The nation's most prestigious honor for outstanding contributions to medical research will go to two cancer researchers whose work on the role genes play in cancer broke new ground. Peter C. Nowell, M.D., Gaylord P. Harnwell Professor of Pathology and Laboratory Medicine, and Alfred G. Knudson, Jr., M.D., Ph.D., an adjunct faculty member here and a geneticist at the Fox Chase Medical Center, are two of three scientists who received the Albert Lasker Clinical Medical Research Award Sept. 25 in New York City.
Nowell found the first evidence that abnormal chromosomes can cause cancer, and Knudson's suggested how genes might cause cancers that were not inherited. The work of both men was met with skepticism at the time they each made their discoveries.
The Lasker Awards, first presented in 1946, are often called America's Nobels, and 59 Lasker Award recipients have subsequently received the Nobel Prize.
Nowell spent most of his research career at Penn. His work in the 1950s on the effects of radiation on bone-marrow transplants in mice led to modern bone-marrow transplants for treating cancers.
His discovery in 1960, with the late David Hungerford of Fox Chase Cancer Center, of the role an abnormal chromosome played in leukemia was ground-breaking. It was only four years earlier that the precise number of human chromosomes had been fixed at 46, and chromosome studies were, by today's standards, quite primitive.
The discovery that individuals suffering from chronic myelogenous leukemia had a defect in chromosme number 22, now known as the "Philadelphia chromosome," is a basis for his now widely accepted hypothesis concerning the clonal nature of cancer and the concept of clonal evolution as a basis for tumor progression.
With a teaching award in pathology and laboratory medicine named after him, Nowell is a winner of the Lindback Distinguished Teaching Award in 1967 as well as numerous honors and awards, among them the Parke Davis Award and the Rous-Whipple Award of the American Association of Pathologists.He was the organizer and first director of the University of Pennsylvania Cancer Center and is currently its deputy director.
Knudson's 1971 theory helped explain why some tumors are hereditary and some appear to be sporadic. His "two-hit" hypothesis provided a unifying model for understanding cancer that occurs in individuals who carry a "susceptibility gene" and cancers that develop because of randomly induced mutations in otherwise normal genes.
In studying children with retinoblastoma, he observed the variable number of tumors that develop in those who inherit one retinoblastoma gene. He proposed that a second mutation, after conception of the child, was necessary for a tumor to develop. The same gene, known is RB1, is involved in the non-hereditary form, but both mutations, or hits, occur after conception.
Hits can occur in many ways - from an environmental toxin, dietary factors, radiation, or the kind of random mutation that sometimes occurs during the intricate process of normal cell replication.
Originally published on October 1, 1998