call us a virtual institute because we don't have our own research facility or programs," Dr. Pérez said. "We seek systematically to identify niches that are of strategic interest to the nation and then to encourage others to develop them." Though the genome projects have led Fapesp to apply for several patents and to open a clone bank, the research is not yet generating profits. If and when that happens, Dr. Pérez said he expected that gains would be divided according to Fapesp's usual formula: one-third to Fapesp, one-third to the participating institutions and one-third shared among the individual researchers.
Early on, Fapesp began to invest in training young scientists, offering scholarships for them to study abroad. But it was largely able to avoid the problem of brain drain by requiring beneficiaries to return to Brazil for at least four years and by guaranteeing them university teaching positions even before they left. "This program was extremely important to Brazil at the time because it allowed us to be trained in areas where we did not have competence," said Dr. Glaucius Oliva, director of the Center for Structural Molecular Biotechnology at the University of São Carlos, a Fapesp affiliate. "But you also had a signed contract that established a tie and made you a university employee, so that you would have to pay back the salary you had earned if you didn't return."
With only 80,000 researchers, compared with more than a million in the United States, Brazil is still struggling to develop a critical mass of scientists. "We have quality, but not quantity, because we lack the financial resources to train more researchers and create more research institutes," said Francisco Romeu Landi, Fapesp's director-president. But Fapesp has sought to diminish that handicap with an "induced research," which pushes scientists into areas it sees as most promising or important. It also stresses cooperation over competition. "If you have dozens of groups with dozens of researchers, it's fine to have a competitive model in which those who get the best and most rapid results get the financing," Dr. Oliva said. "But for developing countries with limited resources like ours, it's suicide."
Almost always, Brazilian science emphasizes projects that will produce a practical return, like the aeronautical programs that led to the formation of Embraer, which is now the world's fourth-largest aircraft manufacturer. Indeed, that was the motivation when Fapesp began its genome effort in 1997. "We were asking ourselves, what can we do to stimulate the formation of a biotechnology industry in this country," Dr. Pérez recalled. "The traditional answer would be to send a group abroad to be trained, but that is slow and expensive and doesn't guarantee success. So we decided to create not a single genome project, but to mobilize behind a series of efforts."
The initial success and experience gained with the plant pathogens have led to more ambitious efforts. Scientists supported by Fapesp and local sugar cooperatives, for instance, have just finished sequencing the genomes of sugarcane, one of Brazil's most traditional exports. "These research efforts are of great economic importance because Brazil is the leading world exporter of these products," Mr. Landi said. "If we can identify the genes of sugarcane and activate those which increase the index of sweetness and the rate of growth, we will increase productivity in the field." This year, 25 laboratories associated with Fapesp are to begin sequencing the genomes of the eucalyptus tree, cultivated here by a paper and cellulose industry because it grows faster than native trees.
The private sector will pay part of the cost. In March, Fapesp announced a plan to sequence the genes of the worm that causes schistosomiasis, a parasitic infection that afflicts millions. Fapesp officials also hope other genome projects will lead to the development of drugs to fight endemic tropical diseases like malaria, leishmaniasis and Chagas' disease. "I think that what Brazil has done is brilliant, because they have selected research projects that are important to them and the rest of the developing world but are low down on the list of priorities of funding groups" in the United States and Europe, Dr. Fraser said. "They have carved out a unique niche for themselves, making an important contribution in terms of their own economy, and in a sense regaining control of their own destiny."