'The Gravest Show on Earth; America in the age of Aids'
Elinor Burkett
Houghton Mifflin Co. USA 1995, 400 pages,
ISBN 0-395-74537-3.

BOOK REVIEW:

Elinor Burkett portrays the AIDS culture wars as a kind of circus in which a series of clowns and villains perform on stage while the audience slowly dies from neglect. She does not purport to give the complete story of AIDS. Her book has nothing to say about Africa or Asia, and very little about hemophiliacs, intravenous drug addicts, or infants. Burkett's story is about the relationships between the gay activists, the scientists, the drug companies, and the media -- as seen by a Miami-based reporter who describes her own book as a "howl of venom, wrath, hysteria, fury, and desperation."

The theme of the book as a whole is encapsulated in the first chapter, a dual biography of two flamboyant egotists who became allies: the biomedical scientist Robert Gallo and the gay playwright and founder of ACT-UP Larry Kramer. Gallo was determined to prove that a human retrovirus discovered in his laboratory at the National Cancer Institute was responsible for some disease serious enough to merit a Nobel prize for the discoverer. Kramer played the role of spokesmen for gay rage, freely accusing scientists and government officials of sponsoring a "holocaust" or "genocide" because they had not taken swift enough action to prevent or cure AIDS.

The accusations were absurd, but the liberal media culture found it easy to believe that the hated Reagan administration was uninterested in curing AIDS because it didn't care about the victims. In this climate of opinion health officials were under enormous pressure to do something -- *anything* -- to show that they had a viable program. The immediate result was the famous press conference in April, 1984 at which the Secretary of Health and Human Services announced on shaky evidence that one of Dr. Gallo's retroviruses (later named HIV) was the "probable" cause of AIDS. The Secretary spectacularly rebutted the barrage of criticism with the prediction that, with the pathogen known, a vaccine would follow in a couple of years. The resources of government were soon devoted to exploiting the breakthrough. AIDS research became HIV research, and funding for studying other possibilities became unavailable.

The second major step that was taken to stem the criticism was the approval of AZT as a treatment. Burroughs Wellcome, the manufacturer of AZT, took advantage of the panic to rush through FDA approval of a drug that it had on the shelf as a failed cancer cure. Activist demonstrators, with help from conservative politicians pushing an agenda of deregulation, intimidated FDA scientists who found the evidence of efficacy inadequate. The FDA, which had stoutly resisted the claims of terminal cancer patients in the laetrile episode, caved in to the far more potent AIDS lobby. Whether AZT gives any substantial benefit to AIDS sufferers is still hotly debated, but nobody disputes that it has immensely benefitted Burroughs Wellcome stockholders.

Burkett never pins down exactly what she is so angry about. No doubt AIDS politicking has involved lots of greed, paranoia, and hypocrisy, but that doesn't distinguish AIDS from a lot of other things going on in government and business. The promised vaccine or cure is nowhere in sight, but the AIDS advocates persuaded the government to provide "a level of Federal attention, support and services that were the envy of people with cancer, multiple sclerosis, and heart disease." Progress has been made treating some AIDS-related conditions, and new antiviral drugs that might be better than AZT are on the way. That AIDS has proved so difficult to cure or even understand is cause for disappointment, but where's the scandal?

Burkett actually gives her readers the facts needed to answer that question, but it takes a bit of background to separate the wheat from the chaff. The AIDS failure has been less a product of the faults of individuals than an illustration of the adage that it's no advantage to travel faster unless you are going in the right direction. In science as in law, meticulous attention to established procedure is essential for accuracy but it is also extremely expensive, especially when delay may cost lives. Scientists like other people tend to see what they want to see, and they have no immunity from traits like impulsiveness or greed. Ordinarily, these traits are held in check by rigorous peer review before claims even get published, and by the still more rigorous criticism that really important claims will receive from other laboratories for months or years thereafter.

If government officials had waited for Robert Gallo's virus hypothesis to survive that kind of criticism before making it the basis of a huge research program, however, they would have been excoriated for going about business as usual while multitudes were dying. The path of least resistance was to go for broke with the best idea currently available, and that is why the campaign against "the virus that causes AIDS" was announced at a press conference before the scientific community had a chance to evaluate whether the virus really does cause AIDS.

Once the scientific army was on the march, with everybody's research program based on the premise of HIV-causation, the time for debating the starting point had passed. When the prestigious Berkeley molecular biologist Peter Duesberg published a review article in 1987 opposing the HIV hypothesis, he was ignored for two years and then ridiculed and deprived of all funding. If the same arguments had been widely circulated in the spring of 1984, they would have received a respectful hearing and the course of events might have been entirely different.

The same sense of urgency accounts for the hasty approval of AZT, and the drastic easing of previously established drug testing procedures. Drug tests must be placebo-controlled and "double-blind," meaning that neither the doctors nor the patients know who is getting the drug and who the placebo. They also should be continued long enough so that long-range as well as short-term effects are measured, and repeated so that it is clear that different research teams get similar results. These precautions are important because of the notorious "placebo effect" on patients, and because doctors who understandably want the drug to work may see benefits that aren't really there or are only temporary.

Rigorous design and evaluation of trials is particularly necessary because the drug companies who are seeking approval fund the studies and even select the researchers. Scientists may have a lot to gain by putting the most favorable possible spin on the data, especially when (as in the case of AIDS) their superiors in the scientific hierarchy desperately want to announce the discovery of an effective treatment. Independent evaluators need to make sure that unfavorable interpretations of the data were not overlooked.

Burkett correctly reports that the crucial study that purported to establish the efficacy of AZT adhered to standard criteria only in a formal sense. Patients and doctors knew who was getting AZT because the drug caused such severe anemia (among other unpleasant effects) that many patients required blood transfusions to survive. After seven months, however, 19 members of the placebo group had died as opposed to only 1 in the AZT group. The trial was then halted before completion on the ground that efficacy had been established and it would be unethical to continue giving any AIDS patient a placebo. Three months later, 13 of the placebo group who had been switched to AZT had died, along with 7 who had been on AZT from the beginning. Despite serious reservations by its staff over what this ambiguous trial had proved, the FDA gave in to the pressure and speedily approved AZT for the market.

When the later and far more extensive European Concorde trial showed that AZT did not extend life for asymptomatic HIV-positives, enthusiasm was dampened but not extinguished. AZT remains in very widespread use for both AIDS patients and asymptomatic HIV-positives. Because it is considered unethical to include a placebo group in tests, AZT is also the "gold standard" against which other drugs are compared in efficacy tests. As a result AIDS patients now have the dubious benefit of being able to take a variety of drugs with uncertain benefits and damaging side effects.

Twelve years after the 1984 press conference, knowledgeable AIDS patients have learned to distrust the press releases about impending wonder drugs. Vaccine trials have been put off into the indefinite future, amid confusion over exactly what a virus should be expected to do. Robert Gallo remarked in a statement reported in the the New York times on December 6, 1995, that "The No. 1 reason that we don't have a vaccine today is that we don't know what to induce in humans." Such statements reflect a significant gap in the theoretical knowledge needed to design a treatment strategy, and indeed the scientists are still trying to find a mechanism by which HIV can be destroying far more immune system cells than it actually infects.

In a better world, the journals would be full of demands for a fundamental reconsideration of a premise adopted in such dubious circumstances, especially now that the campaign based upon that premise has resulted in so much scientific failure. But too many reputations are at stake for that to be allowed to happen. Instead the President met with the AIDS lobbies in December 1995 to reassure them that the national effort will continue to proceed along the same lines, but with more money.

The scandal of the circus of death is not so much that essential scientific procedures were short-circuited in a time of emergency, as that after a decade of failure the researchers are unwilling to go back to the starting point to figure out where things began to go wrong.

Elinor Burkett is like many other reporters who have become emotionally involved with the tragedy of AIDS. She provides a lot of the important facts, but in the end can do no more that express her frustration that things have turned out so badly. What this story needs is a reporter who can describe the scientific fiasco that resulted when the activists succeeded in pressuring the scientists to commit themselves to a theory, and to a drug, before they understood the nature of the disease.

Source: First Things, March 1996.