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    Articles > The Queen Of AZT


To our only weapon against AIDS, Margaret Fischl owes everything:
Her fame and her infamy
By Elinor Burkett
Miami Herald

23 Sept. 1990 Dr. Margaret Fischl was 32, one year out of residency - an obscure assistant professor at an obscure medical school in Miami. She was a hard-working, serious young woman without any particular spark or brillance. She had been a good student at the University of Miami, and looked to be on course for an average career in academic medicine. Her research was hardly on the frontiers of medical science. The one study she had published was entitled: "An index predicting relapse and possible need for hospitalization in patients with acute bronchial asthma."

Then came the young men whose bodies disintegrated before her eyes, refusing to respond to the most aggressive treatment medicine could devise.

It was then that Dr. Fischl did something out of the ordinary, something that would mark her for the rest of her life: She paid attention.

Just eight years later, Margaret Fischl flew to San Francisco to reap the benefits of her foresight. She had been invited to appear before the 12,000 delegates to the Sixth International Conference on AIDS to give a major address before some of the greatest medical scientists in the world. On the speaking platform with this young woman, a general practitioner, were highly specialized virologists and immunologists from three continents and at least 10 years her senior. She stood among them as an equal, one of the most powerful members of the AIDS research establishment in the United States. It should have been a moment of honor and glory.

But it was more than that: Fischl was escorted onto the stage by a bodyguard of burly men. Outside the convention center she was being tried in absentia by the very people she had presumably dedicated her life to saving. The charge: "Crimes against people with AIDS."

"Guilty, guilty," the crowd of AIDS activists from across the nation cheered after the open-air mock court accused her of putting careerism before compassion, self-interest before science.

The intensity, and irony, of the moment says a lot about the life and work of Margaret Fischl, and about the agony of the national effort to stem a tide of death.

As she strides purposefully across the campus of Jackson Memorial Hospital, Margaret Fischl turns few heads. The tall, serious woman radiates none of the power and authority she has earned. She slumps at the shoulders as she walks, as if to disguise her height. Her demeanor is self-contained, almost timid; she eschews calling attention to herself.

In the early '80s, when the first young men began showing up at Jackson with weird cancers, exotic pneumonias and baffling brain infections, Fischl, still a resident in general medicine at the University of Miami, enlisted in the struggle against AIDS. The disease still had no name. She had no way of knowing that it would not kill the doctor, along with the patient.

Fischl became a one-woman crusade in her hospital, her university, and the state Legislature for funds to educate the public to prevent what has since become an epidemic and to build a treatment program to cope with it. She was the first person in Florida to try to awaken both physicians and politicians to the looming threat. She was one of the first researchers in the nation to warn about heterosexual transmission of the virus.

That should have made her an American heroine. But the fight against AIDS is not like the race for a polio vaccine, or the Manhattan Project. It is a politicized battleground in which the disease's primary victims are suspicious of and increasingly hostile toward the very people who are charged with saving them.

The conflict was inevitable from the moment that AIDS became known as a "homosexual disease." While it has become virtually taboo to express prejudice against any other minority group in American society, in many quarters homosexuals are still openly scorned.

As some fundamentalist ministers preached that AIDS was "God's judgment against homosexuality," the president of the United States refused to so much as mention the word for the first six years of the epidemic. There were serious proposals in state legislatures to quarantine known AIDS carriers, or even brand them. The disease spread unchecked for five years before the federal government began a coordinated research effort aimed at stopping it.

So even when the effort began in earnest after years of neglect, thanks to people like Margaret Fischl, many AIDS activists remained skeptical. They had an attitude: They were not prepared to accept just any crumb thrown in their direction as manna from heaven.

And the biggest crumb of all was AZT.

The Bottom Line Is Death

AIDS is more than a disease: It's a multibillion dollar growth industry.

Government bureaucrats compete to make sure their agencies get a share of the $3 billion the federal government is doling out annually for AIDS education, treatment and research. Private scientific laboratories line up at the government trough for some of the millions the administration and

Congress are handing out. Scientists race for a cure that they know will carry the Nobel gold. Pharmaceutical companies scramble to strike their own mother lode in the form of chemical compounds that prove deadly to the AIDS virus, and not to the AIDS patient.

Given the more than eight million people worldwide infected with a communicable killer disease with no cure, such a drug would have seismic implications for the bottom line. Even the prospect has pharmaceutical stock prices as jumpy as a Mexican hat dancer.

But before the cash can flow, a drug has to be anointed by a tiny group of scientists totaling no more than two dozen, who by controlling the AIDS Clinical Trials Group have unprecedented power to set priorities, hand out the federal funds, and evaluate the progress of AIDS drug research.

A drug company could theoretically strike out on its own, without the support of these scientists. But the expense, and the odds against success, would be so high that the possibility is likely to remain theoretical.

As a practical matter, without this group's blessing, there will be no stock surges, no windfall profits, no big headlines in The Wall Street Journal.

Few corporate executives are holding their breath. After four years, and a billion tax dollars, the national effort is monopolized by one drug-and one drug company. In 1985, a giant British pharmaceutical firm called Burroughs Wellcome pulled an old compound out of its stockroom. It was an extract from-of all things-herring sperm. Originally developed in 1964 as a possible cancer treatment, it had been discarded as too toxic. But 20 years later, the same scientists who would become the gatekeepers of the national research effort declared AZT a promising AIDS treatment.

The effect was galvanic-both on the thousands dying horribly in and out of AIDS wards, and on the corporate fortunes of Burroughs Wellcome, which has exclusive rights to produce AZT for 17 years. The company's profits-which were already considerable from the sale of drugs like Sudafed, Empirin and Actifed-doubled in two years to almost $200 million. Then in 1989, the federal government announced that AZT, then the most expensive prescription drug ever manufactured, might also be effective in delaying the onset of AIDS symptoms in apparently healthy people infected with the AIDS virus.

The company's stock surged by 33 percent in a single week. The Wall Street Journal estimated that by 1992, Burroughs Wellcome will have annual AZT sales of $1.2 billion-half of that pure profit.

Despite the windfall, the same scientists who gave AZT credibility voted to allocate millions more tax dollars to fund the drug's continued testing-a program that has made it potentially even more profitable.

Meanwhile, most of AZT's potential competitors languish on the shelves untested. Virtually all the federal research money is already taken: AZT research. Even if a big drug company was willing to pay for testing a new drug on its own, virtually all the labs and the scientists are busy: AZT.

Such are the fruits of gaining a stranglehold on the biggest government medical research project in history. For its good fortune, Burroughs Wellcome can thank the elite group of scientists in the Aids

Clinical Trials Group, and most especially, it can thank Margaret Fischl.

And for the same reasons, a growing number of scientists, physicians, AIDS patients and their families damn her.

"As AIDS villains go, Margaret Fischl is pretty low on my list," says Michael Callen. "She's a middle-level, third-string scientist who the big boys shoved out front. But I think that my people have paid a hellish price for AZT. To the extent that Margaret is part of that, despite her best of intentions, she is complicit in the deaths of thousands."

An extreme view from an ironic source. Michael Callen was diagnosed with AIDS in 1982. "Six to 18 months," the doctors in New York gave him. Of the thousands of people who have been handed that death sentence, nobody else has lived as long. And Callen has survived with no help from AZT. In fact, he is convinced his refusal to take AZT is the main reason he is still alive.

In his forthcoming book about long-term survivors of AIDS, Callen writes: "If I saw a friend about to drink a glass of Drano, I would without hesitation knock it from his hand. I consider AZT to be Drano in pill form."

Callen has been worried about AZT ever since the patients in the first major study of the drug-many of them friends of his-began turning up with anemia. Transfusions became part of their weekly schedules. Then his friends started suffering from nausea and insomnia. Their muscles began to ache, and then disintegrate until there was literally nothing but skin and bone. Callen was used to seeing his friends get sick, but this was different. The medicine seemed more like poison.

But that's not what researchers-led by Margaret Fischl-reported. AZT Prolongs Life of AIDS Patients the headlines declared. During the study period, the findings showed, subjects taking placebos were 19 times more likely to die than those taking AZT.

Still, Callen remained suspicious. Then in late 1988, he saw the report of a team of French researchers in the British medical journal Lancet. These scientists had studied AZT, too, but they described its benefits as "disappointing": The drug so damages the blood cells that the average patient could expect only six months' benefit before the therapy began to backfire. The American researchers had had no way of knowing that: They ended their study abruptly before any of the subjects had taken the drug for that long.

About the same time that Fischl was delivering her paper in San Francisco this summer encouraging the use of AZT for 650,000 Americans infected with the AIDS virus but not yet sick, the National Cancer Institute announced that almost half the people who have taken AZT for three years can expect to develop an aggressive form of lymphoma, a deadly cancer.

AZT's supporters rushed to the defense of the drug.

AZT does not cause lymphoma, Fischl insisted in San Francisco. "I cannot fathom why AZT would be causing lymphoma. It's just that people are living longer," and therefore increasing their chances of contracting lymphoma unrelated to AZT.

"Whatever is going on, it's certainly not as simple as: AZT causes lymphomas," said Paul Volberding, head of the AIDS program at San Francisco General Hospital and one of Fischl's closest colleagues on the various AIDS studies.

"If used correctly, AZT is an extremely good drug," says Dr. William Reiter, a Ft. Lauderdale physician who specializes in AIDS treatment. "You can't rule out the possibility it is causing lymphoma, but I don't believe it."

The problem is that no one is sure: No one has compared the lymphoma rates of AIDS patients who have refused to take AZT with those who have not. No one has studied differences between the patients who reacted badly to AZT and those who didn't. No one knows what effects long-term use of AZT will have.

The AZT Elevator

In 1987, Margaret Fischl's name appeared on a credit line in the New England Journal of Medicine as principal author of the single most important AIDS treatment study to date: the publication of the first research on AZT. Her major co-author, Douglas Richman, was a world-famous virologist. While Margaret Fischl was still in medical school, he was already producing trail-blazing work on immune responses to viral infection and on anti-viral vaccine development.

That Fischl, a relative newcomer, would get the lead billing on such a crucial study was extraordinary. How did it happen?

"You have to ask Burroughs Wellcome that," is Fischl's response.

It's almost impossible to get much closer to the truth. A spokeswoman for Burroughs Wellcome said: "Most of the sites were picked based on (the local researchers') reputations with anti-viral work."

Margaret Fischl had published no anti-viral work.

Says Richman, the famous virologist, "The initial group was chosen by Burroughs Wellcome. Someone at Burroughs Wellcome must have figured out she was good."

Whatever the reasons, the drug company plucked Fischl from obscurity and put her career on rockets. Since then, Fischl has been either the lead or second author on virtually every important study of AZT. She is one of only 10 members of the executive committee of the AIDS Clinical Trials Group, which directs the $100 million-a-year government research effort.

She is the sole U.S. representative to the International AIDS Society, which coordinates the global effort against the disease. At the University of Miami, she is a franchise player: Fischl's research brings in more than $10 million a year in federal and private grant money, half of which goes directly into the university general fund.

All of which raises an uncomfortable question. If Margaret Fischl owes her dazzling rise to prominence to the same corporation whose drug she is testing, can she possibly be objective about her findings?

Some take that even further: Many American AIDS activists assume Margaret Fischl is on the take. She makes advertorials for AZT-television spots explaining the virtues of AZT, bought and paid for by Burroughs Wellcome. Her face is prominently displayed in literature advertising the drug in glossy magazines distributed to physicians. She must be taking money-honoraria or consulting fees-from Burroughs Wellcome, her critics conclude. After all, last December Dr. Martin Hirsch, the former chairman of the same elite group of scientists that includes Margaret Fischl, acknowledged at a federal hearing that almost all the federally funded AIDS researchers were receiving money from the pharmaceutical companies whose products they were testing.

In January 1989, the National Institutes of Health-attempting to pre-empt conflict of interest legislation brewing in Congress-decided to take a straightforward approach to the problem: It announced it would prohibit federally funded researchers from having a financial stake in any company "that would be affected by the outcome of the research or that produces a product or equipment being evaluated in the research project."

The research establishment exploded.

"The proposed guidelines are inoperable, are an affront to the personal integrity of the vast majority of scientists, are an invasion into the private lives of multitudes of individuals," a prominent cancer researcher wrote in a typically indignant letter to the federal agency. Of the 700 letters NIH received, more than 600 were hostile. U.S. Secretary of Health and Human Services Louis Sullivan quietly canceled the new regulations.

Fischl herself did not oppose the prohibition. "This is not relevant to me," she explains. "We are not salaried through pharmaceutical companies. I do not own stock in pharmaceutical companies... I have never gotten a 'kickback' from Burroughs Wellcome, if that is the terminology."

Fischl makes $120,000 a year, paid out of UM's share of the grants she brings in.

Dr. Bernard Fogel, dean of the UM medical school: "Margaret Fischl gets a single check from the University of Miami. Every other dollar she receives-from a drug company, patient or grant -- comes to the University of Miami."

Many would argue that that does not guarantee that Fischl-or any other researcher in her position-is not influenced by the pharmaceutical industry.

U.S. Rep. Ted Weiss, D-N.Y., is the driving force behind the disclosure movement in Congress. "It's not that we think that scientists are greedy bastards," says Diana Zuckerman, Weiss' spokeswoman. "It's that we have to ask if close working relationships with scientists and officials at drug companies, if becoming friendly with folks there, does not bias what a scientist decides to study or thinks, whether he knows it or not.

"Money is only one way that people are influenced. There is the pressure to publish that is facilitated when a drug company gives you a grant; the tremendous desire to say something new works; the prestige that bringing in grants and consultancy fees earns you within your university."

Fischl thinks that's nonsense: research cannot be influenced that easily. "It's not just the pharmaceutical company, you're also working with the FDA. They are involved with designing the study from the beginning."

Daniel Hoth, the federal official who runs the AIDS drugs research effort: "We all have bias, but there are checks and balances. I wouldn't tolerate for a second anything that looked like bias."

Dr. Joseph Sonnabend, a New York physician who has probably treated more AIDS patients than anyone else in the world, isn't impressed: "These people fly you around the country to speak at conferences. They promote you and your research. You get a bit of fame and glory. Maybe being on the emotional take is ultimately more insidious than being on the dollar take."

Just Say Yes To Drugs

From the beginning, there were signs that AZT was trouble. Two months into the first major trial that began in February 1986, dozens of the 145 patients on AZT were developing anemia. Researchers started panicking, says Robert Yarchoan, a researcher at the National Cancer Institute. The new drug was killing healthy bone marrow cells at an alarming rate. One possible result: aplastic anemia, an often fatal ailment. Physicians who had supplied patients for the tests were threatening to pull them out. The pressure was mounting to simply close the experiment down.

Margaret Fischl, the principal investigator, turned it around. Despite the pressure to stop the study, she resisted-and prevailed. "She was convinced AZT was working," Yarchoan says. "She was convinced it was worth the risk. She kept the ball rolling."

The study continued. None of the subjects died of anemia. But by the middle of September, 19 of the placebo patients had died of AIDS-related causes. Only one patient taking AZT had died. Researchers had intended to keep the trial running through December, a total of 11 months. Instead, they shut it down after seven months. How could they allow patients to keep taking placebos when the benefits of AZT seemed so apparent?

Members of the media were called and told that a "promising" drug had been discovered. On Jan. 16, 1987, the Anti-Infective Drugs Advisory Committee of the Food and Drug Administration met to make a decision that would affect almost every AIDS patient in the country. Burroughs Wellcome sent a team of nine; billions were at stake. Fischl was there. She had just turned 37 a few days before. This was her study, her reputation, her future. Dr. Itzhak Brook, the committee chairman, and his colleagues were given one day to make their decision.

No one was under any illusions about the bind the committee was in: AIDS activists and politicians were screaming for the federal research effort to produce something.

But some of the committee staff objected to the hurry-up atmosphere. "We're all under tremendous pressure and there's no question that politics is a much greater part of AIDS drug development than approval and availability of drugs in less publicly visible diseases," said Ellen Cooper, the FDA medical investigator who had analyzed the AZT drug study.

Cooper opened the meeting. She didn't like what she had seen in the research data. She worried about approving a drug on the basis of a single trial that was stopped before its completion. She worried about approving a drug on the basis of a trial with fewer than 300 people, most of whom had taken AZT for fewer than six months. She worried about approving a drug without knowing anything about its long-term effects.

Cooper worried especially about judging the effectiveness of the drug when so many of the subjects were being treated with a host of other drugs. That kind of contamination would have certainly discredited almost any other drug trial. Approval, she said, would be a "significant and potentially dangerous departure from our normal toxicology requirements."

When the reviewers sorted through the data, they bumped up against one puzzle after another. When the study was terminated in September, patients on placebos were switched to AZT. Even so, in the following three months, 13 more people from the original placebo group died, and there were seven deaths among those who had been on AZT from the beginning. Suddenly, the mortality differential between the two groups didn't look quite so dramatic-not 19 to 1, but less than 2 to 1.

The FDA committee members were concerned. Dr. Stanley Lemon of the University of North Carolina Medical School: "After 16 to 24 weeks -- 12 to 16 weeks, I guess-the effect seems to be declining."

Committee Chairman Brook told the packed meeting room, "I was struck by the fact that AZT does not stop deaths. Even those who were switched to AZT still kept dying."

Brook concluded: "There are so many unknowns that it is hard to exactly know the truth. We do not really know what will happen a year from the beginning. The data is just too premature and the statistics are not really well done. The drug may actually be detrimental. We do not know."

Nonetheless, the FDA committee members kept harkening back to the 19 to 1 fatality differential in the early part of the study. The final vote was 10 to 1 in favor of approval. Brook was the only dissenter.

Sloppy Research?

When Dr. Joseph Sonnabend first read the AZT study report, he had lots of questions, but the first one had nothing to do with AZT: Why had so many placebo patients died?

"I was suspicious of the study from the beginning because the mortality rate was simply unacceptable," Sonnabend says. "My patients were simply not dying in those sort of numbers that rapidly."

Sonnabend reviewed the data and tried to figure out what had happened.

His conclusion: The research was not good enough.

Sonnabend speaks with some authority. A medical researcher trained in infectious diseases at the University of Witwatersrand in Johannesburg and the Royal College of Physicians of Edinburgh, Sonnabend did research on anti-viral treatments and the immune system at the prestigious

International Institute for Medical Research in London in the 1960s, before the field had even entered the scientific mainstream.

He wound up in New York in the 1970s and put his expertise in sexually transmitted diseases to work in the gay community. The shy, soft-spoken South African was among the first physicians to notice that something new-something terrifying-was menacing his patients.

He published the first article demonstrating that something was destroying the immune systems of gay patients. Without any government assistance, he conducted much of the first research on the new phenomenon.

When he began investigating Fischl's research, Sonnabend was frustrated because there was no detailed information about what had actually killed the placebo patients: (No autopsies had been performed). AIDS, after all, does not kill; it simply allows other infections to do so. Sonnabend had an added difficulty: The causes of death provided to the FDA did not quite match those in the article on the research Fischl had written for the New England Journal of Medicine. "Sloppy research," Sonnabend said. He pressed on.

As he puzzled through the death reports, Sonnabend began to worry that the patients on placebos might have died because they were neglected. Was it that the physicians caring for them had had insufficient experience warding off and treating these infections, he asked, or were they unwittingly treating placebo patients differently from those on AZT?

That should be impossible, he knew. Carefully controlled scientific experiments are almost always double-blinded: Neither the physician nor the participant knows which patients are on the drug being tested and which are on a placebo. And Fischl's New England Journal article was specific: This had been a double-blinded study.

Except, FDA scientists openly acknowledged it was not.

The side effects of high doses of AZT are so extreme that researchers knew who was on AZT simply by how frequently the participants needed blood transfusions. (Another thing that bothered Sonnabend: Could the short-term benefits attributed to AZT actually have been the result of so many transfusions of fresh blood?) And beyond the transfusions, the standard lab tests-in which the action of AZT on the blood was clearly visible-would have told researchers instantly who was on the drug and who was taking a placebo. In other drug tests, such information is simply whited out by lab workers to keep clinicians from seeing it. In the testing of AZT, it was not.

Didn't need to be, says Fischl. The lab-profile of AZT users, and their need for transfusions, was something discovered during the study. The double-blind wasn't compromised, she argues, because researchers didn't know about the reactions in advance-though she admits some might have "surmised" the connection.

In Good Intentions, a new book on AIDS by Bruce Nussbaum due out at the end of October, Dr. Samuel Broder, director of the National Cancer Institute, defended the integrity of the study in a slightly different way. The whiting-out was not necessary, he said, because researchers can be trusted not to be biased. In fact, Broder takes heated exception to Sonnabend's entire line of reasoning.

"That's an accusation of fraud, not bad scientific design," he told Nussbaum. "There was no fraud in the study."

Sonnabend says he is not accusing Fischl of fraud: He is asking why, if unblinding presented no significant problem, Fischl, as author of the study, claimed to have overseen a double-blinded study.

Sonnabend: "Double-blinding exists for a very clear reasons: to ensure that no unconscious bias can creep into the way we treat patients. If there were not a need for it, it would not exist.

"What I am saying is that the study doesn't tell us what we need to know. It was technically substandard. For all we know from that study AZT may even be better than they claimed. But it may be worse."

In October 1987, a year after Fischl's study ended, Dr. Gordon Dickinson, Fischl's research collaborator at the University of Miami, presented the results of his own study of patients receiving long-term AZT treatment. During their first six months on the drug, patients gained weight and produced a larger number of "T-cells"-the blood cells that give our natural immune systems the power to fight infections. But after that, they began losing both weight and T-cells and developing serious infections.

"I'm pessimistic about AZT," he told The Miami News.

Fischl took sharp exception to his analysis, although she did not dispute the findings. She reminded reporters that she, not Dickinson, was the chief AIDS researcher at the University of Miami.

"We absolutely recommend continued therapy despite falls in T-cells and infections," she told The News.

The Pressure Cooker

Margaret Fischl has been under siege for almost a decade. "The phone in her office rings off the hook with patients begging for appointments and patients' families screaming 'murderer' into the receiver," says Fischl's boss, Dr. Robert Rubin, vice provost at the University of Miami.

Physicians in the community want advice, reporters want comment on every new development, and her researcher colleagues from around the country want to talk.

Meanwhile, she moves swiftly between the Old Elliott Building where her clinical trials are conducted; the Special Immunology Clinic, where she oversees care and treatment of 5,000 AIDS patients; and the wards of Jackson Memorial Hospital.

Of the 600,000 physicians licensed to practice medicine in the United States, only 2,000 list themselves as willing to accept AIDS referrals.

In the early days physicians snored during Fischl's Continuing Medical Education presentations on AIDS. Callers snarled wrath of God speeches at her. Members of the Legislature refused to take her seriously. Even the head of her medical school, Dr. Bernard Fogel, admits that he did not want to believe her predictions that Jackson was going to need special units and specially trained personnel. "When a young faculty member comes up and says, 'We're going to have an epidemic of X proportions,' it is easy for people to think she is being an alarmist," he says.

In those days, Margaret Fischl was easy to dismiss. She was, Fogel says, fragile, even a little scared. And for good reason: Suddenly she found herself at the center of a maelstrom.

"She started as a pretty naive serious young woman who just got overwhelmed with the tragedy of the disease," says Rubin. But it was more than tragedy that overwhelmed her. Fischl was confronting for the first time the ritualized promiscuity of the gay community, the anything-goes sexuality. "She was shocked-and had to be trained both formally and informally-by the whole issue of the life style of her patients, her gay patients."

Then, of course, there was the politics: The politics of getting federal grants; the politics of prying resources out of a hesitant university; the politics of dealing with colleagues jealous of the sudden prominence of a young upstart.

And along with the jealousy of her peers came the competition from her seniors. "A lot of famous people-much more famous than her-got into the act," Rubin says. These were international experts in virology, in vaccine development, in immunology and genetics. "Margaret was thrown right into the center. She is not a basic scientist. She is not going to win a Nobel in virology. She is a clinical scientist. Suddenly she was competing with people twice her age and ten times her experience."

Her grants began getting turned down because she had no experience in gene cloning or retrovirology, he says. "So added to the burden of the press, patients and parents, there was the intellectual stress of being told, 'You're not a real scientist.'"

At the same time, there were people telling her she wasn't a good doctor either. Many doctors who treat AIDS patients are lionized. But Fischl's adoration became mixed with invective. She was accused by some of being unfeeling, secretive and uncooperative. Others defended her.

"She is a private person," says Sally Dodds, another of Miami's pioneers in the war against AIDS who has worked closely with Fischl for almost a decade. "Margaret catches an awful lot of heat because she symbolizes medicine, and there are a lot of patients who want everyone who has an MD after her name to make it better."

Robert Rubin: "The part that never comes out is seeing her break down and cry when she is attacked by the families of the people she's trying to help. She's taken on this burden, and families call up and say she is killing their son or their brother, calling her the worst pornographic names in the world. This is harder than the ego-deflation of academia. Sometimes she sits down and cries. If the public could see that, they would be less critical."

"That woman doesn't cry for anyone but herself," says Albert Julbe, founder of Share Your Gift, an AIDS buddy program. "Don't ask us to believe something that could not be true."

"If she was crying, it must be because she had a gnat in her eye, or her dog died," says Doris Feinburg, founder of the AIDS resource center Body Positive in Miami.

All the pressure took a toll.

"Somewhere about five or six years ago," Rubin says, "everyone was driving her crazy. Something snapped in her psyche."

She responded, he says, by retreating behind a wall of privacy. Whatever the intended effect, it only served to deepen the suspicions and inflame the hostility.

Getting the most rudimentary information about Margaret Fischl is like trying to break a secret Pentagon code. Her office refuses to hand out her complete resume. Even county officials who run the hospital where she works could not get one when they tried.

Information on the programs Fischl directs for the tax-funded Public Health Trust is public. But when The Herald requested that information, it did not appear: There was a confusion in processing, agency officials said. A request for documents evaluating her personal performance as a physician during her internship and residency at Jackson Memorial Hospital was initially denied: Margaret Fischl was never employed by Jackson, its personnel director insisted. Two weeks later, when another official admitted that she had been, the records request was waylaid by University of Miami lawyers. Releasing such information could damage the quality of health care in the city, the lawyers said.

Members of the public relations staffs of both the University of Miami and the Public Health Trust openly admit that Fischl is a PR "nightmare."

A spokeswoman for Jackson Memorial Hospital, where Fischl directs all AIDS programs through the University of Miami, does not even know where Fischl is from. Joyce Goldberg, the hospital spokeswoman, tried to find that information for an article she was preparing for the hospital magazine. She asked Fischl directly. Fischl refused to answer.

It took elaborate investigative reporting techniques to determine: that she is from New Jersey; that her father is a baker. In dozens of interviews with people who might have some knowledge of Fischl, only two other personal facts surfaced: Fischl herself is a fine baker. And she plays the harpsichord.

Even her marital status is a matter of debate among people who work with her. Some say she is married to Dr. Karl Magleby, a University of Miami physiologist who shares a home with her. Some say she is not. Neither Fischl nor Magleby will address the question.

"The less people know about her the better," Magleby says. "Then she can get some work done."

Deadly Data

On Aug. 17, 1989, newspapers around the world announced a dramatic new finding: Early treatment with AZT can hold off AIDS.

At that moment 1.4 million Americans were assumed to be infected with the AIDS virus, known as HIV.

"Eventually all of them may need to take AZT so they don't get sick," said Dr. Anthony Fauci, head of the federal agency that sponsored the two studies on which the conclusion was based. The major study, on which Fischl was a second author, was supposedly based on 3,200 Americans infected with the virus who had not yet progressed to full-blown AIDS. Over a two-year period half had been given AZT and half a placebo. The authors' conclusion: "HIV-positive patients are twice as likely to get AIDS if they don't take AZT."

Once the data became available, the advance seemed less dramatic. The research, it turned out, was based not on 3,200 subjects, but on less than half that many -- 1,338; the remainder either dropped out of the study or had been enrolled too late to be counted. The average subject was followed for one year. While only 25 of the 910 participants on AZT progressed to AIDS, only 33 of the 428 placebo-takers joined them -- 7.6 percent got sick while taking a placebo, 3.6 percent got sick on AZT.

Some say there's a problem: considering the small numbers in each group who got sick, the statistical difference between them is not great.

But Fischl does not accept that argument. "A two- to three-fold difference," she insists, "is not attributable to chance."

The good news everyone accepted was that an AZT dose one-third the strength of that used in Fischl's 1986 study was shown to be as effective in hobbling the AIDS virus as the earlier one, vastly reducing the toxic side-effects of the drug. Nonetheless, patients on low-dose AZT were still five times more likely to suffer anemia than others, and 15 times more likely to suffer severe nausea.

Despite their enthusiasm, the researchers on the federally funded study concluded: "... the data provide no information about the possible long-term benefit or safety of (AZT). Thus it is possible that the eventual risks of disease progression in the three treatment groups could become similar after a longer time period... it is possible that even if (AZT) persistently delays the onset of AIDS, it may not have an ultimate effect on survival."

Fischl told journalists these findings were "a quantum leap" in the treatment of AIDS.

But not everyone was buying it. In November, a group of European AZT researchers published an article in Science magazine challenging the Americans. The article's authors suggested that the study data had been withheld from them, complaining that it had taken three months of begging before the study results arrived. And when they did, the Europeans concluded, they did not prove what the Americans said they proved.

Ian Weller, a British researcher, concluded that AZT had been recommended for wider use for political-not scientific-reasons. Their article received virtually no press attention on this side of the Atlantic.

Meanwhile members of the Veterans Administration AIDS research team were also examining the new data carefully. They were two years into their own three-year study of the effects of AZT on patients infected with the AIDS virus but not yet sick. If Fischl's study had already proven that AZT delayed the onset of AIDS, how could the VA ethically continue a study in which half the patients were given placebos instead?

VA researchers took an early look at their data. They met with representatives from the National Institutes of Health and the Food and Drug Administration. There was something wrong: Their results were not tracking Fischl's study. The VA scientists were finding no statistical difference in progression to AIDS between AZT patients and placebo patients.

So the Veterans Administration decided to continue. The study will end in January.

One of the members of the VA research team was Gordon Dickinson-Fischl's former colleague at UM. Despite his concerns about AZT, he believes the drug has value. "AZT has unequivocally been shown to have a beneficial effect, although a limited one," he says. His primary concern is this: If you're spending your time working with AZT, you're not working with other drugs that may prove to be of lasting benefit to AIDS patients.

Almost 80 percent of all patients enrolled in federally sponsored AIDS drug trials are in studies related to AZT. As of August 1989, the government was supporting twice as many drug trials-and spending four times as much money-on AZT than on all other potential AIDS treatments put together. Of the six new anti-HIV studies announced for 1990, four involve the use of AZT in combination with other drugs.

Most researchers believe that more than 100 other theoretically promising compounds have been left by the wayside as limited funds have been channeled into deciphering precisely how toxic AZT really is-or isn't-and precisely how effective and dangerous its cousin compounds might prove to be.

Some of the most promising drugs are owned by small corporations that do not have the money to prime the research pump-wine and dine federal officials, fly scientists around the country, provide 30 million capsules of their drug free-all of which Burroughs Wellcome did when AZT testing began.

Many physicians critical of the AIDS research effort are beginning to ask questions. They note that many promising drugs are derived from food products and thus not easily patentable, and wonder if any drug company will sponsor research on a substance from which it can derive no profit. Can a research program dependent on the initiative of pharmaceutical companies-and researchers working closely with them-pursue all possible therapies objectively?

Now their concerns are shared at the highest levels of government. In August, the National Commission on AIDS, a blue-ribbon presidential panel, issued a report to President Bush concluding that the AIDS research effort simply isn't producing.

The federal government, the commission cautioned, needs to respond to the perception of possible conflict of interest between federally funded scientists and private pharmaceutical companies.

The Mystery of Margaret Fischl

Is Margaret Fischl a heroine, or a dupe? Is she making a selfless sacrifice in the name of medicine, or simply grabbing for personal glory?

Whenever there is as much to lose, and gain, as there is in America's response to the AIDS crisis, the motives of the prime movers in that response will always be questioned.

For Fischl, those questions are complicated by her self-enforced silence, her insistence that who she is, and what she thinks beyond the specifics of her research, are nobody's business. However the debate over AZT plays out, the woman behind the drug will remain enigmatic.

A Thursday afternoon, Special Immunology Clinic at Jackson Memorial Hospital. An emaciated young man sits uncomfortably in his wheelchair waiting to see Fischl. His body is covered with scabby purple lesions: Kaposi's sarcoma. Extra oxygen enters his lungs from a tank on the floor next to him.

"Dr. Fischl, Dr. Fischl," he moans weakly as his physician walks past on her way to a treatment room. Two dozen patients turn their heads awaiting her response. She does not turn her head in his direction.

"Dr. Fischl, Dr. Fischl," he tries again when she re-emerges and moves toward the nurses' station. The patients again await her response. It never comes.

Months later. Early evening, Three North, Jackson Memorial Hospital. A young man lies dying in his hospital bed on the AIDS ward. Fischl examines him and then sits on the side of his bed, holding his hand and speaking gently to him.

When she leaves the room, tears are streaming down her face. She looks around, regains composure and moves on to the next patient. *


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