New ideas are constantly being generated and tested in modern science; it is an intrinsic part of the process of scientific growth. At the same time, many of these new ideas are scoffed at when first introduced.

By the early 1990s, enormous advances had been made in the study and understanding of Lyme disease-not only in terms of what physicians knew about the disease but also in terms of understanding Lyme disease as a public health problem. Nevertheless, by the early years of the last decade of the twentieth century, Lyme disease was developing a political twist, with two main "parties," or camps, that had differing points of view, mostly concerning the treatment of Lyme disease.

These two camps are descriptively called conventional and alternative. Neither term is meant in a pejorative sense; "conventional" simply describes the fact that these people support the treatment standard that most organizations and physicians support. "Alternative" describes the fact that some medical practitioners and communitybased patient groups believe that there is another, more effective way to treat some patients with Lyme disease. This does not necessarily refer to "alternative" medicine in the sense of herbal remedies, acupuncture, biofeedback, and the like. It is simply a competing paradigm.

Allen Steere typifies the conventional camp. Of mainstream physicians and scientists, the majority would agree with Steere's view of Lyme disease. The alternative camp is typified by Dr. Joseph J. Burrascano Jr., an internist based in Long Island who specializes in Lyme disease and who has written many treatment guidelines for the disease. The view, or paradigm, of the conventional camp can be summarized thus: " EM [erythema migrans; the rash of early Lyme disease] is seen in 90 percent or more of patients with Lyme disease. " Lyme disease can be diagnosed relatively easily. " Currently available blood tests are highly accurate in latepresenting cases. " Existing treatment works in most patients. " Antibiotic therapy beyond one month (or at most two months in resistant cases) is unnecessary and possibly harmful.

The paradigm of the alternative camp is noticeably different: " EM occurs in only approximately 50 percent of cases. " The currently available serologic tests are inaccurate in as many as 35 percent of late-presenting cases. " Many patients will fail to respond if given medication that follows existing treatment recommendations. " Long-term antibiotic therapy is frequently necessary to control, if not to cure, Lyme disease.

During the 1980s and 1990s, people with Lyme disease began to come together in support groups all over the country. Lyme disease- related Web sites also sprang up. An Internet search for "Lyme disease" on October 30, 2001, yielded more than 171,000 hits. These sites may be associated with universities or various Lyme disease organizations, or they may be the Web sites of individual patients or support groups. Emotions can run high; the language on some of these sites is quite provocative. And the accuracy of the statements on some of these sites must be questioned. Web-based information in all fields has exploded over the past decade; however, there is no arbiter for accuracy, and considerable variability in quality exists.

In 1990, Leonard Sigal, a Yale-trained rheumatologist philosophically aligned with the conventional camp, published a paper in the American Journal of Medicine reporting on the first one hundred patients who came to his Lyme disease clinic at the Robert Wood Johnson Medical School in New Jersey. Sigal concluded that only thirty-seven of those patients actually had Lyme disease. Twenty-five of the one hundred were diagnosed with a malady called fibromyalgia. Three years later, in 1993, Steere and colleagues published a similar paper of their experience at the New England Medical Center in Boston. Steere reported on nearly eight hundred patients who had been referred for probable Lyme disease. Steere thought that Lyme disease was causing the symptoms in only 23 percent of that group. He, too, diagnosed fibromyalgia, as well as chronic fatigue syndrome, in many of these patients. Steere also claimed that patients who were sero-positive in other labs were sero-negative in his lab.

Both Sigal and Steere believed that most of the courses of antibiotics that had been given to these patients had been administered in error and that the most common reason for lack of improvement after antibiotic treatment was the incorrect diagnosis of Lyme disease in the first place. The alternative camp rallied against these articles, especially Steere's, which was titled "The Overdiagnosis of Lyme Disease" and was published in the high-profile journal JAMA.

Just four months later, on August 5, 1993, the U.S. Senate Committee on Labor and Human Resources conducted hearings to examine "the adequacy of current diagnostic measures and research activities in the prevention and treatment of Lyme disease." The hearings had originally been scheduled for the week before but were changed at the last minute, even after many people had traveled to Washington to testify. Because many of them could not return to the capital on August 5, their testimony was included in written form. Counting these written testimonies, more than four hundred statements were placed into evidence.

During governmental hearings, panels of four or five witnesses often make prepared statements and are then questioned by members of Congress. Each panel usually consists of four or five people sitting at a long oak desk behind microphones and identification placards. Perhaps nowhere was the gap between the thinking of the conventional and alternative camps more apparent than when the second panel of witnesses gave its testimony. Both Allen Steere and Joseph Burrascano were seated on that panel.

Burrascano began: "There is in this country a core group of university-based Lyme disease researchers and physicians whose opinions carry a great deal of weight. Unfortunately, many of them act unscientifically and unethically. They adhere to outdated, selfserving views and attempt to personally discredit those whose opinions differ from their own. They exert strong, ethically questionable influence on medical journals, which enables them to publish and promote articles that are badly flawed. They work with government agencies to bias the agenda of consensus meetings and have worked to exclude from those meetings and scientific seminars those with ultimate [sic] opinions.

"They feel that when the patient fails to respond to their treatment regimen, which is a common occurrence, it is not because the treatment has failed, but because they have developed a new illness, what they call the 'post Lyme syndrome.' They claim that this is not an infectious problem but a rheumatological or arthritic malady due to activation of the immune system.

"Because of this bias by this inner circle, Lyme disease unfortunately is both underdiagnosed and undertreated in this country to the great detriment of many of our citizens."

Then Steere, seated only two seats to Burrascano's left and testifying just a few minutes later, spoke: "There is no evidence that many months or even years of antibiotic therapy are necessary to eradicate the Lyme disease spirochete. Because of the success of early antibiotic therapy in acute Lyme disease, chronic active Lyme disease has become an unusual illness. However, infection with B. burgdorferi may occasionally trigger several puzzling syndromes that appear to continue after apparent eradication of the spirochete. . . . we have reported, as have others, that infection with B. burgdorferi may trigger chronic fatigue syndrome or a chronic pain syndrome called fibromyalgia. In our experience, these patients are not helped by further antibiotic therapy.

"Finally, it is important to point out that chronic Lyme disease has become a catch-all diagnosis for a number of confusing and diffi- cult-to-treat conditions. Of 788 patients evaluated at our center in the last five years who were referred with a presumptive diagnosis of chronic Lyme disease, . . . we thought that the majority had other illnesses, particularly chronic fatigue syndrome or fibromyalgia, not triggered by spirochetal infection."

This counterpoint was not lost on the senators. At one point during the testimony about diagnostic testing, Senator Howard Metzenbaum of Ohio interrupted Burrascano and said, "This gentleman [speaking of Steere] says exactly the opposite of what you said." Burrascano and Steere then debated the relative merits of serologic testing for Lyme disease. At several points during their testimony, the crowd, filled with patients from Lyme disease support groups, alternately cheered or booed.

One of the biggest differences between the conventional and alternative camps regards the duration of antibiotic treatment for all stages of Lyme disease, but especially for late-stage Lyme disease. It became clear in the late 1980s and early 1990s that some patients, especially those who had been diagnosed and treated late in the natural course of infection with B. burgdorferi, developed chronic symptoms. On this point, nearly everyone agreed. At some time after being treated for Lyme disease, these patients experienced pains, numbness, and sleep disturbances. They also had trouble concentrating, as well as a profound sense of fatigue, often requiring twelve to eighteen hours of sleep per day.

There are only so many logical possibilities to explain such persistent symptoms. The alternative camp believed that the correct explanation was persistent infection with B. burgdorferi. To use a war analogy, this would be comparable to the fact that all of the enemy soldiers had not been eliminated. They might have been hiding in buildings or in caves, and when the friendly troops left (when the antibiotics were stopped), the enemy (the spirochetes) reemerged to wage war on the body.

Another explanation is that the symptoms could be the result of permanent tissue damage from the initial infection. Even though the spirochete was gone, the damage left behind could still cause nerve cells to misfire or other injured cells to malfunction. This would be akin to having persistent problems after a battle because some of the infrastructure had been permanently damaged. If the war damaged the train tracks and the electrical and water systems in a region, persis- tent "symptoms" in the war-ravaged areas would continue for some time until these services were restored, even though the enemy had been vanquished.

A third possibility is that the problem could be an autoimmune response triggered by molecular mimicry. Rheumatic fever is such an example. The streptococcus bacteria may be killed, but antigens on the surface of the bacteria share common shapes with antigens on host cells in the heart and nervous system. Thus, the heart valves and parts of the nervous system can be attacked-not, however, by the bacteria, but by the patient's own lymphocytes and antibodies. This is like collateral, unintended damage in a war. The host defenses target the spirochetes, but because some of the good guys (that is, the cells in the nervous system) have a similar appearance, they are attacked as well. Because these cells persist after the real enemy has been wiped out, they may cause ongoing problems in identification of who is enemy and who is not.

Still another possible explanation for these persistent symptoms is that Lyme disease triggers a second process-such as fibromyalgia, chronic fatigue syndrome, anxiety, or depression. This would be similar to the effect of a war on the economy. The bombs or missiles do not directly affect the economy, but the shifts in consumer and defense spending or consumer confidence do. The war is over, but this new problem, triggered by the war, is set in motion and causes its own set of problems that have their own set of solutions. Similarly, the immune system could be nonspecifically "revved up," and the immune cells or their by-products could damage host cells. This is the likely mechanism for some patients with persistent joint swelling in Lyme disease. The war analogy here is that army or intelligence personnel have been activated, but after the war is over, they persist in their activity, sometimes a bit overexuberantly.

Even another explanation for persistent symptoms after treatment for Lyme disease is that a second disease is present-either a coinfected tick-borne organism or a second disease altogether. To continue the war analogy-there are two factions of the enemy; one has been wiped out, but a second faction (the coinfecting organism) is still fighting. Or in the case of a second disease, there is in fact a new war against a different enemy. Although patients can be reinfected by a second tick bite, these arguments largely apply to patients with persistent symptoms from a single initial infection.

Of course, the possibility also exists that one of the above mechanisms is operating in some patients, with others relevant to other patients, or that multiple mechanisms are at work in any individual patient.

The conventional camp believed that the active infection with B. burgdorferi had been eliminated in these patients and that these symptoms were from a variety of causes-most commonly fibromyalgia or chronic fatigue syndrome. The alternative camp believed that these patients still harbored active infection with the Lyme spirochete. It is easy to see why these two groups' ideas on therapy diverged in such opposite directions. If these persistent symptoms were being caused by fibromyalgia or chronic fatigue syndrome, then the treatment should be directed against those problems. But if symptoms were due to persistent infection, then more antibiotics would be a reasonable option.

The conventional researchers could find no evidence of the spirochete (by culture) or its DNA (by PCR) after one to two months of therapy. They believed that any symptoms that persisted, at least in most cases, were not due to the persistence of living borreliae. The alternative camp felt that to say that one's Lyme disease is cured and to pronounce any new symptoms to be due to a new disease-chronic fatigue or fibromyalgia-was making a big assumption, pointing to three lines of evidence against this assumption.

First was their own "in-the-trenches" experience with large numbers of patients whom they were seeing with severe, persistent symptoms that seemed to improve after repeated courses of antibiotics. The second line of evidence was experimental. Experiments suggested that B. burgdorferi could be enveloped by lymphocytes and macrophages or become cloaked by the lymphocyte cell wall, thus helping it evade the patient's immune system. Other experiments showed that B. burgdorferi could live inside cells even when those cells were bathed in otherwise toxic amounts of the antibiotic ceftriaxone. Still others showed that the spirochetes could change their outer coat membranes, typical of borreliae, and some have suggested that B. burgdorferi can morph into a dormant form. The third line of evidence in support of the notion that live B. burgdorferi remained in chronically symptomatic patients was the occasional case reports of actual patients, such as Dr. Leigner's, who were treated with "curative" amounts of antibiotics but then later had a positive culture for B. burgdorferi.

The conventional camp accused the alternative doctors who were prescribing long courses of intravenous antibiotics of profi- teering from these desperate patients, either from the fees they received from the patients themselves or from kickbacks from the companies behind home intravenous therapy. Likewise, the alternative camp accused the conventional doctors of lining their pockets with consulting income from big insurance companies, which favored shorter courses of antibiotics because it would cost them less money. They also believed that the conventional physicians had cornered the market on NIH grant money.

All this controversy led the different groups of physicians to consider different treatments.

Excerpt from Bull's-Eye: Unraveling the Medical Mystery of Lyme Disease by Jonathan A. Edlow, M.D., published by Yale University Press. Used by permission.