The First Successful Therapy for a Viral Infection in Animals

Horsfall, Frank

In the late 1930s and early 1940s a form of pneumonia which came to be called primary atypical pneumonia emerged as a public health concern, and during World War II it was a frequent cause of morbidity in military personnel. Frank L. Horsfall (1906-1971), who had previously worked extensively on the therapy of pneumococcal pneumonia and had developed highly active rabbit antibodies to various types of pneumococcal to treat the disease, turned his attention to primary atypical pneumonia when his antiserum approach to pneumococcal pneumonia was eclipsed by the discovery of antibiotics.

Horsfall and others attempted to isolate the cause of primary atypical pneumonia. Horsfall obtained some suggestive results with the transmission of pneumonia in cotton rats, but it was more than a decade before the cause of the disease was shown to be due to a newly recognized class of microbes called mycoplasma. However, in the course of his studies Horsfall isolated a new virus from mouse lungs that caused pneumonia in mice, which he named pneumonia virus of mice (PVM). Horsfall and Maclyn McCarty (1911-2005) were exploring the effects of co-infection with PVM and a bacterium, streptococcus MG, which had been isolated from some cases of atypical pneumonia. They made the surprising finding that streptococcus MG had a beneficial effect on PVM pneumonia, and this was shown to be due to a carbohydrate component of the bacterium's capsule. Subsequently, Horsfall and Harold S. Ginsberg showed that a similar carbohydrate from another bacterium, Friedlander's bacillus Group B, was a highly effective therapeutic agent for pneumonia caused by PVM even after the disease was well established, and it was also effective on mumps virus infection. This work was the first instance of successful therapy for a viral infection, clearly showing that curative treatment was possible although the bacterial carbohydrate approach for treatment for human infections was not practical.

Demonstration of reduction
of multiplication of pneumonia virus (PVM) in the mouse lung. From J Exp Med, 1951, 93: 161-171

Frank L. Horsfall Jr. received his bachelor's degree from the University of Washington and the MD from McGill University (1932). After serving a year as house officer in pathology at Peter Bent Brigham Hospital in Boston, and interning at the Royal Victoria Hospital in Montreal, Horsfall joined the Rockefeller Institute in 1934 as a physician on the Hospital's pneumonia service. In 1937 he became head of a laboratory at the Rockefeller Foundation's International Health Division, located on the Institute's campus. Horsfall returned to the Rockefeller in 1941 as a member (full professor) of the Institute. He served as acting head of the Hospital during World War II, while the Hospital's director, Thomas Rivers, took many of the staff to Guam as a unit of the Navy. Many researchers trained in Horsfall's laboratory went on to distinguished careers, including Lewis Thomas, Edward Curnen, Harold Ginsberg, D.A.J. Tyrrell, M.R. Hilleman, E.D. Kilbourne, F.M. Davenport, and G.S. Mirick. In 1953 Horsfall was appointed to the new positions of vice president of the Institute and Physician-in-Chief of the Hospital. In 1959 Horsfall became director of the Sloan-Kettering Institute. Among many awards and honors, Horsfall received the Eli Lilly Award in Bacteriology and Immunology (1937), the Casgrain and Charbonneau Award in Medicine from McGill University (1942), the John Lewis Prize from the American Philosophical Society (1959), and the 50th Anniversary Gold Medal Award of Peter Bent Brigham Hospital (1963). He was elected to the U.S. National Academy of Sciences (1948). With Thomas Rivers, Horsfall edited the authoritative text, Viral and Rickettsial Infections in Man, a later edition of which was co-edited with Igor Tamm.

Selected Publications

Horsfall FL Jr and McCarty M. The modifying effects of certain substances of bacterial origin on the course of infection with pneumonia virus of mice (PVM). J Exp Med, 1947, 85:623-646
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Ginsberg HS and Horsfall FL Jr. Therapy of infection with the pneumonia virus of mice (PVM): effect of a polysaccharide on the multiplication cycles of the virus and on the course of the viral pneumonia. J Exp Med, 1951, 93:161-171

Horsfall F. Chemotherapy of respiratory viral diseases. (Special Reviews edited by Joseph Stokes, Jr., MD) Pediatrics, 1954, 13:593-598

Further Reading

Hirst GK. Frank Lappin Horsfall, Jr. (1906-1971): A Biographical Memoir. Washington, DC: National Academy of Sciences, 1979, pp. 231-267 H