Calls For Research Into
The Poppers-Kaposi's Sarcoma Connection
By John Lauritsen
Native 13 June 1994
Maryland, 24 May 1994.
Institute on Drug Abuse (NIDA) sponsored a high-level meeting, "Technical
Review: Nitrite Inhalants", held outside Washington, DC on
the 23rd and 24th of 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 sarcoma (KS). The meeting was organized by Harry Haverkos
of NIDA, who has been writing since 1985 about the health hazards
of the nitrite inhalants.(1)
as unofficial voice of the AIDS 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.
had implications that went beyond the 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 predictions.
Peter Duesberg, the foremost 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 Native.(2)
For the rest
of this article, I'll give some background information on poppers,
followed by a chronological account of the NIDA meeting and my own
Poppers and their toxicities
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 inhalants (amyl 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.(3)
The FDA re-instated
the prescription requirement in 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 gay
men who were no longer able to perform sexually without the use
of the volatile nitrites were well 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 highlights:
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
Also in 1980
appeared the first of several studies to demonstrate that the volatile
nitrites are powerfully mutagenic.(6) (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.
studies, both in vitro and in vivo, 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 killers.(7)
When the first
cases of AIDS were identified in 1981, or the predecessor cases
of GRID (Gay Related Immune Deficiency), poppers were high on the
list of etiological suspects. Here, after all, 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 spurious. First,
the CDC found AIDS patients who had never used poppers; therefore,
argued the CDC, poppers could not be the cause. The CDC's assumption
was that "AIDS" constituted a single, coherent 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
of Nitrite Use
After a welcome
by Richard A. Millstein, Deputy 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".
of NIDA discussed the ambiguities involved in such phrases as "inhalant
abuse". The inhalants 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 questions in 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.
of the Johns Hopkins School of 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 entry into the study) had much higher
poppers use. Among all groups in the study, the use of poppers declined.
a physician living in the Boston area, was among the first to sound
the warning about poppers to gay men.(8) 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 HIV-antibody-positive
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?
of the morning session was "Advertising Trends", presented
by Hank Wilson, a San Francisco activist who in 1981 founded the
Committee to Monitor Poppers.(9) 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 message that 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 early 70s ads for poppers appeared in all of the gay press-ads
for special inhalers-an ad for a brand named "Discorama",
specifically targeted at disco dancers. One ad gave an 800 number,
with the message, "We'll pay you to try..." (The free
trial tactic has 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.
about the dangers of poppers began 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 even to people who
just glanced at it on the newsstand. A Pittsburgh paper. OUT,
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 News 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 dangerous.
But the poppers
industry had its own resources. A 1983 pamphlet published by the
CDC, "What gay and bisexual men should know about AIDS",
claimed that there was no relationship 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 AIDS
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 the Advocate, entitled "Blueprint For Health",
which gave the impression 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 poppers 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
concluded his presentation by making the point:
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.
Lead to Increased Risky Sexual Behavior and HIV Transmission?
session of 23 May began by considering 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 that HIV is even pathogenic, and consider
the survey research (a.k.a. "epidemiology") performed
by academics, physicians, and 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
In the discussion
period I put two questions to Mayer: 1) "What is the basis
for determining 'HIV infection'? The antibody tests?", and
2) "Is 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
Blot 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.(10)
Paul, an AIDS prevention specialist in San Francisco, discussed
the complexities of classifying events as "risky" or "safe".
There are many confounding 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.
Suppress the Immune System?
afternoon session on 23 May dealt with in vivo toxicological
studies, two involving mice and one involving human subjects.
First was Daniel
Lewis of the National Institute for 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 extremely low, approximating levels
to be encountered as background exposure (used as "room odorizer",
workers in a poppers factory) rather than those encountered when
using poppers as a drug (i.e., inhaling directly from the bottle).
that, in determining the dose, they had to adjust it below the level
where they were "losing" the mice- however, the supplier
of the mice later disclosed that 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 to 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 inhaling IBN vapors developed a "yellowish
tinge". Although there were 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 sharply.
In the question
period I stated that other mice 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 and length of exposure".
mice study was presented by Lee 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).
his colleagues reached the conclusion that exposure of mice to nitrites
via inhalation impaired:
In the question period Peter Duesberg raised the issue of reversibility:
What about something that goes on for years? Analogies here would
be the length of exposure required to 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
The third speaker
was William Adler of the National 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 amyl nitrite can induce changes in immune
function even after short exposure to moderate doses."
Act as a Cofactor in Kaposi's Sarcoma?
day of the meeting, 24 May 1994, addressed the key question: Do
poppers play a role in causing KS? The first speaker was Harry Haverkos,
who began by showing a slide indicating that there appear to be
four kinds of KS:
KS, occurring among older men, indolent.
KS: 25-40 age group, first indolent then fatal in 5-8 years.
KS (e.g., renal transplant): indolent or fulminant.
or AIDS KS: gay white males, fulminant, survival 1-3 years.
And he posed the question: "Are these all the same?"
the cases of HIV-negative cases of 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 did not.
He cited a
recent study which found that the 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
a slide: REASONS TO CONSIDER NITRITE INHALANTS A COFACTOR IN THE
PATHOGENESIS OF KAPOSI'S SARCOMA (KS) IN AIDS:
- Four epidemiologic
studies have demonstrated a strong association.
- Decline in
proportion of cases among gay men parallels decline in nitrite inhalant
abuse among gay men.
of KS lesions correlates with areas of nitrite vapor exposure (nose,
face, chest) in many cases.
mechanisms of action have been proposed:
of cholesterol nitrite (carcinogen)
- 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 TRANSMITTED AGENT:
- Very little
KS reported outside gay male population.
- Among gay
men, KS is associated with white race and high socioeconomic status.
- KS in women
with AIDS no more likely among sexual partners of bisexual men that
sexual partners of heterosexual drug abusers.
- No one can
find the infectious agent.
In conclusion Haverkos presented a series of recommendations:
- All clinicians/researchers
should take a drug history, including inhalants, from patients with
- A multisite
study of KS cofactors is needed (similar to what was done for Reye's
- Women and
heterosexual men with KS should be thoroughly evaluated to identify
- 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 CDC, who said that he would
take a "con position" for the purpose of 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 that the 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.
presentation, Haroutune Armenian 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 correlation 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.
Revises the Paradigm
The final speaker
on the question of whether poppers 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- whether 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
To my knowledge,
this was the first time for Gallo or any other top "AIDS expert"
to admit publicly that HIV was not the primary cause of KS. He said:
"We believe that HIV in 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
we say they are, any more than all leukemias are the same? Leukemias
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 that 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.
went on to revise the most basic premise of the AIDS construct:
the assumption that an underlying condition of "immune deficiency"
is responsible for causing, indirectly, the various 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 have Kaposi's
in the absence of immune suppression. I don't think there's any
evidence that in the older classic Kaposi's sarcoma-among 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:
who here has evidence that Kaposi's is a true malignancy? Is it
only polyclonal hyperplasia that can harm and even kill? Or does
it really evolve into a true cancer? And if so, how often? There's
an enormous increase of Kaposi's in HIV-infected gay men. What's
the role of HIV?
proceeded to present a summary of findings from his laboratory regarding
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
cytokines ... were the very likely initiatory events in creating
this cell. We said, "Oh, the role of HIV is likely to be in
increasing these inflammatory cytokines." But we have learned-this
should be of interest to everybody that isn't completely married
to HIV-that the inflammatory cytokines are reportedly increased
in gay 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. I believe 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 it's 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 tumor 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.
question period Harry Haverkos responded 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 case of KS among blood
recipients where the donor had KS.
admitted: "The nitrites could be 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
raised the point that HIV couldn't always play a role in KS, to
which Gallo replied:
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. Why? I don't know.
asked, "What are the inflammatory cytokines?"
"The inflammatory cytokines are IL1 [interleukin 1], TNF [tumor
necrosis factor], and gamma interferon. In gay men, the inflammatory
cytokines are increased before HIV infection."
to a question about AIDS-related dementia he replied: "The
mechanism of dementia in HIV-infected people is totally unknown."
an activist from Los Angeles, raised 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."
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.
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 toxicology and 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
used them. The hypothesis would have to be something like this:
The volatile nitrites play a role, as either primary cause or
co-factor, in the etiology of "epidemic" or "AIDS
2) Animal research
should be conducted, using high 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) research should 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 survey research standards in terms of study design,
sampling, questionnaire design, analysis, etc.
of the nitrites are well 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 signal of 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
1. Harry Haverkos
et al., "Disease manifestation among homosexual 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, editors; *Health Hazards of Nitrite
Inhalants*, NIDA Research Monograph 83, 1988.
2. John Lauritsen,
"Saying No To HIV: An Interview With Prof. Peter Duesberg,
Who Says, 'I Would Not Worry About Being Antibody 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 R. 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,
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
Mayer and James D'Eramo, "Poppers: A Storm Warning", *Christopher
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.
Unfortunately it is now out-of-print.
10. Eleni Papadopulos-Eleopulos
et al., "Is a Western Blot Proof of HIV Infection?", *Bio/Technology*,
June 1993, pp. 691-707.
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