Rous and the chicken sarcoma virus

In 1909 Peyton Rous, a Johns Hopkins graduate with two years of research behind him, joined the Rockefeller Institute in New York to run its cancer laboratory. Soon afterward he was given a barred Plymouth Rock hen with a large spindle-cell sarcoma on its breast. Birds were known to get fibromas, carcinomas and sarcomas, but none had been passed from bird to bird.

Rous grafted pieces of the tumor into hens from the closely related stock in which it had arisen, and they grew the same sarcoma; market-bought fowl of the same breed, mixed-breed birds, pigeons and guinea pigs did not. He reported this in 1910. Some months later the tumor had become much easier to transmit, and he tried a cell-free extract, passed through a Berkefeld filter to hold back cells and bacteria. Chickens injected with the filtrate developed the same tumor. His 1911 paper in the Journal of Experimental Medicine concluded that the cause was a filterable agent, as viruses were then known.

Rous was not the first to pass a chicken malignancy this way. In 1908 Ellerman and Bang in Denmark had transmitted a chicken leukemia by filtrate, but leukemia was not recognized as neoplastic until after 1930 and their work was largely ignored. Rous’s tumor was solid, and he soon found others. Attempts to pass mouse and rat tumors by filtrate failed, and most researchers took the chicken tumors for curiosities with no bearing on mammals.

When the First World War began Rous turned to blood transfusion, helping to set up the first American blood banks, and never went back to the chicken tumors. In the 1930s he encouraged his Rockefeller colleague Richard Shope to study rabbit skin papillomas, which Shope found could be transmitted by cell-free extracts. Rous then showed that these benign growths could turn malignant, especially after small doses of chemical carcinogens, a stepwise change he called tumor progression.

Later work showed the agent to be an RNA virus (1961), and after the discovery of reverse transcription in 1970 it was classed as a retrovirus. Its src gene became the prototype oncogene, and in 1980 the src protein was the first shown to be a tyrosine kinase. Rous was 87 when he shared the 1966 Nobel Prize in Physiology or Medicine with Charles Huggins, 55 years after his filtrate paper. He died in 1970.