Subject: Race to Develop Vaccine Against AIDS Mobilizes Researchers Date: Published: 9/4/84 254 lines Source: Wall Street Journal. Copyright Dow Jones Inc. Long Shots: The Race to Develop Vaccine Against AIDS Mobilizes Researchers --- With a Virus Now Isolated, Production of Preventive Is Engrossing Scientists --- A Nobel Prize to the Winner? --- By Marilyn Chase Staff Reporter of The Wall Street Journal WASHINGTON -- When medical sleuths unmasked the virus they believe is responsible for AIDS, spirits soared and so did rhetoric. "A triumph over disease," it was said. Rhetoric can't cure an epidemic. By now, 5,500 Americans have contracted acquired immune deficiency syndrome, and almost 2,500, or 45% of them, are dead. But identifying the virus -- called HTLV-111 here and LAV in France -- was the breakthrough that changed a medical mystery into a practical problem that might someday be solved. Now, scores of scientists here and abroad are working to make experimental vaccines against AIDS. This is high-stakes science, involving a fatal virus that poses risks to those who make and test any vaccine. Rewards also are high: survival for people at risk, recognition and probable riches for the scientists who get there first. This struggle of men and microbes has historical echoes. It was a century ago that Louis Pasteur replaced "the hair of the dog that bit you" with the first real rabies vaccine. A folk cure used unsuccessfully for centuries involved pulling a hair from the rabid dog, singeing it and rubbing it into the bite wound of the human victim. Pasteur tried instead a bit of dead rabies virus, injecting it to save the life of a nine-year-old boy in 1885. Conquering AIDS won't be that easy. "It may be a disease for which we can't immunize," warns William Haseltine of Dana-Farber Cancer Institute in Boston. "But it doesn't mean we shouldn't try." To understand the odds, first consider the nature of viruses and vaccines. Of all the agents of disease, a virus is the smallest. Invisible to ordinary microscopes, the supposed AIDS virus is only 1/80 the size of a single red blood cell. It doesn't eat or breathe and -- consisting simply of genes inside a protein "coat" -- lives only to spawn copies of itself. For this, it invades the cells of its victim and multiplies. The body's natural defenses against viral invaders are led by antibodies -- proteins that block the virus from attacking the host cell. "Killer cells," a second line of defense, destroy infected host cells where the virus hides. These defenders take action when they recognize the virus's protein coat. Vaccines prime these defenses. By injecting a bit of the enemy virus -- crippled or killed so the vaccine itself can't cause sickness -- doctors rally the body to a state of immunological combat-readiness. But AIDS is a stealthy target. It belongs to a family of so-called retroviruses that can hide in latent form like a time bomb, passing disease from even healthy carriers via blood or semen. Some scientists think the virus may also live in saliva. With retroviruses, Dr. Haseltine says, "Once you're infected, you're probably always infected." AIDS also appears to be a moving target. Even as scientists hasten their work, the virus is mutating, making vaccine-development trickier, says Flossie Wong-Staal of the National Cancer Institute, who plans to publish her findings soon. "That's an advantage for the virus, if it can escape the body's immune surveillance," Dr. Wong-Staal says. History's most successful vaccines -- shots against yellow fever and polio -- were made from live virus. But AIDS's mortality rate -- 100% after four years -- makes many scientists reject that route as too risky. "I know this virus," warns Robert Gallo, the National Cancer Institute scientist who identified the AIDS agent as HTLV-111 last April. "I'd be afraid to put it into healthy humans, even if it were safe in monkeys." Against such risks, researchers are devising new strategies that could advance the state-of-the-art in human vaccines. At the National Cancer Institute, Dr. Gallo and his team are proposing to fragment the virus for a "sub-unit vaccine." That means taking a piece of the protein coat -- free of dangerous viral genes -- and trying to spark protective immunity with it. Eventually, Dr. Gallo says he hopes to use recombinant DNA (deoxyribonucleic acid) to mass-produce purified viral proteins safely and cheaply. In Durham, N. C., Dani Bolognesi, the deputy director of the Duke University Cancer Center, wants to go the "sub-unit" idea one better. Dr. Bolognesi says two layers of protein from the virus's coat are needed. Under an electron microscope, AIDS virus looks like a sphere wrapped in protein, much as a candy apple is coated with caramel and nuts. On the outside are nuggets of a substance called glycoprotein, clinging to a caramel-like layer called transmembrane protein. Dr. Bolognesi wants to try peeling off those two layers and forming them into little balls he calls "rosettes." "My guess is, that's all you need," he says. Others defend different hunches. In Boston, Dr. Haseltine says, "I'd push for a vaccine type called the empty virus" -- using the whole virus minus the genes inside it. Exploring the most exotic vaccine is the task of Hilary Koprowski, director of the Wistar Institute of Anatomy and Biology in Philadelphia. He is harvesting antibodies from AIDS patients' mothers, who have been exposed to the virus but aren't sick. He plans to inject these particles into animals, which would produce within their bodies a second wave of antibodies called "anti-idiotypes." These mysterious substances would contain the mirror image of the original AIDS virus, and he believes the mirror image alone might rally the body's defenses againt AIDS. "The advantage is complete safety," asserts Dr. Koprowski, who has successfully tested anti-idiotypes against rabies in animals. Harvard University also has applied for a patent on such techniques. A test-tube triumph by these researchers, or by Luc Montagnier or Jean-Claude Chermann at the Pasteur Institute in Paris, may take many months or even years. Then, any experimental vaccine must undergo animal tests, human clinical trials, and commercial production before those most vulnerable can receive inoculation. Each step entails risks and uncertainties. Dr. Gallo recently unwound over dinner and wine with colleagues and asked, half in jest: "Once we have this vaccine -- Dani, Hilary, and I -- what are we going to do with it? " Moving a vaccine from test tube to factory requires huge investment and liability that repels both government and industry. Nobody has forgotten the billion-dollar swine-flu fiasco of the 1970s. A vaccine that was rushed out caused cases of paralysis and engendered lawsuits. The anticipated outbreak of influenza didn't occur. "I don't think the government will want to be involved this time," says Peter Fischinger, associate director of the National Cancer Institute. "It should be done by a commercial entity." A multi-company licensing program, like that recently launched to develop an AIDS blood test, is one possibility. But today, who the players might be is anyone's guess. Names mentioned include Merck & Co., and Genentech Inc. The AIDS epidemic arrived at a time when most major pharmaceutical companies are avoiding vaccines like the plague. Long development, the high costs of human trials and liability for accidental cases of disease have meant "profits from vaccine have been less than profits from antibiotics and tranquilizers," says Stanley Plotkin, who developed rubella (measles) vaccine. "Fewer and fewer companies are willing to assume the risks." Merck, the most obvious candidate, because of its recent work on hepatitis vaccine, now has "no interest in AIDS vaccine, though that's subject to change," says a spokesman for the Rahway, N. J., company. Genentech, of South San Francisco, is known to have approached Dr. Gallo about possible collaboration but declines all comment on AIDS vaccine. Smaller companies, backed by powerful partners, might take the plunge. "We're very interested in vaccines," says Robert L. Ting, the scientific director of Biotech Research Laboratories Inc., a Rockville, Md., firm now collaborating with Du Pont Co. on an AIDS blood test. Another small contender in the vaccine stakes is Cambridge Biosciences Inc., which boasts Dr. Haseltine and other Harvard faculty members on its scientific board. Who will make the vaccine is one question; who will take it is another. Paul Volberding of San Francisco General Hospital worries that people will shrink from playing guinea pig. Whole-virus vaccines risk causing illness, he notes, and sub-unit vaccines might not be much safer, having already induced an AIDS-like immune deficiency in cats. "I disagree with Paul," says Anthony Fauci, a top NIH immunologist. "I think the gay population will be breaking down the door just as soon as we have a vaccine." New and disturbing intelligence complicates vaccine plans. Recently, San Francisco researchers reported that the majority of promiscuous homosexuals tested there already have antibodies against AIDS virus -- raising questions about whether they would even benefit from a vaccine. AIDS, furthermore, may jump the boundaries of usual risk groups -- homosexuals, Haitian immigrants, intravenous drug abusers and blood recipients -- to be passed by heterosexual contact. Indeed, the Centers for Disease Control cites 40 such cases in the U. S. that mimic the widespread heterosexual AIDS that has been found in Africa. "What we're going to see are great increases in women with heterosexually transmitted AIDS," predicts James Curran, the head of AIDS activity at the CDC. All this may mean "we'll have to think more about a vaccine for the general populace," says Myron Essex of the Harvard School of Public Health. Vaccines, of course, offer no hope for those already afflicted with AIDS. So far, efforts by the National Institutes of Health to shore up the immune systems of of AIDS patients by using bone-marrow transplants, gamma interferon and interleukin-2 have failed. "It was like pouring water into a bucket with holes in it," says Dr. Fauci of NIH. The next experimental treatments will be anti-parasitic drugs that may block the virus's reproduction, and monoclonal antibodies -- so-called magic bullets armed with toxins and radioactive substances. On a hopeful but guarded note, Samuel Broder of the National Cancer Institute says, "We're now on the threshold of attempting some rational therapies." When AIDS investigators assess risks to themselves, and the rewards, they tend to play down the danger. Still, garish orange biohazard signs flash a graphic reminder of risk. Even trash is bagged in biohazard-orange and sterilized before disposal. Jay Levy of the University of California at San Francisco had to fight for a mere 80 square feet of lab space because, he says, "the university was so frightened." Despite one researcher's joke about taking nightly bleach baths, most rate the risks of casual exposure as low. They give themselves blood tests quarterly, but so far no one has taken ill despite accidental needlesticks. A doctor's family can get skittish. "My wife was going crazy because I put some AIDS tissue culture in our refrigerator," Dr. Gallo admits. "Of course, it was triple-boxed and sealed with miles of tape. But maybe I should ask NIH to buy me another refrigerator." The rewards of the work are complex, of course. There is a private psychic payoff and public acclaim to be won, as well as money to be made. For Dr. Gallo, whose sister died of childhood leukemia, the passion to defeat disease is great. As a contender for a Nobel prize, he admits worldlier motives as well. But he fears that bitter competition with the French -- who named the virus first but whose work, some say, wasn't as detailed -- may tarnish his chances. Two years ago, Dr. Gallo won the Lasker Foundation award, and his champions remind him that 65% of Lasker award winners go on to win the Nobel prize. "Yes," he acknowledges warily, "but 35% don't." Moreover, he adds, "If you took away the media and the recognition, I'd still work in science. It's a neurotic curiosity." The allure of research grants is strong, too. But "right now, I'm doing all this AIDS work for no money," says Dr. Haseltine in his cramped cubicle. "Why? Because it's one of the most interesting questions in science today. We have a chance to use knowledge to intervene in an epidemic." For Dr. Koprowski, a vaccine victory might mean the niche in scientific history that has eluded him for decades. In 1950, he developed an oral polio-vaccine but lost the laurels when developers picked a version made by his competitor, Albert Sabin. "Politics," shrugs Dr. Koprowski. "Besides," he adds impishly, "Sabin is much easier to pronounce. Just imagine all those kids saying: 'I have to take my Koprowski oral vaccine.'" [This article is made available here by Dow Jones Co. for the personal and non-commercial use of callers to this bbs, in the hope that it will be of some help to those who are suffering from the disease and others who are seeking to help them.]