ROUS, PEYTON (1879-1970)

American physician

Francis Peyton Rous was a physician-scientist at the Rockefeller Institute for Medical Research (later the Rockefeller University) for over sixty years. In 1966, Rous won the Nobel Prize for his 1910 discovery that a virus can cause cancer tumors. His other contributions to scientific medicine include creating the first blood bank, determining major functions of the liver and gall bladder, and identifying factors that initiate and promote malignancy in normal cells.

Rous was born in Baltimore, Maryland, to Charles Rous, a grain exporter, and Frances Wood, the daughter of a Texas judge. His father died when Rous was eleven, and his mother chose to stay in Baltimore. His sisters were professionally successful, one a musician, the other a painter.

Rous, whose interest in natural science was apparent at an early age, wrote a "flower of the month" column for the Baltimore Sun. He pursued his biological interests at Johns Hopkins University, receiving a B.A. in 1900 and an M.D. in 1905. After a medical internship at Johns Hopkins, however, he decided (as recorded in Les Prix Nobel en 1966) that he was "unfit to be a real doctor" and chose instead to concentrate on research and the natural history of disease. This led to a full year of studying lymphocytes with Aldred Warthin at the University of Michigan and a summer in Germany learning morbid anatomy (pathology) at a Dresden hospital.

After Rous returned to the United States, he developed pulmonary tuberculosis and spent a year recovering in an Adirondacks sanatorium. In 1909, Simon Flexner, director of the newly founded Rockefeller Institute in New York City, asked Rous to take over cancer research in his laboratory. A few months later, a poultry breeder brought a Plymouth Rock chicken with a large breast tumor to the Institute and Rous, after conducting numerous experiments, determined that the tumor was a spindle-cell sarcoma. When Rous transferred a cell-free filtrate from the tumor into healthy chickens of the same flock, they developed identical tumors. Moreover, after injecting a filtrate from the new tumors into other chickens, a malignancy exactly like the original formed. Further studies revealed that this filterable agent was a virus, although Rous carefully avoided this word. Now called the Rous sarcoma virus RSV) and classed as an RNA retrovirus, it remains a prototype of animal tumor viruses and a favorite laboratory model for studying the role of genes in cancer.

Rous's discovery was received with considerable disbelief, both in the United States and in the rest of the world. His viral theory of cancer challenged all assumptions, going back to Hippocrates, that cancer was not infectious but rather a spontaneous, uncontrolled growth of cells and many scientists dismissed his finding as a disease peculiar to chickens. Discouraged by his failed attempts to cultivate viruses from mammal cancers, Rous abandoned work on the sarcoma in 1915. Nearly two decades passed before he returned to cancer research.

After the onset of World War I, Rous, J. R. Turner, and O. H. Robertson began a search for emergency blood transfusion fluids. Nothing could be found that worked without red blood corpuscles so they developed a citrate-sugar solution that preserved blood for weeks as well as a method to transfuse the suspended cells. Later, behind the front lines in Belgium and France, they created the world's first blood bank from donations by army personnel. This solution was used again in World War II, when half a million Rous-Turner blood units were shipped by air to London during the Blitz.

During the 1920s, Rous made several contributions to physiology. With P. D. McMaster, Rous demonstrated the concentrating activity of bile in the gall bladder, the acid-alkaline balance in living tissues, the increasing permeability along capillaries in muscle and skin, and the nature of gallstone formation. In conducting these studies, Rous devised culture techniques that have become standard for studying living tissues in the laboratory. He originated the method for growing viruses on chicken embryos, now used on a mass scale for producing viral vaccines, and found a way to isolate single cells from solid tissues by using the enzyme trypsin. Moreover, Rous developed an ingenious method for obtaining pure cultures of Kupffer cells by taking advantage of their phagocytic ability; he injected iron particles in animals and then used a magnet to separate these iron-laden liver cells from suspensions.

In 1933, a Rockefeller colleague's report stimulated Rous to renew his work on cancer. Richard Shope discovered a virus that caused warts on the skin of wild rabbits. Within a year, Rous established that this papilloma had characteristics of a true tumor. His work on mammalian cancer kept his viral theory of cancer alive. However, another twenty years passed before scientists identified viruses that cause human cancers and learned that viruses act by invading genes of normal cells. These findings finally advanced Rous's 1910 discovery to a dominant place in cancer research.

Meanwhile, Rous and his colleagues spent three decades studying the Shope papilloma in an effort to understand the role of viruses in causing cancer in mammals. Careful observations, over long periods of time, of the changing shapes, colors, and sizes of cells revealed that normal cells become malignant in progressive steps. Cell changes in tumors were observed as always evolving in a single direction toward malignancy.

The researchers demonstrated how viruses collaborate with carcinogens such as tar, radiation, or chemicals to elicit and enhance tumors. In a report co-authored by W. F. Friedewald, Rous proposed a two-stage mechanism of carcinogenesis. He further explained that a virus can be induced by carcinogens or it can hasten the growth and transform benign tumors into cancerous ones. For tumors having no apparent trace of virus, Rous cautiously postulated that these spontaneous growths might contain a virus that persists in a masked or latent state, causing no harm until its cellular environment is disturbed.

Rous eventually ceased his research on this project due to the technical complexities involved with pursuing the interaction of viral and environmental factors. He then analyzed different types of cells and their nature in an attempt to understand why tumors go from bad to worse.

Rous maintained a rigorous workday schedule at Rockefeller. His meticulous editing and writing, both scientific and literary, took place during several hours of solitude at the beginning and end of each day. At midday, he spent two intense hours discussing science with colleagues in the Institute's dining room. Rous then returned to work in his laboratory on experiments that often lasted into the early evening.

Rous was appointed a full member of the Rockefeller Institute in 1920 and member emeritus in 1945. Though officially retired, he remained active at his lab bench until the age of ninety, adding sixty papers to the nearly three hundred he published. He was elected to the National Academy of Sciences in 1927, the American Philosophical Society in 1939, and the Royal Society in 1940. In addition to the 1966 Nobel Prize for Medicine, Rous received many honorary degrees and awards for his work in viral oncology, including the 1956 Kovalenko Medal of the National Academy of Sciences, the 1958 Lasker Award of the American Public Health Association, and the 1966 National Medal of Science.

As editor of the Journal of Experimental Medicine, a periodical renowned for its precise language and scientific excellence, Rous dominated the recording of forty-eight years of American medical research. He died of abdominal cancer in New York City, just six weeks after he retired as editor.