CBC Radio One  6/3/99
Canadian Broadcasting Corp., c. 1999

	Bacterial Bombshell

New technologies can uncover hidden germs -- have we found the possible cause of heart disease, M.S. and  maybe even AIDS? 

By COLMAN JONES 

NEW YORK CITY-- At the sedate 12th International Conference On Lyme Disease, I have one of those electrifying moments familiar only to those who have tracked a mystery beyond the point of good sense and then discovered some other intrepid soul on the trail just ahead. 

It occurs when Willy Burgdorfer, the white-haired discoverer of the tick-borne Lyme microbe, shuffles his papers at the podium and offers an idea so seismically unconventional that shivers run down my spine. 

Traditional medical tests, he says, often proclaim a patient cured of Lyme disease when the bug is really still hanging around in the body. The microbe has a shrewd capability, he says -- it can form cysts and hide in body tissue despite the exterminating effects of antibiotics. 

After a decade on the AIDS beat, I can hardly believe my ears. What Burgdorfer is saying about Lyme is exactly what a fellow lay researcher and I have been saying could be happening with the closely related syphilis germ. 

For years we've been obsessed by the riddle of what happened to the estimated half a million cases of syphilis that went untreated in gay men during the 70s and 80s. Though deemed heretics by the mainstream AIDS community, we continue to wonder if there's a chance that the undetected syphilitic infection could wear down the immune system over time, resulting in the symptoms ascribed to HIV. 

While there aren't many rebel researchers asking this particular question, there are now, fortunately, many more scientists preoccupied with bacteria and their relationship to chronic disease. 

By means of new laboratory and genetic techniques, researchers are uncovering hitherto undiscovered germs that may be responsible for a host of conditions previously thought to be uninfectious -- from stomach ulcers, Crohn's disease, rheumatoid arthritis and lupus to heart disease, Alzheimer's, multiple sclerosis and cerebral palsy. 

And while it's strange to think that everything from heart attacks to bouts of depression might one day be prevented by a dose of antibiotics, there's no question we're in the midst of a bacterial revolution that is paving the way for a new medical paradigm for the next millennium. 

*** 

Bookstore owner and AIDS heretic John Scythes and I have come to this conference inspired by the announcement of a new culturing method that can allegedly find cyst-like forms of the Lyme bacterium (a member of the spiral-shaped spirochete family of germs) in the blood of patients who have supposedly been cured of the disease. 

We have submitted a paper suggesting that the technique be applied to uncover hidden syphilis spirochetes in AIDS patients. To our surprise, our humble laypersons' offering is given the thumbs-up; it's one of only16 papers accepted for display at this meeting. 

Thus, we are allowed our poster display in the conference foyer. 

We've been aware for a long time that during the 70s and 80s, syphilis infected vast numbers of people who then went on to develop AIDS. But we didn't have a lot of modern-day support for the idea that the syphilis germ -- notoriously difficult to detect after the initial infection -- might be hiding in AIDS patients in some altered form. 

Until Burgdorfer. During a break in the conference proceedings, the esteemed scientist himself walks up to look at the reproductions of cyst-like forms of spirochetes that Scythes and I have compiled from old syphilis texts, some of the same images he used in the overhead to illustrate his lecture. 

"We can demonstrate cysts by microscopy (in the case of Lyme), and once they are in the tissues of the patient we can no longer detect them," he tells me. "It is quite possible that this material we cannot see is responsible for producing prolonged and chronic disease," he says of the illness carried by ticks in wooded areas of the U.S. and Canada. 

Desert termites 

Does he think that everything he's suggested about the Lyme spirochete taking on cyst-like forms and escaping detection would apply to the syphilis spirochete as well? 

"Of course. The ability of T. pallidum (the syphilis spirochete) to undergo development into cyst forms has already been proven," he tells me. 

A few days later, in her lab at the University of Massachusetts at Amherst, biologist Lynn Margulis, more famous for her advocacy of the Gaia hypothesis -- the Earth as a living organism -- plays me a live-action videotape she's made of spirochetes called spirosimplokos, which are found in the hind guts of desert termites. 

I'm amazed to watch the vigorous recoiling of the organisms into little balls, exactly the kind of behaviour described by Burgdorfer and Moayad, only with a different species of spirochete. 

"It's likely that organisms like Borrelia (Lyme) and Treponema (syphilis) can burrow into tissue and make the same kind of resistant bodies, and wait and come out when conditions are suitable 20 years later. I mean, I've got a couple of years in mud, why not in human bodies?" 

*** 

Whether or not undetected spirochetes are wreaking havoc in AIDS patients, the hunt for "stealth pathogens'' is in full swing, thanks in part to new technologies enabling scientists to "see" hitherto invisible organisms. 

David Relman, professor of medicine and microbiology at Stanford University, is one of a growing number of researchers who note that traditional criteria for establishing infectious causes of disease may not be adequate for finding organisms that are difficult or impossible to cultivate in a petri dish. 

One way of testing for microbes is through polymerase chain reaction (PCR), a technique for homing in on the genetic material that makes up a disease organism and duplicating that genetic material millions of times. Using PCR, medical detectives have been able to find previously undetectable microbes in all sorts of illnesses. 

Gone undetected 

One of these medical detectives is Garth Nicolson, scientific director at the Institute for Molecular Medicine in Huntington Beach, California, who studies chronic illnesses. 

Nicolson has found that much long-term sickness is due to stealth bacteria that have gone undetected. "Without these new technologies, it would not be possible to detect these infections," he says. 

Relman adds that one of the most interesting things about these molecular approaches is the new concepts of causality they give rise to. 

He cites the example of molecular mimicry, in which certain bacteria can fool our immune systems into attacking not just the invading organism, but our own bodies as well. 

This is the case, for example, with the bacteria Chlamydia pneumoniae, which researchers at Princess Margaret Hospital recently found shares genetic sequences with our heart muscle. 

Josef Penninger, whose findings linking heart disease with chlamydia infection were published a few months ago in the pages of Science magazine, tells me he discovered the similarity between the bacterium and heart muscle by logging on to the Net and entering their DNA codes into online databases. 

*** 

Establishing new procedures for making visible what was formerly deemed nonexistent has its challenges. 

Take the case of the new culturing method developed by a team under Greenwich, Connecticut, internist Steven Phillips aimed at locating Lyme spirochetes in patients who are supposed to be cured. The publication of his paper in the European journal Infection opens up a Pandora's box for patients and researchers alike. 

Many are doubtful that the test does what it says it does. Says Lyme researcher Deiter Hassler from Heidleberg, Germany, "To my knowledge, nobody worldwide has found as much (Lyme bacteria) in culture as Phillips has, and we don't know exactly why. I can't believe that so much survives, but I'm not sure." 

Walter Marget, editor of Infection, declares from Munich that "our reviewers are very, very skeptical. I'm not very enthusiastic about this study." 

But the Phillips team is insistent that its finding will forever alter concepts about Lyme, a disease that can take many forms from fatigue to arthritis. 

Hamid Moayad, a neurologist from Fort Worth, Texas, and co-author of the paper, says, "This would actually be the gold standard for diagnosis of Lyme disease, because if you are able to culture the bacteria then no one can doubt the diagnosis any more, especially in the chronic late stages, which the controversy is about. This paper proves without a shadow of a doubt that it is a chronic infection." 

Sam Donta, a leading Lyme specialist who works at Boston University's school of medicine, concurs that you can't conclude there is no infection if blood tests are negative. 

Donta has compared the standard blood tests for Lyme disease with more sophisticated tests, and now questions the criteria for the lab diagnosis of Lyme established by the U.S. Centers for Disease Control. He notes with concern that "physicians are still relying on a negative test as meaning that a person does not have Lyme disease." 

Also banking on negative tests are U.S. insurance companies. Karen Vanderhoof-Forschner, who chairs the board of directors of the Lyme Disease Foundation (sponsors of the New York conference), notes, "There is a lot of money out there to be made by having expert witnesses at trials for insurance companies who feel they can clearly and easily separate those who have the infection from those who are disease wannabes." 

At bottom, if Phillips and team are correct, Lyme disease may prove itself much more widespread than was previously thought. "Given the flaws in currently accepted diagnostic criteria, it is likely that Lyme is vastly underdiagnosed," warns the Phillips paper. 

*** 

Now that doctors have better techniques for zeroing in on hidden infections, they're finding spirochetes in all kinds of patients -- even those who don't show the typical symptoms of Lyme. 

For example, a doctor from New Jersey, Martin Freid, tells me he has found infection with the Lyme germ in at least two of his patients with Crohn's disease, an inflammation of the bowel that affects some 50,000 Canadians and whose precise cause has eluded medical researchers. 

Gordon Greenberg, professor of medicine at the University of Toronto and head of the gastroenterology division at Mount Sinai, says it's not clear exactly what causes either Crohn's disease or ulcerative colitis, another inflammatory bowel disease. 

"There has always been the concept that a single infectious etiology might be the cause of Crohn's or ulcerative colitis," he notes, "but to date no single bacterium or virus has been linked with either disease. What is clear, however, is that bacterial flora within the gut, at least in a secondary way, perpetuate the inflammatory process in Crohn's." 

Greenberg cites several lines of evidence, including studies from his own centre, on the effect of specific antibiotics he's found to be particularly effective in helping to control the inflammation of Crohn's disease. His initial data suggest improvement or remission in up to 63 per cent of Crohn's patients treated with antibiotics. 

"More and more, the concept is emerging that bacteria do play an important role and that selected antibiotics are quite helpful in the management of patients with Crohn's disease," Greenberg notes. 

Lida Mattman, professor emeritus of microbiology at Wayne State University, has spent many decades studying all the different forms bacteria can take and has written two editions of a textbook entitled Cell-Wall Deficient Forms. 

Mattman continues to find odd-shaped bacteria in the blood of patients with all sorts of chronic diseases, at a facility I've come to visit just outside Detroit. 

"I would like a neurologist to tell me why he can't believe that multiple sclerosis (MS) is due to a spirochete," she insists, pounding her fist on the table, "when all you have to do is take a drop of spinal fluid and look at it and you can see them. You don't even have to concentrate it," she says, citing the work of German pathologists published in the scientific literature. 

"Look at the people having trouble with MS, and no research being done on this -- it's criminal." 

The kind of research Mattman is doing isn't exactly familiar to most doctors. Nicolson says much of the new molecular microbiology is not taught in medical schools today, and none of it was presented to physicians trained 10 or 20 years ago. 

But now, he says, there's growing awareness of the role of these infections in a variety of different diseases, and this awareness will only increase with time. 

Paul Ewald, an evolutionary biologist at Amherst College in Amherst, Massachusetts, has advanced the radical idea, dubbed the "new germ theory of disease," that most of our chronic killers -- from heart disease to Alzheimer's to cancer -- must be due to infection. 

Negative effect 

"If diseases have strong negative effect on the survival and reproduction of humans, and they're common, it's unlikely that they have a genetic cause." 

A good example is the epidemic of infertility among women in the 1970s, which mystified researchers at the time. "Let's say they had some sort of bad gene," Ewald hypothesizes. 

"Think what would happen over the next few generations. Those genes would be lost in quite short order. The fertility problem decreases fitness so much that it would disappear." (As it turns out, the epidemic of infertility was caused by an epidemic of Chlamydia trachomatis.) 

Ewald notes how quickly conventional thinking about diseases can change. He points to the complete about-face on what causes ulcers. 

"If you open a medical text from the 1970s, you'll see almost everything listed as a cause of ulcers, except infection. And now we know that it's infection that is the main culprit and that all these other factors -- stress, maybe smoking, things like that -- are exacerbating the problem but are not the primary causes." 

Obviously, identifying the main culprits in chronic diseases is important, Ewald says, because it suggests where we should be putting most of our effort. 

"If we are interested in reducing atherosclerosis, if we knock out the organism, maybe some of these other risk factors are not going to be particularly important. So it's very important to distinguish what is just another risk factor from what is the primary cause of the problem."