Viral Terrorists

In the late 1960s and early 1970s, Bishop's laboratory was one of many studying cancer-causing viruses. Although no virus had yet been shown to cause cancer in humans, researchers widely believed that such viruses would be found and that they would be similar to the ones that produced the disease in animals.

Francis Peyton Rous, a New York researcher, had identified the first cancer suspected to be caused by a virus in 1910. (At the time, no one had actually seen a virus, but indirect evidence led scientists to predict their existence.) The virus that produced this cancer, a muscle tumor (sarcoma) in chickens, was later isolated and named the Rous sarcoma virus. Other viruses were found to cause cancer in mice, rats, cats, monkeys, and other animals. These viruses could also transform normal cells grown in the laboratory into wildly multiplying forms that had many features of cancer cells.

Researchers in the early 1970s found a form of the Rous sarcoma virus that had lost its power to cause cancer. Comparing this virus with the normal one, they found that the cancer-causing form had one large gene at the end of its tiny genome that the harmless type lacked. Somehow, the scientists reasoned, that gene must produce cancer when the virus inserted it into a cell's genome. They called the gene src, for sarcoma. Other scientists identified different cancer-causing genes in other viruses. Robert Huebner and George Todaro of the National Cancer Institute, part of NIH, gave all these genes the name oncogenes, after a Greek word meaning "cancer." Huebner and Todaro proposed that when tumor viruses infected cells, the viruses slipped oncogenes into the cells' genomes much as a terrorist might smuggle in a bomb to blow up a building or a plane.

These genetic "bombs," however, might not go off for centuries. Huebner and Todaro suggested that normal cell genomes contained

Connections: Cancer to AIDS

Most viruses that cause cancer in animals belong to an unusual group called retroviruses ("backward viruses"). They were given this name because their genetic material is made of RNA rather than DNA. Instead of copying their DNA into RNA, as most living things do, retroviruses copy their RNA genomes into DNA and insert the DNA copy into the genomes of the cells they infect. When an infected cell copies its DNA before reproducing, it copies the virus's inserted genes as well. In this way, it makes more viruses.

In the 1960s and 1970s, many researchers were sure that sooner or later, someone would discover retroviruses that infect humans. Some thought that such viruses would prove to be a common cause of human cancer. Robert Gallo of the National Institutes of Health found the first human retrovirus in 1981 and showed that it caused a type of leukemia, a blood cancer. Gallo called the new virus HTLV, short for human T-cell leukemia virus. Shortly afterward he found a related virus that he named HTLV-2.

Only a few viruses have been proved to cause human cancers, and the types of cancer they trigger are uncommon. The discoveries that Gallo and others made about retroviruses became important in another way, however. Around the time Gallo discovered HTLV, medical journals were beginning to describe mysterious clusters of infections that attacked homosexual men. Researchers found that these men's immune systems had been destroyed. Scientists suspected that the cause of the disease was a retrovirus.

Gallo and his coworkers noticed that the mystery disease appeared to be transmitted in the same ways and affected the same cells as the leukemia produced by HTLV, and Gallo began to wonder whether a relative of HTLV might cause the new illness. His earlier work with the cancer retroviruses helped him isolate the virus that causes what came to be known as AIDS (acquired immunodeficiency syndrome) in 1983. Luc Montagnier and others at the Pasteur Institute in France independently discovered the virus, later called HIV (human immunodeficiency virus), at the same time. As Gallo had suspected, HIV proved to be a retrovirus similar to HTLV, and earlier discoveries about cancer-causing retroviruses helped scientists both to learn how HIV attacks immune system cells and to develop treatments for AIDS.

potential oncogenes, which they called proviruses. The researchers theorized that these proviruses had been placed into the cells during viral infection in the distant evolutionary past and were passed on to descendants along with the cells' other genes. The pro-viruses caused cancer only if activated by exposure to agents that changed DNA, such as X-rays or certain chemicals.

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