Cancer Discovery Earns Nobel Prize for 2 at UC
Two UC San Francisco scientists who unearthed “the seeds of cancer” buried deep in the genetic makeup of both humans and animals won the Nobel Prize in medicine Monday. Their discovery is widely credited with sparking a revolution in cancer research.
Drs. J. Michael Bishop and Harold E. Varmus received the award for their finding in the mid-1970s that certain genes that guide normal growth can be converted into cancer-causing genes--called oncogenes--that transform healthy cells into tumor cells.
“The first time I read the thesis, I thought I had misunderstood it,” said Prof. Gosta Garthon of Sweden’s Nobel awarding committee. “Imagine: The likely cause of cancer comes from us, and all that the outside factors have to do is to push the right button.”
Cancer researchers hailed the committee’s choice as a powerful acknowledgement of the importance of research into oncogenes, about 40 of which have now been identified and linked to 20 forms of cancer, including cancers of the lung and breast.
“The discovery of oncogenes was a great, seminal discovery that has determined the course of cancer research ever since,” said Peter Vogt, a prominent USC microbiologist who collaborated with Bishop and Varmus. “I think cancer research has been completely transformed by this discovery.”
However, the announcement was marred Monday when a French researcher who worked with Bishop and Varmus complained bitterly that he should have shared in the award and that the Nobel committee ignored his contribution.
Dr. Dominique Stehelin, now at the Pasteur Institute in Lille, told Agence France-Presse, “I did all the work by myself, from A to Z.” He called his exclusion from the award “very unfair and rotten.”
In a press conference in San Francisco, Bishop described Stehelin as a post-doctoral fellow at the time “who carried out the bulk of the experiments.” Varmus and others said the complex evolution of oncogene research has made it difficult to determine how to allocate credit for pioneering work.
“All work that goes on in science was not done in a vacuum,” said Dr. Stuart Aaronson, chief of the laboratory of cellular and molecular biology at the federal National Cancer Institute. “Their work built on critically important work done by many.”
Bishop, 53, and Varmus, 49, both professors of microbiology at UCSF, arrived at their discovery through research into so-called retroviruses, a group of viruses suspected of being the most prevalent viral cause of tumors.
In the mid-1970s, the researchers found that a particular virus gene responsible for transforming a normal cell into a cancerous cell was actually derived from a normal gene present in chromosomes of all animals, including humans.
That gene and others like it, called proto-oncogenes, can be converted into oncogenes by outside influences such as viral infections or exposure to carcinogens, including chemicals and radiation. Once converted, they then transform normal cells into cancerous cells.
“The idea (had) been around for a long time that . . . cancer cells happen because something goes wrong with the genetic machinery that runs our cells,” Bishop said Monday. “The idea is that something happens to those genes. They get damaged and cause cells to run amok.
Part of ‘Genetic Dowry’
“Our work gave substance to the idea that our cells contain genes that if damaged can give rise to cancerous growth,” he added. “So, if you will, we have the seeds of cancer in our own genetic dowry.”
That discovery, published in 1976, opened up two areas for further research.
Scientists began searching for other oncogenes capable of setting in motion other forms of cancer and they began examining the role of their precursors, or proto-oncogenes, in normal growth and development.
“These genes control normal rates of growth and development of tissues and body parts,” said Dr. Laurence Kedes, chairman of the department of biochemistry at USC School of Medicine. “That’s the brilliant insight--that these cancer genes are closely linked to normal cellular division and development.”
A gene is the basic unit of heredity. It is contained within the nucleus of a cell and influences its workings. Every human cell holds more than 50,000 genes which, all together, direct the development and functioning of all organs and systems in the body.
Researchers said the oncogene findings may eventually produce new approaches to diagnosing and treating some cancers. The discovery that different cancers are caused by different, and very specific, genes suggests the need for a wide range of approaches, they said.
Question for the Future
“Can we, by knowing what turns on oncogenes, figure out how to turn them off?” wondered Dr. John Laszlo, senior vice president for research at the American Cancer Society, who said researchers are exploring ways of “putting the brakes back on the oncogenes.”
Laszlo also suggested that understanding which oncogenes trigger which cancers might make it possible to screen people for particular susceptibilities, thus enabling public health authorities to better target education and prevention activities.
It may also be possible to develop products that would counteract the effects of oncogenes on normal cells.
The Nobel Prize is awarded by the 50-member Nobel Assembly of the Karolinska Institute in Sweden. Bishop and Varmus were chosen for the 1989 prize in medicine from about 250 scientists whose names were submitted by nominating organizations.
It is not uncommon for Nobel Prizes to be awarded for work done many years earlier.
Bishop and Varmus received word of the prize, which carries a $460,000 award, before dawn Monday. Varmus was awakened by a call from a radio reporter looking for a comment; Bishop, whose son woke him, described the experience as “surreal.”
They celebrated with a champagne press conference at UCSF at 8:30 a.m.--early enough to get out in time to watch the San Francisco Giants play the Chicago Cubs at Candlestick Park in game five of the National League Championship Series.
Asked whether they had received advice on what to do with the money, Varmus said his wife had suggested a built-in dishwasher.
Born in York, Pa., Bishop is a graduate of Gettysburg College and Harvard Medical School. After two years of post-doctoral training at the federal National Institutes of Health, he joined the UCSF faculty in 1968.
Varmus was born in Oceanside, N.Y., and holds a bachelor’s degree from Amherst College, a master’s from Harvard and a medical degree from Columbia University. He, too, worked briefly at the NIH and went to work at UCSF in 1970.
Both men are married with two sons.
