An Italian and American biologist, Rita Levi-Montalcini (born 1909) discovered the nerve growth factor (NGF), a protein molecule that enhances differentiative processes of the sensory and sympathetic neurons and may exert a modulatory role on neuro-immuno-endocrine functions of vital importance in the regulation of homeostatic processes.
Rita Levi-Montalcini was born in Turin, Italy, on April 22, 1909. Together with her twin sister Paola, a renowned painter, she was the youngest in an upper-middle-class non-observant Jewish family which included a stern, industrialist father, a gentle but resourceful mother, a son, and three daughters, all of whom were gifted in either artistic or scientific pursuits. The profound gender inequality in her parents' household persuaded Rita (and Paola) that raising a family was incompatible with the devotion needed to pursue the call of creativity by a woman. The twin sisters were vindicated in their choice as each became famous in her respective career, while never regretting the choice of staying single. The close bond between them, as well as that between Rita and their mother, may have supplied a lifelong emotional reservoir, one which most people, creative or otherwise, seek to fill via the more conventional avenue of forming their own families.
In 1936 Levi-Montalcini obtained the M.D. degree, with distinction, from the University of Turin, and served there as an assistant in neurobiology in the clinic headed by the professor of anatomy Giuseppe Levi until 1938. Then the passage of the racial laws by the Fascist régime that barred Jews from Italian universities and other public institutions forced her to continue her research first in a Belgian laboratory and, after the outbreak of World War II, in a makeshift laboratory in her refuge home outside Turin. During the German invasion of northern Italy, she resided clandestinely in Florence (1943-1944), eventually becoming in 1944 a volunteer physician with the Allied Forces there. In 1945 she resumed her career as assistant to Professor Giuseppe Levi, who as an outspoken anti-Fascist scientist had also been in hiding during the war while working on the study of nerve cells grown in vitro.
In the fall of 1946, Levi-Montalcini arrived for a one-term research visit in the Department of Zoology at Washington University in St. Louis, Missouri, while responding to an invitation from its chairman, Professor Viktor Hamburger, a pioneer of experimental embryology. Hamburger had noticed her follow-up, in a paper published in 1939 during her stay in Belgium, of transplantation experiments in neuroembryology that he had published in 1934 while still in Germany as an assistant of Hans Spemann, an experimental embryologist who received the Nobel Prize in 1935. Hamburger, a refugee scientist from Nazi Germany who settled in St. Louis in 1937, suggested that they reinvestigate together the topic of the regulatory mechanisms governing the development and differentiation of motor and sensory nerve cells or, in experimental terms, the effects of amputation on the development of the nervous centers in charge of the innervation of the excised limbs in the chick embryo. Shortly after her arrival in Hamburger's laboratory, Rita observed in histological sections of chick embryos various differentiative processes of the nervous system, such as active migration, elimination, and separation of cell populations. These observations convinced her of the ultimate solvability of the then almost uncharted mechanisms of neurogenesis.
Inspired by the preliminary results of experiments with transplantation of neoplastic tissues, which a former student of Hamburger reported in a letter while seeking further advice, Levi-Montalcini focused her work on two tumors that had the capacity to greatly stimulate the proliferation of nerve fibers in host embryos. She eventually concluded that the effect was "radically different" than that observed following transplantation of normal limb buds or other embryonal tissues. She further deduced that the tumor exercised a neurotropic effect by releasing a humoral or fluid factor able to accelerate differentiative processes in sympathetic and, to a lesser degree, sensory cells, as well as to cause excessive and precocious production and abnormal distribution of nerve fibers.
In order to convince potential objectors of the humoral effect of neoplastic tissues on nerve cells, Levi-Montalcini decided to conduct these experiments in vitro. For that purpose she traveled to the Institute of Biophysics in Rio de Janeiro where a former collaborator of Giuseppe Levi, the German refugee Hertha Meyer, set up an in vitro culture unit. In Rio Levi-Montalcini conducted the experiments that would determine the direction of all her future research, while following the in vitro impact of tumor and non-tumor released humoral factors on proliferation and differentiation of cells of various origins.
The most exciting phase in Levi-Montalcini's research came upon her return to Hamburger's laboratory where the arrival of biochemist Stan Cohen as a research associate provided her with a like-minded collaborator. Their complementary skills enabled them in the following six years (1953-1959), especially after discovering that snake venom and mouse salivary glands were richer sources of nerve growth factor (NGF), to characterize NGF both biologically and chemically. Their further use of immunological methods demonstrated the fundamental role of NGF in differentiation and survival of sympathetic cells.
In 1961 Levi-Montalcini, who had become full professor at Washington University in 1958, began a commuting life divided between her newly established Center of Neurobiology in Rome and Washington University in St. Louis where she continued to teach. In 1969 the Italian National Research Council (CNR or Consilio Nazionale de la Richerche) transformed her research unit, previously attached to an Institute of Public Health, into an official CNR research center called the Laboratory of Cell Biology. In addition to neurobiology, it also included departments of cell biology, physiological genetics, and immunology. Between 1979, when Levi-Montalcini retired as director of this laboratory, and 1989, when she became guest professor at CNR's Institute of Neurobiology in Rome, she continued to work in the Laboratory of Cell Biology as a guest researcher.
Advances leading to an upsurge in NGF research in the 1990s include the identification and synthesis of the genes coding for murine and human NGF by means of recombinant DNA technology and genetic engineering. Other recent advances include the realization that the spectrum of action of the NGF molecule is not restricted to stimulating the differentiation of the sensory and sympathetic neuronal cell lines but also includes the hemopoietic-immune system, the cholinergic system of the basal forebrain nuclei, and other cell populations in the central nervous system involved in neuroendocrine functions.
The rise in the biological relevance of NGF in the 1980s also led, after a period of relatively modest reception, to a reevaluation of Levi-Montalcini's research in the 1950s. In 1986 she shared the Nobel Prize in physiology/medicine with Stan Cohen. Levi-Montalcini received honorary citizenship of many towns and cities, including Rome and Turin, and numerous awards in Europe and America, including membership in the U.S. Academy of Sciences (1968), the Pontifical Academy (1974), the Italian National Academy "dei Lincei" (1976), the Belgian Royal Academy of Medicine (1979), and the French Academy of Sciences (1989). She was also the recipient of many honorary degrees, from the University of Uppsala, Sweden; Weitzman Institute of Science, Israel; the University of London; the University of Brazil; and Harvard, among others. In 1987 she was awarded the highest honor for an American scientist, the national medal of Science.
Levi-Montalcini remains active in the scientific community, upholding status as professor emeritus at Washington University since 1977, as well as contributing greatly to scientific studies and programs in her native country of Italy. Since winning the Nobel Peace prize she has also been appointed president of the Italian Multiple Sclerosis Association. Levi-Montalcini also established fame as the first woman to attain full membership to the Pontifical Academy of Sciences in Rome. She still continues research at the Institute of Cell Biology in Rome. Along with her sister, they have established educational youth programs that provide counseling and grants for teenagers interested in the arts or sciences.
Further Reading
The best source on Rita Levi-Montalcini is her autobiography, In Praise of Imperfection, My Life and Work, translated by Luigi Attardi (1988). On her work, see her writings "NGF: An uncharted route" in F. G. Worden and others, editors, The Neurosciences: Paths of Discovery (1975), and "The Nerve Growth Factor: Its Mode of Action on Sensory and Sympathetic Nerve Cells" in The Harvey Lectures, Series 60 (1966). See also Viktor Hamburger, The Heritage of Experimental Embryology: Hans Spemann and the Organizer (1988). Additional information can be found in the series "New Hopes, New dreams" by Roger Rosenblatt Time (August 1996).
