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COLUMN ONE : Hero With Something to Prove : Jonas Salk freed the world from fear of polio. But many scientific colleagues have long ridiculed his work. His AIDS research may be taking him down the same path a second time.

TIMES MEDICAL WRITER

Oh, how he annoys them.

“Salk?” they say, questioningly, derisively, with a roll of the eyeballs and clucking of the tongue and a stiffening of the back.

“I’ll tell you right off the bat,” one declares bluntly. “I don’t think Salk is a good scientist.” Adds another: “He doesn’t really understand what he’s doing. He just forges ahead.”

Of course, this is not for publication. No, no, no. They mustn’t be quoted. It would be unprofessional, untoward, to cast aspersions on a legend, although some do. But for the most part, they grumble in private, these wizards of the medical Establishment, irked to no end that Jonas Edward Salk--the man whose name became a household word four decades ago when he developed a vaccine that virtually wiped out polio in this country--is back in their game.

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This time, he faces a far trickier and enigmatic adversary: AIDS. And they are waiting, the wizards, waiting to see him fail.

Seven years ago, having retired from his laboratory at the scientific institute he founded in La Jolla, Salk embarked on a quest to develop an AIDS vaccine. Soon, he and his collaborators hope to present the Food and Drug Administration with the results of a nationwide test of his “therapeutic vaccine,” which--unlike traditional vaccines--is not intended to prevent infection with the virus that causes AIDS, but rather to render the virus harmless in those infected.

If the FDA approves it, a new Salk vaccine--the so-called Salk Immunogen--could be available to AIDS patients by the end of this year or early 1994, under a new federal accelerated approval policy that permits the marketing of drugs and other treatments for HIV-infected people while testing continues. Should that occur, Salk’s innovation could be the first AIDS vaccine, therapeutic or preventive, to reach the marketplace.

And Salk, at age 78, would stand the chance of becoming a hero all over again, this time to a generation for whom polio is but a distant memory, if a memory at all.

“Twice in a lifetime,” muses Dennis Carlo, the chief scientist at Immune Response Corp., the Carlsbad biotechnical company that Salk helped found to produce the vaccine. “How many scientists get a chance to do something twice in a lifetime? I think that of anybody, he has a very good chance of doing it.”

And doing it in spite of his critics, who he knows are out there. In the highly complex and competitive world of AIDS vaccine research, no other scientist is using Salk’s approach, which involves using a killed form of the AIDS virus, mostly because no other scientist believes it will work. As always, Salk is going at it alone--the skeptics and the naysayers be damned.

It would be a risky venture for any researcher but is especially so for Salk. Others labor in obscurity, their failures and triumphs duly recorded in medical and scientific journals to be pored over by those who wear white coats and squint under microscopes. Occasionally, their findings hit the newspapers, or perhaps the network evening news. But their names are quickly forgotten, and back to their laboratories they trundle, insulated from the watchful eye of the public and the hounding of the press.

But Salk is, well . . . Salk. Larger than life. The doctor-savior of our times. “He’s like a rock star,” one colleague said. “He can’t get any peace.”

And for nearly 40 years, this has been his blessing and his curse.

*

“Of course,” Salk is saying, “I know that there are those that are waiting for failure, but my answer to that is that there is no such thing as failure. You can only fail if you stop too soon.”

His life, he says, is a “consistent pattern” that began early in his career. “I’ve been told, by one of my mentors, ‘Damn it, Salk, why don’t you do things the way everybody else does them?’ ”

So it was with polio and with the founding of the Salk Institute for Biological Studies, and so it is now, more than ever, with AIDS.

At times, Salk seems resigned to the role of outsider. “I accept the pattern as understandable,” he says quietly. At times, he seems defiant: “Well, I go back to something my mother said many times. Sticks and stones will break your bones, but names will never hurt you.”

But on the rare occasion that he lets his guard down with a stranger, he seems profoundly troubled and saddened by it: “I’ve tried to do harm to no one,” he says, shaking his head in bewilderment. “I’ve tried to take nothing away from anyone.”

It is difficult, no doubt, for those who remember Salk as the man who saved a generation to think of him as an underdog. He has been out of the scientific spotlight for so long that some people don’t even know that he is still alive--or what kind of man he has become.

There is an image of Salk that is fixed in the public mind, an image perhaps best captured by a black-and-white photograph of the serious young doctor during what he now calls “the polio days” or, alternately, “the beginning.”

In this picture, Salk’s hair, dark and receding, is combed back neatly from his forehead, his spotless lab coat covering a starched shirt and plain dark tie. He peers through rounded glasses at a square rack of test tubes that he is holding up to the light, as though these tubes held the answers to great and mysterious questions of science.

Today Salk wears not a lab coat and tie, but a black-and-blue silk jogging suit over a brightly colored, plaid flannel shirt, open at the neck. He cuts a small, elegant figure. His hair has gone white and thinned considerably, and he still wears it combed back, over a scalp that bears the brown spots of age. Perhaps in keeping with the times, his locks are longer now than then, with tufts that curl in soft corkscrews against the nape of his neck.

No longer does Salk spend his working hours in the laboratory. Instead, he passes his days in his spacious fifth-floor office at the renowned institute that bears his name. It is here, on Torrey Pines Mesa, a spectacular bluff perched above the Pacific, that the outsider scientist finds serenity.

It is here, also, that Salk turned from science to philosophy.

In recent years, he has published several tomes, dense tracts with such titles as “Anatomy of Reality: Merging of Intuition and Reason” and “The Survival of the Wisest.” His writing is culled from dozens of notebooks in which he records whatever thoughts and ideas strike him. Often, they strike in the middle of the night.

He is interested in the evolution of the human mind, in the interplay between nature and humanity, in the blending of science and art. He is interested, as well, in what ails mankind. At a recent dinner party at the Salk house, a guest recalls, the host treated his company to a discourse on intolerance, as illustrated by the fighting in Bosnia.

Ever the scientist, Salk drew a biological analogy. In immunology, he noted, tolerance refers to the body’s process of accepting or rejecting a foreign organism, such as a transplanted kidney or a skin graft. It is well-established that infants are more tolerant than adults. And so, Salk theorized, is it not possible to teach children tolerance, even when their elders resist?

Conversations with Salk tend to be sprinkled with such meditations and phrases, and often they require the listener to think twice. “There’s an inner and an outer to everything,” he is wont to say. “Even a line drawing has a shape that bespeaks either that which is observed or the observer.”

Or: “We are the product of the process of evolution, and we have become the process itself.” And: “As I like to say, the answer pre-exists. It is the question that must be discovered.”

To his friends and admirers, such musings are evidence that the man is a great thinker way ahead of his time, that he approaches science with a mind so open and unconventional that he is somehow more capable than others of finding simple answers to complex questions--or perhaps questions to fit the answers.

Says his wife, the painter Francoise Gilot: “He is of the species of the discoverers.”

At the same time, some admit, they don’t always quite understand him.

“It is not sometimes very easy to figure out exactly what Jonas is saying,” says Inder Verma, a professor of molecular biology at the Salk Institute. “I think it is partly because Jonas is thinking deeper than I am able to think. . . . He is a visionary, and people sometimes don’t appreciate his vision. What frustrates Jonas, I think, is that people don’t always agree with his ideas.”

Salk’s vision, and his impatience with others who don’t share it, is precisely what drives some of his fellow scientists up the wall.

Here is vaccinologist Maurice Hilliman, a contemporary: “He’s a different sort of person. He’s philosophical and he will present his ideas very forcefully, as if there were no challenge. With some people you can say. ‘Look, my good friend, I think you’re full of crap.’ And with other people you would just invoke wrath.”

The implication, although Hilliman politely declined to say so, is that Salk is among the latter.

And here is virologist Joseph Melnick, another Salk contemporary who participated in the war against polio: “He went into philosophy for a while, thought he was a philosopher. And he was the only one who thought he was a philosopher. . . . If he had stayed in science, let’s say, after working on polio, I think he would have been one of the group. But he didn’t do that. . . .

“Why did he come back now? He’s like Rip Van Winkle in a way. The Rip Van Winkle of virology. He came back after a long sleep. And when he came back, he thought science was exactly where he left it.”

And then, in the very next breath, with absolute sincerity, Melnick adds: “Give Jonas my regards.”

*

To understand the forces that have created this lingering scientific snippiness about Salk, one must hark back to the days when fear of paralytic poliomyelitis gripped the land.

It was a terrifying plague, far more mercurial than AIDS. Like AIDS, polio is caused by a virus--in the case of polio, a virus that invades the body by way of the intestinal tract, eventually making its way to the spinal cord or the brain. Like the common cold, it is transmitted hand-to-mouth. Unlike the cold, polio left many of its victims either paralyzed or dead.

Whereas AIDS strikes people in patterns and can be guarded against through safe-sex practices, polio struck randomly. No one knew where or when it would hit--or who would be cut down next, except that children suffered more than adults. Newspapers ran photographs of huge hospital wards filled with youngsters in iron lungs, row after row after row of them. Last year, 50,000 new AIDS cases were recorded in this country. In 1952, the worst year of the polio epidemic, 57,628 people were afflicted.

It was a disease that made parents crazy with fear. In the heat of summer, people slept with the windows shut tight, lest polio creep in through the cracks. Swimming was verboten , either in pools or at the beach. Wash your hands before and after you eat, children were told. Don’t drink out of the same glass as anyone else. Don’t put that toy in your mouth. Even a President of the United States, Franklin Delano Roosevelt, was relegated to a wheelchair by polio, a reminder to the nation of the power of this beast.

And then, out of nowhere it seemed, came Salk.

In this atmosphere of polio panic, there was intense public pressure to find its causes and a cure. Much of the research was financed by the National Foundation for Infantile Paralysis, later known as the March of Dimes. The foundation was run by a man named Basil O’Connor, who happened to be Roosevelt’s law partner.

Salk’s close affiliation with the March of Dimes, a relationship that lasts to this day, began in 1948. That year, the foundation established a committee of scientists to identify and type different strains of polio. The work was a necessary, if somewhat tedious, precursor to developing a possible vaccine. Salk, who had worked on influenza vaccines and was establishing his own laboratory at the University of Pittsburgh, was asked to help.

Then, as now, Salk’s ideas about vaccines were unconventional.

The prevailing theory at that time was that to produce immunity a vaccine would have to create an infection inside the body--albeit a minor infection that would not cause disease. This was accomplished through “live attenuated” vaccines, manufactured using a weakened form of virus--a tried-and-true technique invented by the legendary French biochemist Louis Pasteur.

Salk believed that the immune system could be triggered without infection. His idea was to deactivate the virus--at first he used ultraviolet light, later formaldehyde--to produce a so-called killed virus vaccine. The killed virus, Salk believed, would be just as effective as live-attenuated but safer because there would be no chance that the virus could revert to a deadly form inside the body. He saw it, he says now, as a way to “improve upon nature.” He had tried it with influenza, and he wanted to try it with polio as well.

The trouble was, there was no way of mass-producing enough polio virus to develop any type of vaccine--killed-virus or live.

In 1949, Harvard scientist John Enders solved that problem. Enders and his team showed how to grow polio virus in test tubes--a monumental discovery that won them the only Nobel Prize given for research on polio.

Salk immediately went to work, and within three years he was testing his vaccine on residents of a children’s home near Pittsburgh. While others plodded along in their attempts to develop live attenuated vaccines, Salk moved quickly--too quickly, some of his colleagues complained. Soon, nationwide field trials would begin on schoolchildren, the so-called Polio Pioneers--a remarkable experiment that, in today’s safety-conscious bureaucracy, would probably not be permitted.

On April 12, 1955, at 10:20 a.m., a news bulletin clacked across the Associated Press wire. It was one sentence long: “The Salk Polio Vaccine is safe, effective and potent, it was officially announced today.”

Overnight, Salk became a national hero.

This earned him the undying love and trust of a grateful public, and a lifetime of derision from his peers.

The result is a man who has purposely drawn a curtain around himself. He feels “attacked and assaulted,” he says, and so, “I just closed up. What is there to say? Damned if you do, and damned if you don’t. I find the less said the better.”

When he does make an exception, he wants the conversation to be about science, not about Salk. He despises much of what has been written about him; the stories rarely move beyond caricature, he says. He loathes being interviewed, yet is hounded by requests. And after suffering through 90 minutes worth of questions on a recent afternoon, he regrets it. “It is,” he said, “a voluntary submission to torture. I don’t know why I was moved to ask for this punishment.”

And so he is the most reluctant of subjects, refusing to look his interviewer in the eye, alternately gripping the cushions of the couch or wrapping his arms around himself. His body tightens noticeably when he is asked about his fame.

“What comes to mind,” he says now, “is something that Edward R. Murrow said to me on the evening of April 12, 1955, which is quoted from time to time. He said: ‘Young man, a great tragedy has just befallen you. You have lost your anonymity.’ Well, you can see the nature of the tragedy. I’ve become a celebrity. That’s contrary to what a person in the field of science is supposed to be.

“I remember what Leo Szilard (the renowned Manhattan Project physicist who later joined the Salk Institute) once said to me: ‘They’ll never forgive you for being right.’ ”

Some say it was O’Connor--whose March f Dimes later financed the Salk Institute and who believed that the nation needed a polio hero if his foundation was to continue to raise money--who created the image of Salk as savior. Others say Salk, despite his protestations that he never wanted publicity, seemed to enjoy the limelight a little too much.

His critics think he is too full of himself, and listening to him talk one might conclude that he is not the most humble of men. Yet his close friends say that, at heart, he is less arrogant than he may seem.

“It’s simply his manner,” said Al Rosenfeld, a former science editor for Life magazine and a longtime friend of Salk’s. “When he talks, he’s absorbed in what he’s saying, and it sounds to people as if he is being an oracle or something, the wise man speaking to the multitudes. But that’s not the way he feels.”

Arrogant or humble, intentionally or not, Salk broke the unwritten commandments of scientific research: Thou shalt remain anonymous. Thou shalt give credit to others. Thou shalt discuss one’s work in the medical journals and not in the newspaper. And while the polio statistics plummeted, the back-stabbing had only just begun.

They tried to take his success away from him, to say it wasn’t really his. They said he wasn’t all that good a scientist, not very creative, just one of the pack. The brilliant breakthrough belonged to Enders; Salk’s work was simply applied science, developed on the principles that the Harvard team had established.

How they belittled him, and belittle him still. “Any graduate student could have done what Salk did,” said one in a recent interview. “It’s like a child playing with blocks,” said another. “When you get to be a certain age, you put one block on top of another and you can get to build a house.”

And for God’s sake, they crowed, he even named the vaccine after himself! (In fact, the March of Dimes was responsible for the name.) Why not just call it a polio vaccine, like smallpox or rabies or flu?

To be certain, there are divergent views.

“They’re bloody jealous that he did it and they didn’t!” exclaims Jack Obijeski, a senior virologist at Genentech, the San Francisco-based biotechnical company that is working on its own AIDS vaccine. “Some people consider themselves highfalutin scientists, and that this stuff was just an application of a well-proven principle. They’re thinking that they’re doing all the world’s greatest work and goddamn it, Jonas gets all the attention of the reporters. Well, so be it.”

Meanwhile, to add insult to Salk’s injury, his polio vaccine is not the one in use today.

Early on, questions were raised about its safety when one of the manufacturers producing the vaccine, Cutter Laboratories, accidentally shipped out batches containing live virus--a deadly mistake that cost 11 people their lives and left about 150 paralyzed.

Then, a live-virus vaccine was developed by a respected polio researcher who was to become Salk’s nemesis, Albert B. Sabin. Sabin, who died Wednesday, had long been an outspoken critic of Salk’s killed-virus approach, arguing that it could not provide as lasting and strong an immunity as a live-virus vaccine.

“It was pure kitchen chemistry,” Sabin once said of Salk’s vaccine. “Salk didn’t discover anything.”

In turn, Salk became an ardent opponent of Sabin, insisting that the live-virus vaccine was inherently dangerous. In fact, Sabin’s vaccine does account for a small number of polio infections each year.

The dispute between the two aging scientists--Salk once likened it to “a religious war"--continued until Sabin’s death. Sabin spent the last months of his life confined to his Washington, D.C., apartment, so ill that he was barely able to talk. But, when asked via fax machine his opinion of Salk, the 86-year-old scientist quickly faxed back a pithy, handwritten note:

“I see no scientific basis for Salk’s tests of his AIDS ‘vaccine'--and disagree with him scientifically on most other concepts.”

*

It was in part to escape this nastiness, Salk says, that he fled the East for the peaceful, and at that time relatively undeveloped, shores of La Jolla, where more than three decades ago he set about to found the institute that bears his name.

The story of the building of “The Salk” is local legend--how Salk, ever the exacting taskmaster, worked hand in hand with noted architect Louis Kahn to fashion a design that has been hailed over and over as a masterpiece.

Their creation is all sharp lines and geometric shapes. Two large buildings of smooth white concrete zigzag in mirror images of one another, united by an open courtyard. Between them runs a narrow stream of water that appears to flow right into the sea. It is as though this place could lift all constraints off the human imagination--and that, says Salk, is exactly what he intended.

He hoped that it would inspire the scientists who worked there to achieve great heights in an atmosphere of beauty and harmony. “An experiment on humans,” he calls it. “A positive reaction to a negative experience.”

Yet in a sense, Salk is an outsider even in the house he built.

Last year, to mark the occasion of its 30th anniversary, The Salk published a four-color, slick brochure as elegant and tastefully designed as the institute itself. In it, Salk writes that his beloved creation “stands as a tribute to all the scholars who have contributed in ways both modest and grand to doing together what no one could do alone. Together they have made the institute truly a cathedral to science.”

At the end of the brochure, there is a page titled “Hallmarks of Excellence.” It lists the names of those at the institute who have achieved the two greatest honors that science has to bestow: the Nobel Prize and membership in the National Academy of Sciences.

The name Salk is not on that list.

Although many assume that Salk abandoned science after his polio breakthrough, that is not the case. Although he never followed his success with an encore, he remained active in research, particularly with influenza, and maintained a laboratory at his institute until 1984.

By then, a new scourge, AIDS, had swept the land. And the wizards were tearing their hair out, with little success, trying to stop it.

Salk, meanwhile, had no intention of joining them. Having shut down his lab in La Jolla, he was prepared to spend his twilight years in quiet contemplation, writing books and working on projects that were important to him, including a 100,000-square-foot, $21-million addition to the institute. A close friend, Joan Abrahamson, urged him to get involved in AIDS. His answer, she recalls, was a pointed no.

Robert C. Gallo changed Salk’s mind.

Gallo is the noted AIDS researcher who shares credit with French scientists as the discoverer of the human immunodeficiency virus, which causes AIDS. (In the mid-1980s, there was a nasty battle between Gallo and the French over who should get credit. In 1987, Salk helped broker the agreement that settled the dispute; Gallo, meanwhile, was recently cited for scientific misconduct in connection with the discovery.)

Salk knew of Gallo but the two had never met. In 1986, Gallo traveled to La Jolla to ask Salk what he thought about a possible vaccine for AIDS. Intrigued, Salk visited Gallo’s lab at the National Cancer Institute. That same year, Salk attended the International AIDS Conference in Paris, where, he says, he “got a large dose of the state of the art” in AIDS research.

And so he was back.

Although he does not say so himself, those close to Salk say he did not make his re-entry into this high-profile world without trepidation. He knew, of course, that the tongue-cluckers and the eye-rollers would be there, watching and waiting.

“I think he almost didn’t get involved because of that,” Abrahamson said. “He knows that people have always been critical of him, and he doesn’t like that. I told Jonas: ‘Look, if your theory works, you will have removed fear from the lives of every human being, because everyone in their lifetime was either worried about polio or AIDS.’ ”

Today, AIDS vaccie research is proceeding with cautious optimism on many fronts. The National Institutes of Health is funding a broad spectrum of AIDS vaccine research. In December, NIH announced that two experimental vaccines designed to prevent infection with the AIDS virus are now being used in large-scale tests on uninfected people. The announcement was a milestone in the years-long quest for a vaccine.

But when Salk began, the prospects for an AIDS vaccine seemed dim. Although a potential preventive vaccine was being tested in Zaire and France, most experts doubted that a successful AIDS vaccine ever would be developed. The theory went that the human immunodeficiency virus, with its uncanny ability to mutate inside the body and to hide for years before triggering an infection, was far too cagey an invader to be shot down by a single vaccine.

Salk, being Salk, refused to accept it.

“Why should I?” he asks. “I follow my own drummer. There must be a way.”

John James, publisher of a highly respected newsletter about AIDS, praises Salk as “one of the first major proponents of the idea that we could have a vaccine.” He adds: “Salk was there, getting the early ideas out. I think his work has been tremendously valuable. I don’t know about the vaccine, or how well it is going to work, but he had a lot to do with keeping interest in the field going when most other scientists were just giving up.”

To thousands of HIV-infected men and women, and to those at risk of infection, the revelation that Salk saw possibilities for an AIDS vaccine was a blessing. The epidemic was more than five years old. Hospital wards were filling and newspaper obituary pages were growing fat and the pace of medical research seemed staggeringly, devastatingly slow.

Maybe, just maybe, Salk would have the answers. Maybe he could do it again.

“Here’s a guy who has enormous credibility with the public,” said Bill Snow, a San Francisco AIDS activist. “He has a magical name and the word vaccine has a magical feeling about it. Vaccines have been medical miracles in the way that a lot of treatments aren’t, so it sounds great to a layman.”

*

It did not sound great to many other scientists.

From the beginning, they laughed at him, said he was crazy. Or they dismissed him out of hand as a graying scientific geezer who was caught in some kind of a time warp, riding a steam engine locomotive while other, younger researchers were zipping around in spaceships.

Clarence Gibbs, a virologist at the National Institutes of Health who helped Salk test his vaccine on chimpanzees, said: “They looked at him and sort of chuckled, that the old man was trying to do it again.”

To begin with, the vaccine that Salk was talking about was not even a vaccine. He called it “immunotherapy” (although somehow the word vaccine has stuck), because its goal was to boost the immune systems of people already infected with HIV. This he calls his “live and let live” philosophy--the virus lives in a dormant stage, and the patient survives.

A vaccine after infection? Preposterous, the critics said.

Only one vaccine--the rabies shot--works this way. With rabies, the shot must be given immediately after exposure. But with AIDS, it can take months or even years just to figure out that a patient has been infected.

This, Salk argues, is precisely why immunotherapy can work. If an infected person can live with the virus for months without developing symptoms, he reasons, why not for a lifetime? The key, he says, is to create and maintain the same conditions inside the body that nature creates in a person who has HIV but is not sick.

What’s more, Salk suggested, he would formulate his vaccine using the old killed-virus approach that had worked so well for him with polio.

A killed-virus vaccine? The scientific community let out a collective gasp. How dated, they sniffed. How quaint.

Moreover, it would be dangerous, maybe deadly. What if live virus accidentally slipped in? (Remember polio and Cutter Laboratories?) What if injecting AIDS victims with additional virus failed to boost the immune system but revved up the HIV instead? Salk, however, was confident that the vaccine would be safe. He does, he notes wryly, have a bit of experience in the area.

*

In today’s world of high-tech science, most AIDS researchers are staking their hopes on genetically engineered vaccines, in which a protein from the AIDS virus’ outer envelope is snipped off using recombinant DNA technology. These so-called sub-unit vaccines are thought to be safer, and most scientists believe the envelope proteins are all that is necessary to produce an immune response.

But in the Salk vaccine, the envelope and its proteins drop off during the process that kills the virus. Salk maintains that the envelope is not necessary, noting that some infected people develop antibodies to the envelope but die nonetheless. It is the virus core, he says, that is essential to producing an immune response broad and varied enough to stave off HIV in whatever shape it takes.

And he wonders about his juniors, so caught up in splicing this gene and snipping that protein that they sometimes ignore the big picture. “My training and experience comes from the days when it was not technology that determined what we did,” Salk says. “We just developed techniques that were simple, to allow the experimentation to go on. What was important was the questions and the approaches.”

Yet even among his supporters, few think Salk will succeed.

“Jonas’ vaccine is depleted, or vastly deficient in what the scientific community and all of the data to date says is the most important protein,” said Obijeski of Genentech. “So the question is, how can you elicit an immune response that is going to be worthwhile? I think that’s where he gets in trouble with his colleagues.”

Salk has unconventional ideas, as well, about the type of immunity that is required to neuter HIV. Most vaccines cause the immune system to fight back against disease by producing antibodies--custom-made proteins that attach themselves to a virus, rendering it harmless. This is known as “humoral immunity.”

But there is another type of immunity--"cellular immunity"--in which certain immune cells recognize and kill any cells that they find infected with virus. Salk has long maintained that cellular immunity, rather than humoral, is the key to fighting AIDS--a view that puts him clearly outside the mainstream of AIDS research.

Such scientific debates aside, there was a more practical matter at hand. The Food and Drug Administration would not touch the Salk vaccine. Salk knew it, and so did Carlo, the chief scientist at the Immune Response Corp. in Carlsbad.

“People thought we were crazy,” Carlo recalls. “They thought we would kill people.”

So Salk and company did not even approach the FDA. Instead, after trying the vaccine in chimps and monkeys, they took advantage of a unique new California law that permitted human testing of experimental AIDS treatments. Apparently, the Salk Immunogen is the only AIDS vaccine to be tested in the United States without FDA approval.

With the go-ahead from California authorities, tests in HIV-infected men began on Nov. 5, 1987, at County-USC, under the direction of a respected AIDS researcher, Dr. Alexandra Levine. No announcements were made, no press releases published. This time, Salk was determined to keep things quiet, although news of the trial leaked about a year later.

In the five years since the USC tests began, clinical trials of the Salk vaccine have shown that it does AIDS patients no harm, although whether it does any good has not been proved. The Food and Drug Administration, meanwhile, eventually gave Salk the go-ahead to expand those trials nationwide.

Those studies are complete and will soon be analyzed. The Immune Response Corp. plans to bring the results to the FDA and hopes that the findings will look good enough to persuade government officials to allow the company to market the vaccine while conducting further tests on as many as 10,000 HIV-infected people.

NeitherCarlo nor Salk will disclose details of the trial results, although both say that nothing in their work has given them any indication that they should change course. “There is no need to abandon the hypothesis,” Salk said.

Those who know Salk say he is completely immersed, single-minded in his desire to make this vaccine work, just as he was single-minded in the polio days, and in the founding of the institute.

It is in Salk’s nature to move quickly and circumvent whatever obstacles come his way. He was once likened to a fighter pilot, a description that Renato Dulbecco, the Nobel laureate who recently stepped down as president of the Salk Institute, said is apt: “He will avoid this danger, avoid that, and he finally comes back and gets his enemy. He never gives up. Never.”

Whether, in the end, Salk “gets his enemy,” one thing is clear: He has already contributed to the scientific debate about AIDS. More researchers are now contemplating the killed-virus approach, and more are questioning the importance of the envelope, and more are talking about cellular immunity.

Even some of his biggest doubters, among them Dani Bolognesi, a well-known AIDS researcher at Duke University, give Salk credit for that.

“He has stuck to his guns, and it’s interesting, how the findings as they are emerging right now don’t belie him completely, either about the envelope or the role of cellular immunity,” Bolognesi said. “So you can’t say he was wrong. He hasn’t been totally out of bounds here.”

For Salk, this alone is cause for satisfaction.

“There is this wonderful way of putting it, which I like very much,” he says. “When something is suggested, or some evidence is produced, the first response is, ‘It can’t possibly be true.’ And then, after a bit, then the next response is, ‘Well, if it’s true, it’s not very important.’ And then the third response is, ‘Well, we’ve known it all along.’ ”

*

It is easy to assume that Salk is after some greater legacy, that he is driven by a desire to, once and for all, persuade the scientific community that he is indeed the legend the public thinks he is.

The truth, he insists, is much simpler. He saw a line of scientific inquiry that he thought should be pursued and so he pursued it, realizing that if he didn’t test his own ideas, nobody else would.

“Others do not see what I see. I don’t see what they see. That’s a matter of perception and now I simply say: ‘Fine.’ . . . I get into a dialogue with nature and put the question to nature, not to my colleagues, because that’s from whence the answer must come.

“I’ve learned enough in my life span to know that I must go my own way. And I’m not competing with anyone, mind you. This is not competing, it’s performing. Life is a performing art, science is a performing art. . . . Now if others feel competitive to me, that’s something else again.

“Just this morning, I met someone who thanked me for the freedom from fear of the polio virus. That’s what it was all about. There was real terror in those days, of parents and of children. Freedom from fear. That’s the most powerful of all emotions. I’ll always remember Franklin Roosevelt saying there is nothing to fear but fear itself. I sure learned how important freeing people from fear would be.”

Salk holds out the hope of someday developing a preventive vaccine that would free the world of its current fear, although he says he has come to learn that AIDS is a far cry from polio and may not so easily be conquered. And yes, he says--in answer to an oft-asked question--if he does develop such a vaccine, he will test it on himself, as he did with his polio vaccine. To do so would simply be a declaration of faith in his own work.

Even if the Salk Immunogen is found to boost the immune response, it will likely be years before anyone knows whether it actually will save lives. And, Salk acknowledges, it may be years beyond that before he or anyone else creates a vaccine that would prevent infection with the AIDS virus. Possibly, the answers will not come until long after his lifetime.

So the jury is still out on Jonas Salk. He is reminded that, in another publication, he was quoted as having told a colleague that he would be remembered for his work with AIDS.

“I said that?” he asks, both angry and incredulous. “I said that? God, no. Can you imagine me saying that? Of course I would never say anything like that.

“I would like to see an AIDS vaccine. I would like to see a way for ameliorating this problem, whether it is through something that I have contributed or something that others contributed. . . . I look upon this as the scientific way of thinking, of reasoning, of exploring, of discovery. In a way, it’s a game. It’s a way of trying to outthink the virus, to outsmart it. Thus far it has outsmarted us and now the question is: ‘Can we outsmart it?’ ”

And if he does outsmart the elusive human immunodeficiency virus? Is Jonas Edward Salk prepared, after all that has gone before, to become a hero once again? Will he be able to bear it if the pattern of his life is repeated one final time? His reply comes quickly and easily:

“Once you are immunized, you stay immunized for life.”


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