By Lamar Graham

GQ Nov. 1993

There are rare individuals who think the unthinkable and ask the unaskable. Robert Root-Bernstein is such a person. His question is a simple one: What if HIV doesn't cause AIDS?

"The fatal tendency of mankind to leave off thinking about a thing which is no longer doubtful is the cause of half their errors."

- John Stuart Mill

On a late-April evening, in Butler auditorium at the State University of New York School of Medicine, in Buffalo, Robert Root-Bernstein is about to deliver the twenty-third annual Ernest Witebsky Memorial Lecture in autoimmunology. His subject is the destruction of the human immune system.

The program handed out at the door list all twenty-three Witebsky lectures. To the slight, bespectacled Michigan State University physiology professor, however, there is only one name that matters - five from the bottom, four above his own: 1989, Luc Montagnier of Paris's Pasteur Institute.

Four years ago, more than 300 scientists and students packed this auditorium and spilled out the hallway to hear the latest theory from the dashing French AIDS researcher.

Four years ago: Luc Montagnier, the man who told the world that the human immunodeficiency virus, HIV, causes AIDS.

Tonight: Robert Root-Bernstein, the man who says it doesn't.

Hardly anyone recalls anymore that HIV wasn't always considered the cause of AIDS.

When the first odd cases of pneumocystis carinii pneumonia (PCP), a rare protozoal pneumonia, and Kaposi's sarcoma, a skin tumor that usually afflicts old men of Mediterranean descent, began showing up among young gay men in New York, San Francisco and Los Angeles in 1979, they were inexplicable anomalies. Only as the tide of death began to swell along New York's Christopher Street and San Francisco's Castro Street did epidemiologist begin to suspect that a mysterious new pathogen was on the loose. When the disease showed up in other populations - junkies, hemophiliacs, Haitians and blood-transfusion and organ transplant recipients - it became AIDS. And it appeared to be spread via semen via semen and blood, common media for viruses.

In those days, Root-Bernstein barely noticed the body count piling up in Morbidity and Mortality Weekly Report. In 1981, only months after graduating from Princeton University with a doctorate in the history and philosophy of science, he was notified that he had been selected by the John D. and Catherine T. MacArthur Foundation as one of the first winners of its now-famous "genius" grants: $152,000, tax-free, over six years.

Root-Bernstein sat down with his wife of three years, the former Michele Root, a Ph.D. in French whom he had met in graduate school. They were young, they had no children. They could sock the money away, find academic jobs and work on tunure... or they could go to Los Angeles. He could now accept a postdoctoral fellowship, exploring theories in biology, at the Salk Institute for Biological Studies, with an office directly below that of Jonas Salk himself. He could earn the necessary laboratory chops to explore his theories about how simple proteins called peptides interact in the human body. He could also concentrate on what had always intrigued him most: the process by which scientific theories develop.

There was plenty of talk about AIDS at the Salk Institute, and Root-Bernstein sometimes listened in. Occasionally, he ran across an intriguing article on the subject, and he would drop it into a file. Sometimes the gardener in his condo complex, a gay man, stopped him to talk about friends who were dying mysteriously. But Root-Bernstein never took much interest in the disease. He was having to much fun writing defences of Darwin in the burgeoning evolution-creationism debate. His lab work absorbed him, too: Peptides had led him to autoimmunity, a complex disease process in which the immune system attacks itself. There was also his research for what would become Discovering, his highly regarded 1990 book about scientific creativity.

Besides, the best minds in virology were at work on AIDS, Root-Bernstein figured. What room was there for a historian, philosopher and theoretician?

Finally, on April 23, 1984, almost four years into the epidemic, U.S. Secretary of Health and Human Services Margaret Heckler made a long-awaited announcement. Two independent teams of researchers on two continents - one led by Robert Gallo at the National Cancer Institute (NCI), in the United States, the other by Montagnier - had each discovered the cause of AIDS: the retrovirus soon to be dubbed HIV. Heckler promised a definite test for infection within six months and a vaccin - a cure - within two years.

Root-Bernstein joined scientists around the world in heaving a collective sigh of relief and didn't think much about AIDS again until 1986. By then, he and a colleague were using peptides to suppress the immune system of lab rats. Root-Bernstein had begun to suspect that if peptides and other substances could alter immune response, there might be reason to suspect that HIV wasn't the only immune suppressant at work in people with AIDS.

For a while, Root-Bernstein toyed with the idea of a research project that would examine the role of various immune suppressants in triggering AIDS, but reality soon intruded. His appointment at the Salk Institute was over, a teaching job at UCLA had fallen through, his Mac Arthur grant was about to run out, and he had two kids now. He needed a job, needed to finish Discovering, needed to make some money. Then, in 1987, he landed a position in the physiology department at Michigan State University, in East Lansing, teaching introductory biology.

He liked teaching, liked talking about theories, liked working with students. But toward the end of his first year, as he was explaining Koch's Postulates - the laws by which the cause of rabies, anthrax and virtually every controllable infectious disease known to man have been determined - he began to feel apprehensive. AIDS didn't seem to fit the model. HIV correlated closely with AIDS - fulfilling the first of Koch's four requirements - but it seemed to fail on the other three: It couldn't be isolated in pure form, it had failed to produce AIDS or AIDS-like symptoms in infected lab monkeys, and, thus, it couldn't be reisolated and passed on to other animals as a proof.

"Here I am, teaching the germ theory of disease," Root-Bernstein says, "and then I start talking about AIDS. 'How do we know HIV causes AIDS?' And I'm thinking, Uh-oh, we're in trouble."

While a graduate student at Princeton, Root-Bernstein worked for two years as an assistance to the science historian Thomas Kuhn. By the time Root-Bernstein joined him, Kuhn was already something of a celebrity in scientific circles. In 1962, Kuhn had published The Structure of Scientific Revolutions, a classic treatise on the nature of scientific progress. In it, he concluded that there is no such thing as an instantaneous breakthrough, that science is advanced not by the Eureka! Phenomenon but by the "paradigm shift," an arduous and often-hostile intellectual process in which a prevailing school of thought is slowly crushed under the weight of a new school's discoveries.

In putting his mind to AIDS, Root-Bernstein applied the method he learned from Kuhn: Read as much of the original research as you can, read it chronologically, and try to spot the discoveries that created forks in the theoretical road.

Thus, beginning in 1988, each evening after classes, Root-Bernstein would lug home reserve books and stacks of photocopies from the library and hole up in his small study off the dining room. Over the following four years, he found what he says is compelling evidence that HIV is not the Virus. In fact, he believes that the Virus - that is, a single infectious agent - probably doesn't exist. He even has doubts that AIDS is an infectious disease per se.

These conclusions form the basis of the 40-year-old researcher's recent book, Rethinking AIDS; The Tragic Cost of Premature Consensus, a 512-page volume (including 102 pages of footnotes) that has made Root-Bernstein the most prominent theoretician among a growing community of scientists dissatisfied with the HIV orthodoxy. During the past two years, more than 300 scientists from around the world have signed the charter of the San Francisco-based Group for the Scientific Reappraisal of the HIV/AIDS Hypothesis, which calls for the formation of an international panel to evaluate the merits of the HIV theory.

According to a recent analysis by the Philadelphia-based Institute for Scientific Information, researchers world-wide have published more than 36.000 AIDS studies since the beginning of the epidemic. Lost in this morass of information, says Root-Bernstein, is overwhelming evidence that AIDS is not behaving like a disease caused by a single agent.

For one thing, viral epidemics don't dawdle. Once they "emerge"- once they jump from a traditional reservoir (say, animals) to a new host group (say, people) - they typically spread quickly and geometrically. But HIV has dawdled - and for far longer than most researchers realize.

While most scientists date the emergence of HIV in humans to the late 1970s, blood samples from around the world, frozen decades ago by mystified clinicians and thawed only recently, prove HIV infection dating to at least 1959. Just as important, however, is what Root-Bernstein found in the musty pages of medical journals circa 1872: hundreds of isolated cases of what appear to be pre-epidemic AIDS-anomalous incidences of Kaposi's sarcoma; cases of PCP; disseminated fungal infections like candidiasis and cryptococcosis; cytomegalovirus; a brain-impairing disorder called progressive multifocal leukoencephalopathy.

To Root-Bernstein, these are pieces of an epidemiological puzzle: If HIV has been around for at least thirty years and something akin to AIDS may be more than a century old, why didn't the disease go ballistic long ago?

The list of anomalies goes on. If HIV is the cause of AIDS, it's the only human retrovirus (a family of viruses that reproduces by means of RNA, not DNA) known to be a direct cause of death; it's the only virus of any type that kills everyone it infects; and it's the only virus that infects far more men than women (by a 9-to-1 ratio in the United States). And if HIV is a "slow" virus that supposedly lies dormant for a period and then inevitably manifests itself during the period leading up to death, why do estimates of its latency period continue to creep higher, from two years in 1986 to ten to fifteen years by last year?

In Dragon Within the Gates, Stephen Joseph, the former New York City health commissioner, argues that AIDS is entering a new phase in the United States. Although more straight men, more women, more teenagers and more children are showing up as AIDS statistics, he says the numbers indicate not that the disease is spreading but that it's burrowing in. The new AIDS victims represent a shift, a waxing and waning among long-established risk groups, with the burden of death shifting from gays to IV-drug users, their sex partners and their new-borns. Joseph's conclusion jibes with one reached last year by the National Research Council, an arm of the National Academy of Sciences. It is also borne out by statistics from the Centers for Disease Control, which indicate that 97.6 percent of all AIDS cases still fall within the risk groups established at the beginning of the plague. Indeed, the transmission of HIV to heterosexuals outside those risk groups is so rare that we know many of the victims - Kimberly Bergalis, Allison Gertz - by name.

That the disease is not migrating into the general population is central to Root-Bernstein's ideas about the cause of AIDS. The disease's discriminating behaviour indicates that there are other conditions - "cofactors"- that either determine a person's susceptibility to AIDS or create the conditions under which it becomes activated.

He believes there is a common denominator among those who contract AIDS: a history of exposure to immunosuppressive agents.

In the early days of the epidemic, researchers looked at a number of microbes as possible culprits: cytomegalovirus, the Epstein-Barr virus, various strains of herpes and hepatitis, even syphilis and gonorrhoea, all of which were known or believed to have immunosuppressive effects. They were also ubiquitous among the first gay men to die from AIDS. Research into the role of these microbes in the causation of AIDS was dropped, however, upon the discovery of HIV. Nonetheless, Root-Bernstein says, these infections and a dozen or so others still show up consistently in people with AIDS. Hemophiliacs, for instance, show high levels of infection by various strains of hepatitis, cytomegalovirus and Epstein-Barr. There is also a large body of literature detailing the immunosuppressive effects and anti-rejection drugs used by organ-transplant recipients.

Implicit in Root-Bernstein's critique of the HIV theory is the controversial notion that an individual's behaviour is a much more important determinant of susceptibility than once believed: that the condition of your body if and when you encounter HIV may be as important as whether you encounter HIV. "Healthy people," Root-Bernstein says, "do not get AIDS."

Drug abuse, he surmises, is inherently risky not just because dirty needles provide a conduit for HIV but because shooting dope may create a weakened immune system in which AIDS can take hold. For the same reason, Root-Bernstein believes that the very act of anal sex may bear a great deal of the blame for fuelling the AIDS epidemic: Not simply because tears in the rectum allow HIV to enter the bloodstream but also because scientists have known for more than a century that the immune system can be thrown out of whack when semen comes into contact with the bloodstream, a common occurrence in unprotected anal sex.

What Root-Bernstein sees is that when you take a careful look at the risk groups that bear the brunt of AIDS, prior exposure to immune suppressants of one nature or another seems to be just as common - and perhaps just as important - as contact with HIV.

Root-Bernstein doesn't claim to know exactly what causes AIDS. But, he say, neither does the AIDS Establishment: "We're talking about a disease into which we have poured more money than any other disease in the history of mankind, and we haven't saved anybody. And it turns out we have huge holes in our understanding on the most fundamental levels. Given the effort, that's inexcusable."

Since he began to challenge the prevailing AIDS dogma, nearly five years ago, Root-Bernstein has been alternately ignored and attacked by both mainstream AIDS researchers and AIDS activists-groups that have seldom agreed on the course of the AIDS policy.

"The kind of message he sends out is very much an us-against-them theory," says David Eng, a spokesman for Gay Men's Health Crisis, a New York City-based activist organization. "Us being the heterosexuals, them being gays and IV-drug users and what have you."

After being summarily rejected by the prestigious journals Science and Nature, Root-Bernstein's first AIDS paper made the rounds for two years before finally being published, in Perspectives in Biology and Medicine, in 1990. In early 1992, he was cut loose as a columnist for a respected magazine called The Sciences, after submitting a piece asserting a multifactorial cause of AIDS.

Robert Gallo, arguably the world's most famous HIV researcher, declines to discuss the merits of Root-Bernstein's research, although he does devote three pages in his recent autobiography, Virus Hunting, to describing Root-Bernstein's arguments as "pure sophism." Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, also has no time to talk about Root-Bernstein.

"To say that we don't totally understand the pathogenesis of HIV is true," says James Curran, chief of the AIDS division at the CDC. "But it's a big jump to say the virus doesn't cause AIDS.

"[Root-Bernstein] is sort of taking all kinds of gaps in knowledge and piecing them together to form an argument," Curran continues. "Well, there are gaps in knowledge - but there are gaps in his knowledge. It's true that we don't know precisely how cigarettes kill, either. But it's sort of ignorant and dangerous to suggest they don't cause lung cancer. It's almost implausible to me that a scientist could be arguing this."

Indeed, for every glitch Root-Bernstein and other heretics find in the HIV hypothesis, Establishment researchers have counterarguments. But in the end, Curran maintains, the debate over the cause of AIDS boils down to one point: AIDS follows HIV. "There was no presence of AIDS in southern Africa in 1980, for example, but since the virus has spread, AIDS has spread.

"I don't understand people like Root-Bernstein," Curran adds perplexedly. "I don't see how they can put this information together and form these conclusions. They've been told by hundreds of their colleagues that they can't be right."

Root-Bernstein is perplexed too - at criticism like that. Correlation has never amounted to proof, in science. "It doesn't really matter how many people vote one way or the other," he says. "Correctness in science is proved by doing the right experiments. And if you were to forget what we know about HIV, would you, given all the information we have now, be compelled to believe we have a single infectious agent?"

Until Root-Bernstein published Rethinking AIDS, the most famous of the so-called heretics on the fringe of the AIDS debate was Peter Duesberg, the brilliant UC-Berkeley microbiologist who believes that AIDS is caused solely by drug abuse. Duesberg has grown so frustrated by the way the scientific Establishment has treated his theories that he has offered to shoot himself up with the HIV to prove that it's harmless. (So far, he hasn't done it.) Nature recently banned him from its pages, citing his "tendentiousness." And several months ago, his National Institutes of Health Outstanding Investigator Grant - a government sponsored award recognizing genius - was not renewed.

Duesberg blames the medical-industrial complex - self-aggrandizing researchers, greedy drug companies and the "imperial" NIH - for pushing the HIV theory. "Look, the same virus wouldn't cause Kaposi's sarcoma in homosexuals, pneumonia in transplant recipients and 'slim disease' in Africa," Duesberg maintains. "The HIV theory doesn't make sense.

"But we have a totally totalitarian science environment today. You have to become a government contractor to do research. And if you don't concur with the government - with HIV, with Gallo - you don't get any money. The fringes are growing," Duesberg says, "but the majority of researchers are conformists. We have a million Ph.D.'s in this country, and they can't all be Einstein's. Most of them are just good soldiers; they'll do as they're told."

Root-Bernstein's view of why the Establishment refuses to reconsider the validity of the HIV theory is more organic, more systemic - a historian's view.

In The Structure of Scientific Revolution, Thomas Kuhn proposes that the history of science is a succession of competing paradigms - the assumptions of Ptolemaic astronomy giving way to the formulations of Copernicus, the fundamentals of corpuscular optics drowning in the tide of wave optics, and so on. A paradigm arises because it brings order to chaos; it declines when it begs more questions than it answers.

The HIV-theory - now less a hypothesis than a foregone conclusion - arose because it satisfied a number of conditions, not the least of which were scientific. Almost ten years after it was proposed, the HIV theory provides a perverse comfort, a measure of security in the face of the unknown: There's still no cure... but at least we know what to avoid. HIV has created a sense of shared responsibility. Or at least shared risk. Our determination to stop the Virus has given a focus to AIDS education, prevention, treatment and research. Thousands of scientific careers - including those of the nation's top AIDS researchers - are now staked to HIV. Hope of foiling the Virus has given tens of thousands of AIDS patients the wherewithal to toxify their bodies with experimental drugs. Making treatment and housing benefits available to people with HIV has given form and size and power to the gay-rights movement. Over the past decade, HIV has infected every facet of American life. In addition to whatever it does inside the human body, it now exerts great power over the collective psyche.

HIV equals AIDS. It must. To consider any other possibility "means we don't have control any more," Root-Bernstein says. "It means we don't have the answer."

Near the beginning of his Witebsky Lecture, Root-Bernstein fires his laser pointer at a projection of the human immune system on a screen behind him. For nearly a decade, there has been only one acceptable interpretation of how AIDS fits the picture: You pick up the Virus. You come down with something a little like the flu. Then you're fine. Maybe for years. Inevitably, though, the Virus turns on. Slowly, inexorably, it begins to destroy your immune system. Opportunistic diseases take hold. Eventually - no reprieve - you die.

Root-Bernstein peers out into the tiers of long curvilinear desks, searches the faces in his audience. Perhaps it is time, he suggests, to consider other possibilities. For instance, what about his own pet area of interest - autoimmunity? Virtually all AIDS patients show some signs of autoimmunity. And the maddening thing about autoimmunity is, once the immune system turns on itself, the process becomes self petuating; the initial catalyst is no longer important. What if HIV kills not by overwhelming the immune system but by turning it against itself? To the assembled immunologist, Root-Bernstein's point is clear: Even if we ever cook up drugs to stop HIV, they still might be worthless to those in whom the cycle of self-destruction had already begun.

Some AIDS researchers maintain that the scientific Establishment is already softening toward the notion of cofactors to HIV and the role of processes like autoimmunity. The NIH, for example, recently began funding research by mycoplasmologist Shyh-Ching Lo, whose work on bacterial cofactors at the Armed Forces Institute of Pathology had previously been ignored. Robert Gallo's lab at the NCI has begun to make noise about the prospect that human herpes virus-6 has some relationship to HIV. And this past spring, Joseph Sonnabend, one of the nation's most prominent alternative AIDS theorists, was invited to Gallo's lab to lecture on the role of interferon in AIDS, a possible cofactor he's been touting for years.

The heretics aren't sure, however, whether such gestures mean much. "An orthodoxy can come into being much faster than in can be dismantled," Sonnabend says. "It's going to take maybe thirty years to undo it."

For Root-Bernstein, time is not the issue. The history of science is a history of dogmatism and resistance. Galileo died under house arrest, waiting for a realignment under the cosmos. Darwin still has critics. Given the weight thrown behind the HIV theory since 1984, Root-Bernstein says, he would be foolish to expect overnight change.

And yet, despite a brutal tendency to revile its most unconventional thinkers, the history of science also reveals to Root-Bernstein an enormous capacity for vindication. The earth really revolve around the sun. Natural selection survives because it's theoretically fittest. If HIV no longer sufficiently explains the cause of AIDS - if there are to many anomalies, too many contradictions, too many exceptions - it may be evidence of more than just a flawed hypothesis. Perhaps HIV doesn't pass etiologic muster, Root-Bernstein says, because AIDS doesn't fit our customary understanding of disease. Perhaps AIDS is pushing us beyond the germ theory of disease, showing us that disease is a more complex and interactive process than we ever dreamed. Perhaps the paradigm has begun to shift.

In June, Michael Merson, head of the World Health Organization's AIDS program, closed the Berlin AIDS conference with the dejected assessment that "progress seems desperately slow." AZT, the most commonly used HIV-treatment drug since 1987, took a beating in the wake of new studies that question whether it slows the onset or progression of AIDS or whether it further suppresses the immune system. Recently, the National Research Council issued a report suggesting that an aggressive campaign of AIDS education and prevention targeted at twenty-three to thirty American neighbourhoods with the highest rates of HIV infection could go farther toward eradicating the disease than a vaccin. The council also concluded that such a strategy had previously been ignored because of essentially ideological reasons: fairs that straight, sober Middle Americans would consider themselves safe, that they would ignore safe sex and that they would be unlikely to support research into a disease that largely afflicts marginalized minority groups.

Root-Bernstein agrees. You don't necessarily need to know the cause of a disease to stop its progress, he says. Taking the handle of the public pump clobbered cholera long before bacteriologists isolated Vibrio cholerae. "If getting people off drugs make people less susceptible or extends their lives," Root-Bernstein says by way of illustrating the example, "then we've got not only a new way of looking at disease but also a new way of treating it." He is heartened by another development: a declaration by HIV codiscoverer Montagnier that the virus alone is not enough to cause AIDS - that HIV is active only in the presence of certain bacterial cofactors.

Root-Bernstein has no delusions; he claims no breakthrough. He knows full well that he's tilting his lance at politics and public-health policy and drug policy and gay rights and the drug industry and every other element of the AIDS epidemic. He's a historian, a theoretician, a visionary, not a leader. He knew he'd be cast as a member of the lunatic fringe - he predicted it. He understands the implications of what he's suggesting. He understands the existential dangers. But he believes he has glimpsed a new pathway.

"I believe that science is a way of asking questions that can be answered," Root-Bernstein says. "What I've always criticized historians and philosophers of science for is failing to apply what they know to the actual practice of science. They write books about how a good scientific theory should be [constructed], but that's all. One of the things I set out to do from the very beginning, in the very long term, well beyond Discovering, was to apply what I know about the history and philosophy of science to some real scientific problems. That's what got me into AIDS.

"The whole idea of science," he adds, "is that paradigms have to be challenged." Without conflict, there is no progress. And yet for nearly a decade, there has been only one hypothesis. "Right or wrong isn't the issue here," Root-Bernstein says. "The issue is to force people to look at the entire field of possibilities." *