Peyton Rous

American pathologist

• Born: October 5, 1879
• Birthplace: Baltimore, Maryland
• Died: February 16, 1970
• Place of death: New York, New York

Rous found that solid tumors, or sarcomas, in animals could be transmitted using filtered cell-free extracts. The agent was later called the Rous sarcoma virus, or RSV.

Early Life

Peyton Rous (PAY-tun rows) was born to Charles and Frances Anderson Rous. His father, a grain merchant, died when Peyton was a child, leaving his mother to care for three children. After completing his secondary education in 1896, Rous entered Johns Hopkins University in Baltimore and graduated in 1900. Rous immediately entered the medical school at Johns Hopkins.

During his second year in medical school, Rous contracted a systemic form of tuberculosis, which Rous believed came from being exposed during an autopsy. Though he had recovered, Rous left school for a year on the advice of physicians. He traveled to Texas, where he lived with members of his mother’s family. Rous always felt the time he spent on a cattle ranch helped him develop a sense of humanity and empathy for others less fortunate than he.

After a year, Rous returned to Baltimore to complete his education. He received his medical degree in 1905. After completing a year of residency at Johns Hopkins Hospital, Rous accepted the position of instructor in pathology at the University of Michigan, a job he held from 1906 to 1908. During this time he also spent several months in Dresden, Germany, studying morbid anatomy.

Upon Rous’s return to the United States, the Rockefeller Institute for Medical Research in New York provided funding for Rous’s research in experimental pathology at Michigan. Specifically, Rous carried out studies of lymphocytes and published his results in the Journal of Experimental Medicine, a journal edited by Rockefeller Institute scientist Simon Flexner. Flexner and Rous ultimately developed a mutual professional admiration. In 1909, Flexner decided to change his research area to the study of poliomyelitis, so he invited Rous to join the institute and continue his studies of cancer pathology.

Life’s Work

The first evidence that certain forms of cancer may be associated with viruses came in 1908, when Vilhelm Ellermann and Oluf Bang demonstrated that leukemia in chickens could be transmitted using filtered extracts of blood. The significance of the work was initially overlooked, mainly because leukemia was not considered a form of cancer at the time. Nobel laureate J. Michael Bishop suggested, however, that a lack of interest in the chickens themselves also contributed to the work being overlooked. Rous was on the staff at the Rockefeller Institute in 1909 when a farmer from the Bronx brought him a Plymouth Rock chicken that had developed a tumor in its breast. Rous’s interest in tumors led him to successfully transplant cells from the tumor into another chicken of the same species had it been otherwise, the cells could have been rejected. The transplantation proved successful, and the recipient likewise developed a similar tumor. The malignant nature of the tumor was confirmed both by its ability to metastasize and by the histological appearance of the cells.

After several successful transplants, Rous carried out a transfer using filtered cell-free extracts prepared from the tumor tissue in a manner analogous to that carried out several years previously by Ellermann and Bang. Similar attempts had been made to transfer tumors in mammals dogs and mice without success. In retrospect, the attempts failed most likely because of transplant rejection among outbred species. Rous’s attempts in chickens, however, proved successful, and quantities as small as 0.2 ml were sufficient to transmit the cancer. He further demonstrated that the tumors could be serially transmitted in a like manner using extracts. He concluded that a filterable agent, an “ultramicroscopic parasitic agent” (Rous avoided the term virus at first) was involved.

For a time, Rous continued with his study of filterable agents, and with other experiments he demonstrated that embryonic chicken eggs could also be used to grow the “virus,” as a filterable agent became known. It should be noted that at the time, the term “virus” was meant literally (from the Latin for “poison”). However, it quickly became apparent to researchers that the agent, whatever it might have been, replicated. During the next several years, Rous and his colleagues isolated several other agents thought to cause malignant disease in chickens, but the difficulty in demonstrating similar agents in mammals led Rous to abandon his studies with chickens.

With the entrance of the United States into World War I, Rous shifted his interests to the development of a means to preserve blood needed for transfusions. Karl Landsteiner had already discovered the concept of blood types, and so Rous’s work had direct application in the storage of blood. Along with colleagues Oswald Robertson and Joseph Turner, Rous developed a preservative known as the Rous-Turner solution, which allowed blood to be stored for weeks in a sort of blood bank. The “banking” of blood that had been preserved with the Rous-Turner solution remained the primary means of storing blood for decades. Following the war, Rous researched how the liver and gall bladder functioned in animal physiology, and he discovered how the liver plays a part in the production of bile.

Rous returned to the study of tumors during the 1930’s. He collaborated with Richard Shope to discover a wart virus in rabbits. Rous gradually reached the conclusion that many cancers were caused by viruses, a simplistic understanding of the disease but one that nevertheless made sense given contemporary data. Because these tumors generally were benign and because Rous and others could not demonstrate a similar phenomenon in mice, most colleagues dismissed his studies as showing, simply, a benign tumor unique to certain animals. It would be years before the phenomenon was demonstrated in other animals. Rous showed that cancers could also develop if an animal were exposed to a variety of what became known as carcinogens: agents or substances such as chemicals that caused uncontrolled cell proliferation.

Though at the time the significance of Rous’s discoveries was not appreciated, Rous would receive numerous honors after scientists began to isolate dozens of similar cancer viruses and to understand their relevance to cancer. Recognition of Rous’s role in cancer biology culminated in his being awarded the 1966 Nobel Prize in Physiology or Medicine. The virus he discovered became known as the Rous sarcoma virus (RSV), one of the most important members of a group later known as retroviruses.

Rous retired from the Rockefeller Institute at age sixty-five with emeritus status. He also served as editor of the Journal of Experimental Medicine from 1922 until just before his death in 1970. As Rockefeller Institute colleague René Dubos commented after Rous’s death, Rous felt so competent in so many fields of biology and medicine that he rarely needed to consult others when deciding on which manuscripts to accept for publication in the journal.

Significance

Rous’s studies became the basis for a field in molecular biology called retrovirology. Retrovirology studies how the RNA genome of some viruses is copied by an enzyme (reverse transcriptase) into DNA following infection of the cell. The significance of Rous’s early work was not immediately apparent, because at the time tumors in chickens were not considered equivalent to human cancers. Others scientists, including Rous’s colleagues, later demonstrated that cell-free filtrates were capable of transmitting a wide range of cancers in mammals.

The seemingly simplistic structure of RSV and its genome allowed the agent to serve as an ideal “organism” for the study of those cancers caused by viruses. The results of these studies led to the discovery of the reverse transcriptase as well as the first of numerous oncogenes, pieces of cellular genetic information whose products are associated with the regulation of cell reproduction. The vast majority of cancers have been shown to be associated with inappropriate expression or mutations in these genes.

Bibliography

Bishop, J. Michael. How to Win the Nobel Prize. Cambridge, Mass.: Harvard University Press, 2003. Autobiography of the Nobel laureate. The author also addresses a brief history of the evolution of disease, including the discovery of tumor viruses and how they led to an understanding of oncogenes and the regulation of cell division.

Coffin, John, Stephen Hughes, and Harold Varmus. Retroviruses. Plainview, N.Y.: Cold Spring Harbor Laboratory Press, 1997. Extensive review of the structure and replication of retroviruses. Also addresses the early work of Rous and others.

Colome, Jaime. “Peyton Rous.” In The Nobel Prize Winners: Physiology or Medicine, Vol. 2. Pasadena, Calif.: Salem Press, 1991. Scientific biography of Rous, including a summary of his 1966 Nobel lecture.

Dimmock, N. J., A. J. Easton, and K. N. Leppard. Introduction to Modern Virology. 6th ed. Malden, Mass.: Blackwell, 2007. Examines the molecular biology of viruses. Includes a chapter explaining the role of cellular (and viral) oncogenes in the regulation of cell reproduction. Definitions help clarify the material.

Pelengaris, Stella, and Michael Khan, eds. The Molecular Biology of Cancer. Malden, Mass.: Blackwell, 2006. Collection of articles addressing causes and treatments of cancers and the role of viruses in some cancers. Includes a brief history of the subject.

Tooze, John, and Joseph Sambrook. Selected Papers in Tumour Virology. Plainview, N.Y.: Cold Spring Harbor Laboratory Press, 1974. Among the first collections of historical papers on the subject. Rous’s original paper is included, as well as a discussion of its contemporary significance.