Flight from Vienna
Ruth Sonntag was born in Vienna on June 20, 1928, the daughter of two Jewish physicians, Baruch (Barouch) and Eugenia Sonntag. Her father was not religious. When Nazi Germany annexed Austria in March 1938, he was imprisoned. While Ruth’s mother was waiting in line to visit him in prison, she was recognised by a prominent Austrian Nazi whom her husband had once helped, and the man arranged for his release.
The family escaped on a harrowing train journey to Belgium, where they hid until 1939, when they were able to emigrate to Brazil and settle in São Paulo. Ruth was ten when she left Vienna. She finished school in Brazil and grew up a Brazilian, a refugee who never forgot what it meant to be driven out of a country.
A partnership born in São Paulo
Ruth studied medicine at the University of São Paulo, where she became involved in left-wing student politics and met a classmate, Victor Nussenzweig. He became her husband, her lifelong companion and her scientific partner for more than 65 years. They were married in 1952 in, of all places, the library of the medical school’s parasitology department.
As medical students the couple studied Chagas disease, a parasitic infection common in Latin America that can be passed on through blood transfusions. In a 1953 paper they reported that the dye gentian violet killed the Chagas parasite in infected blood. On the strength of their work, gentian violet was adopted to treat blood intended for transfusion in Brazil and other Latin American countries, protecting patients from infection; it was a remarkable contribution from two people who were still students. Ruth graduated in 1953 and became an assistant professor of parasitology at the university. From 1958 to 1960 the couple worked in Paris, Ruth at the Collège de France.
Exile again
In 1963 the Nussenzweigs went to New York University on research fellowships, Ruth to the laboratory of the immunologist Zoltán Óváry and Victor to that of Baruj Benacerraf. They intended to return home. But after the military coup of 1964, conditions at the University of São Paulo became impossible: many friends and colleagues were jailed by the new regime, and Victor was singled out for questioning by the school’s military-appointed administration. Through Benacerraf’s help both obtained assistant professorships at NYU, and in 1965 they moved to the United States for good. Ruth returned briefly to São Paulo to defend her doctoral thesis, receiving her PhD in 1968.
For the second time in her life politics had forced her to start again in a new country. She would spend the rest of her career at NYU, becoming a full professor in 1972.
The 1967 breakthrough
Malaria is caused by Plasmodium parasites, passed to people by the bite of infected mosquitoes. The mosquito injects a form of the parasite called a sporozoite, which travels to the liver, multiplies, and then invades red blood cells, causing fever, anaemia and, especially in young children, death. Before the 1960s there was little or no evidence that people could ever be completely protected against malaria by a vaccine.
In 1967 Ruth Nussenzweig and her colleagues reported in Nature that mice could be protected against a rodent malaria parasite, Plasmodium berghei, by immunising them with sporozoites that had been weakened with X-rays. The irradiated parasites could not cause disease, but they trained the immune system to stop live ones. Inspired by her report, by 1974 two research groups, one including NYU scientists, had shown that humans could be protected by exposure to mosquitoes carrying irradiated sporozoites of Plasmodium falciparum, the deadliest human malaria parasite. For the first time a malaria vaccine looked possible.
Finding the target
Ruth and Victor then set out to discover what, exactly, the immune system was recognising. In 1980 they and their colleagues reported that an antibody against the main protein on the surface of the sporozoite protected mice from malaria. They named it the circumsporozoite protein, or CSP. The finding, wrote the malaria vaccine researcher Stephen Hoffman, launched a scientific revolution in malaria molecular biology and vaccine research. In 1984 the NYU team was one of two groups that published the gene sequence of CSP, and a few years later NYU was again one of two groups to show that a vaccine based entirely on CSP could protect people against malaria infection.
Her team went on to describe the immune mechanisms behind protection, showing that antibodies and immune cells both play a part, and created reagents that field researchers used to study how malaria spreads.
Vaccines for Africa’s children
The first malaria vaccine to be widely used, RTS,S (Mosquirix), developed by GlaxoSmithKline, is built on the circumsporozoite protein that the Nussenzweigs identified: it fuses part of CSP with a hepatitis B virus protein to provoke a strong immune response. A São Paulo immunologist who worked with the family said simply that the RTS,S structure would not have been possible without the gene structure of CSP. The World Health Organization recommended RTS,S for children in 2021, and in 2023 recommended a second vaccine, R21/Matrix-M, which is also based on CSP. Dozens of African countries are adding malaria vaccines to their childhood immunisation programmes. Malaria still kills nearly half a million children in Africa every year, and WHO’s regional director for Africa has said that, rolled out widely, the vaccines can help save hundreds of thousands of young lives.
Her other line of work also continues. A vaccine made from radiation-weakened sporozoites, the direct descendant of her 1967 experiment, is being developed by the company Sanaria. As Hoffman put it, the vast majority of all humans ever protected against malaria by a vaccine have been protected by vaccines based either on CSP or on whole sporozoites, both of which stem from the Nussenzweigs’ seminal reports of 1967 and 1980.
Leader and teacher
In 1976 Nussenzweig became head of the Division of Parasitology at NYU, and in 1984 she was appointed chair of the new Department of Medical and Molecular Parasitology, a post she held until 2002. She was the first woman ever to chair a department at NYU School of Medicine. She trained scores of students and fellows from around the world, many from Brazil, and many became leaders in the field. Colleagues described her as extremely persistent and compelling, someone who could convince researchers, company directors and politicians alike that a malaria vaccine had to be made.
She published more than 230 scientific papers. Her honours included the Paul Ehrlich and Ludwig Darmstaedter Prize, the Albert B. Sabin Gold Medal, the Warren Alpert Foundation Prize (shared in 2015 with Victor and the Chinese scientist Tu Youyou), and in 2017 the first Clara Southmayd Ludlow Medal of the American Society of Tropical Medicine and Hygiene. In 2013 she became the first Brazilian scientist elected to the US National Academy of Sciences.
She was a prolific and determined scientist. Between 1967 and 1970 alone she published papers in Nature in four successive years, and she remained an active member of the American Society of Tropical Medicine and Hygiene for more than half a century after joining in 1965. The whole-sporozoite approach she pioneered has been hard to turn into a practical vaccine, and some recent studies have found its protection lower than hoped, but she and Victor kept testing new ideas into their eighties, including a vaccine candidate against Plasmodium vivax developed with Brazilian colleagues.
A Jewish refugee’s life
Nussenzweig’s life was shaped by two exiles: from Nazi-ruled Austria as a Jewish child, and from military-ruled Brazil as a young scientist. Her parents were secular Jewish doctors, and the family survived because of a chance act of gratitude and a dangerous escape across Europe. She carried the refugee’s sense of displacement and loyalty to the countries that took her in; she missed Brazil all her life, and from about 2012 she and Victor spent months each year doing research at the Federal University of São Paulo, working on a vaccine against Plasmodium vivax, the malaria parasite most common in the Americas.
Science ran in the family. Her husband Victor is a professor emeritus at NYU; her son Michel Nussenzweig is a professor at Rockefeller University; her son André is a distinguished investigator at the US National Institutes of Health; and her daughter Sonia Nussenzweig Hotimsky is an anthropologist in São Paulo.
Death and legacy
After a serious fall left her in poor health for several years, Ruth Nussenzweig died of a pulmonary embolism in New York on April 1, 2018, at the age of 89. She was survived by Victor, their three children and six grandchildren. She did not live to see the wide rollout of the vaccine her work had made possible; the following year, pilot programmes began giving RTS,S to hundreds of thousands of infants in Ghana, Kenya and Malawi.
For most of history malaria was considered impossible to vaccinate against. Ruth Nussenzweig proved otherwise in a mouse experiment in 1967, then spent half a century finding out why it worked and pushing the world to build on it. Every child in Africa who receives a malaria vaccine today is protected by a line of research that began in her laboratory.
Sources & further reading
In Memoriam: Ruth S. Nussenzweig, MD, PhD (obituary by Stephen L. Hoffman), American Society of Tropical Medicine and Hygiene · The malaria vaccine pioneer, Pesquisa FAPESP · Ruth Nussenzweig, Malaria Researcher, Dies, The Scientist · WHO recommends R21/Matrix-M vaccine for malaria prevention, World Health Organization · Ruth Sonntag Nussenzweig, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.