The Shot Heard 'Round theWorld: The Development of the Salk Polio Vaccine 1947-1955

An Age-Old Disease

Paralytic poliomyelitis, or polio, is a disease that can attack the motor nerves in the spinal cord, leaving one's legs or arms paralyzed. In the most severe cases, the muscles of the respiratory system and throat are affected, impairing speech, swallowing, and breathing. For more than 5,000 years, from the ancient Egyptians to the Europeans of the 1800s, the poliovirus occasionally took its toll, primarily in infants, causing the disease to be known as infantile paralysis. Yet, the disease remained endemic, only sporadically striking individual infants.

A New Disease

Early Twentieth Century

In 1916, the first major U.S. epidemic struck, paralyzing young children and horrifying the nation. Following the 1916 epidemic, increasing numbers of epidemic outbreaks began to occur each year in the United States, gradually including older children and young adults. Each summer brought the fear of polio, for it was in the summer season that epidemics struck. The incidence of polio in the United States rose steadily, with a marked increase in the 1940s. Swimming pools, movie theaters, beaches, and other public places closed throughout the country in fearful reaction to the disease. Hospital wards were filled with row after row of iron lungs. Tens of thousands were treated for polio, many of whom were left crippled and fitted with leg braces. As the virus continued to take its toll, President Franklin D. Roosevelt, himself a wheelchair-bound polio victim, in 1938 created the National Foundation for Infantile Paralysis, known today as the March of Dimes, to support care and treatment of polio victims and scientific research about polio. As the twentieth century unfolded, the search for a prevention of polio became a national rallying cry.

1947 - 1948

Dr. William S. McEllroy, dean of the University of Pittsburgh School of Medicine, in 1947 recruited Jonas Salk from the University of Michigan to develop a virus research program at the University of Pittsburgh. Salk began to set up a research laboratory in the basement of The Municipal Hospital for Contagious Diseases (now Salk Hall). Previously, during his five and one-half years at Michigan, Salk had become known for his expertise on the immunology of influenza. During World War II, he had helped develop the killed virus vaccine that continues to be used against influenza. In 1948, Dr. Isabel M. Morgan demonstrated definitively that chemically inactivated poliovirus derived from monkey spinal cords would induce immunity when injected into monkeys. Drs. H. S. Loring and A. Milzer had previously reported similar results injecting inactivated poliovirus into rats and mice, respectively. These studies supported what Jonas 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.

1948 - 1949

By the end of 1948, Jonas Salk had built laboratories and had assembled a core group of scientists. Dr. Julius S. Youngner, Major 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 strains of poliovirus.  Scientists now knew that there were at least three different types of poliovirus that could each cause disease. To develop an effective vaccine, it was necessary to find out if there were more than three. The Pitt team developed improvements in the virus typing methods, and, over the next four years, the cooperative group evaluated more than 100 strains of poliovirus isolated from patients. Ultimately, they discovered that there were, indeed, only three immunologic varieties of poliovirus.

1949

In 1949, 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, Weller, and Robbins would later receive the 1954 Nobel Prize for their contribution to virology. Salk's experience with killed virus influenza vaccines and the discoveries of scientists such as Morgan, Loring, and Milzer, culminating in the pivotal breakthrough by Enders, set the stage for the ensuing research by the Pitt team.

1950

Salk and his team began using Enders' methods to grow poliovirus in tissue cultures. Each member of the team had his or her own area of specialization. Youngner with Ward developed new methods of measuring the amount of virus grown in culture and the levels of antibody against poliovirus in blood. 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.

1951

The Pitt team began immunization experiments on monkeys, using polioviruses killed by formalin (37% formaldehyde). Contrary to the 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. Two major questions were studied. First, the Pitt researchers wanted to discover which strains of poliovirus, once inactivated by formalin, would induce the most antibodies - initially in monkeys, and, ultimately, in humans. Second, they searched for the optimal amount of formalin to use to render the virus noninfectious without reducing its ability to stimulate production of protective antibodies. Salk was convinced that the answers to the latter questions would lie in the discovery of the principles governing chemical reactions between poliovirus and formalin, wrote Richard Carter in Breakthrough.

January - February, 1952

Salk and his team found monkey kidney tissue to be the most fertile environment for virus growth and were able to grow the virus to unprecedented levels. This same winter, the team established 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! The team was now ready to begin trial inoculation of humans.

Summer, 1952

While the Pitt researchers made swift progress, the worst recorded polio epidemic in U.S. history took place with 57,628 cases reported.   At the same time, a grass roots national campaign was under way 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."   People of all ages and backgrounds were united in their dedication to fight polio, making this the largest private fundraising campaign ever.

1952 -1953

On June 12, 1952, Salk went to the D. T. Watson Home for Crippled Children in Leetsdale, Pennsylvania to take blood samples from recently paralyzed polio patients, find out the type of antibodies they had, and then inoculate them to see if vaccines made in the Pitt research lab would raise their antibody levels. He initially took blood samples from 45 children and 27 staff members.  By the end of the summer, the answer was clear. The children whose blood had contained antibody before inoculation had even higher levels of antibody - an "impressive booster effect." Those who had no antibody before inoculation had levels of antibody similar to those following natural infection. Eventually, a total of 161 subjects were studied at the Watson Home and at the Polk State School in Polk, Pennsylvania. Salk was now convinced that basic immunologic principles could be applied successfully in practice. During 1953, human trials were extended to include almost 500 children and adults, the majority of whom were residents of Allegheny County. In that same year, Salk began to address problems related to the mass production of the vaccine in collaboration with laboratories at several vaccine manufacturers.

1954

The largest controlled field trials in the history of medicine got under way in the spring of l954 in anticipation of the summer polio season. Dr. Thomas Francis, Salk's mentor at the University of Michigan, was the study leader. 1.8 million grade school children were enrolled in the trials at 217 test sites in 44 states. More than 300,000 doctors, teachers, nurses, and volunteers helped administer the program. 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." The vaccine used in the field trials consisted of inactivated poliovirus with all three immunologic types:  Type I (Mahoney strain), Type II (MEF - 1 strain), and Type III (the Saukett strain), the donor of which was a paralyzed boy in Municipal Hospital named James Sarkett, whose name was misspelled on the sample.

April 12, 1955

At a Convocation at the University of Michigan, Dr. 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!" With this announcement, people in towns all across America rejoiced in what was their victory, too, for the nickels and dimes that millions of Americans had donated to the March of Dimes in this fight against polio had now borne fruit. Their joyous celebrations throughout the country reflected a magical moment in this country's history. As Richard Carter describes in his book Breakthrough, "people observed moments of silence, rang bells, honked horns, blew factory whistles, fired salutes . . . hugged children. . . .  More than a scientific achievement, the vaccine was a folk victory." Salk received thousands of letters, especially from mothers and children - a spontaneous outpouring of thanks symbolic of the entire nation's gratitude.

Since 1955

During the first three years of widespread use of Salk's polio vaccine (1955 - 1957), the incidence of polio in the United States fell by 85 - 90%. Before 1962, when an oral live poliovirus vaccine developed by Albert Sabin began to be widely used in the United States, the incidence of polio had decreased by 95%. With the use of these two polio vaccines, naturally occurring poliomyelitis was eradicated from North and South America and western Europe. To eliminate the remaining occasional cases of paralytic poliomyelitis caused by the live polio virus vaccine in the United States, the U.S. Public Health Service recommended in 1999 that its routine use be discontinued in favor of the killed poliovirus vaccine that had originally been developed at the University of Pittsburgh. The goal of the World Health Organization is to eradicate poliovirus from the world so that vaccination is no longer needed. Salk's team brought under control an escalating health problem and a dreaded virus that had inflicted fear and suffering well into the twentieth century.  In addition, their scientific breakthrough established that basic principles of immunology could be applied to develop effective noninfectious vaccines.  For these reasons, the Salk vaccine is considered one of the most significant medical achievements of the twentieth century.