Cancer Work Earns Nobel For 2 In U.s.

October 10, 1989|By Peter Gorner.

The crucial discovery that we all carry the seeds of our own destruction within our genes-and when they go awry they can cause cancer-won the Nobel Prize in medicine Monday for virologists J. Michael Bishop and Harold Varmus, of the University of California, San Francisco.

Bishop, 53, and Varmus, 49, are leaders in the hottest area of cancer research-studies of the cancer-causing genes called oncogenes-and have won many awards for their discoveries of the relationship between viruses and cancer.

Both scientists seemed surprised by the Nobel, although colleagues had been predicting it for years. Bishop told a news conference that he was sound asleep when his 17-year-old son took a phone call from NBC at 3:30 Monday morning and rushed to wake up his parents.

Varmus said he was ``bewildered`` by the sudden attention. ``You know you`re in the running, but so are a lot of other good people,`` he said.

``I thought: `Jesus, why didn`t they win?` ``

The men said they had not decided what to do with their $455,000 prize, although Varmus` wife told him to count on a built-in dishwasher.

But a French colleague who trained under the two Americans during the landmark 1975 experiments that won them the Nobel reacted to the news with bitterness, complaining that he carried out the work and should at least have shared science`s highest honor.

``I am very disappointed,`` said Dominique Stehelin, a director of research for the National Center for Scientific Research at the Pasteur Institute in Lille. ``I find all that very unfair and rotten.

``I did all the work by myself, from A to Z,`` Stehelin told the French news agency Agence France-Press. ``I spent three years in their San Francisco lab, from 1972 to 1975, at a time when nobody other than me was working on the subject and I am not even associated in this distinction (the Nobel).``

Asked about Stehelin`s contribution, Bishop and Varmus were quick to credit their former student`s technical contribution.

``He was a postdoctoral fellow conducting experiments that Harold and I had conceived,`` Bishop said. ``This issue (of credit) is debated every year, almost, and has to be left to the Nobel committee. We were both at the (lab)

bench as well, but Stehelin did do the particular experiments reported in that paper.``

The paper he referred to was published in the March 11, 1976, issue of the British scientific journal Nature. The study, titled ``DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA,`` lists Stehelin as the first author, followed by Varmus, Bishop and another postgraduate student, Peter Vogt.

There is, however, no standardized way to determine who did what from the listings of names in scientific papers. Sometimes, the senior researchers list themselves last, sometimes first or in alphabetical order.

Other young scientists in their laboratory also contributed to the

``brutally difficult work,`` noted Varmus, singling out Vogt, now at the University of Southern California, who analyzed the genes of the virus that permitted the prize-winning experiments to be performed.

Bishop and Varmus teamed up in 1970 on the theory that a cause of cancer in humans and animals may be due to renegade genes within cells. The scientists were among four competing groups working with the Rous sarcoma virus that causes cancer in chickens by inserting its own genes into the genetic material (DNA) of a cell.

The virus was discovered in 1910 by Peyton Rous, who lived long enough to receive the Nobel Prize in 1966 when science was ready to accept the notion that a virus could cause cancer.

By the 1970s, other scientists had found the actual gene in the virus that was responsible for the chicken tumor, but Bishop and Varmus wanted to know if the gene was native to the virus, or had the virus pirated it from chickens eons ago.

They resolved to find out, in effect, which came first: The chicken or the virus?

The scientists found that the sarc (for sarcoma) oncogene is present in the chromosomes of normal chickens. That proved two things: the virus had stolen it originally, and the chicken sarc gene was capable all by itself of causing cancer if it somehow was mutated by an environmental factor.

But then, the scientists probed further and showed that the oncogene was present in other species. They studied other birds, such as geese and ducks before moving up the mammalian ladder to human beings. They proved that the gene has been conserved during evolution and must serve an important function in normal human development.

Scientists now have discovered at least 50 so-called ``proto-oncogenes,`` a term coined by Bishop, that are crucial for normal cell division and development of the organism. But mutations by carcinogens can turn friendly proto-oncogenes into killers.

Thus, as Bishop says, ``we proved that cancer always arises from our own genes, and that damage to those genes is fundamental to the growth of cancer cells.

``In this way, we can say that all cancer is genetic, although that doesn`t mean that cancer is always inherited.``

Their findings are considered a major advance in science`s attempt to understand how cancers originate, and hopefully to develop better treatments and possibly cures.