Timeline Development of the Salk Polio Vaccine at the University of Pittsburgh
1947
Dr. Jonas Salk was recruited from the University of Michigan by Dr. William S. McEllroy, dean of the University of Pittsburgh School of Medicine, to establish a virus research program at the University of Pittsburgh. Salk was known for his expertise on the immunology of influenza, and during World War II, with Dr. Thomas Francis, developed the killed-virus vaccine that remains in use against influenza.
1948
Dr. Isabel M. Morgan of Johns Hopkins University demonstrated definitively that chemically inactivated poliovirus derived from monkey spinal cords would induce immunity when injected into monkeys. These studies supported what Salk suspected from his work with inactivated influenza vaccines: Active infection with a living poliovirus was not required to induce immunity – a killed virus vaccine might work.
1949
By the end of 1949, Salk had built laboratories in the basement of the Municipal Hospital for Contagious Diseases (now Salk Hall), and had assembled a core group of scientists. Dr. Julius S. Youngner, Maj. Byron L. Bennett, and Dr. L. James Lewis formed Salk's original team. Dr. Percival L. Bazeley and Dr. Ulrich Krech joined the team later. Together with Elsie N. Ward, a key research assistant, and numerous other technicians, this team would produce one of the world's revolutionary scientific achievements. With grants from the National Foundation for Infantile Paralysis, the Pitt team and three others around the country began the laborious task of classifying more than 100 strains of poliovirus isolated from patients. At least three strains were known to cause disease, and in order to develop an effective vaccine, researchers needed to know if there were others.
Working independently of Salk, Dr. William Hammon, inaugural chairman of the Department of Epidemiology and Microbiology at the University of Pittsburgh Graduate School of Public Health, hypothesized that passive immunization – by injection of blood gamma globulin with specific antibodies against polio – would temporarily halt infection, prevent clinical disease and confer life-long immunity. In a few years, he would lead a major breakthrough in the prevention of polio in the first large double-blind, placebo-controlled clinical trials ever to be conducted.
A team of Harvard researchers led by Dr. John F. Enders found that the poliovirus could be grown in non-neural tissue cultures. Their discovery not only made for a cleaner preparation of poliovirus, without the contaminants associated with monkey spinal tissue, but also paved the way for new analytical and production methods. Enders, Dr. Thomas Weller and Dr. Frederick Robbins would later receive the 1954 Nobel Prize for their contribution to virology.
1951
Salk and his team began using Enders' methods to grow poliovirus, and soon thereafter, Youngner developed new methods for growing the virus in culture using a technique called trypsinization. Their work also focused on selecting the best non-neural monkey tissue for growing large quantities of virus. Bennett worked on the inactivation process and the preparation of experimental vaccines, while Lewis worked on all associated monkey studies.
1952
The Pitt team developed improvements in virus typing methods, making it possible for it and its three collaborators to confirm there were only three immunological varieties of poliovirus.
The Pitt team began immunization experiments on monkeys, using polioviruses killed by formalin (37 percent formaldehyde). Contrary to prevailing scientific dogma that only a living virus vaccine could work, Salk believed that an effective killed virus vaccine could be developed by following basic principles of immunology. The Pitt researchers aimed to identify the strains of poliovirus, that once inactivated by formalin, would induce the most antibodies – initially in monkeys, and, ultimately, in humans – and to determine the optimal amount of formalin that would render the virus noninfectious without reducing its ability to stimulate production of protective antibodies.
In September, Hammon conducted the first placebo-controlled field trial of gamma globulin that, in just three days, enrolled 5,768 children in Provo, Utah.
Between January and February, Salk and his team found monkey kidney tissue to be the most fertile environment for virus growth and were able to grow the virus at unprecedented levels, thanks to Youngner’s development of trypsinization, the standard approach still used in labs worldwide today. The team also refined their methods to reliably kill the virus with formalin while preserving its ability to induce protective antibodies. Monkeys injected with this vaccine showed no ill effects and developed high levels of protective antibody within 21 days. After only one year of trials, animal immunizations had proven successful.
On June 12, 1952, Salk went to the D. T. Watson Home for Crippled Children in Leetsdale, Pa., to begin taking blood samples from recently paralyzed polio patients and staff members in order to determine the types of antibodies each had. He hoped that after inoculation their antibody levels would be increased. The first were inoculated July 2. Indeed, the children whose blood had contained antibody before inoculation had even higher levels of antibody afterward – an "impressive booster effect." Those who had no antibody before inoculation had levels of antibody similar to those following natural infection. In 1952, 98 subjects, mostly children, were studied at the Watson Home, and 63 more were inoculated at the Polk State School in Polk, Pa.
The summer of 1952 recorded 57,628 cases, the worst polio epidemic in U.S. history. This added greater urgency to the grass-roots national campaign begun in 1938 where mothers and fathers, boys and girls, and people from all walks of life across America gave their nickels, dimes and dollars to the "March of Dimes." Everyone was united in their dedication to fight polio, making the “March of Dimes” effort the largest private fundraising campaign ever.
In June and July, Hammon continued with his gamma globulin field trials and enrolled an additional 33,137 children in Houston and 15,868 in Sioux City, Iowa, for a total of 54,722 enrolled in less than a year. In October, published results provided the first evidence that antibodies to polio could prevent disease. Because gamma globulin only provided temporary protection and blood plasma was limited in supply, the approach was eventually deemed not practical for widespread use. Within a year’s time, the medical community would hear of promising results from Salk’s initial trials.
1953
March 28, Salk and his team published a landmark article in the Journal of the American Medical Association reporting results of the first 161 subjects who had been inoculated. Convinced that basic immunologic principles could be applied successfully in practice, he and the other Pitt researchers inoculated themselves and their family members.
On May 16, Salk initiated the first community-based pilot trial of the vaccine in the Pittsburgh suburb of Sewickley, drawing volunteers from the practices of two area physicians. By year’s end, nearly 700 children and adults had received the vaccine. Youngner developed a method to more efficiently measure antibody levels in order to accommodate the increasing number of blood sera samples coming into the lab. The color change test replaced the more laborious roller tube technique.
In anticipation of a large, national trial, Salk began discussions with laboratories at several vaccine manufacturers to address the challenge of mass producing the vaccine.
1954
In February, first-, second- and third-grade students from five suburban schools were the first to be inoculated in a second, expanded pilot trial. These schools were Leetsdale, Emsworth, Sewickley, Fair Oaks and St. James in Sewickley.
On February 23, students of Arsenal Elementary School were the first to be inoculated of the more than 5,000 6- to 9-year-olds from 19 City of Pittsburgh schools. These schools were: Arsenal, Belman, Bennett, Burgwin, Clayton, Colfax, Conroy, Crescent, Davis, Dilworth, Forbes, Frick, Fulton, Linden, Madison, Rogers, Sunnyside and Wightman. On March 11, Salk reported that 7,000 children had been already been inoculated.
On March 22, Salk’s team began giving inoculations of a commercially prepared vaccine to some 2,500 children from seven parochial schools. These schools were St. Lawrence, St. Stephens, Holy Rosary, Sacred Heart, Resurrection, St. Basil and St. George. All inoculations given before this date were with a vaccine prepared in Salk’s lab at the University of Pittsburgh.
On April 25, the Vaccine Advisory Committee of the National Foundation for Infantile Paralysis recommended a large-scale national trial of Salk’s vaccine based on a report involving more than 9,000 who had been inoculated in pilot trials since May 16, 1953. These included 5,320 who received vaccine prepared by Salk’s team in his lab. (At a June 7, 1955, meeting of the American Medical Association and in a paper published in the August 6, 1955, issue of the Journal of the American Medical Association, Salk indicated that some 15,000 had participated in the pilot studies that preceded the national trial.)
On April 26, the largest controlled field trial in the history of medicine got under way. Dr. Thomas Francis, Salk's mentor at the University of Michigan, led the study involving 1.8 million grade school children and 217 test sites in 44 states. More than 300,000 doctors, teachers, nurses and volunteers helped to administer the program. The vaccine used in the field trials consisted of inactivated poliovirus with the three immunologic types: Type I (Mahoney strain), Type II (MEF - 1 strain), and Type III (the Saukett strain), derived from the fecal specimen of a child hospitalized in Pittsburgh’s Municipal Hospital, a paralyzed boy named James Sarkett, whose name was misspelled on the original sample. According to a Gallup poll from May of 1954, "more Americans were aware of the polio field trials than knew the full name of the President of the United States."
1955
April 12, a convocation was held at the University of Michigan, where Francis announced that the killed poliovirus vaccine developed at the University of Pittsburgh was “safe, effective and potent.” Headlines around the world proclaimed, "The Vaccine Works!" The news was cause for celebration by the millions of Americans who had donated to the March of Dimes in the fight against polio. Salk received thousands of letters, especially from mothers and children – a spontaneous outpouring of thanks symbolic of the entire nation's gratitude. Six firms were immediately licensed to manufacture the Salk vaccine.
On April 26, officials first noticed an increase in reported polio cases in California. Soon it was learned that 200,000 had been inoculated with a vaccine produced by Cutter Laboratories that contained live virus. The “Cutter Incident” resulted in 200 children developing permanent paralysis and 10 deaths. Inoculations continued with vaccine produced by the five other companies, and by the end of 1955, 10 million children in five countries had been inoculated.
1964
Salk left the University of Pittsburgh to devote his full attention to the Salk Institute for Biological Studies in La Jolla, Calif. He remained there until his death in 1995 at age 80.