"A Diffusible Agent of Mouse Sarcoma, Producing Hyperplasia of Sympathetic Ganglia and Hyperneurotization of Viscera in the Chick Embryo," by Rita Levi-Montalcini and Viktor Hamburger, appeared in 1953 in the Journal of Experimental Zoology. The paper provided the first evidence that nerve growth factor is a diffusible substance. Nerve growth promoting tumors were implanted into developing embryos to determine whether the tumors stimulated growth by direct contact or by a diffusible substance. The tumors were implanted into different parts of the embryo; one set of experiments implanted the tumor directly in the embryo, while another set of experiments placed the tumor on an exterior membrane. The membrane provided a barrier to direct contact with the nervous system, and allowed some chemical interaction between the tumor and the embryo. The tumor stimulated growth in both orientations, demonstrating that nerve growth factor was a chemical agent. The paper ends with two possible conclusions for the mechanism of nerve growth, the tumor may have been directly stimulating the ganglia by a diffusible signal, or it may have reduced the resistance of the chick tissues to the nerve growth. The term "nerve growth factor" is not explicitly used in this paper, and is referred to as a "diffusible agent" or a "growth promoting agent."

In "The Outgrowth of the Nerve Fiber as a Mode of Protoplasmic Movement," Ross Granville Harrison explores the growth of nerve fibers in vitro. The purpose of this experiment was to test two possible hypotheses for the growth of nerve fibers. Santiago Ramón y Cajal suggested that nerve growth is due to the extension of nerve fibers as they push through tissue. Victor Hensen's syncytial theory proposed an opposing view of nerve growth. He proposed that each neuron was connected by threads of cytoplasm and the successful connections stimulated further differentiation of the correct neural connections. Using hanging drop tissue cultures, Harrison provided significant evidence for Ramón y Cajal's theory by showing discrete cell membranes between cells and observing the growth of individual neurons.

Rita Levi-Montalcini is a Nobel Laureate recognized for her work in the discovery and characterization of nerve growth factor. Nerve growth factor (NGF) promotes the growth and maintenance of the nervous system in a developing system. The majority of her career has been devoted to investigating the many aspects of NGF.

Nerve growth factor (NGF) is a signaling protein and growth factor implicated in a wide range of development and maintenance functions. NGF was discovered through a series of experiments in the 1950s on the development of the chick nervous system. Since its discovery, NGF has been found to act in a variety of tissues throughout development and adulthood. It has been implicated in immune function, stress response, nerve maintenance, and in neurodegenerative diseases. It is named for its effect on the critical role it plays in the growth and organization of the nervous system during embryonic development.

Viktor Hamburger was an embryologist who focused on neural development. His scientific career stretched from the early 1920s as a student of Hans Spemann to the late 1980s at Washington University resolving the role of nerve growth factor in the life of neurons. Hamburger is noted for his systematic approach to science and a strict attention to detail. Throughout his life he maintained an interest in nature and the arts, believing both were important to his scientific work.

"In vitro Experiments on the Effects of Mouse Sarcomas 180 and 37 on the Spinal and Sympathetic Ganglia of the Chick Embryo" were experiments conducted by Rita Levi-Montalcini in conjunction with Viktor Hamburger and Hertha Meyer and published in Cancer Research in 1954. In this series of experiments, conducted at the University of Brazil, Levi-Montalcini demonstrated increased nerve growth by introducing specific tumors (sarcomas) to chick ganglia. Ganglia are clusters of nerve cells, from which nerve fibers emerge. This work led to the discovery of nerve growth factor (NGF) and later the Nobel Prize in Physiology or Medicine in 1986.

Epidermal growth factor is a signaling molecule that stimulates the growth of epidermal tissues during development and throughout life. Stanley Cohen discovered epidermal growth factor (EGF) during studies of nerve growth factor as a side effect of other experiments. EGF stimulates tissue growth by initiating a variety of cellular mechanisms. This work led to the 1986 Nobel Prize in Physiology or Medicine awarded to Cohen and Rita Levi-Montalcini. At the Nobel Award ceremony Levi-Montalcini focused her acceptance speech on nerve growth factor, while Cohen focused his on epidermal growth factor. Although they presented different topics, they were close collaborators and their combined effort led to the discovery of nerve growth factor. They had worked together in Viktor Hamburger's laboratory at Washington University in St. Louis.

Stanley Cohen published "Purification of a Nerve-Growth Promoting Protein from the Mouse Salivary Gland and its Neuro-Cytoxic Antiserum" in the Proceedings of the National Academies of Sciences in 1960. This paper outlined the successful purification and identification of nerve growth factor (NGF) as a protein, the developmental effects of depriving an embryo of NGF, and the discovery that NGF is also required for the maintenance of the nervous system.

Stanley Cohen is a biochemist who participated in the discovery of nerve growth factor (NGF) and epidermal growth factor (EGF). He shared the 1986 Nobel Prize in Physiology or Medicine with Rita Levi-Montalcini for their work on the discovery of growth factors. His work led to the discovery of many other growth factors and their roles in development.

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