Masters in Memoriam: Celebrating Rita Levi-Montalcini

Rita Levi-Montalcini_The Washington Post

Rita Levi-Montalcini, winner of the 1986 Nobel Prize in Physiology or Medicine/Courtesy of The Washington Post 

Between today’s economic and political turmoil, the tension between employees and employers, and COVID-19 panic only just beginning to wane, it’s no surprise that the conversation about what makes a healthy work-life balance is rife with new ideas and controversial lifestyle ‘takes’.

What seems to be missing, however, is anything that really addresses the pinnacle of the ideal: the mythical keystone of “doing a job you love, so you don’t work a day in your life”. This was something perfectly embodied by one very dedicated and extremely intelligent scientist, Rita Levi-Montalcini.

Aside from her many, many accolades and the abundance of influence she left behind upon her death in December 2012, her career could perhaps be best summarized by a quote from Primo Levi's 1978 novel The Monkey’s Wrench, which Rita Levi-Montalcini purportedly favored when discussing her life’s work: “If we exclude prodigious and individual moments that fate presents us with, loving our work (which unfortunately is the privilege of few) is the best concrete definition of happiness on Earth.”

Professional Journey of Rita Levi-Montalcini

This is far from a comprehensive description of her passion – the woman herself was a pulled ripcord, a research powerhouse bent on her craft. She graduated from medical school in 1936, the same year that Mussolini barred non-Aryan Italians from professional or academic careers. Even after the German army had rolled through Belgium in early 1940 and Anglo-American air forces began dropping bombs on her hometown of Turin, Italy, Rita Levi-Montalcini set up a personal research station in her bedroom to pursue her interest in the growth of nerve cells. With improvised tools that included sharpened sewing needles, watchmaker’s forceps, a pair of ophthalmologist's scissors, a microscope and her expertise, she was able to observe the development and subsequent decay of nerve cell growth in chickens who had a limb removed via microsurgery during embryonic development, in between nighttime dashes to the bomb shelter across the street.

While she certainly didn’t stop there, Levi-Montalcini is perhaps best known for her award-winning work in the discovery and isolation of Nerve Growth Factor (NGF) in 1956, for which she and her colleague Stanley Cohen, Ph.D., were awarded the Nobel Prize in Physiology or Medicine in 1986. That made her the fourth Nobel Prize winner from Italy’s old and well-established Jewish community, and in April 2009 she became the first Nobel Laureate to claim the title of centenarian.

Exactly what it says on the tin, NGF is a protein that serves to support the development, proliferation, differentiation and survival of neurons. Rita Levi-Montalcini originally started down the path that would lead to NGF’s isolation by reproducing another experiment by Elmer Bueker, Ph.D., in which certain tumors seemed to encourage nearby nerve growth when grafted onto chicken embryos. Follow-up experiments with embryos injected with tumor extracts did not yield the same results; however, experiments where a tumor sample was placed near (but not in direct contact with) isolated chicken embryo nerve tissue, or directly on the embryonic membrane itself, exhibited excess nerve cell growth.

Most notably, this neuron development occurred in regions both near and far from the location of the transplanted tumor, even burrowing into the blood vessels leading away from the tumor in spite of the nerves themselves refraining from making any direct connections to tumor cells. By 1954, Levi-Montalcini and Cohen had managed to derive a solution of proteins and nucleic acids from mouse sarcomas that could reliably reproduce a tumor’s effect on nerve growth in culture and were later able to use snake venom to identify and later extract a protein capable of instigating neuron development – what would then come to be known as Nerve Growth Factor.

Achievements of Rita Levi-Montalcini

In addition to this truly field-defining research, Rita Levi-Montalcini held numerous offices of portent, including serving as a professor at Washington University in St. Louis, Missouri from 1958 until her retirement in 1977. During that time, she also established a research unit in Italy, splitting her efforts between St. Louis and Rome, and served as director of the Institute of Cell Biology of the Italian National Council of Research in Rome from 1969 to 1978, where she became a guest professor upon her retirement.

Then in 2001, she swept back onto the neuroscientific stage with a grand proposal at the annual Ambrosetti Forum: the foundation of a neurological research facility in Italy. Established in 2002 and fully operational by 2005, the European Brain Research Institute (EBRI) still fosters a rich, collaborative environment for the research and study of all things neurological, from synapses to behaviors to neurodegenerative diseases.

Levi-Montalcini’s contributions to science and society still don’t end there. She helped found the Fondazione Idis-Città della Scienza, a museum in Southern Italy that works to build a knowledge-based economy; she was nominated as a Senator for Life by Italy’s then-President Carlo Azeglio Ciampi on the basis of her contributions to the scientific community, a position in which she served until her death in 2012; she became the tenth woman elected to the United States National Academy of Sciences in 1968, which was followed by a National Medal of Science in 1987.

Her last research project was conceived in late 2007, wherein she endeavored to investigate whatever additional functions NGF must have to merit its presence in an embryo several days before the nervous system begins to develop. Shunning knockout mouse models that could be used to study the early roles and mechanisms of NGF, Rita Levi-Montalcini opted instead to return to the chicken embryo, for which there were no knockout models so that she could observe the effects of NGF inhibition at different stages of embryonic development. She treated the embryos with a special anti-NGF antibody derived from a phenotypic NGF knock-out mouse model, observing that the embryos would fail to rotate their trunk to align with the head and upset the symmetrical development of organ tissues.

She never married, had no children and seemed to have been ever-reiterating her lack of regrets and deep love for her work. Almost in spite of her career in the biological sciences, she was reportedly of the optimistic opinion that, “Life does not end with death. What you pass on to others remains. Immortality is not the body, which will one day die. I don’t care about dying. That does not matter… of importance is the message you leave to others. That is immortality.”

Though it’s been nearly a decade since her departure from the mortal world, in Rita Levi-Montalcini’s own words, she is far from truly leaving those of us who remain here in the world of science.

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