University of Pittsburgh Dr. Jonas Salk, left, and Dr. Julius Younger together in a research lab during the development of polio vaccine. Click photo for larger image. More polio coverage From Pittsburgh: The Salk vaccine / 50 years later Part one: Developing a medical milestone: the Salk polio vaccine Celebrations, symposiums to mark 50th anniversary of Salk polio vaccine Part two: Tireless polio research effort bears fruit and indignation Youngner's role in polio vaccine a springboard to success From Nigeria: Polio's Final Chapter Once nearly eradicated, polio makes a comeback in Africa Photo Journal: Polio's Final Chapter With little government aid, polio victims unite to lift themselves Teen polio survivor, now a beggar, aspires to be a banker Nigerians turn to traditional healers for medical needs Nigerian woman lives a full life, despite the burden of polio For a fortunate few, early treatment and therapy minimize the ravages of polio Rotary International committed to polio eradication effort Learn more about the polio eradication effort

For Dr. Jonas Salk and his University of Pittsburgh team, work on developing the first safe and effective polio vaccine went on 16 hours a day, seven days a week.

Salk famously never held staff meetings and never did much to cajole or inspire his troops. But then, he didn't have to.

"Nobody had to give us motivating speeches," said Julius Youngner, Salk's expert in growing polio in cell cultures in the lab and the only surviving member of the core research team.

Everybody was well aware of the kids in iron lungs on the floors above them at the old Oakland Municipal Hospital, now Salk Hall. Many of them had children of their own, such as Youngner's son, Stuart, and his baby daughter, Lisa. "It was 100 percent effort, without question."

Youngner nevertheless always made it back to his apartment at Fifth and Wilkins avenues for dinner with his family each night. He'd talk about his work, about his colleagues, about Salk. "I remember him getting excited about it," recalled Stuart, who then attended Falk School along with Salk's son, Peter.

By 1952, things were moving rapidly on the vaccine front. Youngner's tissue cultures were producing plenty of polio virus and the team was refining its ability to kill the virus with the formaldehyde solution known as formalin -- both key steps in producing the Salk vaccine.

And while many scientists had raised doubts about whether the killed-virus vaccine would work, Pitt researchers had no such qualms. They had begun injecting the killed virus into monkeys and found that the animals produced antibodies against the virus within 21 days.

"We were believers, we really were," Youngner said. "I mean, come on. When you have a chance to do something against a disease as terrible and debilitating as polio and you see that your work is working in monkeys, I mean ... wow!"

As if any more motivation were needed, the worst polio epidemic in U.S. history occurred that summer of 1952, when more than 57,000 cases were recorded.

Salk's rival at Pitt

While the 1952 outbreak was frightening, the public would learn later that year that a researcher had for the first time prevented polio in children.

	The Associated Press Children in critical condition are treated in "iron-lung" respirators in the emergency polio ward at Haynes Memorial Hospital in Boston, Mass. in 1955, Children and parents were horrified by the prospect of life in an "iron lung," a metal coffin-like ventilator where victims with collapsed respiratory systems lived, sometimes indefinitely. Click photo for larger image.

The researcher was not Salk, but a rival of his in Pittsburgh ---- William Hammon, the prominent chairman of epidemiology and microbiology at Pitt's new Graduate School of Public Health.

When Hammon died in 1989, obituaries in both Pittsburgh newspapers emphasized how he worked with Salk to develop the polio vaccine.

The truth is that Hammon, an internationally known microbiologist who had beaten out Salk for the public health school post in 1949, opposed the polio vaccine.

Hammon never spoke out against the vaccine in Pittsburgh, but as a scientific adviser to the National Foundation for Infantile Paralysis, he criticized vaccines as too risky, costly and inefficient.

He advocated an alternative: passive immunization with gamma globulin, the fraction of blood that contains antibodies.

Gamma globulin includes antibodies against polio, and studies at Yale and New York University had shown that human gamma globulin could protect monkeys against polio.

Hammon proposed injecting children during the early phase of an epidemic; the injections might not prevent polio infections, but he argued that they would prevent the disease or reduce its severity.

He convinced the foundation to fund a pilot trial in Utah in September 1951 and a larger trial in 1952 in Houston, Texas, as well as parts of Iowa and Nebraska. More than 54,000 children received the gamma globulin shots.

It was one of the first large "double-blind, placebo-controlled" clinical trials ---- today's gold standard. At the time, however, the idea that some participants would receive a placebo instead of antibodies, and that neither the participants nor the researchers would know which people got which one until after the trial was over, was a strange new concept, said Charles Rinaldo, a microbiologist at the Pitt public health school who has studied Hammon's career.

Hammon determined that 26 cases of paralytic polio occurred in the gamma globulin group, compared with 64 cases in the placebo group. The findings were hailed nationwide as the first successful prevention of poliomyelitis, and Hammon was named Pittsburgh's man of the year for science and medicine in 1952.

The enthusiasm was short-lived.

Gamma globulin was expensive and attempts to use it during polio outbreaks in 1953 were hampered by short supplies. And in January 1954, an expert panel concluded that the mass inoculations were ineffective; most children received the shots too late to do much good.

Had a polio vaccine not come along, many of the obstacles to gamma globulin use might have been overcome. But scientific support was beginning to shift in favor of the Salk vaccine.

In June 1952, even as Hammon was preparing for his larger, second prevention trial of gamma globulin, Salk's team was ready for the vaccine's first safety tests. Blood samples were taken from paralyzed polio patients at the D.T. Watson Home for Crippled Children in Leetsdale.

The plan was to determine which type of virus had infected each patient and then inoculate the patients with killed polio virus of the same type. In that way, no child could be harmed by the vaccine because each already would have antibodies against the virus. If the vaccine increased the patients' antibody levels, however, the researchers would have evidence that it worked.

Salk himself injected 98 patients at the Watson Home and later inoculated 63 residents of the Polk State School, which had experienced a polio outbreak a year earlier.

The encouraging results were reported to the national foundation in January 1953 and published in the Journal of the American Medical Association two months later.

Word of the vaccine -- and of Salk -- was spreading, and a clinical trial to determine its effectiveness was soon to come.

'I really hated getting shots'

Stuart Youngner has only a vague recollection of getting his first polio shot.

"I was probably overwhelmed by the fact that I was getting a shot," he said, trying to explain why one of the first polio guinea pigs could forget such an event.

Unlike today's superfine hypodermic needles, the large-bore needles of the '50s caused both adults and children to dread the painful shots. "I hated getting shots. I really hated getting shots."

It's not unusual for medical researchers to experiment on themselves, but the Salk crew was so confident that they inoculated their family members as well.

Dr. Mary Bailey, a pathologist who worked with Salk, remembers bringing her son and two nephews to the Watson Home to get the polio shots.

"I knew [Salk]; he was very cautious," she said, so she had no trepidation. "He wouldn't do anything he wasn't sure about."

But her son and nephews hated getting the injections. "One [nephew] would hide every time we took him for the shots," she said, recalling one time when Salk found the boy hiding under a table.

"Do you know who I am?" Salk asked the boy.

"You bet I do -- that's why I'm hiding."

In May 1953, Salk began his first community-based trial, inoculating volunteers drawn from the practices of two Sewickley physicians. By the end of that year, almost 700 children would face the needle, as Salk, Bailey and a cadre of nurses took blood samples and administered a series of three shots to each volunteer.

The mark of success would be evidence from blood samples that a child had produced antibodies to the polio virus after receiving the shots.

Antibody tests were laborious then. Monkey kidney cells would be grown in a culture tube for several days, then a blood sample and some poliovirus would be added and incubated a few more days. The cells would then be examined under a microscope; viral damage to the cells was evidence that the blood did not contain antibodies.

But Youngner found an elegant shortcut.

He would simply mix the kidney cells with virus and blood and incubate them in a medium colored with phenol red. Normally, cell growth would cause the medium to change color from red to yellow. But if the blood lacked antibodies, the virus would kill the cells before they could grow and cause the color change.

So now they had a quick color test: yellow meant antibodies, red meant no antibodies.

"It was a simple idea," Youngner said. "There's something very satisfying about that."

The Salk core group had expanded to include Dr. Percival Bazeley, who had become a national hero in Australia during World War II for building a penicillin factory. Bazeley used his production knowledge to help scale up production of the vaccine, developing a 55-page protocol that would be turned over to pharmaceutical companies.

Despite the greater use of cell cultures, the monkeys housed at the Pitt labs remained essential to the effort.

First, of course, they were the source of kidneys for the cell cultures. But they also were the ultimate test of the vaccine's safety. Samples of each batch of vaccine were placed in the brains of monkeys. If a monkey got sick, the batch was destroyed. If a monkey didn't get sick, it was sacrificed a month later and inspected for signs of polio-related tissue damage. Each batch was tested three times.

At the national level, scientists continued to argue against a trial of the killed-virus vaccine, particularly Dr. Albert Sabin of the University of Cincinnati, who was working on a weakened live virus vaccine that eventually would replace the Salk formulation.

But leaders of the National Foundation for Infantile Paralysis, encouraged by Salk's preliminary results and feeling pressure from a public still panicky following the 1952 outbreak, moved ahead with plans for what would be the largest controlled trial in the history of medicine.

By contemporary standards, the jump from animal studies to clinical trial seems remarkably swift. But the times were different in the early 1950s and the researchers had no trouble finding volunteers.

"With tens of thousands of children being paralyzed each year," Youngner said, "it wasn't a hard sell."

After trials, polio numbers plummet

After initial trials involving about 15,000 children in the Sewickley area and the Pittsburgh public and parochial schools, the national foundation's vaccine advisory committee gave its go-ahead on April 25, 1954, for a national clinical trial.

It began the next day under the direction of the University of Michigan's Thomas Francis. About 440,000 children ages 6 to 9 in 44 states would receive the vaccine, another 210,000 would get placebo injections and 1.2 million children would receive no injections, but would be observed as controls.

The statistics tell the story of just how dramatic the impact of those trials was.

More than 38,000 new cases of polio were reported in 1954 in the United States, the third highest annual total.

But the electrifying announcement on April 12, 1955, that the Salk vaccine worked would send those numbers plummeting.

Six pharmaceutical companies were immediately licensed to produce the vaccine and by the end of the year, 10 million children in five countries had received the shot.

By 1960, the number of paralytic polio cases in the United States had dropped to 2,525.

The Salk vaccine, said Dr. David Heymann, director of communicable diseases for the World Health Organization, "was very important because it was the first. It proved that you could prevent polio. It prevented polio in untold numbers of children who otherwise might have been paralyzed."

But it's not unusual for vaccine technology to evolve, he added, and the Pitt vaccine was only the beginning.

In the late '50s, Sabin finally struck success with his oral vaccine, which used a weakened, or attenuated, virus that generally caused only a low-grade infection.

The Salk vaccine was by then so popular in the United States and Europe that Sabin had to test his vaccine in the Soviet Union. But those trials were successful and an oral vaccine effective against all three types of polio was licensed in 1963. Mass immunizations in the United States were called "Sabin Sundays," as millions lined up to ingest vaccine-infused sugar cubes.

The number of paralytic polio cases in America dropped to 61 by 1965.

"It was very important to get the oral polio vaccine if we wanted to eradicate polio, particularly in tropical countries," Heymann said. As Sabin and others had long argued, the low-grade infection of a weakened virus triggered a more complete immune response in the body, resulting in longer lasting immunity.

"The live vaccine was the sine qua non of eradication," Youngner agreed. Injections were unpopular and the vaccine was too expensive for mass immunization.

What's more, the oral vaccine resulted in intestinal immunity, Heymann said. People who received the Salk vaccine could continue to harbor virus in their gut and thus continue to spread polio infections in a community. Not so a recipient of Sabin's vaccine.

A recipient of the oral vaccine does shed the vaccine virus for a short time, though, so it's possible for close contacts to be immunized if conditions are unsanitary. "It can spread in a community, passing from child to child," Heymann said. "You really can immunize a whole community by vaccinating a few."

"The two vaccines together have done the job," Heymann said.

Columbia microbiologist Vincent Racaniello, whose health was protected by both the Salk and Sabin vaccines as a youth, now expects his career as a polio researcher to be cut short by the vaccines' success.

With global eradication in sight, officials from the U.S. Centers for Disease Control and Prevention told Racaniello five years ago to get prepared to destroy his stocks of polio virus.

"It's unprecedented in a way," he said. "Most scientists don't have their projects stopped in that manner."

A shocking lack of credit

When the success of the national polio vaccine trials was announced in Ann Arbor, Mich., in April 1955, many scientists were distressed by the circus-like atmosphere, but none were as let down as Youngner and other members of the Pitt team.

When Salk got his chance to speak at the press conference, he never mentioned his Pitt colleagues.

Listening to the radio broadcast of the announcement back in Pittsburgh, a then 10-year-old Stuart Youngner waited in vain to hear a mention of his father's name.

"Oh, how incredibly shocked and disappointed we were," said Stuart Youngner, now a physician and director of medical bioethics at Case Western Reserve University. "My father and others working on the vaccine were left out of the publicity, totally left out ... There was just a tremendous sense of injustice. It was just overwhelming."

Later, in a star-making turn on television with CBS newsman Edward R. Murrow, Salk was asked who else had contributed to the polio vaccine. Salk cited the invention of the hypodermic syringe.

According to historian David M. Oshinsky, author of the new book "Polio: An American Story," Byron Bennett, who had shouldered much of the lab work after Salk recruited him from Walter Reed Medical Center, wept most of the way back to Pittsburgh on the train following the Ann Arbor announcement.

Youngner had an inkling this might happen.

A year earlier, he and Elsie Ward had prepared a scientific paper on their color test for polio virus and had given a copy to Salk for his comments. Salk later said he had lost the paper, but had reconstructed it based on his notes; in the process, Salk had added himself as the paper's first author.

Youngner would go on to have a long and distinguished career as a microbiologist, but "I think [the polio vaccine] is the thing that he's most proud of," said fellow Pitt microbiologist Patricia Whitaker-Dowling. "Everything else pales compared to this."

"Salk sort of went out of his way to give the appearance he had done this himself," she added. "Even a lot of [Youngner's] colleagues don't recognize the role he played."

"I saw him as a father figure at the beginning and, at the end, an evil father figure," Youngner said of Salk. He confronted Salk with his grievance in 1993 when Salk returned to Pittsburgh for the unveiling of his portrait.

A year later, in a Post-Gazette interview, Salk acknowledged that the issue of sharing credit had dogged him throughout his career.

"Perhaps a more conscious attempt might have been made and perhaps should have been made to list the names of each individual more prominently rather than, as was implied, that the satisfaction came from the work itself," Salk said.

Youngner, who stepped down as chairman of the Pitt molecular genetics and biochemistry department in 1991 and is now a distinguished service professor emeritus, admits he's disappointed that development of various vaccines has lagged, despite the success of the polio vaccine.

"One of the problems is the pharmaceutical companies have almost gotten out of the business because there's not enough money to be made," he said. They find it more profitable to sell drugs that treat disease than to sell vaccines that prevent disease, he said.

		Coming Sunday The Post-Gazette features the stories of people who lived through America's polio era -- doctors, children who got the first shots, polio patients and others. Plus, a look at why so few drug companies want to make vaccines.

Of the communicable diseases responsible for the most deaths worldwide, including AIDS, tuberculosis, pediatric diarrhea and measles, the WHO's Heymann noted, the only one in decline is the only one for which a vaccine exists ---- measles.

The polio vaccine's most enduring legacy, besides the possible eradication of the disease, may be the effect it had on medical research funding, Youngner said. Though the federal government had nothing to do with the polio vaccine, the project demonstrated what could be accomplished when scientific talent was given major financial support.

The tremendous growth in federal support for medical research over the past 50 years is in part a response to public expectations that were elevated by the polio vaccine, he contends.

"If you can conquer polio, why can't you conquer other diseases?"