Subject: Salk's AIDS-Vaccine Research Draws Criticism Date: Published: 6/16/88 122 lines Source: WALL STREET JOURNAL. Copyright Dow Jones & Co. Inc. Salk's AIDS-Vaccine Research Draws Criticism --- By Marilyn Chase Staff Reporter of The Wall Street Journal STOCKHOLM -- At the Fourth International AIDS Conference here, Jonas Salk yesterday made his case for a controversial strategy against the disease. But the 73-year-old father of the polio vaccine is having a difficult time winning converts to his cause. While other researchers are using synthetic virus fragments in their search for a vaccine against the epidemic of the 1980s, Dr. Salk advocates applying a principle he used in fighting the paralytic scourge of the 1950s. As a form of immunotherapy, he proposes using whole but inactivated AIDS virus to inoculate people already infected. "It's Nature's way," Dr. Salk argues, "and it's protective." Skepticism about Dr. Salk's approach, much of it based on concern about the possibility of infection from using whole virus in a vaccine, erupted into the open at the conference. In an address, Dr. Salk and Clarence Gibbs, a National Institutes of Health researcher collaborating with him, presented the results of their first experiments with chimpanzees and humans. They reported that in response to Dr. Salk's vaccine a previously uninfected, or seronegative, chimp produced AIDS antibodies that lasted eight months. On hearing this, Jorg Eichberg, the head of veterinary virology at the Southwest Foundation for biomedical research in San Antonio, Texas, publicly challenged Dr. Salk. Such a response from a single shot of inactive virus would be "impossible," Mr. Eichberg asserted. Other scientists agreed it would be unusual, but withheld judgment for now. Mr. Eichberg charged, too, that lab error must have resulted in the animal's being infected by live AIDS virus -- something Dr. Salk and his collaborators absolutely deny could have happened. Mr. Eichberg also stunned the audience by asking if human subjects in a second part of the study received vaccine from the same batch -- raising the question of whether they, too, might have received live virus. (All nine human patients in the study already carry the AIDS virus and have lymphadenopathy syndrome, a precursor of AIDS.) Alexandra Levine, a physician researcher at the University of Southern California who is caring for patients who have received the Salk vaccine, says the virus used was certainly dead, adding that she's seen no short-term or long-term toxicity, nor any allergic reaction, in her patients since the November inoculation. "We've seen no evidence of infectivity" in the vaccine, adds NIH's Dr. Gibbs. Where other researchers use genetically engineered or synthetic virus proteins, Dr. Salk has chosen to use live virus killed with gamma radiation. He says he tries to culture the virus for four weeks to make sure it is dead, although some AIDS researchers prefer six weeks as a measure of insurance. In addition, other vaccine researchers are focused on the outer envelope of the AIDS virus as the agent most likely to induce an immune-system response. Dr. Salk, on the other hand, uses everything but the envelope. He removes it in processing, believing it doesn't help the vaccine's effectiveness but might help the virus. Arguments about whole-virus vaccines, and about the possibility of contracting disease from them, aren't new to Dr. Salk. "When I began working on polio," he told the packed auditorium, "people also assumed you couldn't get antibody (response) from a noninfectious strain." However, he insists, it is possible. Part of the present schism stems from a scientific generation gap. Many of Dr. Salk's listeners are scientists a fraction of his age, weaned on such techniques as gene splicing and the cloning of exotic proteins in microorganisms. This new generation believes that noninfectious particles manufactured in bulk through biotechnology make for safer, purer medications. Still others recall that a few cases of paralytic polio resulted from early Salk-vaccine experiments, although Dr. Salk and others insist this was the result of production error not of his making. In an interview, Dr. Salk reproaches the doubters. "We need thinkers as well as tinkerers," he says. Noting that his method is intuitive rather than academic, he adds, "I enter into a dialogue with Nature, as opposed to (a dialogue with) my colleagues." Dr. Salk's approach has already won him some venture-capital backing to start a company called Immune Response Corp. in La Jolla, Calif. Moreover, if his approach hasn't been proved successful, neither has any other AIDS vaccine. Attendees at the conference here have heard presentation after presentation about test animals and, in two cases, human patients that have mounted antibodies and killer cells against the virus. But no one knows if they could withstand a challenge by live virus and remain protected. Even more sobering is that several of these synthetic vaccines have yet to protect test animals against the AIDS virus. A number of groups working with chimps -- including Genentech Inc. of South San Francisco, Calif. -- reported here that when exposed to live virus, the vaccinated animals developed an infection. "We're at a critical juncture" in vaccine development, said Dani Bolognesi, a Duke University vaccine researcher. Dr. Salk told the conference that his human trial -- essentially a safety study designed to see whether humans can tolerate the vaccine -- also demonstrated that patients could develop inhibitors against reverse transcriptase, a viral enzyme that the AIDS virus needs in order to replicate. But he noted that while several subjects remained virus free for two months after inoculation, he isn't making claims about the effectiveness of the therapy. "I'm not stretching this; I'm not interpreting," he said, adding, "We'll know quite soon about the different approaches," and what holds the most promise. [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.]