by Colman Jones .
This is the final draft of an article originally commissioned for SPIN Magazine’s “AIDS: Words from the Front” Column. Editing by Alyssa Katz.
In the AIDS era, it’s easy to forget that sex has always been fraught with complications. Before the release of penicillin during World War II, syphilis evoked particularly widespread terror, thanks to its ability to lie dormant, undetected, producing hideous and often life-threatening symptoms years later.
“Duties of the Health Department in Syphilis Control” – Public Health Service Poster, c. 1945 The fear 50 or 75 years ago of acquiring syphilis was not all that different from the fear of getting AIDS today. As seventysomething author Gore Vidal explained in a 1992 interview in Vanity Fair, “It’s very difficult for younger people to understand. We are the syphilis generation before penicillin. Every time we fucked, no matter what we fucked, there was the danger of syphilis, and of a hideous death, and of never knowing you had it until you suddenly began to have grotesque symptoms.”
The paranoia over casual transmission of HIV, exemplified by attempts to bar HIV-infected children from school, or by physicians refusing to treat AIDS patients, echoes back to the old anxieties over acquiring syphilis from drinking fountains, shared cutlery, toothbrushes. The stigma associated with both diseases has driven many an infected person underground, allowing each epidemic to spread unchecked.
And syphilis is still with us. The World Health Organization recently stated that many more people contract STDs than was previously believed, and it seems that such infections “greatly increase the risk of contracting HIV,” the organization said. This ominous announcement comes on the heels of numerous studies from around the world showing people with STDs are up to 100 times more likely to subsequently test HIV-positive than their STD-free counterparts.
There’s increasing reason to believe that the link between AIDS and syphilis goes even deeper. Some researchers strongly suspect that undiagnosed syphilis is wreaking havoc in AIDS patients, and that the presence of HIV is merely an indication of problems in the immune system.
The CDC estimates that there were hundreds of thousands of syphilis cases during the ’70s and early ’80s, most of which went untreated. Yet today, very few people with AIDS also have syphilis. How could such a huge reservoir of a highly deadly infection have simply vanished with the arrival of AIDS?
John Scythes Chief among the heretics who believe that syphilis is the cause of sexually transmitted AIDS is John Scythes, a self- described “AIDS revisionist” in Toronto. “I’ve never heard of an AIDS patient dying of syphilis,” he says. “This is impossible– the British warned the Americans in the ’70s that only a third to a half of syphilis cases were being treated, and along comes HIV disease and syphilis disappears? I can’t accept that. It can’t have gone away.”
As the owner of Glad Day Bookshop, a gay bookstore in Toronto, and as someone who’s lost countless friends to AIDS over the years, Scythes is determined to get to the bottom of what’s causing them to die. His passion has taken him around the world several times over, flying to dozens of medical conferences at his own expense. Scythes’ credentials consist of a B.A. and a plumber’s license. Yet he has succeeded in getting some of the top experts in the field to listen to his views, and several of his provocative papers and lectures have been presented at major AIDS and STD conferences for the last six years. Scientists who’ve written to him in support often mistakenly address him as “Dr. Scythes.”
Scythes has closely followed the contentious debate over the cause of AIDS from the very beginning, and takes the position that HIV is not enough to explain the collapse of the immune system. In the late ’80s, when New York physician Stephen Caiazza and Berkeley physiologist Joan McKenna began sounding the alert over the possible role of syphilis in AIDS, Scythes undertook the job of medical detective, gathering evidence from classic syphilis textbooks, meticulously scanning them for overlaps with modern-day AIDS. The bookcase in the study of his Victorian mansion sports a truly impressive collection of dusty old tomes on syphilis dating back over a century. Scythes can easily pull out one of these volumes and find case after case of syphilitic deaths that bear an uncanny resemblance to what is now called AIDS. “The scientific literature from the ’40s and ’50s appears full of references to AIDS-like deaths in populations known to be suffering from untreated or inadequately treated chronic syphilis”, Scythes said. “Yet we ignore that in the AIDS era.”
John Scythes and Istvän Horväth in New Orleans Although most syphilis experts on this side of the Atlantic would prefer it if Scythes would just go away and leave them alone, this eccentric, at times abrasive character has now placed himself firmly on the STD map, and he has no plans to disappear. He will not rest, he says, until he can conclusively determine whether this ancient disease has made an insidious comeback – in the form of AIDS among his friends.
In the ’70s, there was a disastrous spread of STDs among sexually active gay men, and syphilis, in particular, spread like wildfire. Unfortunately, a lot of the syphilis may never have been detected. Part of the problem was an unquestioned reliance on blood tests that were never designed to detect multiple infections. Even assuming the tests were working properly, the initial symptoms of syphilis are easily overlooked. And since much sexual activity was anonymous, very few people who actually turned up with a chancre or rash were able to identify their partners so they could be notified and treated. Also complicating the situation was the effect of antibiotics given for other conditions, which can mask the symptoms of syphilis without actually curing the disease.
Researchers in 1970 looked at all of these factors and warned that “the ominous prospect of a widespread resurgence of the disease in its tertiary forms looms ahead.” In the mid-’70s, British venereologists estimated that between half and two-thirds of syphilis cases in the United States were going untreated. By 1981, the CDC estimated there were 325,000 cases of undiagnosed and untreated syphilis in the U.S., and other authorities concede the number was closer to half a million. It’s generally acknowledged that most of this syphilis was infecting gay men.
So where has all this syphilis gone? And why is it not more of a problem among AIDS patients? Syphilis is not even on the CDC’s list of AIDS-related opportunistic infections. Recent estimates put the incidence of neurosyphilis, one of the later stages of syphilis, among HIV-positive people at about 2 percent. It’s the mysterious absence of this deadly disease in the age of AIDS that has people like John Scythes worried.
Though syphilis occasionally shows up in people with HIV, with the odd exception it seems to behave very much as it does in HIV-negative people. But as HIV-positive people progress towards the full-blown AIDS syndrome, the incidence of syphilis grow increasingly rare. Scythes notes, “It’s conspicuously absent in HIV disease in its later stages. It’s a 100 percent correlation– no AIDS patient ever dies of syphilis, and that’s impossible. An untreated reservoir of syphilis infection in immune suppressed people does nothing? Syphilis kills–on its own–more efficiently than any of the other infections purported to be operating as STDs within the sexual framework of AIDS.”
The cellular immune system, which the body uses to control syphilis, is profoundly lacking in AIDS patients. If anything, one should expect an explosion of syphilis among gay men with AIDS.
As regular readers of this column know, the questions surrounding HIV, and the assumption that it is the cause of AIDS are many. It remains unclear how the virus destroys the immune system. There’s no consistent strain that’s always associated with the disease. Powerful anti-HIV treatments, such as AZT, are disappointing failures.
Even Luc Montagnier, the French scientist whose team originally discovered HIV, no longer believes the virus is sufficient to bring on the disease by itself, and has long called for research into possible “co-factors”. Indeed, the rate at which different groups of HIV-positive people develop AIDS, and the astonishing diversity of symptoms, suggest that something more than HIV is at work.
Recent findings by immunologists at the National Institutes of Health seem to indicate that HIV can be harmless under certain conditions. They have identified many people whose immune systems have unquestionably been exposed to, and even infected by the virus, but who do not make HIV antibodies or get sick. By measuring the response of key immune cells, known as T-cells, the NIH researchers have discovered that a surprising large number of these poeple who have HIV but test negative for HIV antibodies have been able to control the virus through a strong response by the cellular arm of their immune system.
Scythes is convinced that only people whose immune systems become activated or disregulated by other factors will trigger HIV out of latency, resulting in a burst of virus activity and the production of HIV antibodies. This would explain the fact that people with full-blown AIDS, whose immune systems are clearly a mess, almost always test positive for HIV antibodies.
He points to research on a group of gay men in Vancouver, Canada, that showed that unprotected anal sex was not as important a factor for turning HIV-positive as was a previously existing defect in the cellular arm of their immune system. HIV may have been lying dormant in these people all along, it seems. The NIH researchers believe the activation of HIV out of latency may reflect a fundamental shift in the immune system itself, from a response in which T-cells work to control infection, to a response in which antibodies predominate.
Such a deviation in the immune response is increasingly recognized as the mechanism behind not only HIV activation, but also why a host of other bacterial diseases can become chronic, while others are successfully resolved. The problem seems to stem from immune responses being shut off too early. They’re tricked into leaving behind a few residual organisms that then slowly multiply, and give rise to persistent infection. Chronic diseases that work in this fashion include tuberculosis, leprosy, sleeping sickness–and syphilis.
Scythes feels AIDS should be renamed “Acquired Immune Deviation Syndrome”, in which certain cells start sending inappropriate levels of chemical signals (known as “cytokines”) to each other. This eventually burns out the immune system. He believes that many “co-factors” can alter the immune system in this way – cytokine poisoning of blood products, chronic opiate abuse, tropical diseases in Africa, to name just a few.
“There are many ways to get AIDS”, Scythes declares, “and there always have been.” But he is convinced that unresolved syphilis is at the heart of sexually-acquired AIDS, owing to the profoundly deviating effect syphilis has on the immune system.
To back up his concerns, he also points to numerous epidemiologic studies showing that a history of syphilis is one of the best predictors of subsequently turning HIV-positive. A study of 500 gay men in Amsterdam showed that while those who had unprotected receptive anal sex and/or multiple partners were roughly twice as likely to be HIV-positive as those who didn’t, those with a history of syphilis were over 20 times as likely to be HIV-positive than those without a history of syphilis. A large U.S. Army study had similar findings.
Most AIDS researchers feel the sores produced by syphilis simply represent an easier portal of entry for HIV. But Scythes feels syphilis also plays an intimate immunological role that’s currently going unrecognized. If he’s right, it wouldn’t be the first time that medical science has been fooled by this disease, historically known as “the Great Masquerader”.
Woodcut, 1496, attributed to Albrecht Durer, the first visual representation of a syphilitic “A mysterious epidemic, hitherto unknown, which had struck terror into all hearts by the rapidity of its spread, the ravages it made, and the apparent helplessness of the physicians to cure it”. Sir William Osler, widely considered to be the father of internal medicine, used these ominous words to describe the sudden appearance of syphilis 500 years ago. The plague was phenomenally lethal in the first few decades. Eventually it passed into a chronic form, no longer immediately fatal but still dreaded for its capacity to cause long-term disabilities.
Syphilis is generally recognized to have three stages. In the primary stage, a sore known as a chancre may appear at the site of infection. Chancre on penisDepending on where it appears, this painless lesion can often go un-noticed, in which case it heals by itself after a month. The disease then moves into a generalized secondary stage, the symptoms of which can include swelling of the lymph nodes, rashes, and skin lesions.
After a six- to nine-month struggle with the organism, most healthy people go into a state of latency. Latent means “hidden” in Latin–an apt description, since it’s unclear what happens to the relatively few organisms that are known to remain in the body during this stage. Studies done earlier this century, of people who did not get treatment for their syphilis, found that about a third of them eventually relapsed into a late, tertiary stage. The violent tissue destruction of late syphilis can produce damage to internal organs including the liver and heart; blindness; crippling arthritis; brain and central nervous system disorders; and soft, fleshy tumour-like growths called gummas.
These late-stage relapses were often accompanied by a rise in a particular set of antibodies directed not against Treponema pallidum, the spiral-shaped germ that causes syphilis, but against the connective tissue holding the body together.
Scythes points out that the classical symptoms of late syphilis happen because of a vigorous cellular response, in which the body’s cells are sensitized, or primed, against the organism.Primary chancres (syphilitic sores) – early drawing from 18th century medical textbook “All the outward symptoms of syphilis are a direct consequence of immunologic well-being”, he explains. “They rarely occur in immune-suppressed people, and with T-cell deficiencies, they will not occur.” He’s not so sure, however, that syphilis is only dangerous when the immune system is sensitized to it. He strongly suspects that, in people who become de-sensitized–whose immune systems have grown tolerant to syphilis–the disease could have chronic effects on the immune system, like those seen in AIDS, without producing any of the typical symptoms of late syphilis.
Indeed, earlier this century, there were two distinct schools of thought as to how syphilis caused damage to the body. The first, which persists to this day among American researchers, is that syphilis is only dangerous in the presence of its lesions. This paradigm settled into place in the mid-’50s, dominating the field much the way the HIV model governs the world of AIDS.
The second, espoused by many leading syphilologists earlier in this century, was that syphilis could also cause death by rendering people more susceptible to other life-threatening infections and cancers. Increased susceptibility to other infections and cancers is, of course, the characteristic feature of AIDS.
“A shadow on his future.” British Ministry of Health poster, circa 1950. Long-term studies of people with untreated infection– including the infamous Tuskegee study, in which dozens of black men were deliberately denied treatment–found that syphilis significantly reduced lifespans. Syphilis alone could not explain this. According to a widely-used insurance manual from the ’40s, even syphilitics who were treated and presumed cured had a death rate 47 percent higher than non-syphilitics, the chief causes of death being pneumonia, cancer, and TB–the hallmark complications of AIDS.
Since the immune system was poorly understood earlier this century, there was no awareness of the now well-recognized phenomenon of immune suppression. In spite of the increased death rates from other causes found among syphilitics, reviewers of one study could conceive of no mechanism by which the disease could exert such a weakening effect, and instead chalked the excess mortality up to the poor socioeconomic status of the study’s subjects. Was chronic syphilis acting directly, upon the immune systems of these people? There was no way to count T-cells in such patients like we can today. However, in retrospect, the few tools that were able to shed light on immune function suggested a profound loss of T-cells.
One of these old techniques was skin testing, which is still used today to test for tuberculosis. Components of the bacterium is injected under the skin. Swelling and redness at the site of injection indicates someone has already been exposed to that particular organism, and that the immune system is fighting back against an old enemy.
In the ’30s, about 80 percent of the world’s urban populations gave a positive reaction to the TB test. But one syphilis researcher discovered that only 20 percent of his patients with late syphilis tested positive for TB. The implication is that these late-stage syphilis patients were severely immune-suppressed–though many of them had surely been exposed to TB at some point, their immune systems couldn’t muster the expected reaction.
Subsequent experiments in animals offer still more evidence for immune suppression as a result of syphilis. An investigator at Yale, Paul Rosahn, found that chronic syphilis shortened life expectancy in mice by one-third, whether or not they showed symptoms. Monkees exposed to syphilis in the ’60s later developed pneumocystis carinii pneumonia, a common killer in people with AIDS, and died. And more recently, syphilitic mice studied by Hungary’s top syphilis expert, Dr. Istvan Horvath, are surviving only half as long as non-syphilitic mice. Some of them have developed a series of strange tumours.
Eastern European experts interviewed for this article, in contrast to the U.S. authorities, are convinced that syphilis has profound effects on the immune system. They’re not prepared to rule out a role for syphilis in AIDS.
Horvath has also done similar experiments on rabbits. “The syphilis-infected rabbits were vulnerable to many diseases, and they died very soon, not by syphilis, but by other infections.” The syndrome looks eerily familiar. Are these rabbits really dying of AIDS brought about not by HIV, but by a chronic syphilis infection?
Treponema pallidum, the cause of syphilis
The precise effects of a syphilis infection on the immune system are ultimately an enigma. “The mechanism of immunopathology is so complex”, says Konrad Wicher, a renowned syphilis expert affiliated with the New York State Department of Health. “Nobody really knows syphilis, even if we claim that we know.”
From what little we do know, there are many basic parallels with the initial immune responses seen in the early stages of syphilis, and the more profound alterations seen in AIDS. Research conducted throughout the ’70s showed that early syphilis is marked by an abnormally high production of various kinds of antibodies, including some directed against the body itself. These auto-antibodies, as they’re known, can target any number of bodily organs and tissues–even T-cells–and often persist well into the latent stage even if the infection is treated. Researchers also noted pronounced defects in T-cell responses among people with early syphilis.
But according to some syphilis researchers, that’s where the similarity ends. Sheila Lukehart, a top expert at the Harborview Medical Centre, dismisses the idea that syphilis is a co-factor in AIDS. “All of the work that we have done in our lab, and a number of other laboratories have conducted, does not concur with some of those findings that were published in the late 1970s,” she says. Lukehart has argued that, although it takes a while to get going, there is in fact a very powerful immune response in syphilis, which results in the disease eventually becoming latent and non-infectious.
But this latency is clearly a precarious one, since at least a third of the afflicted eventually relapse into late syphilis. How and why the treponemes emerge to cause the late manifestations of the disease in some people but not others still remains a mystery.
Scythes and his peers are also asking what exactly happens when someone gets re-infected with syphilis. This is a critical issue, since many gay men in the ’70s and early ’80s were at high risk of being repeatedly exposed to the disease. Scythes contends that re-infection with more syphilis on top of an old infection is a guaranteed recipe for AIDS, and there is little in the older literature to counter this notion.
Unlike many other infections from which people only get sick once, such as chicken pox and measles, the body does not reliably produce the normal immune reaction again when a person is exposed to syphilis more than once.
Scythes points to studies in which animals, and even human volunteers, who had already had syphilis once were re-inoculated with the bug a second time. The studies show that typical symptoms and blood test reactions, the things doctors rely on to diagnose a new infection, only appear consistently again if the first infection was treated early on. If the previous infection was treated later on in the course of disease, or not treated at all, there was usually no outward indication that re-exposure took place. However, the available evidence shows that the new virulent organisms were able to enter and spread throughout the body.
One of these studies was performed in the mid-’50s, on a group of 62 prisoners at Sing Sing prison. As Professor James Miller, a veteran syphilologist at UCLA, points out, “there were five patients with untreated late latent syphilis in that study, and they were challenged with [virulent T. pallidum], and none came down with a lesion. As a matter of fact, none of them came down with a [blood test] response. They were considered to be immune.”
The critical issue, however, is whether they were truly immune, or whether their bodies simply had lost the ability to properly respond to the new infection. In earlier experiments re- inoculating rabbits with a second round of syphilis, researchers were able to create an ‘asymptomatic reinfection’. Even though no lesion developed where the animal had been re-inoculated, they could still prove that the animal had been successfully re- infected. They did this by taking lymph node material and injecting it into another rabbit, who then developed syphilis.
Scythes is worried that hundreds of thousands of gay men became silently re-infected this way all throughout the ’70s and early ’80s, without showing any outward evidence of infection, yet with new virulent organisms spreading throughout their bodies.
UCLA’s Miller can conceive of such a scenario. “Let’s say you were infected, and you were treated, and then you were re- infected and you didn’t get primary syphilis, you didn’t get secondary syphilis, all you got was a latent infection. By the time you got to the doctor, you could have brain damage.”
Or worse. Miller is referring to the tissue destruction form of syphilis, in which connective tissue is destroyed. Scythes would go one step further: In the absence of a proper vigorous immune response, he proposes, the latent syphilis would just simply eat away at a person’s immune system – i.e. exactly what we see in AIDS.
Other syphilis experts, although they’re not ready to admit that their disease may be at the root of AIDS, appear to be edging towards accepting the possibility that it’s been a mistake to assume that syphilis only manifests itself in the classic way.
In a presentation at the 1991 conference of the International Society for Sexually Transmitted Disease Research, Dr. Sandra Larsen, a top syphilis expert at the CDC, asserted that “the clinical manifestations of syphilis, which have taken various forms over the centuries, have now been transformed to mimic the appearance of the opportunistic infections and cancers that may accompany HIV infection, as well as the clinical symptoms of AIDS itself.” In a recent interview, Larsen indicated that this was another way of saying how little we’re able to tell the two apart.
Dr. Stephen Caiazza If syphilis is really a Trojan horse operating under the cover of HIV infection, going undetected by current tests, it’s natural to consider treating AIDS in the same manner as syphilis. Unfortunately, penicillin doesn’t seem to be of much help, and has even proved dangerous. It was tried back in the late ’80s by a few brave physicians, including Stephen Caiazza, who suspected they may be missing a lot of the syphilis among their HIV- positive patients.
Scythes remembers these episodes all too well. “When Steve Caiazza came here, a number of patients elected to take penicillin therapy and their doctors kindly obliged them. It precipitated some terrible reactions: massive pains in the leg nerves, terrible fevers.” Although the treatment didn’t cause any patients to improve, it caused a number of people who had been negative in syphilis blood tests to revert back to positive. Scythes interprets these reactions as evidence that T. pallidum is indeed at work. In his view “it’s a reaction to the effects of the drug, trying to deal with latent syphilis infection and failing.”
Merck advertisement for benzathine pencillin In Germany, anasthesiologists Klaus Dierig and Urban Waldthaler claim to have successfully treated a couple of dozen AIDS patients, using megadoses of penicillin over a 30-day period. However, when I contacted them, neither was able to supply hard evidence to support their claims. There are good reasons to doubt them. It’s well known that penicillin only affects organisms that are actively proliferating. That’s why late syphilis, in which the treponemes are no longer dividing, has always been exceptionally difficult to treat.
James Miller and his colleagues at UCLA are working on a syphilis vaccine, based on the theory that specific proteins of T. pallidum might be used to immunize people against syphilis. They call it Treponemal Rare Outer Membrane Protein–TROMP for short.
Miller’s team is positively bubbling with excitement over this discovery. “We have been in competition with other labs to try and get this out../.and we’ve succeeded where others have failed. Everybody would agree that this particular molecule plays an important role in the organism being able to escape the immune response.”
Scythes actually thinks TROMP might not only work as a vaccine but potentially as the basis of a successful AIDS treatment that would reinvigorate syphilis-ravaged immune systems. Miller doesn’t necessarily embrace Scythes’ theory, but is willing to consider the possibility. “Sure, I would say, try it. I think anybody would be willing to try anything to help save these individuals.” But an AIDS treatment based on TROMP is still a long way off.
Perhaps not surprisingly, research directed at a possible AIDS- syphilis connection has been slow in coming. The medical community is dominated by HIV-related research and funding, with few resources available for other strategies.
As the CDC’s Dr. Sandra Larsen put it, “We have not looked at some of the concerns that you have expressed, because we just haven’t had the funding, nor the time, nor the means for doing it. Institute of Immunology and Experimental Therapy in Wraclaw, PolandWe have a limited budget, and a limited number of people, and we’re shrinking daily.”
Why is it so hard to get funding? “Well,” says Larsen, “people feel that syphilis can be controlled with penicillin. I mean, you have to realistic: syphilis is not in the favored populations.”
Scythes feels the onus lies squarely on the gay communities around the world to get this research started. “The questions, in the eyes of the syphilologists, are correct”, he contends. “Now, if the communityEarly ACT UP banner won’t go to these people and say `Hey, can you help us with AIDS, can you demand some money to do more research?’, they’re not likely to do it alone.”
Bob Lederer, an investigative journalist and member of ACT UP in New York, is helping to co-ordinate a major campaign against the NIH and its blue-ribbon task force that seeks to re- structure AIDS research. But Lederer, who has followed the AIDS- syphilis connection for years, admits there just hasn’t been enough awareness about the issue to create a critical momentum. “I have not been able to follow this, because I’m just so involved in other aspects of AIDS, and yet I still deep in my heart think that this is – absolutely – a central aspect of the pathogenesis of AIDS. Even the few people in the activist community who were interested in it have moved on to other stuff.”
Istvan HorvathIn the meantime, the layman from Toronto is doing what he can to help the research along. Scythes recently paid $500 to have antibodies that count rabbit T-cells shipped to Hungary, so that John ScythesIstvan Horvath can analyze the immune systems of his dying rabbits, to see whether they are suffering from an AIDS-like syndrome. As millions of dollars continue to be spent in the U.S. on HIV research, it would be ironic indeed if an answer to sexually-transmitted AIDS came out of a collaboration between a lab in Budapest and a former plumber.
Note: This article was originally commissioned by SPIN Magazine in June 1995, and travel expenses were provided for the author to attend the New Orleans conference. In late September 1995, just prior to going to press, publisher Bob Guccione, Jr. decided not to run the column, and requested a letter “summing up the main evidence”. To read the author’s letter to Guccione, click here