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Friday, August 17, 2012

How Joseph Stalin Invented 'American Exceptionalism'

How Joseph Stalin Invented 'American Exceptionalism'

The phrase is often attributed to Alexis de Tocqueville, but the real author was the Soviet dictator -- and it wasn't a compliment.
Reuters (Gingrich); Wikimedia Commons (Tocqueville and Stalin)
Rick Santorum and the rest of GOP presidential gang all have a man-crush. Considering he was an outright intellectual elitist, a shaggy-haired liberal, and -- horror of horrors -- French, the object of their adoration seems a bit surprising, but the French aristocrat Alexis de Tocqueville and his 1835 United States travelogue, Democracy in America, have surged into national politics this campaign cycle -- often linked to the nascent expression "American exceptionalism."
Across the nation, from Plano, Texas, to Keene, N.H., Santorum has brandished Tocqueville, lecturing onhow America got revolution right while France didn't. Last year Gingrich published A Country Like No Other: Why American Exceptionalism Matters, a book overflowing with praise for the Parisian writer. Going further still, the former speaker narrated a 2011 documentary called City Upon a Hill, which is produced by Citizens United (yes, that Citizens United). If you guessed that it leads with Tocqueville, you're right.  
The trailer opens like something out of Lord of the Rings: inspirational music, horses galloping through verdant terrain, and the soothing voice of the biggest hobbit of them all -- Gingrich. "During his travels in 1831, French writer Alexis de Tocqueville observed that America was an exceptional nation with a special role to play in human history," he intones. "American exceptionalism has been at the center of our nation's experience for nearly 400 years."
There's only one problem with that: It's not strictly true. Although a superiority complex has long pervaded the national psyche, the expression "American exceptionalism" only became big a few years ago. (In the Federalist Papers, Alexander Hamilton called on Americans to "vindicate the honor of the human race.") What's more, Tocqueville didn't invent the term. Who did? Joseph Stalin.
In the 1920s, the lingering specter of World War I and austere German reparations battered Europe's market-based economy, giving rise to class tension and stark inequality. For worn-down workers, socialism and communism started sounding like pretty good ideas. A world revolution -- indeed, the rise of the proletariat -- seemed possible, and the Communist International was stoked.
But the Americans just wouldn't fall into line. The United States had long since passed the United Kingdom as the world's largest industrial power, but hadn't yet plunged into the Great Depression. To members of the U.S. Communist Party, it was a paradox. Why, in the what appeared to be the purest capitalist Western economy wasn't there any desire for egalitarianism? Had Marx been wrong when he wrote socialism would, inexorably and universally, emerge from the ruins of capitalism? 
America's radical left considered the national condition, contrasted it with Europe, and concluded leftism would be a hard sell stateside thanks to characteristics forged along the frontier. Americans were different: individualistic, profit-crazed, broadly middle class, and as tolerant of inequality as they were reverent of economic freedom. The nation had "unlimited reserves of American imperialism," lamented Communist propaganda at the time. 
In 1929, Communist leader Jay Lovestone informed Stalin in Moscow that the American proletariat wasn't interested in revolution. Stalin responded by demanding that he end this "heresy of American exceptionalism." And just like that, this expression was born. What Lovestone meant, and how Stalin understood it, however, isn't how Gingrich and Romney (or even Obama) frame it. Neither Lovestone or Stalin felt that the United States was superior to other nations -- actually, the opposite. Stalin "ridiculed" America for its abnormalities, which he cast under the banner of "exceptionalism," Daniel Rodgers, a professor of history at Princeton, said in an interview.
Stalin, to say the least, wasn't happy with Lovestone's news. "Who do you think you are?" he shouted,according to Ted Morgan's biography of Lovestone. "(Leon) Trotsky defied me. Where is he? (Grigory) Zinoviev defied me. Where is he? (Nikolai) Bukharin defied me. Where is he? And you! Who are you? Yes, you will go back to America. But when you get back there, nobody will know you except your wives."
As the Great Depression enveloped the United States, Stalin's argument -- if not his bluster -- seemed well grounded. "Exceptionalism was a disease, a chronic disease," wrote communist S. Milgrom of Chicago in 1930. "The storm of the economic crisis in the United States blew down the house of cards of American exceptionalism," the American Communist Party declared at its convention in April 1930. 
Communist leader Jay Lovestone said the American proletariat wasn't interested in revolution. Stalin responded by demanding that he end this "heresy of American exceptionalism."
Of course, the predictions failed: with the help of war, and despite Franklin Roosevelt's new welfare state, the U.S. economy stayed on the capitalist track. As American communism receded, so did talk of exceptionalism in leftist circles. Dismissive references appeared in academic research now and again, but usually in relation to communism's failure in America. Not until the 1980s did it suddenly reemerge, charged with a new connotation of national superiority. According to a Factiva survey,The New York Times was the first mainstream outlet to revive "American exceptionalism," when in 1980 Richard J. Tofel implored Jimmy Carter and Ronald Reagan to defend this distinctive cultural aesthetic: "As our unquestioned supremacy recedes, we need to decide what "America" means to us, and what it means to the world."
Sound familiar? Over the following 20 years, there was a lot more talk like this; exceptionalism appeared in national publications 457 times. The next decade had it 2,558 times. But since 2010, it's gone viral, leaping into print and online publications roughly 4,172 times.   
How did a phrase intended as derision become a rallying cry of American awesomeness? 
As significant portions of the electorate -- think Southern Democrats -- shifted toward the GOP in the 1960s and 1970s, conservative thinkers charted a new Republican identity emboldened by triumphalism and uncompromising patriotism. Doubting exceptionalism became "un-American." Looking to history for more evidence, conservative intellectuals stumbled across Tocqueville, who in Democracy in America had described a nation as "exceptional" for its devotion to practicality over art or science. He lent enough oomph to credibly define America as categorically transcendent, Rodgers said.
It worked. In a 2010 Gallup Poll, 80 percent of Americans agreed that based on history and the Constitution, the United States was the "greatest country in the world." American exceptionalism, along with flag pins shining from one's lapel, is one of the rare issues where Republicans and Democrats agree. In 2009, President Obama said in Strasbourg, France, that he subscribed to American exceptionalism (just as other nations, he stressed, should feel the same about their own country). Gingrich used the phrase 44 times in his recent book. For whatever reason, its author, Stalin, didn't even get a cameo.
Then last year during a debate in early September -- with dissatisfaction toward the economy as high as late 2008 -- Republican presidential candidates harped on American exceptionalism time and again. Before that, not a single incumbent or candidate had employed the expression in a presidential debate, transcripts at the American Presidency Project's website show.
It's hardly surprising such talk has accelerated recently. Everywhere you look, headlines, pundits, and academics prophesy the demise of Pax Americana and the "rise of the rest," as Fareed Zakaria termed it. We're gripped by concern we'll soon be a nation of austerity and dependency, not opportunity, that America's spiraling into insolvency with Greece. It's the same context in which Tofel revived the term 32 years ago.
In 2008, candidate Obama said fear makes people cling to religion, guns, and xenophobia. He was flayed for it in the media -- and, in some respects, rightly so. But there was an element of truth to his remarks, and there's a powerful parallel to the nation overall. In our secular state, the Constitution and Declaration of Independence are as close to sacred relics of an established religion as it gets. Just look at how their air-tight casings in Washington, D.C. mimic saints' reliquaries. 
Belief in America has taken on the desperate certitude of zealotry, as if the more we express it and the firmer our conviction, the more we might somehow succeed at wishing it true. And that it will stay true forever. Peel a few layers back and the rise of faith in American exceptionalism doesn't evince superiority. It indicates fear.

John Lauritsen-AZT ON TRIAL

By John Lauritsen
New York Native 19 Oct. 1987

I argued in a previous article (Native #215) that the theory behind AZT (now known by its trade name of Retrovir) was false, inasmuch as the hypothesis that HIV causes AIDS has been refuted by Prof. Peter H. Duesberg, a world-renowned molecular biologist at Berkeley; that AZT's alleged benefits were not backed up by reliable evidence; that its toxicities were firmly established and severe; and that therefore the drug should not be prescribed, recommended, or used.
In his interview with me (Native #220), Prof. Duesberg referred to AZT as "a poison" and as "cytotoxic" (lethal to body cells). Duesberg said that the theories behind AZT were false, that there was "no rationale for treating with AZT", that prescribing AZT was "highly irresponsible", and that AZT was "guaranteed" to be harmful:
AZT hits all DNA that is made. It is hell for the bone marrow, which is where the T and B cells and all those things are made. It's hell for that. It has a slight preference for viral DNA polymerase compared to cellular DNA polymerase, and that's based on in vitro studies only, but that's certainly not absolute. It kills normal cells quite, quite extensively.
At the time these articles were published, the only reports on the Food and Drug Administration (FDA) trial that was the basis for granting government approval to market AZT, were in the popular media or a promotional film produced by AZT's manufacturer, Burroughs-Wellcome. Doctors who prescribed AZT did so on the basis on very limited information, along with the assurances of the Public Health Service that AZT represented the "best hope".
This appears to have changed. The 23 July 1987 issue of the New England Journal of Medicine (NEJM) contains a two-part report on the FDA's "Double-Blind, Placebo-Controlled Trial"-"The Efficacy of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS -Related Complex" and "The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex". Margaret A. Fischl, M.D. is identified as the primary author of the first article, and Douglas D. Richman, M.D., of the second.
It quickly became clear to me that there were serious problems with the reports. The description of methodology was incomplete and incoherent. Not a single table was acceptable according to statistical standards-indeed, not a single table made sense. In particular, the first report, on "efficacy", was marred by contradictions, ill-logic, and special pleading.
In the meantime, I received about 500 pages of material which Project Inform in San Francisco had obtained from the FDA under the Freedom of Information Act. This material showed the dark underside of the double-blind, placebo-controlled trial-falsification of data, sloppiness, confusion, lack of control, departure from accepted procedures-things not even hinted at in the NEJMreports. Martin Delaney of Project Inform gives a fair summary of what emerges from the FDA material:
The multi-center clinical trials of AZT are perhaps the sloppiest and most poorly controlled trials ever to serve as the basis for an FDA drug licensing approval. Conclusions of efficacy were based on an endpoint (mortality) not initially planned or formally followed in the study after the drug failed to demonstrate efficacy on all the originally intended endpoints. Because mortality was not an intended endpoint, causes of death were never verified. Despite this, and a frightening record of toxicity, the FDA approved AZT in record time, granting a treatment IND in less than five days and full pharmaceutical licensing in less than 6 months.
After reading through the FDA material several times, I called Drs. Fischl and Richman, and spoke with each of them for about half an hour. The conversations were not very enjoyable for any of us. Neither one of them could explain the tables in the reports that they themselves had supposedly written. They both repeatedly said that I should call Burroughs-Wellcome to find out how the tables were developed or to obtain answers on other questions. Dr. Richman became quite truculent at one point, saying that I was "fixated" on the tables; that I should "forget about the tables"; that the report would be "just as good without them". Their ignorance regarding these tables is really amazing. As a market research analyst, I am accustomed to working with tables, and I can say that I have never written a report containing even a single table I could not explain and interpret.
Despite abundant reports of the horrible physical consequences of taking AZT, several of the New York City physicians most prominent in treating AIDS and ARC patients are not only prescribing AZT, but actively proselytizing for it. I think that history will judge these doctors harshly. This article will argue that no credence should be placed in the NEJM reports, that the "benefits" attributed to AZT remain unsubstantiated.
But first, an update on the central question: What causes AIDS?
HIV is not the cause
AZT (Retrovir) is officially defined as a drug for "symptomatic HIV infection". Its label states it is for the "management of certain patients with serious manifestations in infections caused by the human immunodeficiency virus (HIV)." Therefore it is crucial to know whether or not HIV really is the cause of AIDS, or whether HIV infection is even harmful. According to Duesberg, HIV is a benign passenger virus, and HIV "infection" is nonpathogenic. If so, prescribing a poisonous drug to attack a harmless virus would be utter madness.
Colleagues in the sciences have told me that we should now consider it highly probable that HIV is not and could not possibly be the cause of AIDS. I agree. Not only are the arguments compelling that are put forward by Drs. Peter H. Duesberg, Joseph A. Sonnabend, Nathaniel S. Lehrman, and others-but no attempt to rebut these arguments has been made by any of the leading HIV champions, including Drs. Robert Gallo, William Haseltine, Myron Essex, or their faithful colleagues in the Public Health Service.
The HIV edifice appears to have collapsed, and the "AIDS virus" crowd have resorted to stonewalling. A British television team recently attempted to interview Gallo. They were informed by National Cancer Institute (NCI) officials that it would first be necessary to submit in writing a list of all questions he would be asked, and that under no circumstance would the world's premier "AIDS researcher" discuss etiology, or whether or not HIV was the cause of AIDS.
Secrecy and censorship versus science
Ideally science is supposed to be a public activity, where scientists verify each other's work in a mutual endeavor to establish the truth. Scientists are expected to describe their experiments precisely, and to make their data available, so that other scientists working independently could replicate their experiments and verify their findings. Likewise, scientists are expected to enter into scientific dialogue, to respond to the criticisms and arguments of other scientists. It is therefore disgraceful that the NCI scientists refuse to respond to Prof. Duesberg's arguments.
Censorship is also incompatible with the ideals of science.
Government agencies, like the FDA, ought to be willing to make their materials public, so that their work can be verified independently. Although the FDA did release material under the Freedom of Information Act, it was heavily censored. As many as a dozen pages at a time were missing. Individual pages had words, lines, or paragraphs whited out. And most of the pages were entirely or almost entirely illegible-they looked as though the copy machines had been badly out of focus. There is no excuse for this. We live in the age of the copy machine, and the FDA could have produced legible copies. The lives of thousands of people are affected by the AZT trials, and it is wrong to treat information about these trials as though it were classified military secrets.
The aborted trial
The "double-blind, placebo-controlled" trial of AZT was conducted by the FDA at twelve medical centers throughout the United States. Although the patients did not enter the study all at one time, each patient was intended to undergo a full 24 weeks of "treatment"-either with AZT or with a placebo.
Midway through the study it was observed that only one patient on AZT had died, whereas more than a dozen on placebo had. According to the received version, it was then decided it would beunethical to continue the study, since AZT was so spectacularly (if unexpectedly) prolonging the lives of those who took it. The study was terminated; all patients were told whether they had been taking AZT or a placebo, and all were given the opportunity to take AZT. As I'll argue later, there are good reasons for being skeptical of the mortality data, as well as the motives for prematurely terminating the study.
Owing to the early termination, only 15 patients (5% of the total) completed the full 24 weeks of treatment. Twenty-three patients were treated for less than four weeks. On the average, patients had received treatment for about 17 weeks at the time the study was aborted. (See Table 1.)
Very Few Patients Finished the Full 24-Week Protocol
Base: Total Who Began Trial(282)(145)(137)
Finished Trial (24 Weeks)5%6%4%
Did Not Finish Trial95%94%96%
    "Still Participating" (But Finished Less Than 24 Weeks Of Treatment)
    Dropped Out Of Study
Weeks Of Treatment (Mean)(17.3)(17.6)(16.9)
As might be imagined, the premature termination invalidated the original study design and caused chaos from an analytical standpoint. Tables which would have been entirely straightforward if all patients had finished their 24 weeks of treatment had to rely upon controversial statistical projections. For example, instead of showing the percentages of patients in each group who experienced opportunistic infections during the 24 weeks, it became necessary to develop a projected probability of their experiencing opportunistic infections within 24 weeks. This is analogous to estimating the probability of developing arthritis by the age of 70, using a sample in which only a few people had reached this age, and in which some were still teenagers. The method used (Kaplan-Meier Product-Limit Method) is a statistical attempt to estimate what results would have been if the study had not been terminated. Like mopping up milk, it may be the best thing to do-but it would be better not to spill the milk.
With poignant restraint, an FDA mathematical statistician registered his misgivings over the early termination:
There are a number of disquieting aspects concerning this NDA. It contains only one controlled clinical trial, and thus there is no independent confirmatory evidence for that study's results. It contains a relatively small number of patients (<200) who have been treated with AZT. The controlled clinical study is relatively short (i.e., 24 weeks) and WAS TERMINATED EARLY ON THE BASIS OF UNANTICIPATED FAVORABLE RESULTS IN A MANNER THAT HAS NEVER BEEN ADEQUATELY DEFINED IN TERMS OF ITS IMPACT ON THE SUBSEQUENT STATISTICAL ANALYSES. [Emphasis added.]
The unblinded trial
The study was planned as a "double-blind" trial, which means that the drug was supposed to be labelled and the study conducted in such a way that neither doctors nor patients knew whether AZT or a placebo was being administered.
In practice, the AZT trial became unblinded rather quickly.
An FDA medical officer writes: "the fact that the treatment groups unblinded themselves early could have resulted in bias in the workup of patients".
The study became unblinded among the patients as a result of differences in taste between AZT and the placebo:
Initially the placebo capsules, which were indistinguishable from the AZT capsules in appearance, were distinguishable in taste. This difference was corrected and the placebo capsules replaced with new ones after early reports were received of patients breaking the capsules and tasting the medication.
Anyone who has spent time with PWAs is aware of the keen interest with which they compare treatments. And anyone who has observed the gay grapevine is in awe of the speed with which information can travel around the world. I can well believe that from the time the first two patients compared notes on how their capsules tasted, it was only a matter of days until many or most of the patients knew whether they were getting AZT or a placebo.
Other patients discovered what medication they were receiving by taking their capsules to chemists for analysis.
In some instances patients pooled and shared their medication, thus ensuring that all of them could receive at least some AZT. Other patients, who found out their medication was only a placebo, took Ribavirin that had been smuggled in from Mexico.
From the standpoint of the doctors, the study unblinded itself through the strikingly different blood profiles of the two treatment groups. (See "Toxicity" below.) No attempt was made to blind the blood results from any of the doctors in the medical centers at which the trials were held. According to an FDA analyst:
The treatment groups may have unblinded themselves to a large extent during the first two months due to drug-induced erythrocyte macrocytosis.
There are very good reasons why blind studies are required for the approval of a new drug. The potential biases are so great, for both patient and doctor, that a drug-identified trial would be scientifically useless.
Many patients entered the trial out of desperation, believing that death was immanent without the intervention of a new "wonder drug". For these patients, the psychological consequences of finding out that they were receiving only a placebo must have been devastating. A sense of despair and hopelessness may well have contributed to the high mortality in the placebo group.
Doctors, and scientists in general, are often extremely gullible people. In their book, Betrayers of the Truth: Fraud and Deceit in the Halls of Science, William Broad and Nicholas Wade devote an entire chapter to "Self-Deception and Gullibility". Scientists unconsciously see what they want to see. Even the most absurdly crude hoaxes, like the Piltdown man, were believed for many years by eminent scientists. With high expectations engendered for AZT, it is not unreasonable to assume that unconscious biases affected not only how data were interpreted and recorded, but also how patients were treated. The shockingly high death rate among the placebo patients suggests that these patients may not have been managed well by their attending physicians.
When I spoke to Drs. Fischl and Richman, they both vehemently denied that the trial had become unblinded before it was terminated. This suggests that they had little control over, or knowledge of, what was happening-or, that they were not telling the truth. As FDA analyst Cooper stated, it was fact that the study became unblinded early on. And since the AZT trial was not blinded, the entire study was invalid and worthless. On this basis alone, FDA approval of the drug was neither proper nor legal.
Sloppiness, improprieties, false data
The AZT trial was characterized throughout by sloppiness and lack of control. Recording forms were poorly designed, leading to confusion when doctors were asked to make judgments. For example, doctors were asked to record 10 subjective symptoms "often associated with HIV infection", and to decide whether they were symptoms of AIDS or adverse reactions to the drug treatment. Understandably it was hard to differentiate among "malaise, fatigue, and lethargy", let alone to decide whether these were caused by drug or by disease. Midway through the trial the "sponsor" (Burroughs-Wellcome) substituted a 33-item "AIDS-related signs and symptoms" sheet, at which point confusion became utter chaos. Most of the medical centers were unable to relate one form to the other, or even to comprehend the 33-item form, and so in the end the incomplete data on the 10-item form served as the patients' only baseline data.
When FDA analysts reviewed the Case Report Forms, numerous improprieties were observed:
* Symptoms previously checked off on the 10-item sheet were crossed out or otherwise changed, usually without the principal investigator's initials, and sometimes with a date of change much later than the date the form was originally filled out, without explanation as to why changes were made.
* "Transcription" of data from 10-item symptom form to the 33-item form was performed, sometimes without date of initials of who did the transcribing. Sometimes the original form was not submitted.
* Adverse experiences were sometimes crossed out months after initially recorded, even though "possibly related to test agent" had been checked off originally by the investigator or his designee.
The last set of improprieties is especially serious, as it appears to be tendentious, favoring AZT by reducing the cases of adverse reactions to the drug. If done deliberately this would constitute cheating and fraud, things that people controlling and directing studies must constantly be vigilant against. If there can be cheating in little things, there can be cheating in big things as well.
Having detailed these various improprieties, the FDA analyst insouciantly dismissed the whole mess with a sentence that caught me completely off guard:
Whatever the "real" data may be, clearly patients in this study, both on AZT and placebo, reported many disease symptom/possible adverse drug experiences.
"Whatever the 'real' data may be..."! I can't get over this phrase. Is this an expression of bureaucratic cynicism, a sardonic form of humor, simply indifference, or what? Do FDA analysts even care whether their data is "real" or not?
Serious problems were uncovered at one of the 12 medical centers. According to an FDA analyst:
The FDA inspector found multiple deviations from standard protocol procedure, and SHE RECOMMENDED THAT DATA FROM THIS CENTER BE EXCLUDED FROM THE ANALYSIS OF THE MULTICENTER TRIAL. [Emphasis added.]
The FDA inspector's report did not reach an appropriate department until late December 1986, three months after the trial had been terminated. The decision was then made...
...to request inspection of all twelve centers which participated in this trial, due to the importance of this drug, its high public visibility, and because one of the early inspections had revealed "significant deviations" from FDA regulations regarding the proper conduct of clinical investigations.
At this point inspecting all 12 centers was like locking the barn after the horse was stolen. Of grave concern is the fact that one of the problems noted in the delinquent center had to do with "drug accountability", perhaps the most serious impropriety that could be imagined. If there is even the slightest reason to doubt that all "AZT patients" really were getting AZT, and all "placebo patients" really were getting placebos, then the study has fallen apart at its very core.
In addition, there were numerous cases of "protocol violations". When the study was designed, various conditions were defined as constituting "protocol violations", as a result of which a patient's data would be excluded from the data base. Most of the protocol violations concerned the unauthorized use of other drugs in addition to the treatments administered in the study. These restrictions were necessary in order to avoid drug interactions, confounding results, and so on. At an FDA in-house meeting convened to decide what to do about the patients in whom protocol violations were noted, one FDA officer commented that "if exclusion of all patients with protocol violations were strictly applied, quite a few patients would probably be deleted from the database."
After a certain amount of agonizing over the "highly visible, potentially inflammatory issue" of whether to exclude data from the delinquent center or from patients with protocol violations, it was decided to exclude nothing. False data were retained. Garbage was thrown in with the good stuff. These appalling decisions were made with the following rationalization:
Because the mortality analyses were so strongly in favor on the drug, any slight biases that may have been introduced when minor 'protocol' violations occurred were highly unlikely to influence the outcome."
This is egregiously beside the point. It is irrelevant whether or not throwing in bad data with good data will "influence the outcome". The point is that you don't do it on principle. It is an absolute and iron-clad principle of research that you don't use bad data. No principled analyst would ever proceed to interpret data that he knew were contaminated.
One may note that not a hint of these problems appears in the NEJM reports by Drs. Fischl and Richman.
The mortality data that so dazzled the FDA that they terminated the AZT trial prematurely and accepted bad data are shown in Table 2.
Double-Blind, Placebo-Controlled Trial
Bases: Total Who Began Trial(145)(137)
Cumulative Deaths During Trial1%14%#
Weeks Of Treatment (Mean)(17.6)(16.9)
# Significantly higher than AZT at the 99% confidence level.
Only 1% of the 145 AZT patients, compared to 14% of the 137 placebo patients died during the course of the trial. Statistically, this is highly significant-the probabilities are better than 99 out of 100 that the difference (1% vs. 14%) is real, as opposed to being a product of chance.
One must caution, however, that these mortality data reflect a very short time period-only 17 weeks, on the average. It would be fallacious to assume that the death rate would have continued to be higher in the placebo group if the time period were 30 weeks, or a year, or two years.
In addition, there are good reasons to be skeptical of the mortality data. For one thing, the death rate in the placebo group is shockingly high. According to doctors in New York with extensive experience in treating AIDS patients, with good patient management, nowhere near this many patients ought to have died in such a short time.
In addition, the death rate in the AZT group is suspiciously low when compared with other trials of AZT. After the "double-blind, placebo-controlled" study was terminated, all patients were informed which treatment they had been receiving, and were offered the option of receiving AZT. (See Table 3)
Open-Label Trial Following Termination of Double-Blind,
Placebo-Controlled Trial (18 September 1986 - 13 February 1987)
Received AZT in Extended, Open-Label Trial
Original Treatment AZT
Original Treatment Placebo
Bases: Total Participating(227)(127)(100)
Cumulative Deaths During Open-Label Trial (21 Weeks Of Treatment)10%8%12%
A total of 227 patients accepted the offer, and continued or began to receive AZT (127 who were originally treated with AZT and 100 who were originally treated with placebo). AZT no longer prevented patients from dying. In the 21 weeks of the "open-label" trial, 10% of the patients died. Curiously, not only deaths but also opportunistic infections increased in the original AZT group as soon as the first study was terminated. There is no good explanation why this should be so.
Another trial of AZT occurred prior to the "double-blind, placebo-controlled" trial. (See Table 4) This was a "Phase I" trial, intended to give a preliminary estimate of the drug's toxicities. In the Phase I trial, 12% died during a time period of only 6 weeks. The four patients who died were replaced, and all 33 patients continued to take AZT in an "extended trial", during which an additional 21% died. It is unclear from the FDA material exactly how long the extended trial lasted-but at any rate a cumulative total of one-third (33%) of the patients died, either in the phase I or in the extended trial.
Phase I Trial of AZT (No Placebo Control)
Base: Total Receiving AZT(33)
Deaths During 6-Week Trial12%
Deaths During Extended Trial21%
Cumulative Deaths33%
Burroughs-Wellcome provided data to the FDA on deaths which occurred among patients who began taking AZT following release of the drug. The information was in incredibly garbled form, but I was able to ascertain at least the deaths that occurred during the first 8 weeks of treatment. During this short time period 6% of the patients died. Table 5 shows a comparison of these four studies of AIDS or advanced ARC patients who were treated with AZT.
Mortality Comparisons
(Four Studies Of AIDS/ARC Patients Treated With AZT)
Double-Blind Placebo Controlled Trial
(Mean: 17 Weeks)
Extended Open-Label Trial
(21 Weeks)
Phase-I trial
(6 Weeks)
Following Release of Drug
(8 Weeks)
Bases: Total Patients Participating In Each Trial(145)(227)(33)(2552)
Deaths During Trial1%10%#12%##6%#
# Significantly higher than the Double-Blind, Placebo-Controlled Study at the 99% Confidence Level or more.
## Significantly higher than the Double-Blind, Placebo-Controlled Study at the 95% Confidence Level.
It can readily be seen that the death rate in the "double-blind, placebo-controlled" trial (the first column) is significantly lower than in any of the other studies, especially considering that the trials in columns three and four represented much shorter time periods. In other words, the mortality data from the "double-blind, placebo-controlled" trial are almost certainly wrong, based on comparisons with mortality data from other AZT trials.
In addition, and I regret having to say this, skepticism is warranted by virtue of the stakes involved-hundreds of millions of dollars-and the participants: big business and the FDA. The materials released by the FDA show that Burroughs-Wellcome was quite willing to bend rules or stretch interpretations if doing so would facilitate approval for their product.
The FDA did not come to the AZT trials with clean hands. In fact, the FDA has a long history of collusion with industry. A number of examples can be found in the book, How to Get Rid of the Poisons in Your Body, by Gary Null and Steven Null.
Another example where the FDA catered to the needs of big business can be found in a crude propaganda piece, "Evaluation of Health Aspects of Sugars Contained in Carbohydrate Sweeteners", recently circulated by the sugar industry, and prepared by the Division of Nutrition and Toxicology, Center for Food Safety and Applied Nutrition, Food and Drug Administration. This report, which strives to exonerate sugar from any connection with obesity, diabetes, hypertension, tooth decay, etc., uses pseudo-scientific language and tables, but is conspicuously short on references. It is not hard to imagine that the authors of the sugar report were motivated by something other than scientific ideals.
One more example of the FDA's tainted past: For more than a decade, the FDA has been asked to recognize the fact that poppers are drugs, and to regulate them as such. The FDA has repeatedly refused to do so, claiming that poppers are "room odorizers", since they are labelled as such. This is preposterous, for the FDA has traditionally been concerned with truth in labelling. They would certainly take action if snake oil were labelled as an "AIDS remedy", or if cocaine were labelled as a "nasal decongestant". Why should they accept at face value the cynically ridiculous claim that poppers are used as "room odorizers"?
I am also distrustful of the mortality data because of the fact that problems with "drug accountability" were among those found at the delinquent medical center. Suppose that some of the placebo deaths were really AZT patients who had been posthumously reassigned? There are a number of ways that this could have been done. As a check it would be desirable to have some way of verifying that the placebo patients who died really had been placebo patients. Unfortunately, the causes of death were listed in perfunctory and even incorrect ways ("AIDS", "pneumonia [unspecified]", "suspected TB or CMV" or "suspected MAI or CMV"). Since death was not an endpoint of the study, many of the causes of death were not verified. No autopsies were performed. These might have yielded useful information, and would have verified whether or not there were traces of AZT or other drugs in the bodies of the "placebo" patients.
Project Inform requested copies of the medical records of the patients who died. It would have been possible to determine from these, with considerable accuracy, whether or not the patient had been treated with AZT. The FDA refused to release the medical records, claiming that they were "confidential". It is hard to see why the records would have been "confidential" if the FDA had whited out the names of the patients. And the FDA knows well enough how to white out things. What exactly is the FDA afraid of?
The inadequate descriptions of causes of death, the lack of verification of death causes, the lack of autopsies, the refusal to release medical records-these things are even more suspicious in light of the stringent procedures that the FDA laid down for trials of other drugs. In a recent trial of Ribavirin, autopsies were obligatory, and a Death Report form of more than 30 items had to be filled out for each patient who died.
The mortality data are even more suspect in light of the fact that the "double-blind, placebo-controlled" trial failed to demonstrate that AZT had any benefits, relative to the placebo group. Slight increases in the T-4 cell counts in the AZT group did not persist over time. There is no known mechanism by which AZT could produce benefits sufficient to account for the dramatic differences in mortality.
AZT was found to have "no significant antiviral activity against a variety of other human and animal viruses, including herpes simplex virus type 1, cytomegalovirus, adenovirus type 5, measles virus, rhinovirus 13, bovine rotavirus, and yellow fever virus. It has been shown to inhibit the replication of Epstein Barr virus (EBV)...though the clinical significance of this finding is unknown."
Although AZT (Retrovir) is officially defined as a drug for "symptomatic HIV infection", it was no more effective against HIV than the placebo was. Several measures of viral activity were used, and "no statistically significant changes in the percent of positive cultures or time to detection of virus in culture were observed." After reviewing the failure of AZT to prove efficacious in any known way, an FDA analyst concluded that AZT treatment is likely to be worse than the disease in the long run:
Of particular concern is the possibility that the hematologic toxicity of the drug when administered over a prolonged period of time may eventually debilitate patients to such an extent that they may become less able to resist opportunistic infections and other complications of HIV-disease [sic] than if they had been left untreated.
In summarizing adverse reactions to the drug, the FDA medical officer states, "The majority of patients who were randomized to receive AZT in this trial experienced significant toxicity." This is, if anything, an understatement, especially considering that many AZT patients were treated with the drug for only a few weeks. If all AZT patients had been treated for 24 weeks, as originally planned, the percentages experiencing various toxicities would undoubtedly have been even higher.
AZT patients suffered from many adverse reactions to the drug, the most severe involving blood toxicities. These are summarized in Table 6. In less than 18 weeks of treatment, on the average, almost one-third (31%) of the AZT patients required at least one transfusion; one-fifth (21%) of them required multiple transfusions.
Blood Toxicity
(Double-Blind, Placebo-Controlled Study)
AZT Treatment
Placebo Treatment
Bases: Total Who Began Study(145)(137)
Experienced During Trial:  
Moderate (Hb <7.5)
Severe (Hb <3.5)
Hemoglobin decreases >2g.


Had at least one transfusion
Had multiple transfusions


Grade 3 marrow suppression (Hb <7.5g./deciliter, neutrophile <750, or white cells <1500)
MACROCYTOSIS (Associated With Pernicious Anemia)
Mean corpuscular volume
<100 cubic angstroms
Mean corpuscular volume
<110 cubic angstroms




LEUKOPENIA (white blood count <1500)27%#7%
NEUTROPENIA (neutrophile counts <750)16%#2%
Weeks Of Treatment (Mean)(17.6)(16.9)
# Significantly higher than Placebo at the 99% Confidence Level or more.
Marrow suppression was experienced by 45% of the AZT patients, but only 12% of the placebo patients. Macrocytosis (enlarged red blood cells, associated with pernicious anemia) occurred in 69% of the AZT patients, but in none of the placebo patients. This measure, which clearly distinguished AZT from placebo patients in over two-thirds of the cases, played a major role in the unblinding of the study among the doctors.
In addition to the "double-blind, placebo-controlled" trial, many experiments were performed, which further demonstrated the high toxicity of the drug. The results of the Cell Transformation Assay suggested:
AZT may be a potential carcinogen. It appears to be at least as active as the positive control material, methylcholan threne.
The FDA analyst who reviewed the pharmacology data, Harvey I. Chernov, succinctly summarized the effect of AZT on the blood:
Thus, although the dose varied, anemia was noted in all species (including man) in which the drug has been tested.
Chernov concluded his review of the pharmacology data by recommending that AZT should not be approved:
In conclusion, the full preclinical toxicological profile if far from complete with 6-month data available, but not yet submitted, one-year studies to begin shortly, etc. The available data are insufficient to support NDA approval.
Ethical issues
There is no doubt that AZT is a highly toxic drug, that it will be harmful to patients, many of whom are already severely debilitated. On the other hand, there is no scientifically credible evidence that AZT has any benefits whatsoever. The "double-blind, placebo-controlled" trial of AZT is unworthy of credence. Assurances from representatives of the pharmaceutical industry or the Public Health Service, that AZT represents the "best hope", are also unworthy of credence.
I submit that it is malpractice for physicians to prescribe AZT, a poison which can only harm the patient.
I submit that it was unethical for AZT to be approved on the basis of research which was, to put it as generously as possible, invalid.
The nation's blood supply belongs to all of us. If AZT continues to be administered to thousands of patients-apparently there are almost 10,000 patients on AZT, at last count -- this will mean an intolerable drain on the blood supply, with many AZT patients requiring transfusions as often as every other week. It is one thing when someone becomes seriously ill or has an accident or major operation. Such a person is entitled to receive blood. But AZT is now creating entirely another category of patient-those whose bone marrow becomes irreversibly damaged. A category of iatrogenic vampires. And this is gratuitous, the result of a drug that should never have been administered in the first place. In this sense AZT harms all of us, not just the patients who are being poisoned by it. *
Postscript: 9 March 1988
After I wrote the above article, I learned of a California lawsuit that charged collusion between federal agencies and Burroughs-Wellcome, the manufacturer of AZT. If such collusion did indeed take place as early as February of 1985 (a year before the AZT trials began), then of course it is likely that there was collusion in the trials as well.
Details of the lawsuit are found in an article in the Bay Area Reporter (5 November 1987) by Ray O'Loughlin, under the headlines, "Lawsuit Charges Collusion Between Feds, AZT Maker:
Company Donates $55,000 for Research; Special Status Granted for Marketing Drug". Following are some excerpts:
The two federal agencies which approve and regulate AIDS treatments are accused of colluding with drug manufacturers. The National Institutes of Health (NIH) and the Food and Drug Administration (FDA) are accused of expediting the approval of AZT in exchange for a $55,000 donation by the AZT manufacturer, Burroughs Wellcome. In July 1985, Burroughs received exclusive rights to market AZT for seven years.
The allegation is part of a class action lawsuit filed in June by San Francisco-based Gay Rights Advocates. The suit accuses the NIH of failing to spend $47 million appropriated by Congress for experimental drug treatments. In response to the government's motion to dismiss the suit, NGRA released a series of letters indicating that certain medications are put on a "fast track for approval." They charge that there are unethical conflicts of interest in the agencies' operations.
"If the judge allows this case to go forward, we will prove that government officials have been engaged in unethical and illegal conduct resulting in serious delays of promising new AIDS medications," said NGRA's legal director, Leonard Graff.
According to documents filed in U.S. District Court in Washington, D.C., Dr. Samuel Broder of the National Cancer Institute, part of NIH, encouraged Burroughs Wellcome to fund three research positions in his laboratory.
Shortly after that Burroughs applied to the FDA for "orphan drug" status for AZT. Two weeks later Broder's office received the check for $55,000 from Burroughs. That same day FDA granted the company exclusive rights to market AZT. Originally developed as a cancer treatment, AZT has been in existence for over 20 years.
"We're alleging a special cooperative relationship between sister agencies that put certain drugs on a fast track for approval," said Graff.... Broder's action, he said, "violates conflict of interest as set out in an executive order" issued by Pres. Lyndon B. Johnson in 1965. At the very least, it "indicates a cozy relationship," he said, between the agencies and the drug firm.
Regardless of whether or not there was collusion, the AZT trials were invalid, worthless, and fraudulent. "Fraudulent" is by no means too strong a word to use in describing a study in which false data were knowingly retained, and in which improprieties and violations of protocol were knowingly ignored. It is fraudulent to describe an unblinded study, which the AZT trials most certainly were, as being a "double-blind" study, as Margaret Fischl and Douglas Richman did in their NEJM reports. Either Fischl and Richman were unaware that the study had become hopelessly unblinded, in which case they are guilty of incompetence, or they did know and covered it up, in which case they are guilty of fraud.
On 27 January 1988, Perri Peltz of NBC news did an expose on AZT, which closely followed some of the points of my article (without giving me credit). NBC investigators independently found that:
- The test became unblinded early on. Everyone knew who was getting what.
- A chemist admitted analyzing medications for patients in the trials.
- Patients in the trials shared medications.
- There was mass tampering with the rules of the test-Patients took other medications. Such violations of the rules of the test took place from coast to coast.
- A government memo recommended that Boston be dropped from the study because of gross improprieties. Nevertheless, the bad data from this center were retained. The memo observed that if all patients with protocol violations were dropped, there wouldn't be enough left in the study.
Representatives of the NIH and the FDA resorted to stonewalling. According to Perri Peltz:
"When preparing this report we repeatedly tried to interview Dr. Anthony Fauci at the National Institutes of Health. Both Dr. Fauci and Food and Drug Administration Commissioner Frank Young declined our request for interviews."
1. Peter H. Duesberg, Ph.D.; "Retroviruses as Carcinogens and Pathogens: Expectations and Reality"; Cancer Research, 1 March 1987. 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.
2. Duesberg, op. cit.; Lauritsen & Duesberg, op. cit.
3. J.A. Sonnabend, MRCP and Serge Saadoun, M.D., M.S.; "The Acquired Immunodeficiency Syndrome: A Discussion of Etiologic Hypotheses"; AIDS Research; volume 1, number 1, 1984.
Joseph A. Sonnabend, MD; "Looking at AIDS in Totality"; New York Native, Issue #129.
4. Nathaniel S. Lehrman, M.D.; "Is AIDS Non-Infectious? The Possibility and its CBW Implications"; Covert Action, Number 28. Nathaniel S. Lehrman, M.D.; "A 'Natural' Epidemic?"; New York Native, Issue # ?.
5. Lawrence Hauptman, Ph.D.; "Statistical Review and Evaluation"; NDA# 19-655/Drug Class 1A, Burroughs-Wellcome Company, AZT Capsules; p. 17.
6. Ellen C. Cooper, M.D., M.P.H.; "Medical Officer Review of NDA 19-655"; p. 70.
7. Ibid. p.6.
8. Ibid. p. 70.
9. Ibid. pp. 77-78.
10. Ibid. p. 78.
11. Ellen C. Cooper, M.D.; "Addendum #1 to Medical Officer Review of NDA 19,655"; p. 1.
12. Ibid. p. 1.
13. Ibid. p. 2.
14. Ibid. p. 3.
15. John Lauritsen and Hank Wilson, "DEATH RUSH: Poppers & AIDS", Pagan Press 1986.
16. Cooper, "Medical Officer Review...", p. 128.
17. Ibid. p. 34.
18. Ibid. p. 131.
19. Ibid. p. 39.
20. Harvey I. Chernov, Ph.D.; "Review & Evaluation of Pharmacology & Toxicology Data", p. 4.
21. Ibid. p. 7.
22. Ibid. p. 8.

Poppers & AIDS


Poppers* & AIDS

(With Annotated Bibliography)

John Lauritsen
Hank Wilson

New York 1986

*Nitrite inhalants


                            (The Verso page)

Poppers* & AIDS
(With Annotated Bibliography)

*Nitrite inhalants
by John Lauritsen and Hank Wilson

Cover design by Wulf.

Prepared in collaboration with the Committee to Monitor Poppers

55 Mason Street
San Francisco, CA 94102

This publication supersedes POPPERS & AIDS, by John Lauritsen and Hank Wilson, Second Edition (July 1985). The earlier work has been revised and considerably expanded.

Copyright 1986 by Pagan Press
All rights reserved
Printed in the USA

Library of Congress Catalog Card No. 86-60791
ISBN 0-943742-05-6







APPENDIX A: Koch's Postulates:
The Case Against LAV/HTLV-III's Being the Sole,
Sufficient, or Necessary Cause of AIDS

APPENDIX B: A Toxicologic Model

APPENDIX C: Occam's Razor: The Drugs Connection



Don't use poppers. This is the first and the last thing to be said about them.

Poppers are a liquid mixture of isobutyl nitrite and other chemicals, packaged in small bottles under such names as “Rush”, “Ram”, “Thunderbolt”, “Locker Room”, and “Crypt Tonight” (gallows humor?). Poppers are advertised and sold to gay men, who make up virtually the entire market for the commodity. When inhaled just before orgasm, poppers seem to enhance and prolong the sensation. With regular use, they become a sexual crutch, and many gay men are incapable of having sex, even solitary masturbation, without the aid of poppers.

Poppers have become an accepted, even obligatory part of the gay male lifestyle in some cities. The odor of poppers is ubiquitous in New York City bars, backrooms and baths. At gay discos, men shuffle around on the dance floor, zombie-like, holding popper bottles under their noses.

The subject of poppers is one which arouses intense emotions. Ordinarily rational men become hysterical when it is suggested that the nitrite inhalants are harmful to the health and may play a role in causing AIDS. This is understandable. Since poppers have become necessary for them to function sexually, giving up poppers would seem, at least in the beginning, like giving up sex itself.

Normally every drug in the U.S. must undergo extensive testing before it can be sold legally. Not poppers. They are subject to no testing or quality control whatsoever. In 1981, the Stanford Medical Laboratories tested some samples of different brands of poppers, and found them to contain kerosene, hydrochloric acid, and sulfur dioxide, among other impurities.


The biggest money-maker in the gay business world is believed to be the poppers industry. Gross profits were estimated to be $50 million in 1978, and may well be double or triple that by now. (Sigell 1978)

Poppers manufacturers have impudently labelled their product a “room odorizer”, with the astounding consequence that the federal Food and Drug Administration (FDA), the California and New York Departments of Health, and other government regulatory agencies have intransigently looked the other way. What a farce! Not even an idiot would use poppers as a “room odorizer”. Everyone knows that poppers are inhaled as a drug. A large and growing body of medical research indicates that poppers are dangerous, and almost certainly implicated in causing AIDS. And yet the government agencies blithely accept the lie that poppers are only a harmless “room odorizer”.

Why have the appropriate government agencies refused to regulate poppers in any way? We don't know, but it's doubtful that they really believe the “room odorizer” marketing subterfuge. If a drug like butyl nitrite can be marketed as a “room odorizer”, then anything could be sold as anything. Heroin could be sold as a mosquito-bite remedy (“for external use only”). Live hand grenades could be sold as “paperweights”.

It is commonplace that government regulatory agencies come to be controlled by the very industries they were intended to regulate. One recalls the many recent scandals pertaining to the Environmental Protection Agency (EPA) or, a couple of decades ago, the subservience of the U.S. Department of Health to the tobacco industry. The poppers industry has a large war chest, and they know how to “influence” government agencies.

Poppers are now illegal in New York State. On June 18, Governor Cuomo signed into law Assembly Bill #890, making it illegal to possess or sell “hazardous inhalants”, including amyl and butyl nitrite, that cause intoxication.

It can be anticipated that some gay men will protest the new law as an intrusion of the state into their private lives, an infringement of their right to pursue chemical pleasures. Such protests would be misguided. Anyone who has studied the medical literature on poppers can only applaud the New York State legislature and Governor Cuomo for having done the right thing. Poppers are dangerous, and they should never have been sold legally in the first place.

Poppers as co-factor for AIDS

At present, most if not all AIDS researchers believe that an important role in causing AIDS is played by a virus named Lymphadenopathy-Associated virus (LAV) by the French scientists who isolated it in 1983. (The same virus was “rediscovered” in 1984 by an American government scientist, Robert Gallo, who called it “HTLV-III”, by which name it is known, for political reasons, in the U.S.)

The LAV virus has so far failed to satisfy Koch's postulates; therefore, its role in causing AIDS remains a matter of conjecture. The designation, “AIDS virus”, is not scientifically justified; the most one can say at present is that the LAV virus is associated with AIDS: perhaps as primary cause, perhaps as a subsidiary co-factor, or perhaps only as a harmless marker.1

For several years, government agencies have discouraged any approaches to AIDS other than the single-infectious-agent hypothesis. Researchers who advanced drug abuse or multifactorial hypotheses tended to be ostracized and unfunded. After Robert Gallo's “discovery” of HTLV-III, it became obligatory to regard this as the primary or even sole cause of the Syndrome.

However, preliminary testing has shown that up to 80% of urban gay men have LAV antibodies, and yet only a minute percentage of them have developed AIDS. It would seem that LAV is not sufficient by itself to cause AIDS, that co-factors (like drug abuse) may be necessary for AIDS to develop.

Many AIDS researchers now believe that mere exposure to the putative virus is not sufficient to cause AIDS-that a necessary precondition may be an already weakened immune system. Attention is being focussed on possible co-factors in the lifestyles of gay men and IV drug users, the two major risk groups.

Toxic effects of amyl nitrite (the pharmaceutical predecessor of “Rush”, “Locker Room”, etc.) have been known for years. With the outbreak of the AIDS epidemic, medical researchers began to suspect that poppers may play a role in causing AIDS in gay men — either as the primary cause or in conjunction with other factors. (Durack 1981)

Few gay men, physicians, or AIDS researchers seem to be aware how extensive and powerful the evidence against poppers is. Anyone who has studied even a portion of the medical literature can only shake his head in amazement that this dubious commodity has not been banned — except in Massachusetts, Wisconsin, and, as of June 1985, New York State. (In Massachusetts, where poppers have been banned for years, only 378 cases of AIDS had been reported as of 31 March 1986. In contrast, there had been 6265 cases in New York, where poppers had been sold legally in sex shops, baths, discos, and even neighborhood smoke shops.)

The evidence against poppers has continued to accumulate. For several years, major articles in the most prestigious medical journals in the world have discussed the immunosuppressive and other harmful effects of poppers, and their possible role in causing AIDS. The question is no longer whether, but rather how much of a role poppers play in causing AIDS. Are poppers a relatively minor or a very major co-factor? So far as the effect of poppers on the health, there is no doubt that they are harmful. For some individuals, even a single episode of snorting poppers can be life-threatening.

The section that follows will summarize medical findings on poppers. However, the reader should bear in mind that this is a summary of hundreds of pages of reports and articles. Researchers concerned with the poppers connection should consult the Annotated Bibliography in Section II of this monograph.


The evidence against poppers comes from many different types of studies, and is remarkably consistent. Whether from epidemiological, mice, or laboratory studies, the data support each other in demonstrating the harmful properties of poppers and implicating poppers in the etiology of AIDS. Despite rumors which originated with the poppers industry in 1983, there is no evidence that could reasonably be interpreted as “exonerating” poppers.

Epidemiological studies

Unfortunately, we know very little about the characteristics of people with AIDS. Most of the published epidemiological studies of gay men with AIDS were conducted several years ago, and had serious shortcomings. CDC studies, in particular, tended to be poorly designed, executed, and analyzed. We cannot assume that gay men diagnosed as having AIDS in 1986 have the same profile as the first 50-100 gay men with AIDS, who were studied in 1981-1982.

In the absence of recent, large-scale, well-conducted epidemiological studies, one may give a cautious hearing to less “scientific” evidence, such as reports from those who have known many people with AIDS. Such evidence should be evaluated critically, though it may actually be worth more than the quantitative “data” from a poorly executed survey.
Following are a few epidemiological highlights:

• 96-100% of the gay men with AIDS used poppers, usually quite heavily. These men were also heavy users of many other “recreational” drugs, including amphetamines (“speed”), cocaine, heroin, quaaludes (“ludes”), LSD, barbiturates (“downers”), and ethyl chloride. (Friedman-Kien 1982, Haverkos 1982/1985, Jaffe 1983)

• Case-control studies have implicated poppers as a statistically significant and important risk factor for the development of AIDS. (Marmor 1982, Newell 1985)

• In gay men who do not (yet) have AIDS, popper usage is correlated with immunological abnormalities similar to those found in AIDS patients. (Goedert 1982)

• Among men with swollen lymph nodes (all of whom had used poppers), heavy popper users were more likely to develop AIDS. (Mathur-Wagh 1984/1986)

• A recent study compared two groups of gay men who were antibody positive to the LAV (HTLVIII) virus: people who were clinically sick with AIDS, and people who were not sick. Usage of the nitrite inhalants proved to be one of the most important risk factors for developing AIDS, and especially, Kaposi's sarcoma. The heavier the popper usage, the greater the risk. (Moss 1985)

• Leaders of People With AIDS, who have known hundreds of PWA's, state that most of them were heavily into drugs, and all of them used poppers.

• W.J. Wallace, the manager of the Mineshaft, stated in an interview, “I really don't know anybody who's had AIDS who hasn't used drugs.”

• Finally, there is the crucial point that for 5 years AIDS, unlike a truly communicable disease, has remained compartmentalized. Gay men accounted for three-quarters of the AIDS cases 5 years ago, and account for the same proportion now in 1986. Poppers are used by gay men.
They are used by very, very few straight men, and by virtually no women at all.


Two different experiments have demonstrated that poppers are mutagenic. That is, they cause genes to mutate. (Quinto 1980, Osterloh 1984) It is very unwise to inhale mutagenic substances, as almost all such substances are also carcinogenic. If nothing were known about poppers other than these two studies, they alone would be sufficient warrant for the categorical recommendation: Do not use poppers.


Organic nitrites like poppers combine with other substances to form deadly, cancer-causing compounds (N-nitroso compounds, nitrosamines — Jϕrgensen 1982, Newell 1984, Osterloh 1984). Danish scientists Karl Jϕrgensen and Sven-Olov Lawesson describe N-nitroso compounds as being so deadly as to have “the capacity to induce cancer after only one dose”.

Several AIDS researchers have suggested that poppers may play a role in causing the cancer, Kaposi's sarcoma, in gay male AIDS patients. KS is found in about half of the gay men with AIDS, but in a very small percentage of PWA's from the other risk groups. It is gay men who use poppers, not straight IV drug users or Haitians.

Blood cell studies (in vitro)
Several different laboratory experiments have shown that exposure of human blood cells to amyl, butyl or isobutyl nitrite causes sharp decreases in immunological function, as well as striking alterations in cell structure (“cytoplasmic protrusions with pseudopod-like extensions”, etc.). (Marmer 1982, Hersh 1983, Jacobs 1983)
One research team concluded:

“These abnormalities can help in explaining the role of amyl nitrite cellular toxicity in immunosuppressed male homosexuals.” (Marmer 1982)

Another research team stated:

“These in vitro studies strongly suggest that the inhalant nitrites may indeed be dangerous, and their use should be condemned by those physicians who treat patients who use these drugs regularly.” (Hersh 1983)

Mice studies

Powerful evidence against poppers comes from experiments on mice, which have firmly established that poppers suppress the immune system and are otherwise harmful in vivo (in a living animal).

• Five different studies found that exposure to amyl or isobutyl nitrite, either through injection or inhalation, caused immunological deficiency in mice. (Watson 1982, Neefe 1983, Lotzova 1984, Gangadharam 1985, and Ortiz 1985)
One research team concluded:

“The results of these studies indicate that immunosuppression should be added to the other reasons why isobutyl nitrite should not be used by man.” (Lotzova 1984)

One of these studies further found that the mice exposed to nitrite vapors suffered gross pathological lung damage, weight loss, and, most significantly, reversed T-cell ratios:

“Our studies do show that chronic inhalation of AN [amyl nitrite] can lead to an altered T-cell helper/suppressor ratio, the same phenomenon which occurs in AIDS victims. It does look, then, that there seems to be a link between AN inhalation and cellular immunity depression.” (Ortiz 1985)

• In a sixth study, mice exposed to low dosages of isobutyl nitrite vapors developed methemoglobinemia and thymic atrophy. (Lynch 1985) The first finding is relevant, since poppers are known to cause methemoglobinemia in humans (Horne 1979, Guss 1985) and since anemia is typically part of the AID Syndrome. (Methemoglobinemia is a form of anemia where the blood turns brown and where the oxygen supply to critical organs is reduced.) The finding of “thymic atrophy” is suggestive. Autopsies of AIDS victims show the thymus gland to be destroyed in 100% of the cases. No thymus gland, no immune system. Obviously any drug that destroys the thymus gland will play a role in causing AIDS.

• A seventh mice study could not be carried through to completion. Regardless of whether the isobutyl nitrite was ingested, inhaled, or injected, all of the mice died. (Maickel 1982)

T-cell ratios

Inhalation of amyl nitrite caused a depletion of the helper (T4) T-cells in mice (Ortiz 1985) and in humans (Gerblich 1984). Some researchers consider this condition — a reversed T-cell ratio — to be the primary immunological defect in AIDS patients.


Quite aside from the risk of getting AIDS, poppers are known to be hazardous to the health in many different ways. Poppers cause Heinz body cell anemia, methemoglobinemia, lung damage, serious skin burns, death or brain damage from cardiovascular collapse or stroke, dizziness, and headaches. Poppers have been used successfully to commit suicide (by drinking) and murder (victim gagged with sock soaked with poppers). (Sigell 1978, Horne 1979, Haley 1980, Dixon 1981, Romeril 1981, Guss 1985, Lynch 1985, Ortiz 1985)

AIDS: Why now?

The chronology is suggestive: Poppers became a fad among gay men beginning in 1972, just seven years before the first cases of AIDS began to be diagnosed. (Newell 1984)

*   *   *

It is obvious from the above that poppers are dangerous and should not be used by humans or other animals. In the context of the AIDS epidemic, when keeping one's immunological system up to par is a life or death matter, the only sane course of action is to stop using poppers immediately.

Risk-reduction guidelines

Even with considerable human resources and millions of dollars committed to finding a solution, it may very well take many years before researchers are able to describe, with scientific rigor, how AIDS is caused. In the meantime, it is imperative that intelligent guidelines for reducing the risk of getting AIDS, based on existing knowledge, be given now. Lives are at stake.

In light of what is known now, gay men should continue to follow “safe sex” guidelines. In conservative terms, this would mean either practising celibacy or limiting sex to simple body contact and mutual masturbation. The simple rule for safe sex is: “On me, not in me.”

At the same time, it is crucial for gay men to bolster their immune systems by living in a healthy way: eating nutritious food, getting enough sleep and rest, reducing stress, and getting plenty of exercise. They should avoid the use of any and all “recreational drugs” — especially including poppers.2


Centers for Disease Control. “An Evaluation of the Immunotoxic Potential of Isobutyl Nitrite”. MMWR, pp. 457-58, 64, 9 September 1983.

This news item briefly described an experiment in which mice were exposed to isobutyl nitrite vapors, in various concentrations, for time periods ranging from 3 to 18 weeks. It asserted, “None of the animals exposed to IBN showed any evidence of immunotoxic reactions”.

The poppers industry used this little item as the basis for an advertising campaign which claimed that poppers had been “exonerated”, and that there was no connection between poppers and AIDS.

When a report on the mice study was finally published two years later, it became clear that the MMWR account had been grossly misleading. The dosages administered were too low to test the hypothesis that poppers might be immunosuppressive or otherwise harmful to men who inhaled them as “recreational” drugs. The study had selected exposures “to mimic an occupational exposure setting...rather than to conduct brief, high level exposures to imitate exposure by nitrite abusers.” (See entries under Lewis and Lynch.)

It should be noted that other mice experiments (Gangadharam, Lotzova, Maickel, Neefe, Ortiz, and Watson) have demonstrated that mice exposed to alkyl nitrites do develop immunological deficiency, as well as being harmed in other ways.

The anonymous author(s) of the MMWR piece stress that the nitrite inhalants are not harmless, for “these drugs do have toxic effects”, and they proceed to list a number of toxic effects, ranging from “dizziness” to “sudden death”. They add that “their role as a cofactor in some of the illnesses found in this syndrome has not been ruled out.”

D'Eramo, James E. “Poppers: The Writing on the Wall”. New York Native, p. 9, 4-17 June 1984.

This article reports on recent findings that tend further to implicate the nitrite inhalants as playing a role in causing AIDS.

The popular media are currently touting the LAV/HTLV-3 virus as being the only cause of AIDS. However, D'Eramo reports that one of the French scientists who discovered the virus puts forward a multifactorial model of causation:

“Dr. J.C. Chermann (a member of the Parisian Pasteur Institute team that discovered the probable viral cause of AIDS - LAV-HTLV-3) presented a model for the development of AIDS during a lecture on May 22 at Sloan-Kettering Memorial Hospital in New York City. He believes that the T-cell population must be repeatedly stimulated with foreign antigens (like LAV, sexually transmitted diseases, and drugs) for full-blown AIDS to develop. Repeated usage of poppers may play an important role in the antagonistic stimulation of the helper T-cell population. According to Dr. Chermann's model, very limited or infrequent exposures to LAV would not in themselves lead to the development of full blown AIDS.”
D'Eramo concludes:

“The untoward effects of inhaling poppers are becoming clearly recognized, especially as a co-factor in the development of AIDS.”

Dixon, D.S.; Reisch, R.F.; and Santinga, B.S. “Fatal Methemoglobinemia Resulting from Ingestion of Isobutyl Nitrite, a ‘Room Odorizer’ Widely Used for Recreational Purposes”. Journal of Forensic Sciences, pp. 587-93, July 1981.

A clinical account of a 30-year old black male who died from “acute nitrite poisoning”. He had apparently swallowed some poppers liquid. Contains a description of unsuccessful emergency procedures used, results of the autopsy, as well as a discussion of other butyl nitrite-related fatalities and the various hazards of alkyl nitrite inhalant abuse.

Durack, David T. “Opportunistic Infections and Kaposi's Sarcoma in Homosexual Men”. New England Journal of Medicine, pp. 146567, 10 December 1981.

This lead editorial poses the question of why AIDS is apparently new, since both viruses and homosexuality are at least as old as history:

“Some new factor may have distorted the host-parasite relation. So-called ‘recreational’ drugs are one possibility. They are widely used in the large cities where most of these cases have occurred, and the only patients in the series reported in this issue who were not homosexual were drug users.... Perhaps one or more of these recreational drugs is an immunosuppressive agent. The leading candidates are the nitrites, which are now commonly inhaled to intensify orgasm.... Let us postulate that the combined effects of persistent viral infection plus an adjuvant drug cause immunosuppression in some genetically predisposed men.”

Friedman-Kien, Alvin E.; Laubenstein, Linda J.; Rubenstein, Pablo; et al. “Disseminated Kaposi's Sarcoma in Homosexual Men”. Annals of Internal Medicine. pp. 693-700, June 1982.

A study of 19 men with KS. “All of the patients had used amyl or butyl nitrite inhalants.”

Gangadharam, P.R.J.; Peruman, V.K.; et al. “Immunosuppressive Action of Isobutyl Nitrite” (Presentation to the International Congress on Immunopharmacology, Florence, Italy, May 1985.) (Also press release reported in various newspapers)

Researchers at the National Jewish Center for Immunology and Respiratory Medicine in Denver found evidence confirming long-held suspicions that the “recreational” use of nitrite inhalants (poppers) greatly increases the risk of developing the Acquired Immune Deficiency Syndrome (AIDS).

Their studies involved exposing mice to RUSH\ (isobutyl nitrite) “by inhalation in a closed environment, simulating the practice of the homosexual patient”. One group of mice was exposed to RUSH\ daily; another group, every other day; and a third group, twice per week. According to the principal investigator, P.R.J. Gangadharam, PhD, after breathing isobutyl nitrite the animals became highly susceptible to disease and death caused by Mycobacterium intracellulare. This group of organisms, related to tuberculosis, is among the leading killers of people with AIDS. Mice of the same breed, who were exposed to the bacteria but not to the drug, had far lower illness and mortality rates.

The Denver scientists also linked specific, dose-related immune-system damage to isobutyl nitrite exposure:

“The animals exposed to the compound had decreased numbers of lymphocytes and macrophages, blood cells that are important in defending the body against infections.”

Dr. Gangadharam made the point that only a very small percentage of people exposed to the putative AIDS virus (LAV) become sick, and even fewer develop AIDS. “This makes is very important to investigate other possible contributing factors.”

The researchers concluded:

“We believe our findings establish that inhaling isobutyl nitrite should be considered dangerous to homosexuals and others at high risk for developing AIDS.”

Gerblich, Adi A.; Campbell, Ann E.; Schuyler, Mark R. “Changes in T-cell Lymphocyte Subpopulations After Antigenic Bronchial Provocation in Asthmatics”. New England Journal of Medicine, pp. 1349-52, May 1984.

In this study it was found that some kinds of inhaled agents caused a depletion of the helper (T4) T-cells. Some researchers consider this condition--a reversed T-cell ratio--to be the primary immune defect in AIDS patients.

In a communication to Dr. D'Eramo of the New York Native, Dr. Gerblich stated: “The same results have been found upon inhalation of amyl-nitrites.”

Goedert, James J.; Neuland, Carolyn Y.; Wallen, William C.; et al. “Amyl Nitrite May Alter T Lymphocytes in Homosexual Men”. The Lancet, pp. 412-16, 20 February 1982.

This study collected clinical, virological, and immunological data on 2 homosexual men with KS and on 15 healthy homosexual volunteers. Both men with KS had been regular amyl/butyl nitrite users. Of the men who did not have KS, 8 were regular nitrite users (1-20 times per month) and the other 7 were not (i.e., fewer than 10 doses ever).

Immunological abnormalities were found in all of the nitrite users, but in only one of the non-users. The authors conclude:

“The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of KS and opportunistic infections in homosexual men.”

Guss, David A.; Normann, Sven A.; and Manoguerra, Anthony S. “Clinically Significant Methemoglobinemia from Inhalation of Isobutyl Nitrite”. American Journal of Emergency Medicine, pp. 46-47, January 1985.

A case report of a 21-year old gay man who almost died from methemoglobinemia which resulted from an episode of inhaling poppers. The night before admission to the emergency room he had swallowed methaqualone (Quaalude), had inhaled cocaine, and had inhaled 'Hardware' (isobutyl nitrite) every 2-3 minutes for a period of 5-6 hours. His skin was purplish (“cyanotic”), and he had “severe headache, nausea, vomiting, chest pain, and shortness of breath.” “Arterial blood gas samples were extremely dark.... Methemoglobin was 37% of all hemoglobin.” Emergency measures were successful; the patient survived, and was found to have normal methemoglobin reductase levels.

The authors comment:

“Compared with the patient reported by Horne and associates [see Horne entry], our patient presented with severe systemic symptoms, had a methemoglobin level of more than twice that previously reported, and had normal methemoglobin reductase levels. In addition, our patient presented more than 12 hours after his last exposure to nitrites. Considering that the estimated half-life of methemoglobin is 55 minutes, this suggests peak levels of methemoglobin were probably considerably greater than those measured.”

This report is important for two reasons: First, it demonstrates that life-threatening methemoglobinemia can result from butyl nitrite inhalation, even in an individual whose body has a normal ability to reduce methemoglobin. Second, it strongly suggests the possibility of drug interaction effects, whereby the combination of butyl nitrite plus one or more other “recreational” drugs may be much more deadly than any one of these drugs by itself.

Haley, Thomas H. “Review of the Physiological Effects of Amyl, Butyl, and Isobutyl Nitrites”. Clinical Toxicology, pp. 317-29, 1980.

Contains a two-page summary of “human toxicology” re nitrites. 115 references listed. A few 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. Hypertrophy of the left ventricle occurs in workers handling nitroglycerine, and they suffer from shortness of breath on undue exertion. 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.”

Haverkos, Harry W.; Pinsky, Paul F. et al. “Disease Manifestation among Homosexual Men with Acquired Immunodeficiency Syndrome (AIDS): A possible role of nitrites in Kaposi's sarcoma”. A study of the CDC AIDS Activity, Center for Infectious Diseases, 1982. Abridged version published in Sexually Transmitted Diseases, pp. 103-08, October-December 1985.

87 of the first cases of homosexual men with AIDS were classified according to disease manifestation: Kaposi's sarcoma (KS) only, Pneumocystis carinii pneumonia (PCP) only, or both KS and PCP. Each group was compared to the others as well as to controls from an earlier CDC study. (See Jaffe 1983.)

The researchers concluded that “using nitrite inhalants may be associated with the occurrence of KS in patients with AIDS.”

The Haverkos study gives us important information on the lifestyle characteristics of the homosexual men who were diagnosed as having AIDS in 1981 and early 1982. Dr. Haverkos and his colleagues found a high degree of drug abuse. Among the total 87 gay men with AIDS, the following levels of drug usage were recorded: Nitrite inhalants (poppers) - 97%, marijuana - 93%, amphetamines - 68%, cocaine - 66%, LSD - 65%, quaaludes - 59%, ethyl chloride - 48%, barbiturates - 32%, heroin - 12%, any drug intravenously - 17%.

Multiple drug usage was the rule: 58% of the subjects used five or more different “street drugs”. Furthermore, the 87 gay men with

AIDS tended to use their drugs heavily. Following are the median numbers of different days on which the various drugs were used: Marijuana - 720, nitrite inhalants - 384, amphetamines - 120, barbiturates - 96, quaaludes - 60, LSD - 36.

Hersh, Evan M.; Reuben, James M.; Bogerd, Hal; et al. “Effect of the Recreational Agent Isobutyl Nitrite on Human Blood Leukocytes and on in Vitro Interferon Production”. Cancer Research, pp. 1365-71, March 1983.

The effect of isobutyl nitrite on cellular immunological functions was studied. The experimenters found that minute quantities of isobutyl nitrite caused irreversible impairment of immunological function. They conclude:

“We speculate that these immunosuppressive effects, combined with the ability of nitrites to convert amines to nitrosamines, may be related to the development of opportunistic infections and Kaposi's sarcoma in homosexuals who use this agent.”

Dr. Hersh and his colleagues further state:

“These in vitro studies strongly suggest that the inhalant nitrites may indeed be dangerous, and their use should be condemned by those physicians who treat patients who use these drugs regularly.”

Horne III, McDonald K; Waterman, Michael R.; et al. “Methemoglobinemia from Sniffing Butyl Nitrite”. Annals of Internal Medicine, pp. 417-18, September 1979.

A man was admitted to a hospital emergency room, “complaining of a grayish complexion which developed after inhaling butyl nitrite”. He was diagnosed as having methemoglobinemia, a form of anemia where the blood turns brown, and where the oxygen supply to critical organs is reduced. Several months later, the same man reappeared, again suffering from methemoglobinemia, again after butyl nitrite inhalation.

The patient was found to be methemoglobin reductase deficient, as was his father.

An experiment was performed in which the patient and 6 non-familial subjects were asked to sniff butyl nitrite (Locker Room “room odorizer”) directly from the bottle for 12 minutes. As a result, the patient “clearly became gray”, and had high methemoglobin concentrations. The 6 normal subjects also developed methemoglobinemia, to a lesser degree. The authors conclude:

“Sniffing butyl nitrite theoretically could lead to significant methemoglobin accumulation even in normal subjects, if the nitrite exposure were intense or if inadequate time were allowed between nitrite inhalations for methemoglobin reduction. The risk of clinical methemoglobinemia would, of course, be much higher in a person whose methemoglobin clearance rate is abnormally slow and who therefore requires a longer interval between sniffs to reduce the newly formed methemoglobin.”

Jacobs, Richard F.; Marmer, Daniel J.; et al. “Cellular Immunotoxicity of Amyl Nitrite”. Journal of Toxicology- Clinical Toxicology, 20(5), pp. 421-449 (1983).

[Abstract] “Functional deficits in lymphocyte interaction following occasional or chronic exposure to inhaled nitrites may be a potential contributing but not the [primary] etiologic factor in the acquired immunodeficiency syndrome (AIDS). We evaluated the effect of amyl nitrite vapors on mononuclear cell function and demonstrated functional deficits and structural alterations in these cells. In this closed, in vitro system, exposure of cells to amyl nitrite for up to 30 minutes did not affect cell viability. The functional deficits demonstrated were: inhibition of lymphocyte erythrocyte (E) rosette formation, a suppression of lymphocyte mitogen (phytohemagglutinin) and antigen (cytomegalovirus) transformation, a block in the S, G2 and M phases of cell cycling and diminished cell cytotoxicity to CMV infected cells. These effects on cellular function were demonstrated following 5, 0, and 15 minutes of amyl nitrite vapor exposure; some effect on all cellular functions was demonstrated at 5 minutes. The structural alterations seen on scanning and transmission electron micrographs were: reduction of filopodia, smoothing of the cell profile, cytoplasmic protrusions with pseudopod-like extensions, an increase in rough endoplasmic reticulum with swollen cisternae, alterations in size and distribution of golgi components and exocytotic vesicles in the outer membrane of the nuclear envelope. These vesicles and increased membrane proliferation suggests an effect on the membrane synthesis mechanism in these cells. These effects may be a potential factor in the alterations of phenotypic markers on T Lymphocyte populations, as well as, a potential contributing factor in the functional deficit of mononuclear cells in patients with AIDS.”

Jaffe, Harold W.; Keewhan, Choi; Thomas, Pauline A.; et al. “National Case-Control Study of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia in Homosexual Men: Part 1, Epidemiologic Results”. Annals of Internal Medicine, pp. 145-51, August 1983.

In this study of the first 50 AIDS patients, 96% used nitrite inhalants (and this would be 100% if the 2 “non-users” had misunderstood the question). Moreover, the AIDS patients were extremely heavy users, with a median lifetime exposure to nitrite inhalants of 336 doses. Most of the AIDS patients were also heavy users of many other “recreational drugs”, including marijuana, cocaine, heroin, amphetamines (“speed”), barbiturates, quaaludes (“ludes”), LSD, ethyl chloride, and phencyclidine.

The control sample selected for this CDC study proved to be seriously flawed. Drawn from venereal disease clinics and private practices, many of the controls were far from healthy. Some had immunological abnormalities and swollen lymph glands, and several of them developed AIDS after the study was completed. Further, many of the controls appeared to belong to the “fast lane” segment of the gay male community, as witness such findings as that 51-60% of the controls were cocaine users, or that 21% of the private practice controls had been fist fucked.

Aside from the major sampling problems described above, the inherent bias of this study design is a bias towards unity. That is to say, the tendency would be falsely to overlook real risk factors, rather than falsely to identify risk factors that were not real. The authors of the study admit as much:

“The expected impact of these potential problems in control selection and classification would be to minimize differences between cases and controls rather than to create false differences.”

In light of the fatal flaws in sample design and selection, all analyses based upon comparison between the AIDS patients and the controls would be dismissed by most survey research professionals as “garbage in, garbage out”. The comparative data are worthless, and should be ignored. The authors of this study did draw comparative conclusions, but they were wrong to do so.

Jϕrgensen, Karl A. and Lawesson, Sven-Olov. “Amyl Nitrite and Kaposi's Sarcoma in Homosexual Men”. (letter) New England Journal of Medicine, pp. 1893-94, 30 September 1982.

The authors give the chemical formula whereby amyl or butyl nitrites can form carcinogenic N-nitroso compounds in the body — compounds so deadly as to have “the capacity to induce cancer after only one dose”.

They conclude:

“We therefore find it appropriate to suggest that amyl nitrite may cause Kaposi's sarcoma in homosexual men.”

Jϕrgensen's and Lawesson's theories are developed more fully in an article in the Danish medical journal, Ugeskr Laeger, of 13 December 1982).

Lewis, Daniel M.; Koller, Wayne; et al. “Subchronic inhalation of Isobutyl Nitrite in BALB/c Mice: II. Immunotoxicity Studies”. [See also Lynch 1985 below.] Journal of Toxicology and Environmental Health, pp. 835-47, 1985.

This is a belated report on the research conducted in 1982-83, which the CDC newsletter MMWR of 9 September 1983 had summarized as indicating no “evidence of immunotoxic reactions”. (See Centers for Disease Control 1983.) The MMWR news item was used by the poppers industry as proof that poppers had been “exonerated”. As reports on other experiments began to appear (Gangadharam 1985, Lotzova 1984, Neefe 1983, Ortiz 1985, and Watson 1982), all finding that exposure to alkyl nitrites was immunosuppressive and otherwise harmful for mice, the CDC/National Institute for Occupational Safety and Health study became “odd man out”.

Now that a report on the study has finally been published, it is clear why the government researchers failed to find “immunotoxicity”, when all of the independent researchers did find it. The dosages administered, via inhalation of vapors, were far too low. The study, in effect, evaluated the effect of nitrite vapors approximating levels to be encountered as background exposure (“room odorizer”, workers in a poppers factory), rather than those encountered when using poppers as a drug (i.e., inhaling directly from the bottle). The study is thus in the tradition of the “Poppers Bible”. (See entry under Nickerson.) At the end of their “discussion”, Lewis et al. issue a revealing disclaimer:

“The relevance of these dosages to human usage of these compounds is uncertain because persons who abuse aliphatic nitrites recreationally would have intermittent exposures of variable frequency at very high dosages with chemicals of unknown purity. Thus, this study did not attempt to model the recreational use of these drugs [emphasis added], but rather to simply evaluate the immunotoxic potential, if any, of these compounds.”

Lotzovà, Eva; Savary, Cherylyn A.; Hersh, Evan M.: et al. “Depression of Murine Natural Killer Cell Cytotoxicity by Isobutyl Nitrite”. Cancer Immunology Immunotherapy, pp. 130-134, vol. 17, 1984.

This important mice experiment demonstrated that isobutyl nitrite was NK-cell-suppressive in vivo after intravenous administration and, most importantly, also after inhalation.

In their “discussion” the authors state:

“Since in experimental animals NK cells have been implicated in the mediation of immune surveillance against tumors and resistance to various types of infections, the depression of NK-cell cytotoxicity by this agent could underlie the susceptibility of homosexual men to opportunistic infection and Kaposi's sarcoma. Furthermore, the observation that cytotoxic potential of activated NK cells was also reduced by this agent suggests that an attempt to augment NK-cell activity to promote resistance to infections and malignant disease in patients with severe immunodeficiency syndrome could fail in patients who continue to use isobutyl nitrite. Since a multifactorial depression of immunity and a certain duration of this depression probably sets the stage for successful infection of the presumed AIDS agent, the continued and prolonged use of isobutyl nitrite may play an important role in AIDS.”

They conclude:

“The results of these studies indicate that immunosuppression should be added to the other reasons why isobutyl nitrite should not be used by man.”

Lynch, Dennis W.; Moorman, William J.; et al. “Subchronic Inhalation Toxicity of Isobutyl Nitrite in BALB/c Mice: I. Systemic Toxicity”. [See also Lewis 1985 above.] Journal of Toxicology and Environmental Health, pp. 823-33, 1985.

This CDC/NIOSH study was intended to “present the toxicologic results of subchronic exposures of BALB/c mice to inhaled IBN.” (“Subchronic” apparently means something like “less than acute”.)

The salient point of their methodology is that the dosages administered were low, simulating those experienced by workers in a poppers factory3 (or by a feeble-minded individual using poppers as a “room odorizer”). Lynch et al. are reasonably candid in making their disclaimer:

“Exposures were selected to mimic an occupational exposure setting in order to fill this gap in the existing literature, rather than to conduct brief, acute high-level exposures to imitate exposure by nitrite abusers.”

In light of the low dosages administered, it would not have been surprising if the mice had suffered no ill effects whatever, but this was not the case. The main toxic effects observed were mild damage to the lung tissues and the formation of methemoglobin. In addition, some of the mice developed thymic atrophy. The finding of methemoglobinemia is relevant, since poppers cause methemoglobinemia in humans (see Dixon, Guss, and Horne entries) and since anemia is typically part of the AID Syndrome. The finding of thymic atrophy is most suggestive: in autopsies of AIDS victims, the thymus gland is found to be destroyed in 100% of the cases. No thymus gland, no immune system. Obviously any drug that destroys the thymus gland will play a role in causing AIDS.

Maickel, Roger P. “Acute Toxicology of Butyl Nitrite”. Research Communications in Chemical Pathology and Pharmacology, 26:75-83, 1979.

This paper discusses laboratory techniques for analyzing the various butyl nitrites. Butyl nitrites were administered intravenously to mice, with liver damage and death resulting.
“Administration of isobutyl , n-butyl, sec-butyl or tert-butyl alcohols to mice produced similar hepatoxicity, suggesting that butyl alcohols may play a role in the hepatotoxicity observed after sBN or tBN administration.”

___ (interview). Moneysworth, January, 1982.


CHICAGO — Butyl nitrite — a legal but potentially lethal substance used to enhance sexual pleasure and drive disco dancers to ecstatic frenzy — is creating a new type of hazard, a toxicologist warns.

“If you get enough of it in your body, the chances of saving you are zero,” Purdue University professor Roger Maickel says of the chemical marketed variously as “Rush”, “Locker Room”, “Climax”, and “Discorama”. “And you may be an unwitting victim,” he adds. “It has been reported that these compounds are sprayed out over disco floors to rev up dancers.”

Although no deaths from inhalation have been reported, Maickel says, in the last year there have been at least two reported deaths from swallowing the drug.

He says a Purdue study found butyl nitrites were fatal to mice in fairly small doses. “The blood turns brown — it can't carry oxygen,” he says. “What's interesting is that the butyl nitrites were fatal no matter how they were administered — orally, by injection or just by exposing the mice to the compound in the air.”

Government agencies have not banned butyl nitrite, he says, because they have not been marketed as drugs. “Some federal agency ought to take a stand,” Maickel asserts, “before there is a spate of deaths that could have been avoided.”

Marmer, D.J.; Jacobs, R.F.; and Steele, R.W. “In Vitro Immunotoxicity of Amyl Nitrite.” Clinical Research, p. 5, vol. 30, no. 5, 1982.

Exposing mononuclear cells to amyl nitrite vapors resulted in various cellular abnormalities. The authors conclude:

“These abnormalities can help in explaining the role of amyl nitrite cellular toxicity in immunosuppressed male homosexuals.”

Marmor, Michael; Friedman-Kien, Alvin E.; Laubenstein, Linda; et al. “Risk Factors for Kaposi's Sarcoma in Homosexual Men”. The Lancet, pp. 1083-87, 15 May 1982.

A study of 20 homosexual men with KS and 40 healthy controls. All  of the men with KS had been nitrite users. Multivariate analysis indicated that use of amyl nitrite was an independent and statistically significant risk factor for KS.

In the light of their data, the authors consider a tenable hypothesis to be:

“Use of amyl nitrite may have caused Kaposi's sarcoma either by directly causing immunosuppression, thereby allowing expression of a sexually transmitted oncogenic virus; or by allowing an unknown carcinogenic agent, otherwise controlled by the immune system, to operate; or by acting as a direct or metabolically activated carcinogen.”

Mathur-Wagh, Usha; Enlow, Roger W.; et al. “Longitudinal Study of Persistent Generalised Lymphadenopathy in Homosexual Men: Relation to Acquired Immunodeficiency Syndrome”. The Lancet, pp. 1033-38, 12 May 1984.

The authors conducted a 30-month tracking study (commenced in February 1981) of 42 homosexual or bisexual men with persistent lymphadenopathy, not attributable to an identifiable cause.

Although intravenous drug users were excluded from the sample, “Non-parental [non-needle] recreational use of drugs, including amphetamines, marijuana, and cocaine, was common, and all had inhaled nitrite.” (emphasis added)

In the course of the study, 8 subjects (19%) developed AIDS. Previous heavy nitrite inhalant use proved to be the most important factor distinguishing the 8 patients who developed AIDS from the 34 who did not.

“The nitrite use/outcome association was still statistically significant (p<0.01) after adjustment for numbers of sexual contacts. The contacts/outcome association was only marginally significant after adjustment for nitrite use (p<0.1).” [In other words, based on this study, nitrite inhalant use is implicated more strongly than multiple (100+/year) sexual partners as a factor in causing AIDS. “Promiscuity” might therefore be regarded as a marker for the use of poppers, rather than the other way around.]

Mathur-Wagh, Usha; Mildvan, Donna; et al. “Follow-up at 4 1/2 Years on Homosexual Men with Generalized Lymphadenopathy”. (letter) New England Journal of Medicine, 12 December 1985.

The authors report on their study of 42 male homosexual patients with lymphadenopathy (unexplained and persistent lymph gland swelling). They had observed these patients medically for four and a half years, making this the longest tracking study of its kind so far.

By this time, twelve of the 42 patients (29%) had developed full-fledged AIDS. A previous history of moderate to heavy use of nitrite inhalants appeared to be implicated in causing these men to develop AIDS, and in particular, Kaposi's sarcoma.

“Nitrite inhalants may act alone or in combination with other, as yet unidentified cofactors after AIDS retrovirus-induced immunodeficiency, by promoting the specific disease manifestation of Kaposi's sarcoma.”

Mayer, Kenneth H. “Inhalation-Induced Immunosuppression: Sniffing Out the Volatile Nitrite-AIDS Connection”. Pharmacotherapy, pp. 235-36, September 1984.

In this editorial, accompanying the article by Guy Newell and colleagues (which see), Mayer states:

“Newell at al. develop several interesting lines of reasoning as to how nitrite inhalation could be clinically important. Volatile nitrite inhalation might potentiate the development of AIDS because of perianal vasodilation that could enhance the absorption of an immunosuppressive substance or infectious agent. The nitrites could be significantly immunosuppressive themselves, or the conversion to nitrosamines could result in increased mutagenic or carcinogenic events. These are plausible theories that are not deflated by the elucidation of HTLVIII/LAV....”

“They have raised sufficient concern about the use of volatile nitrites to warrant unequivocal disapproval of the use of these drugs at this time.”

Mayer, Kenneth and D'Eramo, James. “Poppers: A Storm Warning”. Christopher Street, pp. 46-49, issue 78.

A useful summary of medical knowledge about poppers, their deleterious side effects and possible role in the etiology of AIDS.

Moss, Andrew. “A Case-Control Study of Risk Factors for AIDS in San Francisco”. (Presentation to the CDC AIDS Conference in Atlanta, 15 April 1985)

This study compared two groups of gay men who were antibody positive to the LAV (HTLV-III) virus: people who were clinically sick with AIDS, and people who were not sick.

Usage of the nitrite inhalants proved to be one of the most important risk factors for developing AIDS, and especially, Kaposi's sarcoma. The heavier the popper usage, the greater the risk.

Neefe, J.R.; Ganjii, A.; and Goedert, J.G. “Daily Amyl Nitrite Inhalation Decreases Mouse Splenocyte Response to Concanavalin A”. (abstract 3850) Federation Proceedings 42 (4): 949, 5 March 1983.

Inhalation of amyl nitrite for 2 minutes, 5 days per week, caused progressive immunosuppression in mice. “After as little as 5 days exposure, a trend to decreased response to the T cell nitrogen Con A... was noted.”

The authors conclude:

“These data suggest that nitrites may have a primary or contributory role in AIDS.”

Newell, Guy R.; Adams, Stephen C. et al. “Toxicity, Immunosuppressive Effects and Carcinogenic Potential of Volatile Nitrites: Possible relationship to Kaposi's Sarcoma”. Pharmacotherapy, pp. 235-36, September 1984.

This article provides an overview of research demonstrating the adverse effects of poppers. Especially useful for its chronological history of the abuse of nitrite inhalants as recreational drugs and for data on how deadly, cancer-causing N-Nitroso compounds are formed by an interaction of nitrites with any of a long list of common drugs and chemicals, including artificial sweeteners, antihistamines, pain killers and methadone.

Newell, Guy R.; Mansell, Peter W.A.; Wilson, Michael B.; et al. “Risk Factor Analysis among Men Referred for Possible Acquired Immune Deficiency Syndrome”. Preventive Medicine, pp. 81-91, January 1985.
In this case-control study, lifestyle factors of 31 homosexual men with AIDS were compared with those of 29 symptom-free homosexual men. The object was to identify risk factors for developing AIDS.

Use of nitrite inhalants proved to be a highly significant risk factor for the development of AIDS. Further, the nitrite inhalants showed a “dose-response gradient”: the heavier the nitrite usage, the greater the risk of developing AIDS. For the nitrite inhalants, the “odds ratio” (OR) increased from 4.0 for occasional users [once per 6 months to once per month] to 6.3 for frequent users [once per month or more often].

Other statistically significant (95% confidence level) odds ratios were found for cigarette smoking (OR = 3.4), marijuana use (OR = 3.7), frequenting bathhouses (OR = 7.6) prior syphilis (OR = 3.4), and fist-rectal sexual practices (OR = 3.5).

The authors compare their results with those of the other two case-control studies of homosexual men (Marmor 1982 and Jaffe 1983), and note that both of these also identified use of poppers as a risk factor for the development of AIDS. “We confirmed the finding of nitrite inhalation as a significant risk factor for KS/OI.... In the CDC study, lifetime use of nitrites was significantly greater among patients than for either of the control groups.”

They comment:

“We believe there are several compelling reasons for considering nitrite inhalation a possible causal factor for development of AIDS and KS/OI. These are (a) volatile nitrites used as recreational drugs have been shown to be immunosuppressive both in vitro and in vivo; (b) metabolic properties of N-nitroso compounds produce mutagens, teratogens, and carcinogens; (c) of 290 N-nitroso compounds tested, 252 (87%) are carcinogenic; (d) of 39 different animal species, none is known to be resistant; (e) N-nitroso compounds are among the most highly potent chemical carcinogens for animals; (f) their use is extremely common among male homosexuals; and (g) a definite dose-response relationship was shown by both Marmor et al. and us. The combination of cigarette smoking, marijuana use, and nitrite inhalation could predispose the lungs to opportunistic infections.”

Nickerson, Mark; Parker, John O.; Lowry, Thomas P.; and Swenson, Edward W. “Isobutyl Nitrite and Related Compounds”. 95 pages. Published by Pharmex, Ltd., 1978.

Known as the “Poppers Bible”, this work was commissioned by the late W. Jay Freezer, chair of Pharmex, Ltd, the company that makes the popper brands Rush and Bolt, at a cost of $200,000. It was instrumental in a decision by the California Department of Health to permit poppers to be sold free from regulation, testing, or control of any kind, provided they were advertised as “room odorizers” or “incense”. As a piece of special pleading published by the poppers industry, the scientific value and credibility of this study are nil. Nevertheless, it is still cited by defenders of poppers.

The falseness of this report is revealed in the very first sentence:

“For the past several years there has been considerable controversy regarding the use of butyl nitrite in consumer products used for odorizing purposes.” [Emphasis added.]

This is the tack of the hired “experts” (each of whom has an MD degree): to lend credence to the claim that poppers are used as “room odorizers”, and to determine whether or not they are safe when so used. Not surprisingly, given the underlying “room odorizer” premise and the interests of their patron, the authors conclude that the product studied (not referred to as “poppers”) is quite safe. They enthusiastically fulfill their assignment:

“It is difficult to envision any product with a better record of public safety.”

Appendix V, by Parker, is a study of the effects of ambient popper fumes upon workers in a poppers factory. In his Introduction, Parker begins by stating, “Butyl nitrite and isobutyl nitrite are employed in preparations intended for use as room odorizers.” [Emphasis added.] Then, he states the purpose of his “study”:

“This study was undertaken to ascertain whether the inhalation of isobutyl nitrite in concentrations far in excess of those encountered in its normal usage [emphasis added] would have any significant clinical, circulatory or hematological effects.”

Through this verbal trickery, Parker has defined “normal usage” of poppers as being usage as a room odorizer. His conclusion 6 pages later is hardly unexpected: “This study has shown that inhalations of isobutyl nitrite, far in excess of those encountered during the normal use<><> [emphasis added] of this agent, exert no harmful clinical, cardiovascular or hematological effects.”

It is stated in the Preface, “This study took nearly two years to accomplish....” It seems odd that in two years of collaboration with Pharmex, Ltd., the academics who wrote this study were not informed that Rush, Bolt, etc. are used as drugs, not as room odorizers. The “room odorizer” claim is a lie, and the report as a whole is therefore a lie. These lies may have led to the deaths of many men.

Ortiz, Jesse S. and Rivera, Vilma L. “The Effect of Amyl Nitrite on T-Cell Function in Mice”. (Presentation to the American Public Health Association Convention, November 1985)

Mice were exposed to amyl nitrite inhalation 5 days a week, for 21 weeks. A matched control group of mice was maintained in an identical environment, but was not exposed to amyl nitrite.

The main findings were:

1. In the mice exposed to amyl nitrite: “A decrease in mean body weight was found after accumulative exposure time of 8 weeks, and this decrease continued until the end of the experiment. After 21 weeks of exposure time both body weight and weight gain were significantly decreased (p<0.2; p<0.01).”

2. “Mice exposed to AN had extensive pathological damage to the lungs and this damage was statistically significant (p<0.01). The gross pathology observed in the lungs of the AN-exposed group consisted of: a) hemorrhagic spots, b) petechiae all over the lungs, c) collapsed consolidated sections which were red and showed the appearance of an emphysematous lung, and d) air pockets with large air bubbles.... It is therefore apparent that the chronic use of amyl nitrite may have profound pathological damage to the lungs.”

3. Amyl nitrite inhalation caused a severe depletion of the helper T-cells, and consequently, an inverted T-cell helper/suppressor ratio. In the group of mice exposed to AN, the helper/suppressor ratio was only 0.25, whereas in the control group it was 1.69 (p<0.01). A significant degree of correlation (p<0.01) was found between T-cell ratio and the independent variables (body weight and weight gain) in the exposed group, whereas in the control group, no significant degree of correlation between these variables was found, thus further confirming the causal relation between AN inhalation and the reversed helper/suppressor T-cell ratio.

“Our studies do show that chronic inhalation of AN can lead to an altered T-cell helper/suppressor ratio, the same phenomenon which occurs in AIDS victims. It does look, then, that there seems to be a link between AN inhalation and cellular immunity depression.”

Osterloh, J. and Goldfield, D. “Butyl Nitrite Transformation In Vitro, Chemical Nitrosation reactions, and Mutagenesis”. Journal of Analytical Toxicology, pp. 164-69, July/August 1984.

The authors studied “the transformation of n-butyl nitrite added to whole blood, plasma, and water, using anion exchange high pressure liquid chromatography, spectrometry, and gas chromatography”.

They confirmed the findings of Quinto (which see) that butyl nitrite is mutagenic (and therefore likely to be carcinogenic as well).

Osterloh and Goldfield conclude:

“Chemical reactions indicate that nitrosation of amines is possible and mutagenicity studies have been confirmed. Because these experiments indirectly suggest the potential in vivo nitrosation by butyl nitrite, the authors join Jϕrgensen and Lawesson in warning that use of alkyl nitrite may be hazardous and requires further study.”

Quagliarello, Vincent. “The Acquired Immunodeficiency Syndrome: Current Status”. Yale Journal of Biology and Medicine, pp. 443-52, 1982.

This lead editorial reviews current research and theories, stressing the likelihood that amyl nitrite may be a causative factor, perhaps in conjunction with an infectious agent.

Quagliarello puts strong emphasis on the “drug hypothesis”, making the point that all of the non-homosexual AIDS cases were drug abusers. He refers to studies of heroin addicts “demonstrating evidence for opiate receptors on lymphocytes in vitro, as well as depression of T-cell number and function in vivo opiate addicts.”

Quinto, I. “The Mutagenicity of Alkylnitrites in the Salmonella test”. (translation from the Italian) The Institute of Biological Chemistry, Faculty of Medicine, University of Naples. Bolletino Societa Italiana Biologia Sperimentale, 1980, 56:816-20.

The effects of 5 forms of alkylnitrites on bacteria were studied, using “the Salmonella method, which is currently believed to be one of the best tests of mutagenesis”.

Both amyl nitrite and isobutyl nitrite were found to be direct mutagens, “with or without metabolic activation”. This finding is significant because:

“During the last 5 years, the problem of the correlation that exists between mutagenicity and carcinogenicity in chemical products has been studied with great attention. The results of the experiments obtained up till now (about 90% of chemical carcinogens are mutagens) have revealed that an actual correspondence exists between the two properties.”

Quinto concludes by relating his findings to the abuse of nitrite inhalants in the U.S.:

“The originality of our experiment is the presentation of alkylnitrites as a new class of chemical mutagenic agents and the importance of stressing the oncogenous risk linked to the use and abuse of amyl nitrites and isobutyl nitrites. In particular, isobutyl nitrite has had a rapid and increasing diffusion as a drug on the American market during the past five years. In fact, in 1978, the companies manufacturing the chemical estimated that about five million Americans used their product. The accusation of mutagenicity of this compound urgently calls for a more thorough inquiry into the oncogenous risks to which millions of users of this drug may be exposed.”

Romeril, K.R.; and Concannon, A.J. “Heinz Body Haemolytic Anaemia after Sniffing Volatile Nitrites”. The Medical Journal of Australia, pp. 302-03, 21 March 1981.

The authors report on two separate cases in which young Australian men developed Heinz body hemolytic anemia (anemia characterized by excessive destruction of red blood cells). Each of the men had used amyl nitrite over the two days before being hospitalized, and had been regular users of the drug for at least 3 months, sometimes sniffing the drug up to 20 times per session. Each of them would feel “tired and washed out” for several days after a sniffing episode.

Extensive tests ruled out other possible causes of the Heinz body hemolytic anemia. In both cases the men were warned of the dangers of amyl nitrite sniffing and were released from the hospital. Both men returned to the hospital after one month, during which time they had avoided the use of poppers; their blood was tested again: the anemic condition had gone away, and their red blood cell morphology was normal.

Sigell, Leonard T.; Kapp, Frederic T. et al. “Popping and Snorting Volatile Nitrites: a Current Fad for Getting High” American Journal of Psychiatry, pp. 1216-18, October 1978.

A valuable pre-AIDS history of volatile nitrite drug abuse, with insights into the business aspects.

“Common settings in which these agents are used include the bedroom, parties, backrooms of pornographic bookstores, pornographic theaters, bars, and dance floors. Some users have told us that a few discotheques use special lighting effects to indicate that they are about to spray nitrite fumes over the dance floor.” [emphasis added]

“The snorting of volatile liquid nitrites for hedonistic purposes has created a large business estimated to total $50 million a year. Sales have reportedly averaged 100,000 bottles a week in one city alone.”

Sonnabend, Joseph; Witkin, Steven S.; Purtillo, David T. “Acquired Immunodeficiency Syndrome, Opportunistic Infections, and Malignancies in Male Homosexuals: A Hypothesis of Etiologic Factors in Pathogenesis”. Journal of the American Medical Association, pp. 2370, 6 May 1983.

This article, an influential statement of the “multifactorial hypothesis”, takes issue with the prevailing view “that a yet-to-be-identified virus causes AIDS”. The authors develop a model whereby “Multiple factors, rather than a novel virus, probably induce AIDS”.

The main emphasis in this model is placed upon the exposure of “a subset of men to the immunosuppressive impact of sperm and CMV”. However, various other potentially immunosuppressive co-factors are considered, including “the recreational use of drugs”.

The important point is made that the etiology of AIDS in homosexual men may not be identical to the etiology of AIDS in other risk groups:

“We cannot, at this time, explain why AIDS is thought to be occurring in Haitians, hemophiliacs, and others. Acquired immunodeficiency has many causes, including malnutrition, hormonal alterations, use of opiates and other IV drugs, and acute viral infections.”

Walters, C.L. “The Exposure of Humans to Nitrite”. Oncology, pp. 289-296, vol. 37 (1980).

This article does not deal with the nitrite inhalants, but rather nitrite in food and the environment in general. Nevertheless, it makes an important point relating the intensity of nitrite exposure to the carcinogenic potential. It seems the potential for formation of the deadly, carcinogenic N-nitroso compounds is much greater from a brief, high-level dosage (the situation involved in snorting poppers), than from a longer, low-dosage exposure.

“Since the rate of nitrosation of an amine is dependent on the nitrite concentration to a power of greater than unity, it is probable that nitrite ingested in one application over a short period will be more active in the synthesis of N-nitroso compounds than a continuous supply at lower concentrations over long periods.”

Waterson, A.P. “Acquired Immune Deficiency Syndrome”. British Medical Journal, pp. 743-46, 5 March 1983.

In evaluating theories on the etiology of AIDS, Waterson considers the most promising to be:

“Firstly, the 'hot bed' theory argues that the traffic in human material in certain quarters by abnormal routes has reached such a level that, combined with the effects of drug abuse of various kinds, the sheer weight of chemical and microbial insult to the body in general, and to T lymphocytes in particular, goes beyond the tolerable limit. Eventually irreparable damage is sustained, which becomes manifest clinically in one or other of the variety of components of the syndrome.”

“Secondly, the drug theory points to drug abuse as the common denominator between the non-homosexuals and the main mass of patients. Much attention has focused on amyl and butyl nitrite as relative newcomers to the scene, but they are scarcely enough alone to cause all the damage.”

Watson, E. Sue; Murphy, James C. “Use of Amyl Nitrite May Be Linked to Current Epidemic of Immunodeficiency Syndrome”. Unpublished letter sent to the Journal of the American Medical Association, October 1982.

The authors report on an experiment which investigated the “effects of amyl nitrite on the primary humoral and cellular immune responses of mice”.

“Groups of mice were exposed to a single capsule of amyl nitrite (Vaporole\, 0.3 ml capsule, Burroughs Wellcome\) in an 18 liter sealed container for 4 minutes, twice daily for 5 consecutive days beginning the day of immunization. The humoral immune response to sheep red blood cells was normal in mice exposed to amyl nitrite. However the cellular response to DNFB was reduced by 30-45% in mice exposed to amyl nitrite.”

Dr. Watson also sent a letter to Robert McQueen , Editor of the Advocate, in which she stated:

“Our studies show that amyl nitrite strongly suppresses the segment of the immune system (cellular immunity) which normally protects individuals against Kaposi's sarcoma, Pneumocystis pneumonia, herpes virus, Candida, amebiasis, and a variety of other opportunistic infections. The upshot of this research is that persons using nitrite inhalants may be at risk for development of AIDS.... Publication of this letter in the Advocate will serve to alert the community to the health risks of using amyl nitrite. I hope you will see fit to include this information in the news section of the Advocate.”

After receiving no response from the Advocate, Dr. Watson telephoned Editor McQueen. She was told, “We're not interested”. It may be noted here that:

1. The Advocate was interested in AIDS, as several pages in every issue were devoted to this topic.

2. Since the Advocate is the world's largest gay paper, tens of thousands of gay men looked to it for guidance on how they could reduce their risk of getting AIDS.
3. For years the poppers industry had been the Advocate's largest advertiser.4



According to a 1978 study, the poppers industry was grossing $50 million a year--a figure which may well have doubled or tripled since then. (Sigell 1978)

In a 1981 article5, Arthur Evans cited some disturbing aspects of the poppers industry. In 1978 a major poppers manufacturer, W. Jay Freezer6, hired “experts” (at a cost of $200,000) to prepare a study which concluded that butyl nitrite products were safe “when used for odorizing purposes”. 7  On the basis of this impudently irrelevant study, the California Department of Health permitted poppers to be sold, free of any regulation, testing, or control, provided only that the products be advertised as “room odorizers or incense”.

Evans charges:

“In fact, both the popper makers and the California Department of Health committed a criminal fraud. By hiding behind the lie that poppers are being used as a room odorizer or incense, they have completely circumvented the normal safety net of testing which every drug in this country must be subject to in order to be sold.”

The point to be noted here is that the poppers industry can afford to spend large amounts of money in “influencing” research, government agencies, and public opinion, and was apparently quite successful with the California Department of Health.

A major campaign of “disinformation” commenced on 1 April 1983, when a press release was issued by Joseph F. Miller, “president of Great Lakes Products, Inc., the nation's largest manufacturer of nitrite-based odorants”. It was entitled, “U.S. Government Studies Now Indicate that Nitrite-Odorants Not Related to AIDS!” [New Footnote]

According to Miller, “the assistant director of the Center for Infectious Diseases (a part of the Centers for Disease Control in Atlanta), Dr. James Curran, invited him to Atlanta in late November of last year to discuss the work being done by CDC relative to its AIDS investigations”. [If true, this meeting would be a very serious indiscretion on Curran's part, raising the possibility of collusion between the poppers industry and CDC officials.] According to Miller's press release, the CDC assured him that “no association exists between nitrite-based odorants and AIDS”.

In a charming exercise of equivocation, Miller's press release states:

“Although his company does not advocate the misuse of HARDWARE or QUICKSILVER as inhalants, Miller says the company is greatly relieved to know that recent Government studies clearly show that such misuse poses no health hazard.”

Six months later (27 September 1983) Dr. James Curran sent an angry letter to the poppers manufacturer, with a copy to the Advocate (which never printed it). Curran did not deny having met with Miller in Atlanta, but he objected strongly to some of his statements:

“Other health hazards from misuse of these drugs have been documented. Your press release and advertisements in the Advocate are misleading and misrepresent the CDC findings and their implications.”

Curran's letter concludes:

“While it is unlikely that nitrites will be implicated as the primary cause of AIDS, their role as a cofactor in some of the illnesses found in this syndrome has not been ruled out. I must insist that you discontinue the misuse and misinterpretation of CDC findings.”

Comment: No study has ever been done, as of November 1982 or subsequently, that could reasonably be interpreted as “exonerating” poppers — as demonstrating, in the words of Miller's press release, that “no association exists between nitrite-based odorants and AIDS”. The little MMWR news item (CDC 1983), which asserted an absence of “immunotoxic reactions” in mice exposed to popper fumes, was grossly misleading. When the study was finally reported on, two years later, it turned out that the mice had been exposed to low dosages intended to “mimic an occupational exposure setting” rather than the much higher dosages that would “imitate exposure by nitrite abusers”. (Lewis 1985, Lynch 1985) No fewer than six other mice studies (Gangadharam 1985, Lotzova 1984, Maickel 1979, Neefe 1983, Ortiz 1985, Watson 1982) have demonstrated that exposure to amyl, butyl, or isobutyl nitrite is highly immunotoxic and otherwise harmful to mice.

The CDC weasels on poppers

For several years the Committee to Monitor Poppers has regularly sent copies of research to the CDC and other public health agencies. On 21 April 1985, Hank Wilson of the Committee to Monitor Poppers wrote a letter to Dr. James Curran, requesting that the CDC assist in the formulation of risk reduction guidelines by issuing a statement condemning the use of poppers:

“There should be no question that popper use is quite extensive among gay males. Inhalant nitrites continue to be marketed and promoted to the gay male community as if they had no harmful health effects, nor any role in the development of AIDS.”

“CDC should issue an alert to popper users. Popper users need to know that initial research indicates that poppers may be immunosuppressive. Users need to know that epidemiological research links poppers and KS. Users need to know that inhaling nitrites may result in cellular changes which make them vulnerable to an AIDS virus infection. A warning can be issued with the qualification that 'more research is needed', but the least CDC can do is to alert the popper users about what is already known. Better to err on the side of caution than to say nothing.”

Curran responded with a most evasive letter:

May 6, 1985

Dear Mr. Wilson:

Thank you for your letter of April 21 and the enclosures.

Some of the studies you cite are outdated and some are quite current. You have edited and amalgamated them skillfully. The data presented by Haverkos and Moss and their respective collaborators at the recent International Conference on AIDS are intriguing and deserving of further attention. The issues they raised warrant further investigation into the whole field of cofactors and their role in AIDS causation. It is possible that heavy use of nitrites, or another factor correlated with such use, may contribute in some as yet undefined way to the development of Kaposi's sarcoma in those already infected with HTLV-III or who have AIDS.

I agree that this information should be disseminated and I acknowledge the active role you have played in this effort. On the other hand, the present data do not justify an absolute “anti-popper” campaign.

We certainly wish to point out that no data exist to indicate that using nitrites is a safe, risk-free practice. Gay men should consider decreasing use of this substance until more data are available to assess those risks that may exist.

Thank you for your interest in this issue.

Sincerely yours,
James W. Curran, M.D., M.P.H.
Chief, AIDS Branch
Division of Viral Diseases
Center for Infectious Diseases

Some comments on the Curran letter: What does it mean to say, “Some of the studies you cite are outdated”? Which studies? And how so? — because they have been a) superseded by better studies?, or b) contradicted by later studies? At any rate, what about the really important studies, any one of which provides a reasonable warrant for banning poppers now, not just issuing warnings about them. Why does Curran refuse to address himself to a single specific issue? And what does Curran mean, “the present data do not justify an absolute ‘anti-popper’ campaign”? Would it be an “absolute ‘anti-popper’ campaign” to come right out and say “Don't use poppers”, or “Poppers are harmful to the health”, or “Poppers are a risk factor for AIDS”? There is plenty of information right now to take a stand on poppers, and no excuse for weaseling on the issue.

Curran's statement, “Gay men should consider decreasing use of this substance until more data are available to assess those risks that may exist”, is preposterous. Gay men should not “consider” anything at this point; they should act. And they should stop using poppers, not just decrease the use of them.

Setbacks for the poppers industry

In Wisconsin last year, the poppers industry, under the leadership of Joseph Miller, waged an all-out battle to prevent poppers from being banned. A formidable legal brief was prepared, which sanctimoniously adhered to the “room odorizer” tack. (“Those who denigrate the room odorizer effect of Great Lakes' products...are actually expressing nothing more than their personal distaste for the butyl nitrite odor.”)

Paid experts were flown in to testify as to the harmlessness of poppers, including the Professor of Medicine, John Parker, a co-author of the “Poppers Bible”.8

Another expert witness for Great Lakes Products, Inc. was Bruce Voeller, a founder and former Co-Director of the National Gay Task Force. According to a Wisconsin paper, “Voeller said all studies linking AIDS and butyl nitrite were 'utterly flawed and without foundation'”. Another paper noted dryly that Voeller's “expenses for appearing at the hearing were paid by a butyl nitrite manufacturer”.

The legislators were not favorably impressed by the “expert” testimony, and poppers are now a “banned hazardous substance” in Wisconsin.

In California, both San Francisco and Los Angeles have moved to ban the use of poppers in public, and to require point-of-sale warnings that their use is linked to the development of AIDS. In testifying in Los Angeles, Joseph Miller took several steps backwards:

“We recognize that the nitrites can be misused as inhalants. We have a responsibility for consumers; that's why we have warning labels that they should not be inhaled.” [Emphasis added.]

If poppers continue to be sold legally, this is due in part to disinformation from the poppers industry, disinformation which undoubtedly lies behind the striking disparity between current medical knowledge regarding the nitrite inhalants, as reported in the best medical journals, and the near-blackout on such information in the popular press and much of the gay press.

Government regulatory agencies have behaved shamefully in accepting the “room odorizer” lie. (“The makers have done their homework”, said Edward Nida, an FDA spokesman, “there's not a damn thing we can do about it.”) This is utter madness. Everyone knows that poppers are inhaled as a drug. Everyone who has studied the issue knows that poppers are dangerous, and almost certainly implicated in the etiology of AIDS. And yet the popper profits continue to roll in, and gay men continue to die.

As long as public officials refuse to do their duty, it is up to each of us individually to spread the word about the dangers of using poppers.

Critical judgment is called for. The bottom line is:



APPENDIX A: Koch's Postulates: The Case Against LAV/HTLV-III's Being the Sole, Sufficient, or Necessary Cause of AIDS

In medical science, the standards for proving that a particular micro-organism causes a disease are three classic laws known as “Koch's Postulates”. So far, the so-called “AIDS virus” (LAV or HTLV-III),9 has ignominiously failed to fulfill even one of the bacteriologist Dr. Robert Koch's three laws for “establishing the specificity of a pathogenic micro-organism”.

Koch's first Postulate requires that the microbe be found in all cases of the disease. In various samplings of AIDS patients, anywhere from 20% to 64% do not have the LAV virus, and about 10% do not even have antibodies. CDC officials cavalierly attribute this awkward finding to “poor testing methods”, failing to acknowledge that the burden of proof is on those who claim that the “AIDS virus” is the cause of AIDS.

Koch's second Postulate requires injection of the micro-organism into susceptible animals, with the result that the same disease is produced. For years researchers have been injecting several species of monkeys with fluids from people with AIDS. Whatever microbes were in the blood of the AIDS patients — whether viruses, bacteria, or other — whether named LAV or HTLV-III or ARV or something else — these microbes would have been transmitted, in large quantities, to the blood of the monkeys. And none of the monkeys has yet developed AIDS.10 Further, there have been several hundred carefully monitored cases of health care workers who accidentally stuck themselves with needles that had been used on AIDS patients. In no case has AIDS resulted from one of these inoculations.11

The third Postulate requires that the agent create the disease upon transfer from animals made ill by inoculation. Obviously this condition has not been met, as no animal has yet been made ill by inoculation.
It is certainly possible that the LAV virus may play some role, perhaps even an important role, in causing AIDS. However, LAV clearly cannot be regarded as a necessary factor in causing AIDS if substantial proportions of AIDS patients do not have the virus. This is the inescapable logic of Koch's first Postulate.

Considering that up to two-thirds of the AIDS patients do not have the virus in their bodies, one may question the wisdom of treating these patients with toxic and experimental antiviral drugs, such as ribavirin, which at best may prevent the virus from replicating. If the virus is not present in the patient's body, there is nothing to prevent from replicating.12

The government's insistence that the “HTLV-III” virus is the cause of AIDS, sole and sufficient, has stifled independent research and thinking, and has dangerously misled people as to the risk-factors for AIDS. Intravenous drug users have not been told to quit using drugs, only that they must stop “sharing needles”. (Actually, there is no evidence that all, or even most, of the IV drug users with AIDS did “share needles”.) Gay men have been told that they must restrict their sexual activities, but not that they ought to stop using cocaine, heroin, quaaludes, amphetamines, ethyl chloride, PCP, marijuana, LSD, barbiturates, poppers, and the other “recreational drugs” (a sick euphemism) that are prominent in the lifestyle of many gay men.

The government's unreasoning dogmatism is well expressed in Robert Gallo's statement: “If you get run over by a truck, you don't need co-factors.” The “AIDS virus” is hardly a truck, and it may be the “co-factors” that cause AIDS.


The “AIDS virus” etiology has been put forward thousands of times in the media, complete with color fluorescence micrograph photographs, and the public has come to believe it. Nevertheless, the “virus only” theory is not tenable. Repeating a hypothesis does not verify it. Propaganda is not science.

Any theory of how AIDS is caused must come to grips with the fact that for five years AIDS, unlike a truly communicable disease, has remained compartmentalized. More than nine out of ten AIDS cases are either intravenous drug users or homosexual/bisexual men.

Medical science recognizes that illnesses can have infectious causes, or non-infectious causes, or both types of causes acting together. Some illnesses are caused primarily by communicable microbes. Others — like radiation-induced leukemia, black lung disease, alcoholic cirrhosis of the liver, emphysema from cigarette smoking, or the dioxin (“Agent Orange”) syndrome of diseases — are caused by toxins.

For reasons unknown, the U.S. Public Health Service adheres with military rigidity to the line that AIDS must be explained in terms of the “AIDS virus”, and that research efforts must be based solely on this premise. Risk-reduction measures are to be predicated solely on preventing transmission of the putative virus.13

Government officials have taken an adversary stance against the possibility that toxic agents play a role in causing AIDS. They have, for example, laid down the line that IV-drug users develop AIDS, not from the drugs they use, but from allegedly “shared needles”, an unproved assumption. Considering that heroin is known to be immunosuppressive, and specifically to cause depression of T-cells, the government's intransigent dismissal of the drugs, while focussing on “shared needles”, is bizarre and irresponsible. It is truly a case of “straining at a gnat and swallowing a camel”.

In actuality, such epidemiological information as we have seems more consistent with a toxicologic than with the prevailing microbial model. To illustrate another way of looking at AIDS, we have developed the accompanying diagram, in which toxins represent the primary causative factor. By no means a finished explanation of how AIDS is caused, the model is intended to portray possible relationships, to generate hypotheses and provide directions for research.

Everything in the diagram is part of the typical AID Syndrome, though the exact relationships involved, or the relative importance of the various components, remain to be determined. Some factors may be relatively trivial, while others may be crucial. In the center are various toxins, some peculiar to the lifestyles of IV-drug users and/or urban gay men, others affecting much of the population. The model is multifactorial, for disease, like health, is multifactorial. However, one should bear in mind that some drugs are capable of causing AIDS all by themselves.

Several vicious circles are in operation, for example, “Dietary/Metabolic Imbalance”, a condition caused by many different drugs. There are addicts who seem to live on nothing but candy bars and sugar water. When the carbohydrate diet is joined to an impaired immunological system and the use of antibiotics (like tetracycline), a yeast infection (“thrush”) commonly develops, which further depresses immunological functioning and creates even greater craving for carbohydrates.

In another vicious circle, the inhaled “recreational” drugs cause lung damage (Newell 1985, Ortiz 1985), which depresses the immune system (of which the lungs are a crucial component) and prepares the way for pneumocystis carinii pneumonia, which further impairs the immune system, damages the lungs, and requires antibiotics, which themselves aggravate the condition.

Much research needs to be done, as there is amazingly little information on the characteristics of people with AIDS. To begin with we need studies of large, representative samples of AIDS patients — information on their diets, before and after diagnosis; their drug habits in detail, including combinations, amounts, and frequency of use; cigarette smoking; infectious disease histories; medical drug histories, with special attention to antibiotics. Were there many PWA's in good health prior to developing AIDS? — who had not smoked cigarettes, used drugs, drunk excessively, or had a history of venereal infections with antibiotic treatment? — who had followed a well-balanced diet? The “virus only” theory (“you don't need co-factors”) would imply many such people; the toxicologic model, very few.


APPENDIX C: Occam's Razor: The Drugs Connection

Nowhere have we argued that poppers are the cause of AIDS. Obviously poppers are not, as there are AIDS patients who have never used them. At the same time, the “AIDS virus” (LAV or HTLV-III) cannot be the cause either, as substantial numbers of AIDS patients do not have the virus in their bodies, and yet remain sick. To be honest one must say that the cause of AIDS is unknown. There may be more than one route to AIDS, or it may be that multiple factors in combination are required to cause the condition.

Science generally prefers the “most parsimonious” explanation that accounts for the facts. The principle was formulated by the 14th-century philosopher, William of Occam, whose Razor states, “What can be done with fewer [assumptions] is done in vain with more.”

Certain drugs, such as the medications used during transplant operations, can cause the AIDS condition, immune deficiency, all by themselves. It is also known that “recreational” drugs, like heroin, are immunosuppressive. And it is now firmly established that poppers are immunosuppressive. More than a quarter of the AIDS cases have occurred among intravenous drug users, and most of the remaining AIDS cases have occurred among gay men who used poppers (as well as other “recreational” drugs).

When injectors of immunosuppressive heroin, or inhalers of immunosuppressive poppers, develop AIDS, Occam's Razor suggests parsimoniously assuming that their drugs were the cause. Microbes, diet, and other lifestyle and environmental factors probably played a role, but these represent superfluous assumptions.

In any event, common sense dictates not using immunosuppressive drugs. Do not use poppers.



1. See Appendix A: Koch's Postulates: The Case Against LAV/HTLV-III's Being the Sole, Sufficient, or Necessary Cause of AIDS.

2. By “recreational drugs”, we are not referring to coffee or chamomile tea. The drugs that were used heavily by the gay men with AIDS who were studied in 1981-1982 included not only poppers, but barbiturates, amphetamines, cocaine, heroin, ethyl chloride, LSD, PCP, and quaaludes (“ludes”). (Haverkos 1985) Looking at this menu of drugs, the question is not, “Could it be that one of these drugs is harmful?” They are all harmful. Ethyl chloride, for example, causes brain damage every time it is inhaled. Heroin is known to be immunosuppressive, causing, among other things, a depression of T-cell number and function in opiate addicts. (References in Quagliarello 1982.)
    And then there is alcohol, which may be benign when used in moderation, but which is one of the most toxic of all drugs when used heavily. Physicians in New York City, who have treated many hundreds of patients with AIDS, have stated that a large proportion of these men were alcoholics. Anyone who feels he may have a drug/alcohol problem should get help. Unless emergency medical attention is needed, the best first step would probably be to telephone Alcoholics Anonymous or Narcotics Anonymous, depending on the nature of the addiction.
3. Such workers were the focus of Appendix V by John O. Parker in the “Poppers Bible”. (See entry under Nickerson.) Oddly, the government researchers list this poppers industry publication under their “References”, as though it were a legitimate source.

4. In a letter of 25 March 1983 (a copy of which is in the archives of the Committee to Monitor Poppers), to Peter Frisch of The Advocate, Joseph F. Miller, President of Great Lakes Products, Inc., urged The Advocate to publicize his press release, which claimed that CDC studies had exonerated poppers from any connection to AIDS. Miller was fully confident in the power of his advertising dollars:

“As the largest advertiser in the Gay press we intend to use the extensive ad space we purchase each month as the vehicle for sending a message of good health and wellness through nutrition and exercise to the North American Gay communitites [sic].”

The Advocate then ran full-page advertisements for the Great Lakes brands of poppers; the series was called, “Blueprint for Health”. The Advocate's health expert, Nathan Fain, whose credentials consisted of journalism experience covering the theater, wrote that poppers had been exonerated by a CDC study. Fain criticized researchers who warned about the dangers of poppers, attacked the New York Native for printing anti-popper editorials and news items, and ridiculed the City of San Francisco for banning poppers sales to minors and requiring warning signs to be posted at point of sale. For more information on Miller's activities, see the section immediately following, “The Poppers Industry and its Influence”.

5. Evans, Arthur. “Poppers: An Ugly Side of Gay Business”. Coming Up! November 1981.

6. W. Jay Freezer died of complications due to AIDS on 27 March 1985. Freezer was not the first poppers manufacturer to die from AIDS. He was preceded by the New Yorker known as “Poppers Bill”.

7. See entry under Nickerson.

8. See entry under Nickerson.

9. Now known as the “Human Immunodeficiency Virus”: HIV-1.

10. The infra-human primates did become “infected”, since their bodies formed antibodies to what is now called HIV-1. However, none developed “AIDS”. As of now, the Spring of 1992, they are still healthy.

11. This devastating argument against the AIDS-from-shared-needles hypothesis became even stronger after this passage was written. A 1988 CDC study, of health care workers who had been stuck with hypodermic needles that had been used in AIDS patients, found that out of 1428 workers who had thus been accidentally inoculated with the plasma of AIDS patients, only four (0.3%) seroconverted (i.e., developed HIV antibodies), and none developed AIDS! Not a single case of AIDS from a needle-stick injury has ever been demonstrated. (Centers for Disease Control, “Update: Ac quired Immunodeficiency Syndrome and Human Immuno defi ciency Virus Infection Among Health-Care Work ers”, Morbidity and Mortality Weekly Report, 22 April 1988 [vol. 37, No. 15], pp. 229 et seq.)

12. Although the AIDS Establishment claims that techniques for detecting the virus have improved greatly since 1986, the fact remains that in a substantial number of AIDS patients neither HIV-1 itself nor HIV-1 antibodies can be detected, even using the most sensitive techniques.

13. At the time this passage was written, the CDC reported AIDS statistics by using a “hierarchical presentation”. Data on “AIDS cases by Patient Characteristics” were reported by listing the largest category (homosexual men) first, after which a patient was included in a subsequent risk group only if he had not already been counted. A gay man who used IV drugs was a homosexual, but not an IV-drug user.
    CDC tables showed 17% of AIDS cases as being IV-drug users, with no indication that these 17% were only the exclusively heterosexual IV-drug users. They concealed the substantial overlap group: gay men who were also IV drug users. In fact, anywhere from 26% to 34% of the total AIDS cases were IV-drug users.  The effect of the CDC's statistical trickery was to underreport IV-drug users as an AIDS risk group by at least 50%; the effect was to construe AIDS as a venereal disease, rather than a drug-induced condition.


Hank Wilson, a long-time gay activist in San Francisco, founded the Committee to Monitor Poppers in the fall of 1981. Since then, Wilson and the Committee have assembled a formidable collection of medical and other literature on the nitrite inhalants, have corresponded with researchers and public officials internationally, and have played a leading role in sounding the tocsin on the dangers of poppers. Wilson was a founder of the Gay Teachers Coalition, a founder of the Harvey Milk Gay and Lesbian Democratic Club, a founder of the Butterfly Brigade (a gay self-defence group), and a founder of Community United Against Violence.

John Lauritsen received his A.B. degree from Harvard (Department of Social Relations), and has twenty years of experience as a market research executive and analyst. Lauritsen is co-author of The Early Homosexual Rights Movement (1864-1935) and has edited the John Addington Symonds anthology, Male Love: A Problem in Greek Ethics and Other Writings.