Dr. Cohen made his first contributions to biological research as a post-doctoral investigator with Dr. Rita Levi-Montalcini. He performed biochemical studies of nerve growth factor (NGF), including those which showed that the substance was, in fact, a protein. He prepared antibodies to NGF which destroyed the embryonic nerve cells whose growth depends on this substance and revealed its significance in the development of the nervous system.
In the course of this work he found that the crude NGF extracts from salivary glands contained another material with striking effects on epidermal cells. This new substance accelerated the maturation of epidermal tissues in newborn mice, causing their teeth to erupt and their eyelids to open sooner than normal.
Using standard biochemical procedures, Dr. Cohen isolated, purified, and determined the structure of this substance, calling it epidermal growth factor (EGF). Later experiments revealed that it could also affect other types of cells. Dr. Cohen deduced that any cell which could respond to EGF must have on its surface a specific receptor protein to catch and bind EGF.
He discovered and analyzed this EGF-receptor molecule, and discovered that after EGF binds to the receptor, the two entities, linked together, enter the cell. This was the first biochemical explanation of the way that growth factors act upon the cells they govern.
In 1980, Dr. Cohen determined that EGF-receptor is an enzyme with the potential ability to add phosphorus to an amino acid. This type of enzyme is known as a protein kinase. EGF-receptor becomes a fully functional protein kinase only when EGF binds to it. Dr. Cohen discovered that activated EGF-receptor adds phosphorus to an amino acid known as tyrosine. This specific biochemical step is common to the action of several oncogenes, and its growth-stimulating action may be central to some types of carcinogenesis.
Through his discovery and analysis of EGF and its receptor, Dr. Cohen uncovered a general mechanism of cell growth which brings us closer to understanding such apparently different processes as embryonic growth, wound healing, tissue regeneration, endocrine disorders, and cancer.
To Dr. Cohen, for his discovery of epidermal growth factor (EGF) and its power to activate the crucial enzyme tyrosine kinase, illuminating the dynamics of cell growth, this 1986 Albert Lasker Basic Medical Research Award is given.
A prime mover in the evolution of several profound and advanced biological concepts, Dr. Levi-Montalcini was decades ahead of her time in perceiving the biochemical communications network that enables specific groups of cells to respond to the needs of the organism as a whole. Her discovery of nerve growth factor (NGF) created a broad new field of scientific inquiry and propelled later investigators to look for and to trace the influence of other growth factors.
Dr. Levi-Montalcini's initial observation that tumor tissue, implanted in chick embryos, causes sympathetic and sensory nerve fibers to grow and branch into the tumor tissue, prompted her elegant series of studies leading to the conclusion that a soluble substance, NGF, released by the tumor tissue is responsible for this effect. She then showed that the same tumor tissue, implanted in the membrane of a fertilized egg without direct contact with the embryo, causes nerve cells to grow into inappropriate organs and tissues. She later found the same substance in snake venom and mouse salivary glands, and devised a simple in vitro assay for it which is still in use in laboratories around the world.
In inspiring and extraordinarily fruitful collaborations with Dr. Stanley Cohen and other investigators, Dr. Levi-Montalcini pursued increasingly refined studies of NGF, demonstrating that it alters neuronal metabolism, increases the production of neurofilaments and microtubules, directs the growth of nerves in vivo, and stimulates specific cells to mature and become functioning neurons.
NGF has been indispensable to laboratory research on nerve cells, with potential implications for neurological and psychiatric disorders. Even more far-reaching has been the influence of Dr. Levi-Montalcini's vision of soluble factors regulating the growth and function of specific cells throughout the body. The consistent quality of her work, pursued without the techniques which today's investigators take for granted, shines as a beacon for every scientist whose imagination exceeds the resources at hand.
To Dr. Levi-Montalcini, for her profoundly original concept that cell growth is governed by powerful soluble substances, and for her discovery of nerve growth factor (NGF), this 1986 Albert Lasker Basic Medical Research Award is given.