Rita Levi Montalcini – The Discoverer of Growth Factors

What does a developing neuron in its embryonic phase have in common with a tumorous cell? How do these cells survive, extend and proliferate? The answer is that their fate is orchestrated by the fine balance in the concentration of trophic factors. Rita Levi-Montalcini and co-worker Stanley Cohen co-won the Nobel Prize in 1986 “for their discoveries of growth factors”, for the first time in history, namely the isolation of nerve growth factor (NGF) and the following discovery by Cohen of the epidermal growth factor (EGF). But, before being a Nobel-Prize winning neurobiologist, Rita Levi-Montalcini had to fight vigorously for her passion in science. Here’s a slice of her inspiring story.

From the War drama to the American dream: toward the discovery of NGF
Rita’s story starts in 1909 in Turin, where she was born to an Italian Jewish family. In keeping with the customs of the time, her father discouraged her to enter college to avoid interference to her life as a wife and mother. But she said: “At 20, I realized that I could not possibly adjust to a feminine role as conceived by my father and asked him permission to engage in a professional career”.

Rita succeeded to change his mind and she graduated summa cum laude from the medical school in 1936. During her medical studies she got inspired by anatomist and histologist Giuseppe Levi to pursue a career in neurology and psychology. Despite Mussolini’s racial laws barring Jews from academic and professional careers, Rita Levi-Montalcini took her first steps towards her ground-breaking discovery. Using tools from ophthalmologists and watchmakers, she studied the growth of nervous fibres by dissecting chicken embryos with her mentor Giuseppe Levi. In this simple working set-up, they found that the amputation of wing buds – the first structure of the developing embryo that will form the wing  in chick embryos, leads to the loss in the number of motor neurons in the spinal cord and reduces the sensitive nerve cells innervating the cut member. From this result, they hypothesized that a factor released by peripheral tissue, which was missing after amputation of the wing buds, is necessary to the survival of the neurons.

Being interested in her theory, Viktor Hamburger, a German-American researcher who thought that the absence of neurons was due to a lack of differentiation during early embryonic development, offered her to stay for one semester at the Washington University of St. Louis. One semester became 30 years of work, during which she revolutionized neuroembryology and re-interpreted the ontogeny of the nervous system by introducing new concepts in neuronal development: proliferation, migration, differentiation, survival and death.

In the early 50s, Rita took advantage of the tissue culture unit built by her friend Herta Mayer at the Biophysics Institute of Rio de Janeiro to study in vitro tumour engraftment in the body wall of chick embryos. When she observed a halo of fibres facing the tumour after co-culturing chick neuronal ganglia and mouse fragments of sarcoma, she confirmed that a soluble factor favours the growth of nerve fibres. Back in St Louis, she worked with biochemist Stanley Cohen on the isolation of a nuclear protein from the tumours responsible for the growth of nerve fibres: the nerve growth factor (NGF). NGF was the very first growth factor identified in an animal body – more than one hundred have been identified since then.

Back to Italy and her legacy
In 1961, Rita Levi-Montalcini returned to Italy as the director of the Research Centre for Neurobiology in Roma, to continue her work on the role of NGF and its target. In her later work, she analysed the activity of NGF in vitro and in vivo. In 1979, she officially retired from her position as director and continued as a guest professor. When Rita Levi-Montalcini and Stanley Cohen received the Nobel Prize in Medicine in 1986, the decision to leave out Prof. Hamburger who set the foundation with initial experiments and hosted Rita and Stanley created a great controversy. When she died in 2012 at the age of 103, she was the first Nobel laureate to become a centenarian.

Levi-Montalcini used her popularity to take action in areas that concerned her. In an interview, she said: “I can do things that are very, very important, which I would never have been able to do if I did not receive it [the Nobel Prize]. It has given me the possibility of helping a lot of people.” In 2001, she created an educational foundation to support the education of children and women, especially in Africa. The Fondazione Rita Levi-Montalcini Onlus provides tools to women for the full development of their capacities to escape gender discrimination and to actively participate in the society’s life. By promoting women’s education, the foundation aims at increasing their involvement in the economic, social and cultural development of their nation. Until now, 152 projects were funded to help more than 12,000 people in 35 countries. For example, in poor regions of Ethiopia, the foundation is providing professional support to women, in the form of access to a micro-credit, to open their own business (mostly groceries or restaurants).

Rita Levi-Montalcini also founded the European Brain Research Institute (EBRI), a non-profit research institute. This multidisciplinary centre is focussing on the role of NGF in several pathological conditions, e.g. Alzheimer’s disease, Parkinson’s disease, etc. in order to develop therapeutic strategies. Having faced many challenges, Rita Levi-Montalcini wanted to ensure that young scientists have access to funds, equipment and support. This is not the only legacy Rita left behind, it was her grit, determination and passion for biology that was her greatest gift to others. I’ll leave you with Levi-Montalcini’s wise words, ‘’Above all, don’t fear difficult moments. The best comes from them’’.

Written by Isabelle Arnoux; Edited by Chiara Galante & Radhika Menon. Featured Image: NGC/Design.

Note of the editor:
Rita’s legacy is in danger: the EBRI is suffering from lack of money, making the planning of long-term projects difficult and the institute less competitive. Because it’s a private institute, the EBRI cannot access the public funding in Italy. The EBRI’s researchers are asking the possibility to apply since their work could have a great impact on public health and an appeal has been addressed to the President of the Italian Republic Sergio Mattarella in late 2018. What will happen to the institute founded and wanted by the only Nobel Prize for Medicine that Italy had in the past 40 years?