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The Long Shadow of Salk


WHEN DR. JONAS SALK DIED IN 1995, at 80, he was hardly the comeback kid he so desperately wanted to be.

Nine years earlier, he had begun development of an experimental HIV vaccine, Remune, in hopes of once again ridding the world of one of its deadliest and most feared diseases. But the quest soon appeared quixotic. Clinical trials were ambiguous, and some scientists argued Remune was mired in outdated technology. At the same time, there was mounting concern in the scientific community over the Salk team’s aggressive promotion of the drug as the answer to the monumental threat of the AIDS epidemic. The same year Salk died, the U.S. Food and Drug Administration issued a terse warning to Immune Response—the Carlsbad biotech Salk had cofounded in 1986 to develop the vaccine—about publishing data that had been manipulated to show positive results. The FDA demanded the data be corrected.

Dr. Jonas Salk in his laboratory in the late 1980sIt was a sad epitaph for San Diego’s most celebrated hero of medicine. Way back in 1954, Salk had developed the first vaccine for polio, effectively ending one of the greater scourges mankind has ever known. Prior to Salk’s vaccine, there had been three major polio outbreaks in the United States, in 1916, 1949 and 1952. The 1952 epidemic involved nearly 60,000 reported cases and killed 3,300.

Hailed as one of the greatest scientific triumphs of the 20th century, Salk’s historic discovery 50 years ago would one day lead Time magazine to list him among the 100 most important people of the 20th century, in the company of Winston Churchill, Albert Einstein, Sigmund Freud and John F. Kennedy.

“Dr. Salk was a savior,” says Dr. Jacquelin Perry, a worldfamous polio expert at Rancho Los Amigos National Rehabilitation Center in Downey, which in the 1950s and 1960s treated more polio victims than any other medical facility in the country. “At the time, polio was scaring everybody,” she recalls. “Kids couldn’t go into a public swimming pool or play sports in the summer, because their parents wanted to protect them. To suddenly be paralyzed is quite a frightening thing. And Dr. Salk truly conquered polio with his vaccine. The number of cases went down very dramatically, very quickly.”

Dr. Susan Perlman, director of the Post-Polio Clinic at UCLA, elaborates. “Polio was widespread and communicable, and the severity could not be predicted in any case,” she says. “In a single family there could be multiple people infected, some with mild or unnoticed symptoms and others with severe symptoms requiring hospitalization and isolation.”

Like Perry, Perlman has nothing but high praise for Jonas Salk. “His vaccine has prevented at least 150,000 deaths and 2.5 million cases of paralysis over the past 50 years,” she says. “And that’s only in the United States.”

Salk Institute president Dr. Richard Murphy Fifty years after Salk’s celebrated discovery, the Salk Institute for Biological Studies, which he established in the early 1960s, continues to generate headlines. In June, National Public Radio and the Bloomberg and Reuters news services reported the discovery by Salk researchers that a nap of between 60 and 90 minutes is as good as a full night’s sleep for restoring visual alertness. Salk plant biologist Joe Ecker was a guest on CNN’s Lou Dobbs Tonight during a weeklong series on issues surrounding biotechnology and genetically modified food. And Salk researcher Ned Landau’s recent work on HIV—his lab identified a defense mechanism built into the virus and illuminated one way the virus overwhelms human cells—was covered by newspapers the world over, from the San Francisco Chronicle to the Times of India.

Salk president Dr. Richard Murphy is pleased the institute continues to be on the cutting edge of research. He says faculty members “are given absolute freedom to pursue their curiosities. Their primary function is to do research that uncovers how cells function—and from that information, new clues are uncovered that help explain human diseases and ways they can be treated.”

Since Murphy’s arrival in October 2000, the institute has grown to employ 56 faculty investigators, 11 of whom have been hired over the past three years, and a scientific staff of more than 850, including visiting scientists, graduate students and postdoctoral fellows from more than 50 countries. Molecular biology and genetics, metabolic diseases, neurosciences, infectious diseases and plant biology are the major areas of study. New programs are being developed that encompass six key areas: chemistry and proteomics (the study of the full set of proteins encoded by a genome); stem-cell biology; cell biology; regulatory biology; metabolic research; and computational and theoretical biology.

Nobel laureates James Watson (left) and Francis Crick, who broke the code to the structure of DNA “The revolution in molecular biology that began with James Watson’s and Francis Crick’s discovery of the structure of DNA is the most important development in the history of biological and medical research,” Murphy says. “Its power in the hands of talented and creative people is limitless, and we have only just begun to realize its true potential. Over the next decade or two, I expect to see breakthroughs in our understanding of cells and disease that today are unimaginable. I can’t remember a more exciting time to be doing biological research.”

ONE CAN IMAGINE Jonas Salk expressing similar sentiments during his tenure as director of the Virus Research Laboratory at the University of Pittsburgh School of Medicine, ground zero for his great discovery of a half-century ago.

It was a plum assignment. Salk had earned his medical degree from the New York University School of Medicine in 1939 and briefly worked as a staff physician at Mount Sinai Hospital in New York City. During World War II, he became a research fellow at the University of Michigan and worked to develop a vaccine for influenza for the U.S. Army.

By the time he came to Pittsburgh in 1947, Salk was fully fascinated by the principle of vaccination: Artificial exposure to a harmless form of a virus would cause the body to produce antibodies that would resist or kill the dangerous form of the virus, if later exposed. Existing vaccines for rabies and smallpox used living viruses; Salk believed protective immunity could be induced just as well using noninfectious, killed viruses.

Salk’s research brought him to the attention of the National Foundation for Infantile Paralysis (precursor to the March of Dimes), an organization that had been founded by President Franklin D. Roosevelt, himself a victim of polio. The foundation agreed to fund Salk’s research into developing a killed-virus vaccine for paralytic poliomyelitis, the most dreaded disease of the time.

Using poliovirus grown in test tubes, Salk went to work. He discovered formaldehyde would kill the poliovirus yet keep it intact enough to trigger the immune response. He developed an injectable vaccine and tested it first with monkeys and then on polio patients at the D.T. Watson Home for Crippled Children, outside Pittsburgh. The vaccine was subsequently given to volunteers who had not had polio, including Salk, his family and his laboratory staff. The volunteers developed anti-polio antibodies; none had bad reactions.

In 1954, national testing began on 1 million children between 6 and 9 who became known as the Polio Pioneers. Half received the vaccine; half, a placebo. A nation held its breath during the monumental field trials; Time put Salk on the cover with the tagline “Is this the year?”

It was. On April 15, 1955, it was announced that Salk’s polio vaccine was safe and effective. Mass vaccinations were carried out, with phenomenal results. In the two years before the vaccine was made widely available, the annual number of polio cases in the United States was more than 45,000. By 1962, that number had dropped to fewer than 1,000.

Richard Daggett, president of the national Polio Survivors Association, is among the polio victims for whom the vaccine came too late. He contracted the disease in 1953, when he was 13, and to this day remains in a wheelchair —and on a respirator. But he’ll never forget the day he heard of the vaccine’s success.

“I was in a hospital at the time when they made the public announcement, and everybody was overjoyed,” Daggett recalls. “All of us kids, we would have yelled if we could have, but most of us were on respirators, so we couldn’t make a lot of noise. But it was very good news.”

Daggett remembers meeting Salk during his stay in the hospital. “He was a very gracious, humble man,” he says. “The first thing he said to me when we met was that he was sorry that he hadn’t been able to get the vaccine out earlier so that I could have benefited, which I thought was a very nice thing to say.”

HIS DEVELOPMENT of the polio vaccine brought him international celebrity, and yet Jonas Salk never took out a patent or earned any money from his discovery. It was his gift to the world, and he wanted it distributed as widely as possible.

The world was grateful. Salk dreamed of creating an independent research facility where scholars could come together to study different aspects of biology.

San Diego Mayor Charles Dail, who’d had polio, wooed the eminent doctor to town. The city of San Diego donated the site, 27 acres on a mesa in La Jolla, as a tremendous civic thankyou gift; the March of Dimes provided seed money. Salk recruited famed architect Louis Kahn to bring to life his vision of free-flowing labs overlooking the Pacific Ocean. In June 1962, ground was broken on the Salk Institute for Biological Studies.

The first labs were set up in temporary buildings in 1963, four years before core building construction was completed. Since then, the Salk Institute has become one of the leading research institutions in the world, having trained more than 2,000 scientists, many of whom have become leaders at other research centers. Six scientists trained at the institute have won Nobel Prizes, and three current resident faculty members are Nobel laureates. A fourth laureate, Dr. Francis Crick, codiscoverer of the structure of DNA, died in July after spending 28 years as a Salk faculty member.

Joe Panetta, president and chief executive officer of Biocom, the regional trade association for San Diego’s lifesciences community, calls the Salk Institute “one of the cornerstones of the local research community.

“It’s in the top 10 in the country in dollars brought in from federal grant money,” Panetta says, “so it brings in enormous amounts of capital. It’s really where many of the innovative products and therapies [biotech] companies get their start. It’s one of the engines, along with Scripps and UCSD, that drives biotechnology research.”

Panetta, like others, believes history will be kind to Dr. Jonas Salk, despite his ill-fated quest to develop a vaccine for AIDS. “What Salk did was so monumental,” he says, it will never be forgotten —or overshadowed.

UCLA’s Perlman agrees. “He will never be forgotten for what he did for polio and the people of the world,” she says. “The quest for the AIDS vaccine goes on, but it is a more difficult organism to work with.

“Most of us in our professional careers hope to be able to contribute even just a small amount to the legacy of science. Few are given the opportunity that Salk embraced to truly change the world for the better.”
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