The Birth of the Concept of Autoimmune Demyelinating Disease and Creation of An Animal Model to Test New Therapies for Multiple Sclerosis
Courtesy of the Rockefeller Archive Center
By the early 1930s scientists knew that vaccination against rabies occasionally harmed a person's central nervous system, causing paralysis. Similar complications sometimes resulted from infection with smallpox or measles, notably brain inflammation and demyelination—the loss of a lipid-rich sheath that normally surrounds parts of nerve cells and helps them conduct electrical impulses. Beginning in 1932, Thomas M. Rivers (1880-1962) and colleagues at the Rockefeller Hospital undertook a series of experiments to find the cause of demyelination. Their work resulted in the first evidence that immune cells can attack the brain. In addition, they created an animal model, now known as the experimental autoimmune encephalomyelitis (EAE) model, that is today the most-studied model of autoimmunity and has provided a means for testing treatments for multiple sclerosis.
Rivers had learned from published studies that injecting rabbits with foreign brain tissue could cause paralysis. In addition, the sometimes-harmful rabies vaccine contained brain extract. So Rivers and coworkers designed a series of studies to test whether injecting rhesus monkeys with emulsions and extracts of rabbit brain would produce the same effects. Indeed, over the course of nearly a year, the monkeys developed symptoms that were shown on necropsy to be the result of loss of myelin. The researchers eliminated the possibility that an infectious agent had caused the changes. And in another experiment, in which rabbits were injected with the brain extracts, they found antibodies against myelin—a component of the extract. This was a sign of immune response to the extract, and accounted for inflammation in the brains of injected animals.
Thomas M. Rivers received the BA from Emory College in 1909 and the MD from The Johns Hopkins University Medical School in 1915. After an internship and residency in pediatrics, he joined the Army in 1918, serving on commissions with the U.S. Army Medical Corps that investigated outbreaks of pneumonia and empyema. He returned to Johns Hopkins for a research appointment in 1919, and joined the Rockefeller Institute Hospital in 1922. In 1937 Rivers became director of the hospital, a position he held until 1953, when he became Vice President and Director of the Institute. He retired in 1955. Rivers was elected to the U.S. National Academy of Sciences. He served as president of the American Society for Clinical Investigation, the American Association of Immunologists, the Society of American Bacteriologists, and the Third International Congress for Microbiology, and received honorary degrees from Emory University, the University of Rochester, the University of Chicago, and the Rockefeller Institute.
Sprunt DH, and Berry GP. Observations on attempts to produce acute
disseminated encephalomyelitis in monkeys. J Exp Med, 1933, 58: 39-53
Schwentker FF and Rivers TM. The antibody response of rabbits to
injections of emulsions and extracts of homologous brain. J Exp Med,
1934, 60: 559-574
Rivers TM and Schwentker FF. Encephalomyelitis accompanied by myelin
destruction experimentally produced in monkeys. J Exp Med, 1935, 61:
Van Epps HL. Thomas Rivers and the EAE model. J Exp Med, 2005, 202: 4
Horsfall FL Jr. Thomas Milton Rivers (1888-1962). Biographical Memoirs of the National Academy of Sciences, 1965, 38:262-294
Benison S. Tom Rivers: Reflections on a Life in Medicine and Science. An Oral History Memoir. Cambridge, MA: The MIT Press, 1967