An Egyptian stele from about 1500 B.C. portrays a young man with a withered leg, symptomatic of poliomyelitis.
The Procession of the Cripples by Hieronymus Bosch also captures the cruel effects of the disease. In the late 19th century and first half of the 20th, what had been isolated instances erupted, unpredictably, into devastating epidemics.
Outbreaks in Sweden in 1881, 1887, and 1905 killed hundreds of children and crippled over 1,000. The year 1916 saw a severe epidemic in the United States with over 27,000 cases and over 7,000 deaths in the 20 states requiring victims to file a report. New York City, where over 9,000 were hit, was panic-stricken. Many bolted their doors and locked their windows in terror of infection. Others fled to the suburbs and effectively spread the disease. At this time it was believed that polio entered through the nose and passed on to the brain. Some tried zinc-plating their nostrils.
One of the first breakthroughs in tracking the elusive disease came in 1909. Medical scientist Karl Landsteiner of Vienna removed nerve cells from the spinal cord of a four-year-old killed by polio. He injected these cells into a baboon, which subsequently died, and a monkey, which became crippled. He kept the infectious microbe alive in a broth made from nerve tissue and went on to find that one monkey, able to survive a first infection, was thereafter immune altogether: something in its blood serum, in fact, killed the microbes in the test tube.
In the same year, Simon Flexner and P. A. Lewis of the Rockefeller Institute succeeded in transmitting a human infection from one monkey to another. The infectious agent, which could multiply within its victim, was able to pass through extremely fine filters and could not be seen. (That would change with the discovery of the electron microscope in 1931.) Flexner and Lewis called the agent a filterable virus. Despite the now obvious clue in their findings, too little was known at the time about viral infection and immunization for anyone to bring the evidence to a fruitful conclusion. Polio continued to find its victims: not only infants but, increasingly, older children and adults. Franklin D. Roosevelt was stricken at 40.
By 1935 little had been revealed about the nature of the polio virus. Nevertheless, two men independently created vaccines and prematurely injected thousands of children—with disastrous results. One was Maurice Brodie, who, with Dr. William H. Park of the New York City Department of Health, ground up spinal cords of monkeys infected with polio, then inactivated the virus with formaldehyde. After injecting only 20 monkeys with the solution, he tried it on himself and 3,000 children. Several got polio and one died. Dr. John A. Kolmer of Temple University in Philadelphia concocted a vaccine employing a live, but chemically altered, virus. His lethal potion resulted in 6 deaths among the 12,000 injected. These cases naturally left the public somewhat skeptical about vaccines and did nothing to support the use of killed virus, held in disregard by the scientific community, but championed, finally, by one Jonas E. Salk.
Salk was an extremely bright, ambitious, inscrutable young man who grew up at 106th Street and Madison Avenue in New York City and took his medical degree from New York University, although he did not want to be a doctor. Salk’s interests lay in the challenging and largely unexplored field of virology. As a research fellow at the University of Michigan he developed a vaccine against the influenza virus. In 1947 he became director of the Virus Research Laboratory of the University of Pittsburgh’s School of Medicine, and the following year was approached by the National Foundation of Infant Paralysis.
Established by FDR in 1938, the foundation was spearheaded by a flamboyant and celebrated Wall Street lawyer, Basil O’Connor. When the foundation’s scientists were delayed in their polio research by a dearth of monkeys, O’Connor launched a massive monkey business, gaining export clearances from India and the Philippines. Over 17,000 were used in a virus-typing program in which Salk took part. From the start, Salk concentrated on the immunological rather than the infectious capacity of viruses and furthermore believed in the immunological effectiveness of killed virus. On both stands he faced open hostility in the established scientific community.
In 1949—a year in which 43,000 cases of polio were reported in the United States—a revolutionary discovery was made by Boston scientists John F. Enders, Thomas H. Weller, and Frederick C. Robbins, who later received a Nobel Prize for their efforts. The Boston group succeeded in growing polio virus in a test tube of nonnervous human tissue. Since the virus could thrive in cells other than nerve cells, its entry point might not be the nerves of the nose. Subsequent experiments over the next few years would show that the microbes were swallowed and passed through the intestine, where they multiplied and entered the circulation, thereby reaching the central nervous system and damaging muscle controls situated at the base of the brain. This circuitous route was welcome news. Now scientists had some hope of intercepting the lethal virus before it struck the nervous tissue.
Although the foundation originally thought Salk should confine his efforts to the virus-typing program, he forged ahead, convinced that polio could be prevented by immunological means.
He obtained tissue cultures from Enders, and in 1950 a grant from the foundation. Aided by Julius Youngner and Elsie Ward, Salk studied the effects of different strains of virus on tissue cultures. “Three of them,” reported Salk, “gave brilliant, startling results, destroying monkey and human tissue right before our eyes. It was thrilling. These three strains, chosen at random to see how they might behave in the test tube, were obviously the best candidates for our subsequent experiments with mice and monkeys. Lo and behold, they then turned out to be the strains best suited for the experimental vaccines we later tested in human beings. They were the most antigenic strains, the most stable, the most reliable. It was a fantastic accident, choosing those particular strains as we did. Others have spent years trying to find better ones. So have I. But nobody has found one.”
Salk soon began immunizing monkeys with his viruses, attenuated by exposure to Formalin. But the number of variables and details was still staggering: what amount of Formalin was necessary to inactivate the virus but not destroy its capacity to serve as an antigen? Salk had to determine proportions that could be used with certainty by future generations.
He had to be sure no fraction of the virus remained active, and potentially lethal. Salk studied the chemical reactions between poliovirus and Formalin and evolved a formula for the inactivation process: virus and Formalin combined in a proportion of 250 to 1 at a temperature of 33-34°F for one to three weeks. Adjustments were constantly made in the non-nervous monkey tissue to obtain cultures most nourishing to the viral strains. Kidney tissue (rather than testes, which had been used previously) proved most effective, and the Connaught Laboratories of the University of Toronto soon produced a synthetic nutrient solution to sustain these tissues.
By 1952, there was still much to do. “All we had,” said Salk, “were several dozen different experimental preparations, some with adjuvant (oil emulsions that increase the antigenicity of viruses), some without, some containing one type of virus, some another or a third or all three, some made with monkey kidney, some with testes, some inactivated for ten days, some for thirteen, some for twenty-one.” Salk continued to work meticulously, indefatigably, and soon took the courageous step of endorsing human experimentation.
In June 1952 Jonas Salk obtained blood samples from 45 children and 27 members of the staff of the D. T. Watson Home for Crippled Children in Leetsdale, Pennsylvania. He typed the antibodies in the blood in order to determine which type of vaccine to use. Salk knew there were three types of poliovirus and that each would produce immunity only to the same type. Thus one person could have three attacks unless inoculated against all three strains.
On July 2, he gave 43 children either Type I, II, or III vaccine. “When you inoculate children with a polio vaccine,” commented Salk, “you don’t sleep well for two or three months.” Later, he also injected people who had no antibodies at all. He waited in nervous anticipation throughout the summer. When he again took blood samples he found that those which had had some antibodies to begin with now had far more, and those which had begun with none now showed high levels. He placed these blood samples in tissue cultures containing poliovirus. Miraculously, the tissue cells continued to grow. The antibodies had done their work on the virulent virus.
On March 26, 1953, Salk spoke to the nation on the CBS radio network and overnight became a hero in the eyes of a public long plagued and bewildered by the killing disease. He outlined his experiments and findings to date. Antibodies effective against the three types of virus had been stimulated in 160 persons without ill effect, and at levels comparable to those produced after a natural infection. While the nation eagerly waited, Salk stressed the need for further experimentation before a dependable vaccine could be made available. So throughout the year he continued to work. Nineteen fifty-four saw a massive field trial in which 1,830,000 children were inoculated, with positive results. In April 1955, news broke that Jonas Salk had developed a safe and effective vaccination. The U.S. Department of Health, Education, and Welfare licensed its commercial production, and plans were made to inoculate 30 million children that year.
Americans, of whom 100 million had supported the venture through the March of Dimes and another 7 million had collaborated in some capacity with the foundation, now longed to embrace their hero. They sent money, flowers, food, telegrams; they offered cars and glamorous vacations; colleges offered honorary degrees; and the press went wild. Salk did not welcome such adulation and fame. It disrupted his work and embarrassed him. Then only 40, he simply wanted to get back to the lab.
