Saturday, June 29, 2013
No rash developed, and Kaleigh was fine—strong enough to become an all-American swimmer both in high school and at Union College. There were times during high school when she felt mentally hazy and not quite right physically, which she attributed to allergies or a teen-age bout of mononucleosis. But at the end of her freshman year in college she found herself crippled by anxiety, depression, and insomnia. She was beset by searing headaches, her muscles often felt as though they were on fire, and her brain seemed wrapped in a dense fog. Kaleigh tested positive for Lyme disease. Like most physicians, her doctor followed the standard medical practice, endorsed by public-health officials throughout the United States, and prescribed a three-week course of antibiotics. "I was so happy to know what was wrong with me," Kaleigh said. "For a while, I didn't mind the pain."
The drugs didn't work, though. At her mother's insistence, the doctor extended the prescription three more weeks, but Kaleigh only got sicker. This brought the Aherns to a clinical impasse. The Centers for Disease Control and Prevention has established highly specific criteria for the diagnosis of Lyme disease: an acknowledged tick bite, the appearance of a bull's-eye rash, and, for those who don't live in a region where Lyme is common, laboratory evidence of infection. Most people who fit the profile respond well to antibiotics, even months or years after the initial infection. Many Lyme specialists, however, believe that short-term antibiotic therapy may suppress symptoms but rarely cures the disease. Kaleigh switched doctors and began a course of antibiotics that lasted eight more months.
There was no change. Furthermore, there is no evidence that prolonged antibiotic therapy helps patients with Lyme disease, so insurance companies almost never pay for it. "I realized that my parents were shovelling thousands of dollars into these antibiotics," she said. "After the oral approach failed, I was recommended to go onto I.V. treatment, but I had had enough." Kaleigh's condition had become so grave that she withdrew from school. "I would have episodes where I would just lie on the ground writhing. And my parents could do nothing but watch. I wish they had taken videos and put them online, so people would know."
Kaleigh turned to alternative treatments often recommended by Lyme patients with similar experiences. She took herbs—turmeric and ginger, which are thought by some to strengthen the immune system—and she gave up gluten, grains, refined foods, and sugar. The goal was to reduce inflammation caused by her body's production of insulin and to inhibit the growth of the bacterium that causes Lyme. She also began treatments with a Rife machine, an electromagnetic device invented in the nineteen-twenties which emits radio signals that, some researchers suggest, can destroy harmful bacteria. Although thousands of people are convinced that Rife therapy has helped them with Lyme and other diseases, little empirical evidence exists to demonstrate that it works. Nonetheless, Kaleigh began to feel better. She still has headaches and severe muscular pain at times, but she returned to Union a year ago and graduated this spring. She knows that her approach to Lyme disease is controversial and acknowledges that the improvements might be due to her dietary regimen or to Rife treatments or to a placebo effect. She doesn't mind; after enduring such pain, she has found that fine points don't matter.
Lyme disease is the most commonly reported tick-borne illness in the United States, and the incidence is growing rapidly. In 2009, the C.D.C. reported thirty-eight thousand cases, three times more than in 1991. Most researchers agree that the true number of infections is five to ten times higher. Although some of that increase is due to heightened awareness, transmission is rising in areas, like New England, where the disease is well established, and is spreading to regions as far south as Florida, through changes in climate and the movements of infected animals.
The disease is caused by the bacterium Borrelia burgdorferi. In the Northeast and the Midwest, B. burgdorferi is transmitted by the bite of a black-legged tick, Ixodes scapularis. (In the Western United States, a related tick, Ixodes pacificus, prevails, and in Europe the main vector is Ixodes ricinus.) Lyme was all but unknown until 1977, when Allen Steere, a rheumatologist at Yale, produced the first definitive account of the infection. The condition was initially thought to have been an outbreak of juvenile rheumatoid arthritis in and around Lyme, Connecticut. In 1982, Willy Burgdorfer, a medical entomologist at the National Institutes of Health's Rocky Mountain Laboratories, determined that the infection was caused by the previously unknown spirochete borrelia. As is common in scientific practice, the bacterium was named for him:Borrelia burgdorferi.
Those facts are undisputed. But nearly everything else about Lyme disease—the symptoms, the diagnosis, the prevalence, the behavior of the borrelia spirochete after it infects the body, and the correct approach to treatment—is contested bitterly and publicly. Even the definition of Lyme disease, and the terminology used to describe it, has fuelled years of acrimonious debate. The conventional medical assessment is straightforward: in most cases, the tick bite causes a skin rash, called erythema migrans, which is easily identified by its bull's-eye. If left untreated, the bacteria can spread to muscles, joints, the heart, and even the brain. Public-health officials say that a few weeks of antibiotic treatment will almost always wipe out the infection, and that relapses are rare. In this view, put forth in guidelines issued by the Infectious Diseases Society of America, Lyme is normally easy to treat and easy to cure.
For many people, though, the clinical situation is far more complicated. Some who have been infected with borrelia don't notice the rash. Others—up to a quarter of those with Lyme, including Kaleigh Ahern—never even get one. Most troubling, some patients who are treated continue to suffer from a variety of symptoms long after their therapy has ended. Nobody really knows why they fail to get better. Infectious-disease experts refer to the phenomenon, which can affect up to twenty per cent of patients, as Post-Treatment Lyme Disease Syndrome. Researchers have attempted to resolve the mystery in experiments with monkeys, mice, and dogs; human studies are also under way. As the number of infections grows, so does the number of people struggling to figure out what is wrong with them.
Many of these patients say that medical officials pay little attention to their persisting symptoms, and that Lyme disease is anything but easy to treat or to cure. They believe that the bacteria can hide in the body for years, potentially causing harm long after treatment ends. This condition, they say, is pernicious, difficult to diagnose, rarely cured, and widely ignored. Moreover, at least four pathogens, in addition to the Lyme bacterium, can be transmitted by the black-legged tick: Anaplasma phagocytophilium, which causes anaplasmosis; Babesia microti, which causes babesiosis; Borrelia miyamotoi, a recently discovered genetic relative of the Lyme spirochete; and Powassan virus. Some of these infections are more dangerous than Lyme, and more than one can infect a person at the same time. Simultaneous infection, scientists suggest, may well enhance the strength of the assault on the immune system, while making the disease itself harder to treat or recognize.
"I am not sure why we act as if we know the answers," Brian Fallon told me. Fallon, a psychiatrist who has studied the neurological impact of Lyme for years, is the director of the Lyme and Tick-Borne Diseases Research Center, at Columbia University. "The evidence that something more complex is going on is tantalizing and substantial."
Fallon is right, yet the medical issues have largely been eclipsed by the attention generated by another faction in the Lyme wars. These people—patients, advocates, politicians, and "Lyme literate" physicians, led by the International Lyme and Associated Diseases Society—refer to the illness as "chronic Lyme," and argue that the traditional approach to diagnosis and treatment, put forth by most American physicians, all but guarantees failure. The Lyme Action Network, one of many political groups that have formed to increase awareness and raise funds, recently released a pamphlet called "It Might Be Lyme." The group lists dozens of possible symptoms, including headache, joint pain, neck stiffness, chest pain, bladder dysfunction, hypersensitive skin, unexplained fevers, weight loss, sweats, chills, fatigue, blurry vision, heart murmurs, sleep disturbances (including too little or too much), difficulty with concentration, lightheadedness, and mood swings. Physicians associated with the network argue that a cure requires not weeks but months or years of strong antibiotics, and that relapses are common.
"There are two standards of care when it comes to Lyme," Holly Ahern said. "One in which patients are diagnosed and treated until they get better, and the other where people are treated for three weeks with antibiotics—and, if you don't get better, then there must be something else wrong with you, or perhaps you are making it up." Ahern is a scientist, and hers is a measured critique. But emotion and despair are often the driving forces behind Lyme activism. The documentary "Under Our Skin: The Untold Story of Lyme Disease" essentially accused organized medicine of ignoring the illness. Scores of highly read blogs—Lyme Policy Wonk, Touched by Lyme, Living the Lyme Life—regularly overflow with fury.
Nobody disagrees that more research into the long-term effects of Lyme is needed. But most doctors reject the term "chronic Lyme," in part because many people who say they have it are not infected with borrelia. Without biological proof—a positive blood test or the telltale skin rash—the symptoms are vague and varied and could apply to many conditions. Infectious-disease experts say that the lingering symptoms might be an autoimmune response to the original illness or residual damage to tissues caused by the infection. "There is no doubt that people can have symptoms after being treated for Lyme disease," Roy Gulick told me when I visited him recently in his office at the Weill Cornell Medical College, where he is a professor of medicine and the chief of infectious diseases. "They can hang on for weeks or months. But you have to be specific about whether it's plausibly related to Lyme.
"I am sympathetic to people who are suffering," he continued. "And I have no doubt that they are. But if you have not been infected with borrelia you can't have Lyme disease. We don't have all the answers. We never do. These people are true believers. But I'm an infectious-disease doctor. I understand pathogens that cause disease and I understand the manifestations of those infections. Believing or not believing is not part of the process."
I grew up in Connecticut, attended college in the Hudson Valley, and graduated in 1977, the year Lyme was first identified. I don't recall hearing about the disease. I do remember going to a professor's house for dinner one night that year and having him urge me to arrive before dusk, so that we might look for deer. We drove around for an hour without luck, and I wondered whether to believe him when he said he had seen one just the day before.
Today, deer are no longer exotic in the Hudson Valley, and the area has the highest rate of Lyme disease in the country. If you drive the back roads of Columbia County at dusk, deer are nearly impossible to avoid, and accidents are common. Ticks are constantly on residents' minds, and watching children run barefoot to the edge of the bucolic woods is no longer a carefree delight. Deer are not Ixodes's most important host, but they have come to symbolize the spread of Lyme, and represent an ecology that has changed dramatically in the past thirty-five years. "Once you have Lyme disease in the area, and once you start to carve up the forest into little bits, and especially when the fragmentation is done by suburban development, you get an increase in Lyme risk," Richard Ostfeld told me recently when I met with him at the Cary Institute of Ecosystem Studies, in Millbrook, New York. Ostfeld, a senior scientist there, has studied Ixodes for more than a decade. "The best host for the tick and pathogens is not deer but white-footed mice," he said. "And they do beautifully when you chop the forest into bits. They thrive. And competitors do not."
Ixodes scapularis is surprisingly sophisticated for an organism that, until it is engorged with blood, is less than half the size of a pea. "These ticks are nimble, durable, and adaptable," Ostfeld said. The black-legged tick passes through three distinct phases—larva, nymph, and adult—and females require a blood meal at each stage. They usually pick up the spirochete, which under the microscope looks like a spiral French fry, in their first meal, and pass the disease to the host—small mammals, birds, deer, and sometimes humans—during the second or the third. To insure that it becomes engorged, the tick can attach its barbed mouth to a host for up to a week. First, though, the tick releases a series of anti-inflammatory chemicals and antihistamines to numb the skin and make a bite difficult to notice. It then secretes a compound called cementum, a kind of glue that helps the tick adhere to its prey. With those tasks accomplished, the tick bores its mouthparts into its host. While it feeds, the tick can inject borrelia, and other pathogens, into the bloodstream.
Ostfeld is a thoughtful, soft-spoken man, not unduly excitable. But when he talks about the Lyme bacterium he sounds like a proud parent. "Borrelia is a remarkable creature," he told me. "It has all my respect." He went on to explain that the bacterium, after slipping through the tick's mouthparts, can change its form, cloaking itself in the surface proteins of the tick's saliva. Then, much like H.I.V., the bacterium hijacks the immune system. "It doesn't stay in the bloodstream for long," he said. "Instead, borrelia manages to insinuate itself into parts of the body that have fewer circulating antibodies, where it is harder for antibiotics to reach."
The relationship between the tick and borrelia can be compared to the deadly, symbiotic partnership of Plasmodium falciparum parasites and the anopheles mosquitoes that transmit malaria, which have evolved together for thousands of years. Genetically, the bacteria are so adaptable that it is possible to find different strains of borrelia in the same tick. "Some of these infections are really very worrying," Ostfeld said, as we sat, one sunny morning, in his green, airy office at the institute. "We can't even know yet how big a problem a bacterium like miyamotoi will become. But it is possible that Lyme will turn out to be among the least threatening of the pathogens carried by Ixodes."
Ostfeld, a field biologist, received his Ph.D. from the University of California at Berkeley, and studies the ecology of small mammals—skunks, possums, chipmunks, and white-footed mice—which are found in large numbers in the Hudson Valley. Soon after he arrived at the institute, in 1990, he noticed something striking about the thousands of mice he had trapped: their ears were often covered in ticks the size of poppy seeds. Those ticks, Ixodes nymphs and larvae, were feeding on the mice. "That was the beginning of my interest in Lyme disease," he said. His 2010 book, "Lyme Disease: The Ecology of a Complex System," describes the environmental relationship in detail. Before European colonists arrived in America, ninety per cent of New England and New York was covered in forest. Lyme was unknown. In the next century, forested areas were cut by half. "But it was a shitty life here," Ostfeld said. "Colonists had a rough go of it. The rocky soil was infertile and difficult for agriculture." In the eighteen-thirties, when the Erie Canal opened the Ohio Valley to agricultural development, the farms of the Northeast were abandoned. The forests returned, along with deer. Mice and other small mammals accompanied them.
Diagnostic failures cause much of the confusion associated with Lyme disease. It takes the tick at least thirty-six hours to transmit borrelia. If ticks are removed immediately, the threat of infection falls dramatically. But it takes weeks, and sometimes longer, for blood tests to detect antibodies; a test taken too soon will produce negative results. Even then, many people who become infected will test negative in error, while others who aren't infected will test positive.
"You get people all the time who have Lyme but who do not know it," Ostfeld said. "Their doctors don't know it." The basic blood tests look for antibodies but are not always sensitive enough to pick out the right ones. Another test for Lyme disease involves PCR, a technique that allows scientists to amplify the number of copies of a specific region of DNA. When done properly, that test can detect the Lyme spirochete directly. Yet it is prone to contamination, and it often produces positive results for people who are not infected. The situation is similar to one in India, where tens of millions of people test positive for tuberculosis. Few of them will actually get sick, but many are mistakenly treated with highly toxic drugs. A relatively new, but expensive, diagnostic machine can differentiate between latent and active t.b. infections. "We badly need that kind of diagnostic certainty with Lyme," Ostfeld told me. "And we do not have it."
Public-health officials stress that if doctors see a bull's-eye rash they should assume that the patient has Lyme and prescribe antibiotics. The advice is often ignored. Nor do many doctors or patients consider the potential impact of simultaneous infection with several pathogens. "This is not resolved science," Ostfeld said. "Clearly, not everyone claiming to have Lyme disease is sick, particularly those who have never tested positive for borrelia. But there are just too many questions we still have to answer about those who are infected: Does the bacterium persist after treatment? If so, is it capable of harm? What is the impact of co-infections, and what is really the best way to treat advanced stages of Lyme?
"The conventional view is that several studies have answered the most important questions about persistence and treatment," Ostfeld went on. "But look at heart disease. How many thousands of studies were conducted on the relationship between cholesterol and heart disease? Over how many decades? And we still go back and forth. When it comes to Lyme, we have a long way to go."
The controversy over Lyme disease is unlikely to diminish until scientists resolve at least two critical, but related, questions. Can the bacteria persist in the body, causing harm and illness months or even years after treatment has ended? And can prolonged antibiotic therapy destroy the remaining bacteria? Here, as with nearly every issue related to Lyme and its treatment, there is disagreement not only about the answers but also about the questions.
Determining whether Lyme spirochetes cause illness after treatment is difficult in part because the symptoms are so diverse. Moreover, it is nearly impossible, with current tests, to know whether the infection has been cured. Recent studies with mice and macaques provide interesting clues. In a study published last year in the online journal Plos One, a team of scientists led by Monica E. Embers, of the Tulane National Primate Research Center, and Stephen W. Barthold, the director of the Center of Comparative Medicine at the University of California at Davis, carried out two experiments on rhesus macaques to determine whether borrelia persists after antibiotic treatments.
First, twenty-four rhesus macaques were infected with the Lyme bacteria in the laboratory. After four to six months, half the macaques received aggressive antibiotic therapy, which, in theory, should have cured them, but the bacteria persisted in some of the animals. Then the scientists used a method called xenodiagnosis to determine if treatment worked in three other monkeys. They planted ticks that had been reared in the lab under sterile conditions on macaques that had received antibiotics, and let them feed for four days. When the ticks were removed and examined, the scientists found small numbers of intact, functioning spirochetes in two of them, which could have come only from the blood of the macaques. A team of scientists led by Adriana Marques, of the National Institute of Allergy and Infectious Diseases, and Linden Hu, of Tufts University School of Medicine, is conducting a similar study in humans. (The scientists have obtained permission from patients to permit ticks to feed on them.)
Other research, by Brian Fallon, the Columbia psychiatrist, found metabolic abnormalities in the brains of patients with confirmed cases of Lyme disease and chronic, post-treatment symptoms, when compared with the brains of healthy control subjects. That, too, suggests the bacterium continues to have an impact. None of these studies provide conclusive evidence, but together they strongly suggest that the infection can survive treatment in a primate. This finding raises the possibility that the bacteria could continue to cause illness long after a patient is supposedly cured. Similar research in mice, published last year in the Journal of Clinical Investigation by a team from Yale Medical School, found that while antibiotics stopped the infection, spirochete antigens persisted in areas adjacent to cartilage—a condition that could produce swelling.
None of these studies have swayed Gary Wormser, the chief of the division of infectious diseases at New York Medical College, and the lead author of the often criticized Infectious Diseases Society of America guidelines for Lyme. He says that, in the absence of new data, doctors should continue to treat Lyme with courses of oral antibiotics that generally take no more than thirty days.
"Right now, in the published literature, there is no evidence of persistence in humans, and if there were I would say, 'So what?' " he told me recently. "You would have to show me that the spirochetes continue to produce disease and you would have to show me that they would respond to antibiotics." Like most established scientists, Wormser maintains that one can rely only on the best current science-based evidence to practice medicine; otherwise, he may as well rely on voodoo. Furthermore, he stressed that it is dangerous to diagnose a disease based on symptoms alone. "There is a group of people with aches and pains and medically unexplained symptoms that are being treated for chronic Lyme." He said these patients often go "from doctor to doctor" without a satisfactory diagnosis. "They are suffering and unhappy, and finally they go to a doctor who says, 'I know what you have, it's chronic Lyme.' Then they get treated and treated and treated for chronic Lyme. And patients are happy because somebody has finally taken interest in them."
Wormser continued, "If you had Lyme and nobody disputes it and you don't feel back to normal, it's logical to ask, 'Does the antibiotic work?' Or maybe the organism is still there. Those questions have been explored, and we continue to explore them." Yet he added that the majority of people who are being treated as if they had post-Lyme symptoms have never had the disease. "Never had the test, the rash, swelling, not the slightest credible evidence of Lyme. If somebody walked into your office and said, 'I have renal failure, I need dialysis,' you would do a test. If it was negative, nobody in his right mind would give the patient dialysis."
Wormser's many critics regard his view of the disease as willfully limited. In response, he and others cite four double-blind, placebo-controlled trials funded by the N.I.H. over the past fifteen years. Each attempted to determine whether prolonged antibiotic treatment, given after the initial courses were completed, helps eliminate persistent symptoms of Lyme disease. The two largest studies reported no evidence of improvement; the results of the other two studies were equivocal. But none of the researchers concluded that the theoretical benefits outweighed the tangible risks of extended intravenous therapy, which included severe infections. In a separate case, a woman on intravenous antibiotics died after a blood clot.
Physicians who regularly see people with Lyme symptoms say that the conventional methods simply don't work. "I think a lot of these people who are set in their ways need to see more patients," Richard Horowitz told me when I called him at his office in Hyde Park, New York. Horowitz is one of the most prominent "Lyme literate" physicians: he is board certified in internal medicine and has practiced in the Hudson Valley for more than twenty-five years. Officials who endorse the Infectious Diseases Society of America's approach to Lyme disease consider Horowitz a pariah, but patients wait for months to see him, and several told me that he had essentially cured them of a disease that nobody else seemed able to treat.
Horowitz told me that he has seen more than twelve thousand patients, all of whom have a tick-borne ailment. Whenever possible, he avoids antibiotics. "Most of my patients do not present simply with Lyme," he told me. "They almost always have multiple co-infections. That means they have a suppressed immune system with complex symptomology. Thirty days of doxycycline"—the most common drug used to treat Lyme—"just isn't going to cure this. Each of these pathogens requires different regimens."
Horowitz offers a complex combination of dietary restrictions and supplements to help "detoxify" the body and starve the bacteria. He argues that organized medicine, by relying on a few double-blind trials, focusses only on borrelia and Lyme. "But we know the ticks can spread many pathogens. More than half of my patients present with babesiosis," he told me. (It causes symptoms similar to those of Lyme, though it more frequently begins with fevers and chills.) The incidence of babesiosis, which is caused by microscopic parasites that infect red blood cells, has been increasing dramatically in the Hudson Valley, according to research done by Wormser. "That infection has to be treated in an entirely different way from Lyme, and together they cause far more harm than either one does alone," Horowitz said. "I have never understood why that is a controversial assertion."
David Roth is not a scientist, but he believes that only science can end the Lyme wars. I met with him one gray, cloudy day on the forty-third floor of the Blackstone Investment Group building in Manhattan, where he is a managing director. Roth was dressed in pinstripes, a crisp white shirt, a yellow tie, and spit-shined brogues. He has an air of distinguished nonchalance, and his brown hair is tousled in the manner of a Kennedy. Three years ago, Roth became very sick, and while it has been difficult for him, and for his family, his illness may be the best thing that has happened for people infected with tick-borne ailments.
"I started working on this problem because I was shocked by the approach of the medical community," he told me. "I felt there was a real social injustice." Roth's story was similar to those of others I had heard. His illness began with flulike symptoms, enlarged lymph nodes, and insomnia. Doctors found no apparent cause. His symptoms worsened; full-body shakes, numbness in his feet and hands, pain in his tendons, and immense fatigue. "I went up and down this city seeing doctors," he said. "I had CAT scans and PET scans and M.R.I.s." Those tests also turned up nothing, but eventually—about four months after falling ill—he tested positive for both Lyme disease and babesiosis. He was treated with antibiotics as well as with malaria medication; they helped, but only for a while. "When I stopped, things got worse," he told me.
The more he looked into the treatment of Lyme, the angrier he became. "Here is what I don't understand," he said. "Somebody can get ill and not know what it is and the symptoms get worse and worse. Two years or more later, they can learn that they have Lyme. They take antibiotics for a month. And then, according to their doctors and insurance companies, they are done. Cured. Sometimes that is enough. But many people continue to be sick, and the government's position, in a world where there are ten times as many bacterial cells as human cells in our body, is that this particular bacteria has been removed forever and the problem must be due to something else."
Roth is forty-six, goes to the gym several times a week, and looks robust. ("One of the problems with Lyme is that people tend to look better than they are," he said.) He has received treatment—dietary supplements and dietary changes—from Horowitz, and his health has improved greatly. Like Kaleigh Ahern, he has difficult days, but they are less frequent. Recently, he was appointed to a federal advisory committee that is working on ways to improve Lyme diagnostics. He was one of the hosts of a gala, held by the Tick-Borne Disease Alliance, earlier this year, which raised eight hundred thousand dollars. "I try to act rationally and work with rational people," he went on. "Sometimes that is hard to do."
For Lyme activists to be taken seriously, they will have to be led more by people like Roth than by those who foster dark conspiracies. I was told by several Lyme activists that the government created the infection on Plum Island, that reporters at the Times have been "muzzled" and prevented from reporting honestly about Lyme, and that the N.I.H. has made a pact with pharmaceutical companies to ignore chronic Lyme. There is now a bill before the legislature in New York that would require insurance companies to reimburse long-term treatment with antibiotics—even though no study has proved their effectiveness, and treatment with I.V. antibiotics can cause serious, and sometimes fatal, complications.
Meanwhile, the scientists sometimes seem to respond more comfortably to data than to people. Researchers at the N.I.H. are pursing several lines of inquiry, including the possibility of bacterial persistence. The atmosphere resembles that of the early days of AIDS activism, when many of the individuals most at risk lost confidence in their doctors and sought their own medical answers. In the end, organizers of ACT UPand the Gay Men's Health Crisis became well known for their public protests, but they succeeded for another reason: they did their homework. Nobody was more knowledgeable about the course of H.I.V. infection than the best-informed activists.
Lyme-advocacy organizations need to rely on similarly well-informed people. Kaleigh Ahern is one of them. She recently presented a paper on the behavior of black-legged ticks at the annual meeting of the Federation of American Societies for Experimental Biology. "It was my thesis at Union," she explained. "I looked at the effects of soil pH on molting success. I wanted to know the ecological factors that make Lyme increase so steadily in this region." She has applied to graduate school, where she hopes to help develop more useful diagnostics for Lyme.
I asked if her parents were surprised that she has chosen to work with Lyme ticks. "They are horrified," she told me, laughing. "But, if I don't do it, who will? " ♦
Thursday, June 27, 2013
As society struggles with the privacy implications of wearable computers like Google Glass, scientists, researchers and some start-ups are already preparing the next, even more intrusive wave of computing: ingestible computers and minuscule sensors stuffed inside pills.
For people in extreme professions, like space travel, various versions of these pills have been used for some time. But in the next year, your family doctor — at least if he's technologically adept — could also have them in his medicinal tool kit.Although these tiny devices are not yet mainstream, some people on the cutting edge are already swallowing them to monitor a range of health data and wirelessly share this information with a doctor. And there are prototypes of tiny, ingestible devices that can do things like automatically open car doors or fill in passwords.
Inside these pills are tiny sensors and transmitters. You swallow them with water, or milk if you'd prefer. After that, the devices make their way to the stomach and stay intact as they travel through the intestinal tract.
"You will — voluntarily, I might add — take a pill, which you think of as a pill but is in fact a microscopic robot, which will monitor your systems" and wirelessly transmit what is happening, Eric E. Schmidt, the executive chairman of Google, said last fall at a company conference. "If it makes the difference between health and death, you're going to want this thing."
One of the pills, made by Proteus Digital Health, a small company in Redwood City, Calif., does not need a battery. Instead, the body is the power source. Just as a potato can power a light bulb, Proteus has added magnesium and copper on each side of its tiny sensor, which generates just enough electricity from stomach acids.
As a Proteus pill hits the bottom of the stomach, it sends information to a cellphone app through a patch worn on the body. The tiny computer can track medication-taking behaviors — "did Grandma take her pills today, and what time?" — and monitor how a patient's body is responding to medicine. It also detects the person's movements and rest patterns.
Executives at the company, which recently raised $62.5 million from investors, say they believe that these pills will help patients with physical and neurological problems. People with heart failure-related difficulties could monitor blood flow and body temperature; those with central nervous system issues, including schizophrenia and Alzheimer's disease, could take the pills to monitor vital signs in real time. The Food and Drug Administration approved the Proteus pill last year.
A pill called the CorTemp Ingestible Core Body Temperature Sensor, made by HQ Inc. in Palmetto, Fla., has a built-in battery and wirelessly transmits real-time body temperature as it travels through a patient.
Firefighters, football players, soldiers and astronauts have used the device so their employers can monitor them and ensure they do not overheat in high temperatures. CorTemp began in 2006 as a research collaboration from the Johns Hopkins University Applied Physics Laboratory and the National Oceanic and Atmospheric Administration.
Lee Carbonelli, HQ's marketing director, said the company hoped, in the next year, to have a consumer version that would wirelessly communicate to a smartphone app.
Future generations of these pills could even be convenience tools.
Last month, Regina Dugan, senior vice president for Motorola Mobility's advanced technology and projects group, showed off an example, along with wearable radio frequency identification tattoos that attach to the skin like a sticker, at the D: All Things Digital technology conference.
Once that pill is in your body, you could pick up your smartphone and not have to type in a password. Instead, you are the password. Sit in the car and it will start. Touch the handle to your home door and it will automatically unlock. "Essentially, your entire body becomes your authentication token," Ms. Dugan said.
But if people are worried about the privacy implications of wearable computing devices, just wait until they try to wrap their heads around ingestible computing.
"This is yet another one of these technologies where there are wonderful options and terrible options, simultaneously," said John Perry Barlow, a founder of the Electronic Frontier Foundation, a privacy advocacy group. "The wonderful is that there are a great number of things you want to know about yourself on a continual basis, especially if you're diabetic or suffer from another disease. The terrible is that health insurance companies could know about the inner workings of your body."
And the implications of a tiny computer inside your body being hacked? Let's say they are troubling.
There is, of course, one last question for this little pill. After it has done its job, flowing down around the stomach and through the intestinal tract, what happens next?
"It passes naturally through the body in about 24 hours," Ms. Carbonelli said, but since each pill costs $46, "some people choose to recover and recycle it."
Doctors diagnosed her with acute pancreatitis, in which pancreatic enzymes begin digesting not just food, but the pancreas itself.
The most likely cause of the girl's condition: toxic side effects from more than 80 dietary supplements, which the girl's mother carried in a shopping bag, says Sarah Erush, clinical pharmacy manager at Children's Hospital of Philadelphia, where the girl was treated last summer.
The girl's mother had been treating her with the supplements and other therapies for four years to treat the girl's "chronic Lyme disease," a condition that, experts say, doesn't actually exist. While some Lyme infections cause pain and other lingering symptoms, the infections don't persist for years. And, according to the Infectious Disease Society of America, the infections don't require years of antibiotics or other risky therapies given by some alternative medicine practitioners.
Doctors were able to control the girl's illness with standard therapies, Erush says, and she was discharged from the hospital after two weeks.
Although the child's story was unforgettable, Erush says, it wasn't unusual. Parents now "routinely" bring children to her hospital with a variety of alternative remedies, hoping that nurses will administer them during a child's stay.
There are an ever-growing number of supplements from which to choose: More than 54,000 varieties sold in stores and the Internet, according to the Food and Drug Administration.
About 50% of Americans use alternative medicine, and 10% use it on their children, notes Paul Offit, Children's Hospital's chief of infectious disease.
The girl's story illustrates the serious but often little-known risks posed by some forms of alternative medicine, a loosely regulated industry that includes everything from herbal supplements to crystal healing and acupuncture, says Offit, author of Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine, (HarperCollins, $29.99), being published Tuesday
Many consumers view alternative medicine industry as more altruistic and home-spun than Big Pharma. But in his book, Offit paints a picture of an aggressive, $34 billion a year industry whose key players are adept at using lawsuits, lobbyists and legislation to protect their market.
"It's a big business," says Offit, best known for developing a vaccine against rotavirus, a diarrheal illness that killed 2,000 people each day, mostly children in the developing world.
"This is not just Mom and Pop selling herbs at the farmer's market," says Josephine Briggs, a physician and director of the National Center on Complementary and Alternative Medicine, part of the National Institutes of Health, who shares Offit's concerns.
Rep. Henry Waxman, D-Calif., who has long fought for stricter regulation of supplements, says the alternative medicine industry is "as tough as any industry I've seen lobby in Washington. They have a lot of money at stake. They want to maximize their profits and they want as little regulation as possible."
There's even a Congressional Dietary Supplement Caucus, composed of legislators who look favorably on the industry.
Combined with alternative therapy research at the National Cancer Institute, the NIH spends a total of $233 million a year on this research, which has included everything from herbal supplements to acupuncture and aromatherapy.
Briggs notes that research conducted by her center and others shows real benefits to certain alternative therapies, which doctors describe as "complementary" if they are used in conjunction with conventional medicine. Last year, for example, The New England Journal of Medicine published a study showing that people with Parkinson's disease can improve their balance and stability by practicing Tai Chi, an ancient Chinese exercise system. A study published last month in the Journal of the American Medical Association found that intensive-care patients on ventilators experienced less anxiety, and required fewer sedatives, if they could listen to their choice of music.
Proponents of alternative medicine say there are clear reasons for its popularity, including frustration with mainstream doctors and people's desire to have more control over their health.
Only about one-third of alternative therapies have safety and efficacy data behind them, critics note. Yet conventional doctors don't always follow the evidence, either, says Adriane Fugh-Berman, an associate professor of pharmacology at Georgetown University in Washington and author of a textbook on herbs and supplements. Only about one-quarter of therapies used in conventional medicine are "evidence-based," she says.
Many Americans see modern medicine as increasingly bureaucratic and impersonal, says Deepak Chopra, a physician and one of the best known advocates for mind-body healing.
"Doctors spend more time filling in charts than they spend on seeing patients," Chopra says. "The average doctor stands in the door and does a ritual of examining patients for one or two minutes, then moves on to the next patient."
Arthur Caplan, the director of medical ethics at NYU Langone Medical Center in New York, says alternative healers satisfy patients' needs for more personal attention.
"Medicine does a very poor job of addressing the emotional, spiritual and even psychological side of things," Caplan says. "When you are not good at doing important things, other people rush into that vacuum."
Yet people who put their faith in alternative healers and supplements may be putting themselves at risk, Caplan says.
The alternative therapy industry capitalizes on a number of common sentiments, Offit says, from a naïve belief in the safety of all things natural to distrust of government regulation.
"Just because it comes from a plant, doesn't mean it's not harmful," Chopra says.
About one-third of conventional drugs are derived from plants, Fugh-Berman says. Pharmaceutical companies still make Digoxin, a heart drug, from the foxglove flower, she says. And while some research suggests that kava, a plant in the pepper family, can relieve anxiety, it can also damage the liver.
In the best cases, Offit says, alternative remedies are ineffective but relatively harmless, functioning as expensive placebos that may appear to relieve symptoms such as pain, largely because people expect them to. An example of this is homeopathy, in which key ingredients are diluted to the point of oblivion, making these remedies basically sugar pills, Offit says.
Yet supplements aren't risk-free.
A 2010 report from the Government Accountability Office found supplements were being sold with deceptive marketing practices.
Tests have found heavy metals in ayurvedic medicines, used in India for thousands of years to treat a variety of conditions and also popular in the USA, Briggs says.
In some cases, dietary supplements are just prescription medications in disguise.
The most common offenders tend to be supplements claiming to aid weight loss, build muscles or boost sexual performance, Briggs says. Although such supplements may be marketed as "natural," the FDA has found hundreds of brands actually contain real drugs, from anabolic steroids to the active ingredient in Viagra. Several weight-loss supplements were found to contain the active ingredient in Meridia, a prescription diet drug pulled from the market due to an increased risk of heart attack and stroke.
In April, the FDA announced that it had received 86 reports of illness and death due to body-building supplements that illegally contained a stimulant called DMAA. The FDA says DMAA, which is especially risky when combined with caffeine, can raise blood pressure, leading to problems such as shortness of breath and heart attacks.
In 2012, the FDA estimated that supplements cause 50,000 adverse reactions a year.
In the worst cases, scam artists masquerading as healers push bogus cures on desperate, vulnerable people, charging prices that patients can't afford, says Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, who compares these marketers to "snake oil salesman."
The consequences can be tragic.
Nissen says he's lost patients with serious cardiovascular disease because they opted to take alternative medicines instead of those he prescribed. The practice, Nissen says, is "a national catastrophe in the making."
Alternative medicine doctors sell patients on a variety of unproven therapies, such as chelation, a process of removing metals from the blood, Offit says.
Although chelation has real medical uses — treating acute heavy metal poisoning — doctors also promote the intravenous treatments as an alternative remedy for everything from Alzheimer's disease to cancer.
In 2005, a 5-year-old boy with autism died after treatment with chelation, according to the Centers for Disease Control and Prevention.
Many people with aches and pains are being misdiagnosed with chronic Lyme disease, Offit says, even though studies show that half of these patients really suffer from treatable conditions, such as depression or rheumatoid arthritis. Doctors who call themselves "Lyme literate" often prescribe years of intravenous antibiotics, a therapy with no proven benefits but serious side effects, including infections and the risk of developing antibiotic resistance.
Apple founder Steve Jobs' faith in alternative medicine likely cost him his life, says Barrie Cassileth, chief of integrative medicine at New York's Memorial Sloan-Kettering Cancer Center.
Jobs was diagnosed with pancreatic cancer in 2003. But Jobs, revered as one of the brightest minds on the planet, chose to delay surgery, the only treatment that had a chance to save his life, Cassileth says.
For nine months after his diagnosis, Offit writes, Jobs treated his cancer with acupuncture, herbs, bowel cleansings and a special diet of carrots and fruit juices.
Jobs eventually had surgery, and even a liver transplant. But it was too late.
He died in 2011, eight years after diagnosis.
"He had the only kind of pancreatic cancer that is treatable and curable," Cassileth says. "He essentially committed suicide."
Cancer patients have cashed in their life savings or children's college funds to pay charismatic charlatans, spending $20,000 or more for "absurd" treatments at fringe clinics in the USA, Mexico and Bahamas, Cassileth says.
"There are no viable alternatives to mainstream cancer care," Cassileth says. "We work very hard to dissuade patients who want to go that way, because they are going to die."
And while many in the alternative medicine industry are cashing in, Offit says there are few people looking out for the desperate patients whose hopes — and bank accounts — are being exploited.
"Quackery is an enormous concern," Briggs says.
Consumers are often taken in by outrageous claims, partly because they lack the scientific knowledge to spot phonies, and partly because they fall victim to a huckster's charismatic personality, Offit says.
"Our science literacy is terrible as a nation," Briggs says. "People like magic. I don't know why, but they do."
Many Americans are unaware that supplements, unlike drugs, don't need to be approved by the Food and Drug Administration — or tested for safety — before going on the market, Offit says. One study found that 58% of Americans believe that the FDA must approve herbal supplements before they're sold.
"When a consumer buys a food supplement or dietary supplement, they may think it's really going to do what it says on the label," Waxman says. "That's not necessarily the case. ... Consumers should know that when they buy a dietary supplement, they are really on their own."
And while manufacturers are responsible for making sure that products are safe, the FDA can typically take action only after products are on store shelves.
The FDA expressed frustration with these constraints in an April press release about DMAA.
In making the announcement, the agency said, "FDA is required to undertake what are usually lengthy scientific and legal steps in order to force the removal of dietary supplements that may be unsafe or are otherwise illegal if companies don't voluntarily comply. . . .FDA's response to the use of DMAA illustrates the challenges that the agency faces in addressing incidents involving potentially dangerous dietary supplements. "
Andrew Weil, one of the USA's best known advocates of holistic medicine, says he also favors closer regulation of supplements.
"I would love to see the FDA set up a division of natural therapeutic agents," says Weil, director of the Arizona Center for Integrative Medicine at the University of Arizona,
But Steve Mister, president and CEO of the Council for Responsible Nutrition, notes that supplement regulations, while "not identical to pharmaceuticals" are "very rigorous."
"Consumers can have strong confidence in the products they're buying," says Mister, whose group represents the supplement industry. "There are lots of ways that the FDA oversees the safety of these products."
The FDA sets standards for good manufacturing processes, Mister notes.
While a supplement may claim to "support immune health," the FDA forbids supplement manufacturers from making specific claims about being able to "treat, diagnose, cure or alleviate the effects of disease." Supplement makers are also required to report "adverse events," such as serious side effects or reactions, to the FDA.
Waxman notes that the FDA has only banned one supplement: ephedra — an herbal stimulant taken off the market in 2004 after it was found to increase the risk of heart problems and death.
Because the FDA's authority is mostly "reactive," Waxman says "the agency must wait for people to get hurt or even die before they can remove an unsafe supplement from the market."
In his book, Offit singles out a number of popular alternative doctors for questionable practices:
• Joseph Mercola, an Illinois physician, sells a variety of supplements and alternative medical products on his web site. Although Mercola shuns vaccines, his website sells tanning beds — which have been found to increase the risk of skin cancer.
In 2011, the FDA sent Mercola a letter for marketing an alternative to mammography on his website — the Meditherm Med2000, a camera that measures skin temperature. Although Mercola's site describes its products as "natural," the FDA viewed the machine as an unapproved medical device.
• Rashid Buttar, a North Carolina physician, has used treatments that Offit calls outlandish. According to the North Carolina Medical Board, those treatments have included giving intravenous hydrogen peroxide to cancer patients and topical chelation creams to children with autism.
In a 2010 consent order with the medical board, Buttar explained that the hydrogen peroxide was intended for "detoxifying the patients and improving their immune systems." In the order, the medical board formally reprimanded Buttar and ordered him to inform all patients that his treatments "may not have been approved by the FDA."
In April, the FDA also sent Buttar a letter, claiming that the claims he made for some of his products showed he was marketing them as drugs, not supplements.
In a post on his website, Buttar noted that he has stopped selling the products mentioned in the FDA letter May 15. One of those products, Trans-D Tropin, previously had been marketed as "a clinically proven aging and longevity solution."
USA TODAY was not able to reach Mercola or Buttar by press time.
• Stanislaw Burzynski, who has spent decades promoting antineoplastons, an experimental cancer therapy not approved by the FDA. According to the National Cancer Institute, these drugs have never been proven effective against cancer in a definitive, randomized, clinical trial.
Last year, the FDA sent Burzynski a letter noting that his "websites violate the Food Drug and Cosmetics Act" because they promoted experimental cancer treatments as "safe and effective."
According to FDA spokesman Curtis Allen, responses to FDA letters are not posted on the agency's website, and are available only through a Freedom of Information Act (FOIA) request. USA TODAY filed a FOIA request but has not yet received a copy of the responses by Mercola, Buttar or Burzynski.
In a statement sent by his attorney, Burzynski said he has published 36 articles, presented papers at many international conferences and completed 14 phase 2 trials in brain tumors. Phase 2 trials consider safety and are a preliminary, but not definitive, look at effectiveness, according to the National Institutes of Health. In the letter, Burzynski wrote that, "based on the results of the phase 2 trials, the FDA has granted permission to proceed into two Phase 3 clinical trials in brain tumors."
Offit also criticizes Mehmet Oz, a respected heart surgeon and star of The Dr. Oz Show, for providing an audience for a variety of questionable guests, from Mercola to faith healers and even psychics.
"He gives a lot of good advice," including advice about diet and exercise, Offit says. "But he mixes that in with a lot of terrible advice."
In a statement, a spokesman for The Dr. Oz Show said the TV program is "a conversation about the many sensitive topics surrounding health care, including alternative medicine, and we remain committed to empowering our viewers with comprehensive information about these issues so they can take an active role in their health."
Yet Cassileth, author of The Complete Guide to Complementary Therapies in Cancer Care, says non-traditional approaches can have a place in medicine, when modern medicine has little to offer.
As opposed to "alternative," Cassileth prefers the term "integrative" medicine, which subjects nonstandard therapies to scientific tests. At Memorial Sloan-Kettering, integrative health researchers focus on alleviating pain and other symptoms. But they would never claim that nontraditional therapies can cure cancer, she says.
For example, doctors have had promising early results using acupuncture to restore salivary gland function in patients who receive radiation to the head and neck. Without functioning salivary glands, these patients can't talk or swallow.
While critics counter that acupuncture treatments are simply placebos, Cassileth says, "if there is a placebo effect that brings back salivation to these people who can't eat or talk, who cares?"
Tuesday, June 25, 2013
On average, about 700 Americans kill themselves each week — but in the fine-weather weeks of May and June, the toll rises closer to 800, sometimes higher. Every year, suicide peaks with the tulips and lilacs — increasing roughly 15 percent over the annual average to create one of psychiatry's most consistent epidemiological patterns. It may seem perverse that the period of spring and early summer, as the psychologist Kay Redfield Jamison puts it in her splendid book "Night Falls Fast," should contain "a capacity for self-murder that winter less often has." Yet it does.
This grim spring growth confounds conventional belief that suicides peak in winter. It also confounds researchers — and fascinates them. As they discover more angles into the biology of mood and behavior, they are finding new clues about why suicides rise with the sun's arc. They hope solving this puzzle will help us better understand why people commit suicide at all — and perhaps reduce the numbers year-round.
This effort takes an extra urgency from what Dr. Adam Kaplin, a psychiatrist at Johns Hopkins University, calls a "suicide epidemic" — a sharp increase in both absolute and per-capita rates since the recession that began in 2007, particularly among the middle-aged. More than 38,000 people committed suicide in the United States in 2010 — a 16.5 percent jump from the 32,600 suicides five years before, and a new high. The stakes involved in figuring out the dynamics of self-murder seem only to rise with time.
The spring surge in suicides is actually the largest of a few oscillations throughout the year. After dropping to an annual low in February (October in the southern hemisphere), rates climb sharply through spring; fall slowly in summer; show a slight rise, according to some studies, in fall; and then begin a steep winter drop. The spring peak generally runs 10 to 25 percent above the yearly average and 20 to 50 percent above the February low.
The spring increase was first noticed in 19th-century Europe. Many studies, some examining data hundreds of years back, have documented it since. But explaining it has proved difficult, primarily because of suicide's extreme complexity.
"There's no one reason that people do it," said Nadine Kaslow, a research psychologist at Emory University. Rather, she says, people usually commit suicide because personal, social-system and environmental factors combine to push them to a new place of energized despair.
In this view, spring somehow adds weight to an already unbearable load. But how?
One traditional candidate, favored by both Dr. Jamison and Dr. Kaslow, is the "broken promise effect" — the sometimes crushing disappointment that spring fails to bring the relief the sufferer has hoped for.
In addition, psychiatrists have long observed that for patients with bipolar disorder and depression, spring can create a manic agitation that amplifies the risk of suicide — agitation that has long shown itself in a rising rate of hospitalizations for suicide attempts and for manic or schizophrenic episodes in spring and summer.
Researchers have long suspected that this may be tied to the springtime drop in the sleep-friendly hormone melatonin, a reduction that energizes us for spring's longer days but may sometimes help generate dangerous agitation. Yet that link, like many, remains elusive.
In the past decade or so, some researchers have increasingly focused on another candidate: an apparently intimate relationship between suicide and inflammation.
Dr. Kaplin studies depression in patients with multiple sclerosis, an autoimmune inflammatory disease. In M.S., he says, depression and inflammation feed each other: Even after accounting for the psychological effects of any serious illness, M.S. heightens depression risk, and depression amplifies the inflammation central to the disease's central pathologies.
Driving this relationship, Dr. Kaplin suspects, are immune-system chemical messengers called cytokines. Some cytokines increase inflammation, while others curb it.
Inflammatory cytokines play crucial roles in fighting infection, but they can also cause problems. When people with hepatitis C are given the cytokine interferon to help fight the infection, for instance, up to 40 percent become depressed and one in 50 attempt suicide. Other studies suggest that inflammatory cytokine activity reduces levels of the neurotransmitter serotonin and halts the growth of new brain cells — two hallmarks of depression.
If inflammation heightens the risk of depression, how might that lead to a spring surge in suicide?
Dr. Kaplin and others point to several possibilities — "all speculative," he says, not findings to act on but clues to follow. In every case, the suggested risk comes not from a direct effect but from an additional sensitivity to inflammation that could be a final straw or irritant.
A second possibility involves tree pollen. Dr. Teodor T. Postolache, a psychiatrist at the University of Maryland, believes that large amounts of it may cause cytokine-driven inflammatory responses. A study he did links high spring tree pollen counts with high seasonal suicide rates; another examined the brains of 34 suicide victims and found gene-expression patterns consistent with cytokine-driven inflammation.
Yet another possibility involves vitamin D. The low levels caused by lack of sunlight in the winter are thought to lead to inflammation; one recent study tentatively suggested a link to suicide. Dr. Kaplin thus wonders if people already at risk for suicide may increase their risk if they enter spring with inflammatory systems sensitized by vitamin D deficiencies.
"The answer to this puzzle is probably some form of 'all of the above,' " he said.
Even if these inflammatory factors prove out, they will be just some among many — mood disorders, divorce, job loss, grief, trauma — that fertilize spring's darkest bloom. But the more factors researchers can identify, the better we can understand not just the spring surge but the larger mysteries of suicide.
Still, if researchers are ever to identify the seasonal culprits, they may need to hurry. One of the most intriguing findings in the seasonality of suicide is that this ancient pattern appears to be fading — possibly because we all spend more time indoors.
A study of Switzerland's well-kept monthly suicide records between 1880 and 2000, for instance, showed the spring/summer curve growing flatter with each successive 30-year period. Like too many lives lost as we struggle to comprehend suicide, this spring surge may slip away before we can fully glean its unique offerings.David Dobbs is working on a book about the genetic and cultural roots of temperament and behavior.