Theiler's 17D yellow fever vaccine

Yellow fever research killed its researchers. In June 1927 the West African Yellow Fever Commission, based near Lagos, injected blood from a 28-year-old man named Asibi, who had a mild fever and survived, into a rhesus monkey, and the disease was established in a laboratory animal for the first time. Adrian Stokes of the expedition died of yellow fever soon afterward, and Hideyo Noguchi and William Young died of it in 1928. In 1931 the Rockefeller Foundation's International Health Division counted 32 laboratory infections, five of them fatal.

In 1930 Max Theiler, a South African working at Harvard, found that the virus grew in the brains of mice. Repeated mouse passage made it gentler on the liver and organs of monkeys but more dangerous to the nervous system, and around the 30th passage Theiler caught a mild case himself. A mouse brain vaccine given with immune human serum protected laboratory workers, and in French Africa a serumless version scratched into the skin reached millions, with febrile and neurological reactions.

Theiler, now in the Rockefeller Foundation's laboratories in New York, turned to tissue culture. Simple passage did not tame the virus's attack on the nervous system, so the team grew the Asibi strain in chick embryo tissue with the nervous tissue removed. At the 100th subculture in that medium, the 176th in chick embryo altogether, Hugh Smith found that the virus no longer killed mice injected into the brain. The change could not be reproduced, and the team put it down to a chance mutation. The strain, 17D, protected animals safely and could be given without immune serum.

Smith took 17D to Brazil in 1937. Grown in fertile eggs and freeze-dried, it was given to 59,000 people within a year without severe complications, and to 1.3 million by June 1939. In 1941, 119 cases of encephalitis in Brazil were traced to one lot that had mutated during a few extra subcultures, which led to the seed lot system of frozen master seeds. Human serum used as a stabilizer carried hepatitis: after about 7 million doses went to American forces from January 1941 to April 1942, 26,771 cases of jaundice were reported, later shown to be hepatitis B. The serum was dropped.

Theiler received the 1951 Nobel Prize in Physiology or Medicine for his discoveries concerning yellow fever and how to combat it.