Sunday, February 3, 2002

Rita Levi-Montalicini : Scientist with Spirit

Rita Levi-Montalicini, is an excellent example of a scientist who is hard working, diligent and most of all determined.  During the course of her study, Rita was faced with opposition and grim circumstances but in spite of all the upheaval she chose to continue to do what loved and in the process will help improve millions of people’s lives.
Born in Turin, Italy on April 22, 1909, Rita was the youngest of twin girls. (Frangsmyr, 1986)  Rita Levi-Montalcini grew to be an American/ Italian biologist and won the Nobel Prize in Physiology or Medicine in 1986. (Wilson, 1987) This made her the fourth Nobel Prize winner to come from Italy’s small Jewish community. (Wilson, 1987)   Rita was raised in a Jewish family with three other siblings in what she calls a”wonderful family atmosphere, filled with love and devotion.” (Frangsmyr, 1986) Her parents instilled culture and appreciation for education into each one of their children.  (Frangsmyr, 1986)  Adamo Levi, her father, worked as an electrical engineer and Adele Montalcini, her mother, was a painter. (Frangsmyr, 1986)   Rita combined the last names of her mother and father when she started her professional career, which made up Levi-Montalcini.  (Wilson, 1987)  Rita’s father was a traditional man who believed that women should not pursue professional careers, for fear they would “interfere with the duties of being a wife and a mother.” (Frangsmyr, 1986) By the age of twenty, Rita felt that she could no longer be restricted to the role of a “feminist”.  ( Frangsmyr, 1986)  Much against her father’s wishes she went back to school to pursue a degree in medicine.  (Wilson, 1987)  She entered high school to fill in the gaps in her Greek, Latin and mathematics, which she completed in eight months.  (Frangsmyr, 1986)  Rita then enrolled into the University of Turin Medical School and graduated in 1936 with a Summa Cum Laude degree in medicine and surgery. (Purves and Lichtman, 1985; Wilson, 1987; Frangsmyr,1986) During the course of her medical school education she had the opportunity to work with Giuseppe Levi, the professor of anatomy.  (Purves and Lichtman, 1985)   It was under Mr. Levi’s supervision that Rita performed her first research project on neuroembyological tissue cultures, which at that time was a new technique.  (Purves and Litchman 1985; Frangsmyr, 1986)   Subsequently, working with these tissue cultures caused Rita to second guess whether she should go into neurology, psychiatry or research. (Pruves & Lichtman, 1985)
After Rita graduated, World War II started and Mussolini signed the “Manifesto Per La Difensa Della Razza.”  (Purves and Lichtman, 1985; Frangsmyr, 1986)  This document stated that non-Aryan Italian students could no longer obtain a professional degree.  (Frangsmyr, 1986; Purves na dLicheman, 1985)  Due to her non- Aryan/Jewish background, Rita was forced to find education elsewhere.  Frangsmyr, 1986) She received an offer to attend Brussels Neurological Institute in Belgium, which quickly solved her dilemma.  (Purves and Lichtman, 1985; Frangsmyr, 1986)  She attended the school as a guest and graduated in 1940 specializing in neurology and psychiatry and returned back to Turin just before the Germans were invading Belgium.  (Wilson, 1987)  Her whole family was intent on staying in Italy through the war, despite the fact that the Jewish community was being persecuted. (Frangsmyr, 1986)  To keep herself busy during the war, Rita decided to build a small laboratory in her bedroom to continue to do her research.  (Wilson, 1987; Frangsmyr, 1986; Purves and Litchman, 1985)  While in school, she read an article by Viktor Hamburger, which sparked her interest in chick embryos. (Frangsmyr, 1986) Hamburger’s study on these embryos enabled him to see how well the organism responded to other grafted animal limbs. (Encarta CD ROM, 1998)  The experiment showed that the nervous systems response was far too complex to be interpreted.  (Encarta CD ROM, 1998)  Rita chose to do further experimentation on the chick embryos to gain a better understanding of how the nervous system works.  (Purves and Lichtman, 1985)  Due to easy access of the nervous system with chick embryos, this allowed for the manipulation, experimentation and observable results under less than favorable conditions. (Encarta Encyclopedia CD ROM, 1998)
          During the period of 1938 through 1944, Rita started to experiment and was joined by Guiseppe Levi.  (Frangsmyr, 1986)  They wanted to understand what effect the periphery nervous system had on developing nerve centers in an embryo. (Frangsmyer, Rita’s CV, 1986) Guiseppe Levi was fleeing the Germans with Rita and her family.  (Purves and Lichtman, 1985)  Their work was constantly interrupted by the German invasions and heavy bombing that was taking place and they were forced to set up laboratories wherever they could. (Frangsmyr, 1986; Purves and Litchman, 1985)  Forced to leave Turin, Piedmont, and their final flea was to Florence where they stayed until the end of the war. (Purves and Lichtman, 1985; Frangsmyr, 1986)  In 1944, the American Army stopped the German attack on Florence. (Frangsmyr, 1986)  Rita worked in the Anglo-American Headquarters using her medical training to help the refugee camp.  (Frangsmyr,1986)  By 1945 the war had ended. Rita, her family and Guiseppe Levi were free to return home to Turin.  ( Purves and Lichtman, 1985)  Guiseppe Levi reclaimed his position as a professor of anatomy at the University of Turin, where he asked Rita to be his assistant. (Purves & Litchman, 1985)
In 1947, Viktor Hamburger, one of the original researchers of chick embryos, invited Rita to Washington University to be his partner.  (Wilson, 1986)  Rita accepted the offer and worked in the department of zoology.  (Wilson, 1986)  She performed the same experiments on the chick embryos as had been done with Guiseppe Levi, but with more sophisticated equipment.  (Wilson, 1986)  Their work consisted of grafting mouse sarcoma-180 cells and implanting them into chick embryos. (Montalacini, 1998)  The major discovery came when they figured out that the tumor could release a chemical that was carried throughout the blood stream of the embryo and enhanced nerve growth.  (Encarta CD ROM, 1998) The only problem was discovering what that chemical was. (Montalacini, 1998)  They turned to the new technique of tissue culturing which offered a way to isolate the chemical.  (Encarta CD ROM, 1998)  They called for the help of a biochemist by the name of Stanley Cohen and he agreed to help them on their endeavor.  (Montalacini, 1998)  His job was to figure out what causes the excessive cell growth. “He managed to restrict the growth factor to a fraction of the tumor cells containing both protein and nucleic acids.”(Montalcini, 2000) A series of tests had to be done to determine if in fact it was a protein or a nucleic acid. (Montalacini, 2000)  They tried putting snake venom on a tumor cell.  (Montalacini,2000)  The venom has a high concentration of phosphodiesterase. (Montalacini, 2000)  This phosphodiesterase actually will break down nucleic acids, therefore using it would prove if the “substance” was or was not a nucleic acid or protein.  (Motalacini, 2000)  It was in fact a protein, and the venom increased the nerve growth fibers without sarcoma 180 being present.  (Montalacini, 2000)   The nerve cells elicited a dense halo in the presence of snake venom, which were more abundant and potent than the samples of sarcoma 180.  (Montalacini, 2000)  Cohen was able to extract the NGF (nerve growth factor) and insert it into the chick embryos.  (Montalicini, 2000)  Recent studies conducted have shown that NGF may be found in a wide variety of cancer cells and many tissues, which might secrete what is known as nerve growth factor. (Montalcini, 2000)
Extensive studies concluded that Rita’s hypothesis regarding neurons dying at early stages was correct. (Montalacini, 2000)  In early development, many neurons die when they do not connect with the periphery nervous system.  (Montalacini, 2000)  In order to survive they must receive the protein, NGF, which will cause neurotropism.  (Montalacini, 2000) (Neurotropism: causes nerve fibers to grow toward the periphery nervous system; Dorland, 1995) The neurons that were given NGF were greater in number than those that were not.  (Montalacini, 2000)  This does not mean that the neurons increased in number, instead implies those “extra” neurons were there all along but were not getting the necessary NGF to survive and thrive.  (Montalacini, 2000)  By administering NGF you help to keep the majority of those nerve cells alive.  (Montalcini, 2000)  The main point is NGF alone can keep nerve cells alive without being inter-connected to other cells.  (Encarta Deluxe, 2000)
Today, scientists are hopeful in finding many ways of putting nerve growth factor to use. (Time, 1986)   NGF in the future will probably be used in the following ways: to treat diabetes, insulin helper, healing wounds that will not heal, replacing islets, and saving eye sight.  (Roberts,1995)   Recently scientists discovered that nerve growth factor can repair the “connection between torn sensory nerves and the spinal cord.” (Berger, 2000) The experiment was done on a rat using a “blend of nerve growth factor and brain derived neurotrophic factor, neurotrophin-3, and glial cell line derived factor.” (Berger, 2000) Within a week they discovered by using microelectrodes that the new “nerves” connected with the spinal cord responded to heat and pressure “with appropriate withdrawal reflexes.” (Berger, 2000) In 1998, an uncontrolled experiment with NGF was performed on 12 patients (14 eyes) who had corneal neurotrophic ulcers.  (Lambiase, 1998)  The results showed over a two-week period the restoration of the cornea with no side effects.   (Lambiase.., 1998)  Scientists are recently broadening their horizons by trying to find a cure for Alzheimer’s disease.  (Unknown, 1999)    They have been using animals for their experimentation and say that it has been successful thus far.  Unknown, 1998) The method proposed for human use is to collect cells from the epidermis and collect samples of fibroblasts.“ We would take the bad genes out…. and multiply the good genes, ” Dr. Tuszynski said. (“Bad genes” are implying the Alzheimer’s gene) (Unknown, 1998)  The good genes, (good genes have NGF) would be surgically implanted with a needle into the brain.  (Unknown, 1998)  The genes would be responsible for making the production code for NGF, which will grow and keep brain cells alive, whereby, slowing the effects of Alzheimer’s disease. (Unknown, 1998)
Rita Levi-Montalcini and Stanely Cohen have made great contributions to science, by giving their life’s work to benefit mankind. However, if the Germans and all their anti-Semitic followers had it their way Rita along with all the rest of the Jewish community would have been exterminated. It is a marvelous thing to imagine that under the horrific pressure she faced Rita never gave up her dream of becoming a scientist, even when it almost jeopardized her very existence. I along with the entire science community, am thankful that America stepped in and stopped Germany’s invasion of Florence or we might not have ever known that Rita Levi-Montalcini and her scientific discoveries ever existed.
Rita’s discovery will eventually end up saving many lives and provide a cure for an astronomical amount of diseases. In addition, decrease of suffering experienced by many patients that are ailed with these diseases.  Currently, NGF study is a hopeful cure for Alzheimer’s disease and certain cancers. 

References
{Anomonous} 1999. Gene Rx Aims to Slow Alzheimer’s Slide: Transplants Stimulates Cell-Saving Nerve Growth Factor. Maclean Hunter Ltd : (see original) www.elibrary.com/education ( March 19,2000)
Berger A. 2000. Scientists make rats & #39; Torn Nerves Regenerate (Summary): British Medical Journal; 320: 7229
Frangsmyr T. 1986. Les Prix Nobel: Rita Levi-Montalcini. Sweden: The Nobel Foundation (see original)): www.nobel.se/laureates/medicine-1986-2-autobio.html (Feburary 8,2000)  
Lambiase A, Rama P, Bonni S, Caprioglio G, Aloe L. 1998. Topical Treatment with Nerve Growth Factor for Corneal Neurotrophic Ulcers: The New England Journal of Medicine; 338 ( See original)
Montalcini R, Calissano P.2000. Nerve Growth Factor. USA: Microsoft Corporation
Purves D, Lichtman JW. 1985. Rita Levi-Montalcini: Principles of neural Development. Sunderland, M.A : Sinauer Associates (see original): http://zygote.swartnmore.edu/axonic.html ( march 8, 2000)
Roberts SS. 1995. Cell growth factor relationships and possible therapeutic uses. USA: American Diabetes Association Inc.(no page given)

Time Magazine. 1986. Nobel Prizes of Spirit and Dedication: the world pays tribute to eleven who stirred emotions and laid foundations of Medicine. USA: Time Inc.

Wilson HW, Biographical Dictionary. 1987. Nobel Prize Winners: Rita Levi-Montalcini. New York: The H.W. Wilson Company;625-27 p.