Francis Peyton Rous
Peyton Rous nobel.jpg
Francis Peyton Rous
BornOctober 5, 1879
DiedFebruary 16, 1970(1970-02-16) (aged 90)
NationalityAmerican
Alma materJohns Hopkins University, Johns Hopkins School of Medicine
Known forOncoviruses
Awards
Scientific career
FieldsVirology

Francis Peyton Rous ForMemRS (/rs/) (October 5, 1879 – February 16, 1970) was an American pathologist at the Rockefeller University known for his works in oncoviruses, blood transfusion and physiology of digestion.[1] A medical graduate from the Johns Hopkins University, he was discouraged to become a practicing physician due to severe tuberculosis. After three years of working as an instructor of pathology at the University of Michigan, he became dedicated researcher at the Rockefeller Institute for Medical Research for the rest of his career.

His discovery in 1911 that a chicken tumor was caused by a virus (later named Rous sarcoma virus) led to more discoveries and understanding of the role of viruses in the development of certain types of cancer. He was awarded a Nobel Prize in Physiology or Medicine for his work in 1966,[2][3] 55 years after his initial discovery and he remains the oldest recipient of the Nobel Prize in Medicine or Physiology.[4]

He and Joseph R. Turner studied methods to make use of blood types for blood transfusion. During World War I, they developed a technique for preserving blood sample by using citrate. This enabled the first practical storage of blood samples for transfusion and was introduced by Oswald H. Robertson at the front line in Belgium in 1917 as the world's first blood bank.

Early life and education

Rous was born in Baltimore, Maryland, to Charles Rous and Frances Anderson née Wood. He had two younger sisters. His father, a grain broker, died when he was 11 years of age. He studied at the local public schools up to secondary education.[1] He received a scholarship to Johns Hopkins University from where he obtained a B.A. degree in 1900.[5] He immediately took up medicine at the John Hopkins Medical School.[6]

While in the second year at the medical school, Rous contracted tuberculosis through his injured finger while performing an autopsy. A tuberculous bone (axillary tuberculous lymphadenitis) developed in his armpit and was surgically removed. He was given leave from the medical school for recovery. His uncle got him a job as a cowboy at a cattle ranch in Texas, where he worked for a year. He was able to resume his medical course in 1904. Due to the disease, he considered himself as unfit to be a physician, or a "real doctor," for which he focussed his interest in medical research.[7] He obtained an M.D. degree in 1905.[6]

Career and research

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.[7] He published his first technical paper on white blood cell analysis in the Proceedings of the Society for Experimental Biology and Medicine (now Experimental Biology and Medicine) in 1906.[8] In 1907, he went to Germany for a training course on morbid anatomy at Friedrichstadt Municipal Hospital (Krankenhaus Dresden-Friedrichstadt) in Dresden[6] under Christian Georg Schmorl.[1]

On his way home from Germany, he showed symptoms of pulmonary tuberculosis and was sent to the Adirondack Mountains in northeastern Upstate New York for recovery.[1] After his return in 1908, Warthin informed him of a Rockefeller Scholarship for cancer research at the Rockefeller Institute for Medical Research (now Rockefeller University) in New York.[1][7] Using the grants, he studied lymphocytes on which he published a series of papers in 1908.[9][10][11] 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.[6] In 1920, he was appointed Member of the Rockefeller Institute, and became Member Emeritus in 1945, the position he occupied till his death.[7]

Cancer

Rous started his Rockefeller research on the tumors in rodents,[12][13] and turned to that of chicken (specifically, a sarcoma) in the early 1910. A woman brought to him a Plymouth Rock hen[6] which had developed a "large irregularly globular mass" on its left breast two months earlier.[14] He identified the tumor as a "spindle-celled sarcoma."[15] 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.[5] His first report in May 1910 on spontaneous chicken tumor established the first avian tumor that was transplantable to other individuals. Speculating the medical importance, he noted that "there is no reason to suspect on these points [of growth and transmission] that the neoplasm will differ from the better-known tumors of mammals."[14]

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,[15] describing:

A transmissible sarcoma of the chicken has been under observation in this laboratory for the past fourteen months, and it has assumed of late a special interest because of its extreme malignancy and a tendency to wide-spread metastasis... small quantities of a cell-free filtrate have sufficed to transmit the growth to susceptible fowls.[16]

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 is not an infection.[17] 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 [Rodolf] 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.[1]

He was even accused of using faulty technique and contaminating the tumor samples with cancer cells.[17] But he was convinced the malignancy was as those of any other cancer cells, the only difference being that it could be produced by a cell-free filtrate of a tumor. Experiments he continued with James B. Murphy and published made conclusive evidences for the cancerous nature of the infection.[18][19][20] An experiment they did with W.H. Tytler in 1912 gave the first clue of virus as the filterable agent,[21] but failed to make an exact identification.[22]

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.[7] In 1933, Shope had discovered that a skin tumor (papilloma) in cottontail rabbits was due to a filterable virur,[23] later known as Shope papilloma virus,[24] and showed in 1935 that the virus was transmissible in healthy rabbits.[25] 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."[26] His research during the next three decades helped to confirm that viral papilloma can lead to cancers.[5]

The virus nature of the Rous sarcoma was shown by William Ewart Gye of the National Institute for Medical Research at Hampstead in 1925.[27][28] The carcinogenic property was widely accepted after the discovery of the oncogene in 1960,[29] the exact gene of which was identified in the 1970s as src.[5][30]

Blood transfusion

The outbreak of World War I inspired Rous turn his attention on blood transfusion, as he learnt soldiers dying at the war fronts due to blood loss.[31] In 1915, he collaborated with Joseph R. Turner to work on the methods of blood transfusion.[17] That year, they deviced a method for testing blood compatibility to avoid complications in transfusion.[32] 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."[33]

He and Turner also successfully developed a technique for prolonged blood preservation initially by adding gelatine in the blood sample.[34] In 1916, they replaced the additive with a citrate-glucose solution which extended blood storage from one week to two weeks.[35][36] 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.[31][37]

Physiology

Rous also made important contributions in the physiology of digestion focussing on the liver and gall bladder.[17] With Louise D. Larimore, he described the conditions leading liver damage and the effect on bile secretion.[38] 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 the water as it was released from the liver,[39] and this also help to understand disease associated with bile secretions,[40] such as jaundice[41] and gallstone formation.[42]

Awards and honors

Rous was elected a Foreign Member of the Royal Society (ForMemRS) in 1940,[1] and he won the Albert Lasker Award for Basic Medical Research in 1958[43] and the National Medal of Science in 1965.[44] He was also member of the Royal Society of Medicine, the Royal Danish Academy of Sciences and Letters, and the Norwegian Academy of Science and Letters. He was appointed Honorary Fellow of the Weizmann Institute of Science and Foreign Correspondent of the Académie Nationale de Médecine in Paris. He also received the Kovalenko Medal of the National Academy of Sciences, the Distinguished Service Award of the American Cancer Society, the United Nations Prize for Cancer Research, and the Paul Ehrlich and Ludwig Darmstaedter Prize from the Federal Republic of Germany.[7]

Rouse shared the Nobel Prize in Physiology or Medicine in 1966 with Charles Brenton Huggins "for his discovery of tumour-inducing viruses."[45] As early as 1926, Karl Landsteiner had nominated him and subsequently received other 16 nominations up to 1951,[46] but was selected 55 years after his initial discovery at the age of 87, and he is recorded as the oldest recipient of the Nobel Prize in Medicine or Physiology.[4] His remains "the longest 'incubation period' in the 110 years history of the Nobel Prizes in Physiology or Medicine."[5][6]

Personal life

Rous married Marion Eckford de Kay in 1915 who survived him by five years and died in 1985. He had three daughters, Marion (Marni), Ellen and Phoebe. Marni (1917–2015) was a children's book editor, and the wife of another Nobel Prize winner, Alan Lloyd Hodgkin.[47] Phoebe married Thomas J. Wilson, Director of the Harvard University Press.

In his later life he wrote biographies of Simon Flexner[48] and Karl Landsteiner.[33]

Death

Rous died of abdominal cancer at the Memorial Sloan Kettering Cancer Center in New York.[17] His wife died in 1985.[47]

References

  1. ^ a b c d e f g h Andrewes, C. H. (1971). "Francis Peyton Rous. 1879-1970". Biographical Memoirs of Fellows of the Royal Society. 17: 643–662. doi:10.1098/rsbm.1971.0025. ISSN 0080-4606. PMID 11615431. S2CID 32825036.
  2. ^ Cech, Pavel (2010). "Nobel Prize laureates. Francis Peyton Rous (1879-1970)". Casopis Lekaru Ceskych. 149 (12): 619–620. ISSN 0008-7335. PMID 21387589.
  3. ^ Sulek, K. (1969-06-15). "Nobel prize for Francis Peyton Rous in 1966 for the discovery of carcinogenic viruses and for Charles Huggins for the introduction of hormones for treatment of neoplasms". Wiadomosci Lekarskie. 22 (12): 1161–1162. ISSN 0043-5147. PMID 4896432.
  4. ^ a b "Facts on the Nobel Prize in Physiology or Medicine". NobelPrize.org. Retrieved 2022-03-18.
  5. ^ a b c d e Weiss, Robin A.; Vogt, Peter K. (2011-11-21). "100 years of Rous sarcoma virus". Journal of Experimental Medicine. 208 (12): 2351–2355. doi:10.1084/jem.20112160. ISSN 1540-9538. PMC 3256973. PMID 22110182.
  6. ^ a b c d e f Kumar, Prasanna; Murphy, Frederick A. (2013). "Who is this man? Francis Peyton Rous". Emerging Infectious Diseases. 19 (4): 661–663. doi:10.3201/eid1904.130049. PMC 3647430. PMID 23751005.
  7. ^ a b c d e f "Peyton Rous – Biography". Nobelprize.org. Retrieved 6 June 2011.
  8. ^ Rous, F. Peyton (1906). "The effects of struggle on the content of white cells in the lymph". Experimental Biology and Medicine. 4 (1): 129–130.
  9. ^ Rous, F. Peyton (1908-05-01). "The effect of pilocarpine on the output of lymphocytes through the thoracic duct". Journal of Experimental Medicine. 10 (3): 329–342. doi:10.1084/jem.10.3.329. PMC 2124525. PMID 19867134.
  10. ^ Rous, F. P. (1908). "Some differential counts of the cells in the lymph of the dog: their bearing on problems in haematology". The Journal of Experimental Medicine. 10 (4): 537–547. doi:10.1084/jem.10.4.537. PMC 2124537. PMID 19867147.
  11. ^ Rous, F. Peyton (1908). "An inquiry into some mechanical factors in the production of lymphocytosis". Journal of Experimental Medicine. 10 (2): 238–270. doi:10.1084/jem.10.2.238. PMC 2124515. PMID 19867129.
  12. ^ Rous, P. (1909-11-01). "Parabiosis as a test for circulating anti-bodies in cancer: First paper". The Journal of Experimental Medicine. 11 (6): 810–814. doi:10.1084/jem.11.6.810. PMC 2124743. PMID 19867287.
  13. ^ Rous, Peyton (1910-05-01). "An experimental comparison of transplanted tumor and a transplanted normal tissue capable of growth". Journal of Experimental Medicine. 12 (3): 344–366. doi:10.1084/jem.12.3.344. PMC 2124799. PMID 19867332.
  14. ^ a b Rous, Peyton (1910-09-01). "A transmissible avian neoplasm.(Sarcoma of the common fowl.)". Journal of Experimental Medicine. 12 (5): 696–705. doi:10.1084/jem.12.5.696. PMC 2124810. PMID 19867354.
  15. ^ a b Rubin, Harry (2011). "The early history of tumor virology: Rous, RIF, and RAV". Proceedings of the National Academy of Sciences. 108 (35): 14389–14396. doi:10.1073/pnas.1108655108. PMC 3167550. PMID 21813762.
  16. ^ Rous, Peyton (1911). "A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells". Journal of Experimental Medicine. 13 (4): 397–411. doi:10.1084/jem.13.4.397. PMC 2124874. PMID 19867421.
  17. ^ a b c d e Brody, Jane E. (1970-02-17). "Dr. Peyton Rous, Nobel Laureate, Dies". The New York Times. p. 43. ISSN 0362-4331. Retrieved 2022-03-18.
  18. ^ Murphy, James B.; Rous, Peyton (1912-02-01). "The behavior of chicken sarcoma implanted in the developing embryo". Journal of Experimental Medicine. 15 (2): 119–132. doi:10.1084/jem.15.2.119. PMC 2124960. PMID 19867511.
  19. ^ Rous, P.; Murphy, J. B. (1912-03-01). "The histological signs of resistance to a transmissible sarcoma of the fowl". The Journal of Experimental Medicine. 15 (3): 270–286. doi:10.1084/jem.15.3.270. PMC 2124916. PMID 19867522.
  20. ^ Rous, Peyton; Murphy, James B. (1913-02-01). "Variations in a chicken sarcoma caused by a filterable agent". Journal of Experimental Medicine. 17 (2): 219–231. doi:10.1084/jem.17.2.219. PMC 2125032. PMID 19867639.
  21. ^ Rous, Peyton; Murphy, Jemes B.; Tytler, W. H. (1912-11-16). "A filterable agent the cause of a second chicken-tumor, an osteochondrosarcoma". Journal of the American Medical Association. LIX (20): 1793–1794. doi:10.1001/jama.1912.04270110207011.
  22. ^ Rous, Peyton; Murphy, James B. (1914-01-01). "On the causation by filterable agents of three distinct chicken tumors". Journal of Experimental Medicine. 19 (1): 52–68. doi:10.1084/jem.19.1.52. PMC 2125138. PMID 19867749.
  23. ^ Shope, Richard E.; Hurst, E. Weston (1933-11-01). "Infectious papillomatosis of rabbits, with a note on the histopathology". Journal of Experimental Medicine. 58 (5): 607–624. doi:10.1084/jem.58.5.607. PMC 2132321. PMID 19870219.
  24. ^ Noyes, W. F.; Mellors, R. C. (1957-10-01). "Fluorescent antibody detection of the antigens of the Shope papilloma virus in papillomas of the wild and domestic rabbit". The Journal of Experimental Medicine. 106 (4): 555–562. doi:10.1084/jem.106.4.555. ISSN 0022-1007. PMC 2136805. PMID 13475613.
  25. ^ Shope, R. E. (1935-03-01). "Serial Transmission of Virus of Infectious Papillomatosis in Domestic Rabbits". Experimental Biology and Medicine. 32 (6): 830–832. doi:10.3181/00379727-32-7875.
  26. ^ Rous, Peyton; Beard, J. W. (1935-10-01). "The progression to carcinoma of virus-induced rabbit papillomas (Shope)". Journal of Experimental Medicine. 62 (4): 523–548. doi:10.1084/jem.62.4.523. PMC 2133298. PMID 19870432.
  27. ^ Gye, William Ewart; Gordon, M. H.; McCartney, J. E. (1925). "Discussion On Filter-Passing Viruses And Cancer". The British Medical Journal. 2 (3370): 189–196. ISSN 0007-1447.
  28. ^ "William Ewart Gye, 1884-1952". Obituary Notices of Fellows of the Royal Society. 8 (22): 418–430. 1953. doi:10.1098/rsbm.1953.0008.
  29. ^ Martin, G. S. (2001). "The hunting of the Src". Nature Reviews. Molecular Cell Biology. 2 (6): 467–475. doi:10.1038/35073094. PMID 11389470. S2CID 205016442.
  30. ^ Oppermann, H.; Levinson, A. D.; Varmus, H. E.; Levintow, L.; Bishop, J. M. (1979). "Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src)". Proceedings of the National Academy of Sciences of the United States of America. 76 (4): 1804–1808. Bibcode:1979PNAS...76.1804O. doi:10.1073/pnas.76.4.1804. PMC 383480. PMID 221907.
  31. ^ a b "The Rockefeller University Hospital Centennial – The First Blood Bank". centennial.rucares.org. The Rockefeller University. 2010. Retrieved 2022-03-18.
  32. ^ Rous, Peyton; Turner, J. R. (1915). "A rapid and simple method of testing donors for transfusion". Journal of the American Medical Association. LXIV (24): 1980–1982. doi:10.1001/jama.1915.02570500028011.
  33. ^ a b Rous, P. (1947). "Karl Landsteiner. 1868-1943". Obituary Notices of Fellows of the Royal Society. 5 (15): 294–324. doi:10.1098/rsbm.1947.0002. S2CID 161789667.
  34. ^ Rous, P.; Turner, J. R. (1915-03-01). "On the preservation in vitro of living erythrocytes". Experimental Biology and Medicine. 12 (6): 122–124. doi:10.3181/00379727-12-74. ISSN 1535-3702. S2CID 88016286.
  35. ^ Rous, Peyton; Turner, J. R. (1916). "The preservation of living red blood cells in vitro : i. Methods of preservation". Journal of Experimental Medicine. 23 (2): 219–237. doi:10.1084/jem.23.2.219. ISSN 1540-9538. PMC 2125399. PMID 19867981.
  36. ^ Rous, Peyton; Turner, J. R. (1916). "The preservation of living red blood cells in vitro: ii. The transfusion of kept cells". Journal of Experimental Medicine. 23 (2): 219–237. doi:10.1084/jem.23.2.219. ISSN 1540-9538. PMC 2125399. PMID 19867981.
  37. ^ Hedley-Whyte, John; Milamed, Debra R. (2010). "Blood and war". The Ulster Medical Journal. 79 (3): 125–134. ISSN 2046-4207. PMC 3284718. PMID 22375087.
  38. ^ Rous, Peyton; Larimore, Louise D. (1920). "Relation of the portal blood to liver maintenance: a demonstration of liver atrophy conditional on compensation". Journal of Experimental Medicine. 31 (5): 609–632. doi:10.1084/jem.31.5.609. PMC 2128242. PMID 19868417.
  39. ^ Rous, Peyton; McMaster, Philip D. (1921-07-01). "The concentrating activity of the gall bladder". Journal of Experimental Medicine. 34 (1): 47–73. doi:10.1084/jem.34.1.47. PMC 2128065. PMID 19868541.
  40. ^ Rous, Peyton; McMaster, Philip D. (1921-07-01). "Physiological causes for the varied character of stasis bile". Journal of Experimental Medicine. 34 (1): 75–95. doi:10.1084/jem.34.1.75. PMC 2128064. PMID 19868542.
  41. ^ McMaster, Philip D.; Rous, Peyton (1921-06-01). "The biliary obstruction required to produce jaundice". Journal of Experimental Medicine. 33 (6): 731–750. doi:10.1084/jem.33.6.731. PMC 2128305. PMID 19868532.
  42. ^ Drury, Douglas R.; McMaster, Philip D.; Rous, Peyton (1924-03-01). "Observations on some causes of gall stone formation: III. The Relation of the Reaction of the Bile to Experimental Cholelithiasis". Journal of Experimental Medicine. 39 (3): 403–423. doi:10.1084/jem.39.3.403. PMC 2128469. PMID 19868854.
  43. ^ "The Albert Lasker Awards for 1958". American Journal of Public Health and the Nation's Health. 48 (12): 1664–1667. 1958. doi:10.2105/ajph.48.12.1664. ISSN 0002-9572. PMC 1551844. PMID 18017705.
  44. ^ "Francis P. Rous". National Science and Technology Medals Foundation. Retrieved 2022-03-18.
  45. ^ "The Nobel Prize in Physiology or Medicine 1966". NobelPrize.org. Retrieved 2022-03-18.
  46. ^ "Nomination archive – Peyton Rous". NobelPrize.org. 2020-04-01. Retrieved 2022-03-18.
  47. ^ a b Ann Thwaite. "Marni Hodgkin obituary | Books". The Guardian. Retrieved 2016-03-11.
  48. ^ Rous, P. (1949). "Simon Flexner. 1863-1946". Obituary Notices of Fellows of the Royal Society. 6 (18): 408–426. doi:10.1098/rsbm.1949.0006. S2CID 159733258.

Further reading