A Controversy That Will Not Die: The Role Of HIV In Causing AIDS

While the most quoted dissenter says the virus plays no part, there is a broad diversity of opinion in the scientific community on its function. When the journal Science ran an eight-page special report in December, it got a lot of attention which, after all, is what special reports are intended for. But this one, devoted to a single researcher, was highly unusual. Called "The Duesberg Phenomenon," it presented University of California, Berkeley, retrovirologist Peter Duesberg's unorthodox views of AIDS causation (J. Cohen, Science, 266:1642-9, 1994). Duesberg, a member of the National Academy of Sciences, does not believe that HIV causes AIDS defining-diseases (see Opinion, page 12). Virtually all American AIDS cases, he wrote in Biomedicine and Pharmacotherapy in 1992 (46:3-15), are the result of recreational and anti-HIV drugs. In its December 9 issue, Science considered Duesberg's views seriously and went to great length to examine and, ultimately, rebut them. The report, however, virtually ignored the diversity of opinion within the scientific community with regard to HIV's role in AIDS (see Commentary, page 13). It is increasingly apparent that Duesberg, the most quoted of the HIV dissenters, occupies a lonely extreme in his hypothesis that HIV is a harmless retrovirus having nothing to do with AIDS diseases. Even many former allies, while praising his courage and agreeing that HIV's role in AIDS is not proven, distance themselves from his theory. Many of them maintain that HIV is involved in some way, but in combination with other factors. Some suggest that the attention paid by scientists and the media to Duesberg is a way of sweeping aside all critiques of conventional views. Joseph Sonnabend, a New York clinician and early proponent of a multifactorial AIDS hypothesis, says Duesberg's "criticisms are not difficult to put aside.... Equating all criticism of HIV with Peter Duesberg makes it easy to tear down." Responding to such comments from Sonnabend and others who had once been seen as his allies, Duesberg contends: "What is happening is there is so much pressure in favor of the orthodoxy, that people would rather be identified with orthodoxy than with me." At the other extreme is the view, best presented by David Ho, director of the Aaron Diamond AIDS Research Center in New York, and colleagues in a widely cited January 12 Nature article (D.D. Ho et al., Nature, 373:123, 1995). They wrote: "our findings strongly support the view that AIDS is primarily a consequence of continuous, high-level replication of HIV-1, leading to virus- and immune-mediated killing of CD4 lymphocytes." One of the contentious issues surrounds the semantics of the word "cause," notes Harry Haverkos, director of the Office on AIDS at the National Institute on Drug Abuse. Recently, when a possible herpes virus was implicated as a cause of Kaposi's sarcoma (KS) in people with AIDS (Y. Chang et al., Science, 266:1865-9, 1994), some HIV critics jumped on the news as evidence of backtracking by mainstream AIDS scientists. But Haverkos, who considers himself part of the mainstream, doesn't doubt that HIV is responsible for the immune suppression seen in AIDS. Still, there is a lot of debate, he says, about other factors that influence disease outcome. "I think most people are moving to the middle ground," he comments. "It's the logical place to be. Clearly the KS question has forced us to look at this as not a simple one agent-one disease kind of process." Harold Jaffe is firmly in the mainstream as the director of the Division of HIV/AIDS at the Centers for Disease Control and Prevention in Atlanta, yet he readily acknowledges that it is "almost certain that cofactors play a role in the course of HIV infection and are the reason why some stay healthy for 15 years and others get sick." Much of the give-and-take in the middle ground is over whether HIV is necessary and sufficient to cause AIDS, or just necessary. One who has emphasized this distinction is physiologist Robert Root-Bernstein of Michigan State University, a proponent of the multifactorial hypothesis. He believes the scientific debate on the issue has been poor (R. Root-Bernstein, The Scientist, April 4, 1994, page 1). "The debate has been cast in black-and-white terms," observes Root- Bernstein, the 1981 winner of a MacArthur Foundation "genius award." "Look at almost everything published in Science and Nature: The debate is cast as HIV is the cause or is not the cause, and there is nothing in between." Last year, Charles Geshekter, a historian at California State University, Chico, organized a symposium for the annual meeting of the Pacific Division of the American Association for the Advancement of Science (AAAS), called "The Role of HIV in AIDS: Why There Is Still a Controversy." Geshekter, a member of the editorial board of the Group for the Scientific Reappraisal of the HIV/AIDS Hypothesis, lined up 11 speakers to address the issue, all critical of the mainstream HIV/AIDS theory. He gained approval for the symposium and speakers from Pacific Division executive director Alan Leviton and the program committee. Beginning a little more than a month before the meeting, Leviton and other AAAS officials began receiving complaints from AIDS scientists and others about the one-sided nature of the program. In response, Leviton and program chairman Robert Bowman reconfigured the agenda. First, Leviton informed Geshekter on May 18 that one pro-HIV speaker had been added, according to documents provided by Geshekter. Then, 11 days before the June 21 symposium, Leviton called Geshekter to tell him additional changes: Seven speakers, all espousing mainstream views, were added to the program. In addition, panel discussions, with a separate, pro-HIV moderator, were inserted. When Geshekter protested these intrusions, he wrote in a memo to the Council of the Pacific Division, he was "emphatically and unambiguously" reminded that final authority over the session rested with Leviton. Asked to explain, Leviton says he and Bowman, when informed of Geshekter's plans months before the symposium, "were not immediately aware of the imbalance" in the program; "it didn't sink in." The changes were made without informing Geshekter, according to both Bowman and Leviton, because of the limited time available before the program. A letter from Geshekter to Leviton acknowledging the addition of the first pro-HIV speaker, however, was dated May 23, nearly a month before the symposium. Geshekter, who has since been replaced without explanation as the chairman of the history and philosophy of science section of the Pacific Division, says: "The people I invited were distinguished scientists, with few exceptions [a law professor, a journalist, an actuary, and a graduate student]. My thought was, pure and simple, who can I invite to make a thoughtful and interesting presentation?" Clearly frustrated, he declares, "If you raise the possibility that HIV is not the whole story, the response is, 'Oh, you must believe Duesberg and not believe HIV at all.' That is not our position. It is: HIV is there and plays a role, but it is not the whole story." Root-Bernstein and others contend that the mainstream view that HIV alone is sufficient for immune suppression is not proven. AIDS patients have numerous other active infections, he says, including cytomega-lovirus, herpes simplex, hepatitis, and mycoplasmas "all of which are known to directly infect T cells and cause immune suppression." Media coverage of the debate falls short in the eyes of mainstream and skeptical scientists alike. In a 1992 interview with Steven Epstein, a sociologist at the University of California, San Diego, for the sociologist's dissertation, Duesberg remarked, "The press has been functioning like this [tapping Epstein's tape recorder] for the AIDS establishment." Conversely, in a letter to Science (267:157, 1995), Koen Van Rompay and Marta L. Marthas of the California Regional Primate Research Center at UC-Davis, who study the simian immunodeficiency virus, "question the usefulness of devoting eight pages of a Science Special News Report to 'The Duesberg phenomenon.'" Epstein tells The Scientist that "the media is doing what it usually does in covering controversy, which is to present debate as having two sides, which infuriates mainstream researchers. They say it is not like there are two equal sides." The mainstream scientists frequently point out that few HIV critics conduct any experimental research themselves on HIV or AIDS. They say this despite the fact that many AIDS researchers are actively investigating cofactors. Duesberg acknowledges that many of his own supporters are not testing the hypothesis. He says, "They can't be virologists who have a grant to defend. If they supported me, they wouldn't have any support. They are either elderly virologists or scientists outside my field, or lawyers, or [1993 Nobel chemistry laureate Kary] Mullis, who doesn't run a laboratory or want a grant. They can afford to speak up without consequences." Duesberg, who published his first criticism of the HIV theory in 1987 in Cancer Research (47:1199-1220), maintains that the consequences for him have been severe. Described by friend and foe alike as brilliant and a careful and ethical researcher, Duesberg has been unable to obtain any grant support for several years. In 1985, he was among the first 23 winners of an Outstanding Investigator Grant (OIG) from the National Cancer Institute, for work on oncogenes. The grants were intended to fund star researchers for seven years, lessening the burden of frequent grant applications. Duesberg's 1990 application for a renewal of the OIG was rejected, as was a subsequent appeal. Reviewers commented that in recent years he had "been less productive, perhaps reflecting a dilution of his efforts with non-scientific issues." Nine of Duesberg's other grant applications, including three for an experimental test of his hypothesis that nitrite inhalants ("poppers") cause one or more AIDS diseases, have been rejected. Duesberg was not alone in being rejected for an OIG renewal--four others out of the 19 1985 recipients who applied for renewal were also denied. "I am not claiming I'm unique," he contends, "but there is a difference: For over 25 years, I received all the awards I wanted to do my research. I was California Scientist of the Year and elected to the National Academy of Sciences. But once I became known for advocating controversial hypotheses, I didn't get even one grant in 12." The other four scientists rejected for OIG renewals continue to receive other government grants. Duesberg, meanwhile, has lost his technician, dishwasher, and secretary. "If you don't get your grant renewed, I'll tell you, it's not a very pleasant life as a scientist," he says. Some scientists and AIDS activists have said that Duesberg's lack of funding during an acknowledged period of very tight funding from the National Institutes of Health is not remarkable. But Yale University mathematician Serge Lang, who has compiled a great deal of material on Duesberg, HIV, and AIDS and distributed it to a wide variety of scientists and journalists, including The Scientist, says: "He can't get funding the moment he opens his mouth challenging the HIV/AIDS hypothesis. Something is cockeyed." Duesberg's CV lists 94 publications since the 1987 Cancer Research paper. Twenty-one report on his oncogene work, and 10 of those came in 1987 and 1988. Of the 73 publications dealing with AIDS, about half are letters and perhaps a half-dozen are in major journals. Duesberg complains that he is not allowed to make his own case in Science or Nature though he did write "HIV is not the cause of AIDS" for Science in 1988 (241:514- 6), which was accompanied by a response from the mainstream (W. Blattner, R. Gallo, H. Temin, 241:515-6). Nature editor John Maddox wrote a page-long editorial denying Duesberg "the right of reply" to a commentary criticizing his drugs/AIDS hypothesis (M.S. Ascher et al., Nature, 362:103-4, 1993). Duesberg maintains that the commentary itself documents that every one of 215 people who developed AIDS had used nitrite inhalants, and the raw data show 84 percent had also used AZT. "That falls short of refuting the drug hypothesis," he says. Ascher and his colleagues, however, stated in a letter to Science (267:1080, 1995) that 27 of the 215 had not used nitrite inhalants. "We didn't publish [Duesberg's] writings on the subject," Maddox maintains, "because they were too tendentious. They were designed to cause trouble." However, in a recent editorial (Nature, 373:189, 1995), Maddox invited Duesberg to respond to a pair of papers in the journal that have been cited by researchers and journalists as strong support for HIV's causative role in AIDS. "We thought it was time he said how it affected his views," Maddox says. Duesberg's article, coauthored by Harvey Bialy, research editor of Bio/Technology, was submitted to Nature on February 7. "We'll publish it in some form or another; it's far too long as it stands," says Maddox. In 1991, Duesberg and some fellow critics formed the Group for the Scientific Reappraisal of the HIV/AIDS Hypothesis. One of the group's objectives has been to publish a four-sentence letter calling for an independent review of HIV/AIDS data. After being rejected from Science and other journals over the years, the letter--grown to four paragraphs--was recently printed in Science (267:945-6, 1995) in the aftermath of its coverage of Duesberg. Root-Bernstein had been one of the original members of the group's editorial board, but he was not a signer of the letter to Science and has resigned from the group. Steven Jonas, a professor of preventative medicine at the State University of New York, Stony Brook, another founding board member, has also resigned. They cite a hardening of the group's position from one of broad-based skepticism to one that stressed Duesberg's view above all else. Duesberg should not be surprised by his lack of acceptance by the mainstream, asserts Root-Bernstein, who has published a copiously referenced book critical of premature consensus on HIV (New York, Rethinking AIDS, Free Press, 1993). "If you are going to go out and do maverick-type research, you have to be willing to operate as a maverick. Peter has wanted to operate as a maverick but maintain the perks of the mainstream." Root-Bernstein has gone to a private company to fund his research developing animal models of autoimmune processes. He says he never submitted a proposal to NIH because he did not get much positive feedback from preliminary discussions with funding officials. Another AIDS researcher critical of conventional wisdom that HIV alone causes immune suppression is Shyh-Ching Lo of the Armed Forces Institute of Pathology in Washington, D.C. For nearly a decade, Lo and his colleagues have been investigating the role of mycoplasmas organisms between viruses and bacteria in size and possible involvement of other viruses and bacteria in AIDS. His work, he freely acknowledges, draws criticism from other AIDS researchers. "If your view is not shared by the mainstream, it is evaluated more skeptically," he contends. "It is true that it is harder for us to present our work. It keeps us going and keeps us honest." As it becomes apparent that perhaps not everyone infected with the virus will get sick, Lo says, more and more scientists are willing to believe other factors affect the host's immune system and influence the course of infection. Lo agrees the evidence of HIV involvement is strong, but notes, "We should be open-minded about this. I'd hate to see the entire scientific community bet solely on HIV." For his part, Duesberg has an explanation for why the AIDS community has closed ranks around HIV and for why he cannot get funded to test his drug hypothesis using poppers on mice and it is not because of any scientific evidence. "A whole generation of AIDS scientists, retrovirologists in the last 10 years their names, their papers, not to mention their fortunes, solely and exclusively rest on one thing, on HIV. If HIV is not what it is said to be ... all these people ... would be nobody. "In fact, worse than that: Many would be rightfully blamed for having intoxicated 200,000 Americans with AZT every six hours and panicked millions of people with a positive AIDS test. hypothesis if this hypothesis were proven wrong. So these people cannot afford in the least bit to consider an alternative that might end their careers." Billy Goodman is a freelance science writer based in Upper Montclair, N.J.

A Controversy That Will Not Die: The Role Of HIV In Causing AIDS

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