Bad Medicine   

How the media helped the medical establishment cast doubt on innovative approaches to fighting AIDS.

In his new book, "Acceptable Risks," Jonathan Kwitny chronicles the story of two men, Martin Delaney and Jim Corti, who sacrificed their careers to help find life-extending drugs for AIDS patients. In the process, they waged a citizens' revolt against the establishment medical community, large drug companies and the Food and Drug Administration. Kwitny set out to tell a saga of two unlikely heroes, but in the course of doing research for the book came across numerous examples of inaccurate reporting that harmed their reputations and often undermined their efforts.
 

When Martin Delaney and Jim Corti began smuggling drugs across the U.S.-Mexican border in the mid-1980s, their efforts were considered by many to be a labor of love. They weren't bringing in heroin or cocaine. Instead, they were smuggling promising anti-AIDS drugs, sold over the counter in Mexico but not available in the United States. Neither Delaney nor Corti, who are both gay, was infected by the AIDS virus. Yet they were surrounded by sick friends hoping for anything that might extend their lives — medicines they weren't getting from their doctors or the government, which approves AIDS drugs.

It was the beginning of a decade-long crusade that would challenge and change the medical establishment's and Food and Drug Administration's way of doing business. The two men's efforts quicklyexpanded beyond buying and selling drugs. They organized doctors and patients in an underground network to test the safety and efficacy of potentially useful drugs years before the FDA would have been able to. Standard drug approval procedures typically consume a decade and hundreds of millions of dollars.

Delaney, Corti and others involved with the tests proved that research could be done much faster and cheaper than in the official process, and that many drugs could be offered safely to patients much earlier. They also built a case for a testing system that, while less precise than the FDA's, was still scientifically adequate for many purposes. Many more lives would be saved by speedier access to drugs, they argued, than would be lost by overly hasty access, especially in cases involving deadly diseases such as AIDS. Delaney has since been applauded for his efforts by those benefiting from the drugs and leading government scientists, including some at the FDA. Corti continues to work underground investigating new drugs manufactured in other countries.

But in the early days, Delaney, a successful bank consultant living near San Francisco, and Corti, an artist working as a nurse in Los Angeles, were treated as outlaws by the pharmaceutical industry. They were vilified by research doctors who, though dedicated to scientific service, had grown accustomed to and made their livings from the drug testing system that Delaney and Corti were threatening.

Unfortunately, their efforts were also undermined by the press. Print and broadcast reporters were all too eager to accept the views of the FDA and research doctors with a financial stake in drug testing. These scientists, who often work at university teaching hospitals, rely on research grants provided by drug companies and federal agencies such as the National Institutes of Health.

While the media had every reason to be skeptical of Delaney's and Corti's methods, they also had reason to be skeptical of the FDA. By accepting without question statements made by the FDA and establishment scientists, the media, inadvertently or not, became a mouthpiece for the FDA and the drug industry. Inaccurate coverage damaged the reputations of Delaney, Corti and their supporters in the medical profession. Worse, it contributed to delays in testing and approval that ultimately caused more suffering for the patients Delaney and Corti were trying to help.

"What [Delaney] was trying to do was establish a principle that things needed to be studied quickly and scientifically, [while providing] access on a wide scale to people in need," says Samuel Broder, director of the National Cancer Institute. "What people did was focus on the negative parts of that without providing balance. It's very difficult to tell two sides of a story if you only have one shot at a piece and you have a deadline..and your editor may decide you've already done a story on that and you can't go back to it... It [inaccurate coverage] may be difficult to offset."
 
 

Ribavirin, an anti-viral drug, and isoprinosine, an immune system booster, were developed in California but are unavailable in the United States. Both drugs have long been sold over the counter in dozens of other countries for colds and other ailments. Around 1984, rumors spread among a growing network of HIV-positive patients that the two drugs made AIDS patients feel better and delayed the onset of the disease in HIV-positive patients. In addition, the two drugs were relatively free of side effects in suggested doses. Delaney and Corti, independent of one another, began smuggling the two drugs into the country and distributing them at cost.

As patients clamored for the drugs, Oakland Tribune reporter Peter Aleshire wrote the first story in the mainstream press in September 1985 about the expanding smuggling operation. Delaney agreed to talk to Aleshire in the hopes of spurring change in the FDA approval process. Aleshire's article about Delaney was sympathetic, and soon more stories followed in other news media outlets portraying Delaney and Corti as bringing hope to the hopeless.

By 1985, the FDA had approved clinical trials using ribavirin against HIV; Newport Pharmaceuticals, isoprinosine's manufacturer, was also preparing tests. Although Delaney and Corti found that the drugs seemed most effective when used in combination, the FDA approval system discouraged testing the two drugs together until they had been tested and approved separately.

Frustrated by the official process, Delaney decided to set up a community-based guerrilla drug trial in San Francisco, using cooperative doctors and 400 volunteer patients taking ribavirin with or without isoprinosine. He solicited press coverage to reach potential funders, doctors and patients.

On October 22, 1985, the press turned out at the Valencia Rose, a popular club in the largely gay Castro section of San Francisco, for the inauguration of Project Inform, a nonprofit group founded by Delaney and others to educate the public and advocate new drugs. Surprised reporters expecting the usual ragtag community protest group were greeted by men in business suits handing out press kits.

Reporters from the San Francisco Chronicle and Examiner raised questions. Could you get scientifically acceptable data this way, without government supervision? Had a community- based drug study been done before?

No, Delaney told them, this type of test had never been done. Nor, apparently, had it ever been attempted. "The federal FDA has been treating AIDS as business-as-usual," he said. "Given the nature of this disease, that's just not adequate. Years go by, and we're told to wait for results, even when the diagnosis says we've got six months to live.

"No matter what the medical authorities say, people are using these drugs. What we want to do is provide a safe, monitored environment to learn what effects they are having."

Reporters found doctors who disparaged the experiment. "It seems to be a very well-intentioned effort and I wish them well," Dr. Paul Volberding, then chief of oncology at San Francisco General Hospital, told the Chronicle. But, he added, "to be honest, I don't think the chances are very good that they can find anything that is very convincing."

Delaney, however, was happy with the coverage. The project had been treated with respect. Peter Aleshire's continuing sympathetic treatment in the Tribune helped the rest of the press accept Delaney's underground approach. In his first attempt at a community trial, Delaney failed to get the funding and support from physicians he had wanted. But patients who had taken the two drugs reported substantially less illness than those who hadn't.

In late December 1986, an employee of ICN Pharmaceuticals, ribavirin's manufacturer, told Delaney of dramatic success in FDA-supervised tests at Cornell University, M.D. Anderson Hospital in Houston and the University of Southern California. The tests showed that HIV-infected patients developed AIDS much less frequently if they took ribavirin. That didn't mean patients taking ribavirin wouldn't ultimately develop AIDS, but it did mean they were likely to stay healthier much longer.

ICN announced the results at a press conference. The New York Times ran a front page story on January 10, 1987, written by physician and medical writer Lawrence K. Altman: "In a six-month study, the drug ribavirin appeared to halt the progression of an early form of infection caused by the AIDS virus, a drug company announced today. It is the first time that a drug has seemed to prevent AIDS from developing in patients with early signs of infection with the virus."

The next Monday's Wall Street Journal put a different spin on the story. Reporter Michael Waldholz said AIDS researchers were calling the ribavirin test results "sketchy," "inconclusive" and "premature." The article quoted three critics, including Volberding and his assistant, Donald Abrams. The two dismissed the notion of any quick use of ribavirin.

Delaney was irate. "Nobody mentions that these guys earn their living in part from drug-company grants to do FDA-approved research," he complained. "They've been down on ribavirin for years because we're importing it outside FDA channels. The press quotes them as if they were unbiased experts who have found flaws with ICN's research — which they haven't seen yet."

Faced with the most promising test results yet for an AIDS drug, the FDA might have been expected to forge ahead. Instead, the agency sought to discredit ribavirin and ICN.

In September 1986, the FDA had placed its prestige behind AZT, a drug developed in government laboratories and licensed to the drug firm Burroughs Wellcome. The FDA and Burroughs Wellcome stopped the AZT trials midway to hold a press conference announcing promising initial test results. It was the first drug approved for AIDS. Newsweek ran a full page story on AZT and unapproved drugs, and asked Delaney why AZT had been approved when others had not. "The government looks into a few narrowly defined products from the old-boy network," he told the magazine, "and everything else gets the door slammed in its face."

While the FDA and AZT got positive play in the press, when ICN held its press conference in January, they were criticized. For example, an article in the Wall Street Journal quoted medical authorities who suggested that press conferences were an inappropriate way to preempt peer-reviewed publication; the story didn't note that the FDA and Burroughs Wellcome had just used the same tactic to promote AZT.

Meanwhile, Delaney and others believe, legislative aides from Michigan Democratic Rep. John Dingell's Energy and Commerce Subcommittee on Oversight and Investigation were planting negative stories about ICN. The stories, which quoted anonymous congressional staffers, appeared throughout early 1987 and alleged everything from plots by ICN's president to inflate ICN stock to doubts about the test results.

In February, the Journal quoted a letter to the FDA from Dingell detailing allegations that ICN had covered up harmful side effects ribavirin had on babies being treated with it for a lung disease. The allegations were printed without a response from ICN, whose officers were said to be unreachable. No evidence was ever produced to support the claim, and the FDA never withdrew or modified its approval of an aerosol use of ribavirin for the lung disease. There was no follow-up story.

The same month, the Journal also reported that the Securities and Exchange Commission had initiated "an investigation of possible stock manipulation and insider trading of ICN securities." The investigation was eventually dropped. No exoneration was ever printed.

A month later, Dingell held televised hearings at which the leading AIDS drug officials of the FDA, including then-Commissioner Frank Young and Ellen Cooper, who reviews AIDS drugs, accused the ribavirin researchers of having biased their test results. According to the officials, the researchers had overloaded the placebo group with sicker patients while giving ribavirin to patients who were healthier and inevitably tested better.

The FDA officials also released data showing that in one study significantly more people died after taking ribavirin than after taking the placebo. Their conclusion: Not only was ribavirin useless in slowing the onset of AIDS, it might actually cause the onset of AIDS.

Dr. Peter Heseltine, then a ribavirin researcher, was outraged that the charges were made in the privileged setting of a congressional hearing. "If Cooper had [made those charges] anyplace else I would have sued [her] for the rest of her life," he said. "When the FDA investigated, they found no evidence that this was the case whatsoever."

Nonetheless, Dan Rather announced on the "CBS Evening News" that the government had found that an AIDS patient was more likely to die after taking ribavirin. Other broadcast and print outlets, including the New York Times and the Wall Street Journal, published long stories with the FDA-Dingell spin.

Eventually, some of the world's leading statistical experts endorsed ICN's data. The FDA's own investigation found no bias in the test procedures, which the agency never reported publicly. The data linking ribavirin to patient deaths was an aberration that had already been rectified with more complete data, beforethe FDA took it out of context at the hearing. (Young now says all available data was taken into account before he testified, and that it would "not be appropriate" for him to comment further.)

Today, Dingell's office says that Patrick McLain, who headed the committee's investigation, has left and no one else could answer questions. McLain, reached at his private consulting firm, defended the investigation but declined to comment on particulars.

Ribavirin was dead. Rather than face the same firing squad ICN had, directors at Newport Pharmaceuticals, which manufactured isoprinosine, dismissed the executive who had been its patron and backed off promotion of the drug in the United States. The results of a large Scandinavian trial, published in 1989, found isoprinosine as effective against HIV as AZT with far fewer side effects. It has long been Delaney's contention that all three drugs used together or in rotation, along with more recently available drugs like ddC and ddI, provide the best protection. Many doctors are now beginning to accept his drug combination theories.
 
 

Over the next few years, Delaney established quiet, productive relations with many FDA staffers who had come to appreciate his contributions. Corti says he remained underground, smuggling a wide variety of drugs from countries on four continents. In May 1989, Delaney and Project Inform began secret trials of Compound Q, which Volberding and other University of California researchers were also investigating. The university's FDA-supervised trials were still in the test tube stage and were expected to last years.

The drug, used in China to induce abortions and to treat uterine cancer, was already being acquired by patients who were purchasing it abroad or distilling it from its source, the root of a Chinese cucumber sold in Chinese grocery stores.

Unlike ribavirin and isoprinosine, however, Q could have severe, immediate side effects. The root contains toxins that must be removed in manufacturing; anyone trying to distill it themselves, as some did, could die. The possibility was further incentive for Corti and Delaney to test the drug quickly.

At considerable personal risk in the days of Tiananmen Square, Corti says he bribed a Chinese factory manager to give him the drug, and repeatedly smuggled it out of China. In April and May of 1989, Delaney enlisted doctors to conduct trials in strict secrecy, believing premature publicity might encourage dangerous unsupervised use. Corti helped administer the drug.

The underground tests were conducted by respectable doctors and scientists. Dr. Michael McGrath, a member of Volberding's research team who had discovered Q but was dissatisfied with the glacial pace of the university's testing, agreed to advise Delaney and Corti on the condition his name would be kept confidential. (He has since gone public.) One high-level FDA official was also informed about the trial and given a copy of the test procedures. The official assured Delaney that he wanted quick data on Q and no harm would come to the group.

Delaney's group ordered lab studies of the drug on animals; in just a few weeks the studies turned up evidence the university team hadn't yet discovered. Because of Q's potential toxicity, Delaney's first human tests were with sicker patients who were given half the dose recommended by the Chinese.

Hank Plante with the CBS affiliate in San Francisco had been covering AIDS for years. He knew a treatment experiment was underway and that Delaney was involved. "We know the story and we can go with it on tonight's news," he told Delaney in the spring of 1989. "It would be better with your participation."

Knowing the uproar such a story could trigger, Delaney offered him terms that Plante accepted: With the patient's permission, he could film the trials, but the piece wouldn't be aired until Project Inform gave the go-ahead. "Or until somebody else goes with it," Plante added. Among others given access under the same terms were Robert Bazell of NBC News, Peter Jennings (who was working on an AIDS documentary series for PBS) and Gina Kolata of the New York Times.

In June 1989, a month into the test, a patient died. Robert Parr, very sick to begin with, had been observed overnight in a hospital-like setting after receiving the drug. A day after being sent home, he developed a near-coma and was rushed to a hospital, where Dr. Alan Levin, the AIDS specialist Delaney had chosen to run the San Francisco end of the study, met him. Levin administered an antidote recommended by physicians who had completed trials of similar compounds.

Parr seemed to pull out of the reaction and three days later was moved from the emergency unit. By the end of the week, nine days after the Q injection and long after the drug had left his system, Parr seemed fine when Levin chatted with him during dinner. Levin left town. That night, Parr vomited in his sleep and was found "blue" — alive, but short of oxygen.

The hospital called Levin's partner, Dr. Larry Waites, and told him Parr was breathing through a tube to allow a clean air passage and clear his lungs. When Waites arrived at the hospital two hours later Parr was dead. Twenty minutes earlier, the resident on duty had removed the breathing tube on orders from Parr's brother, who had power-of-attorney authorizing him to stop heroic life-support measures. Waites, who should have been consulted before the tube was pulled, insists Parr had a good chance of recovering.

Delaney was deluged with calls from the press. Bazell said he had just returned from vacation when he got a call from a doctor telling him a patient had died after experimenting with Q. "It's being widely discussed," Bazell said. "If all these doctors are carrying on about it, it's no longer a private story. I'm going to run with it."

Delaney tried to convince Bazell to maintain secrecy, pointing out that many patients died in the FDA-approved trials of AZT and other drugs; these deaths weren't disclosed.

"You guys have been manipulated the whole five years of the AIDS crisis," Delaney argued. "Parr was one of 150 people who died of AIDS Saturday. Parr died trying to save his life. The most important thing is that Q didn't kill the guy."

Bazell wouldn't budge: "I thought the patient's death changed the equation, and he didn't think so."

After learning Bazell had broken the embargo, Plante called with the same decision. They both aired stories that evening. Kolata was angry that Delaney had given what she thought was an exclusive to the networks.

The "death-in-secret-underground-AIDS-study" story led the June 26 "NBC Nightly News" and got prominent play elsewhere. The next morning Delaney appeared on the "Today Show," where Delaney's group was charged with skipping safety tests leading to Parr's death.

"We aren't skipping those tests, we're performing them ourselves," Delaney told host Jane Pauley. He was confronted on a live hook-up with Volberding, head of the AIDS team that had been planning for two years for a major study of Q.

Unaware that one of his staff members had helped design Delaney's test, Volberding accused Delaney of encouraging desperate people to take Q and causing "the disasters that seem to be happening by assuming that we know the dose of this drug." (Actually, patients were begging to get into Delaney's study and were being turned down.) Volberding predicted that FDA studies would be held up because of "reports of these severe and sometimes fatal side effects of this unauthorized use of the compound."

"That's fiction," Delaney broke in, but was told they were out of time.

A July 28 front page story in the Wall Street Journal by Marilyn Chase, a highly-respected science writer, was headlined, "Activist Risk-Takers May Gain Legitimacy in the War on AIDS." She noted that Delaney's group was "helping push forward a revolution in American drug development" by forcing a new look at "the issues of the speed of testing and access to drugs." But overall, the story depicted Delaney and Levin as reckless amateurs who at best might scare responsible professionals into working faster.

The top of the story was devoted to Parr's death. Chase reported that Parr had left the clinic the day after his infusion, went into a coma that same day, and died the next. In fact, more than a week had passed, Parr seemed to have recovered, and, according to Levin the drug had left his system.

Although the story didn't specifically say Q had killed Parr, it quoted a number of people from the medical establishment implying that amateurs overdosed him.

The Journal defends its story, saying that since the hospital wouldn't perform autopsies on AIDS patients, no one can be sure what caused Parr's death.
 
 

To some extent, Delaney's group was the victim of its own need to keep McGrath's role secret. But animal studies and descriptions of the care Delany's group took in running the trials were available. No one reported them, even after Delaney held a press conference following Parr's death.

On September 19, 1989, Delaney, Corti and the doctors working with them announced the results of the Compound Q study to a cheering crowd in San Francisco. Q wasn't the hoped-for cure, they said, but many patients had improved immune cells and lower virus levels. More research was needed to see why the drug seemed to work in some cases and not others.

That same day, Gina Kolata's piece led the "Science Times" section of the New York Times under the headline, "Critics Fault Secret Effort to Test AIDS Drug — Third death may undermine attempts to shortcut time-consuming Federal rules." Scott Sheaffer, a New Yorker who had taken part in the Q trial in July, had died; Kolata blamed the death on the secrecy surrounding the trial. She said he was the third person to die who took part in the Q tests, and cited Parr and another man in the trial who died not from Q, but from an overdose of morphine to escape the pain of an AIDS-related cancer.

At the top of her story, she stated that the Q study was "sharply criticized by many advocates for people with AIDS, ethicists..and leading academic AIDS researchers... Unlike federally approved studies," the Q study hadn't established procedures to protect "desperate patients..from being harmed by the research.

"The study did not start with a very low dose of the drug to look carefully for evidence of dangerous side effects... In addition, because of the secrecy of the study, the doctor who administered the experimental drug to Mr. Sheaffer did not tell either of the two hospitals where he was admitted that he had taken the drug, leading doctors to provide what may have been inappropriate treatment."

Only after a lengthy indictment of the trials was Levin quoted saying Sheaffer had participated voluntarily and that there was no evidence Q had caused his death.

The article was accompanied by two pictures. One, of Delaney, neatly-groomed and in business attire, had someone else's name on it. The other, captioned with Delaney's name, showed a wild-eyed, bushy-bearded man who looked like a turn-of-the-century Russian revolutionary.

Sheaffer died more than six weeks after taking Q. Over the previous 18 months he had had three bouts of AIDS-related pneumonia. Sheaffer had begged Barbara Starrett, the doctor administering the drug, for a chance to take part in the Q tests. After his first dose, he became delirious.

Starrett admitted Sheaffer to a hospital and told doctors that he had taken an experimental drug. (She didn't name it and wasn't asked.) These facts are reflected on Sheaffer's hospital chart, but not in Kolata's report. Howard Grossman, a hospital physician who confirmed the information on the chart for Kolata, says he was outraged by the story. He says he called her the next day and "told her..that none of the stuff [she had written] was true." Grossman says Kolata just said she stood by her story.

Rather than getting inappropriate treatment, as Kolata wrote, Sheaffer recovered and walked out of the hospital two days later. A few days after that, he attended another Q session and on videotape said he was fully recovered. He looked normal and bantered with other patients. He also said he wanted more Q, but because of his previous reaction, Starrett refused. Starrett says she begged Kolata to watch the tape before the story was published but Kolata refused. Kolata declines to comment about the videotape.

On August 28, after a second hospitalization for a problem unrelated to Q, Sheaffer died in the hospital of what could have been any of several AIDS-related causes. Dr. Jeffrey Wallach, Sheaffer's personal physician, told Kolata two days before her story appeared that there wasn't any reason to believe Q contributed to Sheaffer's death. Wallach said he hadn't told the second hospital about Q because he didn't think it was relevant and for privacy reasons, Sheaffer asked him not to. Wallach says he stressed to Kolata that Starrett was unaware of Sheaffer's new condition and second hospitalization, so she couldn't have told the second hospital about Q. None of this appeared in Kolata's story.

Mark Harrington, a well-known New York AIDS activist, also says he was misquoted. Kolata quoted Harrington saying Sheaffer "was healthy and stable" before his Q infusion, then "his decline was so rapid. It was like nothing I have ever heard of in AIDS." Harrington insists that he told Kolata he had never seen Sheaffer, but she asked him for a comment based on a description provided by Sheaffer's roommate. He says he supplied a general comment not intended to be a criticism of Delaney's study.

Kolata also said the death of Parr and another patient in the Q study had "provoked a federal inquiry which is still underway." In fact, the "inquiry" had already been dissolved. Starrett says no government authority has ever questioned her about the incident.

Delaney and Starrett both wrote letters of protest to the Times; neither was printed. Fearing the ruin of her career, Starrett stopped administering Q and other drugs for more than a year.

Kolata says she stands by the accuracy of her story, but after more than two years she doesn't remember details well enough to dispute specific charges of inaccuracy.
 
 

The true story of Delaney's accomplishments in the Q trial never appeared in the mainstream press, even after it was distributed to the FDA and published in a peer-reviewed article.

Delaney and his doctors were invited to Washington to present their results to FDA officials and executives from the pharmaceutical companies involved. Sandoz, a large drug manufacturer, was so impressed with Delaney's work that it gave his group $250,000 to continue its study of Q. Readers and viewers of the exposés on Delaney never learned about that.

The FDA has adopted a new system that often allows doctors to more easily give dying patients drugs that are still being tested, largely thanks to Delaney and Corti. Delaney is praised for his medical knowledge and personal heroism by the government's leading AIDS research scientists. "I know Marty Delaney very well," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases at NIH. "He is very careful, very intellectual and very scientific in his approach."

"Every person who is successful and accomplished is going to have detractors," adds Samuel Broder of the National Cancer Institute. "Marty has accomplished a great deal and certain people are going to be envious... Every great person runs into that." Delaney has since served on FDA and NIH advisory committees.

None of these accomplishments, however, seems to have the same news value as an interim, out-of-context report about deaths of patients on ribavirin, or the deaths, from among thousands of AIDS victims, of three who had experimented with Compound Q.