Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor.

  title={Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor.},
  author={William Maxwell Cowan},
  journal={Annual review of neuroscience},
  • W. Cowan
  • Published 2001
  • Biology
  • Annual review of neuroscience
The announcement in October 1986 that the Nobel Prize for physiology or medicine was to be awarded to Rita Levi-Montalcini and Stanley Cohen for the discoveries of NGF and EGF, respectively, caused many to wonder why Viktor Hamburger (in whose laboratory the initial work was done) had not been included in the award. Now that the dust has settled, the time seems opportune to reconsider the antecedent studies on the relation of the developing nervous system to the peripheral structures it… 
A conversation with Rita Levi-Montalcini.
  • M. Chao
  • Biology
    Annual review of physiology
  • 2010
The neurotrophic theory explains why only half of the neurons produced early in development are needed to form a functional nervous system, and Rita Levi-Montalcini, who formulated this idea, celebrated her 100th birthday on April 22, 2009 in Rome.
Rita Levi-Montalcini and her major contribution to neurobiology
  • P. Strata
  • Biology
    Rendiconti Lincei. Scienze Fisiche e Naturali
  • 2018
The personality of Rita Levi-Montalcini is illustrated and how she first emerged within a prestigious school, while under the direction of Giuseppe Levi, a most inspiring and stimulating figure, to represent a milestone in the development of modern cell biology.
A Pact with the Embryo: Viktor Hamburger,
This paper explores how Hamburger walked this thin line between mechanistic reductionism and metaphysical vitalism in light of his work on the factors influencing growth of neurons into limb buds, and the discovery of nerve growth factor, work carried out with Rita Levi-Montalcini and Stanley Cohen.
Nerve growth factor: from the early discoveries to the potential clinical use
In this review, a comprehensive account is given for almost all of the clinical trials attempted until now by using NGF, highlighting possible limitations in the use of the neurotrophin as a drug.
The studies of Rita Levi‐Montalcini on the effects of tumor transplantation on the chorioallantoic membrane
Rita Levi‐Montalcini grafted fragments of mouse sarcomas on to the chorioallantoic membranes of 4‐ to 6‐day chick embryos and demonstrated that the tumors infiltrated the host blood vessels, and the ganglia showed hypertrophy, nerve fibers reaching to the implanted tumors.
Rita Levi-Montalcini (1909–2012)
Rita Levi-Montalcini received not only a solid training in biological sciences, but also learned how to approach scientific problems in the most rigorous way under the mentorship of the prominent neurohistologist Giuseppe Levi and interactions with the microbiologist Salvador Edward Luria and the virologist Renato Dulbecco.
Viktor Hamburger: A prepared, persistent, and deserving mind favored by many “Fortuities”
  • D. Kirk, G. Allen
  • History
    Developmental dynamics : an official publication of the American Association of Anatomists
  • 2001
Because Viktor Hamburger's accomplishments have been summarized in more conventional form so frequently and so well, it is decided to share accounts of some of the happy accidents and coincidences in his life that he so much enjoyed telling us about.
A Pact with the Embryo: Viktor Hamburger, Holistic and Mechanistic Philosophy in the Development of Neuroembryology, 1927–1955
  • G. Allen
  • Psychology
    Journal of the history of biology
  • 2004
This paper explores how Hamburger walked this thin line between mechanistic reductionism and metaphysical vitalism in light of his work on the factors influencing growth of neurons into limb buds, and the discovery of nerve growth factor, work carried out with Rita Levi-Montalcini and Stanley Cohen.
Early days of the nerve growth factor proteins.
  • E. Shooter
  • Biology, Chemistry
    Annual review of neuroscience
  • 2001
Adult male mouse submaxillary glands served as the preferred starting material for the isolation of the nerve growth factor (NGF) proteins in most of the isolation studies done, and no other source of NGF has been convincingly shown to synthesize the alpha and gamma subunits, and they may well be irrelevant to NGFs actions.


Developmental neurobiology and the natural history of nerve growth factor.
The story of NGF is more like a detective story than a scientific enterprise, since science usually unfolds according to well-defined rules, along the route paved by previous findings, but each finding has signaled a new turning point and opened up a new perspective.
Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions.
This joint paper corroborated the findings reported by Levi-Montalcini and established that nerve degeneration is an integral part of development.
NGF: An Uncharted Route
A disclaimer of personal merit, such as phrased above by Lwoff, is not a disclaimer of the significance of a phenomenon that chance rather than calculated search has brought to one’s attention, and
Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal.
  • S. Cohen
  • Biology, Medicine
    The Journal of biological chemistry
  • 1962
The isolation of the factor responsible for the earlier development of the incisors and eyelids is reported here, a heat-stable, nondialysable, antigenic protein, whose most distinctive chemical characteristic is the absence of phenylalanine and lysine.
Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo.
This study found that the sarcomas stimulated a specific type of sensory nerve, ventrolateral nerve fibers, while mediodorsal fibers did not react to the tumor, which led to the discovery that nerve growth factor was a diffusible chemical and later to discoveries that the compound was a protein.
A diffusible agent of mouse sarcoma, producing hyperplasia of sympathetic ganglia and hyperneurotization of viscera in the chick embryo
The paper provided the first evidence that nerve growth factor is a diffusible substance, and 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 Problem of Distribution of a Nerve Growth Factor Specific for Spinal and Sympathetic Ganglia
The hypothesis that nerve growth-stimulating entities are fairly widespread in the tissues is tentatively submitted, as it is concluded that the growth factor was associated with the protein component.
Motor and Sensory Hyperplasia following Limb-Bud Transplantations in Chick Embryos
The tentative explanation was proposed that a growthcontrolling agent travels in centripetal direction along the pathfinder motor fibers which first reach the peripheral area, and would control, in a quantitative way, either the mitotic activity or certain steps in the differentiation of the neuroblasts which lie in the neighborhood of the path Finder neurons.
Destruction of the sympathetic ganglia in mammals by an antiserum to a nerve-growth protein*
This study finds a remarkable decrease in size of the sympathetic ganglia of the injected mice prompted an extensive investigation of the effects of the antiserum on the sympathetic Ganglia of mice and other mammals.
Reduction of the naturally occurring motor neuron loss by enlargement of the periphery
Motor hyperplasia following the enlargement of the periphery by implantation of a supernumerary leg is not due to “remote control” of proliferation, as shown by motor neuron counts in 6‐day chick