Rita Levi-Montalcini, PhD, a Nobel Prize-winning neurobiologist who performed the majority of her research at Washington University in St. Louis from 1947-1977, died Sunday, Dec. 30, at her home in Rome. She was 103.
Levi-Montalcini discovered nerve growth factor, a cellular “factor” that the body uses to direct the growth of nerve networks. In 1986, Levi-Montalcini shared the Nobel Prize in physiology or medicine with biochemist Stanley Cohen, PhD, also of Washington University, who helped her identify the factor.
Hundreds of growth factors are now known to exist and they affect almost all facets of biology.
In her autobiography, In Praise of Imperfection: My Life and Work, Levi-Montalcini described her years at Washington University as “the happiest and most productive years of my life.”
Levi-Montalcini was born in Turin, Italy, to parents who didn’t want their daughters to pursue college educations.
“It was a very patriarchal society, and I simply resented from early childhood that women were reared in such a way that everything was decided by the man,” she told Marguerite Holloway for a 1993 profile in Scientific American.
When her governess died of stomach cancer, Levi-Montalcini decided to become a doctor, graduating summa cum laude in 1936 from the Turin School of Medicine.
In 1938, Mussolini issued a manifesto barring non-Aryan Italians from professional and academic careers. Levi-Montalcini left the university and continued her research in a laboratory she set up in her bedroom.
She would bicycle to neighboring farms to buy fertilized chicken eggs, she said in an autobiographical essay she wrote for the journal Science in 2000. She told the farmers the eggs were “for her babies” because they were “more nutritious” than unfertilized eggs.
In 1943, Italy switched allegiance to the Allies and the Germans invaded northern Italy. Levi-Montalcini and her family fled to a farm near Florence and went into hiding for the rest of the war.
This period of her life (1940-1945) appears on an early typewritten curriculum vitae in Washington University’s Archives as work for a “private laboratory.”
Work in St. Louis
Levi-Montalcini’s studies of chick embryos were given a new direction when she read a 1934 paper by Viktor Hamburger, PhD, considered the father of developmental neuroscience. In 1935, Hamburger began a nearly 50-year tenure at Washington University, including 25 years as chairman of the zoology department, later renamed the Department of Biology.
Hamburger held that the growth and differentiation of nerve cells depended on some inductive agent emanating from their destination. To test this hypothesis, he removed developing limb buds from chick embryos to see whether nerve cells near the spinal cord would still grow toward the limb.
When the limb buds had been removed, the embryonic nerve cells (motor ganglia) were fewer in number. He concluded that they failed to grow because the limb was not producing an organizing factor on which they depended.
Repeating the experiments in her makeshift laboratory in Turin, Levi-Montalcini made similar observations, but reached a different conclusion. Studying the nerve cells at more frequent intervals, she noted that they did proliferate initially, but then died because the limb bud was not producing some sort of growth factor needed for their maintenance.
Hamburger read one of the papers Levi-Montalcini co-authored during the war and, in 1946, invited Levi-Montalcini to come to St. Louis for a semester so that they could re-examine the problem together. Instead of staying for a semester, she was to remain with the university for more than 30 years.
It took several years to isolate and identify the growth factor. Hamburger thought other rapidly growing tissues, such as a tumor, might produce growth factors and this turned out to be the case.
Trip to Rio de Janeiro
But Levi-Montalcini knew she needed a simpler system than a mouse with an attached tumor to track down the mystery factor. In an episode that is famous in some quarters, she put “two live, tumor-riddled white mice into her handbag” and flew to Rio de Janeiro where a scientist she trained with in Turin was running a big tissue-culture lab.
While she was in Rio, Stanley Cohen, PhD, a biochemist, was recruited to the group to help characterize the factor. Hamburger, according to a 1987 profile in Washington University Magazine, “felt that the subtleties of biochemical analysis were beyond him and bowed out early.”
Return to St. Louis
Within a few years, Cohen had narrowed the candidates down to a mixture of a few proteins and nucleic acids (the chemical units from which DNA is made). To figure out which type of chemical was biologically active, he added snake venom to the mixture, which should have destroyed any DNA in it.
To his surprise, the mixture was more — rather than less — active when the venom was added. Snake venom, it turned out, contained high levels of nerve growth factor. Cohen guessed that mammalian salivary glands, which are homologous to the venom glands of snakes, might also prove to be a rich source of the factor. This also turned out to be the case.
By 1959, Cohen and Levi-Montalcini had developed an anti-serum to purified nerve growth factor. The anti-serum wiped out parts of the nervous system when injected into newborn mice, but there still was little recognition in the science community of the importance of the work.
Return to Italy
In 1962, Levi-Montalcini became director of the Institute of Cell Biology in Italy, splitting her time between St. Louis and Rome.
Louis “Pepper” Dehner, MD, a pathologist at Washington University’s School of Medicine, did his senior project with Levi-Montalcini during this period. “She was a small person physically, but when she arrived from Italy and hit the front door of Rebstock Hall, everyone that was in that building knew it,” he told Michael Purdy, a Washington University writer. “She was a force of nature.”
“It was the scent of Chanel No. 5 that gave her away,” said Gar Allen, PhD, then a graduate student and now professor of biology. Always elegantly dressed, Levi-Montalcini sewed her own clothes.
In 1971, Ralph Bradshaw, Ruth Angeletti and William Frazier of Washington University’s School of Medicine finally sequenced nerve growth factor.
Levi-Montalcini retired from Washington University in 1977, but continued her scientific work in Italy well into her final years.
She was at home in Rome reading Agatha Christie’s Evil Under the Sun when the Nobel committee called to tell her she and Cohen had won the prize. “I was happy about it, but I wanted much more to know the end of the story,” she told Marguerite Holloway in jest.
The committee’s decision to exclude Hamburger from the award aroused considerable controversy and two of Hamburger’s former colleagues argued in Trends in Neuroscience that his initial observations and experimental model provided the foundation for the later work.
Levi-Montalcini published her autobiography, In Praise of Imperfection: My Life and Work, in 1988.
In 1997, Rita and her twin sister, Paola, who was an artist and sculptor, were featured in a science documentary called Death by Design: The Life and Times of Life and Times that focuses on the study of cells but also incorporates animation, footage from old Hollywood films and Paola’s art.
“Rita and Paola were very close, sharing an artist’s eye for detail as well as an overarching sense of pattern,” Allen said.
“When Levi-Montalcini was appointed to the Pontifical Academy by Pope Paul VI, the protocol required her to kneel and kiss the Pope’s hand,” said Tom Woolsey, MD, the George H. and Ethel R. Bishop Scholar in Neuroscience at the School of Medicine. “Rita said, ‘I simply stood and shook the Pope’s hand.’
“In her independence and determination, she was a model for all scientists,” he said.