Salk was born in New York City, the son of a garment worker. He was educated at the City College of New York and at New York University Medical School, where he obtained his MD in 1939. In 1942 he went to the University of Michigan where he worked as a research fellow on influenza vaccine under Thomas Francis. In 1947 he moved to the University of Pittsburgh, serving as professor of bacteriology from 1949 onward. Here Salk began the work that eventually led to the discovery of a successful polio vaccine in 1954. After this breakthrough Salk was invited in 1963 to become director of the Institute for Biological Studies at San Diego, California, known more simply as the Salk Institute – soon to emerge as one of the great research centers of the world.

Salk was not the first to develop a vaccine against polio for in 1935 killed and attenuated vaccines were tested on over 10,000 children. It turned out, however, that not only were the vaccines ineffective, but they were also unsafe and probably responsible for some deaths and a few cases of paralysis.

By the time Salk began his work in the early 1950s a number of crucial advances had been made since the 1935 tragedy. In 1949 John Enders and his colleagues had shown how to culture the polio virus in embryonic tissue. Another essential step was the demonstration, in 1949, that there were in fact three types of polio virus with the inconvenient consequence that vaccine effective against any one type was likely to be powerless against the other two.

Salk had to develop a vaccine that was safe but potent. To ensure its safety he used virus exposed to formaldehyde for up to 13 days and afterward tested for virulence in monkey brains. This, in theory, allowed a large safety margin, for Salk could detect no live virus after only three days.

To test its potency Salk injected children who had already had polio and noted any increase in their antibody level. When it became clear that high antibody levels were produced by the killed vaccine Salk moved on to submitting it to the vital test of a mass trial. Two objections were raised to this. One from Albert Sabin that killed vaccine was simply the wrong type to be used and a second, from various workers, who claimed to find live virus in the supposedly killed vaccine.

Despite such qualms Salk continued with the trial administering in 1954 either a placebo or killed vaccine to 1,829,916 children. The evaluation of the trial was put into the hands of Francis, who, in March 1955, reported that the vaccination was 80–90% effective. The vaccine was released for general use in the United States in April 1955.

Salk became a national hero overnight and plans went ahead to vaccinate 9 million children. However within weeks there were reports from California in which children developed paralytic polio shortly after being vaccinated. After a period of considerable confusion it became clear that all such cases involved vaccine prepared in a single laboratory.

After several days of almost continuous debate, the decision was taken to proceed and, by the end of 1955, 7 million doses had been administered. Further technical improvements were made in the production process. These safeguards would either eliminate any further cases of live vaccine or if a live virus did manage to penetrate all defenses it should make its presence known long before its use in a vaccine.

The courage shown by Salk in persisting with his vaccine was clearly justified by the results for the period 1956–58 – 200 million injections without a single case of vaccine-produced paralysis.