Pioneer in understanding the developmental biology of nerve cells

Rita Levi-Montalcini’s path to becoming a researcher was all but a smooth one. Her father had different plans for his daughter, and political oppression and the events of the Second World War made it practically impossible for Rita to do research. But with passion, persistence, and creativity, Rita overcame the obstacles life presented to her and embarked on a journey to study the secrets of the nervous system. Investigating the mechanisms that make nerve cells grow and survive, she found the first biological growth factor – starting a new era in developmental biology research.

Rita Levi-Montalcini grew up in a traditional Italian–Jewish family in Turin, in which her father as head of the family would take all major decisions. Despite his love for his daughters and great respect for women, he believed that attending university or pursuing a professional career would interfere with Rita’s future role in society: raising children and organising a household. 

Rita resented the role her father envisioned for her – she wanted to become a doctor. When she was 20, she finally convinced him to allow her to go to university, and Rita entered the Turin School of Medicine. There, she was trained in biological sciences by the famous Italian histologist Giuseppe Levi, along with fellow students Salvador Luria and Renato Dulbecco. Giuseppe Levi taught his students to approach scientific problems in a rigorous way, and the training they received must have been superb: Rita, Salvador, and Renato would later become successful scientists, and each of them would receive Nobel Prizes in Physiology or Medicine for their work. Under Giuseppe Levi’s guidance, Rita began to study nerve cells, and decided to investigate brain development in chicken embryos, a commonly studied organism at that time.

In 1936, Rita earned a degree in Medicine and Surgery, but she was still undecided whether she wanted to focus on medicine or continue doing basic research. So, she signed up for a programme to specialise in neurology and psychology, which would leave her with both options. Soon afterwards, however, laws were passed in Italy that prohibited Jewish citizens from pursuing professional and academic careers, and in 1939 Rita had to withdraw from university. Rita accepted an invitation to Brussels to work as a guest researcher at a neurological institute – but had to leave again when Belgium was on the verge of invasion by Germany in spring 1940.

Back in Turin, not allowed to perform research at an academic institution, Rita set up a small makeshift laboratory in her bedroom to continue studying chicken embryos. She was soon joined by her former mentor, Giuseppe Levi, who had also had to leave Belgium. The turmoil of the Second World War forced Rita and her family to flee from Turin to rural Piemonte, and then upon the arrival of German troops to Florence, where the family had to hide. Nevertheless, Rita managed to continue her studies, setting up her private laboratory whenever possible.

In May 1945, the family could finally return to Turin and Rita continued her research at the university. She didn’t stay long though. In 1947, the American neurobiologist Viktor Hamburger, whose work on limb development in chicken embryos had inspired Rita to enter the field back in 1934, invited her to join his lab in St. Louis at the University of Washington as a guest scientist. Hamburger had read about Rita’s research on how nerve cells develop, grow, and survive. Since his and Rita’s theories on the process deviated, he asked her to join him to work together on the question.

What was intended to be a stay for a semester abroad turned into 30 years. During her time as a research associate with Viktor Hamburger in St. Louis, Rita would make her most important discoveries. Noticing that mouse tumour cells caused an accelerated and excessive growth of nerve cells in chicken embryos, she set out to identify the biological molecule responsible for this effect. Together with Stanley Cohen, Rita found other sources of this enigmatic factor: It was present in snake venom, as well as in mouse salivary glands. From these sources, the two scientists managed to isolate Nerve Growth Factor (NGF) – a small protein-like molecule that is essential for nerve cells to develop and survive.

The findings were met with scepticism by other scientists – why would a molecule that’s required for the survival of nerve cells be present in tumours or in snake venom? But Rita and Stanley continued to investigate NGF. Over the next years, the two and their colleagues in the field showed NGF to be essential for the development of nerve cells in chicken and rodents, observed the transport of NGF through nerve fibres, and found that it influenced the growth direction of nerve cells. These groundbreaking discoveries would later earn Rita and Stanley their shared Nobel Prize in Physiology or Medicine.

Rita’s and Stanley’s work on NGF started a new era in developmental biology research. Scientists soon discovered numerous other growth factors, as well as specialised receptor proteins that recognise them. Many cells carry these receptors on their outer surface to register the presence of growth factors and adapt their development accordingly. Growth factors ensure that a developing organism grows the correct organs in the correct places, and these factors also help tissues to regenerate later in life.

But growth factors and their receptors can also lead to the development of tumours. In many cancers, the system that transmits growth signals inside cells is overactive – leading to excessive cell division and tumour formation. Growth factors are therefore of huge clinical relevance. Understanding their biological functions helps doctors to treat cancer patients and may also lead to new treatments against chronic diseases, such as Alzheimer’s and Parkinson’s disease and asthma.

Also available in this series:

• Barbara McClintock – Plant biologist & geneticist who revolutionised our understanding
• Osamu Shimomura – Organic chemist who discovered Green Fluorescent Protein while studying jellyfish