“MMR causes autism.” “Gardasil makes girls promiscuous.” Today’s highly publicized debates about vaccines are often compared (unfavorably) to the heyday of vaccine development in the mid-twentieth century, when smallpox was eradicated and schoolchildren lined up by the millions to be protected against polio. At a time when presidential candidates are asked about their stance on vaccines and when famous comedians make internet videos about how their benefits outweigh their risks, it may be mete to recall that those campaigns were no less political or fraught with uncertainty.
Across the street from the University of Pittsburgh School of Medicine and its Oakland hospital complex is a sand-colored building with many windows: Salk Hall. It is named for one of the researchers who worked on the first successful polio vaccine there in the 1940s and 1950s. The son of Russian-Jewish immigrants, Jonas Salk (1914-1995) was a first-generation college and medical student. While a post-doc at the University of Michigan in the 1940s, he collaborated on the development of the first influenza vaccine, an inactivated whole-virus vaccine. In 1947 he was recruited as director of the Virus Research Laboratory at the University of Pittsburgh School of Medicine. The National Foundation for Infantile Paralysis (NFIP, now March of Dimes) wanted to sponsor him to work on polio. At that time, paralytic poliomyelitis was epidemic in the United States, sickening >50,000 people a year, killing thousands, and putting almost half on crutches, in wheelchairs, or in iron lungs. Summer—when children were free from school to go swimming and buy ice cream cones—had become a season of panic.
Salk was hardly the only researcher looking for a vaccine for this “dread disease.” Marcus Brodie (NYU) and John Kolmer (Temple) had developed killed and attenuated vaccines, respectively, but their clinical trials in 1935 both ended in disaster, with recipients suffering allergic reactions, paralyzation, or even death. Hilary Koprowski and Herald Cox (Lederle Labs, NY) then created an attenuated oral vaccine that they tested on chimpanzees and themselves before giving it to children with epilepsy and intellectual disabilities in 1950. Salk also used disabled institutionalized children for his first human trials, in 1952. Another Pitt researcher, William M. Hammon, showed the efficacy of IVIG for short-term protection against polio. The coup de gras was a randomized, double-blind, placebo-controlled trial of an injectable killed vaccine against all three serotypes involving almost 2 million children funded entirely by the NFIP (i.e. no federal dollars) and run by Salk’s old mentor at Michigan, Thomas Francis, Jr.
On April 12, 1955—10 years to the day since President Franklin Delano Roosevelt’s death(1)—the Federal Drug Administration announced that Salk’s polio vaccine was safe and effective. In those optimistic post-World War II years after the demonstration of nuclear power at Hiroshima and Nagasaki, and before the Tuskegee Syphilis Study became front-page news, most Americans put their faith in science, technology, and medical advances such as Salk’s new shot. That faith was immediately tested, as vaccination was temporarily halted less than one month later after hundreds of children were infected by faulty batches out of Cutter Laboratories in California, and 11 died. Nevertheless, Salk entrusted his laboratory’s work to the common good and never patented the vaccine. What he lost in monetary rewards he gained in fame and public acclamation. The National Foundation for Infantile Paralysis touted Salk as a single, heroic scientist—and he let them.
Salk is often juxtaposed with Albert Sabin (1906-1993), another NFID-supported polio researcher. Sabin was born in Poland and fled anti-Semitism in 1921. During WWII, he developed vaccines for trypanosomiasis, sand-fly fever, and dengue fever. He was one of two scientists to demonstrate that the polio virus does not enter the nervous system via the nasal mucosa but rather via the bloodstream from the gastrointestinal tract. His lab at the University of Cincinnati created an attenuated oral vaccine that was tested in an uncontrolled, unblinded study on 10 million Soviet children from 1957 to 1959.
The FDA licensed it for use in 1960, and it was the standard in the United States from 1968 until the late 1990s. The oral polio vaccine (OPV) stimulates faster individual immunity, fosters herd immunity, and is more palatable to administer but is no more or less efficacious than the intramuscular inactivated polio vaccine (IPV). It is responsible for the near-eradication of polio. However, right here at Pitt someone else’s contributions to “Salk’s” vaccine were overshadowed.
Many other Pitt researchers and technicians had contributed to the discovery, among them Julius Youngner (1920-2017). If Salk was “Mr. Outside,” the public face of the lab, Youngner was “Mr. Inside,” the scientific whiz. The son of a Jewish businessman in New York, Youngner had worked on the Manhattan Project at the University of Rochester during World War II before coming to the University of Pittsburgh in 1949. His contributions to the polio vaccine included devising a way to grow large amounts of poliovirus in monkey cells, figuring out how to reliably inactivate the virus so it could be injected safely, and creating an antibody assay to measure vaccine efficacy after administration. Youngner continued a productive virology career at Pitt, working on interferon gamma and a vaccine for equine influenza, but as his obituary in the Pittsburgh Post-Gazette put it, Youngner “never forgave Jonas Salk for his failure to acknowledge Mr. Youngner and the other members of the research team that created the vaccine against the crippling disease.”(2)
The polio vaccine was Salk’s greatest lifetime achievement. He spent the rest of his career at an eponymous institute in La Jolla, CA, working on other vaccines, notably one for HIV/AIDS. Today, American children receive four injections of IPV, while OPV is used to vaccinate the rest of the world. Only Afghanistan, Pakistan, and Nigeria are still known to have circulating wild-type virus. Twenty two cases were reported in 2017. Interestingly, none of these men received a Nobel Prize. The 1954 Prize in Physiology for Medicine went to Harvard scientists John Enders, Thomas Weller, and Frederick Robbins “for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue.”
Kristen Ann Ehrenberger, MD, PhD (History), is an Internal Medicine-Pediatrics Resident, UPMC.
For further reading:
Jeffrey Kluger, Splendid Solution: Jonas Salk and the Conquest of Polio (New York: Berkley Books, 2004).
Bernard Seytre and Mary Shaffer, The Death of a Disease: A History of the Eradication of Poliomyelitis (New Brunswick, NJ: Rutgers University Press, 2004).
Marc Shell, Polio and Its Aftermath: The Paralysis of Culture (Cambridge, MA: Harvard University Press: 2005).
David M. Oshinsky, Polio: An American Story (New York: Oxford University Press, 2005).
(1) FDR was America’s most famous polio patient, and he co-founded the NFIP, but it is likely he actually had Guillain-Barré Syndrome. He died of a stroke. (2) Mark Roth, “Obituary: Julius Youngner: Last surviving member of Salk vaccine team
Oct. 24, 1920¬-April 27, 2017,” Pittsburgh Post-Gazette (28 April 2017), http://www.post-gazette.com/news/obituaries/ 2017/04/28/Julius-Youngner-Salkvaccine/ stories/201704280215.