San Francisco Chronicle - Wednesday, June 28, 1989
Randy Shilts, National Correspondent

He was convinced that eventually it would make a terrific movie, with smugglers rushing Chinese vials from a country locked in political turmoil, doctors putting their careers on the line, and patients pondering the decision of whether to gamble on a new, untested drug in a last-ditch effort to save their lives.

For Delaney and other participants, the controversy that has erupted over yesterday's disclosure of the trials is but the latest act in a saga that reflects the dramatically changing environment in which AIDS research is now carried out.

"This is the story of how we'll alter the way drug trials are conducted in this country - not only for AIDS, but for all diseases," said the charismatic Delaney, the 43-year-old key organizer of the underground trial.

Word spread among AIDS organizers nationwide in April when University of California at San Francisco researchers announced they had a drug that appeared to selectively kill immune cells infected with HIV.

If the drug worked in people the way it did in the test tube, organizers knew, it could be a virtual cure.

They also knew that the scientists at San Francisco General Hospital who were conducting the first phase of tests said it could be nine months before they could produce results. Private Studies

Heartened by the potential of an extraordinarily promising AIDS drug and frustrated by the time it would take to get official studies moving, Delaney and other organizers of AIDS programs decided to take the unprecedented action of beginning their own studies.

In years past, there had always been complaints about the time it took to get government AIDS studies started.

But this year was different. A handful of doctors were willing to buck the medical establishment and cooperate with guerrilla science. Statisticians were eagerly helping design expedited studies, and lawyers were volunteering to figure out how to circumvent legally the government agencies that strictly regulate such tests.

As co-director of Project Inform, the nation's leading AIDS treatment information organization, Delaney knew all the players. He had meetings and teleconferences to put together what may be the most elaborately designed underground drug trials in the history of American medicine. Test Volunteer

About the same time, Bob Barnett's headaches started to return. Last summer, he had had those headaches, too, as he was falling ill with cryptococcal meningitis. Barnett almost died from this fierce HIV-related brain infection, and he knew he was likely to suffer an agonizing relapse.

Several other friends had died from the same disease in recent months, and with every blood test, the 36-year-old AIDS sufferer was helplessly watching his immune system disintegrate further.

All these things were on Barnett's mind when he contemplated whether to enter the study.

"I knew it might be two years before the drug became available," said Barnett, a former sales manager for KYUU-FM radio. "I just barely escaped with my life last summer. Could I afford to wait? I didn't think so."

For doctors who were beginning to enlist in the study - in Los Angeles and New York, San Francisco and Miami - it was also a time for crucial decisions. Their licenses to practice medicine hung in the balance.

In San Francisco, the decision became clear for two doctors when they saw patients beginning to appear who had toxic side-effects from the Compound Q with which they had injected themselves, usually in their living rooms.

"It was clear what was happening - we've seen it with so many drugs in the past," said Dr. Larry Waites, a physician with 700 HIV-infected patients in his private practice.

"Already, we were hearing that thousands of doses of Q were being imported, and other contacts told us they were getting ready to import hundreds of thousands more," he said. "We looked ahead to hundreds of people taking this very strong drug and dying. We wanted to find out fast whether it worked. We couldn't wait for the General study." Responsibility to Patients

Said Dr. Alan Levin, another doctor involved in the study, "Our first responsibility is to our patients. Not to the government. Not to the medical establishment. That's what decided it."

The trick for lawyers was to figure out how to conduct a study within the letter of the law, knowing full well that they were pushing the limits of laws that demand approval of the Food and Drug Administration for investigational new drug tests.

The decision: Doctors would not give the drug to patients per se. Instead, patients would present the drug to their doctors and ask that their treatment be monitored and supervised.

"A doctor can care for his patient," said Curtis Ponzi, the lawyer who advised Levin and Delaney on the construction of the study. "The study is entirely within the law."

To protect doctors from liability lawsuits and to fulfill the ethical responsibilities of informed consent, Ponzi worked out a 13-page questionnaire that was presented orally to each patient in a videotaped session before it was signed, on camera, and witnessed. Videotape Session

During his videotaped session, Bob Barnett's voice grew impatient when he was asked for the fourth time whether he understood that he could die from taking Compound Q.

"I've seen a lot of people with cryptococcal meningitis who aren't on the planet any more," he answered.

At the end of the session, Barnett asked that his heirs and surviving friends understand and respect his decision to participate in the study - meaning that they should not sue anyone if he died.

Meanwhile, "an experienced smuggler" was in China trying to secure a purified version of the trichosanthin protein, which is the active ingredient of Q.

"There were payoffs in videocassette players and Sony TVs from Hong Kong," Delaney says. "The day before the Chinese declared martial law and started closing off the borders, we were able to get a large supply. It was very close."

The drug came in cheerfully colored red-and-white boxes, a clear liquid in small glass ampules. Laboratory tests at Genelabs, the manufacturer of GLQ-223, confirmed that this substance was chemically identical to the American drug undergoing official testing, Delaney says, a point confirmed last week by a UCSF researcher developing the drug.

The night before he was to go into the clinic as part of the third group of San Francisco volunteers to be injected from one of those glass ampules, Barnett grew very nervous.

"I had the feeling you get when you're getting on a roller coaster and you think, "Here it goes,' " he recalled yesterday. "When I woke up the next morning, I was very excited - for all of us affected by this disease, if it works." First Injection

Every 15 minutes, nurses came into the room where Barnett and four other volunteers were being given first of three treatments of the drug by intravenous infusion. Vital signs were checked. Blood was drawn hourly.

"We wanted this study to be able to pass any FDA audit - it had to be absolutely perfect," Delaney said.

Also to ensure the reliability of the study's results, an observer from the American Foundation for AIDS Research sat in on the infusions and blood monitoring.

In the days after the shots, Barnett experienced nausea and fevers. Now, he says, "I feel like I've got a lot more energy than I did when I started. I get much less fatigued and need less sleep."

His assessment is shared by other study subjects and by early laboratory work that indicates a decrease in HIV viral activity. Delaney said he does not expect definitive results from the tests until 30 to 40 days from now. Support for Project Inform

Even as scientists condemn the unofficial trial and the FDA launches an investigation, other forces are lining up behind Project Inform.

The growing number of militant AIDS organizations that have coalesced in the past year are promising to battle any attempt by the FDA or other federal agencies to try to halt such unofficial studies.

"All hell will break lose if they attempt to crack down on them," said Larry Kramer, an organizer of the New York chapter of the AIDS Coalition to Unleash Power (ACT UP). "It's heroic what they're doing, and there is an immense amount of support for them."

UCSF researcher Dr. Paul Volberding, for one, bemoaned the polarization between traditional science and community organizations that is arising from this controversy. "In the end, we all want to get to the same place," he said. "We shouldn't have this separation."

Other researchers, however, said the Compound Q trials are just the beginning of what will happen with new AIDS drugs. The sophisticated networks of patients, doctors and community organizers increasingly will take treatment issues into their own hands, they said.

"No matter what happens with Q, we'll see this again when the next promising drug comes along," says Dr. Marcus Conant, a veteran UCSF AIDS researcher. "The last chapter in the story has not been written, by a long shot."

Always watch for outdated information. This article first appeared in 1989. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1989. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .