Retroviruses, engineering and the future of science

A conversation with Harold Varmus and David Baltimore

Editor’s Note:  Drs. Baltimore and Varmus were interviewed separately in 2003, and their responses were combined in a question-and-answer format.

Bill Snyder
Published: April, 2004

Two of the nation’s most prominent Nobel laureates discuss recent scientific advances, including the potential to “engineer” the immune system to prevent viral infections, as well as the changing roles of government and the private sector in advancing the research enterprise, and the need to improve the public’s “science literacy.”

David Baltimore, Ph.D., president emeritus and professor of Biology at the California Institute of Technology, is a former director of the Whitehead Institute of Biomedical Research at MIT and former president of Rockefeller University. He shared the 1975 Nobel Prize with Howard Temin for identifying reverse transcriptase, and with Renato Dulbecco for other virological research. The discovery of the enzyme opened up the genomes of retroviruses and then all genomes for investigation. It also was the opening salvo in the very successful attack on the nature of cancer that has taken place since 1970, and set the stage for the discovery of HIV.

Harold Varmus, M.D., is president of the Memorial Sloan-Kettering Cancer Center in New York City, and former director of the National Institutes of Health. He shared the 1989 Nobel Prize with Michael Bishop for their discovery that the oncogene of the Rous sarcoma virus was not a true viral gene but was a normal cellular gene, which the retrovirus had acquired during replication and carried along. This led to the identification of a large family of genes that control normal cell growth and division. Mutations in these “oncogenes” can transform normal cells into tumor cells, and can lead to cancer.

Editor’s note: Drs. Baltimore and Varmus were interviewed separately in 2003, and their responses were combined in a question-and-answer format.

Where is the field of virology headed?

Varmus: One thing that’s happened in the last 20 years that really was unprecedented was the development of drugs that worked to treat viral illness. The idea of using protease inhibitors to counter viral infections had the earliest success with HIV. Now there is reason to believe that people are hot on the trail of developing protease inhibitors for the treatment of hepatitis C. That would be a tremendous advance, because hepatitis C is a virus that is still very difficult to grow.

One of the (other) things we’ve learned is how to work with viruses that can’t even be grown in tissue culture. That seems paradoxical, but we know enough about how to study viral genomes, and pull them apart so we can understand how parts of them work without having to grow the whole genome.

Baltimore: It occurred to me many years ago that … if you could modify the genetic inheritance of the cell, you could put into the cell something which could in principle totally prevent a virus from growing.

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