Two Vaccines

I have just figured out that during the coming summer, thirty or forty thousand children will get polio. About fifteen thousand of them will be paralyzed and more than a thousand will die. If we have the capacity to prevent this, we have a social responsibility... we are supported by the people and it is our duty to save lives no matter how many difficulties may be involved.
Basil O'Connor, president of March of Dimes, 1954

From the early 1900s, researchers pursued two different kinds of polio vaccine. One used inactivated (killed) viruses. The other kind used live but attenuated, or weakened, virus. Jonas Salk was the leading proponent of the killed virus approach, and Albert Sabin became the foremost proponent of the attenuated virus approach.

Albert Sabin (left) and Jonas Salk (center) meeting with Basil O’Connor of the March of Dimes in 1961
Courtesy of March of Dimes

FACTOIDS
  • At its peak incidence in the early 1950s, poliomyelitis occurred at a rate of 13.6 cases per 100,000 population. By comparison, the incidence of cancer in 2005 is 566.1 per 100,000.
  • Edward Jenner created the first successful vaccination for a disease—smallpox—in 1796. At the time of the polio clinical trials, there were three widely used vaccines: for yellow fever (1937), rabies (1885), and smallpox. Today there are over 300 vaccines for about thirty different diseases.
  • There are two kinds of polio vaccine. IPV (Salk’s) is an injected shot used today primarily in the United States and Europe. OPV (Sabin’s) is given orally in drop form and used in global efforts to stop polio transmission.

The Salk Vaccine

The chief advantage of Salk’s killed virus vaccine was safety. If made properly, it could not cause disease. Its chief disadvantage was that the formaldehyde used in its manufacture caused the immune system to recognize killed virus differently from live virus, possibly risking a shortened period of immunity.

Results of trials with small numbers of children in 1952 encouraged the National Foundation for Infantile Paralysis to adopt Salk’s vaccine for a large-scale trial in 1954. Salk called his vaccine “Pittsburgh vaccine,” but reporters named it “the Salk Vaccine.”

Jonas Salk on the cover of Time magazine.

Formaldehyde from Jonas Salk's laboratory. At the University of Pittsburgh in 1952, Salk used formaldehyde to inactivate poliovirus effectively preventing it from reproducing

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While in his second year at New York University Medical School, Jonas Salk heard two lectures that changed his life: “In the first lecture, we were told that it was possible to immunize against diphtheria and tetanus by the use of a chemically treated toxin [to kill it]…. In the very next lecture, we were told that in order to immunize against a virus disease it was necessary to go through the experience of infection. It was not possible to kill the virus…. The light went on at that point. I said that those two statements can’t possibly both be true. One has to be false.
Jonas Salk, 1990

Some of the thousands of children who received free vaccine in the weeks following the announcement, waiting in segregated lines
Courtesy of Memphis Commercial Appeal

Sabin and Salk

While the large-scale clinical trial with Salk vaccine went ahead in 1954, Albert Sabin continued developing his live-virus vaccine. Like many researchers of the day, Sabin strongly disagreed with Salk’s approach of using injected, “killed” virus. He believed that long-term immunity could only be achieved with a live, attenuated—or weakened—virus.

In the race to develop a safe and effective polio vaccine, accidents occurred with both types. In 1955, for instance, insufficiently killed virus in the vaccine from Cutter Laboratories in Berkeley, California, infected some 200 children; many were paralyzed and several died. But the global end to polio transmission would have been inconceivable without both the “killed” (Salk) and “live” (Sabin) vaccines. Neither Jonas Salk nor Albert Sabin patented their vaccines; they donated the rights as gifts to humanity.

Family with fifteen children lined up for oral polio vaccine, around 1963

Albert Sabin of the University of Cincinnati feeding oral polio vaccine to a child, early 1960s
Courtesy of University of Cincinnati, Cincinnati Medical Heritage Center, Hauck Center for the Albert B. Sabin Archives

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The Sabin Vaccine

An important feature of Sabin’s oral polio vaccine was that immediately after vaccination, people shed weakened virus in their fecal waste. Exposure to the shedded weakened virus boosted immunity for others in the community and gradually reduced the number of people susceptible to poliomyelitis.

Between 1963 and 1999, Sabin's live type vaccine largely replaced Salk's killed type vaccine everywhere in the world. However because the live virus in the vaccine occasionally became strong enough to cause actual disease, Salk's killed-type vaccine has replaced Sabin's live type vaccine in the United States.

I have studied the effects of our new lots of polio vaccine in 100 adult volunteers and during the next few days shall give it to my wife and 2 children as well as to our neighbors and their children.
Albert Sabin, 1957

Sabin and the Cold War

Sabin had to go overseas in the late 1950s to find people for his clinical trials in the Belgian Congo and on a massive scale, in the Soviet Union because Salk vaccine was used so extensively in the United States. An American was able to conduct an extensive polio vaccine trial in the Soviet Union at the height of the cold war because the fear of polio was stronger than political differences.

After getting satisfactory results of tests of your vaccine in 20,000 children we are going to prepare from your strains (1956) material for vaccination of 2~3 million people more, and after thorough laboratory tests of this vaccine, to use it in our country in 1959.
Dr. Mikhail Chumakov to Albert Sabin, letter of December 26, 1958

In the first five months of 1959, ten million children in the Soviet Union received the Sabin oral vaccine. Albert Sabin received a medal in gratitude from the Russian government during the height of the cold war.

Albert Sabin with Dr. Victor Zhdanov, Soviet deputy minister of health, 1958
Courtesy of Heloisa Sabin

Albert Sabin's medal, box and vial of Russian oral vaccine, matchbox advertising the vaccine campaign, two photographs of Sabin with Russian scientists, 1956-1958
Medal courtesy of University of Cincinnati, Cincinnati Medical Heritage Center, Academic Information Technology and Libraries; other items courtesy of Heloisa Sabin

Matchbox used to promote Sabin's oral polio vaccine during the 1963 Soviet Union clinical trials

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Sabin's oral vaccine made and used in the Soviet Union, 1963

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Killed or Live Vaccine?

Albert Sabin and other researchers, including John Enders and Hilary Koprowski, had argued that long-term immunity to polio could only be achieved with a live weakened virus and must follow the same route of infection as wild-type poliovirus—through the mouth and infecting intestinal tissue. Weakening the virus required passing it through a succession of animals—rats, mice, or monkeys. This allowed it to become more virulent for these hosts, and less so for humans. Hilary Koprowski carried out the first successful trial of weakened virus vaccine in February 1950.

Rhesus monkeys in laboratory, 1956
Courtesy of March of Dimes

TOUGH CHOICES

Medical Miracles Are Complicated
Although the scientific method of hypothesis formulation, testing, and verification is straightforward, even the most spectacular achievements involve complicated issues and tough choices. The scientists who raced toward effective polio vaccines tested their work on prisoners, institutionalized children, and tens of thousands of monkeys, as well as on themselves and their family members. They believed they were serving the greater good of society and of science.

  • More than 100,000 monkeys were killed in the course of developing the polio vaccines.
  • One rhesus monkey, when killed, supplied sixty-five doses of vaccine.