Martha Rial, Post-Gazette Julius Youngner: Working for years in a basement laboratory in Oakland, he and a group of dogged researchers assembled by Dr. Jonas Salk at the University of Pittsburgh School of Medicine produced 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

When Julius Youngner was growing up in New York City in the 1920s and '30s, his grandmother wouldn't let him go out to play without first hanging a cube of camphor around his neck.

"My grandmother always believed, to her dying day, that she prevented me from getting polio," Youngner said recently. She was convinced the pungent hunk of camphor, the smelly stuff in mothballs, would ward off the virus that had crippled so many other children.

"What she didn't know," Youngner, 84, said, "is that every time I left the house, I took it off and put it in the mailbox."

Camphor cakes weren't much of a weapon against polio, but Americans had been desperate for some measure of protection since 1916, when the first major polio epidemic claimed 27,000 lives. They tried gargling with salt water, killing the family cat, scrubbing the toilet, bagging ashes from the coal stove, serving less meat, all to no avail.

The size of the epidemics varied from summer to summer, but by the time Youngner reached manhood, between 13,000 and 20,000 Americans, mostly children and adolescents, were being paralyzed by polio each year. Some suffered a profound form, called bulbar polio, which left them unable to breathe and dependent on a coffin-size breathing machine called an iron lung.

In the late 1940s, however, medical science produced the tools needed to conquer the polio virus and Youngner, then beginning his career as a microbiologist, was in position to exploit them.

Working for years in a basement laboratory in Oakland, he and a group of dogged researchers assembled by Dr. Jonas Salk at the University of Pittsburgh School of Medicine mastered those tools to produce a polio vaccine.

Some of the finest minds of American medicine in the early '50s insisted that the vaccine, which used killed polio virus, would never work.

Nevertheless, thousands of Pittsburgh schoolchildren offered up their arms to be injected with the experimental solution, providing enough evidence of its effectiveness to launch a large-scale trial of 1.8 million children.

Fifty years ago, on April 12, 1955, the leader of that national trial, Dr. Thomas Francis, of the University of Michigan, made the much-awaited pronouncement: The polio vaccine was "safe, effective and potent."

It was an electrifying moment in medical history. A terrifying, incurable disease that had existed for thousands of years had yielded to the targeted efforts of scientists, bankrolled by the contributions of more than 100 million Americans to March of Dimes campaigns.

"It proved that you could control polio and stop human-to-human transmission," said Dr. David Heymann, director of communicable diseases for the World Health Organization. Cases plummeted as the Salk vaccine was rolled out and plummeted again when an oral vaccine developed by Salk's rival, Dr. Albert Sabin, was introduced in the early '60s.

The last U.S. cases caused by the wild polio virus occurred in 1979, and today, polio is on the verge of eradication worldwide. It could be wiped out by as early as the end of this year, Heymann said, depending on the success of mass vaccination campaigns this spring in Africa and Asia.

The vaccine's success made Salk a household name. Even after the Sabin vaccine eclipsed the Salk vaccine, it was Salk's name that remained inextricably linked with the notion of a polio vaccine.

And Pittsburgh basked in Salk's reflected glory. Boosting the profile of Pitt's quiet medical school, after all, had been one of the reasons Salk had been recruited in 1947. Community leaders, energized by the city's first Renaissance, had provided Salk with additional space and money.

"I don't think that if I'd been anyplace else that things would have happened as they did," Salk said in an interview with the Pittsburgh Post-Gazette in 1994, a year before his death at 80. "Why? Because of the concatenation of circumstances. The magic."

For Youngner, the last surviving member of Salk's core research group, the polio work was just the beginning of a distinguished career as a microbiologist, but also was its highlight.

"I consider myself blessed by good fortune to have played a part in this creation of a medical milestone," he said in February as he accepted Pitt's highest honor, an honorary degree in public service.

Classic whiz kid

Youngner was a gifted child. Growing up on Manhattan's East Side, he leapfrogged his way through elementary and high school and had earned a bachelor's degree from New York University by age 18.

But he was no nerd. He was a pretty good athlete, and his prowess on the baseball field helped bridge what otherwise could have been a social gap with his older classmates. And he was just ornery enough to give his grandmother fits, showing up late for dinner, or failing to tell her where he was going.

"My mother always wanted me to be a brain surgeon. She had high hopes for me," he said. His interest in medicine also was primed by his medical history. "I had every possible disease a child could have," he recalled, including an almost fatal bout of double pneumonia when he was 7.

But a conversation with his family doctor's nephew, who had just earned a degree in bacteriology from the University of Michigan, convinced him that he should shift his focus from clinical medicine to research. Youngner enrolled at Michigan, earning his master's in 1941 and his doctorate in bacteriology in 1944.

In between degrees, he became smitten with an underclassman named Tula -- "It was love at first sight" -- and married her in 1943.

The newly minted bacteriologist entered the Army in 1944. After basic training, he was dispatched with sealed orders to a train station in Knoxville, Tenn. From there, he was hauled to a place called Oak Ridge. He thus became part of the Manhattan Project, the secret program to develop the atomic bomb, and was assigned to a toxicology unit monitoring workers at Oak Ridge's giant uranium enrichment plant.

After his Army stint, he moved over to the U.S. Navy and the Public Health Service in 1947, becoming one of the first science officers at the National Cancer Institute in Bethesda, Md. He worked with cell cultures and was particularly interested in cell cultures for viruses, then a new area that made some researchers nervous.

His interest eventually attracted the notice of Jonas Salk, who, in 1947, had taken charge of the virus laboratory at the University of Pittsburgh.

Salk and Youngner had followed parallel career trajectories, but had never met. Salk grew up in the Bronx. When Youngner was working on his bachelor's degree at NYU, Salk was completing his medical degree in the NYU medical school. In the early '40s, when Youngner was studying bacteriology at Michigan, Salk was working with Tommy Francis, the chief of epidemiology, in the medical school there.

By the time he met Youngner in Bethesda, Salk had secured major funding for his Pitt lab from the National Foundation for Infantile Paralysis. Work on a vaccine was in the offing and Salk needed somebody who knew about cell cultures. Cell cultures would make it easier to study polio virus and eventually would be necessary for producing virus for a vaccine.

"You can work with any virus you want," Salk told Youngner, "but among them, please among them, have polio."

"I said, 'That's a no-brainer, because polio is a very easy virus to work with.' I knew his money was coming from the national foundation." The deal was sealed and Youngner soon became Salk's right hand man.

Sanitation made polio worse

It was an Englishman, Michael Underwood, who first described the crippling disease now recognized as polio, or poliomyelitis, in 1789. But descriptions of similar diseases can be found in literature stretching back thousands of years.

Although not new to humankind in the late 19th and early 20th centuries, the disease was then presenting itself in troubling new ways. Rather than occurring sporadically in infants, polio was causing epidemics, often striking older children and young adults.

Ironically, improved public sanitation was to blame.

Polio spreads because those who have the virus excrete it in their feces, sometimes for weeks. Other people become infected when they drink water contaminated with sewage or eat food contaminated by someone with dirty hands.

About one out of every 200 people exposed to the polio virus develops polio symptoms, usually beginning with a flu-like illness. Everyone exposed to the virus, however, develops lifelong immunity.

Once improved sanitation came along, it prevented babies from being routinely exposed to polio virus at an early age, and many more children grew up without this immunity.

And that set the stage for devastating epidemics.

Most polio cases did not cause paralysis, but virus that reached the central nervous system could destroy nerve cells that controlled muscle movements. Infections in the spinal cord -- spinal polio -- caused weakness and paralysis in the legs. Infections of the brain stem -- bulbar polio -- could damage the cranial nerves that controlled breathing.

This ancient disease, so long overshadowed by killers such as typhoid fever, hepatitis and cholera, suddenly was terrorizing people throughout Europe and America. And it often seemed to strike hardest in prosperous communities and families, those who enjoyed the best sanitation.

"My family was certainly scared to death in the summertime," Youngner said. "Worried about going to pools, worried even about going to the movies." Everybody knew somebody who had polio.

Like other viral diseases, no treatment was available for polio. Doctors could only stand by and let the disease run its course. Then, patients could be fitted with leg braces and undergo rehabilitation to strengthen whatever muscles still functioned.

Franklin D. Roosevelt, who was stricken at age 39 in the summer of 1921, when the general public was still just learning about polio, would be its most famous and influential victim. In 1937, during his presidency, he established the National Foundation for Infantile Paralysis and installed his friend Basil O'Connor as its head.

With fund-raising events such as Birthday Balls and the March of Dimes, the foundation tapped into the generosity of both large and small donors. The well-financed foundation thus was positioned to exert unprecedented influence as a private organization on research into polio prevention.

Crucial role of monkeys

When Youngner joined Salk's Virus Research Laboratory in 1949, it was well along on its first major project. Pitt and three other universities were funded by the national foundation to test every known strain of polio virus to see how many types existed, a necessary first step for developing a vaccine.

"They already knew there were three types," Youngner said. "But what if there were five? What if there were seven? That would make [a vaccine] much more complicated."

The lab was once confined to the basement of Oakland's Municipal Hospital for Infectious Diseases, a building that now houses Pitt's pharmacy school and is known as Salk Hall. But now it filled two floors; elsewhere in the hospital, the largest ward housed young polio patients.

And much of the lab was now lined with cages for monkeys, the animals that were key to the typing effort.

L. James Lewis, a bacteriologist and Waynesburg College graduate, had been working for a pharmaceutical company when Salk recruited him to oversee the monkey experiments. "That was a key part of the effort," Youngner said, and Lewis tackled his tough job with boundless energy.

It was brutal work. One method involved injecting fecal samples of an untyped polio strain into the brain of a monkey; once the monkey showed signs of disease, it was destroyed and the polio-infected neural tissue removed. This tissue was processed and injected into the brain of a monkey that already had developed immunity to a known polio type, such as Type I.

If the monkey resisted infection, then the unknown strain must be Type I, too. If the monkey got sick, then the process was repeated with monkeys immune to other types until researchers were confident that the strain was a Type I, II or III, or knew they had found another type.

The foundation's typing studies required 17,000 monkeys. "The monkeys were the heroes of this thing," Youngner said.

The typing project produced good news for vaccine developers: Three types of polio existed.

ki While his colleagues were slogging through the typing experiments, Youngner was setting up his cell culture lab with the help of his technician, Elsie Ward, a zoologist. Until this time, the assumption in the field had been that polio could grow only in neural tissue, a circumstance that both necessitated the use of live monkeys and limited the prospects for growing virus in the quantities necessary for manufacturing vaccine.

But in 1949, John Enders, of Harvard University, announced that he had been able to grow polio virus in a culture of embryonic cells. The finding would win Enders and two junior colleagues the 1954 Nobel Prize in Medicine.

"That was the discovery that made Salk's work possible," said Vincent Racaniello, a microbiologist at Columbia University and a leading polio researcher today.

But Enders had grown his virus in a culture of human embryonic kidney cells, which posed its own set of problems. Use of human embryonic cells was no less controversial in 1949 than the extraction of stem cells from human embryos is today. Youngner had to find a more suitable source of cells for his cell cultures.

He tried to use cells from monkey testes, which at least would be easy to obtain. But the tissue didn't produce a lot of cells.

Then he tried chopping up the cortex, or outer layer, of monkey kidneys. Initially, the cells tended to form clots in the test tubes, which made them difficult to grow. But then Youngner tried an old trick used by pathologists. He added a pancreatic enzyme called trypsin to the culture to break the tissue into separate cells.

"The rest is history," Youngner said.

Trypsinization, which would become standard in producing cell cultures, made it possible to produce mass quantities of polio virus for vaccine production.

Monkeys still had to be sacrificed to obtain kidneys, but the cell cultures drastically reduced the need for monkey testing.

"He invented modern cell cultures," said Patricia Whitaker-Dowling, a Pitt microbiologist who began working with Youngner in 1979.

Killed virus or live virus?

While Youngner had been studying the dangers of inhaled uranium salts for the Manhattan Project, Salk had been working during World War II with his mentor at Michigan, Tommy Francis, to develop the first influenza vaccine for the Army.

Almost as many U.S. soldiers died in the great influenza epidemic of 1918 as died on the battlefield that year, and the Army was concerned about the possibility of another pandemic during World War II. Though most immunologists believed that only a low-grade, natural infection could trigger immunity against a virus, Francis had done work to suggest that a killed virus also could stimulate the production of antibodies. The killed-virus approach appealed to the Army, which worried that use of a weakened, live virus would always carry the danger of sparking an epidemic.

The flu vaccine, the same used for today's flu shots, was successful in clinical trials. Salk became a believer in Francis' killed-virus approach and in a method used to inactivate the influenza viruses using a formaldehyde-based solution called formalin.

When Dr. William McEllroy , dean of the Pitt Medical School, persuaded Salk to come to Pittsburgh in 1947, the young researcher brought his interest in killed-virus vaccines with him. But no consensus existed within the National Foundation for Infantile Paralysis that a polio vaccine should be a near-term goal or that a killed-virus vaccine would be the best way to immunize people against polio.

Two polio vaccine trials sponsored by the foundation in the mid-1930s had been disasters, causing polio in some cases and violent allergic reactions in others. No one was eager to repeat that debacle.

Moreover, the nation's leading immunologists, Dr. Albert Sabin, of the University of Cincinnati, and Dr. Hilary Koprowski, of Lederle Laboratories, were actively working on live virus vaccines.

Using a weakened but active virus, they argued, would cause a low-grade infection that would trigger all of the body's immune mechanisms, providing a more complete, long-lasting immunity than would be possible with a killed-virus vaccine.

A killed-virus vaccine, Salk argued, could work, as long as the virus was killed in such a way that it retained the proteins necessary to trigger the body to create antibodies against them.

"We were convinced we had the answer," Youngner said.

But Salk had to battle constantly with the skeptics. "There was a very powerful group of senior virologists and epidemiologists, not just Albert Sabin, but a whole bunch of them, who believed that the killed vaccine would never work against polio, that it would have to be a live vaccine, like what Sabin was working on," he said.

The killed-virus vaccine could be dangerous, critics said, if all of the virus wasn't killed. The immunity would be more short-lived than possible with a live vaccine, necessitating booster shots. And the vaccine would have to be administered in a shot, not as an oral vaccine.

But none of those cautions would dissuade the Salk team, which was working furiously in Oakland to develop the vaccine and get it ready for testing.

Tomorrow: Salk's team defeats the skeptics and changes medical research forever