Book Review

By Peter Duesberg

New York Native 29 April 1991

Book Cover In Virus Hunting, Robert Gallo offers a highly personal view of his triumphs and agonies with the human retroviruses he believes cause leukemia and AIDS. Gallo's greatest triumph was the notorious press conference in April 1984 when he and the Secretary of Health and Human Services Margaret Heckler jointly announced that Human Immunodeficiency Virus (HIV) is the cause of AIDS and that Gallo had discovered HIV. It set the unique precedent, that a scientific hypothesis of immense clinical consequences would be nationally accepted prior to a single publication on the subject by Gallo or any other American scientist. Moreover, Gallo managed at the same time to file together with his employer the National Institutes of Health, for a lucrative AIDS test patent. However, subsequent nucleic acid sequence analyses proved Gallo's virus from 1984 to be the same as the virus discovered by Luc Montagnier in 1983. Since Montagnier had sent his virus to Gallo in 1983, it appeared that Gallo had rediscovered Montagnier's virus. In addition, a legal investigation proved that the photograph of HIV in Gallo's first AIDS papers was that of Montagnier's virus ''inadvertently" used ''largely for illustrative purposes" (p. 210-11). That would have been the end for all claims to immortality by ordinary, academic scientists not working for a government that had committed itself to Gallo's hypothesis.

In Virus Hunting, Robert Gallo claims to have achieved two of his most desired goals: to prove that HIV virus is guilty of causing AIDS and that Gallo is innocent of appropriating Montagnier's virus. The bizarre story of how Gallo isolated his HIV is one of the many, too many, stories told to put to rest the suspicion that Gallo had misappropriated Montagnier's virus. Says Gallo, Mika Poppovic took the ''thinking" of infecting cells in culture ''one step further.... He continually reinfected by adding virus back to the cell line or by adding fresh cells as needed.... Now he had virus from ten patients in the pool....To this day, we do not know which patient it was from." (p.179-180) However, if Gallo and Popovic had ever studied retroviral interference, the answer would be embarrassingly clear. The virus was from Montagnier's "patient," because if cells are infected in sequence by related retroviruses, the first one to infect a culture will exclude all subsequent infections. In view of Gallo's and Poppovic's plans that "one day we will tell our grandchildren about this moment" (p. 180), one can only hope that their grandchildren will not know more about retrovirology than their grandfathers did.

In his efforts to legitimize his discovery, Gallo struck one of the biggest deals of revisionist science. In 1987 he coauthored a Nature paper with Montagnier that described 'the scientific chronology of events" (p. 214), claiming that both researchers had "co-discovered" HIV, one in 1983 and the other in 1984, and co-believed that it was the cause of AIDS. It described the two scientific and patent rights rivals as friendly allies in the war against AIDS. Indeed, it is bewildering to see how much time Gallo spends bargaining science for politics or politics for science instead of making his case in the laboratory. Take for example another deal with Montagnier, "When Montagnier and I met in private and had a chance to discuss our views, we agreed to respond to the question with a middle position: the mutation of AIDS [probably means HIV] into casually transmitted virus would be highly improbable. '(p. 233)

However, the entente cordiale with Montagnier did not last forever! In 1990 Montagnier came to the conclusion that HIV cannot be a sufficient cause of AIDS and is thus no longer a satisfactory enemy in the war against AIDS. At the international AIDS Conference in San Francisco, at press conferences and in two scientific papers in 1990, Montagnier cited the chronic dormancy of HIV, the fact that never more than one in about 500 T-cells are infected, and above all, the inability of HIV to kill T-cells, as primary reasons for his change of mind. Ironically, Gallo notes seven years after himself introducing HIV as the cause of AIDS at a press conference, "this surprising view which has been chiefly presented in press conferences, has given, and may do so for a while, added longevity to confused and confusing (to others) arguments that HIV is not the primary cause of AIDS." (p. 286) "In short, he has lent some support to Duesberg..." (p. 297), thus putting the HIV-protestant Montagnier, now referring in the press to HIV as a "peaceful virus," close to the HIV-renegade Duesberg who said HIV was a harmless "dud" (p. 290). Likewise, Gallo writes that "...Duesberg's rush to the media has its dangerous side." (p. 297) But Gallo, the father of science by press release, fails to explain why it is "dangerous" for me, Montagnier, and others to question a hypothesis that in seven years of fierce research and annual investments that currently amount to 3 x 10 9 dollars has yet to stop or contain AIDS, or even predict its spread.

Gallo sets for himself the highest standards of scientific integrity in his efforts to prove HIV as the cause of AIDS: "...until we were able to lay out our proof before the scientific community... no credit came our way," and ''I believe in the value of vigorous debate. It is almost instinctive." (p. 164) "I love the rough and tumble of intellectual debate and usually welcome attacks on my own ideas (though I admit not always... and depending on the source)" (p. 169). Yet lots of credit and patent rights came Gallo's way, before even his first paper on the AIDS virus had been published; and his love and instinct for intellectual debate suddenly disappeared when I challenged his "own ideas" about HIV and AIDS in a paper in the Proceedings of the National Academy of Sciences in 1989 (86:755764). For two years Gallo failed to honor his promise to the editor of the journal to write a rebuttal. Indeed, Virus Hunting shows that Gallo is a paper tiger when it comes to intellectual debate. Clearly he has nothing but soft epidemiological evidence to offer as "proof" for the virus-AIDS hypothesis. His strongest point is that antibody to HIV is found in all AIDS patients "one hell of a good beginning..." (p. 292). However, he fails to point out that AIDS is defined as a syndrome, a collection, of 25 unrelated diseases that are only called AIDS if that antibody is present. In its absence the very same diseases are called by their old names: pneumonia, dementia, tuberculosis, etc. Moreover, Gallo acknowledges that HIV fails the classic criteria of proving a microbe guilty of causing a disease, formulated by the German bacteriologist Robert Koch, who discovered the bacillus of tuberculosis. However, instead of providing alternative proof of HIV as the cause of AIDS, Gallo dumps the timetested postulates of Koch. Says Gallo, "The last one hundred years [from Robert Koch to Robert Gallo!] have also conclusively taught us that the underlying premise of Koch's postulates is wrong" (p. 281)

Gallo emphasizes repeatedly that I am unprepared to understand AIDS, because I am not an M.D. but "a chemist, a molecular virologist" (p. 291). After Virus Hunting, I wonder whether the M.D. Gallo might not have been better cast using his medical training to treat AIDS patients than trying to resolve the "molecular virology" of HIV and the ''chemistry" of AIDS. Here are some samples of Gallo's efforts to prove "How the AIDS virus works":

1. On why antibody to HIV does not protect against AIDS:

a. "Because retroviruses integrate their genetic information upon entry, the immune response to infection shows up too late to serve as protection against it." (p. 206) Obviously Gallo believes that the immune system only protects if it were faster than viral infection. Yet the immune system against any virus, including retroviruses, never responds until millions of cells have been infected and sufficient viral protein is made for an immune response.

b. But even if antibodies could be made available in time, Gallo argues "that most antibodies are not protective. In many instances none are protective" (p. 292). This of course is a heavy blow to the practice of inducing antiviral antibodies by antiviral vaccination, for 200 years the only protection against virus diseases. Unfortunately, Gallo does not identify the sources of this threatening information. Fortunately, it does not apply to antibodies to HIV, detected by Gallo's "all-important AIDS test" (book jacket), because in the presence of such antibodies HIV is so efficiently neutralized that it is, if at all. only detectable by the most sophisticated and expensive AIDS laboratories. Indeed, two recent papers by Ho et al. and Shaw et al. from the New England Journal of Medicine (April 4) just confirm "rapid...and effective immune responses [to HIV] in the host." The fact that antibodies against HIV are not protective against AIDS is not because they don't neutralize HIV, but because HIV is not the cause of AIDS (see Duesberg PNAS 86:755-764, 1989 and 88:1575-1579, 1991).

2. On how homosexuals get AIDS in the U.S. and heterosexuals in Africa:

a. "AIDS is in young gay men... for many obvious and logical reasons.... More blood penetration is likely to take place in rectal sex than in vaginal sex." (p. 291) Perhaps Gallo is not aware of menstruation?

b. In Africa "Other factors may also contribute to the discrepancy, such as ritualistic voodoo practices." (p. 229)

c. "When the man ejaculates, the few HIV particles may lose their outer coat (envelope) and are not infectious...." (p. 240) This sounds like a highly personal observation - because retroviruses are not known to disintegrate upon far greater physical stress than ejaculation, such as centrifugation at several 100,000 gravity units.

d. Then there is a very new Gallo story. "My new co-worker A.A. working with V.F. discovered that two parasites found in fecal material, giardia and amoeba, can be infected by HIV. These parasites are not uncommon in central Africa and in gay men everywhere.. ...We wonder whether this is a factor in HIV communicability" (p. 251). If it were, the host range of HIV would have expanded very far, from human T-cells to amoeba and giardia!

Yet the politician Gallo does not want to offend American homosexuals or central Africans and their microbes by assuring all of us that "sexual transmission from man to woman... is probably the most common pathway of infection in the world not man to man by sex, as we in the U.S. tend to think" (p. 251). That, however, leaves open the question as to why women represent less than ten percent of all AIDS cases in the U.S.

3. On the long latent period between infection and AIDS, that currently averages about ten years: "In the early years however, the immune system is still able to handle the challenge. Not so later." (p. 242) At that point Gallo seems to have forgotten that the immune response comes too late, and is not effective at any time as he points out later (p. 292, see #1,b).

4. On the decline of T-cells in AIDS over 99 percent of which are never infected by HIV: "But it is not only direct killing by HIV that depletes T4-cells. At any given moment... in our experience usually fewer than one in 10,000 cells express virus at most times. Other less direct mechanisms also appear to be operative." (p. 248) This leads him into the theories on cofactors for HIV described below.

5. On AIDS dementia:

a. ''Some of it no doubt is a direct toxic effect of the virus on microglial cells. This in turn may lead to less 'architectural support' to the neurons, whose function may then be compromised." Obviously a speculation.

b. And "another mechanism," as if this one weren't convincing enough, "...another HIV regulatory protein called Nef is also released by infected cells and Nef has some regions of similarity with a brain-poisoning protein from scorpions" (p. 250). Another, totally different speculation for the same question.

6. On HIV causing Kaposi's sarcoma: The same virus that releases cell killing "scorpion poisons" is said also to release growth factors, termed tat proteins, that make certain cells grow into Kaposi's sarcomas. ''To my knowledge, it is the first time a protein of a virus, normally working as a regulator for virus formation, was observed also being released from the infected cell and acting as a growth factor for another cell." (p. 270) Yet another in the inexhaustible repertoire of evils of HIV!

7. On the 20-fold higher incidence of Kaposi's sarcoma in homosexuals compared to other HIV-positives:

a. "These findings appear to require another environmental (external) factor - such as another not yet discovered virus - in gay men." (p. 271) If in trouble, postulate another virus.

b. "Perhaps this is a result of differences in the levels of male sex hormone, testosterone... Perhaps sexually active homosexuals as a group have higher testosterone levels... This is a testable hypothesis... and it is testable hypotheses that advance science" (p. 271). A long discarded hypothesis, which in the past has led to sentences of forced treatments of homosexuals with female sex hormones.

8. On cofactors of HIV for AIDS: Clearly Gallo has initiated his retreat from the once solid HIV-causes-AIDS-front to the minefield of HIV-plus-cofactors cause AIDS. ''I also intuitively agree with the idea that cofactors for HIV progression [he probably means AIDS progression] itself can also exist...."

a. '' ....At this time we can say that the [so-called human leukemia viruses] HTLVs are the only known specific cofactor for AIDS..." (p. 248).

b. ''. . . I suspect that [another virus] HHV-6 is also likely to be a contributing factor to the development of AIDS" (p. 254). "I have suggested we look carefully at two: HTLV-I and HHV-6 [both discovered by Gallo]. There may be more." (p. 254).

c. "Another possible cofactor in the depletion of T-cells is via an abnormality in the production of the T-cell growth factor, IL-2, by T-cells of AIDS patients, even by cells not infected by HIV." (p. 248). No further explanation is offered as to why uninfected cells would kill each other in some people with antibody to HIV.

But Gallo is uneasy about cofactors, in particular, if they come from others. "...Nonetheless I am surprised that Montagnier has suggested a mycoplasma [not even co-discovered by Gallo] as a possible or probable prerequisite for AIDS development with HIV" (p. 297). Gallo realizes that cofactors have been the beginning of the end of many once spectacular hypotheses. Gallo expresses his concern with a quote from Lewis Thomas: "Multifactorial is multiignorance. Most of the factors [and quite possibly even HIV] go away when we learn the real cause of a disease." (p. 148) Adopting cofactors has in fact become the admission of failure in the new era of big science. In view of the large personal and commercial investments in big science, like AIDS or cancer research, it has become virtually impossible to admit a fundamental mistake. Big science can respond to errors no better than the Titanic to icebergs.

Clearly Gallo's offerings on "how the AIDS virus works" are most entertaining and solid proof for his lively imagination. But in terms of scientific proof for the virus-AIDS hypothesis or "intellectual debate" they confirm a quote from a common friend who subscribes to Gallo's virus-AIDS hypothesis, "Gallo cannot argue his way out of a paper bag." Because there is no logical evidence for HIV as the cause of AIDS, Gallo flounders around many, too many, hypotheses and psychological rather than logical drama. Gallo bluffs the outsiders with scientific jargon and inaccessible concepts and engages the insiders either in self-congratulating dialogues with supporters or in pseudoscientific debates with opponents, often in the form of undocumented quotes, in order to achieve his goals with relentless energy and redundancy. For example, "It has been said [by whom?] that this period - roughly 1983 to 1985 - marked the most rapid progress in medical history.... Francis Crick makes this point in What Mad Pursuit. I agree with his sentiment..." (p. 203) Or, "Duesberg simply dismisses [the slow viruses] by saying 'they probably don't cause the diseases.'" (p. 295) Gallo doesn't identify the source of the quote and wins his point with an undocumented counterclaim. However, he gives generous credit to nonthreatening supporters or collaborators - but none whatsoever to independent competitors or opponents. And all this without even a single reference to the scientific and nonscientific literature. In addition, the book is poorly proof-read, containing spelling errors in names and technical terms, and almost all index items are off by several pages.

This leaves us with the most unanswered question of Virus Hunting: Why is there so much faith in virus hunters, even though virus hunters have not provided clinically productive hypotheses since the polio epidemic in the 1950s? Like the Cold War armies after World War II, thousands of virus hunters were recruited since the polio epidemic to defend against further ''deadly" viruses. Since there were no further deadly viruses in the Western World since the '50s, at least some were invented in the laboratories. For example, viruses were blamed as causes of Burkitt's lymphoma, breast cancer, T-cell leukemia, cervical cancer, Alzheimer's disease, subacute sclerosing panencephalitis, and now AIDS and the chronic fatigue syndrome. Since none of these diseases is contagious, the viruses had to become very slow - allowing years, often decades, between infection and disease. For example, Gallo's leukemia virus is currently estimated to cause leukemia only once every 2000 years in human bodies. If it occurs in an individual, it does so only after "many years" (p. 281), on average 55 years after infection - a very slow virus indeed! Further, the viruses were said to be highly selective of their victims to explain the odd, non-random epidemiology of these diseases like AIDS in drug-addicts and male homosexuals and chronic fatigue in female yuppies and viral leukemia in certain Japanese islands. And since the viruses are neither active nor abundant in these diseases, they were accommodated as "deadly" pathogens by the bizarre postulate that even rare and latent viruses cause deadly diseases.

The situation became so absurd and academic that many former virus hunters began to look for more plausible explanations of these diseases. Some, like me, took up oncogenes as causes of cancer, others like Montagnier, began to look for nonviral "co-factors" of HIV, as a cause of AIDS. However, many like Gallo persisted in their quixotic beliefs perhaps because virus hunting is their only expertise. Writes Gallo, the Don Quixote of human retrovirology, ''We believed in the human retrovirus and stuck with our beliefs throughout our own remarkable journey..." (p. 164) chasing forever the windmills of latent human retroviruses. Perhaps even Gallo sees the writing on the wall: "Sometimes we Ivirologists] have a virus in search of a disease" (p.282) that can't be accommodated as a pathogen - even with an AIDS budget.

And all of this Virus Hunting would be just another, albeit expensive, scientific comedy if it weren't the only basis for the chronic treatment of currently 125,000 symptomatic and even healthy HIV-carriers with AZT (Duesberg. PNAS 88, 1575-1579, 1991). AZT is an inevitably cytotoxic terminator of DNA synthesis - and DNA is the central molecule of all life. It is administered to HIV carriers to inhibit HIV DNA, but unfortunately it inhibits human cell DNA synthesis just as well. Since according to Gallo, "...fewer than one in 10,000 cells express virus [and fewer would make HIV DNA] at most times" (p. 248), 9,999 uninfected human T-cells will be killed by AZT for every T-cell infected by HIV - the hypothetical cause of AIDS! This is called a high toxicity index in pharmacology. Obviously, the M.D. Gallo is not unaware of these "side effects...chiefly [on] cells ...of the bone marrow [that] are dividing and, therefore, making DNA. So AZT might cause a decline in the number of certain blood cells." (p. 305) - the very cells AIDS patients are deficient in to begin with! It would appear that AZT is the most tragic consequence of Virus Hunting - inevitably fatal to those who receive it and possibly fatal to the future reputations of those who have prescribed it. *