Conquering polio: the trials of Dr. Thomas Francis Jr.
In the early 1950s, polio was among the things most feared by American citizens, second only to nuclear war. Easily spread and sometimes fatal, the disease was seemingly indestructible. It was left to one researcher to conduct a national trial for a safe, successful polio vaccine, which would hopefully eradicate the disease and the terror surrounding it.
On the morning of April 12,1955, the country's attention was focused on the University of Michigan's (U-M) Rackham Hall. There, about to be released, were the results of America's largest public health experiment--a landmark vaccine field trial that, if successful, could effectively eliminate polio.
Since World War II, there had been a resurgence of polio. The highly contagious disease often struck without warning, leaving behind death and destruction. America's hope hinged on the field trial directed by Thomas Francis Jr., a renowned U-M professor and mentor to the vaccine's creator.
Francis was a scientist who was recruited in 1941 to become chairman of the new epidemiology department at the U-M School of Public Health. He was a recognized pioneer in the rapidly growing field of virology, the scientific study of viruses, and many considered him to be the best epidemiologist in the world. Called Tommy by his friends, Francis grew up in the western Pennsylvania city of New Castle. He then attended Allegheny College and finally Yale, where he received a medical degree in 1925.
While at the Rockefeller Institute in the 1930s, Francis became one of the nation's leading experts on influenza and the first American to isolate a human flu virus. His discovery of the existence of multiple flu strains proved critical to any attempt at creating an effective flu vaccine. He rose through the ranks and, in 1938, became the departmental chair of the New York University (NYU) College of Medicine.
Seeking a cure to infectious diseases caused by viruses, Francis had a revolutionary idea. He hypothesized that inactivated viruses--effectively killed so that they were noninfectious--could be used as vaccines. His contemporaries dismissed his idea, believing instead that vaccine-induced immunity could only be produced by creating a limited infection caused by a greatly weakened virus. That was the basis for an attenuated, or weakened, vaccine.
In 1941, Francis moved to U-M and was selected to head the Army's Commission on Influenza. The Army had not forgotten the flu pandemic of 1918 during World War I, which had left dead nearly as many soldiers as were killed in combat. The Army actively sought a flu vaccine and supported Francis's hypothesis since it seemed to provide a much wider margin of safety than an attenuated vaccine.
As America braced for war in the fall of 1941, Francis received a letter from a former NYU student, Jonas Salk, inquiring about a research position. Recalling the student's brilliance and dedication, Francis pulled strings to ensure that Salk received an occupational deferment from the draft in order to work in his lab. Salk spent six years at U-M as an apprentice under Francis's tutelage, where he learned critical laboratory and administrative skills.
Together, Francis and Salk developed an experimental flu vaccine that could be mass-produced in eggs and inactivated with chemicals. With the Army's approval, they conducted a number of field trials with deployed soldiers as subjects, successfully demonstrating that the vaccine was both safe and effective. Based on those results, the Army began a mass vaccination program in 1944.
The experiences of Francis and Salk during that period laid the foundation for Salk's later groundbreaking work on polio. The two scientists would later cross paths again, both of them contributing to the greater benefit of mankind.
During the post-World War II period, no disease triggered the same terror as polio. Surveys taken at the time indicated that the only thing Americans feared more than polio was nuclear war. It appeared that the disease was at the height of its destruction. In 1952, for example, 57,000 cases of polio were recorded in the United States.
There was no telling who would become infected and who would be spared. Polio killed some and crippled others for life, rendering them dependent on wheelchairs, leg braces, or iron lung respirators. Victims ranged from anonymous children to President Franklin Delano Roosevelt, who had been paralyzed by the disease. For unknown reasons, there were fewer polio cases observed in lower-class communities than in wealthier neighborhoods.
In the 1950s, polio was still largely a mystery to science. Public health officials knew that germs were easily spread from person to person, so they recommended that children avoid crowds, frequently wash their hands, get plenty of rest, and avoid swimming in pools or lakes. To further curb the spread of polio, during the summer, theatres went dark, churches stopped having services, bars and bowling alleys shut their doors, and city councils closed all indoor meeting places. The paranoia even reached a point that, when people met, they would not shake hands.
America was desperate for a vaccine cure. Leading the scientific crusade against the polio scourge were two researchers, Albert Sabin and Jonas Salk. Sabin loudly supported the live, attenuated approach, while Salk pursued an inactivated vaccine.
After leaving U-M, Salk had moved to the University of Pittsburgh and built a lab that exclusively researched polio. There, he discovered that three infectious strains of the polio virus existed. Through principles learned at U-M, Salk developed a vaccine that contained a complex mixture of each strain. A pilot study demonstrated that humans inoculated with the vaccine had increased blood levels of antibodies against polio without any negative effects. Based upon those promising results, a national experiment was organized.
Financing the expensive field trial came solely from the National Foundation for Infantile Paralysis, later renamed the March of Dimes. The grassroots, nongovernmental organization, created in 1938 by President Roosevelt and his former Wall Street law partner Basil O'Connor, had the sole mission of eradicating polio. Through savvy advertising, it gained strong public support, which included the use of "poster children" and celebrity endorsements, and consistently raised more than $20 million in annual public donations. Acting on its own and exhibiting philanthropy on a grand scale, the National Foundation sponsored the largest medical experiment in American history.
The National Foundation desired an internationally recognized expert to direct the Salk vaccine trial, so Thomas Francis, Salk's former mentor, was requested. All involved knew that the experiment was an incredibly arduous task--in scope and magnitude, it was entirely unprecedented. Francis, however, possessed an impeccable reputation. For his critical influenza work, he had been awarded the prestigious Lasker Award for Clinical Research and membership to the elite National Academy of Sciences. Francis agreed to direct the study with the stipulation that he would be responsible for the design, supervision, and independent evaluation of the results.
Knowing that children aged five to nine had the highest incidence of polio, Francis planned to run the trials in elementary schools, where he expected good record keeping and regular attendance. He disliked the original experimental design to inoculate only second graders and use first and third graders as observed controls.
Francis also added a double-blind process, which was not widely accepted at the time. In a double-blind experiment, half of the children would receive the vaccine and the other half a placebo, which was a liquid solution made to look exactly like the vaccine but contained no virus. Neither the patients nor the clinicians would know whether a child received the vaccine or a placebo during the series of three shots. To ensure the experimental vaccine was safe and lacked any residual live virus, each batch produced was triple-tested by the manufacturer, Salk's lab, and the Public Health Service.
Francis also insisted upon a large field trial, which was critical to illustrate statistical relevance and provide persuasive scientific evidence. Participating counties needed to be evenly dispersed across the continental United States and represent a wide range of urban, rural, and suburban populations.
Preference went to those counties that had the most polio cases and a population between 50,000 and 200,000, which was large enough to reflect an area's diversity but small enough to be manageable. Francis eventually chose 211 counties in 44 states, almost half of which he instructed to use the double-blind vaccination process. A small group of students from Canada and Finland also participated.
In February 1954, Francis opened the Vaccine Evaluation Center in U-M's old maternity hospital. To support him in that Herculean effort, the National Foundation effectively gave him a blank check. Francis hired a diverse staff of more than 100, which included statisticians from the Census Bureau. The trials started two months later when a six-year-old boy in McClean, Virginia, received the first vaccine shot.
The scope of the experiment itself was enormous. Support came from an estimated 14,000 school principals; 50,000 teachers; 20,000 physicians; 40,000 nurses; and several hundred thousand non-professional volunteers. Due to the widespread fear of polio, it was not difficult to find parents willing to sign the volunteer informed consent forms so their children could receive the vaccine. The National Foundation dubbed those youngsters "Polio Pioneers," and each received a signed certificate, candy, and a commemorative metal pin.
When the trials were completed in the late spring, more than 1.8 million children had participated. Francis's team collected, processed, coded, and interpreted all of the data, building a record for each child.
National attention was riveted on the Salk field trial, and news coverage of the experiment riveted other sensational contemporary stories such as the Army-McCarthy hearings and Brown v. the Board of Education. It took Francis nearly a year to comprehensively evaluate the enormous amount of data collected in the experiment.
The findings were to be announced at U-M Rackham Hall on the 10-year anniversary of President Roosevelt's death. A crowd of almost 500 was present, and 16 cameras along the back wall broadcast the event on closed-circuit to more than 50,000 anxious physicians watching in movie theatres. On the morning of April 12,1955, Francis released the much-anticipated verdict--the trial had been successful, and the Salk vaccine was unequivocally proven to be "safe, effective, and potent."
Almost immediately after the press release, the Salk vaccine was licensed and a massive children's vaccination campaign launched. It was not long before the vaccine's positive impact became apparent, with the number of polio cases in the United States dropping to 5,600 in 1957 and to a mere 161 in 1961. That same year, Albert Sabin's live, attenuated vaccine, too, was licensed. As advertised, it provided better immunity than the Salk vaccine but came at a cost--it occasionally reverted to its natural form and caused paralysis.
Through the use of those two vaccines, polio was eliminated in the United States in 1979 and in the Americas by 1994. The Salk and Sabin vaccines have almost completely eradicated polio worldwide, reducing reported cases to several hundred annually. Though both vaccines are listed on the World Health Organization's List of Essential Medicines, only the Salk vaccine is currently administered in the United States due to unacceptable risks being connected with the Sabin vaccine.
The Salk vaccine trials remain one of the most significant triumphs in American medical history. The contemporary period of vaccine evaluation began with that landmark field trial. Under Thomas Francis's bold leadership, the American public received what had been promised to them for their financial support: a nation free of polio and a much safer world in which to live.
Peter L. Platteborze, a Michigan native, is a recently retired U.S. Army lieutenant colonel who teaches at St. Mary's University in San Antonio, Texas. In one assignment, while serving as a research biochemist, he built multiple novel live, attenuated viral vaccines that were patented.
Caption: These two "Polio Pioneers" were among the first children to be administered a successful polio vaccine. (All images courtesy of the Bentley Historical Library, University of Michigan, unless otherwise noted.)
Caption: Previous page: Dr. Thomas Francis Jr. (left) and Dr. Jonas E. Salk at a polio evaluation meeting. Left: The University of Michigan School of Public Health, where Dr. Thomas Francis worked during the 1940s, as it appears today. (Photo courtesy of Michael Barera.) Below: President Franklin D. Roosevelt was perhaps the most famous polio victim, confined to a wheelchair after being crippled by the disease. (Photo courtesy of the Franklin D. Roosevelt Presidential Library.)
Caption: Left: Wilbur Ackerman and Thomas Francis (center) look on as Gordon Brown examines a culture of polio virus. Next page: Thomas Francis stands in front of the Special Projects Research Building, where the Poliomyelitis Vaccine Evaluation Center was housed.
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|Author:||Platteborze, Peter L.|
|Publication:||Michigan History Magazine|
|Date:||Sep 1, 2016|
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