Kevin R. Loughlin
Boston, MA, United States

 

Jonas Salk was born in a tenement in the East Harlem section of New York City. Albert Sabin was born in Poland and as a child immigrated to the United States with his parents. From these humble beginnings, they would emerge as two of the preeminent scientists of their era. They would be locked in a rivalry, at times vitriolic, as they raced to develop a vaccine to prevent one of the feared diseases of their time: polio, infantile paralysis.

 

The disease

Only two vaccines existed at the turn of the twentieth century, one for smallpox (Jenner, 1796) and another for rabies (Pasteur, 1885). Other infectious diseases, both viral and bacterial, still ravaged humanity whenever outbreaks occurred.

In 1894 an astute Vermont family physician, Charles Caverly, reported 132 cases of infantile paralysis—probably the first known polio epidemic.¹ He published his observations in the Yale Medical Journal, where he described a recurring pattern of children developing high fever and headache, followed three or four days later by varying degrees of paralysis. In 1908, two Viennese pathologists, Karl Landsteiner and Erwin Popper, deduced indirectly that a virus and not a bacterium caused what was then known as infantile paralysis.² The actual polio virus would not be visible by electron microscopy until the 1950s.

In 1916 a major outbreak occurred in Brooklyn. The disease appeared to have a predilection for infants and children and occurred mostly in the summer. That July over 1100 new cases were reported in New York City alone.³ Haven Emerson, the Health Commissioner of New York, issued an order to quarantine every family where a case occurred. No one understood how the disease spread, and it would be years before it was recognized that the virus was harbored in the digestive tract. For the next four decades, parents would approach the summer months with fear that their children would contract this debilitating disease.

 

FDR

In 1921, the war on polio recruited an unlikely ally. Although the polio virus preferentially struck children, on August 11 of that year, thirty-nine-year-old Franklin Roosevelt became ill after attending a Boy Scout rally on the way to his summer home on Campobello Island off the New Brunswick coast. Within days, he became paralyzed from the chest down.

For the rest of his life, FDR demonstrated great courage in dealing with his affliction. But the war on polio was the direct beneficiary of his power and influence. Although throughout his political career he hid his disability via his “splendid deception,” he became the champion of medical research for the disease. As president, on September 23, 1937, he announced the formation of the National Foundation for Infantile Paralysis and appointed as its president his former law partner, Basil O’Connor. O’Connor possessed a rare blend of energy, vision, and organizational savvy that was invaluable to fundraising for the foundation. Through his contacts with celebrities such as Eddie Cantor, Judy Garland, and Jimmy Stewart, he developed a campaign that would become known as the “March of Dimes.” Common citizens would donate dimes, often in movie theaters, to support polio research. In the first year the March of Dimes raised almost two million dollars. Seven years later the fundraising exceeded eighteen million dollars.⁴

 

Salk and Sabin

Although they would become rivals, Salk and Sabin had much in common. Salk was born in 1914 to immigrants and grew up in East Harlem. He attended the competitive Townsend Harris Hall, an all-boys college preparatory school, and later graduated from the City College of New York and NYU Medical School. He was an outstanding student and was elected to AOA, the medical student honor society. He was accepted to the Mount Sinai Hospital Residency Program.

Albert Sabin was born Abram Sperstejn to Jewish parents in Bialystok, a city in the Russian Empire and later a part of Poland, in 1906. In 1921, he immigrated with his family to Paterson, New Jersey. An uncle financed his education to attend dental school at NYU. When he changed his mind to pursue medicine, he was on his own financially. In 1930 he became a U.S. citizen and changed his name to Albert Sabin.⁵ In 1931 he received his MD from NYU and began his residency at Bellevue Hospital.

Salk and Sabin both became interested in research early in their careers. In his final year of medical school, Salk was exposed to Thomas Francis, Jr., the new chairman of the Department of Bacteriology at NYU. Francis had made his name by discovering a new type of influenza virus. At the time, the only available anti-viral vaccines—smallpox, rabies and yellow fever—relied on weakened or attenuated virus inoculations. Francis started Salk working on a “killed virus” influenza vaccine, which would shape Salk’s belief throughout his career of the advantages of killed rather than attenuated vaccines. Salk would ultimately follow Francis to the University of Michigan before moving to Pittsburgh to start his own research laboratory.

After Sabin completed his residency at Bellevue, took a virology fellowship at London’s Lister Institute, and then returned to the Rockefeller Institute in New York to begin his academic career under Thomas Rivers and Peter Olitsky. While at Rockefeller, Sabin became convinced of the inherent superiority of attenuated over killed virus vaccines. Like Salk, Sabin would keep this belief, embraced early in his research career, throughout his professional life. In 1935 he left to start his own laboratory at the University of Cincinnati.

 

The rivalry and the race to the vaccine

On arriving at Pittsburgh, Salk and his team worked assiduously to develop a killed virus vaccine. They inactivated the virus with formalin and began conducting field trials, sometimes at facilities of the disabled or mentally infirm. Controversy arose when a Chicago physician, Albert Milzer, presented a paper at the American Public Health Association meeting claiming that Salk’s published inactivation technique with formalin failed to kill the polio virus. Sabin viewed this as an opportunity to undermine Salk. He wrote immediately to Aims McGuinness, a powerful leader in the American Academy of Pediatrics, to raise concerns about the validity of the formalin inactivation. It should be acknowledged that Sabin was almost a decade older than Salk and was considered the more experienced investigator. Early on, he criticized Salk at medical conferences and questioned the durability of killed vaccine titers.

Despite the doubts raised by Milzer’s presentation, Salk’s methodology was validated and he published his results in 1953 in the Journal of the American Medical Association. Based on Salk’s work, the National Foundation for Infantile Paralysis financed a field trial on almost two million American children between the ages of six and nine under the supervision of Thomas Francis.

On April 12, 1955, the tenth anniversary of FDR’s death, the trial results were released. Francis announced that the killed vaccine was safe, potent, and effective. Salk immediately became a celebrity and national hero. But resentment awaited him. Although he acknowledged the contributions of his team when he accepted the inevitable accolades, he failed to identify them by name. The estrangement between Salk and some of his research colleagues persisted for a lifetime and was even mentioned in Julius Youngner’s obituary over six decades later.⁶

To meet the enormous interest created by the announcement of the trial’s success, several companies were licensed to produce the vaccine. Shortly after the vaccine’s approval, scattered reports appeared of children developing paralysis after receiving the vaccine. An intense investigation followed and implicated only vaccines produced by Cutter Laboratories and caused by a deviation from the Salk protocol. The error was corrected and the killed virus vaccination initiative then continued unabated.

Sabin was undeterred and continued his work on the attenuated virus. He conducted live vaccine trials in the Soviet Union and Mexico; another investigator, Hilary Koprowski, conducted similar trials in the Congo and Poland, confirming the efficacy of the attenuated vaccine. Ultimately two million Soviet children were vaccinated and Sabin was given the highest Soviet civilian honor, the Order of Friendship Among Peoples.⁷

 

Denouement

Both Salk and Sabin were ultimately proven right. The Salk killed vaccine, given by injection, is the approved vaccine in the United States today because of its greater safety. The Sabin oral, attenuated vaccine is given in many parts of the world, particularly in underdeveloped countries, because of its ease of administration. Polio has been eradicated from the globe except in parts of Afghanistan, Pakistan, and Nigeria. In 1954 John Enders, Frederick Robbins, and Thomas Weller received the Nobel Prize for demonstrating how to cultivate polio virus in a test tube using a combination of embryonic skin and muscle tissue.

Neither Salk nor Sabin ever received the Nobel Prize for their work. It has been speculated that this may have been due to jealousy, that each sought out personal notoriety, or that both had commercial ties to industry. The lessons from the polio vaccine story are manifold. First, today more than ever, it shows that so many contributions can and have been made by immigrants. Second, it demonstrates the power of private philanthropy. Finally, it serves as a reminder of the value of zealots. An individual or small group of individuals who believe in their goal can accomplish much, even against great odds.

 

References

1. Baicus A. History of polio vaccination. World Journal of Virology 2012;1(4): 108-114.
2. Polio cases, deaths and vaccination rates. https://vaccines.procon.org/view. Accessed 1/2/2018.
3. Jacobs, CD. Jonas Salk: A Life. New York: Oxford University Press, 2015, 1-2.
4. Ibid, pp. 71-73.
5. Ibid, pp. 76-77.
6. Roberts, S. Julius Youngner, 96, Virologist Who Helped Create Polio Vaccine, Is Dead. NY Times, 5/7/2017, p. 27.
7. Polio vaccine. Wikipedia, accessed 1/2/2018.

 

Acknowledgments

Dr. Loughlin would like to make two personal acknowledgments. His beloved Aunt Viola was a polio victim. She was born in 1908 and lived her entire life in New York City. She probably contracted polio during the 1916 epidemic. Ironically, her entire career was spent as a laboratory technician in the New York City Health Department. She walked with the assistance of crutches throughout her entire life and never complained.

As a young urologist, Dr. Loughlin had the privilege of taking care of Dr. Thomas Weller who never once mentioned his Nobel Prize. He and his wife were marvelous individuals.

 

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KEVIN R. LOUGHLIN, MD, MBA, received his A.B. from Princeton University, M.D. from New York Medical College, M.B.A. from Boston University and M.A. (Hon.) from Harvard University. He has been a practicing urologist for almost forty years and is currently the Vice President of the American Board of Urology and a member of the board of directors of the American Urological Association. He has had a lifelong interest in medical history.

 

Highlighted in Frontispiece Volume 10, Issue 3– Summer 2018
Winter 2018  |  Sections  |  Infectious Diseases