Max Theiler Biography (1899-1972)

South African

Max Theiler (pronounced Tyler) was born on a farm near Pretoria, South Africa, on January 30, 1899. He enrolled in a two-year premedical program at the University of Cape Town in 1916. In 1919, soon after the conclusion of World War I, he sailed for England, where he pursued further medical training. Despite this rigorous training, Theiler never received the M.D. degree because theUniversity of London refused to recognize his two years of training at the University of Cape Town.

Theiler was frustrated by the ineffectiveness of most medical procedures andthe lack of cures for serious illnesses. After finishing his medical trainingin 1922, the 23-year-old Theiler obtained a position at Harvard Medical School. His early research focused on amoebic dysentery and rat-bite fever. Fromthere, he developed an interest in the yellow-fever virus.

Yellow fever is a tropical viral disease that causes severe fever, slow pulse, bleeding in the stomach, jaundice, and the notorious symptom, black vomit.The disease is fatal in 10%--15% of cases, the cause of death being completeshutdown of the liver or kidneys. Most people recover completely, after a painful, extended illness, with complete immunity to reinfection. The first known outbreak of yellow fever devastated Mexico in 1648. The last major breakoutin the continental U.S. claimed 435 lives in New Orleans in 1905. Despite the medical advances of the twentieth century, this tropical disease remains incurable.

By the 1920s, yellow-fever research shifted away from an all-out war on mosquitoes to attempts to find a vaccine to prevent the spread of the disease. Theiler's first big breakthrough was his discovery that mice could be used experimentally in place of the Rhesus monkey and that they had several practical research advantages. When yellow-fever virus was injected into their brains, the mice didn't develop human symptoms.

One unintended research discovery kept Theiler out of his lab and in bed fornearly a week. He accidentally contracted yellow fever from one of his mice,which caused a slight fever and weakness. Theiler was much luckier than someother yellow-fever researchers. Many had succumbed to the disease in the course of their investigations. However, this small bout of yellow fever simply gave Theiler an immunity to the disease. In effect, he was the first recipientof a yellow-fever vaccine.

In 1930, Theiler reported his findings on the effectiveness of using mice foryellow fever research in the respected journal Science. The initial response to his findings was overwhelmingly negative, even from his immediatesupervisor. Undaunted, Theiler moved from Harvard University, where he was considered an upstart, to the Rockefeller Foundation in New York City. Eventually, yellow-fever researchers began to see the logic behind Theiler's use of the mouse and followed his lead. By passing the yellow-fever virus from mouseto mouse, he was able to shorten the incubation time and increase the virulence of the disease, which enabled research data to be generated more quickly and cheaply. He was now certain that an attenuated live vaccine, one weak enough to cause no harm yet strong enough to generate immunity, could be developed.

A colleague at the Rockefeller Foundation, Dr. Wilbur A. Sawyer, used Theiler's mouse strain, a combination of yellow fever virus and immune serum, to develop a human vaccine. Sawyer is often wrongly credited with inventing the first human yellow-fever vaccine. He simply transferred Theiler's work from themouse to humans. Ten workers in the Rockefeller labs were inoculated with themouse strain, with no apparent side effects. The mouse-virus strain was subsequently used by the French government to immunize French colonials in West Africa, a hot spot for yellow fever. This so-called "scratch" vaccine was a combination of infected mouse brain tissue and cowpox virus and could be quickly administered by scratching the vaccine into the skin. It was used throughout Africa for nearly 25 years and led to the near total eradication of yellowfever in the major African cities.

While he was somewhat pleased with the new vaccine, Theiler considered the mouse strain inappropriate for human use. In some cases, the vaccine led to encephalitis in a few recipients and caused less severe side effects, such as headache or nausea, in many others. Theiler believed that a "killed" vaccine, which used a dead virus, wouldn't produce an immune effect, so he and his colleagues set out to find a milder live strain. He began working with the Asibiyellow-fever strain, a form of the virus so powerful that it killed monkeys instantly when injected under the skin. The Asibi strain thrived in a number of media, including chicken embryos. Theiler kept this virus alive for years in tissue cultures, passing it from embryo to embryo, and only occasionally testing the potency of the virus in a living animal. He continued making subcultures of the virus until he reached strain number 176. Then, he tested the strain on two monkeys. Both animals survived and seemed to have acquired a sufficient immunity to yellow fever. In March 1937, after testing this new vaccine on himself and others, Theiler announced that he had developed a new, safer, attenuated vaccine, which he called 17D strain. This new strain was much easier to produce, cheaper, and caused very mild side effects.

From 1940 to 1947, with the financial assistance of the Rockefeller Foundation, more than 28 million 17D-strain vaccines were produced, at a cost of approximately two cents per unit, and given away to people in tropical countries and the U.S. The vaccine was so effective that the Rockefeller Foundation ended its yellow-fever program in 1949, safe in the knowledge that the disease had been effectively eradicated worldwide and that any subsequent outbreaks could be controlled with the new vaccine. Unfortunately, almost all yellow-feverresearch ended around this time and few people studied how to cure the disease. For people in tropical climates who live outside of the major urban centers, yellow fever is still a problem. A major outbreak in Ethiopia in 1960-62caused 30,000 deaths. The World Health Organization still uses Theiler's 17Dvaccine and is attempting to inoculate people in remote areas.

In 1951, Theiler received the Nobel Prize in medicine or physiology "for hisdiscoveries concerning yellow fever and how to combat it."

After developing the yellow-fever vaccine, Theiler turned his attention to other viruses, including some unusual and rare diseases, such as Bwamba fever and Rift Valley fever. His other, less exotic research focused on polio and led to his discovery of a polio-like infection in mice known as encephalomyelitis or Theiler's disease. In 1964, he retired from the Rockefeller Foundation,having achieved the rank of associate director for medical and natural sciences and director of the Virus Laboratories. In that same year, he accepted aposition as professor of epidemiology and microbiology at Yale University inNew Haven, Connecticut. He retired from Yale in 1967. Theiler died on August11, 1972, at the age of 73.

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