By Elinor Burkett

Miami Herald 23 Dec. 1990

Margaret Heckler stood behind the podium in the auditorium of the Hubert H. Humphrey Building in Washington, D.C. Lights flooded her face, cameras rolled, reporters clutched their notebooks expectantly.

"Today we add another miracle to the long honor roll of American medicine and science," announced the secretary of Health and Human Services. "Today's discovery represents the triumph of science over a dreaded disease. Those who have disparaged this scientific search-those who have said we weren't doing enough-have not understood how sound, solid, significant medical research proceeds."

It was April 23, 1984. Almost 2,000 Americans were dead of AIDS. More than 100 new cases were being reported every week. For the first time since the plague began, the government was offering shreds of hope to the dying: The virus causing the disease had been isolated. An end to the nightmare was finally in sight: Within six months a blood test would be available, Heckler said; within two years a vaccine would be ready for testing.

As Heckler made her dramatic appearance on national television, Dr. Peter Duesberg sat in his cluttered office in Berkeley, Calif., bewildered. Duesberg is one of the world's foremost authorities on viruses. He was the first person to map all the different gene strands that make up a retrovirus, the very type of clever, hard-to-fight bug Heckler said was causing AIDS. To Duesberg, Heckler's announcement just didn't make sense. If her HIV virus was indeed the cause of AIDS, it violated the laws of virology. He decided to withhold his applause and wait for the proof.

Six years and 90,000 deaths later, he's still waiting. And there is still no vaccine.

In the six years since Margaret Heckler's surprise announcement, the federal war against AIDS has become a desperate $3 billion-a-year battle against HIV, Human Immuno-deficiency Virus. In the most intensive disease hunt in the history of mankind, scientists have cross-sectioned and spliced HIV. They have cultured, activated and mapped it. They have figured out how it reproduces. They can draw you a picture of it. But they are missing one important piece of the puzzle:

"We do not yet know how HIV causes AIDS," Dr. John Coffin of Tufts University, a member of the international committee that named the virus, told the delegates to the Sixth International Conference on AIDS last June.

It is that missing link that nags at a growing number of the world's best-known scientists. They have begun to suggest a frightening explanation: HIV alone may not cause the disease. Or it may have nothing to do with it.

The Doubters

By 1987, three years after the HIV discovery was announced, retrovirologist Duesberg's doubts had hardened into a certainty that something was wrong. For one thing, the numbers weren't adding up. Each year since Heckler's announcement, the federal Centers for Disease Control has projected the number of people expected to turn up with the HIV infection. Initially, scientists were confident their projections would prove accurate: They knew from years of experience how quickly a toxic new virus spreads in a human population. But, the predictions were wrong. At the end of each year, the CDC was forced to revise its estimates downward dramatically. In 1986, for example, the CDC estimated that 1 million to 1.5 million Americans were infected with HIV. A year later, they cut that estimate in half. HIV is not spreading at anywhere near the rate expected of a newly introduced sexually transmitted virus. Why? No one knows.

There were other nagging problems with the HIV hypothesis:

  • Two healthy people can have sex with the same HIV-infected person, and one of them will come down with the infection after a single encounter, while the other will still not have it after 500 encounters. Why? No one knows.
  • The vast majority of those known to be HIV-infected remain healthy for years-and there is no proof that they will not live a normal life span. Why? No one knows.
  • Diseases presumed to signal AIDS are cropping up in individuals without any trace of HIV. Why? No one knows.
  • How could a virus found to be active in only minute quantities in the bodies of even the sickest AIDS patients devastate the immune system as HIV purportedly does? No one knows.

While most researchers say such apparent contradictions are to be expected in the early stages of research into a new disease, others aren't so certain.

"There are too many shortcomings in the theory that HIV causes all signs of AIDS," says Luc Montagnier.

In June, when Montagnier, a French AIDS researcher announced his rejection of the established theory, he should have provoked a sensation. After all, Montagnier discovered HIV in the first place.

Montagnier now believes that HIV is "a peaceful virus" that becomes a killer only when combined with another bug-a bug he has already isolated and identified. This finding received none of the attention of his original discovery. The same reaction-which is to say no reaction-had greeted

Robert Gallo, Montagnier's American co-discoverer of HIV, when he also suggested in print two years ago that HIV might need a co-factor to cause AIDS. Now Gallo does not even discuss the matter.

Montagnier, however, persists-and has discovered what earlier dissenters have found out over the years: It's no fun to challenge the common wisdom.

Peter Duesberg, the retrovirologist, has been likened to obsessives who believe AIDS has extraterrestrial origins. He is, CDC researcher Harold Jaffe and his British colleague Robin Weiss wrote recently in a British science magazine, "a flat-Earther bogged down in molecular minutiae and miasmal theories of disease."

Two other dissenters, Robert Root-Bernstein, winner of a MacArthur "genius grant," and Shyh-Ching Lo, director of AIDS pathology at the Armed Forces Institute of Pathology, have been accused of quackery and endangering the public health of the nation by key AIDS policy makers for their insistence that HIV is not the sole cause of AIDS.

Even when they present evidence that their dissent might be justified, nothing happens. Montagnier was not the first one who found a second organism that may be essential to produce AIDS. A year ago this month, the National Institute of Allergy and Infectious Disease-the agency in charge of the war on AIDS-convened a panel of scientists to examine Shyh-Ching Lo's discovery of an extremely toxic micro-organism in AIDS patients. When the organism-the same mycoplasma that Montagnier would report four months later - was injected into experimental animals, the animals quickly sickened and died. That does not happen with HIV. Panel members quizzed Lo for three days, and

concluded that he was onto something important.

A year later, of the $1.8 billion in federal funds NIAID spends on AIDS research, not one dollar has been budgeted to pursue that finding.


The official version of AIDS: In the beginning, there is HIV (a type of virus called a retrovirus) that hits the bloodstream with a burst of fury, looking for one of its favorite cells-a T cell, an essential part of the body's immune system. HIV attacks the T cells, but, initially, does not destroy them. Most newly infected people feel nothing. Some might suffer swollen glands or a mild fever, like a case of flu or a touch of mononucleosis.

The symptoms quickly disappear. Most scientists believe the virus lies almost dormant in a small number of cells, often for years, until it somehow becomes activated. Then the infected cells suddenly mass produce new viral particles that float through the bloodstream, attaching themselves to previously uninfected cells.

This in itself doesn't necessarily mean disaster. Healthy bodies harbor dozens of viruses and other bugs that never cause any noticeable harm. But in the case of HIV, most scientists believe the virus suddenly stops cohabiting with T cells-as it has done for years-and kills them instead.

When T cells are killed off, the body is left wide open to disease. Bacteria, other viruses and bugs that wouldn't hurt a soul under normal circumstances suddenly run riot. When that begins to happen, an HIV-infected person has AIDS.

In the absence of any drug that can kill HIV without killing the body that harbors it, scientists leading the fight against AIDS see the result as inevitable: Once you are infected, your body cannot kill the virus. The virus eventually destroys your immune system. You die.

If this were a murder case, the official case against HIV would be entirely circumstantial. Nobody can see HIV destroying the immune system, or even say how it does it.

But it isn't just the lack of proof that bothers critics of the HIV orthodoxy. They understand that in science, there isn't always a smoking gun. Sometimes, inferences are all you get. But in this case, they argue, even the circumstantial evidence has gaping holes in it.

Robert Koch was a German scientist who had a peculiar obsession with proof. Koch was born in 1843, three years after Friedrich Gustav Jacob Henle made the stunning assertion that living organisms too small to see with the naked eye could cause disease. Koch became one of the first

disciples of the new science of bacteriology, and he considerably advanced it: He discovered both the organism that causes tuberculosis and the organism that causes cholera, eventually winning the Nobel Prize for Physiology and Medicine.

It is difficult to grasp, from the late 20th Century, what an astounding feat that was. When scientists first began studying the world through a microscope, they found it to be teeming with micro-organisms. There was no way to watch them operate in living organisms. So how could the scientists tell which were harmless, and which were killers?

Koch, who had served as a field surgeon in the Franco-Prussian War, became an ace detective. He developed all kinds of new investigative techniques, including what was to become the basic rules for what constitutes definitive proof that a specific germ causes a specific disease:

  • 1. You have to find the germ in every case of the disease.
  • 2. You must be able to isolate it from the body and from other germs.
  • 3. It must cause sickness when injected into a healthy host.
  • 4. After it does, the same germ must be retrieved from the newly diseased person.
  • Koch was flexible. He understood some cases wouldn't fit neatly into his set of rules. In those cases, however, he insisted that a simple association should not be confused with causation. In other words, just because everyone in your neighborhood with measles also has blond hair does not mean that blond hair causes measles.

    Koch-whose principles are still taught to every student of epidemiology-isn't very popular among AIDS researchers these days: HIV fails his test on three of four counts.

    HIV can be isolated, both from the body and from other germs, but only with difficulty, because even the sickest AIDS patients simply don't have much virus to be found. With run-of-the-mill viruses, scientists can find, at the very least, a million units of virus particles in a milliliter of bodily fluid of a sick person. With HIV, finding even one-tenth that many is extremely rare.

    HIV fails the other tests outright. The virus cannot be found in every case of AIDS. In 3 percent of diagnosed AIDS cases, no HIV antibodies have been found.

    No one has tried injecting HIV into a healthy human being, but scientists have stuck all kinds of mice and rats and monkeys and chimpanzees, and none of them got anything resembling human AIDS.

    All this doesn't necessarily disprove the HIV hypothesis, as dozens of scientists have pointed out in attacking Peter Duesberg, the HIV-doubter, who insists on reminding everyone of Koch's postulates as frequently as possible. HIV's failure of Koch's tests can be easily explained:

    • The virus or its antibodies are not being found in all cases of AIDS because tests for it are not yet sensitive enough, the CDC argues.
    • Some germs are specific to a single species, says Dr. Peter Drotman, a CDC medical epidemiologist. HIV may not give other animals AIDS simply because it cannot live in the bodies of most other animals.

    But the most powerful argument against the doubters is also the foundation of HIV orthodoxy: In almost every case of the condition called AIDS-a cluster of diseases frequently accompanied by weight loss, blindness, incontinence and dementia-they find antibodies to HIV. That is just too much of a coincidence to pass up.

    A Matter of Time

    To Robert Root-Bernstein, the number of people with AIDS who are HIV-positive is not as interesting as the number of people who are HIV-positive who don't have AIDS.

    Root-Bernstein, the MacArthur Grant winner, was working on immune disorders in Jonas Salk's laboratory when the discovery of HIV was announced. Given the incredible variety of evils that were included in the definition of AIDS-from diarrhea to dementia-Root-Bernstein was skeptical that a single virus could be blamed for them all. Now he has another cause for skepticism: Fewer than 5 percent of HIV-infected Americans have AIDS.

    Most AIDS researchers say the rest will eventually get sick. It just takes time. "How much time?" Root-Bernstein and others ask. The answer keeps changing.

    When HIV was first discovered, scientists at the Centers for Disease Control suggested that most of those infected would begin to fall ill within 12 to 18 months of infection. They didn't. So the CDC did what it would do again and again: It raised the projected incubation time: first to five years, then seven, then 10, and now, 15.

    In the late '70s, blood samples were drawn from 6,875 sexually active gay men in San Francisco. Scientists had never heard of AIDS or HIV when they froze the blood for research on hepatitis B. But in 1985, when the HIV antibody test was licensed, all that six-year-old blood from the highest AIDS risk group in the nation suddenly became critically important. Sure enough, 67.3 percent of the samples turned out to be HIV-positive. It's now been 11 years since the first blood samples were taken. Only half of the infected men have been diagnosed with AIDS.

    That figure, Root-Bernstein argues, suggests that HIV alone is a poor explanation for AIDS. But it gets even more complicated: Almost all the frozen blood samples were from men who also had hepatitis B, syphilis, gonorrhea and herpes. Their immune systems were already in chaos from the massive assault-which makes them terrible predictors of how HIV would operate in healthier blood.

    Even the CDC's Peter Drotman admits it is "a nonrepresentative sample." Nonetheless, it is the basis for the current 15-year CDC estimate of the median HIV incubation period.

    "Look," says Root-Bernstein, "if they keep going at this rate, we're going to have people who live to 90 who were infected with the virus at 15 and they will still be arguing that HIV causes AIDS."

    But there is another glitch in AIDS epidemiology that Root-Bernstein finds even more disturbing: An increasing number of people coming down with infections typical of AIDS patients are turning out not to have HIV.

    Four leading scientists at the Centers for Disease Control recently suggested in Lancet, a British medical journal, that Kaposi's Sarcoma - a form of cancer that before AIDS had only been found in elderly men - is turning up in young gay men who indisputably do not have HIV. They concluded that KS-one of the diseases that have always been part of the definition of AIDS - "may be caused by an as yet unidentified infectious agent, transmitted mainly by sexual contact."

    The HIV-negative KS group differs from the 3 percent of "AIDS patients" who do not test positive for HIV antibodies in that they have been given the sophisticated, extremely expensive tests for the virus itself, and come up negative.

    This is a stunning development, because the very existence of AIDS was originally hypothesized to explain why young men had diseases like KS. If HIV was not responsible for the outbreak of Kaposi's Sarcoma, then something else is. What? No one knows.

    "Maybe these are anomalies," Root-Bernstein says, "but everyone in science knows that the anomalies are keys. They are nature's way of telling you that something is wrong with your dogma. Look at Copernicus, Galileo, Einstein. That is what they keyed in on.

    "If we insist that HIV is the sole cause of AIDS, then if we have people who aren't infected developing the same symptoms as AIDS patients, we are forced to conclude that we have a second epidemic, or a third or a fourth."

    A Murderous Microbe?

    Every American adult should have a small scar on his upper arm or thigh: a smallpox vaccination. Smallpox once was a deadly scourge-killing millions. Vaccinations have virtually wiped it out. It's an ingenious concept: You introduce a minuscule amount of weakened or dead disease-causing bugs into the human system. The body responds by producing antibodies-a natural antidote that neutralizes the invading bug. Once you have the antibodies, you're immune. So why is it such devastating news when a person tests positive for HIV antibodies?

    Shyh-Ching Lo, the researcher in charge of AIDS programs for the Armed Forces Institute of Pathology, doesn't believe it should be: The presence of the antibodies to HIV-far from being a sign of doom-is proof the body is capable of coping with the virus, Lo contends. Nobody is able to explain how the dormant HIV particles manage to suddenly whip the antibodies.

    "There is no good explanation for why and how the virus breaks out of the antibody protection," says Lo. "I'm not saying that HIV plays no role in AIDS-the data shows a clear correlation with disease. But AIDS is much more complicated than HIV."

    Lo, an obscure microbiologist, with no grants or establishment support, went looking for a new explanation. In 1986 he announced that he had found it: a previously unknown organism that-together with HIV-caused AIDS.

    For nearly three years, his theory was ignored. Shyh-Ching Lo's research was turned down for publication almost a dozen times before the Journal of Tropical Medicine, available in few hospital libraries and on no major electronic databases, agreed to print his findings. His attempts to find funding have failed. Even the presentations he has given at professional meetings have gotten him nowhere; his colleagues don't even show up.

    The problem was that Lo was using a complex new research technique he had devised himself to come up with a revolutionary finding. Given the stakes, no one was willing to give him the benefit of the doubt.

    Until last December, when an official at the National Institute of Allergy and Infectious Diseases decided Lo's work merited at least a closer look. The agency brought a dozen specialists together to look at his data. Experts in AIDS and other infectious diseases flew into San Antonio, Texas, expecting, they admitted, to demolish Lo.

    Lo laid all his cards on the table. He had detected an organism similar to a bacteria, called a mycoplasma, in cells taken from AIDS patients. He could not find the organism in cells of healthy individuals. When he injected the organism into four silvered leaf monkeys, three quickly developed low-grade fevers. All four lost weight. All four died within seven to nine months of infection. When they were autopsied, there was Lo's mycoplasma in their brains, livers and spleens.

    Lo also reported finding the mycoplasma in the damaged tissue of six HIV-negative human beings who had died from unspecified causes after suffering from suspiciously AIDS-like symptoms.

    Lo did not argue that his mycoplasma-dubbed mycoplasma incognitus-caused AIDS. "This might be a key co-factor that promotes disease in HIV-infected individuals," he says. "It might be an opportunistic infection that takes advantage of immune compromise. Or it might be the primary cause of the disease, with HIV perhaps helping it along. All I know is that it is there and that it changes the properties of HIV. But it is too early to know how or what that means."

    The scientists quizzed Lo for two days. They knew that tiny, bacteria-like mycoplasmas can cause immune suppression and debilitating, chronic diseases in animals. But in human beings, mycoplasmas are only known to cause nonlethal diseases: light pneumonias and some genital infections.

    "When I showed the mycoplasmas from my pathology studies, they didn't believe they existed," Lo recalls. "When I showed them that the organism existed and proved it was a mycoplasma, they said my cultures were contaminated."

    Two days later, Lo had turned skepticism into interest. "The documentation was absolutely solid," said Joseph Tully, head of mycoplasma programs for NIAID. Participants formally recommended further study of the link between the mycoplasma and AIDS, and experiments with drugs that could kill the new microbe.

    One year later, NIAID has funded no such research. "We have not been pulled into the AIDS programs in any real way," Tully says.

    When asked for an interview concerning Lo's work, NIAID director Anthony Fauci said through spokesperson Mary Jane Walker that he "will not talk about mycoplasma or any other AIDS co-factor."


    Fifteen minutes just wouldn't be enough. Luc Montagnier knew it. The announcement was too controversial, too important. If the organizers of the Sixth International Conference on AIDS wouldn't give him more time, he would find another way.

    It was June 1990 and the conference was due to open in San Francisco in a week. Montagnier, the French discoverer of HIV, planned to announce he had been wrong for almost seven years. He was about to explode a bomb in the midst of a multibillion-dollar international research and development establishment built on the bedrock truth he had helped create.

    HIV, he announced, is a benign virus that only becomes dangerous in the presence of a second organism. His candidate: a tiny, bacteria-like bug called a mycoplasma. In culture, HIV is harmless and passive, he told the conferees. But when you add mycoplasma, it becomes a vicious killer.

    Three months earlier, Montagnier had suggested in a French journal, Research In Virology, that HIV and his mysterious micro-organism react together to cause the body's cells to burst. Now he was saying that in his test tubes, tetracycline-type antibiotics stopped the bursting. The sort of common antibiotics that people get every day to help them battle common diseases like pneumonia or acne. If true, Montagnier's claim might have startling implications for the treatment of AIDS. In best of possible worlds, it might even mean that AIDS could be treated with common antibiotics. Still, it is such a complex disease that, in any case, the practical uses of such a discovery would be years away.

    As Montagnier spoke, Shyh-Ching Lo basked in vindication. Montagnier, the great man of AIDS, had just hit upon exactly the same microbe as Lo. The two had not shared their data. Separately, they had made the same discovery.

    But Lo was almost the only person in the room who was excited. Of the 12,000 people who attended the conference, only 200 came to hear Montagnier talk, and by the time he had finished, almost half of those had walked out.

    Montagnier was used to skeptical responses and outright dismissals by scientists, especially on this side of the Atlantic. Few American scientists took his discovery of HIV seriously until a year later, when an American named Robert Gallo discovered what turned out to be the same virus. But this time Montagnier came with his HIV credentials behind him. He had hoped for a better reception.

    In a confrontation after his presentation, Jay Levy, a University of California virologist and one of the most respected AIDS experts in the world, insisted that while Montagnier was claiming he had made a major new discovery, in fact he had simply allowed his experiments to be contaminated-a mistake a graduate student might make. Here, the exchange grew heated. Levy: "I've looked in 20 patients, and I can't find your mycoplasma."

    Montagnier: "They're just very hard to find."

    At this point, Levy cut off the discussion. "We know how to look," he said. Then he turned his back and walked away. Most of the people who control the course of AIDS research agree with Levy. The official reaction from CDC spokesperson Peter Drotman is typical: "It's just a hypothesis. We don't believe it. HIV is not a benign infection."

    But the small number of dissenters who had hoped Montagnier's support would be a turning point in their struggle to be heard were horrified.

    Peter Duesberg: "There was Montagnier, the Jesus of HIV, and they threw him out of the temple."

    "Who were these people who are so much wiser, so much smarter than Luc Montagnier?" asks Harry Rubin, the dean of American retrovirology. "Heb became an outlaw as soon as he started saying that HIV might not be the only cause of AIDS.

    "The minute someone suggests that the orthodoxy might be wrong, the establishment starts to call him crazy or a quack. One week you're a great scientist; the next week, you're a jerk. Science has become the new church of America and is closing off all room for creative, productive dissent." Rubin has been mocked as a has-been, an old fool.

    But no one has felt the heat more keenly than Peter Duesberg, the most aggressive of HIV's disbelievers-the only one who insists that HIV has nothing to do with AIDS.

    Three years ago Duesberg began arguing in print that HIV was no more harmful than any of the other myriad viruses and bacteria that live in our bodies and are contained by our immune systems. He is not surprised at the gaps in the evidence. After all, he says, how can a virus be so vicious when it first enters the body, then turn around and play dead for 10, 20, 30 years? What kind of virus one day, out of nowhere, springs into action to destroy a person's immune system with no provocation?

    Levy, the UC AIDS researcher, and others insist that HIV is just that-a time-bomb virus that lies dormant in the body until-for some unknown reason-it modifies its own genetic structure and transforms into a fast-growing, virulent, deadly virus.

    Poppycock, insists Duesberg. "No virus has ever behaved that way."

    Duesberg is accustomed to being listened to, praised and funded for his work. After all, he is the man who discovered the viral gene that can cause cancer, and was rewarded with membership in the prestigious National Academy of Sciences. He was the first man to draw a genetic map of a retrovirus. Now Duesberg is, in his own words, "the enemy within."

    When National Public Radio attempted to stage a debate between Duesberg and a supporter of the HIV hypothesis, it could find no one willing to confront him. "Critiquing a dubious theory would take time away from more productive efforts," Anthony Fauci, head of NIAID, told NPR producers.

    For 22 years, Duesberg had no trouble finding federal funding for his research. For the past five years, he has been the recipient of an Outstanding Investigator Grant from the National Institutes of Health, one of the most prestigious, and liberating, sources of research funding in American science. But on Oct. 26, the Berkeley professor of molecular and cell biology was turned down for continuation of the grant.

    The committee reviewing his application wrote: "Despite the applicant's eminent track record, the relatively low past productivity, the logically and functionally flawed rationale, and the poor prospect of the proposed study for advancing knowledge in important areas, greatly weakens the overall merit of this application."

    Duesberg argues that the review committee was "penalizing me for developing concepts contrary to those of the committee members." Committee members say that it is illegal for them to discuss the grant termination further.

    The Worst Possible News

    What is AIDS? According to the federal government, it is a 10-page single-spaced collection of diseases, conditions under which the diseases must occur, test parameters and pure deduction. The only thing that holds this mind-numbing definition together is: HIV. If you have certain kinds of pneumonia and HIV, you have AIDS. If you have those kinds of pneumonia and you don't test positive for HIV, you're just a poor slob who has been around too many people spewing pneumonia germs.

    If HIV is not the sole cause of AIDS, then the effort to fight the disease is in chaos. In fact, we wouldn't even know what disease-or how many different diseases-we are fighting. HIV is the glue that holds together an amorphous syndrome of usually common and nonlethal ailments that are hitting uncommon groups of people or becoming strangely lethal.

    If HIV is not the sole cause of AIDS, then five years of desperate searching for a way to kill a virus in already infected people-a feat that has never been accomplished with any virus-might have been spent more productively on another course of research.

    For scientists, the idea at this late date that HIV is not a lone assassin is the worst possible news. In the bars outside medical conferences and in off-the-record conversations, dozens of AIDS researchers admit they are disturbed by the persistent failure of the most monumental medical research effort in the nation's history to yield clear proof that HIV is a lone assassin.

    Yet in public, and on-the-record, few will express those doubts. "I'd bet my professional reputation that something more than HIV is involved in this disease," said one federally funded AIDS researcher. "But I wouldn't bet my grants, my ability to work."

    If there is fear about questioning the established line of thought, it is not because there is any conspiracy against skeptics: It is the intuitive understanding that the last thing anybody wants to hear is what the skeptics are saying. It is just too scary.

    "What epidemiologist or federal official wants to admit that the entire thrust of research and education might be misguided?" asks Robin Haueter, an AIDS activist in New York City. "What person with AIDS wants to consider the horrendous thought that we have wasted five years of research, that the end might not be anywhere in sight?" *