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To discuss nerve growth, we must first be able to see the nerves and how they are interacting. Camillo Golgi developed the Golgi Stain which helps the nerve cells and their structural elements to be seen clearly.

This is a photo of Golgi, from around 1920, sitting at his desk in his office surrounded by tissue samples. It is important to know the main techniques used to visualize neurons because Montalcini and her team would not have been able to see the neurons they were studying. Golgi was also proposing ideas how neurons interacted even though his theory ended up being incorrect,

Source: Bentivoglio, M., Cotrufo, T., Ferrari, S., Tesoriero, C., Mariotto, S., Bertini, G., Berzero, A., & Mazzarello, P. (2019). The Original Histological Slides of Camillo Golgi and His Discoveries on Neuronal Structure. Frontiers in Neuroanatomy, 13. https://doi.org/10.3389/fnana.2019.00003

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A scan of Cajal's drawings on the theories of neurotransmission

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Cajal correctly predicts how neurons interact

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Cajal correctly predicts how neurons interact

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The next important discovery of this timeline is the Neuron Doctrine, written by Cajal. He used the Golgi Stain to discover that neurons don't directly touch each other to communicate, they communicate through chemical transmission.

This image is of drawings Cajal made when he was trying to determine the means of transmission, likely drawn in the early 1900s. The first one shows a the theory that the neurons directly touch and the second shows his theory that neurons communicate indirectly, which he observed under a microscope. This is important because knowing how the nerves communicate with each other can help indicate how they grow to be able to communicate with each other.

Source: National Institutes of Health. (2014). Santiago Ramón y Cajal Exhibit - Office of NIH History and Stetten Museum. History.nih.gov. https://history.nih.gov/pages/viewpage.action?pageId=1016727

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Harrison's drawings of axon's extending with time markers and measurement

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Ross Harrison shows how axon fibers can grow outside the body

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Ross Harrison shows how axon fibers can grow outside the body

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Ross Harrison was the first to research and discover that axons could live and grow while in a culture outside the body. This was an important discovery because researchers like Montalcini were be able to observe neurons behavior in a controlled environment and learn how neurons were functioning inside the body.

This image if from 1910 and shows how research of neurons was progressing past just understanding that they exist. Researchers were trying to understand how neurons were like other cells.

Source: Landecker, Hannah. (2002). New times for biology: nerve cultures and the advent of cellular life in vitro. Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences. 33. 667-694. 10.1016/S1369-8486(02)00026-2.

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Paul Weiss cut nerves in animals, and used freeze dried grafts to repair them. He was the first person to create a method for regenerating functional nerves. Even though the mechanisms for how nerves grow and regenerate wasn't completely understood, this was a big scientific discovery because it had a lot uses in the medical field.

He published this study in 1943 and it was a big move because in a couple of year later, Montalcini would publish her study on the nerve growth factor. This was the turning point in starting to understand how nerves grow.

Source: Weiss, P. (1943). Functional Nerve Regeneration Through Frozen-Dried Nerve Grafts in Gats and Monkeys. Experimental Biology and Medicine, 54(3), 277–279. https://doi.org/10.3181/00379727-54-14402p

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An embryo from Viktor Hamburger's study on the development of chicken embryos

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Viktor Hamburger starts testing theories of Nerve Growth on chicken embryos

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Viktor Hamburger starts testing theories of Nerve Growth on chicken embryos

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Viktor Hamburger was one of the first people to begin doing research and tests on embryos. In that research, he first studied how axons grow in an embryo and he discovered the conditions needed for an axon to grow. He then discovered than during embryonic development a lot of neurons die.

His discoveries are important because neuroscientists are finally discovering the mechanism on how a neuron develops and the environment they need. The discovery of embryonic work is important to because it will be used in research for years to come and even today.

Source: Hill, M.A. (2018, August 24) Embryology Embryology History - Viktor Hamburger. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Viktor_Hamburger

Noden, D. (2025). Viktor Hamburger (1900-2001). Sdbonline.org. https://www.sdbonline.org/sites/archive/SDBMembership/hamburger-obit.html

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The apartment building where Rita would start her work. It unfortunately got bombed during WW2

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Rita Levi-Montalcini makes a lab in her bedroom

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Rita Levi-Montalcini makes a lab in her bedroom

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Rita wanted to do neuroscience research but at the time, there was fascist rule in Italy and Jewish people weren't permitted to work at universities. She made up a fully functional lab with a microscope and a space to take apart eggs to analyze embryos. While her Nobel Prize winning discoveries came later, we can't ignore how she got her start in the 1940s. She was highly inspired by Viktor Hamburger's work.

Source: Goldstein, B. (2021, December 1). A Lab of Her Own. Nautilus. https://nautil.us/a-lab-of-her-own-238363/

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Images of cells either in the control group or injected with a counter to a nerve growth protein from Rita's research in 1960.

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Studying mouse tumors implanted in chick embryos

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Studying mouse tumors implanted in chick embryos

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In this study, Rita and her team researched how if a cell's nerve growth protein is inactive, there is a dramatic degeneration in the cells. This is a precursor to her Nobel research because they are finally starting to understand the importance of NGF in the embryo's development and how crucial the correct conditions are for development. It is important to understand where the research started because Rita and the others only build on these theories and continue to add on to how NGF works.

Source: Levi-Montalcini, R., & Booker, B. (1960). Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve-growth protein. Proceedings of the National Academy of Sciences, 46(3), 384–391. https://doi.org/10.1073/pnas.46.3.384

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Rita traveled to the Washington University in St. Louis to work with Viktor Hamburger, and after time, Stanley Cohen joined there work. Prior to joining them, he studied the Epidermal Growth Factor in mice, and this was a precursor to the work he would do on the NGF. His research on the EGF was frequently used as a model in other studies, specifically on the study he completed with Rita.

Cohen was known to be very meticulous in his work so he was a good addition to this team. It is important to know his work before he joined to show that he had solid experience in the field and brings important in theories.

Source: Carpenter, G., & Coffey, R. (2020). Stanley Cohen (1922–2020). Science, 367(6484), 1307–1307. https://doi.org/10.1126/science.abb4095

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An example of cells from the In Vitro experiments done by Rita.

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In vitro experiments were a huge factor and tool in Montalcini and Cohen's research. This is an image of an in vitro experiment done by the team and it is important to understand how to look at the results because a lot of their work and evidence was based on in vitro studies.

This image also contains a written caption that was provided by Montalcini and Cohen so we are able to understand a bit more of their thought process and their personal breakdown of the work. The work in this experiment was important for their later experiments because they were working towards isolating any nerve growth proteins.

Source: Levi-Montalcini, R., & Cohen, S. (1956). IN VITRO AND IN VIVO EFFECTS OF A NERVE GROWTH-STIMULATING AGENT ISOLATED FROM SNAKE VENOM. Proceedings of the National Academy of Sciences of the United States of America, 42(9), 695–699. https://doi.org/10.1073/pnas.42.9.695

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An assay of a nerve cell incubated with NGF (right), and a control not incubated with NGF (left) from their Nobel winning paper.

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Montalcini and Cohen publish their work on the Nerve Growth Factor

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Montalcini and Cohen publish their work on the Nerve Growth Factor

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In their work with chick embryos, Montalcini discovered what the Nerve Growth Factor is and how it works then Cohen purified it and identified it as a protein. They stated that NGF is a neurotrophin that helps support the neurons while they are developing, and it is one of the first cells of this type to be studied. This was the first time that a chemical mechanism for neurodevelopment was suggested then subsequently proved so their work was groundbreaking.

All work that is done now, studying growth proteins follows in the footsteps of this work.

Source: Nobel Foundation. (2019). The Nobel Prize in Physiology or Medicine 1986. NobelPrize.org. https://www.nobelprize.org/prizes/medicine/1986/press-release/

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This study theorizes that NGF's could be a possible treatment for Alzheimer's disease

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In patients with Alzheimer's disease, a large amount of cells are destroyed. Researchers theorized that if NGF's could be injected into a patient, cells in the brain could regenerate and symptoms would improve. There have been some issues getting this treatment to work but they are still working on it to try and provide hope and eventually a cure for Alzheimers.

Without the discovery from Montalcini and Cohen, and the many discoveries that followed theirs, research like this would not have been possible. This also relates to previous entries because without stains and an understanding on how neurons communicate, we wouldn't be able to attack the neurotransmitters researchers believe have an effect on this treatment.

Source: Mitra, S., Behbahani, H., & Eriksdotter, M. (2019). Innovative Therapy for Alzheimer’s Disease-With Focus on Biodelivery of NGF. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.00038

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Rita was born in Italy and went to medical school there. She had started neuroscience research there but unfortunately due World War 2, she had to go into hiding because of her Jewish heritage. She eventually moved to the US to do research at Washington University in St. Louis. The work she did to win her Nobel Prize with Viktor Hamburger and Stanley Cohen was at WashU from 1948 on. She later became an Italian Senator at the age of 97, up until she passed away at 103. Her resilience from all the awful things she experience, from Germany's occupation of Italy to having to fight to go to college, is likely what made her the brilliant, force she was up until died.

Source: Britannica. (2019). Rita Levi-Montalcini | Italian-American neurologist. In Encyclopædia Britannica. https://www.britannica.com/biography/Rita-Levi-Montalcini