The Cure That Failed

By Tom Bethell
National Review 10 May 1993

Did the AIDS lobby know what it was doing when it pressed the government to approve AZT?

Lindsey Nagel was born in Petrosani, Rumania, in October 1990. She was adopted by a Minneapolis couple, Cheryl and Steve Nagel, who brought her back to the States later that year. Within a few weeks, they were dismayed to find that she had tested positive for HIV. Although she showed no symptoms of disease, the Nagels' doctor put her on Retrovir syrup, otherwise known as AZT. In response to protests by homosexual activists this drug had been hurriedly approved by the FDA in 1987. "The government bends to AIDS victims' pleas," was the way U.S. News & World Report headlined a critical story at the time.

Over the next 18 months Lindsey's general health declined. She became "hyperactive," as though "she did not feel comfortable in her body," according to her father. She did not eat properly, avoided milk, and suffered from nausea and diarrhea. Then, in October 1992, things took a turn for the worse. Night after night she woke up screaming. Her parents would find her half sitting up in bed, clutching at her knees and thighs. Sometimes this would happen twice a night.

A month or so before this turn of events, the Nagels had read a couple of magazine articles about Peter Duesberg, a virologist at UC Berkeley. Duesberg says that HIV does not cause AIDS, and that AZT is toxic and not a rational treatment for AIDS. The Nagels wanted to know more, so they wrote and told him about the treatment their daughter was receiving.

"Take her off AZT immediately if you want to see her live," Duesberg wrote back. "Your daughter will die from it, like Kimberly Bergalis, if you continue the treatment."

Kimberly Bergalis was believed to have been infected with HIV by her dentist in Florida. She had a yeast infection, which is common among women, but it is also one of the "indicator diseases" within the Centers for Disease Control's ever-expanding definition of AIDS. (First defined in 1982, AIDS was redefined more and more inclusively in 1984, 1985, 1987, and 1993.) With a yeast infection plus HIV, Miss Bergalis became an AIDS patient by definition, and was duly prescribed AZT. Within a year she was in a wheelchair (as was Rudolf Nureyev toward the end of his life, and he, too, took AZT). Among its other side-effects, AZT causes myopathy, or muscle atrophy. Miss Bergalis died in 1991.

Arthur Ashe also took AZT. After his death, New York Daily News columnist Earl Caldwell reported that Ashe had "wanted to" break away from his treatment, but was worried about giving offense. "What will I tell my doctors?" he said to a friend. Michael Callen, the author of Surviving AIDS, claims that the only long-term AIDS survivors are those who have not taken AZT. Larry Kramer, HIV-positive gay playwright, and unremitting scourge of the government when it doesn't seem to be doing enough, says that AZT is not for him.

AZT was designed in 1964 as chemotherapy for cancer. But it was never approved, because of its side-effects. With an AIDS cure much in demand, it was retrieved from the storage room. After toxicity and efficacy trials seemed to show that it did some good, at least in the short run, the FDA gave the drug its seal of approval. "From a failed cancer medication to the only fully approved AIDS treatment, AZT has made an astonishing comeback," Discover reported in 1990.

Chemotherapy prevents cells from dividing by fooling cellular DNA into accepting a chain-terminator into the DNA chain. It's like putting a caboose (with no rear coupling) into the middle of a freight train that was supposed to incorporate many more cars. Now the train cannot expand beyond the caboose because there's nothing to hook onto.

The problem with chemotherapy is that it stops all cells from dividing, not just cancer cells. Science hasn't been able to figure out a way for it to zero in on the cancer exclusively. Cancer cells divide rapidly, but so do stomach cells and bone-marrow cells and lots of other cells. The formation of new DNA chains is stopped within all of them. That's why long-term chemotherapy is very destructive.

The same problem arises with AZT. The drug doesn't know how to find just the HIV-infected cells (assuming, arguendo, that HIV really does cause AIDS). And that's why Duesberg wrote in a recent article that AZT "must be the most toxic drug ever approved for indefinite therapy in America." Nonetheless, about 100,000 people are now taking it. One is Jeffrey Schmalz, the New York Times reporter who has AIDS. Many people report early beneficial effects from AZT. And Schmalz told me that the drug had saved his life. "The problem is long range," he said, "because it begins to eat away at your system."

What about the efficacy and toxicity studies? Here I warn NR readers that I shall make a "left wing" point, but I wouldn't bother to do so if the news media had shown any interest in it. Surprisingly, they have not. Many of the AZT studies have been funded by the company that makes AZT, Burroughs Wellcome. This was true of the "double-blind, placebo-controlled trials" in 1986 that led to FDA approval of the drug. The results of these trials were published in The New England Journal of Medicine in 1987.

I called Jerome Kassirer, the editor-in-chief of The New England Journal of Medicine, to ask him about "scientific etiquette" with respect to publishing studies funded by the manufacturers of the thing studied. He said that the NEJM's policy was very simple-disclosure. "We disclose, typically on the cover page, what the relationship [of the study] is to the company," he said. And indeed, with the AZT toxicity study, it plainly says on the cover page: "Supported by the Burroughs Wellcome Company....." Likewise the efficacy study includes among its many co-authors "the AZT Collaborative Working Group," which, if you read the fine print, also on the cover page, includes five scientists from the Burroughs Wellcome Company.

"If we have a scientific study," Kassirer said, "we have to assume that the data are the data."

Would The New England Journal publish a smoking study funded by Philip Morris? I asked. "In principle, we might publish it," he said. "But it would have to pass the same kind of scientific standards as any other study."

Flawed Tests

What are those standards? When are the data not the data? Joan Shenton, who produced a program critical of AZT shown in Britain last February, published a letter in The Lancet claiming that "both the U.S. Food and Drug Administration and trial investigators knew that the two trials [mentioned above] had become unblinded." (FDA documents, obtained through Freedom of Information procedure, had disclosed this information.) The patients figured out who was receiving the drug and who was receiving a placebo, and those receiving the drug shared it with those who were not.

Furthermore the trials, planned for 24 weeks, were ended "after an average of only 17 weeks," according to Miss Shenton. It has since come out that 30 (of 145) AZT recipients were kept alive by blood transfusions to compensate for severe bone-marrow toxicity. Burroughs Wellcome concedes "the drug has been studied for limited periods of time and long-term safety and efficacy are not known." The New Scientist reported in 1991 that "there are serious, unanswered questions about its long-term effects."

In early April came the results of a three-year European study of early use of AZT with HIV-infected individuals-the Concorde trials. One group was given AZT immediately; the other, not until they developed symptoms. (It has not been reported how the subjects were chosen, but it is a reasonable assumption that many were drug-users.) The study therefore did not test the efficacy of AZT itself, because most subjects seem to have ended up taking the drug. But early use was shown to have no beneficial effects, and the fine print in The Lancet showed that significantly more of the early users experienced anemia, low white-blood-cell counts, nausea, and vomiting than the late-use group.

The researchers (in Britain and France) came under pressure to stop the study early-as three out of four comparable U.S. studies have been. In Britain, Lawrence K. Altman reported in the New York Times, "health officials are less influenced by pressure from advocacy groups." It's almost as though officials here don't want to know the truth. Even more surprising is that gay activists should have so much faith in government science. The very effectiveness of their protests have shown just how easily government science can be politicized.

What happened to young Lindsey? As soon as the Nagels received Duesberg' s letter, they discontinued her AZT. Her condition immediately improved. "It was dramatic, almost overnight," Cheryl Nagel told me. She stopped crying out in the middle of the night. Her leg cramps ceased. She became much calmer. Her food intake almost doubled. She happily drank the milk that she used to reject. And since then she has gained over five pounds. More recently her mother has spent a good deal of time in the University of Minnesota's medical library, trying to figure out why Lindsey was prescribed AZT in the first place. The label published by Burroughs Wellcome does not "indicate" the use of AZT with asymptomatic infants. At the end of March, the Nagels filed a complaint with the Minnesota Board of Medical Practice, but they do not expect that much will come of it. An FDA official told them that once a drug has been approved by the FDA, "it can be prescribed for dandruff." *

Mr. Bethell, a National Review contributor, is Washington correspondent for The American Spectator.