DAVID CROWE

Oncogenes, Aneuploidy and AIDS: A Book Review

By RFD Columnist, David Crowe

Duesberg’s scientific life clearly has had three phases, although they overlap in time. He became famous through his expertise with oncogenes (cancer causing genes), with this phase ended with him rejecting their significance. He more seriously collided with the scientific establishment through his skepticism over AIDS. This completely shattered his mainstream reputation, almost completely eliminating his ability to publish in scientific journals, or even to obtain grants to fund his research. Most recently he has received much more respectful consideration because of his revitalization of the theory that aneuploidy, not oncogenes, is the carcinogenic trigger.

This book is also partly a biography of Harvey Bialy, a friend and supporter of Duesberg, who was editor of Nature Bio/Technology for much of the time covered. This is both a strength and weakness of this book. This allows greater insight into some events, but sometimes also intrudes. The book starts with a story about Bialy’s disastrous teaching experience in Nigeria. Although this is chronologically the beginning of a close relationship between Duesberg and Bialy the anecdote itself seems to have little significance apart from this.

The book starts with Duesberg’s involvement in oncogene theory, which still dominates cancer research. Duesberg pointed out fatal flaws in this theory in the early 1980’s, something that did not endear him to the army of scientists digging the trenches of the War Against Cancer. One of the similarities between AIDS and Cancer was that oncogenes started as a very simply theory – one gene causes one cancer, but then became more and more complex (to explain growing amounts of contradictory evidence) until eventually so many modifiers and co-factors were required to prop it up that the theory had all predictive value drained out of it.

One flaw in the oncogene view of cancer that Bialy dissects at length is that the prototype for oncogenes is in the human cell. It is difficult to understand why cells would harbor such deadly enemies. Duesberg noted that although the retroviral oncogene originated in the human genome, the cellular prototype differs enough that it might not be carcinogenic. Bialy describes how the oncogene theory evolved to attempt to evade the criticisms, but becoming more complex, making more assumptions and losing value all the time. This description is tough slogging for someone like myself who has not been immersed in oncogene theory for a number of years.

Words and definitions are very important to modern science, although the influence is often corrosive. Those who control the words, control the science. Continually mouthing a word while drastically changing its definition is a way to hide seriously flaws in a theory, particularly when the word is as evocative as ‘oncogene’ or ‘AIDS’. Bialy points out that by downgrading the word ‘activation’, oncogene theory could continue to claim success even though it no longer referred to an increase in production that is necessary to produce cancer. Multiple genes and external agents to activate gradually were admitted to the causal path to cancer, leaving the predictive value of the theory near zero, and placing it far away from the simplistic model that most non-scientists understand.

It is telling that Bialy does not, however, question the use of the word ‘isolation’ which is critical in the discussion of AIDS (and other virus research), and a place where Duesberg, who believes that HIV does exist, departs from more radical AIDS rethinkers. Notable among these are the ‘Perth Group’ who claim that purification of HIV has never been achieved and that the term isolation means nothing. In a description of Koch’s Postulates Bialy himself states that “[a putative pathogen] should be present in all cases of the disease from which it should be possible to isolate it in a pure form, and in such a pure form it should be capable of reproducing the disease in a susceptible host.” Yet, Bialy never notes that no recently discovered virus, and certainly not HIV, has ever been purified, an important point obscured by the use of the word ‘isolation’ to mean much much less than this. The avoidance of this important argument illustrates just how close Bialy is to Duesberg in his point of view.

Another impact of words is that they can be easily ignored even when published in a major scientific journal. Duesberg’s criticisms of oncogenes received the ‘See No Evil’ treatment from many researchers, consequently his ideas had little impact. This does not say much about the role of open discussion in modern science, but is commonly the treatment received by radical ideas. The sheep wait for the sheep dog to react before stopping their placid grazing. For various reasons, Duesberg’s criticisms of AIDS were taken much more seriously both inside and outside the temple of science. It was perhaps this impact that torpedoed his career more than anything, the temerity to make his arguments accessible to the uninitiated. If non-scientific types took Duesberg seriously then the purse strings on research could be tightened. Threatening funding was the ultimate crime.

If Duesberg has an döppelganger it must be another retrovirologist, Robert Gallo, who has also researched both cancer and AIDS. Having claimed ownership of HTLV-I (Human T-Cell Leukemia Virus 1) Gallo tried to morph his personal family of viruses from a T-Cell growth promoter to a bloodthirsty T-cell slayer in HTLV-III (with the ‘L’ subtly changed from Leukemia to Lymphotrophic). The dubious nature of this claims has been thoroughly examined in John Crewdson's book “Science Fictions”.[Crewdson, 2002]

After making himself a leper among oncogene researchers Duesberg moved on to examine the viral theory for the cause of AIDS. He was never an insider on this subject, never a true believer, always a skeptic. One of the reasons, Duesberg admitted to Bialy, was simply because Gallo was an early and fervent believer – “I could not refrain from looking hard at any hypothesis Bob was behind”. But it was not just his distrust of Gallo’s science, “In addition, there was the complete improbability of the virus-AIDS hypothesis on first principle.” This was because retroviruses rely on cells to replicate, so killing their host made little sense.

Bialy includes detailed descriptions of the behind the scenes negotiations that went on after Duesberg published his 1987 Cancer Research paper claiming that HIV did not cause AIDS.[Duesberg, 1987] Editors of major journals were anxious to not publish any more of Duesberg’s work whereas before they would have been falling over themselves to nab a paper. However, they also claimed to use a rigorous and unbiased methodology to choose which papers to publish. Occasionally, after much back and forth described in the book, Duesberg would get a paper published. Other times the editor would cut of the correspondence and reject the paper.

Some of his biggest battles were with John Maddox, then at the helm of Nature, a far more influential journal than Bialy’s Bio/Technology, but ironically also published by Macmillan. Maddox did not hesitate to use his editorial position as a pulpit, in one stating that “Now may be the time [for Duesberg] to recant [his heretical views on AIDS]”. Another revealing quote from Maddox, trying to save the HIV=AIDS theory from the lack of causal evidence, was “HIV causes AIDS, in some manner not understood.”

Nature was not the only journal whose editors tried hard to prevent Duesberg publishing. Science, the US rival to Nature, was even less anxious to publish on this debate, having fought hard to grab the rights to Gallo’s papers which were published shortly after the famous press conference where the claim that the cause of AIDS had been discovered was announced by Margaret Heckler. They did eventually publish a highly truncated debate,[Duesberg, 1988] but no ongoing discussions through the submission of papers and letters was allowed.

Bialy also describes Duesberg’s difficulty getting an article published in the Proceedings of the National Academy of Science (PNAS) which he, as an academy member, should have had easy access to. It took several months and sixty pages of correspondence before it was published.[Duesberg, 1989] Bialy makes the interesting point that this incredible level of scrutiny to his papers should make them difficult to dismiss.

An advantage of Bialy being so close to unfolding events in molecular biology is that he can relate anecdotes that are humorous, shocking and very revealing about how bias and censorship suffuses science. At an early high priced conference on oncogenes organized by Nature, Bialy asked the deputy editor, Peter Newmark, why Duesberg was not invited. The answer was that “Since Duesberg didn’t ‘believe in’ oncogenes, what was the point in having him speak?” Gallo, however, was invited to speak, and used the opportunity to promote his personal family of viruses (HTLV) as both promoters and destroyers of lymphocytes. Another incident, this time related to AIDS, was the cancellation of a White House meeting when AIDS Czar Anthony Fauci blew a fuse after learning that Duesberg would be present, claiming that it amounted to White House interference in scientific matters.

A highlight (or lowlight) of the attempts to silence Duesberg ensued when a paper entitled “HIV Causes AIDS: Koch’s Postulates Fulfilled” was prepared. Duesberg was listed as senior author, and told that it had been accepted by Nature even though he had not written or reviewed a single word. All he had to do was sign, he was assured, to be welcomed back into the fold of true believers. After Duesberg proposed radical edits (including to the title) the other authors gave up. The lack of his signature meant that the paper was published in a more obscure journal with a note indicating that Duesberg had declined an offer to be a co-author.

The third phase of Duesberg’s scientific life documented by Bialy is his revitalization of the Aneuploidy theory of cancer formation. This term refers to an incorrect number of whole chromosomes in a cell, a state found in most cancerous cells, including all tumors. The theory espoused by Duesberg and others (including Ruhong Li and David Rasnick) is that slight alterations in the chromosome count may be more damaging than, for example, a doubling of chromosome numbers. To me, aneuploidy is a bit like tonal music, two notes that differ only a little are discordant, yet those with double the frequency (an octave) sound much sweeter. Twice the chromosomes would produce proteins in the same balance as with a single set, but with one and a bit sets, some would produce at twice the rate as those not duplicated, resulting in greater metabolic disruption. After many assaults on an organism, one cell may achieve a number of chromosomes that is stable enough to allow replication of the cell, but unstable enough to evade the normal limitations on replication.

Surprisingly, Duesberg’s revival and extension of the aneuploidy theory is being taken very seriously. The mainstream magazine Scientific American, for example, in a July 2003 article, devoted considerable space to a discussion of aneuploidy, mentioning Duesberg’s name several times as the most significant contributor to the field. Bialy relates, however, that at about the same time Duesberg was being denied his ordinary merit increase because, the justification went, the aneuploidy-cancer link was tentative and because he has few graduate students or Post-Docs. Well, duh!? What graduate student in their right mind would start their career by ending it by associating with a professor who is treated as a pariah by his peers?

Bialy writes quite well, although every once in a while he produces a sentence that is so complex that the semantics are lost while wrestling with the syntax. This is usually due to unnecessary parenthetical asides, something that should be unraveled by the writer as a service to the reader, not by the reader as a service to the writer. One example is “Peter H. Duesberg had his scientific temperament forged in a molecular biology that was founded in—and which its practitioners adhered to almost religiously—the discipline of hypothesis formulation and testing.” Some people believe that writing simple sentences is pandering to a semi-literate audience. I disagree. When writing about technically complex subjects the style of English used should be simpler than normal, not more complex. Just trying to get a tentative grip on oncogene theory is tough enough for my brain, I don’t need the extra challenge of unknotting convoluted sentences.

Bialy also makes the mistake of resorting to sarcasm. I don’t believe this is solely because he is trying to use this book to defend a friend, but because he believes that many established scientists are wilfully ignoring contrary evidence. However, combined with a tendency for overly long sentences one is never sure whether “Fauci’s own considerable scientific intellect is further demonstrated…” is going to end with a compliment or an insult. Not only is this confusing but, more importantly, it attempts to push the reader to a conclusion before they have a chance to review the evidence.

This book is obviously going to appeal to those who are admirers of Duesberg’s scientific vision or tenacity. It should also be read by those who are interested in AIDS or Cancer and who are also willing to consider the possibility that many mainstream ideas about these diseases are bankrupt. Much of the material is also of historical value.

This is not a full biography of Duesberg and therefore does not shed much light on how a man could rise so high and yet be so uncorrupted by his position that he was willing to give up his established status so that he could continue to express opinions that he believes to be the truth.

Further Reading

[Bialy, 2004] Bialy H. Oncogenes, Aneuploidy and AIDS: A Scientific Life & Times of Peter H. Duesberg. North Atlantic Books. 2004.

[Crewdson, 2002] Crewdson J. Science fictions: A scientific mystery, a massive cover-up, and the dark legacy of Robert Gallo. Little, Brown. 2002.

[Duesberg, 1987] Duesberg PH. Retroviruses as Carcinogens and Pathogens: Expectations and Reality. Cancer Res. 1987 Mar 1; 47: 1199-1220.

[Duesberg, 1988] Duesberg PH. HIV is not the cause of AIDS (with response by Blattner et al). Science. 1988; 241: 514,516.

[Duesberg, 1989] Duesberg PH. Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation. Proc Natl Acad Sci U S A. 1989 Feb; 86(3): 755-64.