VIRUSMYTH HOMEPAGE

PREFACE

By Richard Strohman

Infectious AIDS; Have we been misled?


It is easy enough to find a theory, logically harmonious and with important applications in the regions of fact, provided that you are content to disregard half the facts.... An unflinching determination to take the whole evidence into account is the only method of preservation against the fluctuating extremes of fashionable opinion.

Alfred North Whitehead

If ever there was a rush to judgment with its predictable disastrous results it has been the HIV/AIDS hypothesis and its aftermath. Announced at a press conference prior to the publication of any scientific proof, complicated and confused by early legal arguments concerning theft of the "French" virus by American researchers, the continuing inability of a worldwide scientific effort to muster clear proof for causality of AIDS by HIV, the inability-after 10-plus years and billions of dollars-to generate any progress in prevention or therapy, and amid growing controversy about effectiveness of drugs like AZT to have any benefit, the HIV/AIDS hypothesis remains simply that: a theory with erratic correlation, but no proof of causality, between HIV and AIDS. I say "erratic," because of the many HIV-positive cases with no AIDS and of the many AIDS cases with no HIV (see Chapter Seven), and also because the circular definition of AIDS (no HIV = no AIDS) makes any correlation meaningless to begin with (AIDS patients without HIV are not officially listed by the CDC as having AIDS).

The collected works of Peter Duesberg is the closest thing we have-in the HIV/AIDS controversy-to a steadfast refusal to disregard uncomfortable facts. No one can know all the facts, and the science of HIV/AIDS is fractured among many disciplines so that few scholars can barely keep up with any one of them. This collection of publications, however, leaves out very little. Even so, it can only suggest the staggering amount of work the author has actually done over the years since this effort began in 1987. It is, in its depth and breadth, a magnificent effort dealing with subjects ranging from molecular biology of viruses to immunology, cell biology, and epidemiology. In this age, when even the best of us find it impossible to keep up in our own narrowly-defined fields, the fact that he has kept a careful watch on the literature of the breadth indicated is simply astounding. Since 1987, I have watched Dr. Duesberg spend virtually every day, twelve hours each day, month after month, year after year-at first having some staff, but very soon with none-trying to make sense out of what was, and remains, a scientific enigma: the HIV/AIDS hypothesis.

In 1987 Peter Duesberg was at the top of his career and the future was promising. He was, and is now, a full professor of Molecular and Cell Biology at UC Berkeley, and a member of the National Academy of Sciences (1986). He was the recipient of a seven-year Outstanding Investigator Award Grant from the National Institutes of Health that provided him with hundreds of thousands of dollars to conduct his research on the molecular biology of viruses. His brilliance as an experimental virologist was acknowledged around the world and his prizes for leadership work are many. Now, in 1995, he has no grants from the National Institutes of Health and, therefore, his research has come to a halt. Peter Duesberg is fifty-eight years old, vibrant, capable, full of research ideas, and wants to do much more. What happened?

In 1986 and 1987, Peter was on leave from Berkeley at the National Institutes of Health in Bethesda where he was a prestigious Fogarty Scholar-in-Residence. During his sabbatical time there he had many conferences with his host, Stuart Aaronson, and with Robert Gallo, and other leaders in cancer research and virology. After all, he was himself one of the leaders in molecular biology and the time there was pleasant, provocative, and productive. He had gone there to sit in the magnificent library, to gather his thoughts on the future of virological research, and to ponder what his own contributions might be in the years ahead. One of his interests was cancer biology ... he had isolated the first so-called cancer gene in 1970, and had worked out the genetic structure of several retroviruses. But after more than fifteen years of intensive work he had become convinced that viruses had little to do with human cancer. His conclusions were summarized in a "Perspective" article commisioned by Peter Magee, editor of the prestigious journal Cancer Research.

His article was published 1987 under the title "Retroviruses as Carcinogens and Pathogens: Expectations and Reality" (Chapter One). In this review he made the case against retroviruses (without oncogenes) as cancer-causing agents. While we continue to hear much publicity about cancer genes, many thoughtful biologists and medical researchers agree that the war on cancer, fought mostly on molecular genetic grounds, has not been won and that the strategy needs fundamental change. But that is another story. Peter's case was a strong one and I remember discussing it with some of my own friends at the NIH who were quite surprised that someone of Peter's stature would basically declare obsolete one of the mainstream approaches to such an important disease. That paper still stands with fundamental questions about viruses as carcinogens unanswered. The most fundamental of these was: Why are cancers not contagious if they are caused by viruses? An alarmingly simple question when you think about it; perhaps too simple for a cancer establishment already fully committed to a virus hypothesis.

The last four pages of this review were devoted to HIV and its role in AIDS. It appeared to Peter that many of the same contradictions that appeared in the retrovirus/cancer hypothesis also appeared in the HIV/AIDS hypothesis. He systematically began to discuss the weaknesses in HIV as a retrovirus causing immunodeficiency. Included in his criticism back in 1987 were the following crucial points that stand against the hypothesis and that remain completely unanswered by the scientific orthodoxy in charge of AIDS research:

  1. There is HIV infection and low or no risk of AIDS; therefore, something other than HIV must be involved.
  2. The long latent period between infection and clinical disease is inconsistent with the short generation time of retroviruses which is only 24­48 hours and with everything known about experimental retroviral disease. AIDS remains as the only claimed retroviral disease outside of the laboratory!
  3. The levels of actual HIV found in the blood of AIDS patients is too low to account for observed loss of immune function.
  4. There is no animal model for AIDS.
  5. HIV is not directly cytocidal; it does not kill T cells.

All of these points were then, and are now, defended by a close analysis of available data, as you will see. As the reader goes through this collection, it will become clear how steady are these points and how they remain critical and unanswered. The last point is of special interest since, in 1995, eight years later, we find in Nature, arguably the leading science weekly journal in the world, the commentary that, at the same time (a) confirms Peter Duesbereg's contention (point number 5, above) that the evidence could never have supported direct viral killing; and (b) shifts the standard hypothesis around 180 degrees. The Nature commentary, in an article dealing with HIV, said that: "... an intrinsic cytopathic effect of the virus is no longer credible." (Wain-Hobson, S. Nature, 373: 102, 1995).

What very few people realize, including most professors of molecular biology that I know, is that this shift has occurred: that the orthodox view of HIV as a direct killer of human immune cells has been thrown out. This is a crucial issue since the experiments surrounding this new view, while they have received wide acclaim by the AIDS orthodoxy, are seen to be flawed by many other experts (see Nature, Scientific Correspondence 375: 193­198, 1995).

The new view is that the source of trouble is not direct killing by HIV but rather a cell-mediated killing of HIV-infected cells by the immune system itself (Wei, et al., and Ho, et al. Nature 373: 117­126, 1995). This turn-around was necessitated by the fact that Duesberg's third point (above) was also true. How could HIV kill so many T cells if one could not detect significant numbers of free HIV in a patient's blood? This question has remained unanswered until these recent reports. Using new amplification methods to detect HIV, Wei and Ho conclude that, indeed, free virus is found after all. However, as Duesberg and Bialy, have pointed out (see Chapter Twelve), the new method (PCR) does not measure free virus but only highly amplified amounts of viral RNA. This method amplifies an original HIV-RNA signal by many thousand times so that error becomes a major problem in quantitation. That is, it is extremely difficult to know with any precision exactly what the level of starting material might have been. It is one of the problems in HIV/AIDS and other disease research that highly sophisticated molecular measurements are used as surrogate markers for infectious virus units, the only significant units in biological measurements of this kind.

Kary Mullis, the inventor of PCR, takes a dim view of using PCR in the above manner indicating that it is a very poor substitute for identifying "live" virus (replicating virus) in the blood of an AIDS patient. Most people, including most biologists, do not know that it is almost impossible to isolate live virus from AIDS patients; a crucial point that Duesberg has been making for almost ten years.

A careful reading of Dr. Duesberg's criticisms, and the papers themselves, reveals that when one establishes standards to convert PCR results to actual viral numbers, those numbers reflect the same old low levels of infectious HIV (Duesberg and Bialy, see above). That is, there are still no valid measurements that lead one to the conclusion that AIDS patients have high levels even of infectious HIV. But let us suppose the PCR studies are correct and that AIDS patients actually harbor high levels of infectious HIV and that a war of attrition against the immune system, after ten years, finally takes its toll. But it is precisely because of the fact of latency-Duesberg's second point, above-that such a war is so unlikely. With the high (PCR) viral numbers reported (100,000 HIV per ml blood) every cell in the body would soon be infected. But with this level of infection it becomes impossible to explain the lag period; such an infected person would surely be dead within days or weeks if HIV truly caused AIDS. This is just one of many contradictions present in the latest claims from Nature that the critics of the HIV hypothesis have finally been silenced. In fact, the editor of Nature has, in a flagrant act of censorship, called for Peter Duesberg to quit his role as critic, and he has stealthily used his power as editor to enforce Duesberg's silence in the journal ("Has Duesberg a right of reply?," Nature 363: 109, 1993)

This new research, together with its contradictions and false claims, are just surfacing as the Duesberg collection goes to press. But the reader will get some accurate sense of the state of confusion generated by this research from the recent "Scientific Correspondence" in Nature (375: 193­198, 1995) and from a full discussion of the HIV numbers game by Duesberg and Bialy in Genetica (Supplement, in press,1995), reprinted in Chapter Twelve in this volume.

This change of purported mechanism of AIDS causality is just the latest example of flip-flopping by the HIV/AIDS research orthodoxy where the emphasis on direct HIV killing needs to be modified in order to accommodate the reality of AIDS natural history. The other most recent "shift" in emphasis involved discarding what was the earliest and most telling characteristic of AIDS, Kaposi's sarcoma. Kaposi's sarcoma is no longer considered to be caused by HIV (see Chapter Ten). But very few people take note. Few have the time to follow even the highlights of this enormous literature. Of course, we also are reminded by Dr. Duesberg that the definition of AIDS is completely circular and makes a mockery of its scientific pursuit. If you had Kaposi's sarcoma, or any other AIDS disease, but no HIV, then you would not receive a diagnosis of AIDS. You would simply enter the hospital record book as a patient with Kaposi's sarcoma, or with whatever other disease you actually had. No HIV, no AIDS ... very simple, but also impossibly irrational since causality is built into the definition.

The first paper in this collection begins with a quotation from Sherlock Holmes: "How often have I said to you, that when you have eliminated the impossible, whatever is left, however improbable, must be the truth."

What is left, for many of us, is the clear truth that after more than a decade of intensive research and billions of dollars spent, we have not moved the HIV/AIDS hypothesis from the realm of correlation to the realm of causality. At best, what we have is circumstantial evidence for a theory born under most unfavorable circumstances. We also have, as Peter Duesberg shows us, strong conflict between the HIV hypothesis and reality. The truth is that we really still do not know what causes the immunodeficiency behind AIDS. In view of this, Duesberg has proposed that recreational drugs and AZT cause AIDS. Although the HIV establishment gives him full credit for "the drugs hypothesis," the fact is that such a hypothesis is nothing new. It was, in fact, the first AIDS hypothesis formulated by the CDC. In the early days, many independent investigators called it the "lifestyle" hypothesis. If it were not for Peter Duesberg, and a few others, with the rush to judgment about HIV causality, even this much of the truth would be hidden from us.

What should we do with the information he has given us? AIDS research focuses almost entirely on HIV. For any other disease of this importance, and with an analysis like the one before us in this collection, we would immediately begin to diversify our research portfolio and begin to include lines of inquiry into the vast number of possible causes of immunosupression in addition to HIV that we know about. This is what we should do now. What should we do about what has been called the "Duesberg phenomenon" (Chapter Ten)? With him we have a wise and dedicated analyst and critic of one of the most important developments to come onto the public health scene in over fifty years. If he is correct-or even partially correct-he will have already provided us with invaluable alternative rationale and directions. He has done what Nature editor John Maddox once recommended, and he has lost his research grants and with them, the power to do the kind of work that needs doing. Maddox said,

Is there a danger, in molecular biology, that the accumulation of data will get so far ahead of its assimilation into a conceptual framework that the data will eventually prove an encumbrance? Part of the trouble is that excitement of the chase [for molecular answers] leaves little time for reflection. And there are grants for producing data, but hardly any for standing back in contemplation. (Nature 333: 11, 1988).

Peter Duesberg has stood back in contemplation and concludes that AIDS has been forced into a monolithic pattern of viral causality. The physicist Freeman Dyson recently argued in the New York Review of Books, May 25, 1995, that: "Science flourishes best when it uses freely all the tools at hand, unconstrained by preconceived notions of what science ought to be."

Peter Duesberg argues against a preconceived viral causality, and for pluralism in the science of AIDS. The argument that AIDS research is already a wide-spectrum effort is specious. Of course, funded projects range over a wide variety of disciplines; but all disciplines focus on a single idea-HIV. The expectation is that the more the better, and that sooner or later the details will make the preconceived picture clear. Peter Duesberg argues that we need a new picture, or several pictures. His own alternative view that drugs, and not HIV, cause AIDS, is one of many reasonable possibilities not considered by our present monolithic research establishment centered on a "virus only" approach. Peter Duesberg should be given a medal and a large grant simply to continue this invaluable service of critic-at-large. Instead, he is ignored and discredited by the mainstream scientific community, including Maddox himself (Chapter Twelve).

This collection of scientific analyses of the HIV/AIDS hypothesis will provide the reader with a basis for judgment about this most important public health issue and about the appropriateness of its current research strategy. It will also provide an essential background for an understanding of the ways in which science goes wrong in dealing with internal controversy. There used to be a place for criticism of mainstream thinking, especially from old hands like Peter Duesberg who were recipients of NIH Outstanding Investigator awards that are supposed to encourage "innovative" thinking. It is suggested that it is simply a fantasy to think that open criticism is welcomed within scientific inner circles; for example do not Nature and Science continue to run articles and scientific correspondence on the HIV/AIDS and other controversial issues? The answer, is of course, that yes, they do. But with HIV/AIDS, any reading of these major scientific journals reveals a deep-seated reluctance to engage in an evenhanded exchange (see Chapters Ten and Twelve). What is also revealed is that dissent within the accepted paradigm is allowed; but woe to those who question too deeply and with steadfast commitment the scientific basis of that paradigm. In January 1995, Nature's editor, two years after calling for Peter Duesberg to cease and desist, thought (wrongly) that the HIV/AIDS question had been settled in favor of the HIV hypothesis (the Wei and Ho papers mentioned above) and he confidently reversed himself and publicly requested a scientific response from Duesberg. That response was promptly prepared and offered (see Chapter Twelve) but, as mentioned above, was rejected. Apparently, it was, at 2,000 words, too long and raised too many fundamental questions. As the leading critic, Duesberg was instead offered 500 words with which to mount a critical evaluation of highly technical research results presumably of decisive importance in settling an issue of great scientific and human importance.

Critics in a free society that cares, especially about the existence of an unfettered science, deserve better treatment. We all suffer when they are treated in such a shabby manner. *

Richard C. Strohman UC Berkeley May 1995


VIRUSMYTH HOMEPAGE