Dr. Rita Levi-Montalicini, who won the Nobel Prize for Physiology or Medicine along with Stanley Cohen in 1986, for discovering nerve growth factor (NGF), died on December 30th 2012 at the age of 103. She was renowned not just for her contributions to the field of neurobiology, but also for her dedication to humanitarian causes, establishing the Rita Levi-Montalcini Foundation committed to the education of African girls and young women. In addition to overcoming the normal trials and tribulations faced by many successful scientific researchers, her story also involved overcoming both the fascism and sexual stereotypes prevalent during the 1900s. She writes in her autobiography – In Praise of Imperfection – that “If I had not been discriminated against or had not suffered persecution, I would never have received the Nobel Prize.”
Rita Levi-Montalcini and her twin sister Paola were born on April 22, 1909 in Turin, Italy to Adamo Levi and Adele Montalcini, Jewish Italians. From an early age, Levi-Montalcini was uncomfortable with the patriarchal society in which she was raised and the subordinate role women were expected to play in post-Victorian society. Women were not expected to pursue academic careers instead, “it was taken for granted that awaiting them was a career of being a good wife and mother.” So when Rita, aged 20, decided to study medicine following the death of her governess, Giovannina, from stomach cancer, she had to first convince her father.
Her autobiography is like reading a who’s who of the most influential scientists of the 20th century. She began her freshman year at the Turin school of Medicine in 1930 and the following year began an internship in the Institute of Anatomy with the histologist Giuseppe Levi. Among his other interns were Renato Dulbecco and Salvador Luria. Dulbecco, a name familiar to many cell biologists, formulated DMEM (Dulbeccos Modified Essential Medium) to support the growth of non-transformed mouse and chicken cells in vitro, and received the Nobel Prize in Physiology or Medicine in 1975, along with David Baltimore and Howard Temin, for their work in oncoviruses.
Salvador Luria received the Nobel Prize in Physiology or Medicine in 1969, with Max Delbrück and Alfred Hershey, for their discoveries on the replication mechanism and the genetic structure of viruses. One of Luria’s graduate students was James Watson, who with Francis Crick and Maurice Wilkins received the Nobel Prize for Physiology or Medicine in 1962, for co-discovering the structure of DNA (I would be remiss if I didn’t also mention Rosalind Franklin and Raymond Goslings here, who did not win the Nobel Prize).
During her time under the mentorship of Guiseppe Levi, Levi-Montalcini became adept at the technique of silver impregnation for staining nerve cells. This technique, which was to become essential in her studies of nerve fiber growth using chick embryos, was based on the techniques of two other Nobel Prize winning scientists: Camillo Golgi and Santiago Ramón y Cajal, who discovered the method of chrome-silver impregnation of nerve cells and the affinity of nerve cells for metallic salt, which allowed for their specific identification.
The 1930s saw a rise in anti-Semitism throughout Europe. The publication of the Manifesto of Race on 14th July 1938 essentially declared that Jews did not belong to the Italian race. It stripped the Jews of Italian citizenship and with it all the rights enjoyed by other Italians, including holding positions in government or education and attending or engaging in didactic activity in state schools. In October 1938, Levi-Montalcini was suspended from the academic position she held at the Institute of Anatomy and from the Neurology Clinic and deprived of her ability to practice medicine. At this time, she accepted an offer from Professor Laruelle, director of a neurology institute in Brussels, to continue her research in his lab. Fearing a German invasion of Belgium, she returned to Italy in December 1939.
Unable to attend any university institutes and without funding to continue her research, analyzing the development of the nervous system, she set up a small laboratory in her bedroom. Having assembled everything: one incubator for the chick embryos, another high temperature one for paraffin embedding the embryos, a microtome to cut the embedded tissue into sections, a stereomicroscope for operating on the embryos, a binocular Zeiss microscope, and the necessary surgical instruments, glassware and chemical reagents, she began to study how the excision of limbs from chick embryos affected the differentiation and development of nerve cells at the early stages of embryonic life.
Her results suggested that following excision of limbs, the growth of nerve fibers from the spinal cord proceeds normally and that their death is the result of the absence of a trophic factor normally released by the innervated limbs. This interpretation was contrary to that reported by Viktor Hamburger (an embryologist at Washington University, St Louis) in 1934, who suggested that innervated tissue released an inductive factor that was essential for the differentiation of the nerve cells.
Having read the results of her work, Hamburger invited Levi-Montalcini to St. Louis to elucidate the processes regulating the growth of nerve cells. She arrived in 1946 planning to stay for a semester but stayed until 1961. She was appointed Associate Professor in 1956 and full Professor of Neurobiology in 1958. During this time she began grafting mouse sarcoma tumors onto chick embryos and looking at nerve fiber development. The results suggested that mouse tumors secrete a factor necessary to stimulate nerve fiber growth. These findings led her to Rio de Janeiro to work with Hertha Meyer, an expert in cell culture, at the local Institute of Biophysics directed by Carlos Chagas (whom Chagas disease is named after). Here, she became convinced that these tumors secreted a “diffusible agent”. The challenge then became how to identify this factor.
Stanley Cohen joined Hamburgers lab and between 1953 and 1959 Levi-Montalcini and Cohen set about identifying this factor as a protein, later to be called Nerve Growth Factor (NGF). Cohen left Washington University in 1959 – budget restrictions prevented him from being offered a permanent position – but before he left he identified and purified epidermal growth factor.
In 1961, Levi-Montalcini made the decision to return to Italy. With encouragement from Hamburger, the approval of the dean and a grant from the National Science Foundation, she left for Rome. There she set up a research unit in the Institute of Health in Rome, a collaboration with Washington University that would see her spend six months a year in Italy and the other six in the United States. In 1979, when she reached retirement age, she left her post as director of the Institute of Cell Biology of the Italian National Council of Research. But her commitment to research didn’t stop. Even when she turned 100 Levi-Montalcini was still working at the European Brain Research Institute , which she founded in Rome in 2002.
In her own words “I have become persuaded that, in scientific research, neither the degree of one’s intelligence nor the ability to carry out one’s tasks with thoroughness and precision are factors essential to personal success and fulfillment. More important for the attaining of both ends are total dedication and a tendency to underestimate difficulties, which cause one to tackle problems that other, more critical and acute persons instead opt to avoid.” Dr Rita Levi-Montalcini was a testament to this.
The preceding post was based mostly on information obtained from Rita Levi-Montalcini’s autobiography – In Praise of Imperfection: My Life and Work – Published by Basic Books Inc., New York, 1988.