The 2004 Laureates / Basic Sciences Category / Life Sciences (Molecular Biology, Cell Biology, Neurobiology)

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Alfred George Knudson, Jr.

U.S.A. / August 9, 1922
Geneticist and Physician; Senior Advisor, Fox Chase Cancer Center

"Seminal contribution to the establishment of the theory of the tumor suppressor gene in the mechanism of human carcinogenesis"
In the early 1970s, Dr. Knudson proposed the "two-hit" hypothesis as a genetic mechanism of carcinogenesis through an elegant statistical analysis of retinoblastoma, a pediatric eye cancer. He soon advanced this hypothesis and reached the concept that mutational changes in "anti-oncogene", now termed "tumor suppressor gene", underlie the development of cancer. His "two-hit" hypothesis and the concept of "tumor suppressor" opened a new horizon in modern cancer genetics and played a pivotal role in the major developments in cancer researches.

BRIEF BIOGRAPHY

1922
Born in Los Angeles, California, U.S.A.
1947
Columbia University M.D.
1956
California Institute of Technology Ph.D. (Biochemistry & Genetics)
1956-1966
Chairman, City of Hope Medical Center
1966-1969
Associate Dean, Health Sciences Center, State University of New York at Stony Brook
1969-1976
Professor, University of Texas at Houston
1976-present
Senior Member, Fox Chase Cancer Center (1980-1982 President, 1992- Fox Chase Distinguished Scientist, Senior Advisor to the President)
1976-present
Adjunct Professor, Pediatrics and Human Genetics, School of Medicine, University of Pennsylvania

SELECTED AWARDS AND HONORS

1988
Charles S. Mott Prize, General Motors Cancer Research Foundation, Washington, D.C.
1997
Gairdner Foundation International Award, Toronto
1997
IBM—Princess Takamatsu Cancer Research Fund Lectureship and Award, Tokyo
1998
Albert Lasker Award for Clinical Medical Research
Members:
National Academy of Sciences, American Philosophical Society, American Academy of Arts and Sciences

SELECTED WORKS

1971
Mutation and cancer: statistical study of retinoblastoma, Proc. Natl. Acad. Sci. USA 68-4:820-823.
1973
Mutation and human cancer, Adv. Cancer Res. 17:317-352.
1976
Chromosomal deletion and retinoblastoma (with Meadows, A.T., Nichols, W.W. and Hill, R.) , New Engl. J. Med. 295:1120-1123
1993
Antioncogenes and human cancer, Proc. Natl. Acad. Sci. USA, 90:10914-10921.
2000
Chasing the cancer demon, Annu. Rev. Genet. 34:1-19.
2001
Two genetic hits (more or less) to cancer, Nature Reviews 1:157-162.
2003
Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer (with Vilenchik, M.M.), Proc. Natl. Acad. Sci. USA 100-22:12871-12876.
2003
Cancer genetics through a personal retrospectroscope, Genes chromosomes & Cancer 38-4:288-291 (Special Issue for Knudson).
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