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Remembering a Great One Health Physician Giant in History …   Richard Shope, MD   Submitted by: Russell W. Currier, DVM, MPH, Dipl. ACVPMExecutive Vice President EmeritusAmerican College of Veterinary Preventive Medicine1864 NW 151 CourtDes Moines IA 50325-7850Cell (515) 710-2331; home (515) 987-5541Email: ruscurrier@yahoo.com   In honor of the late great physician researcher, Dr. Currier presents a list of Dr. Shope’s crucial historical contributions to medical and veterinary medical science.   Summary of Richard Edwin Shope Contributions to One Medicine/Health   Richard E. Shope MD (Dec 25, 1901 – October 2, 1966) was one of the pioneer microbiologists to investigate a variety of human and animal diseases and merits recognition for his many accomplishments that supported later research that continues to this very day.  Dr Shope graduated from medical school at The University of Iowa in 1924 and immediately remained on staff there to teach pharmacology and work on the chemotherapy of tuberculosis.  Shortly afterward he was invited to join the laboratories of the Rockefeller Institute at Princeton to work with Dr Paul Lewis, the discoverer of polio virus.  Subsequently in 1928, he left tuberculosis research to investigate hog cholera in the field where he observed his first outbreak of swine influenza.  Later research on influenza resulted in isolation of the virus from pigs and its co-pathogen Haemophilus influenzae suis, and subsequent research that postulated that the swine virus was related to the human 1918 pandemic virus.   Dr Shope acknowledged the influence of the legendary Dr Theobald Smith, at the Rockefeller Institute, on his own career and observed that Smith “although possessed of great imagination and … uncanny foresight, was a meticulously methodical worker, who abhorred the waste of anything – time, material, or animals.”  This set a pattern for Shope’s career and an informal distillation of his key accomplishments are summarized in the bullet form.   From Bernard Easterday, 4th Int’l Symposium on Emerging and Reemerging Pig Diseases, Rome June, 2003:   “It remained for Shope to present the first reliable experimental evidence that influenza is caused by a virus (15).  [Year 1931.]  He demonstrated that he could reproduce swine influenza under strict experimental conditions by inoculating both filtered and unfiltered material from affected pigs into the respiratory tract of normal pigs.  The disease produced by the filtered material was mild (later sometimes referred to as “filtrate disease”) but it could be transmitted repeatedly in this manner.  Subsequently, Shope would describe swine influenza as a “… disease of complex etiology, being caused by infection with the bacterium H. influenzae suis and the swine influenza virus acting in concert.”  Three years after Shope reported the viral nature of SI, Andrewes and Laidlaw (15) would report the viral nature of influenza in human beings. [Ref: Shope, RE 1964 Swine Influenza, In Diseases of Swine 2nd Ed.  Ed by H.W. Dunne.  P. 109-126.]   Note:  Shope and Christopher Andrewes became very good friends and Shope collaborated with the UK investigators on techniques to isolate virus which they subsequently did utilizing ferrets and Andrewes and co-investigators, Smith and Laidlaw, were later knighted for this accomplishment.   1936-1937.  Shope postulated linkage between human and swine influenza.  [Laidlaw also advanced same idea at same time.]   1941.  Shope postulated linkage of “masked or occult” viral infection of pigs with swine lung worm and its intermediate host, earth worms.  This was very controversial and was not entirely corroborated.  The issue became a moot point as husbandry of pigs was changing that precluded importance of this postulated cycle.   From Sir Chrotopher Andrewes biographical memoirs:  “In 1930 Shope’s attention was drawn to “mad itch” [aka pseudorabies], a violent distressing and fatal disease of cattle in the Midwest.  He showed that it was caused by a virus transmissible to rabbits, and that it was endemic among pigs, in which it was comparatively harmless.  Cattle contracted infection through contact with pigs.  He finally proved the identity of cattle ‘mad itch’ with psedudorabies, a disease prevalent in parts of Europe.  Later he studied another disease of pigs – swine pox – and showed that it could be, though it was not necessarily, transmitted through the agency of pig-lice.  He also published evidence that hog cholera virus might persist, as swine flu virus appeared to do, in lungworms.  Ref: Biographical Memoirs vol 50 (1979), p 353-375, © The National Academy of Sciences.   Shope’s three most outstanding discoveries followed each other in rapid succession:  swine influenza in 1931, the rabbit fibroma in 1932, and rabbit papilloma in 1933.”   Andrewes again, “The work [masked rabbit papilloma virus studies by Shope] gained a new dimension when it was found that in many tame rabbits the warts progressed and became carcinomatous [sic].  This change, though common in domestic rabbits, was rare in cottontails.  Shope at this time, was busy with many problems, so he generously gave the material to Francis Peyton Rous.  What Rous did with the rabbit cancers during the next thirty years is a matter of history.”  [Peyton Rous received Nobel Prize for Medicine in 1966 for work demonstrating viral etiology of cancer.]    Viral etiology of cancer.  Shope described papilloma in jack rabbits and the pathological condition bears his name “Shope papilloma [or fibroma]”, and in urban legend mode affected bunnies were referred to as “jack-a-lopes.”  He prompted a colleague at Rockefeller Institute, Peyton Rous, to extend his inquiries to mammals.  Rous had already demonstrated transmission in chickens but not mammals.   During WW II, Shope was attached to the US Army and detailed to a joint Canadian-US project on Grosse Isle in St Lawrence River to develop a rinderpest vaccine for cattle.  There was concern of biowarfare and deliberately introduced rinderpest would be a food production catastrophe.  From Andrewes, “Here Shope, with a staff of five other scientists, worked in strict isolation, and in the course of nineteen months produced an effective vaccine by growing and attenuating the virus in hens’ eggs.  This has since been used on a large scale in the field.”   Shope was then transferred back to the Navy.  He was in first party to set up a lab to study tropical diseases on Guam and on Okinawa after assault began.  Shope was actually fired on.  He found mold from Guam growing on photo of his wife Helen.  He isolated a substance from this mold with in vivo antiviral properties and named it after wife “Helenine”.  Later found to be nucleoprotein that stimulated interferon production.   Approximately two years after WW II:  Shope developed an effective vaccine to a South American rabbit disease that was deliberately introduced to Great Britain to reduce population and extensive burrowing of rabbits in farm fields.  Inadvertent introduction in France however resulted in decimated rabbit populations and adverse effect on commercial rabbitries.  Shope’s vaccine saved the rabbit industry in France.   Circa 1950s:  Shope isolated a second benign-tumor virus from deer.  Also isolated the deer “hemorrhagic disease” virus.    Later when Rockefeller closed the Princeton branch, Shope decided to leave and go to work for Merck in Rahway NJ.  Subsequently he returned to Rockefeller in Manhattan [rented room during weekdays!]  Later died from abdominal cancer October 2nd, 1966.  During lifetime had two serious viral diseases, lymphocytic choriomeningitis and eastern equine encephalomyelitis.     Andrewes, “  Shope received many honors.  He was elected to the American Philosophical Society (1944) and the National Academy of Sciences (1940).  He received honorary degrees from the universities of Utrecht, Rutgers, Giessen, Chicago, Pennsylvania, Iowa, and Yale, as well as many prizes and awards including the U.S. Army Legion of Merit and the Albert Lasker award.    J of Amer Vet Med Ass’n, Nov 15, 1957.  Editorial Comment entitled “Richard Shope, Benefactor of Animals.”  “On May 8, 1957, the Association of American Physicians awarded the Kober Medal to Dr Richard E Shope, the second time this award has been given to a physician for contributions to the health of domesticated animals.  The previous recipient was Dr. Theobald Smith.” [See Harvard Magazine, July-August 2009]   Dr Shope acknowledged influence of individuals on his career specifically Theobald Smith, who worked out arthropod transmission of disease and Paul Lewis who discovered/isolated polio virus and died of yellow fever while studying the same disease in South America.   “Dr Shope then paid tribute to a veterinary practitioner, Dr Fred J. Crow of Iowa City Iowa, “who permitted me to spend … time with him in the field…and who guided me during my initial experience with swine influenza…He got me my first case of swine pox and … of pseudorabies and …served as the connecting link between the practicality of the field and science of the laboratory.”  Ref: JAVMA, Nov 15, 1957, p 486-487.   The following excerpt is from the Souvenir Book published by the Eastern Iowa Veterinary Association on their 25th Anniversary (1913-1938).  It was written by Richard E. Shope MD, of the Rockefeller Institute for Medical Research, Department of Animal and Plant Pathology, Princeton, New Jersey.   “In the summer of 1928, I was in Iowa doing blood counts in hog cholera and other swine diseases with the cooperation of a number of veterinarians in eastern Iowa.  During that time I had occasion to go to Ames to see Dr Charles Murray and it was he who first called my attention to the existence of swine influenza.  Returning to eastern Iowa, arrangements were made with Dr Fred Crow for the collection of material from typical cases when the epizootic should appear during the autumn.  Dr Crow telegraphed me on November 13 saying, ‘Plenty of hog flu – come at once.’  I took the first train west, and on arriving in Iowa City found that there was indeed plenty of ‘hog flu.’  Through the friendliness and cooperation of a number of eastern Iowa veterinarians and their clients, many swine autopsies were obtained and material from the best cases was shipped back to Princeton.  At that time, because we had no idea as to how fragile or easily killed the causative agent might be, we packed our infectious material in iced thermos jugs and sent it by air mail from Cedar Rapids.  After several unsuccessful attempts to establish swine influenza in our experimental pigs in Princeton with the various samples sent, one batch finally ‘took.’  This had been obtained by Dr Crow on the Probst Brothers’ farm near Iowa City.  Dr Lewis, my chief, wired me of his success in establishing the disease experimentally and to return to Princeton as soon as possible.”   Richard and Helen Shope had four children and Richard’s scientific aptitude DNA went into the three sons.  Richard Jr went to Cornell and got a DVM and later PhD in virology at University of Minnesota where I was acquainted with him.  Son 2, Robert became the distinguished arbovirologist at Yale after medical school at Cornell; later moved to Galveston and now deceased.  Son 3, became an academic pediatrician at the University of Michigan.  Daughter attended college in Colorado and married well, and pursued equestrian interests, living happily ever after.   Finally a quote from Dr Peyton Rous’ on the occasion of conferring The Academy Medal to Richard E. Shope, M.D. at the Annual Meeting of The New York Academy of Medicine, January 7, 1965:  “Dr Shope’s theme throughout his scientific life has been the meaning of animal diseases for mankind, though he would never say so.  Yet not alone from this theme has he drawn his wisdom and his strength.  He knows human nature well.  How does he value his fellow creatures including ourselves?  Much as he does the lower animals – with understanding, indulgence, humor, and love.”  Ref:  Bull NY Acad Med, Vol 41, No 4, April 1965.   Russell Currier, 8/09