After completing an internship, Rous joined the
University of Michigan as an instructor of pathology. Alfred Warthin, head of the pathology department, advised him to study German to pursue specialised pathological course in Germany. To earn extra salary, Warthin arranged for him temporary teaching position at the summer school. In 1907, he went to Germany for a training course on morbid anatomy at Friedrichstadt Municipal Hospital (Krankenhaus Dresden-Friedrichstadt) in Dresden
Simon Flexner, director of the Rockefeller Institute and editor of the
Experimental Biology and Medicine which published his papers, recognized his research interest and offered him to lead cancer research at the institute. In 1909, he joined the laboratories as a full-time researcher at Rockefeller. and turned to that of chicken (specifically, a
sarcoma) in the early 1910. A woman brought him a
Plymouth Rock hen After several experiments of attempting to see the effect of the tumor exudate on healthy chicken, he realized that he could induce the same tumour in healthy chickens of the same breed only, so that genetic relatedness was important for the specific tumor. He continued to maintain and transplant the tumor in different individuals. In 1911, he made a seminal observation that cell-free filtrate (using Berkefeld filter that separate bacteria and large microbes) of chicken sarcoma could produce a malignant tumor when transferred to other chickens, This finding, that cancer could be transmitted by a virus (now known as the
Rous sarcoma virus, a
retrovirus), was widely discredited by most of the field's experts at that time as "utter nonsense" as it was a medically accepted fact that cancer was not an infection. As recorded by Charles Oberling:Tumor pathology was then completely under the spell of the German school of pathologic anatomy which, probably as an aftermath of the antagonism between
Robert Koch and [Rudolf]
Virchow, was utterly opposed to any theory of an infectious origin of cancer. And suddenly, in opposition to all these dignified and bearded
Herren Professoren who firmly believed what they said, rose the voice of a young American who claimed to have transmitted by a cell-free filtrate a neoplasm—a chicken sarcoma. Of course this could not be true, and for years they did not even try to repeat his experiments. An experiment they did with W.H. Tytler in 1912 gave the first clue of virus as the filterable agent, but failed to make an exact identification. Rous continued to work on cancer up to 1915, after which he gave up due to failure to obtain other carcinogenic agents from chicken and mice, and general acceptance of his discovery. After 18 years, he returned to cancer research upon the request of a colleague Richard Shope. later known as
Shope papilloma virus, and showed in 1935 that the virus was transmissible in healthy rabbits. Shope realized the similarity as a cancer agent with Rous's virus and requested Rous for further investigation. Rous obliged and soon reported on the details Shope papilloma virus. From his initial study, he knew that such tumor can "undergo progressive changes in the direction of malignancy when they grow vigorously." His research during the next three decades helped to confirm that viral papilloma can lead to cancers. The virus nature of the Rous sarcoma was shown by
William Ewart Gye of the
National Institute for Medical Research at Hampstead in 1925. The carcinogenic property was widely accepted after the discovery of the
oncogene in 1960, the exact gene of which was identified in the 1970s as ''
src.
Blood transfusion The outbreak of
World War I inspired Rous to turn his attention to blood transfusion, as he learned soldiers were dying at the war fronts due to blood loss. In 1915, he collaborated with Joseph R. Turner to work on the methods of blood transfusion. Although an Austrian physician
Karl Landsteiner had discovered blood types a decade earlier, the practical usage was not yet developed, as Rous described: "The fate of Landsteiner's effort to call attention to the practical bearing of the group differences in human bloods provides an exquisite instance of knowledge marking time on technique. Transfusion was still not done because (until at least 1915), the risk of clotting was too great." In 1916, they replaced the additive with a citrate-glucose solution which extended blood storage from one week to two weeks. The use of citrate was the key to the beginning of modern blood transfusion. At the time, blood transfusion was by direct person-to-person so that the preservation method allowed transfusion in the absence of a donor. An English physician
Oswald H. Robertson, serving in the US Army, brought the new technique to Belgium in 1917. It became the world's first blood bank.
Physiology Rous also made important contributions in the physiology of digestion focussing on the liver and gall bladder. He and Philip D. McMaster worked out the main function of gall bladder as the site of bile concentration. He showed that bile was concentrated by the gallbladder from water as it is released from the liver, and this also helped to the understanding of diseases associated with bile secretions, such as
jaundice and
gallstone formation. ==Awards and honors==