Rita Levi-Montalcini: the badass neurobiologist

(Quick shout out to my friend Lauren who suggested I research this awesome scientist- thanks Lauren!)

Born: April 22 1909, Turin, Italy
Studied: Medicine (University of Turin), neurobiology (University of Turin, Belgium, home laboratories, Washington University, St. Louis)
Died: December 30 2012, Rome, Italy

levi-montalcini_lab_photo
(Rita Levi-Montalcini in her laboratory in the early 1960s. Credit: Becker Medical Library)

Early life

Rita Levi-Montalcini (born Rita Levi) was brought into the world with her twin sister Paola on April 22 in 1909. Rita and Paola were born into a well-to-do Jewish family in Turin, Italy (regular readers will recognise Turin as the place where Charles Babbage first presented his idea for the Analytical Engine in 1841). From an early age Rita had to fight for her right to an education. Her father was a domineering and controlling family patriarch who believed that educating women made them less appealing as wives and mothers (hands up who’s glad they weren’t born into this family?). After fighting to attend a proper high school she also had to convince her father to let her attend university. It may have taken three years, but nevertheless she persisted. By 1930, Rita had enrolled in a medical degree at the University of Turin. After graduating (summa cumme laude, of course, nothing but the best for Rita) in 1936, Rita began her independent research with mentor Giuseppe Levi (no family relation, just a common surname) in 1938 (she was his research assistant in between). Levi introduced Rita to her future field of study: the developing nervous system. He also aided her in developing a technique which would pave her way to changing the world: silver staining nerve cells.

agstain

(Golgi Silver Stain, Spinal Cord. Credit: Southern Illinois University)

Science break: Why do we need to stain cells?
For those who have forgotten the biology they “learned” in high school: biologists stain cells so that they can see them more easily under the microscope. Different stains are used for different types of cells, as cells react different to different stains. Staining nerve cells with silver allowed Rita to properly see them and, in fact, see them more clearly than most people due to her staining skill. Without this technique, Rita’s discovery would have come much later.

However 1938 wasn’t only a start for Rita, it was also the end of something. The rise of fascism in pre-war Europe had hit Italy, and Mussolini’s race laws came into power between September 2nd and November 17th. Jews lost the right to work in education and government jobs, property and businesses were confiscated, and thousands of Jews were deported. Rita and Levi left Italy to work in Belgium in 1939, as they were not discriminated against there. They wrote a few papers while working there, and Pontifica Academia Scientiatum and the Belgian Archives de Biologie published them (as these publications did not racially discriminate)

But war was close behind the pair, and Hitler invaded Belgium in 1939, forcing the pair back to Italy. Rita created a home laboratory, her ingenuity quite impressive. All she required was: an incubator, fertilised chicken eggs, and the surgical instruments for dissection that she fashioned herself from sewing needles! Now that’s dedication to science! Levi eventually joined her, and was her assistant. Unfortunately Rita, her family, and Levi were forced to Florence by the bombings in 1942 (where she continued her research), and then forced into hiding in 1943 when Hitler invaded Northern Italy.

Rita’s research was based on a paper by Viktor Hamburger of Washington University in St. Louis; describing how removing the limbs of still developing chicken embryos changed how the nerves spread throughout the embryo. However, Hamburger could only get to a certain point in his experiment, as he couldn’t see the cells clearly enough to draw firm conclusions as to what was happening. So Rita ran the experiments again, but this time used her silver staining technique so she could see the cells more clearly. While Hamburger had said that the cells dying was due to the absence of what he called “an inductive factor”, Rita found instead that it was the lack of a growth-promoting factor (inductive vs. growing, or pulling vs. pushing: that’s the important part, ignore the rest if you like avoiding biology).

After the war Rita and Levi both returned to Turin to work and research, but the dynamic between the pair had changed. Rita was expected to be his assistant, however in her own lab he had been her assistant on occasion. She didn’t want to be anyone’s second fiddle, so when she saw an opportunity, she grasped it with both hands. Hamburger read the papers she had published and was impressed with them. He invited Rita back to his lab in the US to repeat, and extend, the experiment with him (and his fancy equipment not made from sewing needles) in September of 1946. Her original plan was to stay for a semester, but as often happens with life changing events; it didn’t go exactly to plan. Rita ended up staying in the US for over 30 years instead.

Rita’s work in the US was based around proving that the “growth promoting factor” she had theorised was a reality. Eventually Rita and her partner Stanley Cohen found evidence that it did in fact exist, and she called this factor “Nerve Growth Factor” (NGF for short). But the world of science is not kind to new discoveries (because without healthy scepticism, we would believe anything we heard without finding out if it was true). The discovery of growth factors was nothing that the world had seen before, and so, with any paradigm-shifting discovery, it would need a lot more evidence to be believed. Eventually Cohen discovered another growth factor: Epidermal Growth Factor, which helped convert more scientists to the cause. More and more evidence was collected and collated and more people were interested. The protein (yes, NGF is a protein) was isolated in 1952. Rita’s only PhD student, Ruth Hogue Angeletti, and Ralph Bradshaw, determined NGF’s structure in 1971.

 

ngf-pic
ImageSource=RCSB PDB; StructureID=1sgf; DOI=http://dx.doi.org/10.2210/pdb1sgf/pdb;

(Nerve Growth Factor. Credit: Sino Biological Inc.)

Rita and Cohen continued to research NGF and its effects on the body, and won the Nobel Prize for Medicine or Physiology in 1986. This award actually caused some controversy in the scientific community, as the pair did not share the prize with either Levi or Hamburger (I’ll let you judge for yourself whether those claims are justified, but I think Rita and Cohen deserve the prize they received).

Rita continued to research, and continued to set up research institutes for the rest of her life, up until she died at age 103. Thousands attended her funeral, paying respects to “the great woman”. She currently holds the record for longest living Nobel laureate.

MONTALCINI: LA NIPOTE, NON MI ASPETTAVO PARTECIPAZIONE COSI'
I nipoti Piera ed Emanuele Levi Montalcini seguono in prima fila la bara durante i funerali di Rita Levi Montalcini al cimitero Monumentale, Torino, 2 gennaio 2013. ANSA/ ALESSANDRO DI MARCO

(Rita’s funeral procession. Credit: Il Secolo XIX)

Rita’s mistreatment:
Rita, and all the Jews in Italy, were subject to Mussolini’s race hate laws. Jews had been living in Italy since the Roman Empire. Rita’s family could even trace back their lineage 2000 years. However, under these racist laws, they lost their right to jobs, businesses, and their lives. Imagine the kind of science a woman like Rita could have done with access to real scientific resources, instead of hiding for her safety, and hoping the bombs didn’t destroy her family’s home.

Rita was also a woman studying a male-dominated field. While she eventually proved everyone wrong and herself right, many believe that a reason the scientific community was sceptical about NGF was the fact that a woman had made a discovery. Rita was also expected to return as Levi’s assistant after the war, despite being a successful scientist in her own right. And that fact that she was “supposed” to share her Nobel Prize with anyone other than Cohen, even though those two had done the work for the prize, shows the role science wanted to cast Rita in. I’m glad Rita was such a force of nature to contend with. The world is a better place for it.

And yes, Rita had a tiny amount of privilege, in that she was born into a household that had the money to educate her. However, she also had to deal with a very controlling and domineering patriarch of the family who was known for fits of violence. And this father did not want his female children educated, and considered Rita his least favourite child. She had to convince her father to send her to a proper high school, let alone university. Rita eventually took her mother’s maiden name, Montalcini, in an effort to distance herself from her father.

Rita also had to deal with some interesting characters in her most recent role in politics. Conservative politicians had no time for her and her requests for scientific funding. And when fighting for what she believed in, she had to face sexist, ageist, conservatives who didn’t believe that science was worth funding.

Rita’s Legacy
Rita and her discovery of the Nerve Growth Factor literally changed the face of biology. Since then hundreds of other growth factors have been discovered, and their role in the body is being researched. These growth factors are important in understanding diseases, and finding therapies to treat these diseases. For example, NGF has been found to play a role in the body’s immune system as well as neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

“That discovery was huge- it opened up a whole new field in understanding how cells talk and listen to each other” Bill Mobley, neuroscientist, Stanford University.

Rita also created various research institutes that have helped to shape Italian and European science. Rita founded the European Brain Research Institute: Rita Levi-Montalcini (the institute literally bears her name, that’s not a typo) in 2002. This institute helps scientists from Italy and around the world study neurodegenerative diseases, as well as finding therapies for them. It also acts as a training facility for these scientists.

Rita also helped establish the Institute of Cell Biology in 1962, and the Institute of Neurobiology in 1968, becoming the first director of both. These two institutes amalgamated in 2010, along with the Rome Section of the Institute of Neuroscience to become the Institute of Cell Biology and Neurobiology. This research hub aims to break down the barriers common in academia and allow a multi-disciplinary approach to new problems, increasing the exchanges of ideas.

Rita also has a scholarship given out annually in her name: the Rita Levi-Montalcini Award was inaugurated in 1999. It is awarded to young Italian scientists who are studying Multiple Sclerosis, another passion of Rita’s. The European Brain Institute has also held a Rita Levi-Montalcini lecture annually since 2013.

Rita won maaaaaany awards throughout her life: here are some of them below:

  • 1963: Max Weistein Award
  • 1969: International Feltinelli Medical Award
  • 1974: William Thomspon Wakeman Award
  • 1982: Lewis S. Rosentiel Award
  • 1985: Louis Gross Horwitz Prize
  • 1986: Albert Lasker Prize
  • 1986: NOBEL PRIZE FOR MEDICINE OR PHYSIOLOGY (with Cohen)
  • 1987: National Medal for Science (United States)

And Rita was not just an over-achiever in the award field; she was also the head of many boards and institutes (as mentioned above)

  • 1958: Professor at Washington University, St. Louis
  • 1966: Fellow of American Academy of Arts and Sciences
  • 1968: Member of National Academy of Sciences (United States)
  • 1974: Member of Pontifical Academy of Sciences (Vatican City)
  • 1983-1986: President of Italian Association for Multiple Sclerosis
  • 1986-2012: Honorary President of Italian Association for Multiple Sclerosis
  • 1999: Named Ambassador for Food and Agricultural Organization of United Nations to fight world hunger
  • 2008: Member of National Academy of Sciences (Italy)

On top of being amazing as a research scientist, Rita was also a medical doctor at a refugee camp at the end of the war. Rita was hired by the Anglo-American forces and sent to a refugee camp in Florence in 1944 where she worked as both a doctor and a nurse, in difficult conditions with infections spreading fast. Without her help many more people would have died.

Rita also developed a foundation in Africa, wishing to empower more women on the continent. She founded the Rita Levi-Montalcini Foundation (Non-Profit) in 2001. This foundation has a two-pronged approach to helping women in Africa. It helps to train and empower the women to function in communities through health education and farming education, but it also educates the women from early literacy onwards, even sponsoring doctorate degrees. Rita also founded a similar foundation with her sister in 1992, but this is the current form of her charity.

In 2001 Rita became an Italian senator for life. She used her position to campaign for better conditions for academic workers in Italy, better funding for the sciences, tried to help the structural problems of Italy’s bureaucracy, and has been championing women in STEM.

What would Rita like about today’s world:
The world has not changed that much since her death in 2012 (it has only been 4 years), but I’m sure Rita would be both delighted and disappointed with the current state of the world. She would be happy that more women are beginning to study STEM, she would be happy that her work is making a difference in people’s lives, and she would be happy that her legacy lives on through a new generation of scientists. Rita would also be thrilled that so many new technologies are being developed to continue exploring science and making the world a better place.

However, Rita would be disappointed in the way politics is heading in her home country and her adopted country. Let’s make sure we keep the next generation of Rita Levi-Montalcini’s alive, so they can change the world.

Rita Levi-Montalcini made it her mission to make our world a better place, in as many ways as she could. She didn’t take no for an answer. She stood up for what she believed in. She made sure that the next generation of scientists could have better access to resources than she did. Let’s continue Rita’s legacy.

“It is not enough what I did in the past- there is also the future.” Rita Levi-Montalcini

Bibliography

Academia delle Scienze: Curiosity: Nobel and More. URL: http://www.accademiadellescienze.it/accademia/curiosit/nobel-e-altro

American Academy of Arts and Sciences: Book of Members, L. URL: https://www.amacad.org/multimedia/pdfs/publications/bookofmembers/ChapterL.pdf

Abbot, A., One hundred years of Rita (2009). Nature, 458. 564-567.

Aloe, L., and Chadakov, G. N. (2012). The Multiple Life of Nerve Growth Factor: Tribute to Rita Levi-Montalcini (1909-2012). Balkan Medical Journal, 30. 4-7.

Federico, A. (2013). Rita Levi-Montalcini, one of the most prominent Italian personalities of the twentieth century. Neurological Science, 34. 131-133.

EBRI: European Brain Research Institution, Rita Levi-Montalcini. URL: http://www.ebri.it/en/

National Academy of Science: Rita Levi-Montalcini. URL: http://www.nasonline.org/member-directory/deceased-members/53313.html

Network of European Neuroscience Institutes (ENI-NET): The European Brain Research Institute in Rome. URL: http://www.eni-net.org/organizations/the-european-brain-research-institute-in-rome

Rohrlich, R. (2000) Jewish Lives: Rita Levi-Montalcini. Judaism, 49 (1). 36-55

Sandrone, S. (2013) Rita Levi-Montalcini (1909-2012). Journal of Neurology (260), 940-941.

Zeliadt, N. (2013). Rita Levi-Montalcini: NGF, the prototypical growth factor. Proceedings of the National Academy of Science of the United States of America, 110 (13). 4873-4876

(2014). Italy and the Holocaust Foundation: Italian Race Laws. URL: http://www.italyandtheholocaust.org/italian-racial-laws.aspx

(2013) Foundazione Rita Levi-Montalcini. URL: http://www.ritalevimontalcini.org/en/who-we-are/le-nostre-radici/

(2010) Consiglio Nazionale delle Ricerche: Instituto di Biologia Cellulare e Neurobiologica: Home. URL: http://www.ibcn.cnr.it/index.php/en/

Images:

Last Goodbye to Rita Levi Montalcini (January 2, 2013). Il Secolo XIX. URL: http://www.ilsecoloxix.it/p/cultura/2013/01/02/APoEKSME-ultimo_saluto_montalcini.shtml

Rita Levi-Montalcini- Photo Gallery. Courtesy of the Becker Medical Library, Washington University School of Medicine. (2014). URL: https://www.nobelprize.org/nobel_prizes/medicine/laureates/1986/levi-montalcini-photo.html

Sino Biological Inc.: NGF Structure. URL: http://www.sinobiological.com/NGF-structure-a-6611.html

ZOOL 409: Histology. Department of Zoology, Southern Illinois University (2011). URL: http://www.siumed.edu/anatomy/KingCoS/409/z91.htm

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