Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale

23 November 2011

by David Tuller

Note: This account draws from interviews, a close reading of a fraction of the 4608 studies that pop up (as of today; yesterday it was 4606) on a PubMed search for “chronic fatigue syndrome,” and a review of many pages of government documents–in particular the minutes and testimony from meetings of the Chronic Fatigue Syndrome Advisory Committee to the U.S. Department of Health and Human Services, one of many such panels established to provide guidance to federal health officials. Not much here will be a surprise to anyone who has read the better ME/CFS blogs, or Hillary Johnson’s authoritative and prodigiously researched 1996 account, Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic. I want to thank Professor Racaniello for letting me invade his space to post this very long story.

David Tuller is coordinator of a new concurrent masters degree in public health and journalism at UC Berkeley. He was a guest on TWiV 119.

 

In the early 1990s, Mary Schweitzer, a history professor at Villanova University near Philadelphia, suffered through successive bouts of sickness—mononucleosis associated with Epstein-Barr virus, a stomach parasite, repeated episodes of bronchitis. One day, while reviewing student exams in her office, she slumped over and blacked out. Not long after, she received a diagnosis of chronic fatigue syndrome.

In written testimony to a federal advisory committee a few years ago, Dr. Schweitzer described how disabled she eventually became: “On a bad day, I would never get up at all, or would lie in bed curled up under the covers…I experienced pain behind my eyes and in the back of my neck. It felt as if somebody had hit me in the back of the head with a baseball bat, and someone else was trying to unscrew my eyeballs with a pair of pliers.”

Over the years, Dr. Schweitzer has tested positive for multiple viruses. She experiences severe lapses in memory, concentration and other cognitive skills. She suffers from “neurally mediated hypotension,” a form of low blood pressure arising from nerve dysfunction, which causes nausea, loss of balance, and fainting. Her muscle and joint pain can be intense, and she frequently requires a wheelchair. Her white blood cell counts have been way off; her immune system is often out of whack. She left her position at Villanova because of disability and has been unable to work most of the years since.

Like others with chronic fatigue syndrome, Dr. Schweitzer is used to having her illness ignored, mocked or treated as a manifestation of trauma, depression or hypochondria—not only by doctors, colleagues and strangers but by friends, family members and federal researchers, too. So when the U.S. Centers for Disease Control and Prevention reported last year that people with chronic fatigue syndrome are more likely to suffer from “maladaptive personality features”—in particular from “higher scores on neuroticism” and higher rates of “paranoid, schizoid, avoidant, obsessive-compulsive and depressive personality disorders”—Dr. Schweitzer dismissed the research as “incredibly stupid” but “not surprising.” In another recent study, the CDC had reported—also incredibly stupidly, from Dr. Schweitzer’s perspective–that childhood trauma, such as sexual or emotional abuse, was a “an important risk factor” for the illness.

For Dr. Schweitzer, other patients and advocates, and much if not all of the non-CDC research community involved with the illness, those two studies symbolize much of what has gone wrong with the agency’s research program on chronic fatigue syndrome. As the country’s leading public health organization, the CDC has enjoyed remarkable success in the fight against many diseases. But its history with chronic fatigue syndrome, commonly called CFS, is a matter of bitter–and ongoing—dispute.

“We’re talking about a million people who are really, really sick with something,” said Dr. Schweitzer, 61, in one of a series of recent conversations. “And we have been mistreated for years by people who are convinced that it’s just personality disorders or stress or some behavior that we can change and miraculously be well. None of us want to be sick or are doing this to ourselves.”

The CDC’s mandate is to investigate threats to the health and safety of the population; develop ways to prevent, disable or mitigate those threats; and disseminate key information to the public, policy-makers, health care providers and other audiences. Given those varied responsibilities, the CDC’s pronouncements about any topic—in this case, chronic fatigue syndrome–exert an enormous impact on policy, clinical care, insurance reimbursement and public attitudes. Advocates say that when the agency reports that people with CFS suffer from paranoid personality disorder, the public remembers the association, as do other scientists, government officials, health care providers, and insurance adjusters.

In fact, since the CDC first investigated an outbreak of a non-resolving, flu-like illness in the Lake Tahoe area in the mid-1980s, the agency’s CFS program has been marked by financial scandal, an epidemiologic strategy rejected as fatally flawed by the top researchers in the field, and the kind of toxic relationship with much of the patient community that can undermine the trust and cooperation needed for effective policy-making and public health strategies. On a more substantive level, over the past quarter-century, the CDC’s research program has yielded little or no actionable information about causes, biomarkers, diagnostic tests, or pharmaceutical treatments. Nor has the agency done much to track long-term outcomes–such as cancer rates, heart attacks and suicides–among people with the illness.

The reason for those failures, critics charge, is that the CDC has spent years looking in the wrong places. Starting with its 1988 report on the illness, they say, the agency has downplayed or dismissed abundant evidence that CFS is an organic disease, or cluster of diseases, characterized by severe immune-system and neurological dysfunctions as well as the frequent presence of multiple viral infections. Instead, say the critics, the agency has focused major resources on investigating proposed psychiatric and trauma-related factors and associations–the personality disorder and trauma studies were published, respectively, in the journals Psychotherapy and Psychosomatics and Archives of General Psychiatry–even though stress and trauma make people more vulnerable to any number of health conditions.

Moreover, they charge, the CDC’s website on the illness has long been a font of misinformation and has been routinely used by insurance companies to deny legitimate claims for tests ordered by doctors. (After years of complaints from patients and doctors, a paragraph that dismissed the usefulness of many tests, including those for various infectious agents, was finally changed this month.) Critics also note that the CDC website does not incorporate much clinical expertise from doctors who have treated patients for years, but it does highlight a behavioral form of treatment—a gradual increase in exercise, known as “graded exercise therapy”–that is widely discredited in the CFS community. Patient surveys and anecdotal testimony, as well as an increasingly robust body of research, suggest that the therapy might cause severe relapses in CFS patients by encouraging over-exertion.

“The CDC has never taken chronic fatigue syndrome seriously,” said San Francisco writer and former psychotherapist Michael Allen, who suffered a severe flu in the early 1990s and has never recovered his health. “They pay lip service to it being a serious physical illness, but in their hearts they think it’s just a form of mental illness.”

Much of the anger for the CDC’s perceived failings over the years has targeted Dr. William Reeves, an epidemiologist and architect of the CFS research program from 1989 until his abrupt move last year to another division of the agency. With his gruff and sometimes dismissive manner, Dr. Reeves was never popular with the patient community, which came to view him as hostile to the search for viral or other organic causes of the illness; many non-CDC researchers echoed that complaint. When it emerged in the late 1990s that the agency had been diverting funds designated for CFS to other programs and then lying to Congress about it, Dr. Reeves—who was in charge of the program while the financial irregularities were taking place–sought and received whistle-blower protection.

Dr. Reeves also enraged the patient community by his refusal to consider changing the much-hated name of the disease—a name endorsed by the CDC in its 1988 paper and aggressively promoted in a public awareness campaign the agency launched in the mid-2000s. Patients say the name, like the term ‘yuppie flu,’ reinforces stereotypes that they are a bunch of self-entitled whiners and malingerers and that the illness itself is a form of hysteria, the latter-day version of the Victorian malady known as “neurasthenia.” That’s why many doctors, researchers and patients have long promoted a less-stigmatizing clinical name for the illness that predated the selection of chronic fatigue syndrome: “myalgic encephalomyelitis,” or ME, which means “muscle pain with inflammation of the central nervous system.”

It is not possible to exaggerate how much patients despise the name and believe it has hindered public understanding—and how much they fault the CDC and Dr. Reeves for championing it. “If they’d hired a focus group to come up with a name that screams ‘silly’ and ‘meaningless,’ they couldn’t have done a better job than ‘chronic fatigue syndrome,’” said Dr. Schweitzer.

In an interview with The New York Times earlier this year, bestselling author Laura Hillenbrand (Seabiscuit, Unbroken), who has lived with CFS for decades, called the name of the illness “condescending” and “so grossly misleading.” She added: “The average person who has this disease, before they got it, we were not lazy people; it’s very typical that people were Type A and hard, hard workers… Fatigue is what we experience, but it is what a match is to an atomic bomb. This disease leaves people bedridden. I’ve gone through phases where I couldn’t roll over in bed. I couldn’t speak. To have it called ‘fatigue’ is a gross misnomer.”

After Dr. Reeves unveiled a revised epidemiologic method for identifying people with CFS, the CDC estimated in 2007 that there were 4 million people in the U.S. with the illness—a remarkable ten-fold increase over the previous CDC estimate in 2003. Other experts dismissed this dramatic rise as an artifact of the agency’s poor epidemiology. Subsequent research reported that the new CDC approach misclassified people with primary depression as having chronic fatigue syndrome, when they did not; that kind of misclassification could easily lead to increased prevalence rates as well as false and possibly harmful research results.

In the late 2000s, leading patient, advocacy and scientific organizations engaged in an increasingly public revolt against Dr. Reeves’ leadership. In January of 2010, the CDC abruptly appointed him as senior advisor for mental health surveillance in another part of the agency. Dr. Elizabeth Unger, an expert on human papillomavirus who had worked with Dr. Reeves for years, was named to replace him—first temporarily, then permanently–as chief of the Chronic Viral Diseases Branch, which currently houses the chronic fatigue syndrome program.

Now, almost two years after Dr. Reeves’ departure, advocates and researchers say they have seen a shift in tone—some believe it is genuine, others not–but so far little change in substance. (Requests to interview both Dr. Reeves and Dr. Unger, conveyed through the CDC media office, were declined; however, with a press officer acting as intermediary, Dr. Unger responded to questions via e-mail.)

“I’m committed to continuing an aggressive program to address the needs of CFS patients and families for quality medical care and to move CFS into the mainstream of public health,” wrote Dr. Unger. She added that the agency is developing new materials about CFS for medical and health care professionals, and has contracted for studies that will help clarify questions about how to identify the illness.

Dr. Unger has made a point of meeting with patient, advocacy and scientific organizations. In contrast to her predecessor, she has impressed some advocates and researchers with her willingness to listen to their concerns and seek out joint initiatives. But reflecting a widespread view, one activist (who preferred to remain anonymous) said that “overall, I do not feel much has changed under Dr. Unger…I do look forward to changing my mind, though, if appropriate actions are taken.”

Another person with a long history of involvement in the CFS issue offered a similar assessment, noting that Dr. Unger needs to do much more, and do it more quickly, to demonstrate that she’s pursuing a different approach. “I think she has got a window of opportunity, but the patient community is only going to give her so long,” said this advocate. “She can throw off the Reeves mantle and make a break with the past, or she can maintain the past. But there’s not a middle ground here, and she’s got to make a decision.”

Kim McCleary, president and CEO of the CFIDS Association of America, the oldest organization on the illness, said she believes Dr. Unger “is trying to restore some credibility to the CDC’s program.” But, added McCleary, whose organization worked closely with Dr. Reeves for years but ultimately opposed his leadership, “she’s not going to move quickly, she’s not going to do anything bold, she’s going to move pretty methodically along a linear path.”

Although Dr. Reeves’ departure received little public notice, it was a watershed event for patients and advocates, many of whom blame the agency for the prolonged lack of significant progress in CFS research. (They also blame years of inadequate funding from the National Institutes of Health, but that’s another long story; it is worth noting, however, that the NIH online database of spending by disease category indicates only $4 to $6 million allocated annually for CFS in recent years, a small amount compared to other illnesses associated with similar levels of morbidity. While the roles of the CDC and NIH can overlap significantly, the NIH generally focuses more on basic research into disease processes than on epidemiology and the development of public health strategies and interventions.)

The personnel shift at the CDC also occurred during a volatile period in the scientific domain. In October 2009, the journal Science published a headline-grabbing study that linked CFS to XMRV, a poorly understood mouse leukemia retrovirus. The finding thrilled the patient community because it appeared to offer a plausible explanation for the disease and to suggest treatment possibilities. Although a second study found links between CFS and a group of mouse leukemia retroviruses related to XMRV, other research has failed to support the proposed association. The Science report was partially retracted earlier this year, and most researchers now believe the initial findings were an artifact of laboratory contamination. Results expected early next year from a large NIH-sponsored study should settle the XMRV issue, although not the issue of whether another retrovirus might eventually be linked to cases of CFS.

(In the meantime, in a bizarre and unsettling turn of events, the senior author of the original XMRV paper, Dr. Judy Mikovits, is engaged in a fierce legal battle with her former employer, the Whittemore Peterson Institute for Neuro-Immune Disease, at the University of Nevada in Reno. The institute sponsored the XMRV research but has accused Dr. Mikovits, its erstwhile star scientist, of stealing laboratory notebooks and other materials—a charge she has denied. Public feuding between the institute and Dr. Mikovits ratcheted up as the hypothesis they jointly championed appeared to be falling apart. The institute filed a lawsuit against her earlier this month; she has also apparently been charged with “possession of stolen property,” according to a news update in Science. Last Friday, Dr. Mikovits was arrested in California as a “fugitive from justice” and spent the weekend in jail; she was released on bail after a hearing on Tuesday.)

Nevertheless, the heightened focus on CFS during the past couple of years has brought the illness greater attention from a larger group of scientists, including many infectious disease experts who had not previously given it much thought (e.g. the host of this blog, Columbia University virologist Vincent Racaniello). Experts now believe that one or a combination of viral or other infections, or perhaps other physiologic insults such as environmental toxins, can trigger an immune response that never shuts itself off; the immune response itself is likely the cause of many of the symptoms.

Dr. Racaniello said that when he used to question colleagues about chronic fatigue syndrome, they would argue that it was an imaginary illness. “Every time I asked someone about it, they would say it doesn’t exist, it isn’t a real disease, even as recently as the past year,” he said. “But once you start paying attention and reading papers, this looks like a chronic or hyper-immune activation. These patients have a lot of signs that their immune systems are firing almost constantly.” (Note: Dr. Racaniello is on the scientific advisory board of the CFIDS Association of America.)

According to this view, the revved up immune system is actually much less effective at controlling other infections, and studies have found associations between CFS and a grab-bag of pathogens, including members of the herpesvirus, parvovirus, and enterovirus families. Recent research from Norway has also lent support to the hypothesis that at least some people with CFS are suffering from a form of autoimmune disorder, perhaps triggered by one or multiple infections. Neurological impairments are also virtually always part of the complex; a study last year in the journal PLoS One found that people with CFS and a form of Lyme disease have patterns of proteins in their cerebrospinal fluid that clearly distinguish them from each other as well as from healthy controls.

In many cases, additional research has failed to confirm associations from prior studies. Yet there is a reasonable epidemiologic explanation for such divergent results: Most experts believe that there are likely many sub-groups or clusters of CFS patients, with a variety of infectious and possibly environmental exposures; studies that don’t account for such distinctions—and most haven’t–are much less likely to reach consistent results about causation or treatment. Moreover, different research groups have used different methods of identifying people with chronic fatigue syndrome, making it even harder to compare findings across studies—a situation that can encourage speculation that the roots of the illness lie in patients’ psyches.

“This ambiguity over definitions has made it difficult for researchers to pinpoint a biological cause,” wrote Leonard Jason, a professor of community psychology at DePaul University in Chicago and an expert in CFS, in an essay published this year in The Wall Street Journal. “When investigators compare very different samples, it is difficult, if not impossible, to replicate findings from one lab to another. And when consistent biological findings do not emerge, investigators might inappropriately conclude that CFS is only a psychiatric problem.”

In any event, the most promising research into the disease has been taking place not at the CDC or NIH but at academic medical centers; much of the new work is being funded by private donors who have family members with CFS. Researchers from Stanford, Harvard, University of Miami, Columbia, and other leading institutions are all engaged in innovative efforts focused on pathogenesis, diagnosis and treatment, and in particular on such issues as infectious triggers, biological markers, and medical therapies.

Dr. Derek Enlander, a longtime CFS clinician in New York, recently helped to launch an ME/CFS research and treatment center at Mt. Sinai Hospital; his highly regarded team hopes to explore genetic as well as other factors involved in the illness. The center was founded with the aid of a $1 million private donation, said Dr. Enlander, adding that such outside funding allows the group the freedom to pursue promising avenues of investigation. “I believe that an independent organization such as ours, which is not funded by the government or answerable to the government, can be the leader in new research,” said Dr. Enlander.

The Role of Case Definitions

Chronic fatigue syndrome is estimated to afflict about one million people in the U.S., although most remain undiagnosed. Some patients improve over time or have periods of better and worse health, but many remain disabled or even homebound for years. The symptoms include profound exhaustion, especially following minimal exertion, as well as disordered sleep, cognitive impairment, sore throat, and swollen lymph nodes, among others. It is one of a number of so-called “contested illnesses” that have emerged in recent decades to present thorny dilemmas for public policy and medical care; others include chronic Lyme disease, Gulf War syndrome, fibromyalgia, and multiple chemical sensitivity.

These conditions are characterized by shifting patterns of symptoms, a lack of agreed-upon biological markers and diagnostic tests, arguments over the interpretation of evidence, and competing claims of scientific authority. Patients presenting with these illnesses can bedevil doctors, who want to help but have few proven tools at their disposal. They might or might not be willing to try unorthodox strategies; some doctors clearly take advantage of patients who are desperate for relief. Such contested illnesses impact millions of people and their families, cost the U.S. billions in lost productivity, and consume a significant chunk of health care resources—and yet remain poorly understood. With so much at stake, they often emerge as societal and legal battlegrounds, with patients, clinicians, researchers, insurers, health officials and government bureaucrats all seeking to influence and control dialogue, debate and policy.

This conflict often plays out in struggles over a critical epidemiologic tool known as the “case definition”—a set of criteria for research or clinical use that ideally identifies all those who have a condition and screens out all those who don’t. Creating a case definition is easiest when a definitive laboratory test exists, as with HIV or hepatitis C. With an illness like CFS that is identified through symptoms, devising a completely accurate case definition is almost impossible; some people with the illness will always fall outside the parameters of the case definition, and some who have some other condition, or nothing at all, will be misdiagnosed—or will self-diagnose–as having CFS. Yet without a case definition that is as accurate as possible, researchers cannot achieve valid or reliable results.

“If you recognize something is happening, you need a case definition so you can count it,” Andrew Moss, an emeritus professor of epidemiology at the University of California, San Francisco, and an early AIDS investigator, told me for an article I wrote about case definitions earlier this year. “You need to know whether the numbers are going up or down, or whether treatment and prevention work. And if you have a bad case definition, then it’s very difficult to figure out what’s going on.”

Non-CDC researchers say the problem with the agency’s 2005 method for identifying CFS cases is that it mistakenly classifies people with primary depression as having chronic fatigue syndrome instead. Depression and CFS can resemble, overlap and interact with each other in multiple ways; patients with CFS may get very depressed about their situation, and depression often causes fatigue, as can many other ailments. So distinguishing chronic fatigue syndrome from primary depression—in other words, depression that preceded and perhaps caused the fatigue—is important but tricky, and requires nuanced instruments. In epidemiologic studies that conflate the two, treatments that are known to be effective for depression could appear to be effective for chronic fatigue syndrome, even if they might not be.

A case in point is a treatment called “graded exercise therapy,” a slow increase in exercise that has been promoted for CFS patients by the British psychiatric, medical, and insurance establishments; it is also highlighted as a treatment option on the CDC’s website and educational materials.

There is no dispute that exercise can be a very effective treatment for depression. But people with chronic fatigue syndrome generally suffer from a distinctive symptom known as “post-exertional malaise”—a disproportionate depletion of energy following minimal activity that is not a typical feature of depression. (However, the word ‘malaise,’ like the word ‘fatigue,’ is a complete misnomer; post-exertional malaise is much closer to a serious crash or relapse than a Victorian fainting spell.) An emerging field of research—much of it taking place at the University of Utah and University of the Pacific in Stockton, California–indicates that people with CFS suffer from problems with oxygen consumption, energy production and muscle recovery. So it’s not surprising that increasing activity levels could lead in some or many cases to a prolonged resurgence of their symptoms rather than the improvement predicted by proponents of graded exercise therapy.

Patients with CFS are very familiar with post-exertional malaise. Many report having recovered for a period of time, then pushing themselves too hard and suffering a devastating set-back, repeating the cycle multiple times before learning to adjust their pace. When Mary Schweitzer experiences post-exertional malaise, she said, she loses her formidable communications skills.

“I get close to incoherent,” she wrote in a recent e-mail. “I can’t make sense, and nobody can make much sense out of what I say. I am used to it now and try to make a joke out of it, but it’s sad.” As a result, she wrote, she has learned what people with CFS call ‘envelope theory,’ based on published work from Dr. Jason’s research group at DePaul University: how to harness their energy by recognizing their limits, and not pushing beyond them. That approach is essentially the antithesis of graded exercise therapy.

“You learn what will bring on a crash–sitting upright at a restaurant, for example–and you just don’t do it,” wrote Dr. Schweitzer. “You live in what we call your ‘envelope.’ Then if something special comes along like a birthday, you push the envelope, and if you get a push-back, you know you still have the same boundaries.”

Like Laura Hillenbrand, Mary Schweitzer is an author (although the book she wrote from her doctoral research at Johns Hopkins, Custom and Contract: Household, Government, and the Economy in Colonial Pennsylvania, has undoubtedly never reached Seabiscuit-y heights in Amazon’s rankings). She grew up in Richmond, Virginia; boogied in the mud at Woodstock; wooed her future husband, Bob, with home-cooked lasagna (he was the teaching assistant in an economics course she as an undergraduate at Duke); and was teaching, conducting research, and raising two kids when CFS whacked her life upside down.

Dr. Schweitzer said she could never have managed through the years without the support and devotion of her husband, a professor of finance and economics at the University of Delaware. But she has also improved significantly on intermittent treatment with Ampligen, a drug that appears to be effective for some people with CFS. The drug hasn’t been approved by the U.S. Food and Drug Administration, but Dr. Schweitzer currently receives it as part of an ongoing clinical trial. She travels twice a week from her home in Delaware to her doctor’s office in Manhattan for infusions of Ampligen; unlike in most clinical trials, she has to pay for the drug, which costs her $16,000 a year.

When off Ampligen, she has suffered major crashes; at one point several years ago, she tested positive for four herpesviruses—Epstein-Barr, cytomegalovirus, HHV-6A, and HHV-7—and Coxsackie B, an enterovirus. Whenever she can, she addresses public forums, in particular the twice-yearly meetings of the Chronic Fatigue Syndrome Advisory Committee, one of many committees created to offer guidance to the U.S. Department of Health and Human Services; she estimates that she has testified to date at thirty hearings, conferences or meetings. When she speaks, in a public forum or one-to-one, she is articulate, passionate, loud, tender, demanding, funny and fierce. In one of her many statements to the federal advisory committee, Dr. Schweitzer described one of her severe relapses.

“I lost the ability to walk normally and we had to bring the wheelchair back up from the basement,” she wrote. “I dropped things, and when I tried to load the dishwasher I crashed one glass against another…It made no difference that now I knew the names of the various symptoms–ataxia, expressive aphasia, short-term memory loss, central auditory processing dysfunction, etc. My brain had disappeared.”

A Bit of History

The conflict over the nature and definition of CFS–between the CDC and the patient community, as well as between the agency and other researchers–dates back to the initial investigations of an outbreak in Incline Village, Nevada, near Lake Tahoe, of a mysterious illness, possibly associated with Epstein-Barr virus. The outbreak was one of many reports in the mid-80s of what was already being called “chronic Epstein-Barr syndrome” or “chronic mononucleosis.” (Epstein-Barr virus causes most cases of mononucleosis).

In its 1988 paper on the illness, a CDC-led team of researchers cast doubt on the Epstein-Barr hypothesis and rechristened the phenomenon “chronic fatigue syndrome” to discourage unproven assumptions about viral origins. (Ironically, because CFS began as a suspected viral illness, the research program has remained housed in the agency’s viral section.) The paper proposed a complicated case definition requiring six months of unexplained fatigue, plus either six of eleven “symptom criteria” (mild fever, sore throat, painful lymph nodes, muscle weakness, muscle pain, prolonged fatigue post-exercise, headaches, joint pain, neuropsychological complaints, sleep disturbances, and sudden onset of the illness) and two of three “physical criteria” (fever, sore throat, and palpable or tender lymph nodes, documented by a physician twice, at least one month apart); or eight of the eleven symptom criteria, without the physical criteria.

In retrospect, for many patients the CDC’s first big blunder was in not calling the Tahoe illness myalgic encephalomyelitis in the first place. Benign myalgic encephalomyelitis has long been recognized by the World Health Organization as a synonym for “postviral fatigue syndrome,” which is listed as a neurological illness. The term was coined to refer to a similar flu-like outbreak at a major London hospital in the 1950s (although “benign” has since dropped out of common usage.) In practice, many patient and advocacy groups now combine the two terms as CFS/ME or ME/CFS, or use ME alone.

Dr. Reeves was not on hand for the original investigation, but joined the CDC in 1989 as chief of what was then called the Viral Exanthems and Herpesvirus Branch. Dr. Reeves received his B.A. in 1965 from the University of California, Berkeley, where his father was a renowned expert in mosquito-borne illnesses and served as dean of Berkeley’s School of Public Health; he studied medicine at University of California, San Francisco, earned a masters in epidemiology at the University of Washington, and worked at a major medical research center in Panama for a dozen years before joining the CDC in 1989.

A Harvard-led research team described the Tahoe outbreak in far more serious terms than the 1988 CDC report: the patients, they reported in 1992 in the Annals of Internal Medicine, had abnormal MRI brain scans, significant alterations in white blood cells counts and functioning, and signs of active infection with a recently discovered pathogen, HHV-6. The illness, they wrote, was likely a “chronic, immunologically mediated inflammatory process of the central nervous system.”

In a letter to the journal listing more than a dozen purported methodological flaws, the CDC—with Dr. Reeves as the lead author—dismissed the Harvard study and its findings in unusually blunt terms. “We conclude that the disease…described is not the chronic fatigue syndrome or any other clinical entity and that they showed no association with active HHV-6 replication,” wrote Dr. Reeves and his colleagues.

A pattern appeared to have been established. In a subsequent episode in the early 1990s, chronicled in detail in Osler’s Web, the CDC failed to confirm other researchers’ reports of a retroviral link to chronic fatigue syndrome. These and other contradictory results gave rise on both sides to claims and counter-claims and counter-counter-claims (etc.) of methodological flaws, unjustified assumptions, and other scientific sins of omission or commission.

In the early 1990s, a CDC-led team reviewed the complex 1988 case definition and published a revised and somewhat simplified version. According to these 1994 guidelines, a diagnosis of CFS required the presence of six months of disabling, medically unexplained fatigue, along with at least four of eight other symptoms: impaired memory or concentration, disordered or unrestful sleep, muscle pain, joint pain, headache, tender lymph nodes, sore throat, and post-exertional malaise. Although the definition relied on self-reported symptoms rather than biological tests or standardized instruments to measure levels of fatigue and disability, it soon became the most widely used set of criteria in both research and clinical settings.

The Financial Scandal

Two years after the CDC issued its 1994 case definition, Osler’s Web was published to strong reviews. The book documented how the CDC routinely diverted money slated for CFS research to other projects because of lack of concern about the illness. (The CDC did not officially comment on the book at the time, according to a CDC spokeswoman.) Two years later, Dr. Reeves leveled similar charges against his superiors, noting that the CDC lied to Congress about how it spent CFS funding; he received whistleblower protection.

In his statement, he reported that, for example, in 1996 the agency spent $1.2 million for laboratory equipment and supplies for measles and polio and charged it to the CFS account. In 1995, he reported, the agency charged the CFS program $2.6 million for funding spent on unrelated studies. He had, he stated “attempted to rectify this within CDC” before going public.

“I believe that CDC has intentionally misrepresented monies allocated to CFS research and I cannot ethically support this,” wrote Dr. Reeves in his public statement. “The misrepresentations involve systematically charging between $400,000 and $2 million incurred by unrelated activities to CFS between 1995-97 and reporting to DHHS [Department of Health and Human Services], Congress and patients that the monies were used for CFS research.”

A 1999 report from the inspector general of HHS found that of the $22.7 million the CDC charged to its CFS program between 1995 and 1998, less than half was clearly spent on the illness. The report noted: “CDC spent significant portions of CFS funds on the costs of other programs and activities unrelated to CFS and failed to adequately document the relevance of other costs charged to the CFS program…As a result of these inappropriate charges, CDC officials provided inaccurate information to Congress regarding the use of CFS funds.”

The inspector general’s report found that $8.8 million was spent on non-CFS projects and that the documentation on an additional $4.1 million was so poor that it was impossible to determine whether they were used to support CFS research or not. Even as the CDC shortchanged the CFS program, the report noted, it disregarded Congressional requests to support important research initiatives. As an example, the report noted that Congress had urged the CDC to expand its surveillance of CFS among adolescents and to hire a neuroendocrinologist “to enable expansion of its research efforts and pursue promising findings from other Federal agencies and the private sector.”

At the time of the inspector general’s report, however, the CDC had halted an ongoing adolescent study and had not hired an endocrinologist—even as allocated money wasn’t being spent. The report noted: “Internal correspondence… indicated that delays were forced due to a ‘lack of available funds.’ Yet, we found that large portions of budgeted CFS funds had been held in reserve by the Division Director during the year, and were not released until after the deadline for obligations had passed. Thus, while important enhancements were not being implemented, more than $850,000 of FY 1998 budgeted funds were never made available to the program.”

In the wake of the scandal, Dr. Reeves’ boss left his position; the agency agreed to reform its accounting practices and restore more than $12 million to the CFS program over the next several years. Although Dr. Reeves’ whistleblower status effectively solidified his position at the CDC, his statement didn’t answer all outstanding questions. Given the revelations from Osler’s Web in 1996, it seemed unlikely to many patients and advocates that key officials at the agency could have been unaware of accounting irregularities–especially since they apparently continued through 1998, according to the federal investigators.

A subsequent investigation in 2000 from the U.S. General Accounting Office (now called the Government Accountability Office) found that communication between the CDC and the NIH about CFS research programs and priorities was poor. The limited coordination, as well as the CDC misspending, had hampered progress in the search for answers to the illness, the investigators reported.

The financial scandal left many CFS advocates, patients and researchers with a lingering distrust toward the CDC. In the following years, however, some of the CDC’s work in chronic fatigue syndrome—funded by the millions restored to the budget–received praise.

In 2003, Dr. Reeves’ study of CFS in Wichita, Kansas, yielded a disease prevalence of 235 per 100,000 percent of the adult population, or about 400,000 overall in the U.S. That figure was below the generally accepted estimate of one million sufferers, derived from a community-based study in the Chicago area by Dr. Jason’s research group at DePaul University. Yet the new figure was accepted as far more accurate than the agency’s earlier estimates, from research in the 1990s, that less than 20,000 people had the illness; that research had been criticized for relying on doctors’ reports of patients with CFS, a far less effective epidemiologic method of assessing prevalence than community-based surveys. The Wichita research also provided a sense of the societal burden of CFS; the CDC team reported that the illness cost the economy $9.1 billion a year in lost productivity, and people with CFS lost an average $20,000 annually in earnings.

Also praised was the CDC’s partnership with Australian researchers on a study reporting that more than 10 percent of a cohort suffering from acute viral illnesses went on to develop CFS–one of the agency’s few successful efforts to document viral links. And in 2006, the CDC published—with great fanfare–a set of 14 studies in the journal Pharmacogenomics, which found significant variations in CFS patients of gene expression and activity related to how the body handles and adapts to physical and emotional challenges and stress.

Much of the research focused on genes associated with the hypothalamic-pituitary-adrenal axis, which regulates the body’s stress responses, among other functions. At a press conference introducing the studies, Dr. Reeves outlined his understanding of the illness: “The working hypothesis is that the HPA axis and the brain is a plastic organ which changes its actual physical architecture depending on stresses accumulated over the lifetime,” he explained. “So as people experience stress, and that can be childhood abuse, it can be childhood infections, it can be multiple injuries…to some extent the genetics determine how you are going to react to them, they determine how your allostatic load [a stress-related indicator] may accumulate, and more importantly, they actually determine your subsequent reaction to stress applied at a later time during the lifespan.”

Dr. Reeves himself declared the illness to be a matter of great public health concern and expressed empathy for patients. “People with CFS are as sick and as functionally impaired as someone with AIDS, with breast cancer, with chronic obstructive pulmonary disease,” he told me in 2007, when I wrote my first story about the disease for The New York Times.

Some advocates welcomed the genetics studies for providing evidence that the illness had a biological basis and was not a figment of patients’ imaginations. But a news article in Science about the Pharmacogenomics papers reported that other scientists had raised serious methodological questions about the CDC’s approach, with one prominent researcher calling the new findings “meaningless.” Others in the CFS community feared that the focus on stress and trauma as major factors left the door open for the CDC to focus on a wide range of psychologically and behaviorally oriented approaches in the search for both causes and treatments—and they note the recent personality disorder and childhood abuse studies as proof of their concerns.

 The Rejected Empiric Criteria

Other CDC efforts, such as the multi-million-dollar public awareness campaign to brand the name “chronic fatigue syndrome,” dismayed much of the patient and advocacy community, given ongoing and fervent attempts to have the illness officially renamed ME. And in a highly controversial move, Dr. Reeves spearheaded in 2005 the creation of the new, purportedly more precise method of identifying patients; critics feared the approach would wreak havoc with epidemiologic studies by mixing a lot of people with depression but not CFS into samples of people all presumed to have chronic fatigue syndrome.

During the 2000s, researchers—including many clinicians who actually treated patients and understood how seriously ill they could be—had continued to be dissatisfied with the 1994 case definition, which they felt imprecisely described the condition. For one thing, the definition allowed for but did not require the presence of post-exertional malaise (reminder: read “relapse” or “crash,” rather than “malaise”). Yet it was increasingly apparent that post-exertional malaise, and not fatigue alone, was a cardinal symptom for many if not most patients, and one that clearly helped distinguish CFS from primary depression, as well as other chronic illnesses. The CDC definition also allowed for but did not require the presence of cognitive and neurological problems, although these appeared to afflict almost everyone with the condition.

Other research groups were using their own case definitions, making it hard to compare results. The “Oxford criteria” developed in Great Britain required only the presence of six months of disabling fatigue; that single-symptom criterion was criticized as so broad that it was likely to identify many people with primary depression rather than CFS. A more detailed 2003 case definition developed in Canada focused on post-exertional malaise as a cardinal symptom of what it called ME/CFS. Required symptoms also included disordered sleep, pain, and neurologic symptoms, as well as signs of dysfunction in the immune, endocrine and autonomic nervous systems.

Earlier this year, a team of top researchers—not surprisingly, without any participation from the CDC–published a new “international consensus” case definition, which adopted the name myalgic encephalomyelitis and abandoned chronic fatigue syndrome altogether. Using the Canadian definition as a jumping-off point, the new international definition also dropped the construct of “fatigue” in favor of requiring post-exertional malaise, which they renamed “post-exertional neuroimmune exhaustion.” Other required symptoms include neurological and energy production impairments.

In contrast, the 2005 effort by the CDC to “operationalize” the earlier 1994 case definition–by introducing standardized questionnaires and measurement scales to assess levels of fatigue and functional impairment—has found no support outside the CDC itself. In suggesting specific instruments and scales, Dr. Reeves and his research team proposed cut-off points to represent sufficient grounds for identifying CFS.

Yet when the CDC researchers applied these new “empiric” criteria, as they called them, to a population in Atlanta in 2007, they found a prevalence of 2.54 percent of the adult population. Extrapolated nationwide, that meant that four million people—in other words, ten times the CDC estimate from its Wichita research just four years earlier, and four times the widely accepted figure of about one million—had the illness. Dr. Reeves and his co-authors defended the new numbers, attributing the increased prevalence estimates to a broad sampling strategy and “application of more sensitive and specific measures of the CFS diagnostic parameters.”

Others outside the CDC dismissed the new numbers as absurdly inflated and argued that the empiric criteria, like the Oxford criteria but unlike the 2003 Canadian case definition, blurred and expanded rather than clarified the disease boundaries. While some advocates believed the increased estimates would focus more attention on the illness and should therefore be embraced, many others—including leading epidemiologists–believed that the expanded category could make it harder to isolate physiological correlates; that failure, in turn, would make it more likely that others would continue to perceive it to be largely a psychiatric illness.

One study from Dr. Jason’s research group at DePaul University, frequently cited by advocates, found that 38 percent of a group suffering from major depression but not chronic fatigue syndrome were misdiagnosed as having CFS using the new empiric case definition. The researchers reported that the scales, measurements and cut-off points indicated by the CDC group did not sufficiently distinguish between emotional and physiological sources of fatigue and disability; in other words, someone could be identified as having CFS under the new method solely because of fatigue or disability arising largely from psychological causes, such as depression.

“Given the CDC’s stature and respect in the scientific world, this new definition might be widely used by investigators and clinicians,” wrote Dr. Jason and his co-authors. “This might result in the erroneous inclusion of people with primary psychiatric conditions in CFS samples, with detrimental consequences for the interpretation of epidemiologic, etiologic, and treatment efficacy findings for people with CFS.” The authors also noted pointedly that the population prevalence for CFS calculated using the empiric definition was close to that for major depressive disorders.

Although the empiric case definition was published six years ago, it has not found any favor outside the CDC, raising questions about the comparability of CDC data derived from its use to results from other studies. Dr. Unger wrote in her e-mail response that she knew of no other researchers who had adopted the empiric criteria, although she noted that “others have started applying case definitions using instruments as tools, recognizing the improved ability to get consistent results.” Three major ongoing CDC studies have samples selected through use of the empiric criteria.

Dr. Unger appeared reluctant to whole-heartedly endorse the estimate, based on the empiric criteria, that 4 million people in the U.S. have CFS, but she did not back away from it either. “No single study or approach can be considered sufficient to determine the true population prevalence of an illness as complex as CFS,” she wrote. “Like all studies, the 2007 prevalence estimates of CFS based on the Georgia surveillance study are subject to the limitations of the study design. However, the Georgia study, along with those from other investigators, does demonstrate the public health importance of CFS and it is the CDC’s most recent study on the prevalence.”

Dr. Unger indicated that the agency “is in dialogue with other investigators about instruments and methods to best characterize and stratify CFS patients.” The agency is also launching studies with several investigators to enroll and characterize patients from seven clinical practices headed by leading CFS physicians to help clarify issues involving the case definition as well as the name.

“We are planning to collect standardized data on all the domains of illness included in the Canadian Consensus Criteria of CFS/ME, the 1994 CFS definition and the newly proposed International ME definition,” she wrote. “We anticipate that this data will assist researchers and clinicians in considering further refinements of the case definition.” With regards to the name of the illness, she wrote: “Opinions of advocates, clinicians and researchers remain divided about whether CFS and ME are the same or different entities. However, we are following the discussions with interest and would consider any consensus that is reached by patient groups and the scientific community going forward.”

The Website Conflict

Another conflict that has dogged the agency involves its CFS website. Advocates and patients have long complained that it conveys serious misinformation, in particular on aspects of diagnosis, treatment and management of the illness. For example, until this month the website included the following language: “No diagnostic tests for infectious agents, such as Epstein-Barr virus, enteroviruses, retroviruses, human herpesvirus 6, Candida albicans, and Mycoplasma incognita, are diagnostic for CFS and as such should not be used (except to identify an illness that would exclude a CFS diagnosis, such as mononucleosis). In addition, no immunologic tests, including cell profiling tests such as measurements of natural killer cell (NK) number or function, cytokine tests (e.g., interleukin-1, interleukin-6, or interferon), or cell marker tests (e.g., CD25 or CD16), have ever been shown to have value for diagnosing CFS. Other tests that must be regarded as experimental for making the diagnosis of CFS include the tilt table test for NMH, and imaging techniques such as MRI, PET-scan, or SPECT-scan.”

Advocates and patients appealed to the CDC many times over the years to remove the language. They acknowledged that these and other tests were not diagnostic for CFS but insisted that wasn’t the point; even though the tests couldn’t be used to confirm that a patient had CFS, they were important weapons for disease management. Experienced clinicians, like Dr. Enlander at Mt. Sinai and Dr. Nancy Klimas, a top researcher at the University of Miami, have long used tests such as these to identify CFS sub-groups and individualize treatment strategies, given their patients’ histories of immune dysregulation and viral infections. Yet clinicians report that they have received letters from insurance companies citing that paragraph in rejecting claims for tests they have ordered, in some cases as recently as last summer.

The agency finally removed that language this month, after an advisory group reviewed the website and requested a host of changes. “They [the reviewers] provided useful feedback in early October and CDC is incorporating this feedback into our ongoing efforts to improve the CFS website,” wrote Dr. Unger. Replacing the old language is a new passage that suggests that some of the same tests once disallowed for diagnosis of CFS can be useful for disease management—as advocates have been saying all along. Patient groups welcomed the change, but some advocates said it was minimal and long overdue, given that many insurance claims had been rejected unfairly in years past.

Another major complaint about the website has been the agency’s longstanding promotion of two treatments developed and championed in the United Kingdom: graded exercise therapy and cognitive behavior therapy. In the U.K, mental health professionals have dominated research into and treatment of chronic fatigue syndrome; they use the Oxford criteria, requiring only six months of unexplained fatigue. A major British study using this case definition and published earlier this year indicated some improvement with graded exercise therapy and cognitive behavior therapy. But U.S. experts on the illness, at least those outside the CDC’s immediate orbit, generally believe that the U.K. case definition—like the CDC’s empiric definition–is likely to define a cohort that includes a lot of people with depression, and not actual CFS, as their primary complaint.

To those convinced that CFS is a condition of psychogenic and not organic origin, it probably doesn’t matter if people with depression are mixed up in a study sample. In the framework of chronic fatigue syndrome endorsed by the British medical establishment, the prolonged fatigue and associated illness are largely considered to be caused by the patient’s inability or unwillingness to maintain an active lifestyle—an avoidance triggered by some form of stress, psychological issues or perhaps even an infectious illness. That avoidance of activity then leads to a physiological deconditioning that impacts multiple body systems and organs.

“It’s a psychological model,” said Dr. Jason of DePaul University, of the British view of CFS. “It’s an illness that might be caused by some kind of virus or trauma, but what’s maintaining it is that you have some sort of phobic avoidance of activity. The idea is your bone and muscle mass decrease, you become weak. So if you can get a person to slowly increase the amount of activity that they do, they will break this phobic avoidance.”

In the U.K. framework, graded exercise therapy is often paired with cognitive behavior therapy in the treatment protocol for CFS. Cognitive behavior therapy is a treatment modality with widespread application, and is likely to be useful to many people undergoing major stresses–whether from cancer, a back injury, an existential crisis, fear of sex, migraines, a bad divorce, or cognitive fatigue syndrome. However, the kind of cognitive behavior therapy prescribed in Great Britain to treat people with CFS—as Dr. Jason and other researchers have repeatedly noted–is largely geared toward convincing patients to overcome their avoidance phobia and increase activity levels; in other words, to encourage them to participate in something very much like graded exercise therapy.

But for people who experience post-exertional relapses of their symptoms, graded exercise therapy could be harmful, not helpful; in addition to the emerging research about post-exertional malaise, patient surveys in the U.K. have indicated a high degree of unhappiness and increased morbidity among those who have been through a course of graded exercise therapy. And, say critics, cognitive behavior therapy could also be harmful, if the goal is to convince patients to engage in graded exercise therapy or otherwise ramp up activity levels.

Dr. Unger wrote in her response that she was aware of patient concerns about including information on graded exercise therapy and cognitive behavior therapy on the website, and that the agency was reviewing those sections. The goal of the information, she wrote, was to let patients know about treatment options they could discuss with their health care providers. “Though these approaches may not work for everyone, the scientific literature shows that they provide some benefit to some patients,” she wrote.

However, Dr. Unger declined to comment specifically on the contested scientific literature from the U.K. that actually reported the modest benefits from these therapies, noting that “as a rule, CDC doesn’t comment on research not conducted by CDC.”

The View from the Chronic Fatigue Syndrome Advisory Committee

The growing dismay about Dr. Reeves’ leadership and the agency’s problematic CFS research program are evident in the minutes and testimony from the twice-yearly meetings in the late 2000s of the Chronic Fatigue Syndrome Advisory Committee of the Department of Health and Human Services. The mandate of the committee, with a rotating membership of clinicians, researchers, patients and advocates, is to offer guidance and recommendations to the department. In 2007, the committee requested financial records from the CDC’s CFS program. Dr. Jason, a member of the CFSAC, and Dr. Reeves, an ex officio member as the CDC’s representative, sparred publicly over access to the records.

By the time of the next CFSAC meeting, in October of 2008, Dr. Reeves had been replaced as the CDC’s ex officio member (although he retained his CDC position). Another CDC official at the meeting said he hoped the change would help “to leave behind past tensions to make a fresh start.”

At that meeting, however, Kim McCleary, the head of the CFIDS Association of America, testified that the CFS program, based on a review of the CDC financial documents that the committee had sought, suffered from “shameful scientific leadership, zero accountability, invisible outcomes and millions and millions of dollars stuck in suspended animation, if not wasted…Only the government contractors seem to be benefiting from millions spent for which there are no worthwhile outcomes for American taxpayers, or CFS patients.”

The largest chunk of the program’s funding, reported McCleary, went to a single private research organization, Abt Associates in Cambridge, Massachusetts, in sole-source or no-bid contracts for the epidemiologic research that was being widely criticized by other scientists. At least $2.7 million committed to Abt was “in limbo”–obligated to specific projects but remaining unspent—and work on other projects was proceeding slowly and at great cost, she testified. The financial mismanagement, testified McCleary, “has resulted in program management coming often to this committee and telling other investigators that no funds are available for new projects or collaborations.”

(The CFIDS Association of America had been criticized by some other advocates over the years for its previous close association with Dr. Reeves. The organization had provided essential public support for Dr. Reeves during the accounting scandal in the late 1990s; in the mid-to-late 2000s it implemented the agency’s controversial multi-million-dollar CFS public awareness campaign at a time when others were seeking to change the disease name. McCleary’s public rebuke of Dr. Reeves’ leadership, therefore, was viewed as a significant blow to the CFS program and found a welcome audience.)

McCleary’s report further shredded support for Dr. Reeves among committee members; some were researchers struggling with their own funding issues. The financial accounting appeared to confirm a frequently heard complaint about the CDC and Dr. Reeves—that they were not taking full advantage of opportunities to collaborate with outside scientists at academic research centers.

Christopher Snell, a professor of sports sciences at the University of the Pacific in Stockton, CA, and a committee member, stated, according to the minutes: “As somebody who works on a shoe string budget, when I start to look at some of these numbers, I was somewhat appalled… It just does not seem to be the best use of the funds. The thing that we asked for at a couple of previous meetings was for the CDC to consider more collaboration with outside entities. We meant people who work a lot cheaper. It would seem that there are people out there with great ideas who would love to work with the CDC for much less money.”

Dr. Klimas, also a committee member, noted that she had been collaborating with the CDC on a study comparing people with CFS and Gulf War illness, and that the agency had failed to finish its testing on samples, citing funding problems. She also unleashed another common charge: that the CDC was simply not interested in the role of pathogens. According to the minutes, “Dr. Klimas said that CDC has made it known that the agency has no intention of looking for infectious agents. She added that other research organizations are pursuing identification of pathogens and that CDC should be embarrassed not to be looking for them as well…despite the evidence, the CDC is still saying that viruses don’t matter in the illness even though people are already being treated for them. She said that the science is there to provide options way beyond the CDC’s recommended behavioral treatment and exercise.”

At its meeting in May 2009, the committee unanimously voted to recommend “progressive leadership” for the CFS program; although the recommendation, in an apparent nod to decorum, did not cite Dr. Reeves by name, the intent was clear. The request for a top personnel change—essentially a vote of no-confidence in the current leadership–was considered an aggressive move for this kind of federal advisory committee. At the same meeting, the International Association for CFS/ME, a leading scientific and research organization, endorsed the call for new leadership.

In October of 2009, Dr. Reeves committed what many in the CFS world regarded as a major public gaffe: an off-hand remark to a New York Times reporter (not this one) about the mouse retrovirus research that had just sparked a wave of excitement. In the interview, which occurred shortly after the publication of the Science paper reporting the link between XMRV and CFS, Dr. Reeves said his research team would look for the retrovirus but that they were unlikely to find anything. He told the Times: “If we validate it, great. My expectation is that we will not.”

For a scientist to predict his team’s outcomes in a contested field of research during a highly public and volatile debate is not the best way to demonstrate impartiality and open-mindedness (notwithstanding that the XMRV hypothesis appears not to have panned out). Even more so for someone like Dr. Reeves, who was already facing coordinated calls for his ouster from almost every corner.

At the CFSAC meeting later that month, the committee again approved a recommendation for new leadership and emphasized the urgency of the issue. According to the minutes: “CFSAC considers that recommendation important and would like to get some feedback, including whether or not the recommendation is being considered. This has become more important because of certain quotes that have been made in The New York Times concerning the retrovirus by the person in charge of the CDC program.”

The committee also formally rejected the CDC’s empiric case definition—the centerpiece of Dr. Reeves’ epidemiologic approach—and recommended support for “a national effort to arrive at a consensus definition of CFS that is accurate, standardized, and reflective of the true disease.”

Within months, Dr. Reeves was gone from his position, although no public explanation for the move was offered. For the most part, the elements of the CFS program that Dr. Reeves championed—the empiric criteria, the name of the illness, (most of) the disputed website information, etc.—remain in place under Dr. Unger.

Reaction to Dr. Unger’s efforts appears decidedly mixed so far. Yet some members of the research community express optimism about being able to develop, with Dr. Unger, the kind of cooperative framework that many felt was absent when Dr. Reeves ran the program. Dr. Fred Friedberg, president of the International Association for CFS/ME, said that Dr. Unger was “way more responsive” than Dr. Reeves, noting that she had attended the association’s annual conference this fall in Ottawa.

“We reached out to her and she has been very accommodating and engaged in conversation to talk about some joint efforts,” said Dr. Friedberg, a professor of psychology at Stony Brook University Medical Center. “It remains to be seen what goals she’s going to set up and what kind of studies she’s going to do exactly. So this is kind of a work in progress, but the level of cooperation is pretty good. For the first time in years, there’s an opening.”

  • ME too

    WOW …. I’m speechless.  THANK YOU

  • Anonymouse-y

    So the Neurologic Post Treatment Lyme Disease described earlier this year in Schutzer et al does not exist (did you leave a dissenting comment on the PloS website expressing your views on the gullibility of others?), and because this article references it, the entire article is unworthy of consideration? That’s a very interesting proposition. Did Mr. Tuller make this all up? 

    I was wondering what Alan Dove (and other scientists) thought of this article, which seems to have mostly drawn attention from patients; researchers and clinicians are somewhat conspicuous by their absence here. This is hardly shocking to ME/CFS patients who have dealt with a culture of denial for decades. The somatization they are often told they are experiencing is, ironically, a manifestation of a belief on the part of a medical authority who imagines the patient is suffering from something that is not actually the cause of their symptoms. Funny how that works, especially since no medical professional is accountable for this denial. Ever.

    Professor Racaniello deserves kudos for running this here.

  • http://profiles.google.com/daedalus4u David Whitlock

     Very nice article. Lets hope the new and ongoing CFS research doesn’t get hijacked by those with an agenda to prove it is one thing or another. The constellation of symptoms of CFS is unique and not similar to any other disorder we are familiar with (though individual symptoms are), maybe the cause(s) of CFS is unique too, and that is why ongoing research has not found it.

    Because so many metabolic systems are affected, it very likely is a “systems” problem, a problem that relates to the signaling pathways that relate to the coordination of the different metabolic systems that are disrupted.

    My idea is that CFS is due to metabolism being skewed to a low basal nitric oxide level for too long, and I have discussed them in a blog post.

    http://www.chronicfatiguetreatments.com/wordpress/treatments/chronic-fatigue-syndrome-nitric-oxide/

  • Emma

    David Tuller,
    thank you so much for this! Would you consider writing a book on the topic of ME/CFS, the research (or the lack thereof) and the views of the illness in the community (medical and societal)? A similar book with a Norwegian perspective was published in October and is selling really well. I think an American, updated book would be much needed and appreciated!

  • http://www.psychscoop.com Amykaron

    Outstanding piece by David Tuller (my hair stood on end when I read the phrase “maladaptive personality features”). Thanks to The OpenNotebook for recommending it. I had thought that graded exercise was a standard of care for CFS patients and appreciate the chance to learn that this approach is in fact controversial. Kudos to Stanford researchers and others who’ve pushed for a rigorous, standardized case definition for CFS.

  • Paula Carnes

    Mr. Tuller,
    Please follow the study which found different proteins in the spinal fluid of chronic Lyme patients compaired to cfs patients. IF this study continues we MAY be able to determine what the underlying infection(s) are.

  • Sarissass

    I don’t like the “which situation is worse” game; the Tuskegee and ME/CFS situations are both bad.  Some points though to illustrate the situation in ME/CFS -
     1) “were not told they had the disease” — many people with ME/CFS either have not been diagnosed due to skepticism/ poor education on the part of physicians, misdiagnosed with depression,  or when they are diagnosed, are given the impression this is a psychological rather than medical illness2) mistreatment — while there is no standardized effective treatment for ME/CFS at the moment,  again the situation is similar in that graded exercise therapy is considered standard of care by many mainstream medical providers/ academic medical centers despite evidence that it can cause harm. One of the rules of medicine is “First do no harm,” even ahead of  whether a treatment is effective of not. 3) “racist” — the equivalent to this in ME/CFS is “sexist”. Although men are not immune to ME/CFS, many studies show that it is more common in women at a ratio of about 3:1.  Historically, women with different medical illnesses have had their symptoms dismissed and attributed to hysteria, not being married, etc. and have suffered from poor investigation into their medical condition. 

    4) “So many needlessly suffered and died.” — What mainstream sources do not tell you is that people also die from ME/CFS. What really got me angry about this illness was not just the overall situation but that a friend in her early 40s died from ME/CFS  [she's not the first person I knew who died from it but the first I knew personally] yet the mainstream scientific and medical communities do not talk about this at all.  Shortly after I became ill, an MD friend told me a patient, in his 30s, of his also died from this.

    Here are two sources:

    http://www.ncf-net.org/library/CausesOfDeath.pdf  — peer-reviewed article

    http://www.blueribboncampaignforme.org/ME_CFS_Memorial.html

    Don’t feel bad if this is is news to you but do learn about it. I have two graduate scientific degrees and a medical background yet I didn’t know this stuff and it wasn’t conveyed to me in any of my training until I became ill and spent the last several years combing the literature to find out what I had. 

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  • Anonymous

    Thank you Mr Tuller and Dr Racaniello for sharing with your readers many of the historical facts about the decades long coverup of the neurological disease Myalgic Encephalomyelitis.

    Links to further evidence of the truth of this coverup:

    For those who have not read Osler’s Web, please refer to Osler’s Web
    author Hillary Johnson’s speech “The Why” that was presented on the eve
    of the  2009 Invest in M.E. annual international medical conference in
    London. 
    http://www.oslersweb.com/the_why___a_speech_in_london_86981.htm

    CFS and the CDC’s Failure to Respond: Primetime Live (1996), a primetime news report on the “CFS” scandal, demonstrating in 1985 the first brain scans of M.E. patients found to be identical to AIDS patients, and the subsequent CDC dismissal of Elaine de Freitas et al 1991 discovery of a retrovirus, the trashing of her career and her health. http://www.youtube.com/watch?v=AW0x9_Q8qbo (12:46)

    Dr Byron Hyde’s historical account of the facts known about M.E. that were ignored
    by the 1987 CDC definitional committee meeting, where M.E. experts Dr Gordon Parish and Dr Alexis Shelekov walked out in
    protest. From the M.E. International website: Elliot Kieff, M.D.
    (Harvard), who refused to sign on to the CDC’s first (CFS) criteria: “Is the intention to create a new psychiatric classification?”

    http://www.imet.ie/imet_documents/BYRON_HYDE_little_red_book.pdf

    “What is ME? What is CFS? Advice for Clinicians and Lawyers”, 2001 seminal paper by Prof Malcolm Hooper et al explains the political and financial climate that lead to the displacement of ME with CFS.
    http://www.investinme.org/Article-020%20What%20is%20ME%20What%20is%20CFS.htm

    CORPORATE COLLUSION?
    The UK Medical Research Council has a secret file on Myalgic Encephalomyelitis (ME) that contains records and correspondence since at least 1988; the file is held in the UK Government Archive at Kew and cannot be opened until 2023. This present document is an overview of the misinformation and contradictions about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that have pervaded some UK Departments of State and other agencies since 1988. It also considers the involvement of certain UK psychiatrists who have proven vested interests in the propagation of this misinformation that is contrary to world-wide scientific evidence and that for two decades has resulted in the medical abuse of UK patients with ME/CFS. http://www.meactionuk.org.uk/Corporate_Collusion_2.htm

  • Anonymous

    Thank you Mr Tuller and Dr
    Racaniello for sharing with your readers many of the historical facts
    about the decades long coverup of the neurological disease Myalgic
    Encephalomyelitis. FYI some links to further evidence supporting the truth of this coverup:

    For those who have not read Osler’s Web, please refer to Osler’s Web author
    Hillary Johnson’s extraordinary speech “The Why” that was presented on the eve
    of the 2009 Invest in M.E. annual international medical conference in London. 

    oslersweb.com/ the_why___a_speech_in_london_86981.htm

    CFS and the CDC’s Failure to Respond: Primetime Live (1996), a primetime
    news report on the “CFS” scandal, demonstrating in 1985 the
    first brain scans of M.E. patients found to be identical to AIDS patients,
    and the subsequent CDC dismissal of Elaine de Freitas et al 1991 discovery
    of a retrovirus. youtube.com/ watch?v=AW0x9_Q8qbo
    (12:46)

    Dr Byron Hyde’s historical account of the facts known about M.E. that were
    ignored by the 1987 CDC definitional committee meeting, where M.E. experts
    Dr Gordon Parish and Dr Alexis Shelekov walked out in protest. From the
    M.E. International website: Elliot Kieff, M.D. (Harvard), who refused to
    sign on to the CDC’s first (CFS) criteria: “Is the intention to
    create a new psychiatric classification?” imet.ie/ imet_documents/BYRON_HYDE_little_red_book.pdf

    “What is ME? What is CFS? Advice for Clinicians and Lawyers”,
    2001 seminal paper by Prof Malcolm Hooper et al explains the political and
    financial climate that lead to the displacement of ME with CFS.

    investinme.org/ Article-020%20What%20is%20ME%20What%20is%20CFS.htm#How_CFS_displaced_ME_in_the_UK_

    CORPORATE COLLUSION?

    The UK Medical Research Council has a secret file on Myalgic Encephalomyelitis
    (ME) that contains records and correspondence since at least 1988; the
    file is held in the UK Government Archive at Kew and cannot be opened
    until 2023. This present document is an overview of the misinformation and
    contradictions about Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
    (ME/CFS) that have pervaded some UK Departments of State and other
    agencies since 1988. It also considers the involvement of certain UK
    psychiatrists who have proven vested interests in the propagation of this
    misinformation that is contrary to world-wide scientific evidence and that
    for two decades has resulted in the medical abuse of UK patients with
    ME/CFS.meactionuk.org.uk/ Corporate_Collusion_2.htm

  • Max Banfield

    I have studied this problem for more than 30 years and have written various reports about the history of the chronic fatigue syndrome. Prior to the introduction of the wide spread use of that label in the  mid 1980′s I did research at the South Australian Institute for Fitness Research and Training which scientifically proved that chronic fatigue had a real physical basis. The measurements proved that the symptom was not imaginary, and not normal tiredness, and the fact that a dozen patients completed more than 3 months training proved that it was not due to laziness, or the fear of exercise, or the desire to be ill, or remain ill, and or get sympathy. Shortly after I provided scientific proof that all of those ideas were wrong the term chronic fatigue became widely used  See a description of that successful research study here http://users.sa.chariot.net.au/~posture/ChronicFatigueSyndrome.html

  • Guest

    Mr.
    Tuller,

    Thank you
    very much for this article, and to Prof Racaniello for publishing i.

    When
    you said that   “… once you start
    paying attention and reading papers, this looks like a chronic or hyper-immune
    activation. These patients have a lot of signs that their immune systems are
    firing almost constantly.”

    I implore you to read ALL
    of the following papers linked below, and challenge you to come to any other
    conclusion.

    I extend the same plea to
    Prof Racaniello.

    In addition, when reading
    these papers I beg you to always keep in mind the following quote from you
    article:  “When Mary Schweitzer experiences post-exertional malaise, she
    said, she loses her formidable communications skills.”

    http://www.ncbi.nlm.nih.gov/pubmed/15546155

    http://www.ncbi.nlm.nih.gov/pubmed/19157572

    http://www.ncbi.nlm.nih.gov/pubmed/18762240

    http://www.ncbi.nlm.nih.gov/pubmed/17560496

    http://www.ncbi.nlm.nih.gov/pubmed/139400

    http://www.ncbi.nlm.nih.gov/pubmed/21573053

    http://www.ncbi.nlm.nih.gov/pubmed/21629840

    http://www.ncbi.nlm.nih.gov/pubmed/16360218

    http://www.ncbi.nlm.nih.gov/pubmed/18762342

    http://www.ncbi.nlm.nih.gov/pubmed/19135624

    http://www.ncbi.nlm.nih.gov/pubmed/17265454

    http://www.ncbi.nlm.nih.gov/pubmed/20345322

    http://www.ncbi.nlm.nih.gov/pubmed/576606

    http://www.ncbi.nlm.nih.gov/pubmed/7770287

    http://www.ncbi.nlm.nih.gov/pubmed/8935240

    http://www.ncbi.nlm.nih.gov/pubmed/9493492

    http://www.ncbi.nlm.nih.gov/pubmed/1743418

    http://www.ncbi.nlm.nih.gov/pubmed/12369775

    http://www.ncbi.nlm.nih.gov/pubmed/702254

    http://www.ncbi.nlm.nih.gov/pubmed/15288500

    http://www.ncbi.nlm.nih.gov/pubmed/16875710

    http://www.ncbi.nlm.nih.gov/pubmed/21130877

    and last but not least http://www.ncbi.nlm.nih.gov/pubmed/21727249

     

    There
    are many, MANY more papers like these, and many more parallels, on every
    conceivable level.

     

    Thank
    you in advance for your time.

     

  • Guest

    apologies for the formatting gone wrong above

  • http://profiles.google.com/reilly.justin Justin Reilly

    Unfortunately, graded exercise “therapy” is institutionalized abuse of very sick patients which worsens our disease.  It certainly did mine.

  • http://profiles.google.com/reilly.justin Justin Reilly

    I agree.  The medical profession and individual medical professionals have generally shamefully and  uncritically accepted, disseminated and employed these abusive ‘treatments’ and theories.  The time to stand up to these sadistic abusers was thirty years ago when patients, researchers and clinicians first sounded the alarm over this abuse.  

    My demand to the medical professionals reading this: don’t let another day go by before you investigate this iatrogenic near-holocaust and stand up to it!  If you don’t, the blood will be on your hands.  Why should you care? The next person to get ME and be abused maybe you or your children.

  • http://profiles.google.com/reilly.justin Justin Reilly

    Dr. Unger is basically Dr. Reeves just without the publicly aggressively offensive comments.  The ONLY positive thing she has done in her two years on the job is removing some of the lies on the CDC’s website a few weeks ago.  Having taxpayers’ money wasted on Reeves definition studies (three currently ongoing according to Mr. Tuller) is absolutely unconscionable!  She must be replaced with a competent expert TODAY!

  • akrasia

    Yes, thanks to David Tuller and Dr. Racaniello for this fine article.

    The CDCs ineptitude and malfeasance did not arise from nothing.  There is a notorious memo quoted by Hilary Johnson in Oslers Web, http://www.oslersweb.com/index.htm,  known as the “Dear Sirs, I am Sick” memo, a heavy handed parody of desperate letters they had begun to receive around the time of Incline Village.   This was a widely circulated piece and a good summary of institutional malice and indifference.

    How does a citizen, contemplating this unconscionable level of neglect and depravity in both the NIH and CDC, address this?  Where was an intelligent, investigatory adversarial press?  How was so much contempt and mockery of severely ill people allowed to flourish in an ostensibly generous, responsible and open society.  How could an epidemic happening in plain sight not be addressed?

    As someone who has lived through and reported on the AIDS epidemic, I suspect you recognize some of these themes.  Thanks again for your work. 

     

  • Bgreenex

    Abundant thanks for all the efforts of David Tuller and to Vincent Ranciello for the venue.  I lived through all this and more since the late 1980′s.  It’s true and then some.

    Knowing the incompetence of CDC on this disease, one has to wonder about their recommendations on AIDS,  flu shots. breast cancer, autism….

    The facts about the CDC are clear.  Unger et al must all be removed before CDC can start forming a legitimate policy on M.E.  They must start with accepting the international definition published this year by treating physicians around the world in opposition to the CDC’s multiple definitions.  The CDC website must come down immediately and be entirely revamped.  And Congressional funding to CDC should be stopped until an entirely new staff and scientific direction are established at CDC.

    I hope that the NYTimes will take up the exposure of CDC in relation to this disease.  And I hope people will agree to stop using the “CFS” terminology altogether; it really grates.  The new published definition is M.E.; let’s use it and work with it to round out and refine the definition.  At least we would all be on the same page. 

    Again, thank you to Tuller and Ranciello. 

  • http://profiles.google.com/daedalus4u David Whitlock

     Guest, I have looked at the abstracts of each of those papers and have read some of them. I have read many that you have not listed. I have several comments.
    Autism is not a disorder of neuronal damage and injury. Autism-like symptoms can be produced through damage. Neuroinflammation can produce damage that causes autism-like symptoms. Neuroinflammation can also produce autism-like symptoms in the complete absence of damage. Autism is a neurodevelopmental disorder of children, which persists throughout the lifespan. It is not something that one can acquire as an adult.
    When adults acquire autism-like symptoms due to neuroinflammation it is called something else. The neuroinflammation of neurosyphilis causes withdrawal and catatonia. To the uninitiated these might be considered “autism-like” symptoms. Any type of neuroinflammation will cause decreases in functional connectivity because neuroinflammation reduces the background NO level in the brain, and it is the NO level that triggers functional connectivity and it is fluctuations in the NO level that produce the vasodilation observed in the fMRI BOLD technique. Regions of high perfusion are regions of high NO because it is the high NO that causes the vasodilation that causes the high O2Hb levels measured with BOLD.
    The “brain fog” of numerous disorders is always associated with reduced functional connectivity and is always associated with reduced perfusion and is always associated with neuroinflammation. These disorders include neurosyphilis, Alzheimer’s, Parkinson’s Disease, Huntington’s Disease, and essentially all others. What regulates blood flow in the brain and elsewhere is nitric oxide. What regulates functional connectivity in the brain is nitric oxide. What regulates inflammation is nitric oxide (via NfKB and others).

    An early treatment for neurosyphilis was fever therapy. The developer won the Nobel Prize for it, and it was the standard of care for a couple of decades until penicillin was developed. In some cases acute fever due to injection of killed bacteria would resolve neuropsychiatric disorders in less than 24 hours, indicating that the problem was functional connectivity and not actual connectivity (because there was insufficient time for new connections to be made).
    My hypothesis is that physiology induces neuroinflammation to protect neurons from the very high levels of NO that occur during immune system activation. If that neuroinflammation is not resolved, then functional connectivity never returns. I discuss this in considerable detail in the context of acute fever temporarily resolving some symptoms of autism.
    http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-fever.html

    I also discuss how a normal immune system can damage mitochondria and how that can shift physiology into a “bad” state where the inflammation can continue indefinitely. I think this is what happens in neurosyphilis and also what happens in CFS.
    http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html
    CFS is a chronic condition. A chronic condition can only be due to perturbations in the normal control of what ever chronic adverse condition is happening. Either the normal control system led physiology to a bad and chronic state, or the normal control system didn’t lead physiology away from that bad and chronic state. Modulating the control systems that physiology uses is extremely difficult because all of those control systems are under dynamic automatic gain control and feedback. Those extreme levels of feedback and control make physiology very robust and fault tolerant, but they also make it extremely difficult to “hack into” and make arbitrary changes. This difficulty is why drugs have side effects, physiology self-modifies so as to reduce the effects of what ever the drug is doing.

  • Linden

    I read this article increasingly slowly as I couldn’t believe what I was reading – a fair article about M.E.
    I’ve never seen this before. It felt lovely.

    Thank you so much for being fair, for taking the time to look at the evidence, and for the colossal effort it must have taken for you to articulate so clearly the tangle of the uniquely unkind history behind this disease.

  • Bobmiller

    Thank you Dave Tuller for taking the time to investigate the details of this ignored and neglected illness. The truth is within those details. A  thank you to Mary for sharing her story and many thanks to Dr. Racaniello for giving you the space and time to present the facts.

  • Guest

    Thank you for this article. It goes a long way in explaining the mystery of why research in CFS/ME and other contested, but very real diseases like Multiple Chemical Sensitivity/IE, are still being ignored and patients suffering these diseases are ridiculed that they are mistaking depression as illness.  Not all “invisible diseases” are psychological, though the diseases and society’s barbaric reaction to them could cause depression in patients. 

  • Guest

    Thank you for you comment David, nice contribution. But it does not quite answer my original question, which was directed at Mr Tuller and Prof R.

  • guest

    to kdurkin
    re the tuskegee experiment and the treatment of patients with ME, think again about it. think about the indifference, the institutionalized abuse, think gender, ableism, think money and power and healthcare system experiment, think bystanders looking away…

    read this too, this may shock some though
    http://planetthrive.com/2009/12/we-tuskagee/

    thank you to david tuller for writing this piece and dr racaniello for hosting it.

  • http://profiles.google.com/reilly.justin Justin Reilly

    OK… so I’m still waiting for the hordes of people who came out of the woodwork outraged over the supposedly “bad science” committed by WPI, NCI and Cleveland Clinic in the Lombardi et al. paper.  Still waiting after 30 years for one of these guardians of science rectitude to raise a concern about the 30 years of outright fraudulent “science” and abuse millions of disabled by CDC, NIH, UK NHS and the Wessely school.  Where are you??

  • http://profiles.google.com/daedalus4u David Whitlock

    Guest, a point I was trying to make is that the immune system is extremely complicated with myriad pro-inflammatory and anti-inflammatory cytokines which must be in balance for proper function. It is poly-dimensional with hysteresis and feedback and is not well understood.

    The major anti-inflammatory cytokine is nitric oxide. Nitric oxide also happens to be the neurotransmitter that regulates blood flow in the brain and also functional connectivity in the brain as measured by fMRI BOLD. If pro-inflammatory cytokines get the upper hand, then the basal nitric oxide level is reduced and NO mediated signaling is reduced. That can show up as reduced blood flow, reduced functional connectivity, increased mast cell sensitivity, reduced mitochondria biogenesis, hypertension, capillary rarefaction, endocrine disruption, and other things.

    The symptoms discussed in the articles you mention could all be due to reduced nitric oxide levels. All NO signaling pathways only detect the sum of NO from all NO sources including the background level. If the background level of NO is reduced (for any reason), then all NO mediated signaling will be reduced.

    Immune system activation is usually turned on by oxidative stress, by the respiratory burst of immune cells, by the release of pro-inflammatory cytokines by mast cells, by activation of NFkB. NFkB then causes expression of iNOS to generate very large quantities of NO to balance the pro-inflammatory cytokines produced by the rest of the immune system produces, particularly in regions of particular sensitivity such as the brain, and to also prevent bacterial biofilms from forming in the vasculature (NO is a quorum sensing compound that inhibits biofilm formation). That iNOS only hangs around for a day or so and then is degraded and the NO level falls. If the pro-inflammatory cytokines do not fall as well, then a permanent pro-inflammatory state can occur which has hysteresis because it requires nitric oxide to stop the production of superoxide by enzymes such as xanthine oxidase.

    A low NO state is a state of immune hyperactivity because the respiratory burst threshold is reduced. NO inhibits NFkB. This paper

    http://books.google.com/books?id=a3mwmXzpsjkC&lpg=PP1&pg=PA103#v=onepage&q&f=false 

    Discusses the role that the bacteria I am working with may play in the hyperactive immune system observed in the developed world that has led to what is called the hygiene hypothesis. The hygiene hypothesis is an attempt to explain why immune system hyperactivity (allergies, IBD, atopy, asthma) is observed in developed regions but not in rural undeveloped regions.

    The immune system doesn’t need an actual infection to become activated. If the signals that physiology uses to trigger the immune system are present, the immune system will be triggered no matter if an infection is present or not. If the immune system is triggered, there will be inflammation and a reduction in the background NO levels. That will affect all NO mediated signaling pathways.

    An infection can trigger the immune system, but so can other things like trauma and stress. Stress is a low NO state. Conditions that are made worse by stress are likely made worse by the low NO that accompanies stress which affects all NO mediated signaling pathways. To fix conditions that are made worse by stress, you have to fix the signaling that stress is perturbing. If it is the low NO of stress that is perturbing signaling pathways, the only way that signaling can be fixed is by raising NO levels. If the background NO level is low due to the loss of these bacteria, then the only way that background NO level can be fixed is with restoration of these bacteria.

  • Linden

    The suffering that lies behind this story is immense and profound.

  • Sleeper

    There are obviously some very smart people who read and have commented on this excellent article. But the ‘death’ of XMRV leaves me with one question I wish someone would answer. If the problem was contamination, why did ME/CFS patients test 90+% positive while controls only tested 4%. Would they not be the same?

  • Rescindinc Org

    Beautiful! When can we expect to see this baby in the Times?!!!

  • Tom Kindlon

    According to a bit.ly link I made, this has been tweeted 20 times (Twitter), shared on Facebook 223 times (with 392 likes and 171 comments). A bit.ly link has been followed 289 times. (It doesn’t give info for other social media). These are big numbers (compared to what I normally see) – keep it up.

  • Tom Kindlon

    FWIW: I don’t think the number of Tweets is reliable. I thought it was 22 or 23 before but it said 20 so went with that. Now it’s saying 9!

  • Pete

    Thank you, Mr. Tuller!

    Your well-written overview matches what I have seen in endless hours of following Google trails since about 2004, trying to understand what I have, what I’m reading, why and how on earth it is a stigmatized disease, and my own suspicions about why it is brushed under the carpet. 

    The various prejudices, originating from sources who should be working toward the general health of  us all, and lack of financial funding may rival the stigma and hurdles once associated with HIV/AIDS.  You have addressed many concerns of this underestimated and increasingly large group of neglected individuals, of which I am a part, and have given a good history along with recent information to bring the history to date. 

    I love the varied responses below.  To read your article was to see some of the sweet essence of truth.  (Many of us are too ill to write it ourselves due to cognitive impairment!)  Thank you for your significant effort.

  • ME too

    This discussion reminded me about the article, ‘The Heat Is On’ in New Scientist July 31 2010; pp 42-45.

    Online the article is titled ‘Fever: friend or foe?’ http://www.newscientist.com/article/mg20727711.400-fever-friend-or-foe.html but a subscription is needed to read it.

    In the magazine there is an ‘info-box’ about Nobel Laureate Julius Wagner-Jauregg’s use of infection (with malaria) to induce fever in patients with syphilis, as treatment; but you flesh out the details much better in your blog entry of Jan 1st 2008.

    The info-box’s brief account:

    “… [around a century ago] Austrian physician Julius Wagner-Jauregg noticed that some of his psychiatric patients improved after fever attacks.  [He attempted to induce fever in patients but failed, so he injected blood from a person infected with malaria into a patient with syphilis.]  The patient developed a fever – and then began to recover … Trials with more patients showed that the technique could cure people of [syphilis] if used quickly.  In 1927 Wagner-Jauregg was awarded the Nobel prize for medicine.

    His success prompted further research into the benefits of artificially induced fevers.  Hot baths, warm air, electric blankets and even high-frequency currents were used to raise the body temperature to levels thought capable of killing pathogens – typically around 41˚C.  By the mid 1930′s, doctors in the US had treated hundred of patients in so-called Kettering Hypertherms – cabinets equipped with hot air blowers and temperature monitors.  The results were impressive: just one 5-hour session in the devices seemed enough to bring syphilis under control, though permanent recovery typically required 50 hours or more. … Patients deemed unable to cope with the … stress … were excluded. … [Cure rates were up to 80%, but by late 1930s antibiotics emerged, which stymied further research and interest.]”

    The main article questions whether routine use of antipyretics is wise.

    Here are two letters that were published in response to the New Scientist article:

    1.  Don’t fear the fever

    28 August 2010:  From Heinz-Uwe Hobohm, University of Applied Sciences Giessen-Friedberg. Giessen, Germany

    I was extremely interested in your discussion of the effects of fever (31 July, p. 42).  In 1996, while working in Germany on a cancer project at the University of Bremen, I stumbled on a 1951 paper by Louis Diamond and Leonard Luhby on spontaneous remission in childhood leukaemia (Journal of American Medicine, vol 10, p 238).  They noted that a feverish infection preceded remission in 21 out of 26 children they studied.

    I remember jumping up from my chair thinking this cannot be happenstance.  I investigated many publications on spontaneous regression from cancer.  Many, if not a majority, of cases were preceded by a feverish infection – see my paper in the British Journal of Cancer (vol 92, p 421).  Today we know that bacterial and viral chemicals such as lipopolysaccharides, which are strong inducers of fever, are needed to activate innate immune system – the body’s initial immune response which defends against pathogens in a general way without conferring immunity – and that this activation is needed to trigger a full-blown T-cell response against cancer cells.

    Yet whenever I present these findings in medical circles, the reaction is blunt mistrust.  For example, at a recent conference on innate immunity I listened to a talk that revealed that many more patients survive sepsis, a whole-body inflammatory response, if they develop fever.  I asked whether it might be worth considering inducing fever in high-risk patients.  I received a brief response: “No”.

    http://www.newscientist.com/article/mg20727770.100-sweat-it-out.html 

    2. Sweat it out

    08 September 2010:  by Adrian Jones, Edmonton, Alberta, Canada

    Your article on the benefits of not treating fever prompted a déjà vu moment for me (31 July, p 42). In 1972, a small group of chairs of US academic paediatric departments – and me, a youngster from Canada – took part in a three-day workshop entitled “Management of fever” at the Centers for Disease Control in Atlanta, Georgia.

    It was decided that treatment for fever should not be implemented before a patient’s temperature reached 104 °F (40 °C). This was subsequently presented at my medical school, but with little effect. About a decade later, the paediatric residents also presented similar data to show that treatment below that level was rarely necessary, again to little effect. The chief obstacles were nurses and older physicians, who wanted to feel that they were providing treatment. At least we managed to get rid of the alcohol baths, cold baths and cold compresses. …

    I wonder if the Dubbo Infection Outcomes Study looked at use of antipyretic medication

    • during the acute infection that preceded development of ME?

    • for ongoing treatment during the non-recovery period?

  • http://profiles.google.com/daedalus4u David Whitlock

    ME too, I think part of the problem has been one of attributing the curative effects to elevated temperatures, rather than to the (much more complex) physiology which accompanies the natural raising of temperature via natural fever during natural infections.

    Also, the idea of “sweating it out” has been hijacked by CAM and beneficial effects of sweating accompanying fever have been (wrongly) attributed to the removal of (non-existent) “toxins” by sweating.

    There haven’t been (and still aren’t) the techniques to understand what is really going on during sepsis and fever. I think a big problem has been the myth of homeostasis which has blinded researchers and clinicians into thinking that physiology is not as well controlled as it actually is. That myth has given unsophisticated clinicians and researchers the idea that they know what is going on when they are really profoundly ignorant of what physiology is trying to do and how it is trying to do it.

    Raising temperature by itself is not “the same” as physiology causing a fever due to immune system stimulation via an infection. During infection induced fever there are myriad and coordinated physiological changes going on, release of pro-inflammatory and anti-inflammatory cytokines in different tissue compartments, release of signaling compounds that attract specific immune cells to specific tissue compartments, a great many things which we know we don’t understand and have no ability to measure and they are happening in tiny tissue compartments and which may not easily relate to what can be measured in bulk blood.

    Simply raising temperature has been tried and sometimes it works and more often it doesn’t. When physiology raises the temperature, it does so via mitochondria uncoupling which also increases O2 consumption, increases superoxide and H2O2 production (a substrate for myeloperoxidase), increases blood flow, increases temperature gradients allowing differential signaling of metabolic activity via temperature.

    Also, the dominant new medicine paradigm that has taken hold in the US pretty much precludes any potential treatment that doesn’t fit it. The paradigm is (essentially), find a small molecule that does something in vitro and is patentable, spend a few million testing it in vitro, spend a few tens of millions testing it in animals, then spend a few hundreds of millions testing it in humans, then if the FDA “blesses it”, spend a few hundreds of millions marketing it and sell it and make many billions a year until the patent runs out. Any potential treatment that doesn’t fit this paradigm cannot ever be successful because it is never funded. Can all disorders be successfully treated by drugs that can make it through that specific paradigm? I see no reason to thinks so, but by the entrenchment of that paradigm, all others are excluded before they are tested so we will never know.

    What if IV LPS could be used to induce a fever that could cure different kinds of cancer? Who could sell it and make many billions a year? No one, because LPS isn’t patentable.

  • CFSBOSTON

    In my view, if CFS/ME patients truly want billions of dollars of funding to beallocated to studying their illness, they need to first demand of theirgovernment officials’ that our medical establishment conduct a Re-Appraisal of AIDS (i.e., admitting that HIV is not the cause of AIDS).I believe CFS and AIDS should be researched collectively by scientists ratherthan as separate entities. I suggest that the CDC’s AIDS Division be movedunderneath their CFS umbrella so all the infections that AIDS and CFS have incommon are researched together. I am not suggesting that CFS is “AIDS”, as Iknow people don’t like sound of the ‘scarlett letter.’  What I am stating isthat AIDS patients have CFS, which, as CFS patients’, we already know is notcaused by HIV.I have already demanded (of this Adminstration and the last) that Obama, Fauci and the Director of NIH make a public statement that (just from what we know today) in terms of the immune dysfunction and human suffering, CFS is just as serious a public health problem as AIDS.I further submit that an annual international joint CFS & AIDS conference beheld by the World Health Organization, and that next December 1st be declaredthe first World AIDS/CFS Day.  CFS patients are long overdue for the respect, andultimately I am focused on the billions of dollars to back it’s delinquency.  I vote for viral parity, and I measure success based on how much money backs my government’s rhetoric.

    I stopped fighting for myself a long time ago.  My fight now is for humanity.www.cfsstraightttalk.blogspot.com

  • Jann

    Excellent article. Thank you. We have a CFS/ME family member who is being virtually ignored by his current health care system. We know we must stay positive–but it is hard. People like you, Mr. Tiller–add to the process of moving forward.  We are through being angry–we just want forward movement.

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  • J.P.

    My wife, who suffers through the life described in this article, forwarded this to me.  I am thankful for a cogent, careful, sensitive and clear description of what many are currently having to endure with no medical hope.

    It is my hope that a wave of compassion and outrage would overcome the “good ol’ boys” club of modern medicine and that a response to the need would surface in a fight to relieve the real debilities that many of our loved ones endure everyday.

    KUDOS!

  • CFSBOSTON

    AIDS patients are simply more CFS patients.  And it already well-accepted that HIV is not the cause of CFS/ME.  Please write a letter to your representative(s) demanding that the medical establishment conduct a “Re-Appraisal of AIDS.”

    Please ask for funding to support “HIV-Negative AIDS” & “Chronic Fatigue Syndrome” research. Please feel free to suggest any/all of my aforementioned points (from my last post).

    Your representatives can be found here:http://www.senate.gov/general/contact_information/senators_cfm.cfmhttp://www.house.gov/house/MemberWWW.shtmlhttp://www.whitehouse.gov/contact/In the fight for humanity.
    Karen
    http://www.cfsstraighttalk.blogspot.com

  • http://twitter.com/velogubbed Nasim Marie Jafry

    Thankyou, David Tuller.

  • Mclaughlinjill

    This is an accurate history but we seem to get mired in it. Let’s fast forward to the present. 
    The constant drone about “this disease.” Which one? ME is not CFS. 

    It is fairly well accepted that the Incline Village outbreak was ME. It is not just the 
    name that was changed, but it was an extremely cursory investigation done by 
    CDC which failed to capture the salient and hallmark features of ME and thus 
    did not properly identify it. Since that time CFS has been redefined and there 
    are now numerous CFS definitions, all of which differ, but none adequately define 
    or describe what was historically recognized as ME.

    Post exertional relapse is a hallmark of ME, not CFS. In the Fukuda CFS definition, 
    which has been used mainly in the US, it is a minor criterion and optional. 
    That which is optional is not a cardinal feature. 

    CFS is not an illness or disease but is so broad as to include many disparate 
    conditions which share the common and immeasurable symptom of fatigue.
    Patients with depression or mental health problems can be included, and 
    not just the Empiric 2005 CFS case definition. Those promising to solve CFS 
    or find the cause are selling a myth. Or akin to solving an illusion. Something 
    as heterogeneous as CFS is like saying X=ABCDE. Find the cause of X. Or  find 
    “THE cause” of pain or headaches.

    This is why there has been so much confusion and controversy and so little 
    progress. Most “CFS” research has no bearing on ME, if this is what we’re 
    talking about. 

    There is no such thing as “ME/CFS,” it is just another made up term 
    with different meanings and has no real scientific or diagnostic validity or 
    accepted case definition. There is no ICD code for making an official diagnosis. 
    The Canadian ME/CFS case definition used the term ME/CFS and formed a 
    hybrid with features of both ME and CFS but was published in a journal that 
    is no longer in existence.

    CDC has told the truth: “The name myalgic encephalomyelitis (ME) was 
    coined in the 1950s to clarify well-documented outbreaks of disease; however, 
    ME is accompanied by neurologic and muscular signs and has a case definition 
    distinct from that of CFS.” 

    Yet the so called US patient CFS or “ME/CFS” groups (Pandora and 
    Coalition 4 ME/CFS)  that continue to put out the ME=CFS=ME/CFS 
    misinformation and recreate that which caused the problems to begin with.
    http://www.hfme.org/whobenefitsfromcfs.htm

    ME patients continue to fight for proper recognition and diagnosis, not as or 
    combined with CFS, despite the US “CFS” groups misinformation and interference.

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  • MeekPeek4

    It is not reproducible because it used a CFS definition of exclusion.

  • Meek

    Tuller needs to revisit his comment about VP62.  We now know Lombardi et al. did not find those viruses but other MLV-related ones.  

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  • Anonymous

    An extremely interesting and well written piece.  I do so hope David Tuller will continue his work with ME.  I suspect that over the coming years, the debate will become even more controversial as the incidence of ME explodes due to the mass vaccination by the HPV vaccines.

    Immunizations have been cited as a trigger for ME but, as so often happens with ME, the research is sadly lacking.  As teenage girls (and teenage boys now too) are vaccinated against the Human Papillomavirus, the adverse reactions have included ME and autoimmune diseases.  Of course the CDC and FDA will never admit that a vaccine mandated in many states is causing ME across a whole generation of teenage girls (and boys), but the evidence is there, in the Vaers reports and in the anecdotal evidence from the girls and their parents.

    The HPV vaccine/ME connection will eventually be too obvious and the casualties too numerous to ignore, but what a travesty that independent research is not taking place now to minimize the fallout and damage.

    Could the reason for the lack of funding for meaningful research into the causes of ME be that the higher powers simply do not want the complications of the public knowing what it is and what is causing it?

  • http://www.virology.ws profvrr

    It’s not correct to state that ME is caused by the HPV vaccine, based on the VAERS database and anecdotal evidence. The VAERS database lists only adverse events in those receiving vaccines and provides no information about the incidence of such events in the general population. Anecdotal reports cannot be used because the data are not properly collected.

    Finally, the ‘higher powers’ don’t decide what scientific work is done in the US. Research is largely investigator-initiated and grant proposals are peer-reviewed. If scientists are not interested in working on a problem, little will get done.

  • akrasia

     While “higher powers” don’t issue diktats, directly instructing what is studied and what is not, the institutions of society, such as the CDC or NIH, the pressures asserted in academic life, who brings in the most money and cachet, what work will lead to tenure, and the general climate of ignorance and hostility, are de facto methods of control. As you told David Tuller, your colleagues thought M.E. to be an “imaginary” illness.  If someone wanted to investigate M.E. that alone would be enough to discourage them.  There are very few people prepared to risk the stress of straying off conventional paths.  Sometimes, like the fellow who won this year’s Chemistry Nobel, you blunder into a great insight that does not conform at all to prevailing ideas and elect to stand by the finding.  He received a great deal of opprobrium for this.   Asymmetrical crystals was a serendipitous finding; would he have sought it, knowing the scorn he would endure? Most people wouldn’t.  And there is no shame to this.  We are social animals and not all of us are up for marginalization.  That’s why climate matters; the cultivation of open, rigorous inquiry is crucial to a responsible compassionate society. People with M.E. didn’t want heroes, we needed intelligent, imaginative, persistent diligence.  Do you think your colleagues would have been as dismissive if the CDC and NIH had fulfilled their missions in regard to M.E.?  Last week, saw two interviews posted on line: Dr. Ian Gibson, a former m.p., representing Norfolk and Jose Montoya, a professor at Stanford medical school. Gibson describes an atmosphere of threat and intimidation directed at the University of East Anglia for considering the idea of becoming a center for the study of M.E. http://www.mecfsforums.com/index.php/topic,10827.0.html Montoya speaks of his mentor telling him that engaging with M.E. as a researcher or clinician is “professional suicide. http://www.mecfsforums.com/index.php/topic,10824.0.htmlAs recounted in Oslers Web, Jay Levy, one of the authors of the xmrv “refutation,” published in Science,  abandoned M.E. research when he realized that the difficulties obtaining funding were insurmountable. All intellectual life is mediated by many factors, some conscious, others not.   Scientists, like all intellectuals, are neither free agents nor free spirits.