University Times

In 1916, with the Fourth of July holiday coming up, New York City was its usual festive place, it’s residents preparing to celebrate the nation’s 140th birthday.

Electric signs had been erected in City Hall and Times Square, spelling out patriotic messages from the mayor, the governor, even President Woodrow Wilson.

In the evening hours, an incandescent bulb blazed with the brightness of 55 million candles, lighting up central Manhattan.

A great deal of work had gone into planning for that holiday – much of it for naught.

On July 2, as often happened on hot, muggy summer days, the “paralysis bug” was thriving. Throughout the day, the city’s hospitals were knocked back on their heels as 72 stricken children were rushed in by their horror-stricken parents, with 20 of those new patients already destined to die.

The city’s health commissioner issued a series of orders: Many of the events planned for the holiday would be canceled; children under 16 were banned from public gatherings.

As the days wore on, the victim count climbed: 113 on July 5; 87 on July 6; 542 over the course of the week.

Terrorized New Yorkers began to improvise solutions: Many believed that cats spread the paralysis bug. Some 70,000 cats were drowned or bludgeoned to death as a result.

If cats weren’t the bug-carriers, maybe it was mosquitoes. Or rats, or bed bugs. Or unclean milk bottles. Or high-ground water, or excavations, or gases or mercury. Even the bent-over position that school children took at their desks was blamed.

Citizens began fleeing the city. As many as 50,000 left New York in July alone.

That summer, 9,600 children in 33 states were stricken with poliomyelitis, or infantile paralysis, an infectious and contagious nerve-attacking disease that targets young children. Twenty percent of them died. Half of the rest were permanently severely disabled.

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It is against this backdrop that medical researchers throughout the ’20s, ’30s and ’40s sought the cause, prevention and cure of the horrific disease that first reached epidemic level in 1887, a best-selling author said at Pitt last week.

“This is what was on the line; this was what was at stake: Each summer, beginning in April, there came the risk. You could follow its tracks from the southern states northerly as the weather got warm. ‘Here we go again. Will it by my children this year?'” said Jeffrey Kluger, senior writer at Time magazine, who spoke on what he had learned from researching his just-released book, “Splendid Solution: Jonas Salk and the Conquest of Polio.”

Kluger’s lecture kicked off a series of events at Pitt to commemorate the 50th anniversary of the approval of the Salk polio vaccine, which was rated by Association of American Universities scientists as the third most important discovery of the 20th century, behind only the invention of the computer and the products and knowledge derived from America’s space program.

Following his recruitment to Pitt in 1947, Jonas Edward Salk did most of his research developing the vaccine in labs at the Municipal Hospital for Contagious Diseases, now named Salk Hall in his honor. Pittsburgh was the site for the first community-based pilot trial of the vaccine, begun in May 1953, which enlisted some 700 local volunteers by year’s end. In 1954 another 5,000 Pittsburgh-area grade school children were inoculated, all with vaccine prepared at Pitt.

On April 12, 1955, the Salk poliovirus vaccine was pronounced “safe, effective and potent” by the National Foundation for Infantile Paralysis (NFIP), founded in 1938 by polio-stricken President Franklin Roosevelt, and more commonly known as the March of Dimes.

“It was a huge moment in our history, and, indeed, in the history of the world,” said Kluger, who also co-authored with astronaut James Lovell another American success story, “Lost Moon: The Perilous Voyage of Apollo 13,” which was the basis for the movie “Apollo 13.”

Kluger pointed out that his book on Salk is not intended as a full-fledged biography, but focuses instead on Salk’s running battle with the medical establishment, particularly between the years 1952 (when the polio epidemic peaked with more than 57,000 cases nationally) and 1955, when his so-called “killed virus” vaccine was approved.

“I did concentrate more on Salk’s earlier years, because I think they presage what kind of researcher he was to become,” Kluger said.

A pivotal moment for Manhattan-native Salk, Kluger believes, occurred in a biology class at New York University medical school in the early 1940s. Medical dogma then held that viral vaccines could not work unless the virus used in the vaccine is alive. “The thinking was analogous to [the fact that] a hound won’t hunt a dead fox,” said Kluger. “But Salk asked why a viral vaccine must be alive. It was a hinge moment for him,” an early sign of his butting heads with medical orthodoxy, Kluger said.

The medical research community already was hampered by a misunderstanding of the polio virus’s pathology, Kluger said. The then generally accepted “paralysis hygiene guidelines” recommended maintaining extreme cleanliness as protection, Kluger said.

“But polio actually is a disease of good sanitation and good plumbing,” he pointed out.

The poliovirus was first identified in 1909, which roughly coincided with improvements in sanitation, such as more widespread indoor plumbing, better food and water sanitation and the like.

Children previously would pick up low-level background doses of the virus in their normal daily lives or become immune from antibodies passed to them from their mother’s milk, and by age 4 or 5 they had built up a robust immunity, Kluger said. Following sanitation improvements, by ages 5-7 children were highly vulnerable to infection.

Salk was not stymied by medicine’s preconceptions, Kluger maintained. Rather, his work in virology was highly intuitive. “It’s like studying the behavior of atoms. We can’t see atoms, but we know they’re there because it’s the only way to explain the way molecules work. That’s how Salk’s mind worked. He had a kind of visceral conviction that the killed virus vaccine would work.”

Although Kluger never met Salk, who died in 1995 at age 80, his book research included reviewing most of Salk’s personal journals and files – which are so extensive they’re measured in linear feet rather than numbered, Kluger said – and talking with family members, colleagues and friends.

“One thing I can tell you: Salk did not doodle. On one page in a 1946 journal there was one little triangle in the margin; that was the extent of his doodling,” Kluger said. “I think that speaks to the fastidiousness of his mind. He painstakingly kept notes with a mono-maniacal focus on minutia. Page after page after page on [variations in] liver toxicity in mice, for example, details of sample after sample.”

One enlightening journal entry did record the names of Salk’s family members, lab assistants and friends who later would be injected with the vaccine prior to national approvals.

“By 1953, he was comfortable enough in the belief that the vaccine would work to inject himself, his sons, his wife and his lab staff,” Kluger said. “Was it moral to do so? That’s an open question. But I think those people knew the power that was represented by a successful vaccine, and they chose to try to protect children [over] moral reservations. It was a tricky decision.”

One criticism that dogged Salk in his post-vaccine years was his failure to thank his lab staff or acknowledge their contributions publicly, Kluger said.

“He took heat over the years for that, and there was animosity toward him,” he said. “As far as I know, [this oversight] was never explained; Salk was a surprisingly unreflective man. But my gut tells me that he felt it was a given that nobody in the medical field worked alone, that it was always understood to be collaborative.”

A more important setback for Salk occurred the same month that the vaccine was approved for general use, Kluger said. In April 1955, right after the NFIP approval came, the largest controlled field trial in the history of medicine got under way, eventually involving 1.8 million grade school children and 217 test sites in 44 states.

During that summer, rates of polio cases increased dramatically in California, where 200,000 people had been inoculated with a vaccine produced by Cutter Laboratories that mistakenly contained live virus. The so-called Cutter incident resulted in 10 deaths and 200 cases of permanent paralysis.

“Perhaps devastated is too strong a word, but I would say Salk was badly shaken by this incident for two reasons: First that children had died,” Kluger said. “Salk knew early on that he wanted to do research, but he also was an M.D. who liked to be hands-on, especially with children. He enjoyed that personal contact.”

The second reason was more a pragmatic one, Kluger said. “Salk had fought hard enough to get this approved. He knew that the killed virus couldn’t go back to being an active pathogen, and he was rattled that the idea had to be peddled all over again. It’s also clear from this incident that he was never shaken from the belief that the vaccine worked.”

Was Salk bothered that he never was awarded a Nobel Prize?

“I’d love to say he was stoic and gracious about it. But he wasn’t happy,” Kluger said. “But I think more important was his failure to win the philosophical war of killed virus versus live virus during his lifetime.”

An oral vaccine that used a live virus was developed by rival researcher Albert Sabin. In 1957, the World Health Organization (WHO) approved the vaccine for worldwide testing. By the mid-1960s, Sabin’s vaccine sugar cube became the medical industry’s recommended form of polio immunization. The Sabin vaccine was thought to be equally effective as Salk’s killed virus vaccine, was better at producing vital polio viral antibodies in the body and it eliminated the need for periodic booster shots.

The Sabin vaccine’s drawbacks are that it produces a few cases of polio each year, and is rendered less effective in certain populations by the presence of endemic entroviruses.

Eventually, the decision to recommend Sabin’s over Salk’s vaccine was overturned. “The CDC (Centers for Disease Control) and WHO reversed their recommendations and now prefer the Salk vaccine,” Kluger said. “Unfortunately that recognition came in 1996, the year after he died.”

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More information about upcoming events in the “Remembering Polio” series at Pitt will be posted at www.polio.pitt.edu as it becomes available.

-Peter Hart