The Legacy of Thomas McPherson Brown, MD
MIRA Therapy for Connective Tissue Disease
by Henry Scammell
Nothing is likely to ruin a good reputation in medicine faster than being the first to come up with the right answer while the rest of the institution is comfortably bedded down with familiar folly. When the truth finally does come out, even after decades, that doesn't always mean the world immediately stops punishing the prophet. Heretics make great scapegoats, and the process often continues for a time even after they're safely dead.
Thomas McPherson Brown, MD, is a case in point. Working with Albert Sabin (later of polio vaccine fame) at the Rockefeller Institute just before World War II, Brown isolated a bacteria-like agent from the joint fluid of an arthritic woman and speculated that it might be the infectious trigger for her disease. The bug in question, then generically classified as an L-form, was too small to identify precisely, but with the advent of electron microscopy it was shown to be a class of cell-wall-deficient organisms which scientists named mycoplasma, for watery fungus.
Mycoplasma is ubiquitous and not at all easy to get rid of, but Brown found that it usually could be controlled by long-term, low-level doses of tetracycline. As that class of antibiotic evolved, he got even better results with the second and third generation, doxycycline and minocycline. Up to then, the only treatments for the various forms of inflammatory arthritis w ere for the symptoms, and this was the first credible therapy aimed at a probable cause.
Of course, because Brown's treatment generally produced positive results, he became immensely popular with his patients, a vocal, partisan constituency eventu ally some 10,000 strong, which proudly referred to itself as "Doctor Brown's Army." But very possibly for these same reasons, among his peers and many of his colleagues he was variously dismissed as a misguided zealot, a benign eccentric, or a serious, boat-rocking troublemaker, and he found himself progressively cut off from the usual sources for the funding of research. As painful as this must have been, it hardly seemed to slow him down.
After the war Brown headed up arthritis research for the Veterans' Administration, and eventually became Dean of Medicine at George Washington University Medical School and a medical consultant to the White House. By the time I met him 1988, he had retired from GWU but still maintained a thriving clinica l pract ice and directed the Arthritis Institute at the National Hospital just outside Washington. Although he depended on a cane, he still had the handshake of a lifelong tennis player, a warm, gentle laugh, and the smiling, caring attentiveness of a natural healer. It was easy to see why he was so widely loved.
The reason for our meeting was to collaborate on a book that set forth his theory and treatment for the inflammatory forms of arthritis. Our effort gained some poignant urgency from the fact that we both knew he was dying of cancer. Although he was the author of over 100 medical articles in prestigious peer-reviewed journals, the general public was still in the dark about the benefits and promise of antibiotic therapy. A book seemed the only way to continue Tom's lifelong battle against mankind's oldest and most widespread crippling disease, and to make the therapy available to the millions who would still need it when he was gone.
Although in many cases the therapy brought about remission or even reversal of rheumatoid arthritis, Dr. Brown cautioned me at our first meeting against presenting antibiotics as a cure. While they didn't work for everyone, he estimated his success rate at above 90 percent for those who stuck with the therapy (an estimate I have since heard from other physicians who treat large numbers of patients with his protocol.) The timetable and degree of response could vary for individual patients, Brown said, by such factors as how much time had elapsed since o nset of the disease, the severity of symptoms, age at diagnosis, family history, and not least, any damage that already may have been done to the patient's overall health and particularly to their immune systems by the more widely accepted therapies for arthritis. Ironically, many doctors who dismissed minocycline as either unproven or unsafe for rheumatic disease were perfectly happy to prescribe a frightening pharmacopoeia of other "standard" therapies including the potent cancer drug methotrexate, or gold salts, possibly the most lethal prescription drug ever passed by the FDA. None of these other therapies had ever been proven to produce long-term benefits, and most let the disease worsen while masking symptoms.
Tom Brown lived just a year aft er the book's publication. That was plenty of time to experience the further slings and arrows of his peers ("I just hope he isn't hurting anybody," one of them observed piously for the cameras of 20/20), but not nearly long enough for vindication. The first serio us study of his therapy didn't begin until nearly three years later.
The treatment described in our book is now widely referred to as MIRA therapy, from that landmark, NIH-sponsored study of Minocycline In Rheumatoid Arthritis. But the MIRA trials were hardly undertaken as a tardy attempt at salvaging Tom Brown's reputation; quite the contrary. As one of the principals recently told me, at the outset at least half of the six participating centers entered the study with open skepticism. For one thing, Brown's theory and treatment flew in the face of almost everything that was then held to be true of rheumatoid arthritis. For another, because the NIH appeared to be bending to pressure from Congress in the wake of our book, the study rekindled serious resentment against the persistence of his influence even from beyond the grave. Many expected the MIRA trials would simply drive Tom Brown's ghost from the stage, and rheumatology would be able to settle back into its familiar rut of empty hopes and unf illed promises.
That all began to change even before the MIRA trials were finished. Without decoding which patients were receiving placebo and which got minocycline, it was obvious that more of them were improving than would
be expected for that size group. When the results were finally published in Annals of Internal Medicine in 1995, it was revealed that well over half of the minocycline patients had improved by at least 50% according to subjective criteria of joint tenderness and swelling. E ven more experienced dramatic improvements in objective measurements of their blood work.
Not everyone was surprised. When Tom Brown had made his final television appearance on Good Morning America back in 1988, Joan Lunden said his approach to arthritis was "turning the medical world upside down." His answer was a quiet, "I'm trying to turn it rightside up." Seven years later, with the decoding of the MIRA study, for those who still remembered that exchange the words now rang like prophesy. It was only logical to the members of Dr. Brown's Army that the therapy that had turned around their diseases and given them back their lives would work as well for others. That was the whole point of the book.
An editorial accompanying the MIRA study described the outcome as "highly significant...with minimal adverse events." It said that together with similar results from a smaller study in the Netherlands, the results "could be submitted to the Food and Drug Administration as the two positive 'pivot al' controlled clinical trials required for approval of a new drug application."
What are those 'minimal adverse events' sometimes associated with minocycline? The best known is sun sensitivity, which is easily avoided by a good blocker and the pr oper clothing. While none of the MIRA patients showed serious toxicity, seven dropped out of the study, most commonly for dizziness. This is a known problem with minocycline, but apparently not with doxycycline, which Tom Brown would often use as an alter native. Another adverse reaction, so infrequent that it was not reported in the MIRA study, can be hyperpigmentation, a darkening of the skin in patches, usually on the hands and forearms, which disappears when the therapy is stopped. It also can discolor teeth of small children. The most serious-sounding objection to minocycline is that it is an antibiotic, a class of pharmaceuticals under considerable - and legitimate - criticism for wide scale overuse, particularly in diseases where it encourages resis tant forms of the organisms it attacks. But that argument ignores the benign profile of antibiotics in the tetracycline family, proven least prone to this disadvantage in literally billions of doses for conditions no more serious than teenage acne. And it also overlooks the special nature of mycoplasmas. When most bacteria are attacked by an antibiotic, they immediately put up a defense in the form of mutation, based on a decision formed at the point of impact in the cell wall. But be cause mycoplasmas are cell-wall-deficient organisms (toroidal in shape, they look like partially nibbled donuts), the antibiotic action takes place primarily in the cell's core, where no such response occurs. I have met several of Tom Brown's patients who have controlled their connective tissue disease with minocycline for decades, and the only other effect they ever noticed was that they almost never were bothered by the common cold.
There now have been at least seven major studies of Tom Brown's theory and treatment, including publication of O'Dell's landmark trials in Nebraska where one-third of the patients who had improved on minocycline in the first year achieved remission by the end of three years. The results were even better for year four. In 1998, The Lancet published a small, open study of usually fatal systemic scleroderma at Harvard Medical School, sponsored by The Road Back Foundation and the National Institutes of Health; two-thirds of the completers were in remission after 48 week s of this therapy. Today, minocycline and doxycycline are widely prescribed for the various inflammatory forms of arthritis and other connective tissue diseases such as scleroderma, lupus and fibromyalgia. Minocycline is now listed as a standard treatment for both rheumatoid arthritis and Lyme disease by the Arthritis Foundation and the USP.
But at the same time Tom Brown's safe, inexpensive and highly effective therapy is becoming the new standard treatment for many of those diseases, the paradox remains. Even though the specialty of rheumatology proved the treatment works, many practitioners in that field still resent the way the MIRA study happened, and either refuse to give it or they limit its availability to those fortunate few patients who are informed enough to ask for it. Along the way, perhaps because the institution has lost the capacity for change and renewal, rheumatology has become the fastest declining specialty in medicine.
Meanwhile, the rehabilitation of Tom Brown's reputation is progressing nicely, as they like to say in medicine, with full recovery just around the corner. When he and I set out to preserve his theory and treatment for those who would live after him, we had no idea our effort would prove so durable. But the new edition of our book is updated with results of the latest clinical trials and illustrated with new case histories and pictures of recovered patients doing the most improbable things such as rock-climbing and scuba diving. Ten years after we wrote the first version and n ine years since his death, Tom Brown's legacy, updated and reissued as The New Arthritis Breakthrough, was ranked by Library Journal as the #1 best-selling health book in America. I can hear Tom's warm, familiar chuckle at how it's turning out.