Theiler wanted to pursue a career in research, so in 1922, he took a position at the Harvard University School of Tropical Medicine in Cambridge, Massachusetts. He spent several years investigating amoebic dysentery and trying to develop a vaccine for rat-bite fever. After becoming assistant to Andrew Sellards, he started working on yellow fever. In 1926, they disproved Hideyo Noguchi's hypothesis that yellow fever was caused by the bacterium Leptospira icteroides. In 1928, the year after the disease was identified conclusively as being caused by a virus, they showed that the African and South American viruses are immunologically identical.. In the course of this research, Theiler contracted yellow fever, but survived and developed immunity. In 1930, Theiler moved to the Rockefeller Foundation in New York, where he later became director of the Virus Laboratory. He was professor of epidemiology and public health at the Yale School of Medicine and the School of Public Health from 1964 to 1967.
Work on yellow fever
After passing the yellow fever virus through laboratory mice, Theiler found that the weakened virus conferred immunity on rhesus macaques. The stage was set for Theiler to develop a vaccine against the disease. Theiler first devised a test for the efficacy of experimental vaccines. In his test, sera from vaccinated human subjects were injected into mice to see if they protected the mice against yellow fever virus. This "mouse protection test" was used with variations as a measure of immunity until after World War II. Subculturing the particularly virulent Asibi strain from West Africa in chicken embryos, a technique pioneered by Ernest Goodpasture, the Rockefeller team sought to obtain an attenuated strain of the virus that would not kill mice when injected into their brains. It took until 1937, and more than 100 subcultures in chicken embryos, for Theiler and his colleague Hugh Smith to obtain an attenuated strain, which they named "17D". Animal tests showed the attenuated 17D mutant was safe and immunizing. Theiler's team rapidly completed the development of a 17D vaccine, and the Rockefeller Foundation began human trials in South America. Between 1940 and 1947, the Rockefeller Foundation produced more than 28 million doses of the vaccine and finally ended yellow fever as a major disease. For this work, Theiler received the 1951 Nobel Prize in Physiology or Medicine. Theiler also was awarded the Royal Society of Tropical Medicine and Hygiene's Chalmers Medal in 1939, Harvard University's Flattery Medal in 1945, and the American Public Health Association's Lasker Award in 1949.
In 1937, Max Theiler discovered a filterable agent that was a known cause for paralysis in mice. He found the virus was not transmittable to rhesus macaques, and that only some mice developed symptoms. The virus is now referred to as Theiler's murine encephalomyelitis virus. The virus has been well characterized, and now serves as a standard model for studying multiple sclerosis.
Private life
He married Lillian Graham in 1928, and they had one daughter. He died on August 11, 1972 in New Haven, Connecticut.
Publications
Max Theiler contributed to three books:
Viral and Rickettsial Infections of Man
Yellow Fever
The Arthropod-Borne Viruses of Vertebrates: An Account of The Rockefeller Foundation Virus Program, 1951–1970, Max Theiler and W. G. Downs. Yale University Press. New Haven and London..