Health

Malaria and Monogamy

Drs. Nussenzweig have only one love besides each other: the quest for a malaria vaccine.

June 20, 2008
Ruth and Victor Nussenzweig have battled malaria in the lab together for half a decade. [Photo courtesy of New York University]
Ruth and Victor Nussenzweig have battled malaria in the lab together for half a decade. [Photo courtesy of New York University]

In the next few years, prison volunteers were tested. Participants stuck an arm into a container to be bitten by hundreds of mosquitoes. Ruth had to sit that round out. As a woman, she was not allowed into the prison. Vanderberg found the results to be the same in humans. It worked. Dr. Steven Hoffman, a malaria expert and CEO of the biotechnology firm Sanaria Inc., said this work paved the way for all future malaria vaccine efforts. Sanaria is currently developing a malaria vaccine for clinical trials based on the early mosquito irradiation work at New York University.

“There had been work done on sporozoite immunity as far back as the 1940s,” he says. “But it was really the [New York University studies] in ‘67 and ‘68 that established the modern field of sporozoite immunity.”

The immunity was great, but the method was completely impractical. Irradiating endless batches of mosquitoes and exposing humans to possibly thousands of bites to build immunity is no way to run a vaccination campaign.

The Second-Favorite Parasite

The malaria parasite was not the first protozoan the Nussenzweigs had picked a fight with. They began medical school together at the University of Sao Paulo in Brazil. There were no undergraduate studies, so Ruth Sonntag and Victor Nussenzweig were only 18 years old when they enrolled in 1947. Ruth was born and raised in Vienna, Austria, before fleeing during the Nazi occupation in 1939. Eventually she and her family settled in Brazil.

Ruth was already hooked on medicine, but Victor was not. “At that time in Brazil there were really three major choices: law, engineering and medicine.” Victor remembers, “I chose by exclusion.”

Getting into medical school was competitive and each candidate had to take an oral exam in front of other potential students. “That’s the first time I saw Ruth,” Victor says with a smile. “I was impressed with her knowledge and her verve.”

Ruth is much more matter-of-fact about the entire episode. All of the Brazilian candidates were required to read the same books. Coming from Europe, she had the advantage of reading a range of ideas about physics and medicine that gave her a fresh perspective. “I just had a different solution,” Ruth concludes.

Victor was impressed by her knowledge, but not impressed with science overall. He spent his first two years of medical school talking politics, not biology. “I was involved in politics, mostly leftist politics,” Victor remembers, “but she convinced me it would be nicer to do research.”

By the third year of medical school they were dating. Ruth shared many of Victor’s democratic ideals, but thought he should focus on helping people through medicine instead of attending what she describes as “mostly useless political meetings.”

Politics gave way to protozoa, particularly Trypanosoma cruzi, which causes Chagas’ disease. The disease, which still kills about 50,000 people annually in Latin America, usually comes in the night, when a nocturnal triatomine bug carrying the parasite bites someone.

Unlike a mosquito, it is not the saliva but the insect’s feces that get into the wound and transmit the protozoa. There may not be any initial symptoms, but the disease can last 20 years and often leads to heart failure.

Ruth and Victor were inspired by a Russian research paper that suggested the Chagas’ parasite could treat tumors in cancer patients. They were able to devise a new method to harvest T. cruzi but their results were too variable. The Nussenzweigs would not cure cancer before graduating from medical school.

Instead, they began wondering if patients with chronic Chagas’ disease could transmit the parasite through blood transfusions, which most people believed was impossible. At that time, in some areas of Brazil and other South American countries, more than 20 percent of all blood donors were thought to have chronic Chagas’ disease. There was no reliable diagnostic tool.

Under the direction of their professor, J.L.P. Freitas, the Nussenzweigs found that, despite conventional thought, chronic Chagas’ disease patients could in fact transmit the parasite during transfusions. Ruth and Victor began looking for drugs that could be added to the blood to kill T. cruzi.

Eventually they found that a dye disarmed the protozoa. It did not take long for the dye to routinely be added to blood in transfusion bags. “So you saw those transfusion flasks hanging next to the bed, and it was blue,” Ruth remembers. “And there was no more transmission.”

Ruth and Victor joke that they may have peaked as third-year medical students. “The most important thing we did in our life, we did as medical students,” Victor says, only half-kidding. “That was definitely something that we did that was useful.”

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