Science (EUA) online

Fresh Start, Back in Brazil, at 85

Publicado em 25 junho 2013

Por Michele Catanzaro

Ruth and Victor Nussenzweig have reached a point in their careers when most scientist-couples probably would choose a well-deserved retirement. Based at New York University (NYU) in New York City, the Nussenzweigs, who are both 85—they have been married for 60 years—have already had long, successful, independent careers. While Ruth has focused on providing the basis for the development of a malaria vaccine, Victor concentrated on basic immunology, studying the structure and function of various immune components and the parasitology of malaria and Chagas disease. Their research merged into common projects on several occasions, leading, in one case, to the ongoing development of theRTS,S malaria vaccine by the PATH Malaria Vaccine Initiative and pharmaceutical giant GlaxoSmithKline. Between the two of them, the Nussenzweigs have published more than 500 papers.

The Nussenzweigs remain active at NYU and spend several months each year at the Federal University of São Paulo (UNIFESP) in Brazil. For the Nussenzweigs, working in Brazil means returning to their roots and supporting a country they were forced to flee early in their careers.

Fresh starts

Returning to Brazil is one of a string of fresh starts for the Nussenzweigs. Ruth, a nonreligious Jew, left Austria during the Nazi occupation, escaping to Brazil with her family in 1939. This is where she met Victor, a nonreligious Jew as well, who was born in Brazil. Both were 18 and starting medical school at the University of São Paulo. Since those early years, they’ve been inseparable in their personal and professional life.

Ruth knew from the start that she wanted a research career. "I was interested in research, and the only way of doing research was to go to medical school," she recalls. Her influence drew Victor to science. "At that time, I was more interested in doing leftist politics than science, but I started dating Ruth and she convinced me that research would benefit people much more than politics," Victor says.

The couple started doing research during medical school, working as close collaborators in the same lab. Part of this work focused on Chagas disease, a life-threatening illness caused by a parasite that, according to the World Health Organization, infects 7 to 8 million people worldwide. Together, they found that gentian violet dye kills Chagas parasites in transfusion blood without making the stained blood toxic. This led to one of their first papers, which was published in a Portuguese-speaking journal in 1953. Blue-tainted transfusion bags were still common in Latin America until a few years ago, when the decreasing costs and increased reliability of testing finally made it possible to routinely screen infected people.

The Nussenzweigs learned early to trust their scientific judgment and rely on each other. In those days and in that place, "we didn’t have a boss because there was no formal Ph.D. program. You chose your subject, did your research, and in the end you defended your thesis in front of professors: there was nobody to rule what you had to do," Victor says. He got his Ph.D. in 1957, 4 years after finishing medical school, but Ruth continued her thesis research until 1968. In the meantime, the two of them took assistant professorships, still in the faculty of medicine. They went to Paris with a research fellowship from 1958 to 1960, then returned to Brazil.

In 1963, the couple moved to NYU to work as immunology research fellows in the lab of Baruj Benacerraf (who shared the Nobel Prize in Physiology or Medicine in 1980 for his work on the role of genetically determined, cell-surface structures in the regulation of immune reactions). What was meant to be a temporary stay became permanent following the March 1964 coup d’état by the Brazilian military, which ushered in 2 decades of strict military rule and heavy censorship. "We went back to Brazil by the end of the postdoc, in 1965 … and found that all our friends were in jail for some reason," Victor recalls. "I was called by the new director of the school of medicine [at the University of São Paulo]. He was a colonel. He interrogated me and gave me orders. I was shocked, and I said to Ruth that we could not stay there."

The Nussenzweigs returned to NYU the same year. "First, I had to flee Austria, and then Brazil: All this was a lesson of survival that strengthened my resources and hardened my will to be a scientist," Ruth says. She went back to Brazil briefly, in 1968, to defend the Ph.D. thesis that she had developed mostly at NYU.

Complementary research

Ruth and Victor Nussenzweig celebrated a civil wedding in the library of the Faculdade de Medicina da University of São Paulo’s faculty of medicine.

In 1965, Ruth and Victor took assistant professor positions at the NYU School of Medicine and developed independent but intertwined research lines in vaccine development, basic immunology, and parasitology. In 1967, Ruth found that irradiating malaria-infected mosquitoes with X-rays weakened sporozoites, the form of the malaria parasite that is transmitted to humans during mosquito bites. She found that the weakened sporozoites triggered immunity against malaria instead of the disease, paving the way for a potential vaccine.

Victor was doing basic research on a component of the immune system called the complement system, but later he joined Ruth in her work on malaria vaccine. "She was so enthusiastic about that, and she told me: Maybe you could help to discover what is the main immunogen," Victor recalls. This common project was the core of their research for several years. A turning point was their joint discovery in 1980 that targeting a protein on the surface of the sporozoite (known as the CS protein) with antibodies hampered the parasite’s ability to cause infection. This is the basic principle behind the RTS,S vaccine, and while the clinical trial results have been somewhat disappointing, RTS,S is one of the few candidate vaccines to reach such an advanced stage.

As a woman in science, Ruth faced resistance at several points in her career, she says. "It was just not accepted that women could achieve something more," Ruth recalls. She believes that her two emigrations strengthened her resilience and helped her persist in the face of discrimination. "My advice to young women scientists is to love and be dedicated to their research. It is a hard career, but if you persist, it gives a lot of satisfaction." In 1984, Ruth became chair of the Department of Medical and Molecular Parasitology (now part of the Department of Microbiology) at NYU. Currently she is C.V. Starr Professor of Medical and Molecular Parasitology at the NYU Langone Medical Center. Victor is the Hermann M. Biggs Professor of Preventive Medicine at the same institution.

Closed circle

The Nussenzweigs maintained ties with Brazil throughout their careers, exchanging young researchers between their labs and Brazilian universities. These ties grew stronger in 2010 when Ruth and Victor started collaborating with Mauricio Rodrigues, an assistant professor in the Department of Microbiology, Immunology, and Parasitology at UNIFESP, working to develop a vaccine for a type of malaria produced by the parasitePlasmodium vivax, which affects an estimated 2.5 billion people. "The major [biological] problems of Plasmodium falciparum [the cause of the worst form of malaria and the target of the RTS,S vaccine] have been solved, while vivax is more complex, and it has spread in practically all the world except Europe," Ruth says. Together with Rodrigues, they submitted a patent for recombinant proteins that may be useful for a vivax malaria vaccine.

The Nussenzweigs gained the resources to go back to Brazil for 3 months a year when Victor won a 3-year São Paulo Excellence Chair from the São Paulo Research Foundation (FAPESP), in 2012. Victor is using the money to investigate the dormant phases of the Plasmodium (both falciparum and vivax) in the lab of Sergio Schenkman in the Department of Microbiology, Immunology, and Parasitology at UNIFESP. "Currently, I am fascinated by the fact that, during the cycle of malaria, there are stages in which the parasites are dormant … I am trying to understand what makes them rest and wake up again," he explains.

Helping to improve science in what both see as their home country is important to the couple. "FAPESP is putting a lot of effort, money, and good ideas to improve science in Brazil, and I want to support it," Victor says. But, he notes, that objective is not within easy reach. "When the military took over, they expelled a bunch of scientists and thought they could be easily replaced. But they were the best trained scientists, and … progress is very slow." Bureaucracy and a lack of incentives for scientists are also big problems in the country, Ruth adds.

A family story

While Ruth and Victor have worked closely together throughout their careers, they were careful to maintain some distance. "Working together for so many years is not easy, but being married so long is even more difficult!" Victor says jokingly. "There was one thing that helped: Ruth’s lab was six or seven blocks away from mine, so we could only fight at night." They became collaborators in their personal life, sharing chores and responsibilities at home, from cooking and cleaning to childcare.

While they were developing successful careers, Ruth and Victor raised a family of scientists: Michel, their eldest son, is a Howard Hughes Medical Institute immunologist at the Rockefeller University in New York City. Then comes Sonia, a professor of anthropology at Sao Paulo’s Foundation School of Sociology and Politics in Brazil. Finally, Andre, originally trained as a physicist, is working in molecular biology at the Center for Cancer Research in Bethesda, Maryland. "Science was a constant subject of conversation at home," Michel says. "We children saw that science was something that they truly enjoyed; this made it attractive for us, also."

"I think my parents love what they do, and I would suggest [that they] continue to work as long as they want and feel that they can contribute," Michel says. Indeed, retirement is not on their radar. Victor says, "I don’t like to speak of my legacy yet. I still continue to work, so there is still time to make a better contribution than before."

Michele Catanzaro is a freelance science journalist based in Barcelona, Spain.