Elegance in argument
One of the few beautiful things about AIDS and its science that will strike anyone new to this debate, if they actually go and look over the five classic papers Duesberg has written on AIDS and its scientific discontents, is how well written they are. To some discerning minds, this might in itself indicate truth.
One can, frankly, say they are quite superb as literary artefacts. Small wonder one of them (the first one) was chosen by Walter Gilbert as a specimen of excellence for his graduate biology students to study at Harvard. Gilbert felt it would teach them just how a claim might be professionally reviewed in an exemplary way. (One wonders what those students now think of the Duesberg arguments. It seems impossible that they cannot still respect them, but if so, where are they hiding? A naive question, perhaps….)
One does not even need to be fully persuaded by the arguments of thse papers to rate them highly, though it is questionable whether anyone intelligent and educated who reads them thoroughly will find anything lasting to quibble with.
After all, the battalions of hostile peer reviewers who were marshaled by the editors of the respective journals, no doubt out of a healthy sense of editorial self-preservation and caution, could find no permanent flaws or make any objections that that Duesberg could not meet.
In fact, one can notice that Duesberg’s papers put the articles which purport to rebut them to shame in terms of logical precision and academic clarity.
That’s why even before assessing the balance of argument, it is difficult to have much respect for the responses that Duesberg has met with in the pages of Science, Nature and other science journals, simply because of the obviously lower quality of their reasoning and style, lacking in literary poise, order and clean logic of the first class academic kind that Duesberg typically produces.
Ptolemaic goalposts
But what is most striking is the consistent tendency, time and again, to try and escape the force of Duesberg’s critique by embroidering the paradigm (ruling theory) with endless speculative additions and complications. As a historian of science might say, it’s positively Ptolemaic (the theory recorded by Ptolemy that the sun orbits the earth was defended against Copernicus with ever more subtle adjustments in like manner). Since this strategy removes the requirement to meet the objections originally raised, HIV skeptics, borrowing a metaphor from football, like to call the manoever “moving the goalposts”.
All of the papers in his remarkable series are listed on this page of Duesberg’s papers. But it seems to us that Duesberg’s greatest works among equals are these:
1. The Cancer Research paper
The initial Cancer Research paper (Duesberg, P.H. (1987) Retroviruses as Carcinogens and Pathogens: Expectations and Reality (Cancer Research 47: 1199-1220), which is first of all a rejection of retroviruses as cancer causing, and ultimately, of the whole theory of cancer genes, a field Duesberg helped trigger and now in this paper repudiates; the sting for HIV careerists was in the tail, however, as Duesberg reviewed the new theory and decisively rejected it as lacking any laboratory or epidemiological proof, and contrary to all known science and common sense. Far more likely, he concluded, was that the radical immune deficit syndrome that had suddenly appeared among highly active gays was due to the surge in novel drug taking that enabled their newly escalated activities in the expanded club and baths infrastructure.
Here is the full paper, Part II. The first part on cancer is too technical for lay readers, but this second half on whether HIV makes any sense as a cause of AIDS, is surprisingly accessible and convincing.
II. Retroviruses and AIDS
The isolation in 1983 of a retrovirus from a human patient with lymphadenopathy, a typical symptom of AIDS, led to the proposal that the virus, now termed lymphadenopathy-associated virus, is the cause of AIDS (26). Related viruses, termed HTLV-III, ARV, or HIV (209), have since been isolated from about one-half of the AIDS patients that have been sampled (210-214). In the United States about 26,000 AIDS cases and 15,000 AIDS fatalities have been reported between 1981, when the disease was first identified (215), and October 1986 (216). Women represent only 7% of the AIDS cases in the United States (216). The number of AIDS cases reported in the United States has increased from about 100 per 6-month period in 1981 to about 5,000 during the last three 6-month periods from January 1985 (216). At the same time the case-fatality rate has declined from a high of 88% in 1981 to 32% in 1986 (216). In absolute numbers the known deaths have declined from a high of 2,600 in the first 6 months of 1985 to 1,800 in the first 6 months of 1986. This suggests either that the virulence of the disease is dropping or that other diseases were diagnosed as AIDS. Recently the virus was also suggested to cause disease of the brain and of the nervous system (230, 255, 268, 274) and lymphoid interstitial pneumonia (275).
Antibody to the virus is found in about 90% of AIDS patients and correlates with chronic latent infection by the virus (217-221). Because of the nearly complete correlation between AIDS and immunity against the virus, the virus is generally assumed to be the cause of AIDS (13, 27). Accordingly, detection of antiviral antibody, rather than virus, is now most frequently used to diagnose AIDS and those at risk for AIDS (27, 217-224). This is paradoxical, since serum antibody from AIDS patients neutralizes AIDS virus (225-227) and since antiviral immunity or vaccination typically protects against viral disease. It is even more paradoxical that a low antibody titer is equated with a low risk for AIDS (228, 229).
Unlike all other retroviruses, AIDS viruses are thought to be direct pathogens that kill their host cells, namely T-lymphocytes (13, 27), and possibly cells of the brain (230, 255). This view is compatible with the phenotype of AIDS, the hallmark of which is a defect in T-cells (13, 27, 215), and with experimental evidence that many but not all viral isolates induce cytopathic fusion of T-lymphocytes under certain conditions in vitro (Section D). Further it is compatible with neurological disease (231, 232, 255). However, cell killing is incompatible with the obligatory requirement of mitosis for retrovirus replication (16, 25) and with the complete absence of cytocidal effects in all asymptomatic infections in vivo (Section D).
A. Infections with No Risk and Low Risk for AIDS Indicate That the Virus Is Not Sufficient to Cause AIDS
Since their original discoveries in AIDS patients, the virus and more frequently antibody to the virus have also been demonstrated in a large group of asymptomatic persons (212, 214). The virus has been estimated to occur in about 1 to 2 x 106 or about 0.5 to 1% of all Americans (223, 224). In the United States persons at high risk for infection include promiscuous homosexual and bisexual men, of whom 17 to 67% are antibody positive; intravenous drug users, of whom 50 to 87% are positive; and hemophiliacs, of whom 72 to 85% are positive according to some studies (13, 218, 223). On the basis of this particular epidemiology, it was concluded that the virus is not transmitted as a cell-free agent like pathogenic viruses but only by contacts that involve exchange of cells (13, 27).
In these virus-infected groups the annual incidence of AIDS was found to average 0.3% (224) and to reach peak values of 2 to 5% (218, 223, 233). However even in these groups there are many more asymptomatic than symptomatic virus carriers. Other infected groups appear to be at no risk for AIDS. In Haiti and in certain countries in Africa antibody-positive individuals range from 4 to 20% of the population, whereas the incidence of AIDS is estimated at less than 0.01% (223, 229, 234). Several reports describe large samples of children from Africa who were 20 (228) to 60% (221) antibody positive and of female prostitutes who were 66 to 80% antibody positive (221,235), yet none of these had AIDS. Among male homosexuals and hemophiliacs of Hungary about 5% are AIDS virus positive, yet no symptoms of AIDS were recorded (161). Among native male and female Indians of Venezuela 3.3 to 13.3% have antiviral immunity, but none have symptoms of AIDS (236). Since these Indians are totally isolated from the rest of the country, in which only one hemophiliac was reported to be virus positive (236), the asymptomatic nature of their infections is not likely to be a consequence of a recent introduction of the virus into their population. Thus it is not probable that these infections will produce AIDS after the average latent period of 5 years (Section B).
Since the percentage of virus carriers with symptoms of AIDS is low and in particular since it varies between 0 and 5% depending on the AIDS risk group of the carrier, it is concluded that the virus is not sufficient to cause AIDS and that it does not encode an AIDS-specific function. The virus is also not sufficient to cause neurological disease, since it has been detected in the brains of persons without neurological disease and of healthy persons who had survived transient meningitis (230-232).
Thus the virus appears only rarely compatible with Koch’s third postulate as an etiological agent of AIDS. It may be argued that the asymptomatic infections reflect latent infections or infections of only a small percentage of susceptible cells, compared to presumably acute infections with symptoms of AIDS. However, it is shown in Section C that infections of neither symptomatic nor asymptomatic carriers are acute; instead both are equally latent and limited to a small percentage of susceptible cells.
Further, the observations that some virus carriers are at high and others at essentially no risk for AIDS directly argue for a cofactor (218, 237) or else for a different cause for AIDS. The strong bias against women, because only 2.5% (479 of 17,000 cases) of the sexually transmitted AIDS cases in the United States are women (216), is a case in point. The virus-positive but AIDS-negative children and prostitutes of Africa (221) or Indians from Venezuela (236) are other examples.
B. Long Latent Period of AIDS Incompatible with Short Latent Period of Virus Replication
The eclipse period of AIDS virus replication in cell culture is on the order of several days, very much like that of other retroviruses (238). In humans virus infection of a sufficient number of cells to elicit an antibody response appears to take less than 4 to 7 weeks. This estimate is based on an accidental needle-stick infection of a nurse, who developed antibody 7 weeks later (239), and on reports describing 12 (240) and 1 (232) cases of male homosexuals who developed antibody 1 to 8 weeks after infection. During this period a mononucleosis-like illness associated with transient lymphadenopathy was observed. In contrast to AIDS (see below), this illness appeared 1 to 8 weeks after infection and lasted only 1 to 2 weeks until antiviral immunity was established. The same early mononucleosis-like disease, associated with lymphocyte hyperplasia, was observed by others in primary AIDS virus infections (234). This is reminiscent of the direct, early pathogenic effects observed in animals infected with retroviruses prior to the onset of antiviral immunity (Part I, Section B).
By contrast the lag between infection and the appearance of AIDS is estimated from transfusion-associated AIDS to be 2 to 7 years in adults (220, 223, 241, 242) and 1 to 2 years in children from infected mothers (220, 223). The most likely mean latent period was estimated to be 5 years in adults (220, 223). Unexpectedly, most of the AIDS virus-positive blood donors identified in transfusion-associated AIDS transmission did not have AIDS when they donated blood and were reported to be in good health 6 years after the donation (220). Likewise there is evidence that individuals shown to be antibody positive since 1972 have not developed AIDS (228). Further, 16 mothers of babies with AIDS did not have AIDS at the time of delivery but three of them developed AIDS years later (276). This indicates that the latent period may be longer than 5 years or that AIDS is not an obligatory consequence of infection.
In view of the claim that the virus directly kills T-cells and requires 5 years to cause disease, we are faced with two bizarre options: Either 5 year old T-cells die 5 years after infection or the offspring of originally infected T-cells die in their 50th generation, assuming a generation time of one month for an average T-cell (176). It may be argued that the virus is biochemically inactive during the first five years of infection and then activated by an unknown cause. However, AIDS virus is biochemically inactive even during the acute phase of the disease (Section C). Moreover it would be difficult for the retrovirus to become acute five years after it had induced chronic antiviral immunity.
Because of the 5 year latency between infection and AIDS, the virus has been likened to the lentiviruses (277), a group of animal retroviruses that is thought to cause debilitating diseases only after long latent periods (13) (Part I, Section B). However, recently an ovine lentivirus, the visna or maedi virus of sheep, was shown to cause lymphoid interstitial pneumonia in 2 to 4 weeks if expressed at high titer (269). [The same disease is believed to be caused by AIDS virus in humans (see below)]. Therefore lentiviruses are not models for retroviruses that are only pathogenic after long latency (Part I, Section B).
Based on the 5-year latent period of the disease and on the assumption that virus infection is sufficient to cause AIDS, one would expect the number of AIDS cases to increase to 1 to 2 x 106 in the United States in the next 5 years. The virus has reportedly reached its present endemic level of 1 to 2 x 106 in the United States (223, 224) since it was introduced there, presumably, less than 10 years ago (27). Yet the spread of AIDS from 1981 to 1986 has not followed the spread of virus with a latent period of 5 years. Instead, recent statistics (see above) indicate no further increases in the number of AIDS cases and a significant decline in the number of AIDS fatalities in the United States (216, 244).
Clearly, the long lag between infection and AIDS and the large number of virus-positive cases in which as yet no AIDS is observed, even after long latent periods, lead to the conclusion that the virus is not sufficient to induce AIDS and does not encode an AIDS-specific function. Indeed, this conclusion is directly supported by genetic evidence against a viral AIDS gene. Deletion analysis has proved that all viral genes are essential for replication (28, 245), which requires not more than 1 or 2 days, yet AIDS follows infection only with an average lag of 5 years and even then only very rarely.
C. Levels of AIDS Virus Expression and Infiltration Appear Too Low to Account for AIDS or Other Diseases
If AIDS viruses were pathogenic by killing susceptible lymphocytes, one would expect AIDS to correlate with high levels of virus infiltration and expression, because uninfected cells would not be killed by viruses nor would unexpressed or latent viruses kill cells. As yet no report on virus titers of AIDS patients has appeared, despite the record interest in the epidemiology and nucleic acid structure of this virus (13, 27, 223). In view of the consistent antiviral immunity of AIDS patients and the difficulties in isolating virus from them (213), the virus titers are probably low. Titers have been said to range between only 0 and 102 per ml blood (213).8
Proviral DNA has been detected in only 15% (9 of 65) AIDS patients; in the remaining 85% the concentration of provirus, if present, was apparently too low for biochemical detection (246). Moreover, among positive samples less than 1 in 102 to 103 lymphocytes contained the provirus (246). Viral RNA was detected in 50 to 80% of AIDS blood samples. However, among the positive samples, RNA was found in only less than 1 of 104 to 105 presumably susceptible lymphocytes (247). The relatively high ratios of provirus-positive (10-2 to 10-3) to viral RNA positive cells (10-4 to 10-5) of AIDS patients indicate latent infections. Further there is no evidence that the virus titer or the level of virus infiltration increases during the acute phase of the disease. It is probably for this reason that cells from AIDS patients must be propagated several weeks in culture, apart from the host’s immune system, before either spontaneous (210-214) or chemically induced (248) virus expression may occur. Further, the AIDS virus is completely absent from the Kaposi sarcoma (27, 246), which is associated with 15% (216) to 30% (249) of AIDS cases and is one of the most characteristic symptoms of the disease.
Similar extremely low levels of virus infiltration and expression were also recorded in AIDS virus-associated brain disease (274). Likewise, in interstitial lymphoid pneumonia less that 0.1% of lung cells expressed viral RNA (275).
Indeed there is evidence that even latent virus may not be necessary for AIDS, since 85% of AIDS patients lack proviral DNA (246) and since over 10% of AIDS patients have been observed to lack antiviral immunity (214, 221, 222, 234). Further, in a study from Germany 3 of 91 AIDS patients were found to be virus free, based on repeated negative efforts to detect antibody or to rescue virus.9
It is concluded then that the AIDS virus infects less than 1%, and is expressed in less than 0.01%, of susceptible cells both in carriers with or without AIDS. This raises the question of how the virus could possibly be pathogenic and responsible for immunodeficiency or other diseases. For instance even if the virus were to claim its 10-4 or 10-5 share of T-cells that express viral RNA every 24 to 48 h, the known eclipse period of retroviruses, it would hardly ever match or beat the natural rate of T-cell regeneration (176).
All other viruses function as direct pathogens only if they are biochemically active and expressed at high levels. For instance, the titers that correlate with direct pathogenicity for avian retroviruses are 105-12 (31, 35, 250)4 and they are 104-7 for murine retroviruses (12, 38, 40, 42, 251) (Section B). Hepatitis viruses reach titers of 1012-13 when they cause hepatitis (15), and latent infections are not pathogenic (83). Further, the very low levels of AIDS virus expression in vivo are difficult to reconcile with reports based on in vitro studies with synthetic indicator genes that the AIDS virus encodes a potent transcription-stimulating protein (28, 153, 245). Clearly such activators are not at work in vivo.
The extremely low virus titers of symptomatic and asymptomatic carriers also explain why infection by the virus in the United States is essentially limited to contacts that involve transmission of cells (244) rather than being transmitted as a cell-free, infectious agent like pathogenic viruses. For instance, among 1750 health care workers with exposure to AIDS, only 1 or 2 were found to be antibody positive (252). Another study failed to find a single antibody-positive person among 101 family contacts of 39 AIDS patients, all of whom had lived in the same household with an AIDS patient for at least 3 months (253).
D. AIDS Viruses Not Directly Cytocidal
The AIDS viruses are reported to display in culture a fast cytocidal effect on primary T-cells within 1 to 2 months after infection (13, 27, 254). The cytocidal effect was shown to involve cell fusion (27, 238, 254). The effect is thought to reflect the mechanism of how the virus generates AIDS after a latent period of 5 years (27, 254).
This is debatable on several grounds: (a) above all, the in vitro assay cannot account for the large discrepancy between the short latent period of cell death in vitro and the 5-year latent period of the disease; (b) T cell fusion is not observed in vivo in chronic, asymptomatic virus carriers and not in prospective AIDS patients during the long latent period of the disease (255), although virus expression is not lower than during the acute phase of AIDS; (c) T-cell killing is also not observed in T-cell lines in vitro (27) and not in primary lymphocytes under appropriate conditions (238). Further primary lymphocytes infected by AIDS virus were shown to double every 5 days in cell culture for three weeks; at the same time the previously latent AIDS virus was activated to high levels of expression (278); (d) virus strains that do not cause cytopathic fusion in vitro have been isolated from 7 of 150 AIDS patients.9 This demonstrates that the fusion-inducing function of the virus can be dissociated from a putative AIDS function.
Thus T-cell killing by fusion is apparently a cell culture artifact that depends on the virus strain and the cell used, as has been shown for many other retroviruses including HTLV-I (Part I, Section B), and not an obligatory feature of virus infection. As with other retroviruses, fusion involves binding of viral envelope antigens on the surface of infected cells with receptors of uninfected cells. Accordingly, fusion is inhibited by AIDS virus-neutralizing antibody (256). It apparently depends on high local virus titers that in particular in the case of AIDS are not observed in vivo. This view of the cell-killing effect also resolves the apparent contradiction between the postulated cytocidal effects of AIDS viruses and the obligatory requirement of all retroviruses for mitosis in order to replicate (16, 25). Indeed AIDS viruses have been reported to replicate without cytocidal effects not only in T-cells but also in human monocytes and macrophages (257, 278), which share the same virus-specific receptors (258), and in B-cell lines (259), in fibroblasts (261) in human brain and the lung (213, 230, 232, 257, 261).
E. No Simian Models for AIDS
Since retroviruses have been isolated from monkeys in captivity with immunodeficiencies and since experimental viremia can depress immune functions in monkeys, such systems are considered to be animal models of human AIDS. For example, 42 of 68 newborn monkeys died with a broad spectrum of diseases that included runting and lymphadenopathy 4 to 6 weeks after inoculation with Mason-Pfizer monkey virus (91). However, this virus has since been found in healthy macaques (262). More recently a retrovirus termed simian AIDS or SAIDS virus was isolated from monkeys with immunodeficiency (92, 262). Inoculation of three juvenile rhesus monkeys by one isolate was reported to cause splenomegaly and lymphadenopathy within 2 to 5 weeks. One animal became moribund and two others were alive with simian AIDS at the time of publication (92). However, in another study only transient lymphadenopathy but no lasting AIDS-like disease was observed in macaques inoculated with this virus (263). Another simian virus that is serologically related to AIDS virus, termed STLV-III, was isolated from immunodeficient macaques and from one macaque with a lymphoma. Macaques inoculated with blood or tissue samples of the viral lymphoma died 50 to 60 days later with various diseases (93). However, asymptomatic infections by the same virus have since been identified in no less than 50% of wild green monkeys that did not show any symptoms of a disease (264).
Eight chimpanzees infected with human AIDS virus had not developed symptoms of AIDS 1.5 years past inoculation (265). However, each animal developed antiviral immunity about 1 month after infection, followed by persistent latent infection, as in the human cases (265). A follow-up of champanzees inoculated with sera from AIDS patients in 1983 reports no evidence for AIDS in 1986 although the animals had developed antibodies to the virus (243).
Several reasons suggest that these experimental infections of monkeys are not suitable models for human AIDS. Above all, the human virus is not pathogenic in animals. The diseases induced in monkeys by experimental infections with simian viruses all occur fast compared to the 5-year latency for AIDS. Moreover the simian viruses are never associated with a disease in wild animals. Therefore these diseases appear to be exactly analogous to the direct, early pathogenic effects caused by other retroviruses in animals prior to antiviral immunity (see Part I, Section B), and thus are probably models for the early mononucleosis-like diseases which occur in humans infected with AIDS virus prior to antiviral immunity (232, 234, 240) (Section B). Indeed the persistent asymptomatic infections of wild monkeys with simian retroviruses appear to be models for the many asymptomatic infections of humans with AIDS virus or HTLV-I.
F. AIDS Virus As an Indicator of a Low Risk for AIDS
The only support for the hypothesis that the AIDS virus causes AIDS is that 90% of the AIDS patients have antibody to the virus. Thus it would appear that the virus, at least as an immunogen, meets the first of Koch’s postulates for an etiological agent. This conclusion assumes that all AIDS patients from whom virus cannot be isolated (about 50%) (278) or in whom provirus cannot be demonstrated (85%) and the antibody-negative cases (about 10%) and the virus-free cases reported in one study (3%) (Section C) are false negatives. Indeed, the diagnosis of AIDS virus by antibody has recently been questioned on the basis of false positives (234).
At this time the hypothesis that the virus causes AIDS faces several direct challenges. (a) First it fails to explain why active antiviral immunity, which includes neutralizing antibody (225-227) and which effectively prevents virus spread and expression, would not prevent the virus from causing a fatal disease. This is particularly paradoxical since antiviral immunity or “vaccination” typically protects against viral pathogenicity. It is also unexpected that AIDS patients are capable of mounting an apparently highly effective, antiviral immunity, although immunodeficiency is the hallmark of the disease. (b) The hypothesis is also challenged by direct evidence that the virus is not sufficient to cause AIDS. This includes (i) the low percentage of symptomatic infections, (ii) the fact that some infected groups are at a relatively high and others at no risk for AIDS, (iii) the long latent period of the disease (Section B), and (iv) the genetic evidence that the virus lacks a late AIDS function. Since all viral genes are essential for virus replication (28, 245), the virus should kill T-cells and hence cause AIDS at the time of infection rather than 5 years later. (c) The hypothesis also fails to resolve the contradiction that the AIDS virus, like all retroviruses, depends on mitosis for replication yet is postulated to be directly cytocidal (Section D). (d) The hypothesis offers no convincing explanation for the paradox that a fatal disease would be caused by a virus that is latent and biochemically inactive and that infects less than 1% and is expressed in less than 0.01% of susceptible lymphocytes (Section D). In addition the hypothesis cannot explain why the virus is not pathogenic in asymptomatic infections, since there is no evidence that the virus is more active or further spread in carriers with than in carriers without AIDS.
In view of this it seems likely that AIDS virus is just the most common among the occupational viral infections of AIDS patients and those at risk for AIDS, rather than the cause of AIDS. The disease would then be caused by an as yet unidentified agent which may not even be a virus, since cell-free contacts are not sufficient to transmit the disease.
Other viral infections of AIDS patients and those at risk for AIDS include Epstein-Barr and cytomegalovirus in 80 to 90% (222, 268), and herpes virus in 75 to 100%.10
In addition hepatitis B virus is found in 90% of drug addicts positive for antibody to AIDS virus (267). Among these different viruses, retroviruses are the most likely to be detectable long after infection and hence are the most probable passenger viruses of those exposed to multiple infectious agents. This is because retroviruses are not cytocidal and are unsurpassed in establishing persistent, nonpathogenic infections even in the face of antiviral immunity. Therefore AIDS virus is a useful indicator of contaminated sera that may cause AIDS (13, 27) and that may contain other cell-free and cell-associated infectious agents. It is also for these reasons that latent retroviruses are the most common nonpathogenic passenger viruses of healthy animals and humans. For the same reasons, they are also frequently passenger viruses of slow diseases other than AIDS like the feline, bovine and human leukemias (see Part I) or multiple sclerosis (268) in which latent or defective “leukemia viruses” are occasionally found.
It is concluded that AIDS virus is not sufficient to cause AIDS and that there is no evidence, besides its presence in a latent form, that it is necessary for AIDS. However, the virus may be directly responsible for the early, mononucleosis-like disease observed in several infections prior to antiviral immunity (Section B). In a person who belongs to the high risk group for AIDS, antibody against the AIDS virus serves as an indicator of an annual risk for AIDS that averages 0.3% and may reach 5%, but in a person that does not belong to this group antibody to the virus signals no apparent risk for AIDS. Since nearly all virus carriers have antiviral immunity including neutralizing antibody (225-227), vaccination is not likely to benefit virus carriers with or without AIDS.
2. The 1989 Proceedings Paper
The paper in the Proceeedings of the National Academy of February 1989, Duesberg, P. H. (1989) Human immunodeficiency virus and acquired immunodeficiency syndrome: Correlation but not causation (Proc Natl Acad Sci USA 86: 755-764) is the real classic, produced when, after the Cancer Research paper was studiously ignored by everybody, including the White House after initial interest (a meeting on the issue was scotched when NIH (ie Anthony Fauci and Robert Gallo), Duesberg returned to the attack with a full blown analysis of 9000 words backed by 196 references.
The optimistic last paragraph of the definitive piece was a recounting of the “benefits” of the analysis, primarily that HIV had no longer to be feared and that AZT could be studied to see what its contribution to AIDS decline might be, as well as other drugs and risks.
(Here it is - the entire paper, with the paragraph at the end)
Human Immunodeficiency Virus and Acquired Immunodeficiency
Syndrome: Correlation But Not Causation1,2
By Peter H. Duesberg
Proc. Natl. Acad. Sci. USA, Vol. 86, pp. 755-764, February 1989
Contributed June 14, 1988; revision received October 21, 1988
Abstract
AIDS is an acquired immunodeficiency syndrome defined by a severe depletion of T cells and over 20 conventional degenerative and neoplastic diseases. In the U.S. and Europe, AIDS correlates to 95% with risk factors, such as about 8 years of promiscuous male homosexuality, intravenous drug use, or hemophilia. Since AIDS also correlates with antibody to a retrovirus, confirmed in about 40% of American cases, it has been hypothesized that this virus causes AIDS by killing T cells. Consequently, the virus was termed human immunodeficiency virus (HIV), and antibody to HIV became part of the definition of AIDS. The hypothesis that HIV causes AIDS is examined in terms of Koch’s postulates and epidemiological, biochemical, genetic, and evolutionary conditions of viral pathology. HIV does not fulfill Koch’s postulates: (i) free virus is not detectable in most cases of AIDS; (ii) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (iii) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans. Further, HIV violates classical conditions of viral pathology. (i) Epidemiological surveys indicate that the annual incidence of AIDS among antibody-positive persons varies from nearly 0 to over 10%, depending critically on nonviral risk factors. (ii) HIV is expressed in �1 of every 104 T cells it supposedly kills in AIDS, whereas about 5% of all T cells are regenerated during the 2 days it takes the virus to infect a cell. (iii) If HIV were the cause of AIDS, it would be the first virus to cause a disease only after the onset of antiviral immunity, as detected by a positive “AIDS test.” (iv) AIDS follows the onset of antiviral immunity only after long and unpredictable asymptomatic intervals averaging 8 years, although HIV replicates within 1 to 2 days and induces immunity within 1 to 2 months. (v) HIV supposedly causes AIDS by killing T cells, although retroviruses can only replicate in viable cells. In fact, infected T cells grown in culture continue to divide. (vi) HIV is isogenic with all other retroviruses and does not express a late, AIDS-specific gene. (vii) If HIV were to cause AIDS, it would have a paradoxical, country-specific pathology, causing over 90% Pneumocystis pneumonia and Kaposi sarcoma in the U.S. but over 90% slim disease, fever, and diarrhea in Africa. (viii) It is highly improbable that within the last few years two viruses (HIV-I and HIV-2) that are only 40% sequence-related would have evolved that could both cause the newly defined syndrome AIDS. Also, viruses are improbable that kill their only natural host with efficiencies of 50-100%, as is claimed for HIVs. It is concluded that HIV is not sufficient for AIDS and that it may not even be necessary for AIDS because its activity is just as low in symptomatic carriers as in asymptomatic carriers. The correlation between antibody to HIV and AIDS does not prove causation, because otherwise indistinguishable diseases are now set apart only on the basis of this antibody. I propose that AIDS is not a contagious syndrome caused by one conventional virus or microbe. No such virus or microbe would require almost a decade to cause primary disease, nor could it cause the diverse collection of AIDS diseases. Neither would its host range be as selective as that of AIDS, nor could it survive if it were as inefficiently transmitted as AIDS. Since AIDS is defined by new combinations of conventional diseases, it may be caused by new combinations of conventional pathogens, including acute viral or microbial infections and chronic drug use and malnutrition. The long and unpredictable intervals between infection with HIV and AIDS would then reflect the thresholds for these pathogenic factors to cause AIDS diseases, instead of an unlikely mechanism of HIV pathogenesis.
Introduction
The important thing is to not stop questioning.
-Albert Einstein
In 1981, acquired immunodeficiency was proposed to be the common denominator of a newly defined syndrome (AIDS) of diseases that were on the rise in promiscuous male homosexuals and intravenous drug users, referred to as “AIDS risk groups” (1, 2). Since then, about 70,000 persons have developed AIDS in the U.S., of whom over 90% are still from these same risk groups (3, 4). The hallmark of AIDS is a severe depletion of T cells (3, 5-7). By definition, this immunodeficiency manifests itself in over 20 previously known degenerative and neoplastic diseases, including Kaposi sarcoma, Burkitt and other lymphomas, Pneumocystis pneumonia, diarrhea, dementia, candidiasis, tuberculosis, lymphadenopathy, slim disease, fever, herpes, and many others (5, 7-11). The frequent reference to AIDS as a new disease (12-14), instead of a new syndrome composed of old diseases, has inspired a search for a single new pathogen (12). However, it is debatable whether a single pathogen can explain over 20 diseases, whether a clustering of old diseases in risk groups that only recently became visible signals a new pathogen, and whether an AIDS pathogen must be infectious. Indeed, compared to conventional infectious diseases, AIDS is very difficult to acquire and has a very selective host range, usually manifesting only in individuals who have taken AIDS risks for an average of 8 years (see below).
The Virus-AIDS Hypothesis. About 40% of the AIDS patients in the U.S. (5), and many of those who are at risk for AIDS, have been confirmed to have neutralizing antibodies to a retrovirus (3, 7) that was discovered in 1983 (15). These antibodies are detected by the “AIDS test” (3). Less than a year later, in 1984, this virus was adopted as the cause of AIDS by the U.S. Department of Health and Human Services and the AIDS test was registered as a patent, even before the first American study on the virus was published (16). The epidemiological correlation between these antibodies and AIDS is the primary basis for the hypothesis that AIDS is caused by this virus (3, 7, 12, 14, 17, 18). AIDS is also believed to be caused by this virus because AIDS diseases appear in a small percentage (see below) of recipients of blood transfusions that have antibodies to this virus (3, 12, 19-22). In view of this the virus has been named human immunodeficiency virus (HIV) by an international committee of retrovirologists (18) and antibody to HIV became part of the definition of AIDS (3, 5, 7). “… Patients are excluded as AIDS cases if they have a negative result(s) on testing for serum antibody to HIV, do not have a positive culture for HIV” (3). If confirmed, HIV would be the first clinically relevant retrovirus since the Virus-Cancer Program called for viral carcinogens in 1971 (23, 24).
The virus-AIDS hypothesis holds that the retrovirus HIV causes AIDS by killing T cells in the manner of a cytocidal virus (3, 6, 7, 12, 18) and is transmitted by sex and parenteral exposure (3, 7, 12, 19, 22). Early evidence for a T cell-specific HIV receptor lent support to this hypothesis (25). Recently, however, the presumed T cell specificity of HIV has lost ground, as HIV is only barely detectable in T cells and often is detectable only in monocytes (26-28) and other body cells (23, 29-32), displaying the same lack of virulence and broad host range toward differentiated cells as all other human and animal retroviruses (17, 23). In about 50% of those who habitually practice risk behavior or regularly receive transfusions, AIDS is estimated to occur after an average asymptomatic period of about 8 years from the onset of antiviral immunity, and in up to 100% after about 15 years (5-7, 20-22, 33-38). Therefore, HIV is called a “slow” virus, or lentivirus (40). It is on the basis of the relatively high conversion rates of these risk groups that every asymptomatic infection by HIV is now being called “HIV disease” (7), and that some are subjected to chemotherapy (39). Nevertheless, individual asymptomatic periods are unpredictable, ranging from <1 to >15 years (22, 33-38). Once AIDS is diagnosed, the mean life expectancy is about 1 year (35).
The early adoption of the virus-AIDS hypothesis by the U.S. Department of Health and Human Services (16) and by retrovirologists (17, 18) is the probable reason that the hypothesis was generally accepted without scrutiny. For instance, the virus is typically referred to as deadly by the popular press (41, 42) and public enemy number 1 by the U.S. Department of Health and Human Services (43). In view of this, it is surprising that the virus has yet to cause the first AIDS case among hundreds of unvaccinated scientists who have propagated it for the past 5 years at titers that exceed those in AIDS patients by up to 6 orders of magnitude (see below) with no more containment than is required for marginally pathogenic animal viruses (44). It is also surprising that despite 2000 recorded (and probably many more unrecorded) parenteral exposures to HIV-infected materials, unvaccinated health care workers have exactly the same incidence of AIDS as the rest of the U.S. labor force (19, 22, 45, 186). Further, it is difficult to believe that a sexually transmitted virus (7, 12) would not have caused more than 1649 sex-linked AIDS cases among the 125 million American women in 8 years (4)-and this number is not even corrected for the antibody-negative women who might have developed such diseases over an 8-year period. Moreover, it is paradoxical for a supposedly new viral epidemic (12-14) that the estimates of infected persons in the U.S. have remained constant at 0.5 to 1.5 million (46, 47) or even declined to <1 million (7, 38) since the “AIDS test” became available in 1985.
About 2 years ago I proposed that HIV is not likely to be the cause of AIDS (23, 48-50, 180). This proposal has since been fiercely challenged or defended at meetings and in publications (14, 32, 51-65, 180). Here I respond to these challenges.
HIV Does Not Meet Koch’s Postulates
HIV Cannot Account for the Loss of T Cells and the Clinical Course of AIDS. The causative agent of an infectious disease is classically defined by the postulates of Robert Koch and Jacob Henle (66, 67). They were originally formulated a priori by Henle about 50 years before bacteria and viruses were discovered to be pathogens (67). However, their definitive text was formulated by Koch to distinguish causative from other bacteria at a time when bacteriologists applying newly developed tools in the search for pathogenic microbes found all sorts of bacteria in humans. This situation was quite similar to our current increasing proficiency in demonstrating viruses (68). The first of these postulates states that “the parasite must be present in every single case of the disease, under conditions that can account for the pathological lesions and the clinical course of the disease” (67). However, there is no free virus in most-and very little in some-persons with AIDS, or in asymptomatic carriers (69, 70). Virus titers range from 0 to 10 infectious units per milliliter of blood (69, 70). Viral RNA is found in a very low percentage (see below) of blood cells of 50