20th century, Science

Nobel Laureate Rita Levi-Montalcini: the discovery of Nerve Growth Factor

By Pandora Dewan

Rita Levi-Montalcini was jointly awarded the Nobel Prize in Physiology or Medicine, with her colleague Stanley Cohen, for their discovery of Nerve Growth Factor (NGF) in 1986. This protein was the first described growth factor, a term for the biological mediators involved in the regulation of cell growth, differentiation, survival, and function. NGF primarily promotes the growth and maintenance of the nervous system during development, although it is thought to have many other essential roles in human biology, particularly in immune responses. Indeed, recent research has demonstrated an association between abnormal levels of NGF and several neurodegenerative and psychiatric disorders, making this molecule of great interest in the treatment of many life-threatening conditions. The work of Levi-Montalcini made such advancements possible. However, in her early career she  came up against considerable obstacles to her progression as a scientist.

Levi-Montalcini was born in 1909 to a Sephardic Jewish family in Turin, Italy. The first career obstacle she encountered came from her own father. He strongly discouraged his daughters from pursuing a profession, convinced that this would interfere with their duties as wives and mothers. Despite his disapproval, Levi-Montalcini enrolled at the University of Turin Medical School, and though she graduated in 1936, she remained at the university as an assistant to her tutor, the neuro-histologist Giuseppe Levi. Under Levi, she learned the technique of silver staining nerve cells, making them more clearly visible under the microscope. This technique would prove vital in her subsequent research.

Unfortunately, her academic career was cut short when, in 1938, Mussolini introduced laws to exclude Jews from academic and professional careers. Nonetheless, Rita continued her research in secret, making her own microsurgical tools from reshaped sewing needles and performing experiments in a make-shift lab set up in her bedroom. Her studies were greatly inspired by an article written by Viktor Hamburger in 1934, on nerve cell development in chicken embryos. Hamburger had discovered that removing the wing bud from the embryo reduced peripheral nerve cell growth from the spinal column. From this, he concluded that the wing bud must contain some organizing factor that was required for nerve cell growth. Hamburger could not see the nerve fibres in great detail as he was limited by the resolution of his light microscope. Intrigued, Levi-Montalcini decided to replicate his experiments herself, using her silver staining technique to look more closely at the individual cells.

It so happened that chicken embryos made an excellent model system, not only because they have a very consistent pattern of neuronal migration, but also because it was easy for Rita to obtain fertilized chicken eggs from local farmers without raising suspicion. She compared the pattern of nerve cell growth in healthy embryos with that of mutant embryos from which she had removed the wing bud and was surprised to see a normal number of neurons migrating towards the absent bud in the mutants. It was only later in the chick’s development that large number of these neurons died to give a picture similar to that which Hamburger described. From her results she hypothesized that the wing bud released some growth-promoting factor that enabled growing neurons to reach their final destination in the peripheral tissues. It wasn’t until 1944 that Levi-Montalcini was able to come out of hiding and publish her findings.

In 1947, Viktor Hamburger came across Levi-Montalcini’s research and invited her to work with him in his lab at Washington University, St. Louis. It was here, in 1952, that she made her most important discovery. An observation made by Elmer Bueker, a postgraduate student in Hamburger’s lab, provided clear evidence in support of her idea of a neuronal growth-promoting factor. He found that, when grafted onto a chicken embryo, cells transplanted from a malignant mouse tumour attracted and stimulated neuronal growth, suggesting that, like the limb bud, the cancer cells were releasing a substance that was stimulating neuron growth. In 1953, biochemist Stanley Cohen joined the lab. Together, Levi-Montalcini and Cohen identified the mysterious molecule as a protein which they named Nerve Growth Factor.

The discovery and isolation of NGF has had an enormous impact on research into many different diseases, including cancer, Parkinson’s disease, Alzheimer’s, Schizophrenia, and even some autoimmune conditions such as multiple sclerosis. Levi-Montalcini’s pioneering work led the way to the discovery of hundreds of other growth factors involved in regulation of nearly all developmental processes.

It was not only her research that was influential; throughout her life, Levi-Montalcini was deeply involved in cultural and social affairs. She was a passionate advocate of women’s rights, particularly on the difficulties experienced by female scientists. In 1992 she established an education foundation “to support education and schooling, in all of its forms, for children, girls, and women in Africa”, and to this day her charity has supported more than 12,000 women and children. In 2001 she was appointed a senator for life by the Italian senate, a position which she frequently used to further scientific prospects for the country. Indeed, right until her death in December 2012, she persevered in her fight against sexism and anti-Semitism in society, while continuing to act as a key driver for scientific advancement in molecular biology across the world.

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