The appraisal’s authors included many original guideline writers as well as a CDC microbiologist, Barbara J.B. Johnson, who had long published with IDSA Lyme researchers and represented their viewpoints within the agency. Another lead author was Susan O’Connell, a microbiologist who headed the British health services’ Lyme Borreliosis Unit, assuring guideline writers that their dictates concerning Lyme disease would be upheld in the United Kingdom as well. Similarly, scientists from Slovenia, Sweden, Denmark, and Austria have at various times published with the authors of the United States guidelines for Lyme disease care, facilitating the export of a prime American product: medical knowledge endorsed and promoted by the highest echelons of US scientific publishing and government.
So close are these ties that in 2016 the New England Journal of Medicine published the results of yet another treatment study, conducted in the Netherlands, which debunked long-term treatment for Lyme disease. The study used a similar treatment regimen of previous, supposedly failed, trials even as emerging science was questioning the effectiveness of such drugs. Moreover, the study acknowledged uncertainties and mixed findings: Patients in all three treatment groups showed early improvement, while, at fourteen weeks posttreatment, researchers saw significant physical improvement but not in quality of life. The journal’s brand overshadowed these questions, as it long had. The overall findings that more antibiotics “did not have additional beneficial effects on health-related quality of life” were hailed in an NEJM editorial that called the study “well-performed,” while its findings were widely reported as sealing the deal against longer treatment.
In November 2011, Britain’s General Medical Council ruled that a general practitioner from the north of the country near Manchester had “diagnosed an infection similar to Lyme disease in patients with chronic fatigue syndrome (and) adopted an ‘unwavering mindset’ that ignored mainstream medicine.” For prescribing long-term antibiotics and other unconventional treatments, Dr. Andrew Wright, one of the area’s only physicians to treat advanced Lyme disease, was found to be “impaired” to practice. Around that table in the Winchester pub, UK Lyme patients told me of being cut off from antibiotics that had helped them, seeing a succession of doctors unwilling to treat, and being referred for psychiatric care. One had tested negative long after he had had the Lyme disease rash, when the CDC maintains tests “almost always” turn positive. This single “impaired” physician had helped them. “I count my blessings that I found him,” a woman with longstanding Lyme commented online. Wright made the mistake of using unsanctioned diagnostic tests and a procedure not approved for office use that carried risk. But his real offense, like the New York doctor cited for record-keeping errors, was failing to follow the Lyme treatment guidelines. A French physician likened the atmosphere surrounding this disease to the Inquisition. Indeed, as I read the statement on Dr. Wright, in the context of diagnostic uncertainties and evidence of Borrelia burgdorferi’s considerable complexities, it reminded me of historical artifacts from an era of heretics and witches. Soon, I believe, it will be viewed that way.
Monkey Business
Starting in the first decade of the twenty-first century, the other side of the Lyme divide, in that parallel universe that had long agitated on the edges of the debate, began to gain credence and produce research breakthroughs. One of these came from a young scientist at Tulane University, Monica Embers, who had used Borrelia burgdorferi-laden syringes to infect five Rhesus macaques, which are small brown monkeys known for their pink, expressive faces and big eyes. Months after treating three of the animals with oral antibiotics, Embers and her colleagues then looked for evidence that the infection had survived. Among their methods, they used a technique called xenodiagnosis, in which uninfected ticks were put onto the treated monkeys and allowed to feed. Then the ticks were dissected, their mid-gut contents subjected to a stain and put under fluorescent lights. Sure enough, samples from ticks that fed on two of the treated monkeys lit up.
There, on a midnight black background in living lime green appeared more than a few coiled, curved, and entirely whole spirochetes, organisms that were supposed to have been dispatched by modern-day drugs. Evidence of Borrelia DNA also was detected in the monkeys themselves, reinforcing findings of persisting post-treatment infection. True, the animals had been artificially infected, rather than sickened by tick-bite. “Our studies do however offer proof of the principle that intact spirochetes can persist in an incidental host comparable to humans, following antibiotic therapy,” wrote Embers in PLOS One, an online open-access journal. Significantly, the experiment had used ninety-day antibiotic treatments, about three times longer than the guidelines recommend.
Several years earlier, Mario Philipp, who initiated the Tulane study, had infected twenty-four other macaques but was less successful at finding evidence of persistence in the twelve that were treated; he did not use the technique that Embers did. But he did find something else among animals given injections chock full of Lyme spirochetes. Seven of twelve monkeys tested negative 63 to 94 weeks later without ever being treated, lending credence to assertions that patients often do not test positive for infection when, in fact, they are.
Embers et al. weren’t the first to show that the Lyme spirochete survived antibiotic treatment. In the early 1990s, a European study found live B. burgdorferi in the skin of five of twenty-eight people three months after they were treated with antibiotics; at least one other European study isolated the organism from a single treated patient. In animal studies over the previous two decades, Lyme spirochetes had been found to withstand antibiotic onslaught in dogs, mice, and other primates. Those animal studies generally based their conclusions on finding DNA of the spirochete, which is an accepted diagnostic tool, rather than by finding the bug itself. This time, however, Embers recovered actual spirochetes. Hers and the emerging research of others—by scientists at Johns Hopkins, Columbia University, UC Davis, and Northeastern—strengthened the argument that Lyme disease wasn’t always cured by the limited antibiotic courses vigorously defended by guideline writers. Four years later, a Tufts researcher, Linden Hu, would use xenodiagnosis to recover B. burgdorferi DNA from ticks attached to two of twenty-three Lyme patients; the only place they could have picked it up was from people who were supposed to have been cured. Nonetheless, Hu’s team concluded, cautiously, that it did not mean “viable spirochetes” were in the patients themselves.
At a conference in New York City in 2016, I met a physician, Nevena Zubcevic, who had completed her residency at Harvard Medical School’s Spaulding Rehabilitation Hospital in Boston. There, where many of the Boston Marathon bombing victims had been treated in 2013, Zubcevic saw patients come in with all the signs of having suffered traumatic brain injuries—neurological deficits, functioning problems, pain. To her surprise, she concluded many were actually suffering from Lyme disease. Moreover, these patients told stories of having been turned away by many doctors who, following standard protocols, had been told they should not give additional antibiotics so gave nothing at all. “They couldn’t go on,” Zubcevic told a group at Martha’s Vineyard Hospital in 2016, on an island off Massachusetts where Lyme disease rates are among the highest in the United States. “Some patients show symptoms of posttraumatic stress disorder because they’ve been ignored for so long. Marriages dissolve all the time because one spouse thinks the other is being lazy. Many chronically ill patients end up alone.”
In 2015, Zubcevic helped found the Dean Center for Tick-Borne Illness, based at Spaulding. Several decades into the epidemic of Lyme disease, it was the nation’s first, and still only, rehabilitation center for Lyme disease patients. This is startling when one considers that well over two million people have been infected in the United States just since 2004, with perhaps 200,000 to 400,000 suffering lingering posttreatment problems.
To Zubcevic, Lyme disease care is complicated by poor diagnostic tests, multiple species of B. burgdorferi that manifest with different symptoms, and other pathoge
ns that are delivered in a single tick bite. These include coinfections from Babesia and Bartonella, which the Klempner study never addressed. “This is very complex and messy, and I work with that mess every day,” she told the conference. “I don’t have the privilege of just working with Lyme disease. I wish that I did. My job would be a lot simpler.” When I asked whether she followed the prevailing treatment guidelines, Zubcevic was firm: “I don’t practice cookie-cutter medicine,” she said. “We have to go beyond these guidelines.”
“The Lyme Loonies”
In my research for this book, I was always quick to say, since I was often asked, that I was not a long-term or chronic Lyme sufferer. A hastily treated Lyme infection occurred after I began researching the disease in 2012, while another had been resolved years earlier. Both were signaled by rashes. In the controversy over Lyme disease, those seen as having vested interests—mostly the sick and those willing to treat them—have long been denigrated and dismissed. In 2013, I obtained several thousand pages of Centers for Disease Control emails that revealed a disdain for, even a fear of, Lyme patients. In one, an official at the National Institutes of Health wrote to a CDC microbiologist in 2007 to say goodbye upon his retirement. “I will certainly miss all of you people—the scientists,” wrote Phillip Baker, the NIH Lyme program officer, “but not the Lyme loonies.” In another email, an author of the guidelines commented to CDC and IDSA colleagues on a public protest by Lyme patients in Connecticut. “We need to mount a socio-political offensive; but we are out-numbered and out-gunned,” wrote Durland Fish, a Yale University entomologist. In a separate email, Gary Wormser, the lead guidelines author, instructed his CDC and IDSA coauthors on an upcoming article to emphasize the risks of long-term antibiotics: “superbugs, death from treatment, biliary disease, cost, etc etc would be good,” he wrote. There was very little room for opposing views in the echo chamber that is the CDC–IDSA relationship. Patients who had a different view of Lyme disease were a bother there, and so were their doctors.
Testament to the parallel universes I have noted, I did not see a single major Lyme disease researcher from the mainstream side at the Mount Sinai conference at which Dr. Zubcevic spoke. The gathering was not supported by the CDC or National Institutes of Health but by a nonprofit group, the Steven & Alexandra Cohen Foundation, which had also underwritten many of the researchers who presented. These were scientists who believed in something other than the traditional view of Lyme disease and who had plowed ahead largely without government support.
Ying Zhang, a Johns Hopkins University researcher, was one of them. Zhang had done pioneering work in the early 1990s on the mechanism that allowed tuberculosis to survive antibiotic treatment, which represented a leap forward in TB understanding. Starting in 2014, Zhang and his research group published seminal articles on the failure of frontline antibiotics—doxycycline, amoxicillin, ceftriaxone—to kill what have been called Lyme disease “persisters.” This and other test-tube research offered a compelling explanation for why patients remained sick. The organisms changed shape, hid, or otherwise went dormant—the persister cells—in their quest to evade elimination.
Yet Zhang, a scientist with an international reputation at a top university, was rejected for government grants and publications. Reviewers, he told me, said it wasn’t clear if “the few persister organisms” found in such studies caused ongoing symptoms or if patients even had “bona fide Lyme disease” in the first place. Similarly, Richard Ostfeld, a leading researcher on the interplay between ticks and the hosts that support them, was denied funding in a review that called Lyme a “middle-class disease.” So was Monica Embers, the monkey researcher, whose grant reviewer, she recalled, commented, “Lyme isn’t that much of a problem, and there’s a vaccine anyway,” which there wasn’t. Indeed, Embers’ paper on chronic infection in Rhesus macaques was rejected by at least three journals before finding a home in PLOS One. “I absolutely expected it because I knew we were challenging dogma in a way,” Embers said in relating the story. That dogma still held sway even though, as far back as 1997, a young doctoral student at Cornell University, Reinhard Straubinger, had reported the spirochete’s survival in dogs treated with antibiotics, and researchers since had found spirochetes in treated gerbils, rats, hamsters, and guinea pigs. Stephen Barthold, a scientist at the University of California, Davis, and member of the prestigious National Academy of Medicine, had observed the phenomenon in mice in 2008, yet he also faced what he called “prejudicial” reviews for grants.
European scientists have also faced such hurdles. “I’ve tried to publish in many journals,” Christian Perronne, a physician on the infectious diseases faculty at the University of Versailles Saint-Quentin, France, told a conference in Norway in 2014. “If you try to publish a little bit different from the guidelines, it’s anti-science.” He told the story of a colleague who had lost a university position after reporting substantial rates of infected ticks in the countryside. “Maybe I will be next,” said Perronne dispassionately. This from a physician who had served as president of the Communicable Diseases Commission at the French High Council for Public Health and vice president of a working group on European vaccination policy for the World Health Organization.
Yet his and other science, which has time and again bucked the traditional view of Lyme disease, has had to claw and scrape to break through amid denial and dismissiveness. Even letters that have questioned conventional published research, scientists have told me, are routinely rejected by journal editors. The experiences of these and other scientists, who said they approached their Lyme research with healthy skepticism, are emblematic of the ways the disease has been pigeonholed and minimized. They are rooted in the “easy-to-treat” mentality, the group-think that, while acknowledging that some patients suffer a vague array of problems afterward, sees antibiotics as curative and Lyme disease as a single, surmountable disease.
As Zubcevic’s patients attest, the disease is anything but. Kim Lewis, a distinguished professor and director Northeastern University’s Antimicrobial Discovery Center, found evidence in laboratory experiments published in 2015 that the Lyme spirochete had survived recommended antibiotics like doxycycline. A Moscow University trained microbiologist, Lewis spoke at the Mount Sinai conference of Lyme disease patients who do not get well after treatment. “Interestingly, when you show up at the doctor’s office,” he said, “nobody tells you that you have a 10 percent probability that something very unpleasant is going to happen to you, and maybe we won’t have any remedy for that. We’ll just give you some doxycycline and you’ll be fine. A lot of people are not.”
What Embers, Perronne, Zhang, Zubcevic, and Lewis were fighting was the image of Lyme disease enshrined in the IDSA treatment guidelines—and American medicine. The guideline writers, a close-knit, like-minded group, did solid work on the early phases of the disease. But their vision was stuck there while science evolved, their guidelines rife with their own “expert opinion,” which is the basis of half their recommendations. Following suit were the agencies that should have been funding research on the later and protracted manifestations of Lyme disease. “The early part of the disease is only a part of the story,” Zhang told me. “The IDSA line is very restrictive.” So, too, is the official view of Borrelia burgdorferi’s human toll, as captured in the CDC’s proclamation that only a “small percentage” will have ongoing problems after treatment. Nothing to fret about, unless you are in that group, which may not be so small.
In 2005, a statistician from Germany and an epidemiological researcher at Oxford University analyzed five published studies on the after-effects of Lyme disease. Comparing 500 patients to 500 controls, the researchers found that rates were “significantly higher” among Lyme disease patients for “fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years despite antibiotic treatment.” In 2015, four researchers at the University of Freiburg in Germany, reviewed thirty-four studies on post-Lyme conditions for an article in the Jo
urnal of Neurology. They found that 28 percent of patients suffered continuing symptoms after treatment for Lyme neuroborreliosis, a form of the disease in which the spirochete has infected the nervous system, sometimes leading to severe headache, eye problems, lapses of memory and thought, depression, and facial palsy. Even the study used by the CDC to conclude the post-Lyme toll was small dutifully reported that eight other studies had found posttreatment rates as high as 41 percent. Moreover, the study’s supporting editorial—the one that equated post-Lyme symptoms to Americanitis—included this caveat: The study “did not specifically include patients with…neuroborreliosis or late Lyme arthritis. Such patients could answer survey questions differently in the long term,” it said. So why did the CDC rely on the under-5 percent rate—or on this paper at all?
Instead, in adopting the position that a “small percentage” of patients may experience posttreatment symptoms, the CDC brushed aside dozens of other studies that showed quite the opposite: Lyme lingered.
CHAPTER 5: “Little Armored Tanks”
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Bob Maurais runs a tick control company in Portland, a harbor city along the green coast of Maine, where he grew up in the 1950s and 1960s. Back then, Maurais spent a lot of time in the state’s southern hardwood forests, trolling for natural treasure with three older brothers. He cannot recall a single blacklegged tick, or any other tick for that matter, from when he was a boy. Today, they thrive. In the winter of 2013–14, Portland received eighty inches of snow, had ten days of temperatures below zero, and the coldest March in fifty years. The tick population, responsible for a sixfold increase in Lyme disease over the previous decade, shook off its slumber, nonetheless robust and unscathed. “They are not going away anytime soon,” he told me.
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