PNAS PUBLICATION OF AIDS ARTICLE SPURS DEBATE OVER PEER REVIEW
By Anthony Liversidge
The Scientist 3 April 1989
Is the National Academy to be praised or hastened for disseminating
the views of controversial scientist Peter Duesberg ?
Some members of the National Academy of
Sciences no doubt were shocked this past February when the latest edition
of their thick, pale gray journal Proceedings of the NAS - arrived
in their mailboxes. Here was the National Academy-the most respected, and
surely the most cautious, scientific body in the United States - publishing
in its very own "house organ" the work of Peter Duesberg, the
respected but controversial University of California. Berkeley, retrovirologist
who has been arguing for two years now that HIV is in no way the cause
of AIDS. This opinion has earned Duesberg little more than opprobrium throughout
the AIDS research community, since his ideas are totally at odds with the
consensus view in the biomedical field. And yet. there he was in PNAS [volume
86 (3), pages 755764], not only raising the same heretical notions
all over again, but doing so at greater length than ever end with 196 references.
However, after several rounds of published
and public - debates over Duesberg's views, it is not merely the findings
he presents in the recent PNAS that are of concern; it is
also the remarkable set of events that led up to the publication of this
latest paper on the etiology of AIDS. These events may well lead scientists
to question just what constitutes fair play in the science publishing arena.
For as it turned out, PNAS forced Duesberg's paper to clear the
hurdles of no fewer than six separate peer reviews, even though the journal
typically requires no formal screening of papers written by academy members-and
Duesberg, one should not forget, is an academy member. The challenging
procedure left a paper trail of no less than 60 pages of combative correspondence
between academician Duesberg and the journal's editor, Igor Dawid.
Further, the 10,000 wordmanuscript
appeared in print despite the fact that the three main reviews ordered
by PNAS were unfavorable. This raises other intriguing questions,
such as: Had the peer review process been a sham? Or had the negative reviews
failed to shoot down arguments that have been shunned and scorned by every
key player in AIDS research? And if that were the case, what is being said
about peer review? Is the system vindicated by having permitted a controversial
notion to be aired in public? Or is it deficient for having allowed
further dissemination of what most scientists consider a wrongheaded
notion and what some feel is actually a public danger?
In Peter Duesberg's case, the answers to these important questions
may well be embedded in his running
battle with the AIDS research establishment a battle that began long
before his submission of the lengthy (two pages over the usual limit) paper
now published in the academy's journal. This most recent effort,
"Human immunodeficiency virus and acquired immunodeficiency syndrome:
Correlation but not causation." expands on points Duesberg first raised
in the March 1987 issue of Cancer Research [pages 11991220].
Tempered in public debate and tested since then the Duesberg arguments
reappeared most notably in the July 29, 1988, issue of Science.
There, Duesberg was pitted against a seemingly formidable trio:
Robert Gallo. chief of the Laboratory of Tumor Cell Biology at the National
Cancer Institute: his colleague Bill Blattner. and Nobelist Howard Temin.
a retrovirologist at the University of Wisconsin's McArdle Laboratory.
The result was a fourpage confrontation labeled "HIV Is/Is Not
The Cause Of Aids."
In each case. Duesberg boldly some
might say brashly pronounced his conviction that "the AIDS virus
is just the most common among the occupational viral infections of AIDS,
rather than the cause of AIDS." He points out that the virus is
hardly detectable after the initial period of infection, that it is
not biochemically active when it supposedly much later causes the disease,
that the body can easily regenerate any T cells killed by the virus. and
that the lab evidence for the killing of T cells by the virus is no model
for its claimed lethality in the body. An authority on the genetic structure
of retroviruses, Duesberg also asserts that the virus is genetically inadequate
to the challenge of producing a new effect years after infection.
Duesberg suggests that AIDS is almost certainly
not caused by any one virus or microbe but "may be caused by new combinations
of conventional pathogens, including acute viral or microbial infections
and chronic drug use and malnutrition." He says studies are needed
to unbundle AIDS diseases and see "how the nature, frequency, and
duration of AIDS risks generate riskspecific diseases."
Gallo and company roundly reject such arguments,
insisting at least until recently that HIV is both a necessary and
sufficient cause of the fatal immune deficiency, which they say kills many,
perhaps all AIDS patients. Most recently, however, in a magazine interview
[Spin March 1989, pages 5481], Gallo, a National Cancer Institute
virologist seemed to have stepped back somewhat from his total opposition
to Duesberg's view, and to concede that the virus in some variants
may be necessary, but in itself is not sufficient to trigger the deadly
syndrome. In the interview, Gallo said: "You and I could probably
live with the virus for 30 years and die of old age."
Still, Gallo and his fellow researchers
such as Anthony Fauci, director of the National Institute of Allergy and
Infectious Diseases, do their level best to dismiss Duesberg as way off
base. Indeed, only a handfu1 of prominent scientists will defend Duesberg's
efforts. One of these is microbiologist and Nobel Prize winner Walter
Gilbert of Harvard University. Gilbert says, "At one level
some of what Peter does is exaggerated, just for the forms of
argument. At another level, he has made a very serious argument on
the role of HIV in AIDS. It is good to have it questioned, and argued.
I absolutely do consider it a valid debate, and I am glad his article has
appeared in the [NAS] Proceedings. The editors made it too much
of a rough going."
Rough going it was. Duesberg first mailed
his paper to the academy last June. What he expected were the usual delays
of a fortnightly scholarly journal: what he didn't expect was four months
of conflict first, an outright rejection by the editor and then,
later, under the regime of a new editor, months of battling over reviewers'
comments. Normally, papers contributed to the PNAS by academy members
including more than 20 by Duesberg himself are printed without
formal peer review although they are run past one informed colleague before
submission. Duesberg had his paper read by fellow academy member Harry
Rubin and also Steven Martin, both retrovirologists at Berkeley. This,
he expected, would be sufficient for publication.
However, Maxine Singer saw it differently.
As editor of PNAS at the time the paper was first submitted in midJune
of last year, she saw the essay as too similar in its conclusions to Duesberg's
earlier paper in Cancer Research. "I felt on the basis of lack of
originality that it just didn't belong in the Proceedings," she
explains. "I felt he had published his view in full in that prior
article and he didn't add very much."
After consulting with referees Singer decided
to reject the paper. She returned Duesberg's manuscript to him the same
week she stepped down from the parttime post she held as PNAS editor
at the end of June This didn't stop Duesberg, who resubmitted his paper
to Singer's successor, Igor Dawid. The new PNAS editor took a different
tack. He sent the paper out to three referees in what was now to
be a formal review process.
The three official reviews were all unfavorable,
liberally attacking alleged "non sequiturs," "misleading
arguments," "completely incorrect statements," "conceptual
errors," and "partial truths." For all that, in 14 single
spaced pages, they provided only two citations from the published
literature to back their criticisms.
Duesberg's response was of two kinds:
On the one hand, he challenged what he called "worthless,
undocumented opinions." (Dawid requested more references but elicited
only two, both dating from before AIDS was identified.) And on the other
hand, Duesberg made changes and clarifications in his paper that sufficed
to accommodate each reviewer objection.
But none of this came easily. There were
months of sometimes tense exchanges between Duesberg and Dawid over what
was expected and what was reasonable. The 60 pages of correspondence that
grew up between Dawid and Duesberg make lively reading. At one point Duesberg
accuses Dawid of "a profound bias against my paper." At an other Dawid
writes: "It is with a major exertion of selfcontrol that
I answer your letter of October 11 in what I hope will read as a calm and
Duesberg, too, reached a point of no return.
The lengthy process coordinated by Dawid began to seem to Duesberg to be
beyond the bounds of fairness when Dawid raised his own extensive criticisms.
This upped the count to six reviewers in all, seven including Singer, at
which point Duesberg dug in his heels and refused to deal which any more
In the end, though, Duesberg acknowledges
Dawid's "substantial efforts" in developing a paper he is "proud
of," writing that "despite the good battle, there are no hard
feelings." And Dawid, for his part, authorized the paper for publication
in the February issue, along with a caveat of sorts - a promise to present
a divergent view in a future issue. (This never happened - AL)
Two weeks after the public dissemination
of the paper. the major HIV proponents either wouldn't comment on its contents
or were claiming not to have read it properly. Anthony Fauci, director
of the NIH Office of AIDS Research, said he preferred not to make comment.
Fauci, by the way, may have been one of Dawid's reviewers judging from
the fact that some of the most rhetorical reviewer comments match closely
statements Fauci has made in public. To cite one such comment: "What
kind of aberrant lifestyle abnormalities does a monogamous heterosexual
55yearold wife of a hemophiliac have that causes her to develop
AIDS?" the reviewer asks, in what is intended to be a swipe at Duesberg's
claim that aberrant lifestyles, and not the virus itself, are key to the
Asked her view of the final piece. Maxine
Singer says, "I'm still reading the November issue of the Proceedings.
Keeping up is a burden." She then notes that after all, she had
read the initial version very thoroughly. And then there's Robert Gallo,
who has been asked to write a counter review for PNAS. Gallo told
The Scientist that there is a copy on his desk but "No, I haven't
read it. I have to work for a living." Has he changed his mind about
the potential impact of the article? " I haven't heard a single scientist
discuss it for one second." he says. However, Gallo adds, "If
it concludes that HIV is not the cause of AIDS, it is wrong, very wrong."
It does. of course. conclude that HIV is
not the cause of AIDS, and that raises an intriguing question for Gallo:
Was Dawid forced to ignore the universally negative reviews because the
peer reviewers had failed to disprove Duesberg's contentions indeed,
because they somehow did a bad job? Not according to Gallo. "As a
reviewer and I wouldn't dare review it, it is too emotional and too
strange I might have accepted it for publication too, even though
I didn't agree with it. The Proceedings is a great journal, but
you can't stop a member from publishing unless it is totally off the wall.
To support his point, Gallo asserts that
Nobelist Linus Pauling published several papers in PNAS, "which
were disagreed with by the scientific community," even though Pauling's
original paper on Vitamin C and cancer was turned down by PNAS in
1972. Gallo affects a non-challenge about Duesberg: "It mystifies
me." he laughs, "that Peter's [paper] was able to be stopped
for such a long time."
But shouldn't competent peer review have
been able to refute a scientific assertion that, to Gallo, is clearly way
off base? Gallo replies "Maybe they didn't know every argument, maybe
they didn't check every last detail. You would have to ask Dawid. But I
can tell you one reviewer told me he found it abominable."
Dawid's response is guarded, but he confirms
that Duesberg was not forced to go along with every last demand of the
reviewers. (Duesberg insists that, on the contrary, all critical points
raised by the reviewers were answered to Dawid's satisfaction.) Peer review
in this case does not guarantee that the paper is valid, he insists. Says
Dawid; "Review means that people have looked at the paper, and commented,
and after this the editorial board has decided that the paper could be
published. This does not mean that the editorial board of the journal vouches
for the accuracy or validity of the published material."
Despite his own intense familiarity with
Duesberg's manuscript, Dawid, a developmental biologist and chief of the
laboratory of molecular genetics at the NIH Institute of Child Health and
Development, won't say what he thinks of the paper or even whether he believes
the months of review improved the original manuscript. "I certainly
have an opinion," he says, " but I don't count myself
an expert." Likening himself to a family physician who leaves the
deciphering of an electrocardiogram to a heart specialist, Dawid defers
to "the people in the field."
But then the question becomes: Just how
far out does a paper have to be before it will be rejected? For example,
would Dawid have done what Nature editor John Maddox did: that is, would
he have published the claims, later debunked by Nature's own threeman
investigative team, of French chemist and pharmacologist Jacques Benveniste
director of INSERM, a medical research laboratory at the University of
ParisSouth, who asserted that he had proved that water has memory?
As Harvard's Gilbert puts it: "There is Nature happily publishing
Benveniste, and everyone objects, saying they are giving some credence
to homeopathy. But the editors quite rightly say that appearance in their
journal is not a guarantee of truth."
"The Benveniste paper." Gilbert
concludes, "is a perfect example of a paper that is wildly wrong and
contradicts the current view, and yet is published anyway." In that
example, a disclaimer by the editors was published alongside the Benveniste
paper. In Duesberg's case, Dawid published this footnote: "This paper,
which reflects the author's views on the causes of AIDS, will be followed
in a future issue by a paper presenting a different view of the subject."
Gallo has accepted the assignment.
But other academy members who believe the
HIV question is settled resist the notion that PNAS would publish
"wildly wrong" papers on principle. Instead, they cling to
the thesis that Duesberg was able to slip the leash purely because
he is an academy member. Virologist Harold Ginsberg of Columbia University
and retrovirologist Howard Temin not only join Gallo in saying that in
any other journal Duesberg would have had to abide by the views of the
negative reviewers called in by Dawid, but they claim that, despite the
intense reviewing, the paper still has errors. Publishing the paper after
considerable review does not argue for its merit, says Temin. "It
argues only for a belief that any member has a right to publish in PNAS."
Says Ginsberg, "If it had been left up to the peer review system,
[the paper] would not have been published [since] everybody who read it
said it shouldn't be."
Maxine Singer however, does not share this
view. She argues that the paper could have been printed by any journal
despite the objections of the reviewers because peer review stops short
of assessing interpretation. It is intended to evaluate "the design
of experiments and validity of data, bat is almost irrelevant at the point
of interpretation," she says, adding that, at the point where data
is insufficient to prove a point one way or the other, judgment enters.
Says Singer: "You are always left with things the data may suggest
but not prove. Then it is a matter of judgment and this is an activity
of human beings, where peer review will rarely say what is wrong or right.
A reviewer might say 'I don't like this interpretation.' but that would
rarely be a reason to decline a paper." Daniel Koshland, editor of
Science, agrees: "Peer review is designed to find out if a
paper is basically valid in terms of the solid data presented. The leeway
provided for discussion and speculation that goes beyond that is a matter
of editorial policy."
For all the distress the Duesberg paper
may have caused its peer reviewers, the broader scientific community has
yet to react strongly, at least in public. Before it appeared, Gallo was
asked what significance he thought the paper would have. He replied: "Believe
me, it is going to have zero impact." His forecast so far seems to
be accurate. Science ran a news item the week of the paper's release
under the heading, "AIDS Paper Raises Red Flag at PNAS." To
Frances Zwanzig, managing editor of PNAS, that headline meant
the flap might "end up on the front page of the Washington
Post." It didn't. Indeed coverage by the major media has been
Since PNAS does not publish letters
to the editor, the mail goes to Duesberg, who reports several supportive
letters. One is from a former PNAS managing editor, now at the Mayo
Clinic. Bernard Forscher calls the article "a superb example of scientific
scholarship. We have a lot of laboratory mechanics but few thinkers, a
How does Duesberg feel about the wringing
he went through? "Dawid did a very thorough job," he says. "I
give him credit for that he could have behaved more as an impartial arbiter.
But all reviews are beneficial if you can survive them."
To Duesberg, part of his problem is political.
"It is harder to find an objective reviewer on this question than
an AIDS virus in an AIDS patient. Rubin and Martin [the two virologists
at UCBerkeley] are the only two [objective reviewers] I know in the
nation. All the others have companies or contracts or both."
To many, this statement will be nearly
as contentious as Duesberg's theory on the triggering mechanism of AIDS.
But even if he is correct in his perception of the dangers of peer review
in a politicized environment, the question remains: Did the system work
in his case? The final answer and any possible vindication of peer review
must await a judgment on the correctness of Duesberg's theory.
Should Duesberg he proved wrong, then peer
review will be faulted for failing to prevent bad science from reaching
the public. But if he turns out to be right or even right in part
then the peer review system will have been vindicated, since
in this case it will have tested, but not censored some version of the
truth, however unwillingly.
Maxine Singer, who didn't want to publish
Duesberg in the first place, might seem the least likely person to accept
this notion. Yet she views the possibility of Duesberg's turning out to
be right in the end with equanimity. Says Singer: "The history of
science is one of overturning accepted dogma, and I think we are all prepared
for that. If we aren't, I don't think we are very good scientists.*
This article was also published after interventionist editing and in the opinion of the author,
its conclusion was weakened. My own conclusion was that there was no doubt
that politics rather than professionalism dictated the handling of Duesberg's
manuscript. - AL.