Forging A Shield Against AIDS

By ANDREW PURVIS

What might have been a methodical, scientific quest has turned into a wild crapshoot. In more than 60 laboratories around the world, researchers are working with at least 40 different concoctions in pursuit of one of medicine's most urgent goals: the development of an AIDS vaccine. Any team that succeeds will reap fame, fortune and the satisfaction of possibly wiping out a disease that ranks among the deadliest scourges ever to afflict humanity.

But first it will be necessary to bring some order to the bewildering array of options. While there are still some doubts that an ideal vaccine can actually be created, some researchers believe that enough good candidates now exist to warrant drastically narrowing the search and selecting the best and the most effective experimental vaccines for major trials in humans. Last month at a meeting of the Institute of Medicine in Washington, scientists and health officials began to lay the groundwork for trials in the U.S. and other nations. In April researchers from the World Health Organization (WHO) will begin visiting countries in Africa, Asia and Latin America to locate groups in which such studies might be conducted.

But even early planning for such experiments has raised thorny economic, political and ethical questions that some researchers fear could interfere with the introduction of a lifesaving vaccine. "If one of these trials goes badly, we would lose not only time, but we could lose the opportunity to test an AIDS vaccine altogether," said Dr. Jonathan Mann, professor of epidemiology and international health at Harvard. "It's very important that they be done right."

The basic principle behind such human tests has changed little since the 19th century. Several thousand people at high risk for the disease will be inoculated with the experimental agent, most likely an altered version of the AIDS virus (HIV) or some portion of it. The vaccine should not be dangerous enough to cause the disease, but enough like HIV to confer immunity by triggering the production of antibodies and other virus-fighting components of the immune system. The subjects in the trial will be carefully monitored to see if they have a better record of avoiding infection than groups who were not vaccinated.

The theory seems simple enough, but the peculiar epidemiology of AIDS has already raised disturbing issues about how these trials will be conducted. In particular, the populations at greatest risk for the disease -- including drug abusers, prisoners and prostitutes in the U.S., as well as truck drivers and military recruits in some African countries -- are not ideal candidates for a structured scientific trial. Drug abusers and prostitutes may be transients who are not easy to monitor, and inadequate transportation and communications in many African countries will hurt efforts to keep track of volunteers.

Scientists, moreover, cannot guarantee that these trials will be risk free. If a vaccine is made from a whole AIDS virus, for example, there will be a slight danger that some of those vaccinated will get the disease. In 1955, during early testing of the polio vaccine, 80 children in California got the illness from improperly prepared shots. Even if the immunization works and produces large amounts of antibodies to HIV, participants will have to cope with the social stigma of being HIV positive. The antibodies generated by a vaccine are the same ones that doctors look for when they test for AIDS. Thus researchers are concerned that participants in the studies could suffer the same discrimination -- in getting health insurance or a job, for example -- that plagues people with AIDS around the world.

One uniquely troubling aspect of these trials is that many of the subjects in Africa, and elsewhere in the Third World, are unfamiliar with the ways of Western medicine and may not fully comprehend the risks of participating. Explains Dr. David Heymann, chief of the research office at the WHO Global Program on AIDS: "It is vital that African volunteers understand that they are getting an experimental product that might not work." Without such "informed consent," doctors cannot in good conscience carry out their research, and may face charges that they are using people as guinea pigs. "The problem," concluded a report from last month's meeting at the Institute of Medicine, "will be to avoid what has been called 'safari research' or 'medical imperialism' while gathering the necessary data."

The delicacy of these human tests greatly increases the need for cooperation between the drug companies that ordinarily foot much of the bill for vaccine research and various government and intergovernment agencies that are trying to ensure that the product gets to the people who need it most. Yet so far such cooperation has been sporadic at best. A report issued this month by the National Academy of Sciences notes that there is currently no way of telling which of the scores of candidate vaccines are the most promising, since relatively few have been tested against each other in head-to-head comparisons. Unless investigators financed by different companies and by the National Institutes of Health are willing to work together, the report concludes, discovery of a useful vaccine could be dangerously delayed. Dr. Wayne Koff, head of AIDS-vaccine research at the NIH, worries that researchers will be too inclined to stick with their own projects rather than pool their resources.

In addition, some health officials are concerned that drug-company investigators may be ignoring a particular kind of vaccine -- those using a whole virus -- not because they are less promising scientifically, but because they carry a slightly greater risk of infection and, in turn, a greater potential for liability suits. In fact, some scientists contend that the threat of such suits has kept many major drug companies out of vaccine research altogether. To combat this chilling effect, the NAS report urges Congress to provide drug companies with liability protection.

Perhaps the most difficult ethical question is the cost of the vaccine. A successful shot that sells for an exorbitant price will be of little use to most Africans, who have no more than a few dollars a year to spend on health care. Nine years have passed since the discovery of a vaccine for hepatitis B, a viral disease that, like AIDS, is spread by sexual contact and the sharing of hypodermic needles. But the product has yet to reach many people in poor U.S. neighborhoods and Third World countries largely because it costs more than $120 a shot. It would be a gross injustice, says Harvard's Mann, if Africans helped develop an AIDS vaccine by taking part in trials only to see it priced out of the reach of their countrymen. To prevent such a situation, Mann recently proposed that Congress offer drug companies an extension on exclusive marketing rights for other lucrative drugs in exchange for keeping the price of an AIDS vaccine down. Says he: "This is the time to make a deal, not after the vaccine is on the market."

Many researchers are hopeful that regulators, vaccine manufacturers and individual investigators will put aside their differences when the best candidate emerges from the laboratories. If they do not, one of the greatest medical feats of this century may be remembered not just for the lives it saved but also for the victims it failed to reach.

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CREDIT: TIME Diagram by Joe Lertola

CAPTION: WAYS TO TRIGGER IMMUNITY