What causes AIDS?: the debate continues.

In the June issue of REASON, Charles A. Thomas Jr., Kary B. Mullis, and Phillip E. Johnson argued that the hypothesis that HIV causes AIDS has been falsified and that it is important to reopen scientific debate on the question. REASON takes no stand on the former conclusion--though the editors believe the article made a strong case--but it strongly supports the latter.

To further that debate, REASON solicited letters from scientists pursuing AIDS research and others with a strong interest in the subject, some of whom responded. We also received numerous letters from readers. A selection is printed here, along with the authors' reply.

* "What Causes AIDS? It's An Open Question" provided a lucid explanation for skepticism over the role of HIV in AIDS. As an African historian, I am appalled by the unscientific diagnoses of AIDS in Africa and the persistence of Western racist myths about sexual promiscuity on that continent. "What Causes AIDS?" gives my students a valuable introductory source to begin rethinking AIDS in Africa.

As chairman of the History and Philosophy of Science Section for the Pacific Division of the American Association for the Advancement of Science (AAAS), I included Thomas, Mullis, and Johnson at a symposium on "The Role of HIV in AIDS: Why There is Still a Controversy," which I organized for our June 1994 conference in San Francisco. Even though the symposium was approved by the executive committee of the Pacific Division in January and publicized in division newsletters sent to 30,000 members, the AIDS establishment mounted a behind-the-scenes effort in May to either cancel the symposium or seriously reconfigure it.

The increased desperation of the HIV=AIDS orthodoxy among journalists and within the biomedical research establishment will prompt more attempts to stifle debate. Their efforts to mislead the public through scientific censorship are doomed to failure as long as we can count on courageous publications like REASON.

Charles L. Geshekter Professor of History California State University, Chico Chico, CA

* I was glad to see REASON entering the HIV/AIDS fray. My own experience in writing about this subject has convinced me that Thomas, Mullis, and Johnson are right.

Often cited as evidence that HIV, and not drug use, is the real cause of AIDS, is a paper published in Nature, written by Ascher, Sheppard, and Winkelstein. I was surprised to read, in a March 11, 1993, story by Gina Kolata in The New York Times that this Nature article had been written specifically in response to an op-ed piece I had written for the San Francisco Chronicle six months earlier. "Dr. Ascher and his colleagues wrote their paper in response to a challenge by Tom Betbell," Kolata wrote, quoting Ascher as saying that "Tom Bethell threw down the gauntlet," forcing them to do the study. I can only say that this must be the first medical study ever written specifically in response to an op-ed piece by a journalist, and then published by Nature. Any doubts that I may have had about the political character of AIDS vanished when I read Kolata's weird article. The fact is, I am now convinced, AIDS is not a disease at all--it is a government program.

At the June AAAS meeting in San Francisco, Bryan Ellison, a graduate student in Molecular and Cell Biology at U.C. Berkeley, presented a reappraisal of the Ascher study, having obtained the raw data on which it was based. Ascher et al. had examined a cohort of about 1,000 men in San Francisco and had found that, surprise, surprise, all of those who developed AIDS were HIV positive! Once again, however, the definition of AIDS included HIV positivity. The real question was: How many AIDS-defining diseases were to be found in the HIV-negative cohort? Ascher et al. had failed to report this key information. But the raw data from the original survey showed at least 45, and possibly as many as 200, AIDS-related diseases among the HIV-negative men, Ellison told the AAAS gathering.

Tom Bethell Hoover Institution Stanford, CA

* "What Causes AIDS?" exaggerated some facts out of context to reach outrageous and misleading conclusions.

HIV is a silent, fatal, contagious disease that is in fact spreading now into the heterosexual population, especially adolescents, and the usual public-health strategies that have been employed for decades to halt the spread of the virus have not been applied to this illness due to certain political lobbies. These same groups love to utilize "AIDS" data rather than HIV prevalence since, with a silent 10-year latency, AIDS data tells you what was happening 10 years ago.

Recently, the Centers for Disease Control released data from 22 of the 24 states reporting HIV cases (not including California, New York, etc. where rates are highest). For male teenagers, the ratio of HIV to AIDS cases is eight to one. For female teenagers, the ratio is 22 to 1. When you analyze AIDS data, you don't see the epidemic coming because you're looking backward, the wrong direction. For Thomas et al. to claim that the virus "remains almost entirely confined to the original risk groups" is untrue and dangerously lackadaisical. Summarizing the recently released CDC data, AIDS Alert, October 1993, concludes, "the fastest growing mode of infection is through heterosexual contact while intravenous drug use has leveled and homosexual transmission has declined."

Thomas et al. present "evidence" that HIV does not lead to AIDS because many people have HIV without these diseases. This is entirely consistent with the long latency period. And the vast majority of those dying of AIDS have HIV.

The authors wrongly contend that the HIV antibody test is plagued by false positives. The test is extremely sensitive, and final reporting is made specific by the confirmatory Western Blot and other back-up tests. Col. Donald Burke, a research virologist at Walter Reed Hospital, has personally supervised several million HIV blood tests for the routine Army testing of recruits. His statistics demonstrated that HIV testing resulted in less than one false-positive in one million blood tests.

It is frustrating for me to see Thomas et al. use the fascinating mysteries of this disease to bring fuel to the fire of those who have been hindering a prudent scientific approach to this epidemic.

Daniel Cosgrove, M.D. Palm Springs, CA

* As a scientist, albeit not an expert on AIDS, I would like to explain why I did not find the article by Thomas, Mullis, and Johnson to be very convincing. First, it is no surprise that some people who are HIV-negative fall ill with the diseases associated with AIDS (Kaposi's Sarcoma, certain types of pneumonia, etc.). These diseases are not new. Factors other than HIV virus can damage the immune system and may make individuals susceptible to these, and other, illnesses.

What we have been seeing since the early 1980s is a much larger number of immunodeficient individuals exhibiting a number of hitherto uncommon illnesses, who are also infected with the HIV virus. We also see that a significant number of people lacking the symptoms of AIDS soon develop them after being exposed to the bodily fluids of individuals infected with HIV.

In the absence of any other explanation, simple induction leads us to the conclusion that HIV is either the cause, or part of the cause, of AIDS. True, in the absence of a causal mechanism for AIDS this is not final proof that HIV causes AIDS, but currently it is the best explanation we have.

Second, it is also not surprising that some HIV-positive individuals do not develop the symptoms of AIDS. In the population of millions of HIV-infected individuals, it is to be expected that genetic diversity should ensure that at least some individuals are resistant or even immune to HIV. If this were not so, the plethora of other diseases and plagues that humans were subject to before the discovery of vaccines, antibiotics, and modern medicine would have long since caused our species to become extinct. In this respect, HIV infection should be no different.

If the authors and their intellectual ally, Dr. Peter Duesberg, are convinced that HIV does not cause AIDS, then let them put forth an alternative hypothesis and propose a course of research to determine the true cause of AIDS. Creative research is much more difficult than criticizing the efforts of others.

Ron M. Kagan Ph.D. Candidate, Biochemistry University of California Los Angeles, CA

* Is HIV "a conventional retrovirus with a very simple genetic organization"? Well, most retroviruses can get by with three or four genes, whereas HIV has nine. All other viruses in the subfamily to which HIV belongs (the lentiviruses) are responsible for fatal immune-cell disease in animals (sheep, cattle, horses, cats, monkeys), and scientists have not been able to develop a cure for any of these either.

Was the HIV=AIDS dogma established, without scientific foundation, by a press conference? No. Although considerable publicity was attached to a premature announcement by Dr. Gallo in 1984, there was agreement by consensus, not by fiat. The relevant scientific papers were published a few days later in the May 4 issue of the journal Science and served as confirmatory evidence of the strong association between AIDS and a retrovirus similar to one that had been discovered the year before in a wide variety of AIDS patients by researchers at the Pasteur Institute in France.

Several other investigators in this same time period were also in the process of isolating a virus from their AIDS patients (Karpas in England, Rossi in Italy, Francis in Atlanta, and Levy in San Francisco). All of these viruses, initially called by different names, eventually turned out to be variants of the same virus. The name was not standardized to HIV until 1986.

Is there not "even a theoretical explanation for the disease-causing mechanism"? Of course there is. Although the immune response to the initial HIV infection soon eliminates free virus particles from the bloodstream, it is usually unable to eliminate the virus if it has already infected cells in the organs of the lymphatic system. Once there, the virus slowly propagates from cell to cell like a cancer, gradually infiltrating these organs (the lymph nodes, spleen, thymus, tonsils, adenoids, appendix, etc.), many of which are redundant and can withstand a lot of damage before there are any obvious symptoms of impaired function. Blood cells that are susceptible to the virus, called T-helper lymphocytes, continually circulate through the diseased lymphatic organs and are gradually trapped and killed off. The part that is not understood, and for which "increasingly exotic causal mechanisms" have been proposed, is whether the virus kills them directly, or the immune system itself kills them because the mere presence of the virus has made them abnormal.

Are HIV-negative cases of AIDS being ignored or covered up by the medical establishment? Hardly. In 1986, a patient from West Africa with obvious AIDS was found to be negative for HIV. This led to the discovery of a defined AIDS-causing lentivirus now called HIV-2.

Are the opportunistic infections that are characteristic of AIDS sometimes found in the absence of HIV? Of course. They are simply rare in the general population, not non-existent! They were discovered and named long before AIDS came along, and can get the upper hand in anyone whose immune system is temporarily depressed. Thousands of such people "disappear from the official statistics" because they get well, not because the CDC is engaged in some sort of nefarious cover-up.

Nevertheless, since HIV is now so widely used as a diagnostic test for AIDS, the possibility does exist that an epidemic of HIV-negative AIDS could occur without our realizing it from standard statistics. This is why an exhaustive search for HIV-negative patients with profound unexplained immunodeficiency was undertaken in 1992. Less than 100 scattered cases were identified worldwide. They were studied and their disease given a new name (ICL) because their immune abnormalities were found to differ slightly from those typical of AIDS. In any case, the number of such patients compared to the hundreds of thousands of AIDS patients reported around the world is vanishingly small.

If the authors of this article truly believe that there is an epidemic of deaths from sustained immune deficiency that can not be explained by HIV or other known causes, I urge them to avoid the entrenched HIV=AIDS hypothesis by reporting these cases to the CDC as a new disease, rather than attempting to link them to AIDS.

George Fergus Schaumburg, IL

* Thomas, Mullis, and Johnson state that "chimps have repeatedly been infected with HIV, but none of them have developed HIV." True enough, and none ever will. Chimps are not susceptible to HIV because that virus targets the human, not simian, genome. But chimps infected with the SIV (simian immunodeficiency virus, a virus genetically similar but not identical to HIV) do develop suppressed immune systems and the symptoms of AIDS. It is inexplicable that these writers do not recognize that a chimp's failure to contract AIDS from HIV no more addresses the consequences of HIV infection in humans than does the human failure to contract feline leukemia virus indicate that cats cannot contract leukemia either.

This impressive display of epidemiological ignorance casts doubt on their ability to interpret evidence wisely, but there's more.

They say the virus is generally not detectable in people with advanced AIDS; a large body of literature exists confirming that the virus is present and detectable during all stages of the disease. They claim HIV is a simple retrovirus that is not capable of the sophisticated behavior it apparently displays; epidemiologists have described HIV as a complex virus whose full genome is not yet understood.

Thomas, Mullis, and Johnson imply that Warner C. Green in an article in the September 1993 Scientific American acknowledges the supposed tenuous connection between HIV and AIDS. Green does nothing of the sort. In fact, in that article he writes: "I must emphasize that all responsible opinion holds that HIV is indeed the cause of AIDS. A small number of cases of people with immune deficiency who are not infected with HIV received inappropriately widespread publicity last year, which fostered the unsubstantiated notion that there is another cause of AIDS not detected by current blood tests."

The authors also suggest that causality between HIV and AIDS has not been proven; all we have, they say, is a correlation between the two. Science, however, will never be able to "prove" that HIV causes AIDS any more that it can prove that varicella causes chicken pox. Proving a positive is an impossibility (an assertion can only be disproven). All relationships between viral infections and resulting symptoms are ultimately correlational. (With HIV the authors fail to assert that this correlation is strong: virtually everyone infected with HIV develops AIDS-like symptoms within 10 years.)

HIV may not be the cause of AIDS, but the overwhelming body of evidence tells us otherwise. Suggesting, as the authors do, that the government is standing in the way of finding the real cause of AIDS given the amazing lack of evidence for such a statement is irresponsible. The authors should not have made it, and REASON magazine should not have printed it.

Mark W. Nowak Arlington, VA

* The epidemiologic, laboratory, and clinical evidence that HIV is the cause of AIDS is overwhelming. This evidence has been used as a basis for national and international prevention programs and clinical and vaccine trials.

Thomas et al. mix fact with fiction to misinform readers. For example, the authors suggest that AIDS cases are an artifact of the CDC's AIDS surveillance case definition, that there are "thousands of cases of AIDS without HIV," and that "such cases tend to disappear from the official statistics."

The AIDS surveillance case definition was not designed to prove the existence of HIV. However, it provides additional evidence to what epidemiologic and laboratory studies have already told researchers--that HIV causes AIDS. Case definitions of any disease or health condition are basic tools of public health surveillance. They are devised by epidemic investigators in response to clusters or outbreaks of new or unusual health phenomena. The first CDC AIDS surveillance case definition was developed in response to clusters of patients with unexplained opportunistic infections and Kaposi's sarcoma in 1981. Patterns identified from early case reports provided convincing evidence that the new syndrome was caused by an infectious agent. This definition has been expanded three times (in 1985, 1987, and 1993) in response to greatly increased knowledge of the immunopathology and health effects of HIV infection; each expansion served to encompass more persons with symptomatic HIV infection. Thus, far from being an artifact, the CDC's AIDS surveillance case definition is what it was intended to be--a tool to track the many persons in the latter stages of HIV infection.

The authors claimed that there are "thousands of cases of AIDS without HIV." A small percentage of cases reported to CDC have been in patients who have never had an HIV antibody test. The majority of these cases were diagnosed and reported before the first HIV antibody test was licensed in 1985. These cases were diagnosed based on the presence of "indicator" diseases (mainly Pneumocystis carinii pneumonia and Kaposi's sarcoma) that are very rare in immunocompetent persons not infected with HIV. In addition, their supposition that these cases were further defined as idiopathic CD4+ T-lymphocytopenia (ICL) is not true. Investigations show that ICL cases and AIDS cases differ epidemiologically. Thus far, researchers have found that ICL is rare, and that no more than 100 of these cases exist.

AIDS cases do not disappear. Missing or incomplete information that accompanies AIDS cases reported to CDC through state health departments is often updated. Most cases reported without risk information are reclassified as follow-up investigations are completed.

The inevitable conclusions of more than a decade of research are that most people exposed to HIV through sexual contact, injecting drugs, or transfusions are susceptible to HIV infection. Nearly all persons who become infected with HIV will eventually develop AIDS.

Surveillance data have been useful in developing prevention and control programs for persons at risk of HIV infection. AIDS prevention programs continue to be based on our understanding of scientifically defined HIV transmission modes because prevention of AIDS is prevention of HIV. To deviate from or ignore this concept would result in an unconscionable tragedy.

Brenda W. Garza D. Peter Drotman, M.D., M.P.H. Harold W. Jaffe, M.D. Division of HIV/AIDS National Center for Infectious Disease Centers for Disease Control and Prevention Atlanta, GA

* "What Causes AIDS?" contains misleading and incorrect information questioning the contagious nature of HIV infection and its causal role for AIDS. This has serious consequences, as this infection almost invariably results in long, painful, terminal illnesses and death. The authors are distinguished in fields far removed from the epidemiology of HIV and AIDS about which they pontificate. Would any of your readers hire an electrician to repair a faulty toilet?

The authors assert, "The only evidence that HIV does cause AIDS is correlation." Correlation has established the causes of many diseases: smoking and lung cancer, Staphylococcus aureus infection and toxic shock syndrome, and ionizing radiation and leukemia, to name a few. They state, "There are many cases of persons with all the symptoms of AIDS who do not have any HIV infection." This is not surprising as immune suppression, the underlying cause of AIDS, may result from defective genetic mechanisms, toxic chemical exposures, medicinal treatments, and infections other than HIV. They also assert, "There are also many cases of persons who have been infected by HIV...and show no signs of illness." About half of all HIV-infected persons develop AIDS within 10 years and of these, 90 percent are dead within two years. In studies observing HIV-infected persons for more than 10 years, over 85 percent have developed AIDS.

The authors claim that the San Francisco Men's Health Study, for which I am "principal investigator," was "designed not to test the HIV theory but to measure the rate at which HIV-positive gay men develop AIDS. They did not compare otherwise similar persons who differ only in HIV status, did not control effectively for drug use, and did not fully report the incidence of AIDS-defining conditions in the HIV-negative men." These assertions are misleading or just plain false.

The San Francisco Men's Health Study is an epidemiological investigation of the cause or causes of AIDS, its transmission, and the natural history of the disease. Participants were a random sample of 1,000 single men living in AIDS-affected areas of San Francisco in 1984. When a serological test for HIV infection became available in late 1984, the participants were tested to determine HIV-infection status. This allowed the investigators to conduct a large number of important analytic studies of causal factors, modes of transmission, and the natural history of HIV infection and AIDS.

An analysis of drug use, AIDS incidence, and progressive immune deficiency, using appropriate statistical techniques and proper controls, was published in 1993. No relationship between drug use and AIDS incidence or immune deficiency progression was found. The advocates of the drug etiology of AIDS have never accepted these findings nor the findings from several other rigorous studies of the drug hypothesis.

Because an AIDS diagnosis is almost invariably followed by death within two years, deaths may be substituted for AIDS diagnoses to evaluate the occurrence of cases among the uninfected. In the San Francisco Men's Health Study, 581 participants, who were uninfected by the HIV on entry, remained uninfected for over eight years. Among them, eight deaths occurred, for a cumulative rate of 1.4 percent. Of the 400 men infected by the HIV, 169 deaths occurred, for a cumulative rate of 42.3 percent. These data are inconsistent with the contention that there were AIDS cases among the uninfected.

Space precludes a complete refutation of the other misstatements which burden the article. The readers of REASON magazine should not be misled about the consequences of HIV infection. As indicated above, these consequences are very serious. Regardless of whether or not HIV infection causes AIDS, it is a strong predictor of premature death.

Warren Winkelstein Jr., M.D., M.P.H. Professor of Epidemiology (emeritus) School of Public Health University of California Berkeley, CA

* It has now been over three years since I first challenged Peter Duesberg and a co-writer that if they really don't believe HIV causes AIDS they should publicly inject themselves with the virus. It would hardly be the first time a doubter of a pathogen-disease hypothesis has intentionally exposed himself. Nevertheless, Duesberg and fellow have steadfastly refused to do so and neither have any of Duesberg's vocal followers volunteered to take their place. They won't shoot up, but as their article "What Causes AIDS? It's An Open Question," shows, they won't shut up, either.

To address just a few major points:

They write that "after spending billions of dollars, HIV researchers are still unable to explain how HIV, a conventional retrovirus with very simple genetic organization, damages the immune system, much less how to stop it."

Only three retroviruses have been discovered, the first barely over a decade ago. How does one become "conventional"? The authors want us to believe that because it is "conventional" and simple genetically it should have been cured by now, but all viruses are genetically simple and we have cures for none of them. What will make curing HIV all the harder is that it is so very unconventional in that unlike any other human virus we know about, it attacks the very immune system and to date our disease-fighting tools have always relied on the immune system as an ally.

As to how it damages the immune system, there are numerous medical journal articles on the subject, the latest in the June 2 issue of Nature. This doesn't mean we understand how HIV works in the same way that we understand, say, internal combustion in a piston engine. Human physiology is infinitely more complicated than a motor. Still, we certainly know more about the actions of HIV than we do about most viruses simply because HIV has been so heavily studied. Finally on this point, knowing the cause and knowing the cure may have little or no relationship. For hundreds of years, people knew that cigarette smoking caused lung cancer, yet the cure rate for lung cancer even today is dismal.

The authors state, "In the absence of any agreement about how HIV causes AIDS, the only evidence that HIV does cause AIDS is correlation." Aside from ignoring the medical literature, they fail to recognize that epidemiology has always been about correlation. Lung before there were electron microscopes, cell lines, and the National Institutes of Health, epidemiologists were identifying diseases and saving millions of lives from them based strictly on careful observance of who was getting sick and why. Walter Reed didn't have the least idea of what yellow fever did on a cellular level, but he saw that it was transmitted by mosquitoes and he was thus able to practically eliminate it. Edward Jenner developed the first anti-viral vaccine a century before anyone knew what a virus was.

The conspiracists cavalierly dismiss the San Francisco study, reported on in Nature, along with the Vancouver one, reported on in the Lancet, without providing any detail on them. Here is a brief summary of the San Francisco one. Researchers directly tested the Duesberg thesis that "either drug consumption (frequently associated with malnutrition) by recently established behavioral groups or conventional clinical deficiencies are necessary and sufficient to cause indicator diseases of AIDS." They compared a set of heterosexuals who were heavy drug users and were negative for HIV with homosexuals who were heavy drug users who were both positive and negative for the virus. Reporting their results in the March 11, 1993 issue of Nature, they found that among homosexuals who were sero-positive at the beginning of the study, over half had contracted AIDS and most had died. Among the homosexuals who were negative in the beginning and stayed negative, about 2 percent had died but none had been diagnosed with AIDS even when HIV status was excluded as part of the AIDS definition. Among the heterosexuals, less than 1 percent had died and none had gotten AIDS. In addition to devastating the drug-use-causes-AIDS thesis, this study showed as close a correlation between pathogen and disease as one could ever hope to attain.

All this means nothing to the REASON authors. Forget those studies; they weren't set up to our exact specifications, they say. No, and none ever could be. Besides, they say, "the main point they supposedly prove has already been thoroughly disproved: AIDS does occur in HIV-negative persons." But no, it doesn't. Certainly one can get diseases that resemble AIDS, just as one can get a disease that resembles the flu. (How often do we hear of someone suffering a "flu-like illness"?) A chronic cough and expectoration of blood can be symptomatic for bronchitis, tuberculosis, or lung cancer. It doesn't mean these are all the same disease. As the authors themselves point out, the definition of AIDS symptoms covers a wide area. Certainly, it's not difficult for other diseases to mimic that which some AIDS patients may be suffering. This doesn't make them AIDS cases any more than a bloody cough makes TB be lung cancer.

Among hundreds of thousands of sufferers of any given disease there will be a tremendous spectrum in manifestation of symptoms and plenty of anomalies, but with HIV there is a strong pattern of disease progression. After a few years of infection persons begin to lose T-helper cells, then begin to develop outward manifestations of immune dysfunction such as oral candidiasis, then begin to suffer life-threatening diseases such as pneumocystis carinii pneumonia. Outside of persons given immune-suppressing drugs, PCP is remarkably rare, so much so that prior to the AIDS epidemic the CDC was dispensing fewer than 100 prescriptions of pentamidine (at that time the only treatment for the disease) a year. In 1993, however, there were over 12,000 confirmed PCP diagnoses and another 7,000 suspected cases, all in HIV-positive persons. In other words, if you don't have HIV your odds of getting PCP are one in several millions. If you do have it, your odds before the introduction of aerosolized pentamidine as a preventative treatment were better than 50-50. Even now, they may be better than one in four. What an amazing coincidence.

HIV cohorts have shown that after about 10 years of infection, half of all persons will be dying while almost all of the rest will be suffering severe symptoms. The authors make much of the fact that some HIV carriers remain healthy even after 11 years of infection. As always, they ignore the rule for the exception, making us think the edge of the bell curve is the top. Probably no pathogen known kills with 100 percent efficacy; indeed, about 90 percent of persons carrying the bacteria that causes tuberculosis will never manifest the disease. An even smaller percentage will suffer symptoms from infection with cytomegalovirus. Indeed, the correlation between HIV and manifestation of symptoms, and the correlation between HIV and death, may prove to be stronger than that for any pathogen present in the human population.

Much of what the authors say is unquestionably true, and just as unquestionably doesn't support their case.

Certainly there are co-factors that increase the rate at which HIV decimates the immune system, co-factors that if blocked might greatly increase the length and quality of life for persons with HIV. Co-factors commonly play a role in disease causation. But nobody says that because mycobacterium tuberculosis appears to work with co-factors to manifest as TB that mycobacterium tuberculosis isn't the cause of the disease. The reason? Because you can have those co-factors, but without the mycobacterium, you don't get TB. Just so with HIV and AIDS. Further, quite the opposite of what the Duesberg conspiracists would have us think, scientists have already been devoting a tremendous amount of research to finding HIV co-factors, albeit with precious little to show for the effort.

And yes, certainly the African AIDS epidemic has been overstated, with every fatal disease under the African sun being dubbed AIDS because that seems to be the only disease Westerners care about. But this does nothing to support the conspiracists' hypothesis. Likewise, I was writing about--and staking my reputation on--the exaggeration of the American epidemic, especially with regards to middle-class heterosexuals, long before the authors published word one on the subject. I did so by analyzing patterns of both cases and infections. I noted in 1989 that since stored blood samples indicated that HIV infections appear to have peaked out in American cities around 1981 and 1982 and since it takes on average about 10 years for an AIDS infection to manifest, the epidemic was probably on the verge of peaking. Indeed, the CDC noted recently (to the deafening silence of the media), that using the pre-1993 definition of the disease, AIDS cases did decline in 1992.

Of course I have now become one of the AIDS conspirators--that group of persons so callous and vicious that we are willing to let hundreds of thousands of Americans alone die of this horrible disease. That or I've just closed my mind like a steel trap, like John Maddox supposedly has. "Like other leaders of the scientific establishment," write the conspiracists, "Nature editor John Maddox is fiercely protective of HIV theory. He indignantly rejected a scientific paper making the same point as this article."

In fact, toward the end of Rethinking AIDS, a Duesberg conspiracy book, author Robert Root-Bernstein crowed: "John Maddox...has written that he should have given critics of the HIV theory, such as Peter Duesberg, room to express their concerns." So he did. It was only after the aforementioned 1993 Nature article, along with two other Nature articles discussing how HIV causes AIDS, that Maddox editorialized, "Duesberg, having led many people with AIDS on a seductive path, should now admit the likelihood that he is mistaken."

But like the AIDS alarmists against whom they have rightly aligned themselves, neither Duesberg nor his acolytes are ever going to let a little thing like scientific evidence get in the way.

Michael Fumento St. Petersburg, FL

(Michael Fumento is the author of The Myth of Heterosexual AIDS.)

Charles A. Thomas Jr., Kary B. Mullis, and Phillip E. Johnson reply: Many things have happened since our article was written, all of them supportive of our position. Here are some highlights:

1) Harvard Professor Bernard Fields published a commentary in Nature that signalled, in the words of The New York Times, that "a new consensus has emerged among many leading scientists that the nation's $1.3 billion AIDS research program is on the wrong track." Planned trials of candidate vaccines have been abandoned as unpromising and dangerous because, according to Fields, "We still have too many serious gaps in our fundamental knowledge to know how to prevent and treat AIDS, and must return to a broader base to study the scientific questions confronting us."

The primary gap, of course, is the absence of anything but speculation to explain how an ordinary retrovirus can be killing billions of immune cells that it doesn't even infect. (That the PCR technique can find genetic sequences associated with HIV--not active virus--in lymph nodes does nothing to solve the mystery.) Unfortunately, Fields's back-to-the-drawing board stance, which has been endorsed by top NIH officials, does not imply any real reconsideration of the HIV dogmas that have brought the researchers to this dead end. It means only that some of the AIDS money will be diverted to general biochemical research that is only tangentially related to AIDS.

2) Another Harvard professor and member of the HIV inner circle, Max Essex, published with African colleagues a paper in the Journal of Infectious Disease detailing an extremely high incidence of false positive results among both leprosy patients and their uninfected neighbors on HIV antibody tests. In a group of 57 leprosy patients, for example, 70 percent tested positive for antibodies but more extensive testing confirmed the presence of HIV in only 2 patients. The paper concluded that, due to an unexpectedly high rate of false positives on both the ELIZA and Western Blot tests, these standard antibody tests "may not be sufficient for HIV diagnosis in AIDS-endemic areas of Central Africa where the prevalence of mycobacterial diseases is quite high." These results clearly call into question all projections about HIV infection in Africa and elsewhere that are based on antibody testing.

Antibody tests may be more reliable as an indicator of HIV infection in relatively healthy groups like U.S. Army recruits. Our critics misunderstand this subject, however. Both the ELIZA and the Western Blot are antibody tests, not tests for active, replicating virus. Both have also been shown to cross-react with things other than HIV antibodies. To say as Daniel Cosgrove does that the "HIV antibody test" is confirmed by the Western Blot in many cases is merely to say that two faulty antibody tests have produced consistent results.

3) A study by Mulder et al. for the British National Research Council (published in Lancet) has been misleadingly cited by CDC officials and others as proof that a pandemic, caused by HIV, is raging through Africa. The study actually does show that, in a Ugandan village population, persons registering positive on the antibody test had a much higher death rate than antibody-negative persons, especially in the age group 25-34. What the HIV propaganda does not say is that the subjects did not die of AIDS. Of 64 deaths of persons aged 25 to 34, only 5 were diagnosed as AIDS under the very broad "Bangui" (African) definition, which requires only conditions like sustained weight loss and persistent diarrhea. Severely diseased persons are likely to have many microbes in their system, including HIV and other things that produce positive results on the inaccurate antibody tests. That this study of non-AIDS deaths was claimed to support the HIV theory of AIDS and the existence of an African AIDS pandemic is eloquent testimony to the closed mindset that rules the HIV research community.

4) A conference on nitrite inhalants (poppers), held under the auspices of the National Institute on Drug Abuse in May 1994 was attended by such HIV kingpins as Robert Gallo and Harold Jaffe--and dissenter Peter Duesberg. Participants acknowledged that the data do not support the claim that HIV is the sole or even the primary cause of Kaposi's sarcoma (KS) in gay males. This concession is particularly remarkable because KS is still officially one of the prime AIDS-defining conditions, and many gays with KS have been classified as having "HIV disease" on "presumptive" criteria that do not require antibody testing.

The problem with the HIV/KS hypothesis is that there are dozens of known cases of KS in young gay males who have never been HIV infected, and KS is very rare among non-gay HIV positives. Even the HIV stalwarts now admit that the primary cause of KS must be some agent that is specific to gay men, such as a still-undiscovered sexually transmitted microbe specific to gays, or poppers. Thus while evidence pointing to poppers as a causative factor in KS is ridiculed by the HIV propagandists, the research community is increasingly finding the evidence impossible to ignore.

5) Mounting evidence indicates that what is called "AIDS" in hemophiliacs is caused not by HIV but by the (curable) effect of foreign proteins from treatment with unpurified Factor 8, the blood coagulant that saves hemophiliacs from an early death due to prolonged internal bleeding.

The way the good news about hemophiliacs is expressed in an HIV-obsessed research culture is by lengthening the "latency period," a statistical fudge-factor that is different in every risk group and can be adjusted as necessary to explain why so many HIV-positive people are not sick. A recent British study of 111 hemophiliacs showed that so many fewer than anticipated are suffering immune system failure that 25 percent are predicted to be "AIDS free" for 20 years or more.

What is helping hemophiliacs to avoid immune deficiencies is not harmful and ineffective antiviral drugs, but new purified blood products that do not contain foreign proteins. Highly purified Factor 8 has proved so effective in protecting the immune systems of hemophiliacs that some HIV-minded researchers are thinking of employing it against "HIV disease" in non-hemophiliacs. (Complete details on the hemophiliac studies are provided in a forthcoming paper by Duesberg in Genetica.)

This use of the latency period (and mysterious "genetic immunity") to explain away the many healthy HIV positives explains, by the way, why it would prove nothing for Duesberg or anyone else to inject himself with the virus and survive. If he lived 50 years longer and died at 110, HIV science would conclude only that the latency period is sometimes unusually long, or perhaps that Duesberg was one of the lucky folk with genetic immunity. (As for ourselves, we stick to scientific evidence and have no interest in showmanship.)

We find a similar use of this convenient fudge factor in Daniel Cosgrove's argument that the latency period accounts for why nearly 90 percent of AIDS cases are still male in North America and Europe, despite changes in the definition of the syndrome aimed at including more women. That excuse gets thinner every year as confident predictions based upon the "everyone is at risk" ideology fail to come true. We quote again the important finding of the National Research Council: "The convergence of evidence shows that the HIV/AIDS epidemic is settling into spatially and socially isolated groups and possibly becoming endemic within them." This is the opposite of what the HIV theory predicted.

6) The Tenth Annual International AIDS Conference in Yokohama in August 1994 was the last of its kind. The annual gathering of the multitudes who make their living from HIV will be skipped next year, because HIV science is at a virtual standstill and there is nothing of importance to announce. The great breakthrough touted in Yokohama was a study claiming a reduction in the rate of infant HIV infection when expectant mothers and babies were given AZT. The study was terminated abruptly, as has happened with earlier AZT studies that began to show favorable results at an early stage.

In consequence a highly toxic drug that is known to be ineffective and positively harmful in antibody-positive adults will be given routinely to unborn and newborn infants with antibody-positive mothers, although most of these infants would never be HIV infected anyway. The uncertain benefit and great risk would make such a reckless course of conduct unimaginable in normal circumstances, but the AZT lobby backed by HIV hysteria has the power to overrule the prudent standards that protect the public from other dangerous and unproven drugs.

What the Yokohama conference lacked in science it more than made up in scare stories and plans for worldwide social engineering to protect Asia and Africa from depopulation. (As Tom Bethell says, AIDS is not so much a disease as an open-ended government program.) The media as usual reported uncritically the claims that HIV infection is increasing rapidly everywhere in Asia and Africa and that the relatively low number of AIDS cases actually reported is just the tip of the iceberg.

What the media did not report is that the same virus that is supposed to be newly infecting millions of people every year in regions where reliable statistics are hard to come by has been stable in the U.S. population ever since testing began, almost 10 years ago. Every year the AIDS agencies ominously report that "1 million people are now infected with HIV," and the reporters never point out that the figure was exactly the same the year before and the year before that. We call upon the CDC to confirm or deny what The New York Times reported months ago--which is that the most reliable studies show that the actual total number of antibody-positive Americans is well under one million, and not rising. The thoroughly researched American figures utterly contradict the inflated claims about HIV infection rates in Asia and Africa--unless we indulge the kind of racist speculation about non-white sexual habits that Charles Geshekter rightly denounces in his letter.

As one of us (Mullis) has frequently commented, there is no paper in the scientific literature that reviews all the relevant evidence and establishes that HIV is the cause of AIDS. George Fergus to the contrary notwithstanding, the original papers announcing the discovery of HIV in 1984 said only that HIV had been found in some (not all) of a small group of AIDS patients. No proof was presented, but Dr. Gallo and his fellow virologists seemed so confident that the research community wrongly assumed that they had the proof. Once that assumption was set in concrete as the foundation for funding, critics could no longer be tolerated.

Instead of a paper that takes the objections seriously and undertakes to prove the point at issue, we find only polemics that assume the HIV theory and defend it against specific criticisms with question-begging arguments. Mark Nowak, for example, says that the failure of HIV to cause AIDS in the many chimps who have been deliberately infected with the virus says nothing about whether HIV causes AIDS in humans. Our point was that one of the recognized ways of proving that a virus does cause a disease in humans is to cause the disease in animals by infecting them with the virus, and such efforts have failed with HIV. The chimps do get HIV infection, just like humans, and HIV does no damage to their immune systems. Why not? To say as Mark Nowak and the HIV scientists do that "HIV does not cause AIDS in chimps" is merely to restate the question.

The absence of an animal model is not cured by tall tales about the so-called simian immunodeficiency virus. SIV does not cause a syndrome like AIDS in animals. The distinctive and improbable claim of the HIV/AIDS hypothesis is that the HIV supposedly damages the immune system only after the immune system has successfully countered the primary infection and reduced vital activity to negligible levels. "SIV disease" follows the primary infection closely, and does not occur after a latency period of ten years during which viral activity in the blood is practically non-existent. It also occurs only in laboratory animals, who tend to have weakened immune systems already. The same retrovirus is found in wild populations causing no ill effects. Other claims of "lentiviruses" causing diseases in animals many years after infection are also controverted in the scientific literature, and may reflect the enthusiasm of virus hunters to attribute disease conditions to the viruses they have discovered.

Because of the absence of an animal model, or plausible mechanism for T-cell destruction by an inactive virus, the whole case for HIV causation rests on correlation. But very sick persons with damaged immune systems carry many microbes, and it is impossible with correlation studies alone to prove that a particular microbe is the effective cause of the syndrome rather than a mere "passenger." To distinguish cause from effect, studies must be carefully controlled. Above all, the syndrome must be defined in a way that does not prejudice the outcome. But the CDC's response to our article admits that AIDS is defined as a range of disease conditions accompanied by real or suspected HIV infection, so that HIV causation is presumed in the definition of the syndrome. The CDC's response, translated from the bureaucratese, is simply "that is how we do it around here." Use of a biased definition that assumes the very correlation to be proved is professional malfeasance on its face.

Things are even worse than that. Tens of thousands of cases of persons with diseases like KS (this is the "small percentage" to which the CDC refers) have been diagnosed on presumptive criteria without antibody tests, and this practice is still allowed. Duesberg's estimate of several thousand American cases of AIDS without HIV comes from examples in the medical literature where individuals were diagnosed with AIDS on the basis of disease conditions or immune deficiencies and then the diagnosis was reversed when HIV was not found. We consider this estimate conservative, because in logic every person with a condition that would be diagnosed as AIDS if an antibody test were positive (like tuberculosis, for example) is a case of AIDS without HIV. The CDC acknowledges only 100 or so cases because it employs a much narrower definition of "AIDS" when HIV is not present than when it is, and it then dismisses the remaining cases because they "differ epidemiologically" from AIDS--meaning apparently that they are not linked to HIV! That the CDC does not understand the need to define the syndrome independently of the hypothesized cause is further evidence that their experts never did the epidemiological work impartially in the first place.

That brings us to the San Francisco study defended by Warren Winkelstein, which supports a correlation between AIDS-defining diseases and HIV, but not drugs, in a population of San Francisco men. Tom Bethell's letter points out that this study was vigorously criticized at the AAAS meeting in San Francisco in June. We are prepared to pursue this criticism in an appropriate scientific forum. For present purposes, readers need to understand primarily that Winkelstein and Michael Fumento are misrepresenting the scientific method. Epidemiology (i.e., correlation) is a useful tool for identifying a possible causative agent, and especially for rejecting impossible ones, but to prove cause on this basis alone is unwarranted. Fumento's example of yellow fever is instructive. Walter Reed's mosquito hypothesis was confirmed by his success in eliminating the disease. HIV causation could be confirmed by similar success, or by a demonstration of the mechanism of causation, or by meeting Koch's postulates, the traditional rules for confirming a causation hypothesis. If the mosquito hypothesis had produced no results after 10 years of trying, Walter Reed would no doubt have been wise enough to consider other possibilities.

There are three reasons for using correlation as an indicator rather than as sufficient proof of causation in itself. First, even if the putative cause (HIV) is highly correlated with the syndrome (one or more of 30 AIDS-defining diseases), correlation studies cannot tell us whether or not the true cause is a third factor or combination of factors which is correlated with HIV. Gay men in San Francisco who are HIV positive, for example, are also likely to have a lot else in common. The correlation would be much more convincing if it were equally strong in all populations, which is why we recommend strictly controlled studies in all the risk groups, and especially in Africa.

Second, it is naive to present HIV correlation studies as if they were naked data lying around for some unbiased scientist to interpret. The HIV hypothesis was fixed in concrete as "scientific fact" by Dr. Gallo's 1984 press conference, and the studies that followed, including the Winkelstein and Schechter studies, were performed by researchers who never questioned the ruling paradigm and would have lost their grants if they had. A multi-billion-dollar research industry will always be able to produce studies by true believers that support its position; the amazing thing is that the HIV industry has to rely so heavily upon two studies of North American men's groups.

To bring up the reality of bias is not to question the integrity of any individual scientist. It is merely to point out that the reason "double blind" studies are essential in medicine is that even the best doctors tend to see what they expect to see--and systematically fail to see what they do not want to see. When we learn that the NIH and CDC's epidemiologists saw nothing wrong with using a biased definition of AIDS (diseases plus real or suspected HIV) in conducting the studies that supposedly established the correlation, we are on notice to be skeptical of everything they say.

Third, AIDS as officially defined is a complex syndrome defined differently on different continents, and manifesting different disease symptoms in different risk groups. The point is not merely whether HIV causes something, or even something serious. It does seem to cause flu symptoms in some persons during the initial infection, when it is multiplying freely in the blood stream and is easy to find. A positive reaction on antibody tests does seem highly correlated in certain populations of gay men with some of the diseases grouped together as "AIDS." This kind of information may have been sufficient to identify HIV as a suspect, but it is not sufficient to justify disregarding everything else we have learned that puts the HIV theory in doubt. HIV clearly is not the sole or primary cause of KS, despite the status of KS as one of the most important AIDS-defining diseases. There is ample reason to question whether HIV infection causes a spectrum of 30 or so diseases many years later by a mechanism that no one can determine when it often can hardly be found at all. It is highly unlikely that the same virus causes some diseases mainly in men in North America, and different diseases in men and women equally elsewhere. An epidemiological study of a group of San Francisco (or Vancouver) men is inherently incapable of validating a theory that encompasses so many contradictions and anomalies.

We do not necessarily dispute Winkelstein's conclusion that, at least in certain populations, "Regardless of whether or not HIV infection causes AIDS, it is a strong predictor of premature death." Persons who are sick from a lot of different things tend to have a lot of different things in their bloodstream, and some of these cause positive reactions on HIV antibody tests. Our skepticism about the HIV hypothesis should not encourage anyone to engage in risky behavior. We mainly agree with the HIV doctors about prudent health rules, except insofar as they would tell people that they may use poppers and similar recreational drugs without fear of damage to their immune systems.

We would merely add that prudent people should especially avoid poisons like AZT and related drugs, which destroy immune system cells and other cells and provide no demonstrable benefit. They should rise up in outrage against dogmatists who want to administer AZT to pregnant women and infants when no adequately controlled studies have been performed to justify this reckless medical practice. They should start questioning loosely supported claims about the spread of HIV in Asia and Africa, and they should demand that impartial, controlled studies be performed to determine what is really going on.

Fumento to the contrary notwithstanding, we do not urge anyone to "forget" any studies or to ignore any evidence. Our point is that the rethinking of HIV science that the top NIH officials admit is necessary is meaningless unless they also reconsider the basic diagnosis. Our research program is simple: Perform the unbiased, carefully controlled epidemiological studies in all risk groups that should have been done in the first place. Employ an unbiased definition of AIDS. Don't assume the HIV hypothesis and defend it with ad hoc arguments and fudge factors; test its various claims impartially. Why is this scientific common sense resisted so bitterly?

It was not unreasonable for the molecular biologists and the epidemiologists to consider HIV a suspect back in 1984. They all assumed that Dr. Gallo had caught HIV in the act of destroying the immune system, and a high percentage of the cases under study did have something in their blood that reacted positively to the antibody tests. But a lot has changed since 1984.

It turns out that HIV isn't really doing anything observable to the immune system, that predictions based on the HIV theory are continually being falsified, that the HIV stalwarts rely more and more on the least reliable statistics, that the antibody tests aren't reliable indicators of HIV activity in the bloodstream, and that even researchers dedicated to proving a perfect correlation between HIV and AIDS have to admit to a lot of nonconforming examples.

Ten years after 1984, the question is whether a biomedical research establishment that jumped prematurely to a conclusion wants to re-examine that conclusion by proper scientific methods and learn the truth, or whether it would prefer to keep its mistakes hidden as long as possible.