NIDA Meeting Calls For Research
Into The Poppers-Kaposi's Sarcoma Connection *
Copyright 1994 by John
Maryland, 24 May 1994.
The National Institute on Drug Abuse
sponsored a high-level meeting, “Technical Review: Nitrite
Inhalants”, held outside Washington, DC on the 23rd and 24th
May, 1994. The toxicologists, AIDS researchers, and others present
reached a consensus urging research into the connection between the
nitrite inhalants (or “poppers”) and Kaposi's
The meeting was organized by Harry Haverkos of NIDA, who has been
writing since 1985 about the health hazards of the nitrite inhalants.
Robert Gallo, as unofficial voice of the
Establishment, disclosed important revisions in the AIDS-paradigm. It
is now necessary to consider co-factors. No longer is HIV believed to
cause KS by itself; at most it may aggravate KS after it has been
caused by something else. No longer is HIV believed to kill T-cells;
whatever damage it allegedly does, it does indirectly. Speaking
informally, Gallo discussed the latest thinking on the nature and
causes of KS.
The meeting had implications that went
issue of the nitrites, important as that may be. It indicated a
willingness, on the part of the Public Health Service, to re-think the
basic premises of the AIDS model that has prevailed since 1984. It is
high time, for the HIV-AIDS hypothesis has been a total failure, both
in terms of public health benefits and in terms of making accurate
Molecular biologist Peter Duesberg, the
critic of the HIV-AIDS hypothesis, attended the meeting as an invited
observer. He has designed experiments, and is waiting for funding, to
examine the effects of long-term nitrites exposure in animals. From
attacks on Duesberg in the popular and quasi-scientific press, one
might have expected him to be treated as a pariah. This was not at all
the case: the other scientists were friendly, and listened to him with
respect when he discussed points of retrovirology, on which he is one
of the world's leading experts. A reconciliation took place between
Robert Gallo and Peter Duesberg; the two are on friendly terms again,
for the first time since 1987, when the first interview with Duesberg
appeared in the New York
For the rest of this article, I'll give
background information on poppers, followed by a chronological account
of the NIDA meeting and my own conclusions.
Background: Poppers and
As a prescription drug, amyl nitrite was
used by elderly people for emergency relief of attacks of angina
pectoris (heart pain).
Historically, the use of the nitrite
nitrite, butyl nitrite, isobutyl nitrite, etc.) for recreational
purposes has been limited almost entirely to gay men. The first reports
of recreational use date from the early 1960s, after the amyl nitrite
prescription requirement was eliminated by the FDA. The drug appeared
to intensify and prolong the sensation of orgasm. It facilitated anal
intercourse, by relaxing the smooth sphincter muscles and deadening the
sense of pain.
The FDA re-instated the prescription
1969. In 1970 a new industry stepped into the breach, marketing little
bottles containing mixtures of butyl and isobutyl nitrite. By 1974 the
poppers craze was in full swing. Ads for them appeared in all gay
publications. At gay discotheques men could be seen, shuffling around
in a daze, holding poppers bottles under their nose. The miasma of
nitrite fumes was taken for granted at gay gathering places: bars,
baths, leather clubs. Some gay men were never without their little
bottle, from which they snorted fumes around the clock. Two separate
studies in the 70s found that some gay men could no longer perform
sexually without the use of poppers.
The toxicities of the volatile nitrites
known before the advent of AIDS. In 1980 Thomas Haley, one of America's
leading toxicologists, published a two-page summary of nitrite
toxicities, with 115 references listed. Here are a few of the
The toxic effects of amyl nitrite inhalation include
rapid flushing of the face, pulsation in the head, cyanosis, confusion,
vertigo, motor unrest, weakness, yellow vision, hypotension, soft
thready pulse, and fainting. Accidental prolonged inhalation of amyl
nitrite has resulted in death from respiratory failure.... Fatalities
have occurred in workers exposed to organic nitrates after strenuous
exercise 1 to 2 days after cessation of exposure. Nitrite causes a loss
of tone of the vascular bed and pooling and trapping of blood in the
veins of the lower extremities, resulting in marked arteriolar
constriction and the induction of anoxemia in vital tissues, causing
death.... The formation of methemoglobin by aliphatic nitrite
interferes with oxyhemoglobin, causing anoxia of vital organs.... The
use of volatile nitrites to enhance sexual performance and pleasure can
result in syncope and death by cardiovascular collapse.
Also in 1980 appeared the first of
to demonstrate that the volatile nitrites are powerfully mutagenic.
(That is, they cause cells to mutate, they cause damage to the
chromosomes.) This is cause for concern, as almost all known
carcinogens are also mutagens.
Subsequent studies, both in vitro
have shown that poppers damage the immune system. They cause two kinds
of anemia: Heinz body hemolytic anemia and methemoglobinemia. They
damage the lungs. They have the potential to cause cancer by producing
deadly N-nitroso compounds in interaction with many common drugs and
chemicals, including antihistamines, artificial sweeteners, and pain
When the first cases of AIDS were
1981, or the predecessor cases of GRID (Gay Related Immune Deficiency),
poppers were high on the list of etiological suspects. Here was a drug
used heavily and almost exclusively by the group of people getting
sick. Nevertheless, despite compelling epidemiological and
toxicological evidence, the Centers for Disease Control (CDC) hastened
to exonerate poppers. They did so for two reasons, both of which were
the CDC found AIDS patients who had never used poppers; therefore,
argued the CDC, poppers could not be the cause. The CDC's faulty
assumption was that “AIDS” constituted a single,
disease entity with a single cause. Second,
the CDC conducted a brief mice study in 1982-1983, and claimed to find
“no evidence of immunotoxicity”. These results are
contradicted by several other studies, which did
find that the inhalation of nitrite fumes causes immune suppression in
mice. The reasons for the negative findings of the CDC mice study were
explained at the Gaithersburg meeting by one of the investigators,
Daniel Lewis, about which more below.
The Epidemiology of
After a welcome by Richard A. Millstein,
Director of NIDA, Harry Haverkos opened the meeting on Monday, May 23
with a brief overview of the volatile nitrites, their use and
regulation. He then turned the session over to Zili Sloboda of NIDA,
who moderated the morning session devoted to epidemiology. She stressed
the “importance of prevention messages”.
Andrea Kopstein of NIDA discussed the
involved in such phrases as “inhalant abuse”. The
are diverse substances that happen to be defined by the route of
intake. The lack of clarity as to what constitutes an
“inhalant” causes confusion in responses to
surveys. She presented studies of lifetime use of nitrites among sex
and ethnic groups, which showed that use of amyl and butyl nitrite
among U.S. males decreased after 1986, though inhalant use remained
just as high.
Lisa Jacobson, of the Johns Hopkins
Hygiene and Public Health, presented data from the much used and abused
MACS study, a cohort of gay male volunteers. Those men who were
“sero-prevalent” (that is, HIV-antibody-positive on
into the study) had much higher poppers use. Among all groups in the
study, the use of poppers declined.
Kenneth Mayer, a physician living in the
area, was among the first to sound the warning about poppers to gay men.
He discussed surveys, which found that the use of poppers is a risk
factor for becoming HIV-antibody-positive. But what does that
mean? He mentioned two possibilities: being
might be a marker for other health risks, or it might be a marker for
illness. He posed the basic question: which is more hazardous, unsafe
sex or drug use?
The highlight of the morning session was
“Advertising Trends”, presented by Hank Wilson, a
Francisco activist who in 1981 founded the Committee to Monitor Poppers.
He began by saying that, with regard to poppers, gay men had been
uninformed, misinformed, partially informed, and confused. He then
showed stunning color slides of several dozen poppers ads, from the
early 70s through the late 80s. This must rank among the most brilliant
advertising campaigns in history. Within only a few years hundreds of
thousands of men were persuaded that poppers were an integral part of
their own “gay identity”. The ads conveyed the
nothing could be butcher or sexier than to inhale noxious chemical
fumes. Bulging muscles were linked to a drug that is indisputably
hazardous to the health.
Beginning in the early 70s ads for
in all of the gay press — ads for special inhalers
— an ad
for a brand named “Discorama”, specifically
disco dancers. One ad gave an 800 number, with the message,
“We'll pay you to try...” (the free trial tactic
also been used on the street by dealers of heroin, crack, and other
such commodities). An ad for the poppers brand RUSH focussed on the
phrase, “Better Living Through Chemistry”
— and no
irony was intended.
However, warnings about the dangers of
to appear in both the gay and the mainstream press, and for the decade
of the 80s, these messages competed with disinformation from the
poppers industry and their allies. Wilson showed the front page of a
December 1981 issue of the New York
Native, with a banner headline,
“Do poppers cause cancer?”. This message got across
people who just glanced at it on the newsstand. A Pittsburgh
repeated the same heading. The City of San Francisco required than a
warning notice be placed at all points of sale for poppers. The June
4-17 1984 issue of the New York
Native carried an article, “Poppers: The Writing
On The Wall”. On 19 July 1985 the Seattle Gay
published a boxed warning on poppers. And in 1985 poppers were banned
from the most popular disco in San Francisco. The mainstream press in
San Francisco also began to carry the message that poppers were
But the poppers industry had its own
1983 pamphlet published by the CDC, “What gay and bisexual
should know about AIDS”, claimed that there was no
between AIDS and poppers, on the basis of a single mice study (to be
discussed below). In effect, the government gave the green light on
poppers use. The CDC's mice study was cited in a press release sent out
by Joseph F. Miller, President of Great Lakes Products, the world's
largest manufacturer of poppers. Miller's press release, run by most of
the gay press, claimed that “Jim” Curran of CDC's
Branch had given him a guided tour of the CDC and assured him there was
no relationship between poppers and AIDS. When Curran responded with a
letter saying that he had been misinterpreted, and that poppers may
play a role as cofactor in some of the illnesses in the syndrome, his
letter was ignored by the gay papers who had run the press release from
Miller. Great Lakes Products followed through with a series of ads in
entitled “Blueprint For Health”, which gave the
that poppers, like vitamins, fresh air, exercise and sunshine, were an
ingredient in the healthy lifestyle.
In 1987 a San Diego gay paper began
running full-page ads for poppers. The Windy City
Times in Chicago ran full-page ads, as well as articles
attacking the critics of poppers. Heartland,
a mid-west gay paper owned by Great Lakes Products, ran ads and
articles defending their product. The San Francisco Sentinel
ran an ad that warned of an impending ban on poppers ban, and urged its
readers to “STOCK UP!”. In 1992, three years after
had been outlawed by act of Congress, a stand at a gay street fair in
Chicago offered iced tea for $1 and poppers for $5. In 1992 the
manufacturer of RUSH sent out a mail order ad to “preferred
Hank Wilson concluded his presentation
by making the
point: Poppers are easy and cheap to make, they are highly profitable,
and there is a demand for them. Therefore, they will always be
available. For this reason, education is essential.
Do Nitrites Lead to
Increased Risky Sexual Behavior and HIV Transmission?
The afternoon session of 23 May began by
the relationship between use of poppers and becoming
HIV-antibody-positive. Whether this matters depends on whether or not
HIV is the cause of “AIDS”. Since I don't believe
is even pathogenic, and consider the survey research (a.k.a.
“epidemiology”) performed by academics, physicians,
members of the Public Health Service to be far below professional
standards, I took a rather dim view of this session.
In broad strokes — the
speakers indicated that
those who were HIV-antibody-positive were more likely to have more sex
and to use all drugs more heavily.
Ken Mayer presented Boston data
indicating a very
high Odds Risk (OR) of seroconversion for those who always used poppers
when they had passive anal intercourse. He pointed out that this was
biologically plausible, inasmuch as poppers relaxed the smooth
sphincter muscle, dilated the blood vessels, and deadened the sense of
pain (thus increasing the risk of anal trauma).
In the discussion period I put two
Mayer: 1) “What is the basis for determining ‘HIV
infection’? The antibody tests?”, and 2)
there really evidence that these people had a viral infection, and if
so, was the virus sufficiently biochemically active as to cause
illness?” He replied that the ELISA and the Western
antibody tests were used, and that they were sometimes followed up by
viral culture. This question is important, as an article in Bio/Technology
last year demonstrated that the antibody tests are unvalidated and
extremely unreliable — that many HIV-antibody-positive people
have never been infected by the virus itself, which in any event is
virtually never biochemically active to a degree that would enable it
to cause illness.
Jay Philip Paul, an AIDS prevention
San Francisco, discussed the complexities of classifying events as
“risky” or “safe”. There are
effects among sexual behavior, drug use, and other likely health risks.
He emphasized that one could never conduct a controlled study (survey)
to answer the question of causality.
Do Nitrites Suppress the
The second afternoon session on 23 May
dealt with in
vivo toxicological studies, two involving mice and one involving human
First was Daniel Lewis of the National
Occupational Safety and Health. He was one of those who conducted the
1982-93 CDC mice study that was the basis of the MMWR news item (9
September 1983), which claimed to find “no evidence of
immunotoxic reactions”. In that study the doses were
low, approximating levels to be encountered as background exposure
(used as “room odorizer”, workers in a poppers
rather than those encountered when using poppers as a drug (i.e.,
inhaling directly from the bottle).
Lewis explained that, in determining the
had to adjust it below the level where they were
the mice — however, the supplier of the mice later disclosed
the mice were suffering from a low-grade infection. This means that the
deaths of the exposed mice may well have been due to immunotoxicity
— exactly what the study conclusions claimed not to find
rather than the acute toxicity of the nitrite fumes. The end result was
that the dose was far too low to be meaningful.
The study was not blinded, as the mice
vapors developed a “yellowish tinge”. Although
no significant changes in body weight, there were reduced liver and
thymus weights, and an increase in spleen weights. 100% of the exposed
mice developed methemoglobinemia. The white cell count went down
In the question period I stated that
studies had found that nitrite inhalation caused immune suppression in
mice. How did Lewis explain the discrepancy between his findings and
the others? His answer was short and sweet: “Dosage
length of exposure”.
The second mice study was presented by
Soderberg, of the University of Arkansas. His mice inhaled 900 ppm
nitrite fumes for 45 minutes daily for 14 days, then were allowed to
rest for 1-3 days. Then tests were performed. They found that there
were decreases in both body and spleen weight, the cells in the spleen
and in the blood were reduced, the response to conA was reduced (-28%),
the T-dependent cells were very sharply reduced, accessory cell
function was affected (there was reduced ability to support
proliferation of normal T-cells), the macrophage functions were greatly
reduced (especially tumoricidal activity). The recovery of immune
functions generally took about a week; however it took longer for
macrophage cytotoxicity to recover (about 2 weeks).
Soderberg and his colleagues reached the
that exposure of mice to nitrites via inhalation impaired:
• T-dependent antibody responses
• T-mediated cytotoxicity
• macrophage tumoricidal activity
In the question period Peter Duesberg
issue of reversibility: What about something that goes on for
years? Analogies here would be the length of exposure
achieve a causal relationship between cigarettes and lung cancer, or
between alcohol and cirrhosis. Soderberg replied that his team had
“no data on more chronic exposure”.
The third speaker was William Adler of
Institutes of Health. His study was of 8 human volunteers,
HIV-antibody-negative males, who inhaled poppers three times per day
for one week, and then intermittently for another week and a half.
Baseline immunological test batteries were run before, during, and
after exposure. The investigators found that the main change was in
natural killer (NK) cell activity, which dropped very sharply. They
reached the conclusion: “The results showed that exposure to
nitrite can induce changes in immune function even after short exposure
to moderate doses.”
Do Nitrites Act as a
Cofactor in Kaposi's Sarcoma?
The second day of the meeting, 24 May
addressed the key question: Do poppers play a role in causing
The first speaker was Harry Haverkos, who began by showing a slide
indicating that there appear to be four kinds of KS:
1. Classic KS, occurring among older
2. African KS: 25-40 age group, first
indolent then fatal in 5-8 years.
3. Iatrogenic KS (e.g., renal
transplant): indolent or fulminant.
4. Epidemic or AIDS KS: gay white males,
fulminant, survival 1-3 years.
And he posed the question: “Are these all the same?”
Haverkos cited the cases of HIV-negative
gay men with KS (16 in the practice of one physician alone). He
reviewed the epidemiological data, which were inconsistent. Four
studies found a strong and dose-related relationship between the use of
nitrites and the development of KS — however, other studies
He cited a recent study which found that
volatile nitrites are even more powerfully mutagenic than had
previously been thought. Iso-butyl nitrite vapors were 11 times as
mutagenic as iso-butyl nitrite in solution.
Haverkos presented a slide: REASONS TO
NITRITE INHALANTS A COFACTOR IN THE PATHOGENESIS OF KAPOSI'S SARCOMA
(KS) IN AIDS:
epidemiologic studies have demonstrated a strong association.
• Decline in proportion of cases among gay men parallels
decline in nitrite inhalant abuse among gay men.
• Distribution of KS lesions correlates with areas of nitrite
vapor exposure (nose, face, chest) in many cases.
• Plausible mechanisms of action have been proposed:
- Formation of cholesterol nitrite
- Immune suppression.
• Only hypothesis promoted that fits all 4
aspects of national surveillance data.
He followed this with another slide: WHY
AIDS-RELATED KAPOSI'S SARCOMA (KS) IS NOT EXPLAINED BY A SEXUALLY
little KS reported outside gay male population.
• Among gay men, KS is associated with white race and high
• KS in women with AIDS no more likely among sexual partners
bisexual men than sexual partners of heterosexual drug abusers.
• No one can find the infectious agent.
In conclusion Haverkos presented a
series of recommendations:
clinicians/researchers should take a drug history, including inhalants,
from patients with Kaposi's sarcoma.
• A multisite study of KS cofactors is needed (similar to what
was done for Reye's syndrome).
• Women and heterosexual men with KS should be thoroughly
evaluated to identify potential cofactors.
• Animal models should be explored.
• A comparative analysis of nitrite use and KS rates should be
conducted whenever such data are available, e.g., MACS sites.
The next speaker was Harold Jaffe of the
said that he would take a “con position” for the
the meeting, even though he was open to the possibility that the
nitrites might play some role in causing or aggravating KS. He argued
that the KS co-factor is likely to be a transmissible agent, since one
study had found an association between KS and rimming. The risk for KS
is highest among those who lead a particular kind of sexual lifestyle,
characterized not only by nitrites use, but also by multiple, anonymous
In the question period I made the point
nitrites obviously could not be the sole cause of one or all of the
forms of KS. The question is whether they play a causal role in some or
most of the cases of epidemic (AIDS) KS. Their biochemical properties
are consistent with such a role. In contrast, nothing can be said about
a microbe which has yet to be discovered.
Following Jaffe's presentation,
of the Johns Hopkins School of Hygiene and Public Health presented a
re-analysis of data from the MACS study. He found a stronger
association between rimming and KS than between poppers and KS. The use
of marijuana and hashish were found to be high risk factors for KS. Not
only did he not find a dose-related between poppers use and KS, he they
found exactly the opposite: a strong, statistically significant
negative correlation. In other words, the more poppers you use, the
less likely you are to develop KS. Obviously this violates common sense
and contradicts other studies, which found a strong positive
correlation. The most likely explanation is that Armenian's data are
wrong. It should be noted that Armenian merely re-analyzed data that
had been collected by others, in a study designed by others.
Gallo Revises the Paradigm
The final speaker on the question of
play a role in causing KS was Robert Gallo of the National Cancer
Institute, who is still regarded by many as America's foremost AIDS
expert. He began by saying that he wanted to open up basic questions,
and had no fixed opinion regarding co-factors for KS —
chemical, viral, or a combination. Though not in agreement with all
that Harry Haverkos had said, for example the donor recipient or
localization arguments, he was willing to be persuaded.
To my knowledge, this was the first time
or any other top “AIDS expert” to admit publicly
was not the primary cause of KS. He said: “We believe that
KS is an enormous catalytic factor, but there must be something else
involved.” He continued:
Do you believe that
all Kaposi's is one and the same disease? I don't. Why should
say they are, any more than all leukemias are the same?
don't all have the same pathogenesis. Even T-cell leukemias don't all
have the same pathogenesis. So why should we say a benign disease of
old men in East Europe of Mediterranean or Jewish stock have the same
disease as a sudden disease in younger people that is far more
aggressive? And do we believe that the iatrogenic renal
transplant Kaposi's associated with therapies and immune suppression is
the same disease? I'd at least leave open the possibility
these are quite distinct, even pathogenetically. I know there's a great
desire to link the African with the modern or epidemic form of KS, and
I can understand that, because they're both aggressive. But they may
not be. Therefore, what one tells you may not be good for the other....
And when you go to the iatrogenic renal transplant KS, you have to
argue that it's a ubiquitous transmitted agent, because all of the
people that have it in their kidneys weren't involved in rimming.
Gallo then went on to revise the most basic premise of the AIDS
construct: the assumption that an underlying condition of
deficiency” is responsible for causing, indirectly, the
AIDS-indicator diseases. He said:
There's a common
belief that it's immune suppression that is involved. Our data would
argue the opposite — that it's immune stimulation. You can
Kaposi's in the absence of immune suppression. I don't think there's
any evidence that in the older classic Kaposi's sarcoma —
older men — that there's immune suppression. There's not good
evidence that there's immune suppression in the African form. And when
you speak of the immune suppression of the iatrogenic Kaposi's, you
have to keep in mind that there's also immune stimulation.
And he posed a few additional questions:
Ask yourselves, who here has evidence that Kaposi's
is a true malignancy? Is it only polyclonal hyperplasia that
harm and even kill? Or does it really evolve into a true
cancer? And if so, how often? There's an enormous
of Kaposi's in HIV-infected gay men. What's the role of HIV?
Gallo then proceeded to present a
summary of findings from his laboratory regarding KS:
The first thing I
can tell you is that we've been able to regularly culture from Kaposi's
tumors what pathologists say is a tumor cell. We asked: What is the
role of HIV in all this? And we found that inflammatory
... were the very likely initiatory events in creating this cell. We
said, “Oh, the role of HIV is likely to be in increasing
inflammatory cytokines.” But we have learned
should be of interest to everybody that isn't completely married to HIV
— that the inflammatory cytokines are reportedly increased in
men even without HIV infection. Inflammatory cytokines are usually
promoted by immune activation, not by immune suppression. So here was a
paradox.... So the inflammatory cytokines may be increased by HIV, but
I wish I knew what else was increasing them before a gay man was ever
infected with HIV. Maybe it's nitric oxide, maybe it's a sexually
transmitted virus, maybe it's all of them, maybe it has to do with
rimming because it's immune stimulation with non-specific
infections.... I don't want to out-Duesberg Duesberg, but those are
what our observations on pathogenesis are.
Now what I can tell you new —
and it hasn't
been published — is that we have finally demonstrated that at
least sometimes Kaposi's can become a true malignancy. That is, from a
late-stage patient, we have immortalized tetraploid cell lines with
marker chromosomes, a truly malignant cell that metastasizes within a
nude mouse, killing the animal rapidly.... Now comes the difficult
question: That cell looks just like the other cells I've been talking
about, except it's malignant. It looks like it's derived from them. It
is there all the time, but I can't tell, because it's not
morphologically distinguishable, as the tumor cell is in Hodgkins
disease. Remember, Hodgkins disease is a hodgepodge, like Kaposi's. The
tumor cell is a rare cell, but you can see it, because it's got a
distinct morphology. This doesn't. Maybe it's there all the time, and
Kaposi's a malignancy from the beginning. I don't know. The alternative
is that Kaposi's is a benign hyperplasia that gets worse in time, and
that in some people will evolve into a clonal malignancy.
I don't want to get into the semantics.
that HIV obviously plays a role in this disease. I think the
epidemiology is not debatable. But I think that there is more going on.
I don't know what that “more going on” is. For me
whatever is accounting for the increase in inflammatory cytokines.
I don't know if I made this point clear,
but I think
that everybody here knows — we never found HIV DNA in the
cells of KS. So this is not directly transforming. And in fact we've
never found HIV DNA in T-cells, although we've only looked at a few. So
in other words we've never seen the role of HIV as a transforming virus
in any way. The role of HIV has to be indirect.
During the question period Harry
to Gallo's earlier criticisms. When looking at national data, we do see
a decline of KS among US gay men. On the localization phenomenon: the
product, nitrites, is in the lungs and the blood vessels; it is where
the lesions occur, whereas HIV is not there. We do not see the expected
donor-recipient connection — there is not a single reported
of KS among blood recipients where the donor had KS.
Gallo then admitted: “The
the primary factor. What if the nitrites had the ability, interacting
with endothelial cells, to produce to produce a tremendous amount of
'X', of inflammatory cytokines?”
Peter Duesberg raised the point that HIV
couldn't always play a role in KS, to which Gallo replied:
No, Peter, the other
forms could be the classical KS that always existed. That's the point.
You see, you want to make them all the same. Let's realize that those
may be the classical KS that always existed. KS always existed,
probably through all of human evolution. It was described in the 1800s.
But HIV makes something that was rare become something like this. That
happens in a lot of human diseases. We don't know what causes classical
KS at all, or African KS. They may be the same disease; they may be
different. I think they're different. But even if we have no knowledge
of what the etiologic agents are, when I study pathogenesis of HIV-KS,
I come to the importance of inflammatory cytokines, endothelial cells,
and the TAT protein. I used to think all the time, HIV is also
producing the increase in inflammatory cytokines, but it's only in the
past few months that I've learned that in gay men, there's an increase
in these same inflammatory cytokines before HIV infection.
Someone then asked, “What are
cytokines?” Gallo replied: “The
cytokines are IL1 [interleukin 1], TNF [tumor necrosis factor], and
gamma interferon. In gay men, the inflammatory cytokines are increased before HIV infection.”
In response to a question about
dementia he replied: “The mechanism of dementia in
people is totally unknown.”
Glen Hopkins, an activist from Los
the question of high dose, long-term exposure. Poppers, after all, do
promote mutagenesis. To this Gallo replied: “That's the most
important thing, mutagenesis. Also perhaps nitric oxide.”
The final, general discussion, was
moderated by Paul
Stolley of the University of Maryland School of Medicine. Robert Gallo
started to leave, got to the door, hesitated, then came back and sat
next to Peter Duesberg. Within a few minutes he had his arm around him,
and stayed there for the duration of the final session.
When discussion focussed on what
research ought to
be done, Gallo spoke strongly in favor of an animal model, and said
that Duesberg's research ought to be funded.
There was general agreement that the
epidemiology of nitrites use ought to be rigorously investigated.
My own conclusions, which I expressed
inadequately at the meeting, are as follows:
1. The nitrites-KS
hypothesis has to be framed carefully. Obviously the nitrites cannot be
the cause of all cases of KS, or even of all cases of
“epidemic” or “AIDS KS”, as not
all such cases
have used them. The hypothesis would have to be something like
volatile nitrites play a role, as either primary cause or
co-factor, in the etiology of “epidemic” or
2. Animal research should be conducted,
dose and long-term exposure. Ideally, the animals should be those
closest to humans, though cost factors may rule this out.
3. New survey (or epidemiological)
be conducted to obtain in-depth information on drug usage and other
health risks of those who have been diagnosed as having
“AIDS”. The research should be up to professional
research standards in terms of study design, sampling, questionnaire
design, analysis, etc.
4. The toxicities of the nitrites are
established, and have been since at least 1980. As Hank Wilson argued
on Monday, poppers will always be available — therefore it is
important to educate gay men and the youth of America as to the
physical consequences of using them.
In light of the statements made by
Gallo, it is hard
not to think of the tens of thousands of gay men with KS who have died,
and of the treatments they received. If HIV is not the cause of KS,
then how appropriate were the nucleoside analogue drugs, like AZT and
ddI, whose theoretical basis is the HIV-AIDS hypothesis?
Similarly, if KS is really not
a malignancy, how appropriate were chemotherapy drugs based on the
assumption that KS is
a malignancy? Did these men die from KS, or from the
treatments they were given?
It may be hoped that this meeting is a
greater willingness on the part of the AIDS Establishment to
re-consider the basic AIDS paradigm. Kaposi's sarcoma as an AIDS
phenomenon remains a puzzle, and no hypothesis so far put forward seems
fully adequate to explain it. It could be that KS comprises diverse
conditions with diverse causes. Having said that, however, the
nitrites-KS hypothesis is very much alive, more than a decade after its
precipitous rejection by the CDC.
1. Harry Haverkos et al., “Disease manifestation among
men with acquired immunodeficiency syndrome: A possible role of
nitrites in Kaposi's sarcoma, Sexually
Transmitted Diseases”, October-December 1985.
Harry Haverkos and John Dougherty,
Hazards of Nitrite Inhalants, NIDA Research Monograph 83,
2. John Lauritsen, “Saying No To HIV: An Interview With Prof.
Peter Duesberg, Who Says, ‘I Would Not Worry About Being
Positive’”, New York
Native, Issue 220, 6 July 1987.
3. For an excellent overview of poppers and their toxicities, read
“Nitrite Inhalants: Historical Perspective”, by Guy
Newell et al., in NIDA Monograph 83 (cited above).
See also Chapter X: “Poppers:
The End of an Era” in John Lauritsen, The AIDS War,
New York 1993.
4. Ronald W. Wood, “The Acute Toxicity of Nitrite
Inhalants”, in NIDA Research Monograph 83 (cited above).
5. Thomas H. Haley, “Review of the Physiological Effects of
Amyl, Butyl, and Isobutyl Nitrites”, Clinical
Toxicology, pp. 317-329, 1980.
6. I. Quinto, “The Mutagenicity of Alkylnitrites in the
Salmonella Test” (translation from the Italian), Bolletino
Societa Italiana Biologia Sperimentale, 56:816-820, 1980.
7. These points are covered in various chapters in NIDA Research
Monograph 83 (cited above).
8. Kenneth Mayer and James D'Eramo, “Poppers: A Storm
Street, Issue 78.
9. I have collaborated with Hank Wilson since 1983. In 1986 we
published a little book, Death Rush:
Poppers & AIDS, which included an annotated
bibliography. It is now online: to read it click
10. Eleni Papadopulos-Eleopulos et al., “Is a Western Blot
Proof of HIV Infection?”, BioTechnology,
June 1993, pp. 691-707.
11. Sidney Mirvish et al., “Mutagenicity of Iso-Butyl Nitrite
Vapor in Ames Test and Some Relevant Chemical Properties, Including the
Reaction of Iso-Butyl Nitrite with Phosphate”, Environmental
and Molecular Mutagenesis, 1993;21:247-252.
* This article was published in the New York
issue 582, 13 June 1994, and has been posted in various newsgroups on
the Internet. It may be shared electronically or in the form of hard
copy, but it may not be reproduced for profit without permission from
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