Guerrilla Drug Trials: The Underground Test Of Compound Q

By DENNIS WYSS

Bob Barnett sits on an examination table in San Francisco while an intravenous needle drips an experimental AIDS drug into his veins. The drug, called Compound Q, is a purified protein extracted from a cucumber-like Chinese plant and one of the latest promising glimmers in the search for a cure for AIDS.

Across town, researchers at San Francisco General Hospital Medical Center are conducting cautious, federally approved Phase 1 toxicity trials with minute dosages of GLQ223, as Compound Q is officially known. But for Barnett, a 37-year-old former radio sales manager, as for thousands of others afflicted with AIDS, precious time is running out. Barnett wants to know if Compound Q works in larger therapeutic doses. He wants to know now. "My options are death and doing this," he says.

Barnett is one of 51 AIDS patients who, along with six doctors, took part in underground trials of Compound Q this past spring and summer. The clandestine study was organized by Project Inform, a San Francisco-based group of activists who believe the Food and Drug Administration's system for testing potentially life-saving new drugs is unconscionably slow. On Sept. 19, Project Inform director Martin Delaney revealed the preliminary results of the underground trials to an intent crowd of some 500 predominantly gay men in San Francisco. Although many of the trial's volunteers, including Barnett, showed a marked decrease in activity of the human immunodeficiency virus (HIV) that causes AIDS, Delaney said, Compound Q could not be considered a cure. But the desperation of the epidemic guarantees that underground drug trials will continue; AIDS activists say at least two dozen such experiments are under way across the U.S.

Hope flashed through the nation's AIDS community last April, when researchers from the University of California at San Francisco announced that, in test tubes at least, Compound Q could kill HIV-infected cells while leaving healthy cells unaffected. The substance quickly found its way into the U.S. and to desperate AIDS patients, who administered the drug on their own. "Word was out," says Dr. Alan Levin, medical director of the Project Inform trials in San Francisco. "People started getting it and injecting themselves in their kitchens."

To Delaney, such haphazard self-medication posed its own threats. "We said, 'Instead of just passing it out to see what happens, let's channel it into controlled clinical use,' " Delaney recalls. He contacted James Corti, a Los Angeles-based activist and importer of AIDS drugs who shipped 400 doses of Compound Q out of China.

Delaney then asked a group of doctors to design a protocol, or test model, based on an FDA trial for a similar drug called Ricin Toxin. Delaney says several FDA and National Institutes of Health officials in Washington were told of Project Inform's proposed trial, which was planned for patients in San Francisco, Los Angeles and New York City. "At no time did anyone tell us to stop," he says. An FDA spokesman in Washington claims officials did not hear about the clandestine trials until well after they began.

Without revealing the purpose, Project Inform asked Genelabs, Inc., a California biotechnology firm that manufactures the drug in the U.S., to test samples of Compound Q that Corti brought back from China. They wanted to make sure it was identical to the Compound Q used in the FDA-approved study. An attorney drew up guidelines that would keep the trials within federal law. Each patient made a videotaped statement, in the presence of an attorney and a witness, that he was entering the trial of his own free will. "What we wanted was a trial that was faster than the FDA, yet as safe," says Dr. Larry Waites of San Francisco.

The trial's volunteers were all men who had failed to respond to conventional AIDS therapy, including AZT, so far the only FDA-approved drug for treating the AIDS virus. To obtain accurate readings on Compound Q's effectiveness, volunteers were asked to stop using any other approved or unapproved drugs.

The secret trials began on May 24 in San Francisco. For three weeks, patients received infusions of Compound Q, some as high as 17 times the dosage given patients in the San Francisco General Hospital toxicity trials. For the first 48 hours, the carefully monitored volunteers suffered side effects of sore muscles, nausea, fever and fatigue. The side effects eventually went away, and many patients, including Bob Barnett, began to feel more energetic.

The clandestine study became public in late June after a San Francisco volunteer suffocated on his vomit after coming out of a coma ten days following his first dose of Compound Q. The FDA launched an investigation into the underground trials, which Project Inform suspended. Two other volunteers have since died, one in San Francisco and one in New York. Levin says the death of one of the San Francisco men was indirectly related to Compound Q, while the cause of the New York man's death has yet to be determined.

Some researchers raise serious doubts about the methodology of guerrilla drug tests. Project Inform is strongly criticized for bypassing an initial phase to establish Compound Q's safety before proceeding to larger, therapeutic dosages and for not having the trials reviewed by an external monitoring group. Says Jere Goyan, dean of the University of California at San Francisco School of Pharmacy and a former FDA commissioner: "If you get people taking these drugs willy-nilly around the country, you'll lose valuable information, and it will be at the expense of future patients."

To Delaney, such reasoning is flawed because it suggests that some victims who might be helped by experimental drugs may die while the traditional methods of testing drugs work their slow and cumbersome way. Pressure from AIDS activists has resulted in the FDA's allowing wider use of such experimental AIDS drugs as r-erythropoietin, which is used to treat AIDS- related anemia, before studies have been completed. Compound Q faces much more rigorous testing despite the hint of promise. "It's not a one-shot cure," Delaney warned the packed community meeting. But Bob Barnett, a true believer in his right to receive another dose of Compound Q, leaped to his feet with the rest of the crowd to give Delaney a standing ovation.