of HIV and AIDS - Part 3
Part 2 Part 4
Or Not To Fund, That Is The Question:
Proposed Experiments On The Drug-AIDS Hypothesis.
Inform Or Not To Inform, That Is Another Question.
Part 3 - Contents
§1. The Proposal pp 658-661
§2. Non-funding of the Duesberg-Raabe Proposal pp
§3. Journalistic Treatment of the Case by Science
§4. Some Comments pp 667-669
§5. A NIDA Meeting on Nitrite Inhalants pp
§6. Developments in Fall 1994 pp 671-673
References pp 673-674
Appendix 1. pp 674-675
Appendix 2. pp 675-677
press conference with HHS Secretary Margaret Heckler in 1984, the
HIV-AIDS hypothesis that "HIV is the virus that causes AIDS" has
generally been accepted. Some people, notably Peter Duesberg, have
pointed to serious difficulties about the scientific basis for this
hypothesis, and have proposed another hypothesis, the drug hypothesis,
that under certain conditions, involving the quantity and nature
of drugs taken over certain periods of time, drug use may be a cause
of certain diseases which have been listed by the CDC as AIDS related
diseases. I take no position at this time concerning the validity
of any of these hypotheses, but I am concerned here with the history
of a proposal by Duesberg to perform some experiments to test the
drug hypothesis. The bottom line is that the NIH Center for Drug
Abuse refused the funding, and the matter was not reported in the
scientific press, notably Science, at the time, thus raising two
issues: one about the legitimacy of refusing such funding, and
about the way the scientific community is not informed properly
of some events which some scientists regard as important. The documentation
I shall provide can also be used to evaluate the verdicts of scientific
reviewers concerning the funding of a proposal that goes against
Duesberg filed a grant application to the HHS Public
Health Service on 30 August 1993. The purpose of the application
was to examine the effect of some drugs (nitrites) on some animals,
to see if they cause AIDS-related diseases involving both immunodeficiency,
and cancer type diseases. As Duesberg once said, "we'll feed poppers
to mice." Duesberg filled in the box asking for "the application's
broad, long-term objectives, making specific reference to the health-relatedness
of the project" in more standard scientific language, as follows:
consumption of nitrite inhalants has been suggested since 1981 as
a possible contributing factor to AIDS. Epidemiological correlations
have established a dose-response relationship between nitrite consumption
and AIDS risk, and the restriction in their use to the active homosexual
community correlates well with the restriction of Kaposi's sarcoma
in homosexuals with AIDS. Long-term exposure of mice to nitrites
can result in immune suppression. However, such toxicological experiments
have thus far remained inconclusive, because they have not been
carried out at an adequate dose and length of time.
exceeding unfinished studies by others from the mid-1980's, it is
proposed here to determine the effects of the long-term inhalation
of nitrites on mice (e.g. 6 hrs per day, 5 days per week, for 6
to 24 months). To distinguish between the roles of nitrites as autonomous
pathogens and as co-factors of HIV, murine retrovirus-infected and
un-infected mice will be studied in parallel. The parameters to
be monitored include a) weight loss, b) anemia and lymphocytopenia,
c) clinical manifestations of immunodeficiency, particularly Pneumocystis
pneumonia, d) evidence for Kaposi's sarcoma. In addition, we propose
to study the effects of nitrites on the growth rate of human t-cell
lines in culture.
Finally we plan to examine the Kaposi sarcomagenic potential of
nitrites on rodent cells in culture. Avoiding the toxicity to vital
organs, like the lung and the bone marrow, the cell culture system
will permit us to test nitrites at higher-than-in-vivo concentrations.
This is critical to detect sarcomagenic potential, because Kaposi
sarcomas are typically restricted to humans with the highest cumulative
lifetime doses of nitrites.
research would clarify whether immunosuppression and/or Kaposi sarcoma
can result from long-term exposure to nitrite inhalants. Public
health efforts aimed at AIDS prevention might increase their effectiveness
by discouraging the recreational use of nitrites and other psychoactive
drugs, thereby lowering the AIDS risk even of those already infected
It is not generally
realized that the nitrites-AIDS hypothesis (that nitrites play a
strong role in causing AIDS) was the first one offered by scientists,
dating back to around 1980. 1
Footnote for page 659
to [HAV 1988], p. 165: "Nitrite inhalants were investigated as a
possible cause of AIDS early in the epidemic, partly because of
the preponderance of homosexual men who used nitrites among the
early patients with AIDS..."
1981, CDC initiated surveillance in the United States for patients
under age 60 with KS and opportunistic infections... The initial
CDC definition of AIDS did not require immunologic studies or testing
for any possible viral causes, nor did it exclude patients with
normal immunologic results (34)."
experiments were made at that time, and were mentioned in a report
on AIDS by the Center for Disease Control [CDC 1983] (p. 44). The
CDC concluded that "although the data obtained in this study indicate
that IBN was not immunotoxic for mice, these drugs do have toxic
effects... Reported side effects include: dizziness, headache, tachycardia,
syncope, hypotension, and increased intraocular pressure;... Nitrite
inhalants do not appear to be implicated as a cause of the immunosuppression
seen in AIDS, but their role as a cofactor in some of the illnesses
found in this syndrome has not been ruled out." One effect of the
CDC taking this position was to influence others not to do further
experiments in the direction of the nitrites-AIDS hypothesis.
1985, according to that same article by Haverkos: "Following the
identification of human immunodeflciency virus (HIV) as the cause
of AIDS, CDC changed the definition of AIDS to include HIV serology
testing as part of the definition..." [CDC 1985]
book AIDS--The Making of a Chronic Disease [F&F 1990] contains
an article by Gerald Oppenheimer, giving a history of the early
days when the nitrite-AIDS hypothesis was considered seriously,
and studies were made on groups of homosexual or bisexual men, who
were found to use drugs, especially nitrites, extensively. See especially
pp. 57-60. Later in his article, Oppenheimer considers the history
of the HIV-AIDS hypothesis, and concludes (p. 75): "The history
of the epidemic demonstrates that the construction of HIV infection
was and is a dynamic process in which different scientific specialities
negotiated definitions that, to a degree, reflected their relative
grant application was made to the proper agency, the National Institute
on Drug Abuse (NIDA), whose responsibility it is to fund such experiments
as he proposed, and which has funded such experiments in the past.
In 1988 NIDA even published a monograph entitled "Health hazards
of nitrite inhalants" [NIDA 1988]. This monograph dealt with many
aspects of toxicity of nitrite inhalants.2
Among other things it described the strong epidemiological and clinical
evidence, as well as experimental evidence resulting from experiments
on mice. The evidence from these experiments supported the nitrite-AIDS
hypothesis. The NIDA monograph shows that as late as 1988, research
into the nitrites-AIDS hypothesis was regarded by some people in
NIDA as a legitimate field of scientific inquiry.
Duesberg, his proposal was originally solicited by the above monograph's
co-editor (and author of one of the articles in the monograph) Harry
Haverkos, clinical director of AIDS research at NIDA. Thus Haverkos
found it appropriate to NIDA's mission, and according to Duesberg,
Haverkos considers unfortunate that no testing of the nitrite-AIDS
hypothesis is currently being performed, because he and other toxicologists
agree that much evidence indicates an important role for nitrites
in AIDS. The preface to the monograph by Haverkos and his co-editor
is compatible with this view.
of Duesberg's proposal for NIDA wrote a specific positive recognition
in connection with the proposal. They asserted (p. 2 of the review):
"The major strength of this proposal is that it addresses the important
public health problems of whether nitrite abuse acts as a cofactor
in AIDS pathogenesis and if nitrites
Footnote for page 660
of the sections: Nitrite inhalants: Historical Perspective; The
Fate and Toxicity of Butyl Nitrites; The Acute Toxicity of Nitrite
Inhalants; Indications From Animal and Chemical Experiments of a
Carcinogenic Role for Isobutyl Nitrite; Toxicity of Inhaled Isobutyl
Nitrite in Balb/c Mice: Systemic and Immunotoxic Studies; Altered
T-Cell Helper/Suppressor Ratio in Mice Chronically Exposed to Amyl
Nitrite; Effects of Nitrites on the Immune System of Humans; Deliberate
Inhalation of Isobutyl Nitrite During Adolescence: A Descriptive
Study; Nitrite Inhalants: Contemporary Pattems of Abuse; Epidemiologic
Studies---Kaposi's Sarcoma Vs. Opportunistic Infections Among
Homosexual Men With AIDS.
can cause Kaposi's
sarcoma in the absence of retrovirus infection."
The NIDA reviewers
also explicitly recognized the credentials of the applicants. The
proposal involved a collaboration between Duesberg, whose expertise
lies in chemistry and retroviruses, and Otto Raabe, an inhalation
toxicologist. The above evaluation of "the major strength" of the
proposal was followed by an evaluation of the investigators: "In
addition, the proposed investigative team has expertise in retrovirus
research, inhalation research, and immune cell culture and has the
potential to carry out collaborative research in this area." The
NIDA reviewers followed up with a similar statement on p. 4. However,
after recognizing explicitly "the potential to carry out collaborative
research in this area," the reviewers made the apparently contradictory
statement: "However, the lack of direct experience of any of the
researchers with nitrite studies and the lack of publications dealing
with nitrites does detract from the likelihood of success of the
proposed project." We shall deal with this reservation and others
in the next section.
application was supported, among others, by Science editor
Daniel E. Koshland, who wrote directly to the Study Section of the
National Institute on Drug Abuse on 26 August 1993. Koshland stated:
"As an observer, I have in the past been critical of Duesberg for
not suggesting experiments to resolve this controversy. However,
he has now answered my call with a proposal to test the role of
nitrite inhalants as a cofactor in AIDS. Certainly this idea seems
intuitively to have merit, as nitrites have long been known for
their proven mutagenic and carcinogenic effects. He plans to extend
some unfinished work by other laboratories in the mid-1980's on
mice, examining the physiological and immunological effects of long-term
(six months or more) exposure to volatile nitrites."
that "while the early research yielded promising results, including
evidence of immunotoxicity, it was never properly confirmed or followed
up. Duesberg's proposal is a specific, workable one that will be
done in collaboration with an inhalation toxicologist at the University
of California, Davis." Koshland also commented more generally that
"given the critical information that would be generated by such
a study, regardless of its outcome, I believe the time has come
for this experiment to be performed."
of the Duesberg-Raabe Proposal
1993, Duesberg received notice that his application would not be
funded. The boxed official statement to this effect was:
merit review of your application (1R01oA/AI0a3391-01) is complete.
The Initial Review Group (IRG) has recommended that NO FURTHER
CONSIDERATION BE GIVEN TO THIS APPLICATION. Applications so designated
cannot be funded in their current form; therefore, they are not
routinely scheduled for second level review by the National Advisory
Council/Board. An IRG summary statement containing important evaluative
comments will automatically be sent to you in approximately 8
weeks. Until then, no specific information regarding the review
will be available. However, you may call the contact number above
at any time with other questions. After receiving your summary
statement you may also call to discuss the contents, and for advice
regarding a possible re-submission. If you submit a revised application,
you must follow the instructions in the application form and respond
especially to comments in the summary statement.
Thus the proposal
did not even receive a "priority score," or a full review, but was
summarily rejected at the initial stage.
Statement" rejecting the proposal contained several objections:
- One objection
was that "the proposal does not describe any preliminary studies,"
although the Summary Statement recognized that "the preliminary
studies section describes experiments performed by other groups
that should be in the background and significance section." Indeed,
the proposal described systematically many preliminary studies by
other groups. Why it should be a cause for rejection that Duesberg's
lab did not do preliminary studies when others have done them is
beyond me, and I regard this reason as illegitimate. It is now for
the community of scientists to evaluate the legitimacy of this reason.
Aside from that, the Duesberg lab does not have the money to make
preliminary studies, so it's caught in a Catch 22 situation even
if one accepts (which I do not) the legitimacy of the objection
(universally? in some specific case? in the present case?).
- Another objection
is that some studies indicate that certain concentrations of amyl
nitrite proposed in the Duesberg proposal
are too low
to cause immunodeficiency in mice, and thus "may not produce meaningful
results since this dose was not immunotoxic in several studies."
However, the proposal did propose to vary the concentration of amyl
nitrite, starting with low doses and increasing the doses in an
attempt to determine threshholds of toxicity, so the objection is
- A third objection
was that only a "onesided rationale" was presented for the proposal.
"A more thorough and balanced description of the pertinent literature
would instill more confidence in the rationale and design of the
proposed studies." I regard this objection as invalid. The proposal
took place in a well-known history of AIDS, when others, including
those who contributed to NIDA's research monograph "Health Hazards
of Nitrite Inhalants" had found results compatible or even supporting
the nitrite-AIDS hypothesis. Such results need to be complemented
by further experiments instead of being discouraged. It was not
Duesberg's responsibility to present a many-sided rationale for
doing the proposed experiment. The experiment was designed for a
specific purpose, and would add knowledge complementary to other
available results. Let the experiment be made, and we'll see what
- It was claimed
that "the proposed design of the mouse experiments is not clear,"
because of the order in which inhalants would be given after mice
being exposed to virus. But the proposal would give mice simultaneously
virus and inhalants, and see how they progress together to test
inhalants as a "cofactor." The proposal would also give inhalants
alone. Of course, other experiments could be done in giving inhalants
frst, giving virus first, or whatnot. Just because there are several
variations which could give rise to several types of experiments
is not a justification to prevent one among many possible experiment
from being carried out.
The last objection
was the period of 6-24 months exposures for mice. The objection
states: "Twenty-four months is a very large part of the total life
span of laboratory mice. Many mice may not survive the experiment."
But results would already have been obtained for exposures of 6
months, and pushing the exposures to 24 months would not invalidate
the results for 6 months, so the logic of the objection is defective.
In addition, cancer studies on mice which routinely study mice for
periods up to 24 months are routinely funded. Therefore recommending
that the proposal not be funded partly because the period exposure
for mice goes up to 24 months is an illegitimate recommendation.
Treatment of the Case by
In his letter
to the National Institute on Drug Abuse, Koshland recognized the
scientific and public interest of the proposed experiments. He wrote
explicitly: "I believe that this research would add much to our
understanding of AIDS, and I have told Duesberg that I would consider
such data important material for readers of Science if it
As of now,
the material can't develop because it is obstructed by the National
Institute on Drug Abuse and its referees.
seen any report on these matters in Science, I contacted
Science's news editor Ellis Rubinstein. In a letter dated
19 January 1994, I informed him of the above events. I thought that
the difficulties Duesberg was experiencing document an important
case when someone wants to do an experiment which might raise questions
about the current prevalent dogma on HIV and AIDS, but cannot get
funded. I added the comment that an appropriate news report in Science
about these events would be especially relevant because Science's
own editor urged the funding.
letter, Science reporter Jon Cohen contacted Duesberg on
the phone, and also wrote him on 8 February that he was interested
in doing a story about the rejected grant proposal. Jon Cohen stated:
"The main question I have is this: Are the reviewers' criticisms
unjustified?...Any story I might do I'm sure would hinge on that
question." In response, Duesberg submitted the names of four toxicologists
whom Cohen might contact to get their views.
On 21 March
1994, Jon Cohen wrote back to Duesberg that he contacted six "researchers"
about the grant proposal, and that three wrote back. Cohen enclosed
their signed comments. Cohen also stated that two others told him
verbally of "problems" they had with the proposal, and the sixth
did not reply. According to Duesberg, Cohen gave him the names of
all six (including Gallo, who was one of the two expressing his
"problems" only verbally). Four out of the six were retrovirologists.
Duesberg commented that he would consider "none of these retrovirologists
appropriate for reviewing a toxicology proposal such as "the one
he presented. Duesberg's list of four toxicologists was recommended
to him by Harry Haverkos or by Otto Raabe. Cohen chose only one
of them. In any case, the "researchers" consulted by Cohen effectively
became reviewers for Science.
On the basis
of the reviews he got, Cohen wrote to Duesberg that he "did not
see a story for Science about the NIH not funding"
Cohen's letter to Duesberg was under a SCIENCE letterhead.
of the one "researcher" who had been recommended by Duesberg, say
Reviewer R1, were mostly favorable, although mentioning "deficiencies
in detail." As mentioned previously, Reviewer R1 is a toxicologist.
The overall conclusion from reviewer R1 was as follows:
R1. Conclusions. I think it is important that NE be
tested for carcinogenicity in animals with and without infection
with a retrovirus. I think the investigators could perform these
tests if they did some preliminary studies and if they first answered
the criticisms in a future revised application. Hence, I think
a revision of the grant could well be fundable. I consider that
a judgement of "not recommended for further consideration" is
harsh and unfair, and is partly based on wrong premises as noted
above. This judgement may indeed prevent a useful research project
from being carried out. I disagree with most of the views of Dr.
Duesberg about the causes of AIDS, but hope that he is sufficient
of an objective scientist to perform the tests properly (if he
revises the application and does some preliminary studies) and
hope that he will report the results promptly whether or not they
support his views. (He does state that he will report the results
whichever way they turn out.)
The other two
"researchers" who wrote back were not among those suggested by Duesberg.
One of them was extremely unfavorable. I quote from what he wrote
to Jon Cohen.
R2. I must assume that the average quality of NIMD grants
is as high as those funded by NIAID. On this assumption, if I
submitted an application of this standard to NIAID, I would not
expect it to be funded. The overall content is very meager. Firstly,
the background section is strongly biased toward a particular
hypothesis and either ignores or minimally discusses contrary
sarcoma is a focus of this application. There is reasonable, but
not overwhelming evidence for an infectious agent other than HIV
that causes KS. The pathogenic effects of such a microbe may be
facilitated by HIV-induced immunosuppression, and it is possible
that HIV may also promote the development of KS directly. Oral-fecal
linked with later KS development, perhaps due to microbe transmission,
and such sexual activities may be associated with nitrite usage.
But there is no compelling evidence that KS, or AIDS, is caused
by nitrite usage per se,,.
this proposal going to prove that nitrites cause AIDS or AIDS-defining
illnesses such as KS? I very much doubt it...dosing mice chronically
with compounds does not prove that the same conditions will be
found during "normal" human usage. The toxicological limitations
of the experiments have been pointed out by the study section;
I am not qualified to assess the validity of the objections, but
they seem reasonable...
this proposal suffers from a poorly justified hypothesis, a shortage
of preliminary data and a very sketchy set of experimental proposals
that would never in themselves achieve the aim of proving nitrite
usage to cause AIDS...I am convinced that the study section has
reviewed the grant application appropriately and professionally...
also made extremely strong comments against Koshland's letter supporting
Duesberg's grant application, and the propriety of such support.
Short of reproducing both letters in full, which I cannot do for
a number of reasons, I do not want to quote from those comments
because readers would not have the full context for these comments
(that is both Koshland's letter and Reviewer R2's full comments)
to verify their legitimacy.
The third review
shuffled back and forth. Excerpts from it will give its gist.
R3. I agree with Dr. Koshland's letter that Duesberg should
have an opportunity to experimentally defend his proposal that
nitrite inhalants are important factors (or co-factors) in immunosuppression,
K.S. and/or AIDS. I am not sure that without some preliminary
data from his lab, as well as evidence that the collaboration
set up with Otto Raabe is workable, that the application is worthy
of funding. The Study Section Summary Statement also correctly
notes that the design of the mouse experiments is not clear. Based
on these considerations, I think that Peter himself as a reviewer
would not support what might be considered as a "fishing expedition."
On the other
hand, some of the points in the grant application are noteworthy
of study, e.g., determining appropriate
nitrite inhalants in mice that can be validly used to study their
immunotoxic potential. However, I am not a toxicologist and would
defer to such expertise on this point, as well as on which nitrite
derivatives are best to utilize.
Duesberg raises a highly relevant and important set of experiments
that he and his group have the capability to perform; however,
the lack of preliminary data and clear rationale would generate
only moderate enthusiasm for funding at this time. On the specific
issue of whether the application should have been "not recommended
for further consideration" (NERF), that is a judgement call. I
would not have gone that far based on my limited reading of the
proposal; however, if I were present at the actual review, listening
to the primary and secondary reviewers, there might have been
enough concerns raised that I may have supported the NERF view.
I shall comment
on statements by Reviewers R2 and R3. These comments merely give
a sample of my objections to their evaluations.
Reviewer R2 asserts: "Firstly, the background section is strongly
biased toward a particular hypothesis and either ignores or minimally
discusses other views." So what? It is not the responsibility of
the proposal to discuss other views in a major way. The point of
the experiments is to test some aspects of the particular drug hypothesis.
However, it is important that other hypotheses were not disregarded
in the proposal, because the experiments would be conducted on control
groups of mice some of which would be infected with Molony leukemia
virus and some of which would not. This virus is claimed to cause
Reviewer R2 asserts: "But there is no compelling evidence that
KS, or AIDS, is caused by nitrite usage per se." So what? In the
statement preceding this assertion, Reviewer R2 accepted that "there
is reasonable, but not overwhelming evidence for another infectious
agent other than HIV that causes KS." So according to Reviewer R2
the evidence that KS is caused by HIV is also not compelling. Is
this a reason not to perform further experiments to test the extent
to which HIV does or does not cause KS or AIDS? The medical establishment
has tried for a decade to determine the pathogenesis of HIV, without
success. The people who support
hypothesis have only epidemiological evidence (for whatever it's
worth), which is not compelling.
There is also
no compelling evidence that KS, or AIDS, are not caused by nitrite
usage per se. If there was compelling evidence that nitrite use
causes KS or AIDS, there would be no need to do experiments about
Conversely, preventing such experiments from being performed prevents
evidence, compelling or otherwise, to develop one way or the other.
As a scientist, I object to the a priori obstruction placed in the
way of experiments to investigate the possibility that nitrite usage
per se may cause KS or AIDS.
Reviewer R2 asks the question: "But is this proposal going to prove
that nitrites cause AIDS or AIDS defining illnesses such as KS?"
and asserts: "I very much doubt it." Indeed, the proposal makes
no claim as to what it's going to prove. One cannot determine what
a proposal is "going to prove" before having made the experiments.
The experiments themselves could have inconclusive results, for
various reasons, thus not "proving" anything except that a certain
set of results is inconclusive. Even if all experiments eventually
show a uniformity that after taking poppers in sufficient quantity
for a sufficiently long period, mice develop immunodeficiencies
or cancer type diseases, the experiments still would not "prove
that nitrites cause AIDS" in human beings when taken in sufficient
quantities for a sufficiently long period (possibly not the same
period as for mice). Thus, speaking for myself, I don't "very much
doubt" that the experiments "will prove that nitrites cause AIDS
or AIDS related diseases." I know they will "prove" no such thing,
defectively formulated in such absolute generality by Reviewer R2.
experiments might suggest others; they might be preliminaries for
further experiments, on other animals, varying circumstances or
whatever. That's what experiments are for, to test various ranges
of validity of various hypotheses. If the experiments systematically
show the above uniformity, they might also open some people's minds
to consider more seriously the possibility (not certainty) that
nitrites may cause AIDS related diseases in human beings. Conversely,
if they turn out inconclusive or show an opposite uniformity, they
might have the opposite effect. The effect of the experiments will
depend on how they turn
Footnote for page 668
need for such experiments was explicitly recognized in NIDA's "Summary
Statement," which I have already quoted to the effect that "the
major strength of this proposal is that it addresses the important
public health problems of whether nitrite abuse acts as a cofactor
in AIDS pathogenesis and if nitrites can cause Kaposi's sarcoma
in the absence of retrovirus infection."
out, it will
be different on different people, and it cannot be predicted in
advance, partly because it will depend on many factors in many ways.
If a reviewer's
doubts that Duesberg's proposal will prove that nitrites cause KS
or AIDS were taken as a reason not to fund the proposal, and as
a reason not to report the matter in Science, then I object and
I ask the scientific community to evaluate the legitimacy of non-funding
and non-reporting based on such a reason.
I add one comment
about the third review, concerning the nature of scientific research.
writes: "Based on these considerations, I think that Peter himself
as a reviewer would not support what might be considered as a 'fishing
expedition'." I have several objections to this sentence. First,
I find it illegitimate to presume what "Peter" would do, especially
since Duesberg made the proposal for the experiments in the first
I object to such a put-down of "fishing expeditions" in the scientific
context, with the innuendo contained in the term "fishing expeditions,"
which has been used commonly in other contexts. A "fishing expedition"
in the scientific context is quite different from a political context
when some parts of a political establishment go on a "fishing expedition"
against people with a different political opinion. I think "fishing
expeditions" against the great mysteries of nature are the essence
of original scientific research. I agree with Koshland that the
material of Duesberg's experiments would be of great interest for
readers of Science if, as Koshland writes, "this material develops
appropriately"; and I think the material would be of great interest
to other scientists and to the public as well. Having the material
in Science (if it develops appropriately) would be just a start.
But we can't know how the material will develop if the development
is obstructed a priori by funding agencies.
A NIDA Meeting on Nitrite Inhalants
On 23-24 May
1994, the National Institute for Drug Abuse (NIDA) sponsored a meeting
to discuss "the role of nitrite inhalents in AIDS, particularly
in its most visible expression, Kaposi's sarcoma." This meeting
was reported in the article "NIH reconsiders nitrites' link to AIDS"
(Biotechnology, 12 August 1994, p. 762). I have given an
account of this article elsewhere at greater length ("HIV and AIDS:
Questions of Scientific and Journalistic Responsibility,"
November 1994), but it is relevant to report here an about-face
by Gallo. The Biotechnology article stated:
Robert Gallo of the National Institutes of Health (NIH, Bethesda,
MD) surprised some attendees and panelists by arguing that HIV
is not the primary cause of KS [Kaposi's Sarcoma], although it
may aggravate the condition once KS is caused by "something else."
As to what that something else might be, Gallo favored a microbe
that has yet to be discovered, though he allowed that carcinogenic
nitrites could well be a primary cause. In the true spirit of
scientific inquiry, quite different from the rancor of prior discussions
of alternative causes of AIDS, Gallo called for funding of Duesberg's
Gallo inform Science and Jon Cohen of his changed position about
the funding of Duesberg's nitrite experiments? Do the editors of
Science and its reporters read Biotechnology? I sent them
a copy of the above article when it appeared,4
In addition, Koshland wrote another letter on 24 August 1994, iterating
his support of funding for Duesberg's experiments.
Footnote for page 670
this statement of Gallo was subsequently nullified. In an interview
with The Scientist (14 November 1994), answering a question whether
the Biotechnology article was *accurately reporting his views,"
Gallo said: "They were. But listen carefully. The proposal that
Duesberg made in front of me at a Kaposi's sarcoma [KS] meeting
that was organized by the popper people I thought was a reasonable
idea. But that doesn't mean that I saw the thing written up and
that it was written up properly." The Scientist interview with Gallo
on 14 November was published along with an article on an AIDS conference
celebrating Gallo's lab. The article was entitled: "Gallo's Meeting:
A Scientific Folk Festival." These two items (article and interview)
exist as part of the record. I found both exceedingly tendentious,
and suppressive of much information which would give a quite different
aspect to the questions covered by these two pieces, but here is
not the place to document the tendentious and defective journalism
of The Scientist.
in Fall 1994
The first version
of the present article was sent to editors of Science in spring
1994, among many others on the "cc list." In September 1994, I had
a major mailing containing an updated version, together with my
article on "HIV and AIDS .... " Both were then accepted for publication
by the Yale Scientific, with the "HIV and AIDS..." article to appear
in November, while the "funding" article would appear in the next
issue, January 1995. Science editors and reporters again were on
the mailing list for my September mailing to about 100 people. With
these mailings I was attempting to fill the information vacuum which
resulted from Jon Cohen informing Duesberg under a "SCIENCE" letterhead
that he did "not see a story for Science about NIH not funding"
Duesberg's proposal. I was also attempting to put pressure on Science
to report various events.
1994, Jon Cohen asked Duesberg for an interview to be used in an
article for Science. Duesberg accepted, provided Cohen's questions
were put first in writing. Duesberg would then also answer in writing,
and Duesberg accepted having a verbal exchange afterwards. All of
these took place. Cohen submitted a first batch of questions 10
single-space pages long, which Duesberg answered point by point
in 11 single-space pages. Cohen submitted a second batch of questions
again 10 single-space pages long, which Duesberg answered in 7 single-space
pages. The subsequent verbal exchange was several hours long.
some objections to the way Cohen's questions were put together,
since they all assumed implicitly that HIV is the cause of AIDS.
The questions prejudiced the issue toward the HIV causality. To
a large extent, Cohen was asking Duesberg to comment on some scientific
articles purporting to show or to support the causal relation of
HIV and AIDS. The questions were detailed and specialized. Duesberg
found that most of the points raised by Cohen were in effect already
answered in two papers of his ("AIDS acquired by drug consumption
and other noncontagious risk factors," Pharmacology & Therapeutics
55: 201-277; and "Human immunodeficiency virus and acquired immunodeficiency
syndrome: Correlation but not causation," Proc. Natl. Acad. Sci.
USA 86: 755-764). In these papers, among other things, Duesberg
cited much scientific literature, but he did not and could not cite
the entire literature. However, Duesberg claimed that the articles
he cited were typical, and he analyzed many common defects in the
current literature about HIV and AIDS. Cf. Appendix 1 below, which
reproduces a list of the specific objections
scientific articles noted by Duesberg in a letter to Cohen dated
20 October 1994.
asked why Duesberg had not cited other articles which Cohen submitted
for his consideration. In fact, some of the articles brought up
by Cohen had not appeared at the time of publication of the Pharmac.
Ther. and PNAS papers cited above. The defects analyzed by Duesberg
in these papers were similar to defects which he found in the articles
brought up by Cohen.
in the Yale Scientific appeared in the middle of November,
and I distributed several hundred copies, including half a dozen
copies to various people at Science. After internal consultations
and revisions, a final version of Cohen's article appeared in Science,
9 December 1994, under the title "The Duesberg Phenomenon." In this
article, Jon Cohen stated: "But because the Duesberg phenomenon
has not gone away and may be growing, Science decided this was a
good time to examine Duesberg's main claims." Thus Science and Jon
Cohen changed their mind between spring 1994 and fall 1994. In this
published version, Cohen finally reported Koshland's support as
follows: "Also unpersuaded of Duesberg's ideas--but persuaded he
shouldn't be shut out of scientific resources--is Daniel Koshland
Jr., editor-in-chief of Science, who has written letters to the
National Institute on Drug Abuse supporting Duesberg's recent grant
as of December 1994, all recent applications by Duesberg for funding
of his lab were rejected. This was correctly reported by Cohen,
who wrote: "In addition, Duesberg has been turned down by funding
agencies on several new proposals to study both AIDS and cancer."
Cf. Appendix 2 for a summary of these proposals.
article by Jon Cohen in Science 16 December 1994 reported on the
possibility of a new virus causing Kaposi's sarcoma (cf. my article
"HIV and AIDS .... " §6). In a letter to the editors sent 4 January
1995, Duesberg stated:
(16 Dec., p. 1803) about the "mystery" that "KS is almost exclusively
confined to male homosexuals..."
nitrites are some of the best known mutagens and carcinogens (3),
I propose the following experiment to solve the "mystery": Expose
100 mice, or cats, or monkeys to nitrite inhalants at doses comparable
with human recreational use and for time periods approximating
the so-called 10-year latent period between infection by HIV to
the onset of AIDS--possibly a euphemism for the time of drug
for AIDS to develop. (It takes 10 to 20 years of smoking for emphysema
or lung cancer to develop.) I would predict this result: Immunodeficiency,
pneumonia, and pulmonary KS in animals.
2) I also
propose to "mainstream AIDS researchers" an easy epidemiological
experiment to test my hypothesis that HIV is not the cause of
AIDS. According to Science, these researchers argue that it is
"impossible" to eliminate confounding factors from HIV in typical
AIDS risk groups, as for example in hemophiliacs "because [they]
do not keep track of each factor VIII treatment" (9 Dec., p. 1645).
Therefore I propose to compare the incidence of AIDS-defining
diseases in 3650 homo-or heterosexual American men, who are not
on transfusions and recreational drugs or AZT, but are HIV-positive,
to the incidence in 3650 HIV-negative counterparts. These healthy
subjects could be found by the U.S. Army, which tests over 2.5
million per year, or among those contributing to the blood banks,
which test over 12 million a year. If the 3650-day latent period
is correct, every 2 days one of the people that are HIV positive
would develop AIDS. I would predict this result: The percentage
incidence in the HIV-positive group will be the same as in the
If the mainstream
AIDS researchers are not already doing these experiments, I would
be delighted to do them provided I could get funded.
At the time
this article goes in production, Duesberg was not funded.
community is entitled to know of the events I have reported above,
both concerning the non-funding by NIH and the circumstances under
which Science reports or does not report events.
Reports on AIDS, Morbidity and Mortality Weekly Report, 9 September
1983, 457-8, 464 ; compiled in a collection of such reports,
1981-1986, p. 44
Revision of the case definition of acquired immunodeficiency syndrome
for national reporting--United States, Morbid. Mortal. Week. Rep.,
(1985) 34, pp. 373-375
1990] E. FEE and D. FOX, AIDS--The Making of a Chronic Disease,
U of C Press, 1990
Harry Haverkos, Kaposi's Sarcoma and Nitrite inhalants, Psychological
Neuropsychiatric, and Substance Abuse Aspects of AIDS, edited
by T. Peter Bridge et al., Raven Press, New York (1988) pp. 165-172
Health Hazards of Nitrite Inhalants, edited by Harry Haverkos
and John Dougherty, HHS Public Health Services, NIDA, 5600 Fishers
Lane, Rockville MD 20857
Excerpt from a Letter from Peter Duesberg
to Science Reporter Jon Cohen
October 20, 1994
in the HIV-AIDS papers, on which you ask me to comment and which
form the basis of your questions, are entirely similar to the
results in papers I cited in my articles, and they suffer from
similar defects. The defects of these HIV-AIDS papers include:
a priori other possible causes of AIDS (whatever it is) besides
(2) not measuring
lifetime use of foreign proteins transfused or of drugs consumed
in AIDS risk groups and patients;
(3) not comparing
morbidity and mortality of HIV-positive drug users, transfusion
recipients and other risk groups to matched HIV-negatives;
the role of certain factors, notably drugs and foreign proteins,
by averaging certain results for people who may have used drugs
only a short time, with those who have used drugs for a decade
to determine annual AIDS risks of HIV-positive persons of different
risk groups and countries. Instead cumulative AIDS statistics
are reported, and these always go up;
to determine whether outside the known AIDS risk groups, AIDS
has increased mortality and morbidity of the general population
in any country, or whether it is a new name for the normal background
of these diseases. This is a consequence of not comparing the
morbidity and mortality of HIV-positives to HIV-negatives in the
general population. For example, the rare
of HIV and pneumonia in persons of the general populations must
be shown to exceed the normal background of AIDS-defining diseases
in a given risk group before it can be considered evidence for
HIV causing AIDS;
to consider that all AIDS-defining diseases are previously known
diseases that occur at a low rate in all people and at a higher
rate in AIDS risk groups;
the circular AIDS definition. That is to report AIDS-defining
diseases in HIV-positives as AIDS, and either not to report clinically
diagnosed AIDS diseases in HIV-negatives or not to report controls
to recognize that "AIDS tests" detect antiviral immunity which
is a prognosis against rather than for an HIV-disease, if such
a disease exists;
to distinguish between infectious and thus potentially pathogenic
HIV, and DNA or RNA of latent HIV, or even antiviral antibodies
which have no known pathogenic potential;
to account for the unpredictable latent periods from HIV infection
to AIDS, that are claimed to range from 10 months to over 10 years.
These long latent periods are totally incompatible with the short
generation time of HIV, which is only 24 to 48 hrs;
refusal to consider the simplest and most plausible HIV hypothesis-
namely that HIV is a harmless passenger virus. The criteria of
a passenger virus: (i) the time of infection is irrelevant to
the onset of disease; (ii) the passenger virus can be either active
or passive during the course of the disease; (iii) the passenger
virus can be completely absent during the disease. HIV meets all
criteria of a passenger in AIDS perfectly;
to report the toxicity and lifetime dosage of antiviral drugs
like AZT, and failure to report AZT compensating, lifesaving treatments
List of Rejected Grant
Applications by Duesberg
[I reproduce below excerpts from a letter dated
6 December 1994, which Duesberg wrote to me. I had no further
time to look into the references and letters he gave me accompanying
his summary, the way I looked previously into the reports from
the reviewers for Jon Cohen. S.L.]
1) In 1990,
the competing renewal of my Outstanding Investigator Grant (OIG),
"Retroviral onc genes and cellular proto-onc genes" was turned
down. This type of grant had been awarded in 1985 to only about
a dozen outstanding scientists for a 7 year term. My grant resulted
in 86 publications, including research papers, theoretical papers,
reviews and reports during its term period.
sheet of the mail ballot review of this renewal application said
in Oct. 1990: "... his productivity has been a bit lower and his
science, although still solid, is not as sharp and imaginative
as before.," "... much of the investigator's time and effort during
the past period has been occupied by theoretical issues pertinent
to his research and other interests." (copy enclosed)
was appealed on two grounds: 1) Three of the reviewers listed
on the pink sheet as having participated in the review never reviewed
the application .... 2) At least two reviewers had personal and
commercial conflicts of interest... After a lengthy correspondence
with the NIH and the administration of UC Berkeley, UCB signed
a rare appeal to the NIH in March 1992 to re-review my application.
This appeal was granted in the spring of 1993 (see letter by Dr.
Blair from the NIH).
2) In May
1993 my appeal of the OIG review was turned down by the Experimental
Virology Study Section of the NIH with a nonfundable priority:
"Applicant whose productivity has recently diminished both in
quantity and most disturbingly in quality...a vast amount of highly
relevant work from other laboratories is neither acknowledged
nor incorporated into the proposal" (pink sheet enclosed).
3) In May
1993 an application to the Tobbaco-Related Disease Research Program
(TRDR) of the University of California, entitled "The role of
chromosome abnormalities in cancer" was accepted but with the
priority score of only 8% (letter enclosed).
4) In May
1994 a revised application to the same TRDRP again entitled "The
role of chromosome abnormalities in cancer" was rejected with
the nonfundable priority "Not recommended for further consideration"
5) In July
1994, a revised application entitled "The role of chromosome abnormalities
in cancer" was ranked in the
bottom 10% by the American Cancer Society and was not approved
for funding (letter enclosed).
6) In December
1992 a postdoctoral grant application was submitted to the Cancer
Research Coordinating Committee of the
of California entitled "The role of chromosome abnormalities in
cancer." The application was not funded according to a letter
from May 1993 (enclosed).
7) In December
1993, a postdoctoral grant application was submitted to the Cancer
Research Coordinating Committee of the University of California
entitled "Cancer caused by chromosome abnormalities?" The application
was not funded according to a letter from May 1994 (enclosed).
8) In December
1994 a new postdoctoral grant application was submitted to the
Cancer Research Coordinating Committee of the University of Calffomia
entitled "The role of chromosome imbalance in cancer."
9) In February
1993 a grant application was made to the Universitywide Aids
Research Program of the University of California entitled
"Animal test of the hypothesis that amyl nitrites cause AIDS."
The application was ranked "within the fourth quartile." With
regard to its approval a split vote with five for and four against
was reported (see enclosed letter).
10) In August
1993 an application was made to the National Institute of Drug
Abuse (NIDA) entitled "Animal tests of the AIDS risks of nitrite
inhalants." The application was accompanied by an endorsement
from Dan Koshland, editor of Science. The application was "not
recommended for further consideration" in a letter from the NIDA
of January 1994 (enclosed).
11) In August
1994 a revised application was made to the National Institute
of Drug Abuse entitled again "Animal tests of the AIDS risks of
nitrite inhalants." The application was accompanied by an endorsement
from Dan Koshland, editor of Science. Today I received a letter
dated November 30, 1994, that the initial review group has recommended
again "NO FURTHER CONSIDERATION BE GIVEN TO THIS APPLICATION (enclosed)."