With the launch of our growth factor product line, we thought it would be interesting to look back at the history of growth factors. Today we know that growth factors are a powerful tool that researchers can use to study the development of embryonic or induced pluripotent stem cells, and this is all thanks to two researchers that helped deepen our understanding of cell biology. Those two are Stanley Cohen and Rita Levi-Montalcini, who discovered Nerve Growth Factor (NGF) and Epidermal Growth Factor (EGF), and were awarded the Nobel Prize in Physiology or Medicine in 1986.
The story begins in the 1950’s in the lab of Dr. Viktor Hamburger (and yes, that is his real name) at Washington University, St. Louis. Dr. Levi-Montalcini had arrived in 1946, and was there working on an unexplained biological phenomenon (and although it is beyond the scope of this blog post, she has an incredible life story that I strongly encourage everyone read about). She had been studying nerve development in chick embryos, and had observed that if she grafted a certain tumor cell line anywhere on a developing embryo, then nerve fibers would grow very rapidly. She then discovered that even if she grafted the tumor nowhere near the area where the nerve fibers were, they would still develop more rapidly than normal embryos. In order to further study this phenomenon, she even went as far as to develop a special tissue culture system where she placed a sensory ganglion near a tumor fragment, and after only one day of growth, she could see nerve fibers extend towards the tumor. So in 1952 she inferred that there must be some kind of biochemical agent being released from these tumor cells that was capable of inducing the growth of nerve fibers from a distance. Unfortunately she was not a biochemist, so in order to find out what this agent was she enlisted the help of a one working in the Zoology department at Wash U., Dr. Stanley Cohen.
Dr. Cohen began by making a crude extract from the tumor cells, and when he applied this extract to the ganglion he saw that it had the same effect as the live cells. He was then able to determine that the agent in the extract was probably a protein because it was affected by heat, non-dialyzable, and was inactivated by proteases. However he also wanted to make sure it wasn’t a virus that was causing this effect. This caused him to procure some crude phosphodiesterase that had been purified from snake venom, and this was where the big break came in. When the tumor cells were treated with the snake venom phosphodiesterase, the nerve growth in the ganglion was multiple times better than it had been with the tumor extract alone, and even stranger, the ganglion treated with just the phosphodiesterase showed this same growth. Through more experimentation he discovered that there was another protein in the snake venom extract causing the effect, and once purified, and in 1957 Dr. Levi-Montalcini was able to inject this protein into the yolk sac of developing embryo’s and see the same effect as the tumor cells. They named this new protein Nerve Growth Factor. Continuing their partnership and through even more research, they also discovered Epidermal Growth Factor, which could stimulate the proliferation of epithelial cells.
Although the research didn’t make a huge impact at the time it was published, it is viewed as the beginning of our understanding of growth factors and how proteins can influence cell differentiation. Its importance was also aided by the continued work of Dr. Levi-Montancini and Dr. Cohen, and it is thanks to them that we currently have the understanding that we do. Their autobiographies and more can be found on http://www.nobelprize.org/nobel_prizes/medicine/laureates/1986/. Thanks for reading, and if you have any questions about Goldbio’s line of Growth Factors, check our website or contact us at techsupport@goldbio.com.
Levi-Montalcini, R., and Cohen, S. “In vitro and in vivo effects of a nerve growth-stimulating agent isolated from snake venom.” Proc. Natl. Acad. Sci. U. S. A. 42 (1956), 695–699
Cohen, S., and Levi-Montalcini, R. “Purification and properties of a nerve growth-promoting factor isolated from mouse sarcoma 180.” Cancer Res. 17 (1957), 15–20
Cohen S. “Origins of growth factors: NGF and EGF.” J Biol Chem. 283(49) (2008) 33793-33797
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