Levi-Montalcini, Rita (b. 1909)

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Levi-Montalcini, Rita (b. 1909)

Italian-born medical doctor and neurobiologist who won the Nobel Prize for her discovery of Nerve Growth Factor. Name variations: Rita Levi Montalcini. Born Rita Levi in Turin, Italy, on April 22, 1909; youngest of four children of Adele (Montalcini) Levi (a painter) and Adamo Levi (an electrical engineer and mathematician); twin sister of Paola Levi-Montalcini (an artist); sister of Gino Levi (d. 1974), an architect and professor at the University of Turin; graduated Turin School of Medicine, summa cum laude degree in Medicine and Surgery, 1936, granted advanced degree in neurology and psychiatry, 1940; never married; no children; became a U.S. citizen in 1956.

Awards:

William Thomson Wakeman Award of the National Paraplegic Foundation (1974); Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research of Brandeis University (1982); Louisa Gross Horwitz Prize from Columbia University (1983); Albert Lasker Basic Medical Research Award (1986); Nobel Prize for Physiology or Medicine (1986); U.S. National Medal of Science (1987).

Her governess died (1929); admitted to the Turin School of Medicine (1930); her father Adamo Levi died (August 2, 1932); graduated from Turin School of Medicine (1936); fired from Institute of Anatomy (1938); fled to Belgium (1939); returned to Italy (1939); secretly resumed her research (1939); awarded degree in neurology and psychiatry, Turin School of Medicine (1940); read article by Viktor Hamburger (1940); Giuseppe Levi returned to Turin (1941); moved to the country (1942); hid from the Nazis in Florence (1943–44); worked in a refugee camp (1944–46); was reinstated by the Institute of Anatomy (1946); traveled to U.S. (1946); accepted position of research associate, Washington University (1947); promoted to associate professor (1951); undertook research at Institute of Biophysics, Rio de Janeiro (1952); Stanley Cohen joined research team (1953); discovered Nerve Growth Factor (1954); promoted to full professor (1958); death of Giuseppe Levi (1965); established research laboratory in Rome (1961); elected to U.S. National Academy of Sciences (1968); appointed head of the Cell Biology Laboratory of the Italian Council of National Research (1969); retired from Washington University (1977); retired from Italian Council of National Research (1979); jointly awarded the Nobel Prize for Physiology or Medicine with Stanley Cohen (October 13, 1986).

Selected publications:

"Les Conséquence de la destruction d'un territoire d'innervation peripherique sur le dévelopment des centre nerveuz correspondants dans L'embryon de poulet," in Archive de Biologie (1942); "Selective Growth Stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo," in Journal of Experimental Zoology (1951); "A Diffusible agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo," in Journal of Experimental Zoology (1954); "In vitro experiments on the effects of mouse sarcomas 180 and 37 on the spinal and sympathetic ganglia of the chick embryo," in Cancer Research (1954); "NGF: An uncharted route," in Paths of Discovery (1975); "The nerve-growth factor," in Scientific America (1979).

On October 13, 1986, Rita Levi-Montalcini become only the fourth woman ever to be awarded the Nobel Prize for Physiology or Medicine. Her ground-breaking research during the 1950s has been crucial to our understanding of the factors that control the growth of cells, their development, and their maintenance. The Nobel committee jointly awarded the Prize to Levi-Montalcini and Stanley Cohen.

Rita Levi-Montalcini was born in Turin, Italy, on April 22, 1909, the daughter of Adele Montalcini Levi and Adamo Levi, an engineer and factory manager. It was not until the beginning of her medical career that Rita Levi added her mother's maiden name to her own surname. The Levis were of Jewish ancestry, although the family did not regularly attend synagogue. As Levi-Montalcini recalled: "Father could not be considered an atheist or intolerant of those of different ideas from his own in matters of religion…. But he was certainly secular in the deepest sense of the word." Such attitudes often caused friction with more devout relatives.

Adamo Levi's belief that the man was the head of the family and that a professional career would interfere with a woman's duties as wife and mother had a profound impact on his daughter.

My experience in childhood and adolescence of the subordinate role played by the female in a society run entirely by men had convinced me that I was not cut out to be a wife. Babies did not attract me, and I was altogether without the maternal sense so highly developed in small adolescent girls.

Though Rita Levi-Montalcini displayed an aptitude for scholarship as a student, she received a typical Victorian education which did not prepare young women for university. "Our father decided that we should attend middle school and then the girl's high school—from which, in those days, there was still no possibility of going to university," she wrote. "The girl's high school differed from the boy's not so much in the teaching of languages and literature as in the training in mathematics and the so-called exact sciences."

In 1929, the death of Levi-Montalcini's governess Giovanna proved to be a turning point; she decided to study medicine. Her father was skeptical and expressed his belief that a professional career was unsuitable for a woman. He concluded, however, that "if this is really what you want, then I won't stand in your way, even if I'm very doubtful about your choice." After a summer of rigorous private tutoring in Latin, Greek, history, mathematics, and philosophy, Levi-Montalcini passed the entrance examination for the Turin School of Medicine and was admitted as a student in 1930.

Her mentor at the University of Turin was Dr. Giuseppe Levi, a well-known specialist in anatomy and histology. In describing "the extraordinary personality of the master," Levi-Montalcini wrote that he was "celebrated in Turin University for his reputation as a scientist, for the anti-Fascism he professed," and for his "terrible but short-lived fits of rage." She and Levi soon became friends, a friendship which would last until Giuseppe's death in 1965.

In 1928, Giuseppe Levi began research into the growth of nerve cells in vitro. His interest was sparked by the research of Ross Granville Harrison, who had pioneered the field in 1907. In the summer of 1936, Levi-Montalcini graduated from the Turin School of Medicine and began working as Giuseppe Levi's assistant in neurological research. Neurology became her chosen field of specialization, and in 1940 she obtained a degree in neurology and psychiatry. But the rise of Fascism under Benito Mussolini threatened her career. In 1938, when a government decree expelled all Jews from Italian universities and forbade them to practice medicine, Levi-Montalcini was fired from her position at the Institute of Anatomy. Following Giuseppe Levi's lead, she fled to Belgium in March 1939. There, she resumed her research at the Neurological Institute in Brussels. The imminent invasion of Belgium in 1939, however, forced her to return to Italy. In Turin, she began to practice medicine clandestinely, but soon found it impossible to secure prescriptions for her patients.

Instead, Levi-Montalcini secretly resumed the neuroembryological research she had begun in Brussels. With her family's consent, she assembled what she described as "a private laboratory à la Robinson Crusoe" in their small apartment. "The instruments necessary for the realization of this project were few," she wrote, "a small thermostat … a microtome … a stereomicroscope … and surgical instruments." Using chicken embryos, she studied the effects which the removal of peripheral nerve tissues had upon the development of motor cells in the spinal cord and the ganglia.

In 1940, Levi-Montalcini happened upon an article written by Viktor Hamburger of Washington University. In it, Hamburger argued that growing nerve fibers were guided to organs by the organs themselves. Hamburger's article became her "bible and inspiration." When Giuseppe Levi returned to Turin in 1941, after evading capture by the Nazis, he immediately began to assist Levi-Montalcini with her experiments.

With the systematic bombing of Turin increasing nightly, Levi-Montalcini and her family moved to a small farm in the fall of 1942. Giuseppe Levi was a frequent visitor. There, she continued her research and discovered that the cells of the central nervous system in the initial stage of differentiation moved "toward distant locations along rigidly programmed routes." The question, however, still remained. Why? In light of her discovery, she concluded that cell growth functioned in a substantially different way than the medical literature of the day suggested.

With the arrest of Mussolini on July 25, 1943, the tyranny of the Fascists seemed to be at an end. The Allied invasion of Italy, however, prompted Hitler to send in the German army. Levi-Montalcini made an attempt to escape to Switzerland, but the Germans sealed the border. The entire family traveled south in the hope of crossing Allied lines. Unforeseen circumstances led to a prolonged stay in Florence, where the family hid until the liberation of the city in 1944. Following the end of hostilities, Rita Levi-Montalcini worked as a doctor in the refugee camps. She described the episode as her "most intense, most exhausting, and final experience as a medical doctor." After the war, she returned to Turin and was reinstated at the Institute of Anatomy.

In 1946, the work of Levi-Montalcini came to the attention of Hamburger, who had read an article jointly written by Levi and Levi-Montalcini in 1942. Although Hamburger did not agree with her thesis that the programmed death of nerve cells influence the development of the central nervous system, he invited her to spend a semester in the United States. What began as a short stay turned into a sojourn of 30 years. Many years later, Levi-Montalcini still fondly recalled her first impression of St. Louis.

I marvelled for the first time at the splendid autumnal colours of the leaves in the setting sun, which have no parallel to the dull tones of the trees in the hills around Turin during the same season…. I still link that amazing spectacle with the recollection of my first contact with Washington University and the Midwest.

In 1947, Levi-Montalcini became a research associate in the department of zoology. She was plagued by doubts about her research, however, and soon after her arrival recalled being struck by the idea that "the discovery of migrator and degenerative processes affecting nerve cell populations at the early stages of their development might offer a tenuous yet valid path to follow into the fascinating and uncharted labyrinth of the nervous system."

One of her first tasks was to recreate an experiment performed by Elmer Bueker. It involved the transplantation of a cancerous mouse tumor into a chick embryo. The central nervous system of the embryo reacted by sending out masses of nerve fibers. Originally, Levi-Montalcini and Hamburger concluded that the nerve fibers had synchronized their growth rate to conform with that of the tumor. Soon, however, she hypothesized that the tumor itself was releasing a mysterious substance which was influencing the growth of the nerve fibers.

Embryological procedures of the day were slow and painstaking. In order to unravel the chemical composition of the mysterious compound, Levi-Montalcini turned to the developing science of tissue cultures. She traveled to the Institute of Biophysics in Rio de Janeiro to learn the technique in 1952. In Brazil, she worked with her old friend Herta Meyer . By the time Levi-Montalcini returned to the United States, the possibility of identifying the compound was within reach.

She teamed up with biochemist Stanley Cohen to conduct a new series of experiments. They extracted large quantities of what became known as "Nerve Growth Factor" from snake venom and mouse saliva. By experimenting on tissue cultures, Levi-Montalcini demonstrated that the substance manufactured by the tumor could induce nerve fiber growth. She presented her findings to a conference held by the New York Academy of Sciences in 1954. Nerve Growth Factor was the first growth factor to be isolated by science.

The experiments conducted by Levi-Montalcini and Cohen, between 1953 and 1959, formed the basis of Cohen's discovery of another growth agent, Epidermal Growth Factor. It was not until 1970, however, that Nerve Growth Factor was completely analyzed by Ralph Bradshaw, Ruth Angeletti , and William Frazier at Washington University.

In 1961, Levi-Montalcini returned to Italy and established a research facility in Rome with Pietro Angeletti. Their research was jointly funded by Washington University, where Levi-Montalcini was now a full professor. The project also offered her the opportunity to reunite with her family.

In 1968, Levi-Montalcini was elected to the U.S. National Academy of Sciences, only the tenth woman to be honored by this prestigious body. A year later, she established the Laboratory of Cell Biology for the Italian Council of National Research and became its director, dividing her time between the U.S. and Italy. In 1977, she retired from Washington University; she also retired from the Council of National Research in 1979, but retained the position of guest professor.

On September 22, 1986, she and her colleague Stanley Cohen were awarded the Albert Lasker Medical Research Award. A few weeks later, on October 13, the Kalolinska Institute for Medicine in Stockholm announced that Rita Levi-Montalcini and Stanley Cohen were that year's recipients of the Nobel Prize for physiology or medicine. By coincidence, the surprised Levi-Montalcini was in Sweden, attending a scientific conference. As she remembered: "I gave a talk at a neuroscience meeting in Stockholm and everyone was kind to me, but there was no mention of a Nobel Prize." The Nobel committee praised the discovery of Nerve Growth Factor: "As a direct consequence we may increase our understanding of many disease states such as developmental malformation, degenerative changes in senile dementia, delayed wound healing and tumour diseases."

The Nobel committee also noted that the discovery of Nerve Growth Factor was of decisive importance in furthering research into Parkinson's disease, Alzheimer's disease, Huntington's disease, and cancer. Nerve Growth Factor may hold important clues to the basic structure of cancer cells. As Harold M. Schmeck of The New York Times noted, Levi-Montalcini's work offers scientists a glimpse into one of the fundamental processes of human development:

Before her discovery, scientists had few clues to the complicated process by which embryonic nerve cells developed into a network of nerve fibers that pervade the entire body. Today it is known that nerve growth factor is central to this process. The substance exists in mammals, birds, reptiles, amphibians and fishes.

The discovery of Nerve Growth Factor resulted in the identification of many other growth factors, including Colony Stimulating Factors, Platelet-Derived Growth Factor, Fibroblast Growth Factor, the Interleukins, and Cohen's Epidermal Growth Factor. It has been demonstrated that Nerve Growth Factor is a substance manufactured by various target tissues. Unlike Hamburger's original thesis, which postulated that organs guided nerve growth, Nerve Growth Factor is now recognized as an essential guide of nerves to their destination. Rita Levi-Montalcini's discovery has therefore shed important new light on the chemical processes of embryonic development.

In 1987, Levi-Montalcini was awarded the National Medal of Science, the United States' highest award for scientific excellence. As well, she is a member of the Belgian Royal Academy of Medicine, the National Academy of Sciences of Italy, the Pontifical Academy of Sciences, and the European Academy of Sciences, Arts, and Letters. Numerous institutions have granted her honorary degrees, including the Weizmann Institute of Science, the University of Uppsala, the Washington University School of Medicine, and St. Mary's College.

As she turned 90, Rita Levi-Montalcini made her home in Rome. Described by Tyler Wasson as "a vivacious, elegant woman who is warm and considerate in her associations with co-workers and friends," she shared an apartment with her twin sister, Paola Levi-Montalcini , a well-known artist.

sources:

Kass-Simon, G. "Biology is Destiny," in Women of Science: Righting the Record. G. Kass-Simon and Patricia Farnes, eds. Bloomington: Indiana University Press, 1990.

Marx, Jean L. "The 1986 Nobel Prize for Physiology or Medicine," in Science. NY: American Association for the Advancement of Science, October 31, 1986.

Schmeck, Harold M. "Two Pioneers in Growth of Cells Win Nobel Prize," in The New York Times. October 14, 1986.

Wasson, Tyler. Nobel Prize Winners: An H.W. Wilson Biographical Dictionary. NY: H.W. Wilson, 1987.

Who's Who in the World. Wilmette, IL: Marquis, 1990.