Enders' research was pivotal in setting the scene for Salk's and Sabin's lifesaving efforts
By Alvin Powell
In 1954, Boston had so many polio cases that parents drove their sick children to Children's Hospital and sat in their cars on the street while resident physicians decided who would go inside.
"It was basically an outdoor emergency room," said Walt Schalick, a medical historian who is also a resident in pediatrics at Harvard-affiliated Children's Hospital and in physical medicine and rehabilitation at the Spaulding Rehabilitation Center. "Polio caused a phenomenal scare. It was a part of life. It was a tragic part of life."
Polio did more than line up cars in Boston's medical district. It crippled an American president, Franklin Delano Roosevelt, and had fearful parents keeping children out of public places. The symptoms started with fever and, in severe cases, progressed to the point where only an iron lung could keep its victims alive.
Cases of poliomyelitis, or polio, are rarely heard of in contemporary America. In fact, the Western Hemisphere was declared free of wild polio strains (those not introduced from abroad) in 1991. Cases are getting rarer elsewhere as well. World health officials hope the war against polio will soon consign it -- with smallpox -- to the very short list of diseases eradicated from the planet.
Progress has been swift. Just a few decades ago scientists were frustrated. Early vaccines had proven ineffective, even deadly. And while the researchers toiled, children were crippled or died from the disease.
The problem researchers faced was getting enough polio virus to make a vaccine. They knew the virus grew in nerve tissue but couldn't figure out how to grow it outside the body. So they grew the virus in the brains of monkeys. The painstaking process of extracting it yielded only minute amounts.
It took a Harvard Medical School researcher, John Enders, and two colleagues, Frederick Robbins and Thomas Weller, to figure out how to grow polio virus in the laboratory, a breakthrough that has allowed many of us to forget about a disease that terrified our grandparents and that has plagued mankind for thousands of years.
Enders, who was professor of bacteriology and immunology at Harvard Medical School and chief of the research division of infectious diseases at the Children's Hospital Medical Center, won the 1954 Nobel Prize in medicine for his 1948 work, along with Robbins and Weller. But Jonas Salk and Albert Sabin, whose vaccines were built on Enders' work, became household names.
"Salk and Sabin were standing on the shoulders of Enders," Schalick said.
The Stars Align
Like many important scientific discoveries, figuring out how to grow polio took a bit of luck.
Polio research was among the earliest research on viruses and was extraordinarily difficult. Unlike bacteria, which had been tamed with drugs, viruses are so small that at the time they couldn't be seen, even with a microscope.
"The core problem is you can't see these little suckers," Schalick said. "Unless you have a living animal infected in front of you, you don't even know if you have it."
Polio, which scientists believed couldn't live outside nerve tissue, was even more difficult to work with than other viruses, because nerve tissue couldn't be grown outside the body.
In 1948, Enders and his colleagues were trying to grow the chicken pox virus in a mixture of human embryonic skin and muscle tissue when it occurred to them to try the polio stored in a nearby cabinet.
"We had no immediate intention of carrying out experiments with poliomyelitis viruses," the three wrote in describing their work. "Nevertheless, from time to time, we had considered the mounting evidence . . . in favor of the possibility that these agents might not be strict neurotropes [i.e. viruses with a specific affinity for nervous tissue] . . . .
"Such ideas were in our minds when [we decided] . . . to use a mixture of human embryonic skin and muscle tissue in suspended cell cultures in the hope that the virus of varicella [chicken pox] might multiply in the cells of its natural host."
So the cultures were prepared and ready "while close at hand in the storage cabinet was the Lansing strain of poliomyelitis virus. . . . [I]t suddenly occurred to us that everything had been prepared almost without conscious effort on our part for a new attempt to cultivate the agent in extraneural tissues."
After combining the growth medium and the virus, the researchers injected the fluid into the brains of monkeys. When the monkeys developed the symptoms of polio, the researchers knew they had succeeded in getting polio to grow outside the body.
"When they discovered the virus would survive in other kinds of cells, it then became possible to manipulate the virus in ways not possible before," Schalick said. "You opened the door to all kinds of research you couldn't do before because it was impractical and very difficult."
Enders, Robbins, and Weller's discovery made it obvious that the polio virus does not live exclusively in brain and nervous tissue. Their finding sparked further inquiry that led to the discovery that the virus enters the body through the mouth, multiplies in the intestines, and occasionally passes into the bloodstream. Once in the bloodstream, the virus lodges in the brain and in the parts of the spinal cord that control muscular activity.
With large amounts of virus available, several scientists set out to make a vaccine, resulting in successful trials in the 1950s in the U.S., the U.S.S.R., Poland, and Latin America.
"Once the paper [describing their work] came out, people said, 'Whoa! We have a way of working on this virus that we didn't have before,'" Schalick said. "After the discovery, the race was on for the vaccine."
Wandered into Medicine
Enders very nearly didn't make it into medical research. After undergraduate studies at Yale University, he did a brief stint in business, then began studying English literature and language at Harvard, receiving a master's degree in 1920.
He was two years into his studies for a Ph.D. in philology -- the study of languages -- when he had a change of heart and entered a doctoral program in bacteriological studies.
After receiving his degree in 1930, he worked on the Harvard faculty and, in 1946, set up a research laboratory for infectious diseases at Children's Hospital. It was in that lab that the polio discovery was made.
Enders, who died in 1985 at age 88, continued working with viruses in his Boston lab and, in 1957, cultured the measles virus. He also helped cultivate and study mumps and German measles. He was named a University Professor, Harvard's highest professorial honor, in 1962.
Disease on the Run
Polio has been with us for thousands of years. Evidence of polio has been found in mummies from as long ago as 3700 B.C., Schalick said. The disease, which primarily strikes the young, is made up of three different strains.
Polio outbreaks were relatively common before the vaccines were discovered. In 1916, an epidemic in New York City struck 9,000 people, afflicting 2 percent of the city's two-year-olds.
Harold Varmus, director of the National Institutes of Health and Harvard's 1996 Commencement speaker, told graduates that fear of polio when he was young kept him out of summertime swimming pools and nearly killed children in his neighborhood.
"Like my friends, I remember listening to parental concerns about polio, the crippling illness then common among children and famous for afflicting our family hero, Franklin Delano Roosevelt," Varmus told the graduates. "For my generation, the announcement of an effective polio vaccine was a landmark. For us, the recent eradication of naturally acquired polio from this hemisphere still seems unbelievable."
Polio is on the run elsewhere as well.
In 1988, the World Health Assembly, the body that oversees the international World Health Organization, set a goal of eradicating polio worldwide by 2000. Cases have declined dramatically since then, from approximately 31,251 reported cases in 1988 to 6,175 in 1996, with 150 countries reporting no cases of the disease.
"That uncountable children were saved from disability because of the work John Enders and his colleagues did is probably his greatest testimony," Schalick said.
Copyright 1998 President and Fellows of Harvard College