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Historical records matching Alfred George Knudson, Jr.
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About Alfred George Knudson, Jr.
Alfred was a geneticist specializing in cancer genetics. Among his many contributions to the field was the formulation of the Knudson hypothesis in 1971, which explains the effects of mutation on carcinogenesis (the development of cancer).
Knudson received his B.S. from California Institute of Technology in 1944, his M.D. from Columbia University in 1947 and his Ph.D. from California Institute of Technology in 1956. He held a Guggenheim fellowship from 1953 to 1954.
From 1970 to 1976, Knudson served as the Dean of Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston. He has been affiliated with the Fox Chase Cancer Center in Philadelphia from 1976 until his death in 2016.
Knudson is best known for his "two-hit hypothesis," explaining the incidence of hereditary cancers, such as retinoblastoma. Humans inherit two copies of every gene, one from each parent (except for genes on the X and Y chromosomes in males). Some people inherit one mutated version and one normal version of the retinoblastoma gene, which produces the retinoblastoma protein involved in DNA repair. The inherited mutation is "the first hit." Over time, a mutation may arise in the normal version in one cell, thus producing "the second hit," which leaves the cell with deficient DNA repair and a high risk of developing mutations in genes which control cell growth, leading to cancer.
Knudson's insight was to compare the incidence of retinoblastomas, including the number of tumors, the ages of occurrence, and whether tumors occurred in both eyes, among children in families with and without hereditary predisposition to retinoblastomas. Children in families with a hereditary predisposition have more tumors at a younger age and usually have tumors in both eyes. Children in families without the hereditary predisposition usually have only one tumor at a later age.
The differences in occurrence can be explained by the rate of gene mutation during cell division (a somatic mutation), and a model that requires only one somatic mutation per tumor in hereditary cases but requires two somatic mutations in one cell lineage in non-hereditary cases, i.e. the co-occurrence of two rare events. Knudson subsequently showed that the model was not only applicable to retinoblastoma but also to Wilms' tumors of the kidney. These studies led to the concept of tumor suppressor genes, which Knudson called "anti-oncogenes."
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Alfred George Knudson, Jr.'s Timeline
| 1922 |
August 9, 1922
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Los Angeles, Los Angeles County, California, United States
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| 2016 |
July 10, 2016
Age 93
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Philadelphia, Philadelphia County, Pennsylvania, United States
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