JMS Pearce
Hull, England

Rita Levi-Montalcini began her scientific career as an oppressed Jewess in fascist Italy. She ended it in triumph as the neurobiologist who discovered nerve growth factor, a political activist, and a researcher until her death at the age of 103.¹

Born in Turin in 1909, Rita Levi-Montalcini was raised by an authoritarian father, Adam Levi, an engineer and mathematician, and her mother, Adele Montalcini, a painter. Her father believed that a professional career would interfere with a woman’s role as wife and mother and tried to stop Rita and her sisters from pursuing higher education. Ironically, she never married.

Despite her father’s objections, she taught herself Greek, Latin, and mathematics, and read medicine at the University of Turin, graduating summa cum laude in 1936. Inspired by Giuseppe Levi, a distinguished anatomist, she started investigations as his assistant. But her academic career was soon cut short when in 1938 Mussolini issued his philippic “Manifesto per la Difesa della Razza”, signed by a coterie of fascist scientists and intellectuals, banning academic and professional careers to non-Aryan Italians. After a short sabbatical in a Brussels neurological institute, she returned to Turin when the German army invaded Belgium in the spring of 1940.

She was excluded from Turin University, but having been inspired by Viktor Hamburger’s 1934 paper on limb extirpation in chick embryos,² she experimented in her bedroom and made her own primitive apparatus to study the motor neurons and growth of nerve fibers in chick embryos. When the Germans invaded Italy in 1943, the family fled to Florence, and she continued her research in secret, hiding underground from the Nazis until August 1944. She then practiced clinically in a refugee camp, treating epidemics of typhus and other infectious diseases.

After the war, she returned to Turin with her family and published her research, which impressed Viktor Hamburger, head of zoology at Washington University in St. Louis, Missouri. He asked her to join him in September 1947 as a research associate. She remained in Washington for thirty years, and was appointed associate professor of zoology in 1951 and full professor in 1958. In the 1960s, she established a laboratory in Rome in a joint research program with Washington University. In 1969, she formed and directed the Laboratory of Cell Biology in Rome. She retired as professor emeritus of biology in 1977, but continued her experiments after her hundredth birthday.

Nerve growth factor

She is remembered principally for her studies of nerve growth. These began when working with her former teacher Giuseppe Levi, she developed a new theory, subsequently proven, that nerve cell death resulted from the absence of a growth-promoting substance, rather than an inductive factor, released by the target of the growing neurons.⁵

In 1948, in Hamburger’s laboratory, she noticed that when mouse sarcoma cells were transplanted into chicken embryos, they induced rapid vigorous growth of the embryonic nervous system.^3,4 She concluded that the tumor released a polypeptide, a nerve growth-promoting factor (NGF), which regulated the growth, differentiation, and survival of sympathetic and certain sensory neurons. NGF binds to receptors on these neurons, producing a signaling cascade that promotes cell growth and survival.

The research demonstrated a neurotrophic mechanism that might be of fundamental importance in tumors, developmental malformations, and neurodegenerative disorders. It also was linked to the discovery by Stanley Cohen of epidermal growth factor, which stimulates the proliferation of epithelial cells. Levi-Montalcini and Cohen shared the Nobel Prize for Medicine and Physiology in 1986.¹

This discovery revolutionized neurobiology and endocrinology, and set the stage for cell-signalling research. However, the importance of NGF and neurotrophins was not widely recognized until the early 1970s, when evidence for its importance became overwhelming.⁵ The growth response elicited by a tumoral agent showed developing nerve cells could respond to previously unknown humoral, neurotrophic factors³ with therapeutic potential. In 1984, the NGF gene (1p13.2) was located on the proximal short arm of chromosome 1. NGF directly modulates immune responses of B and T cells and the activation of the immune system in inflammatory processes.

In her autobiography, Levi-Montalcini also recorded that with Giuseppe Levi in 1944 she had reported a spontaneous form of neuronal death in the chick embryo, the forerunner of apoptosis, a term first used in 1972.⁶

NGF neural crest derivatives

Sensory neurons

Sympatho-adrenal neurons

Cholinergic & adrenergic neurons

Monocytes & lymphocytes

Mesenchymal cells

Often called Italy’s “Lady of the Cells,” Rita Levi-Montalcini received many honors and awards.⁷ She was elected a Foreign Fellow of the Royal Society in 1995. She established a research unit in Rome in 1962 and was director of the Institute of Cell Biology of the Italian Council of Research, and president of the Institute of the Italian Encyclopedia. With her twin sister, she created the Levi-Montalcini Foundation in 1992 in memory of their father to assist women from developing countries to find careers in science. She championed ethics and women’s rights and published more than twenty books to promote better career education for the young.⁸

She received one of Italy’s highest honors in 2001 when she was appointed a senator for life. Still politically active in 2006, aged 97, despite attempts to mock her on grounds of age, she reversed the Italian government’s decision to cut science funding. She died at the age of 103 on December 30, 2012.

She was a gracious, imaginative, elegant woman, described by the author Primo Levi as ‘‘a tiny lady with an indomitable will and the countenance of a princess.’’ An inspiring figure for aspiring women scientists, this extraordinary pioneer had learned to thrive on opposition. She commented:

I should thank Mussolini for having declared me to be of an inferior race. This led me to the joy of working, not any more unfortunately in university institutes, but in a bedroom.

References

1. Rita Levi-Montalcini. The Nobel Prize: In: The Nobel Prize Women who changed science. https://www.nobelprize.org/womenwhochangedscience/stories/rita-levi-montalcini.
2. Hamburger, V. “The effects of wing bud extirpation on the development of the central nervous system in chick embryos.” J Exp Zool, 1934;68: 449-494.
3. Levi-Montalcini R. “The nerve growth factor: Tthirty-five years later.” Nobel lecture, December 8, 1986. https://www.nobelprize.org/uploads/2018/06/levi-montalcini-lecture.pdf.
4. Levi-Montalcini, R. “From a homemade laboratory to the Nobel Prize: An interview with Rita Levi-Montalcini.” The International Journal of Developmental Biology, 2000; 44 (6): 563–66
5. Bradshaw, R. Rita Levi-Montalcini (1909–2012). Nature 2013;493:306.
6. Levi-Montalcini R. In Praise of Imperfection. New York: Basic Books, Inc., 1988.
7. Dubinsky E. Rita Levi-Montalcini (b. 1909). Medical Journeys: Transplanting Medical Knowledge Across the World. Bernard Becker Medical Library, Washington University School of Medicine. http://beckerexhibits.wustl.edu/mig/bios/levi-montalcini.html.
8. Melino G. Obituary. Rita Levi-Montalcini 1909–2012. Cell 2013;152:379-80.