Rita Levi-Montalcini

Abstract

Developmental biologist and discoverer of nerve growth factor. Born in Turin, Italy, on April 22, 1909, she died in Rome on Dec 30, 2012, aged 103 years. Rita Levi-Montalcini's discovery of nerve growth factor (NGF) is a saga of determination to overcome hurdles that were personal and social as well as scientific. Although born to educated and loving parents, she had to defy her father's conservative views on the role of women before she could enrol for a higher education. On graduating in medicine from the University of Turin in 1936, Levi-Montalcini began to specialise in neurology. At this point her career was derailed by Mussolini's laws that prohibited Jewish people from taking academic jobs. She spent a brief period in Brussels, but returned to Turin in 1940 and set up a small lab at home in her bedroom. Allied bombing drove her out of Turin, and she moved her home and her lab first to a country cottage, and subsequently to Florence. After the liberation of that city in 1944 she practised medicine in a refugee camp, tackling epidemics of typhus and other infectious disease. In 1947, 2 years after she'd finally returned to Turin, embryologist Professor Viktor Hamburger of Washington University invited her to join him in St Louis to repeat some of his earlier developmental experiments involving the removal of limbs from chick embryos. Although she went intending to stay only for a year, the success of her work kept her there until 1977. Back in Italy she continued her research, and remained scientifically active until her death. It was the repetition of Hamburger's chick experiments that led to the discovery of NGF. Hamburger had shown that removing the limbs of chick embryos interfered with the growth of the nerves that were intended to innervate them. He drew the reasonable conclusion that this represented the loss of some attractive factor which would have been released by the tissue to be innervated. Levi-Montalcini repeated his experiments using a silver-staining technique to examine the nerves. “Rita's interpretation was different from Hamburger's, and she turned out to be right”, says Michel Goedert of the MRC Laboratory of Molecular Biology in Cambridge, UK. “She postulated instead that under normal circumstances something is produced to prevent nerve cells from dying. She set out on a quest to purify this factor.” In trying to isolate it she had several strokes of luck, including the choice of an experimental model that depended on grafting mouse tumour cells into chick embryos. Equally fortuitous was her selection of a colleague, biochemist Stanley Cohen, who went on to share the 1986 Nobel Prize in Physiology or Medicine with her for their discovery of growth factors. The clinching demonstration of the importance of the newly discovered protein—a “beautiful experiment”, to use Goedert's adjective—came out of making antibodies against it. “When they injected anti-NGF antibody into newborn mice they found that the whole of the sympathetic nervous system was wiped out. It proved beyond any doubt that NGF was physiologically essential for the functioning of the vertebrate nervous system”, Goedert explains. The scepticism that had greeted Levi-Montalcini's early claims was understandable, Goedert adds. Scientists were familiar with hormones: proteins made in a particular tissue and released into the blood system. “But this was something quite different: a protein produced by a given tissue and not released but acting locally to promote the growth of cells.” Clinically NGF has not yet proved as valuable as originally hoped. But this in no way detracts from the scientific importance of Levi-Montalcini's insight into what is now seen as a fundamental component of the biology of normal development and of disease processes including cancer. Maria Grazia Spillantini, now Professor of Molecular Neurology at the University of Cambridge, met Levi-Montalcini in 1982 as a young graduate seeking a fellowship, and then collaborated with her on and off over the next 30 years. “When I went to see her for the interview she sat with me as if I was an equal”, she recalls. Like everyone she was also struck by Levi-Montalcini's striking grand dame appearance. “Although she was passionate about science she was also very feminine”, says Spillantini. “She dressed very elegantly and had beautiful jewellery. She designed some of it herself.” After the Nobel Prize Levi-Montalcini was elected to the Italian Senate, and was a regular attendee, not least during discussions on the funding of science. She never married, but remained close to her sister Paola, a shy and retiring woman, quite unlike Levi-Montalcini herself.