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 â€œchronic fatigue syndrome,â€ 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 Johnsonâ€™s authoritative and prodigiously researched 1996 account, Oslerâ€™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 onÂ TWiV 119.
In the early 1990s, Mary Schweitzer, a history professor at Villanova University near Philadelphia, suffered through successive bouts of sicknessâ€”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: â€œOn a bad day, I would never get up at all, or would lie in bed curled up under the coversâ€¦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.â€
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 â€œneurally mediated hypotension,â€ 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 hypochondriaâ€”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 â€œmaladaptive personality featuresâ€â€”in particular from â€œhigher scores on neuroticismâ€ and higher rates of â€œparanoid, schizoid, avoidant, obsessive-compulsive and depressive personality disordersâ€â€”Dr. Schweitzer dismissed the research as â€œincredibly stupidâ€ but â€œnot surprising.â€ In another recent study, the CDC had reportedâ€”also incredibly stupidly, from Dr. Schweitzerâ€™s perspective–that childhood trauma, such as sexual or emotional abuse, was a â€œan important risk factorâ€ 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 agencyâ€™s research program on chronic fatigue syndrome. As the countryâ€™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 ongoingâ€”dispute.
â€œWeâ€™re talking about a million people who are really, really sick with something,â€ said Dr. Schweitzer, 61, in one of a series of recent conversations. â€œAnd we have been mistreated for years by people who are convinced that itâ€™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.â€
The CDCâ€™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 CDCâ€™s pronouncements about any topicâ€”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 agencyâ€™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 CDCâ€™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 CDCâ€™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 treatmentâ€”a gradual increase in exercise, known as â€œgraded exercise therapyâ€–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.
â€œThe CDC has never taken chronic fatigue syndrome seriously,â€ said San Francisco writer and former psychotherapist Michael Allen, who suffered a severe flu in the early 1990s and has never recovered his health. â€œThey pay lip service to it being a serious physical illness, but in their hearts they think itâ€™s just a form of mental illness.â€
Much of the anger for the CDCâ€™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. Reevesâ€”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 diseaseâ€”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 â€˜yuppie flu,â€™ 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 â€œneurasthenia.â€ Thatâ€™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: â€œmyalgic encephalomyelitis,â€ or ME, which means â€œmuscle pain with inflammation of the central nervous system.â€
It is not possible to exaggerate how much patients despise the name and believe it has hindered public understandingâ€”and how much they fault the CDC and Dr. Reeves for championing it. â€œIf theyâ€™d hired a focus group to come up with a name that screams â€˜sillyâ€™ and â€˜meaningless,â€™ they couldnâ€™t have done a better job than â€˜chronic fatigue syndrome,â€™â€ 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 â€œcondescendingâ€ and â€œso grossly misleading.â€ She added: â€œThe average person who has this disease, before they got it, we were not lazy people; itâ€™s very typical that people were Type A and hard, hard workersâ€¦ Fatigue is what we experience, but it is what a match is to an atomic bomb. This disease leaves people bedridden. Iâ€™ve gone through phases where I couldnâ€™t roll over in bed. I couldnâ€™t speak. To have it called â€˜fatigueâ€™ is a gross misnomer.â€
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 illnessâ€”a remarkable ten-fold increase over the previous CDC estimate in 2003. Other experts dismissed this dramatic rise as an artifact of the agencyâ€™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. Reevesâ€™ 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 himâ€”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. Reevesâ€™ departure, advocates and researchers say they have seen a shift in toneâ€”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.)
â€œI’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,â€ 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 â€œoverall, I do not feel much has changed under Dr. Ungerâ€¦I do look forward to changing my mind, though, if appropriate actions are taken.â€
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 sheâ€™s pursuing a different approach. â€œI think she has got a window of opportunity, but the patient community is only going to give her so long,â€ said this advocate. â€œShe can throw off the Reeves mantle and make a break with the past, or she can maintain the past. But thereâ€™s not a middle ground here, and sheâ€™s got to make a decision.â€
Kim McCleary, president and CEO of the CFIDS Association of America, the oldest organization on the illness, said she believes Dr. Unger â€œis trying to restore some credibility to the CDCâ€™s program.â€ But, added McCleary, whose organization worked closely with Dr. Reeves for years but ultimately opposed his leadership, â€œsheâ€™s not going to move quickly, sheâ€™s not going to do anything bold, sheâ€™s going to move pretty methodically along a linear path.â€
Although Dr. Reevesâ€™ 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 thatâ€™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 materialsâ€”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 â€œpossession of stolen property,â€ according to a news update in Science. Last Friday, Dr. Mikovits was arrested in California as a â€œfugitive from justiceâ€ 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. â€œEvery time I asked someone about it, they would say it doesnâ€™t exist, it isnâ€™t a real disease, even as recently as the past year,â€ he said. â€œBut 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.â€Â (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 donâ€™t account for such distinctionsâ€”and most havenâ€™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 studiesâ€”a situation that can encourage speculation that the roots of the illness lie in patientsâ€™ psyches.
â€œThis ambiguity over definitions has made it difficult for researchers to pinpoint a biological cause,â€ 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. â€œWhen 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.â€
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. â€œI 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,â€ 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 â€œcontested illnessesâ€ 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 resourcesâ€”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 â€œcase definitionâ€â€”a set of criteria for research or clinical use that ideally identifies all those who have a condition and screens out all those who donâ€™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 misdiagnosedâ€”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.
â€œIf you recognize something is happening, you need a case definition so you can count it,â€ 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. â€œYou 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 itâ€™s very difficult to figure out whatâ€™s going on.â€
Non-CDC researchers say the problem with the agencyâ€™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 depressionâ€”in other words, depression that preceded and perhaps caused the fatigueâ€”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 â€œgraded exercise therapy,â€ 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 CDCâ€™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 â€œpost-exertional malaiseâ€â€”a disproportionate depletion of energy following minimal activity that is not a typical feature of depression. (However, the word â€˜malaise,â€™ like the word â€˜fatigue,â€™ 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 researchâ€”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 itâ€™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.
â€œI get close to incoherent,â€ she wrote in a recent e-mail. â€œI 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 itâ€™s sad.â€ As a result, she wrote, she has learned what people with CFS call â€˜envelope theory,â€™ based on published work from Dr. Jasonâ€™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.
â€œYou learn what will bring on a crash–sitting upright at a restaurant, for example–and you just don’t do it,â€ wrote Dr. Schweitzer. â€œYou live in what we call your â€˜envelope.â€™ 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.â€
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 Amazonâ€™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 hasnâ€™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 doctorâ€™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 herpesvirusesâ€”Epstein-Barr, cytomegalovirus, HHV-6A, and HHV-7â€”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.
â€œI lost the ability to walk normally and we had to bring the wheelchair back up from the basement,â€ she wrote. â€œI 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.â€
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 â€œchronic Epstein-Barr syndromeâ€ or â€œchronic mononucleosis.â€ (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 â€œchronic fatigue syndromeâ€ to discourage unproven assumptions about viral origins. (Ironically, because CFS began as a suspected viral illness, the research program has remained housed in the agencyâ€™s viral section.) The paper proposed a complicated case definition requiring six months of unexplained fatigue, plus either six of eleven â€œsymptom criteriaâ€ (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 â€œphysical criteriaâ€ (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 CDCâ€™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 â€œpostviral fatigue syndrome,â€ 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 â€œbenignâ€ 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 Berkeleyâ€™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 â€œchronic, immunologically mediated inflammatory process of the central nervous system.â€
In a letter to the journal listing more than a dozen purported methodological flaws, the CDCâ€”with Dr. Reeves as the lead authorâ€”dismissed the Harvard study and its findings in unusually blunt terms. â€œWe conclude that the diseaseâ€¦described is not the chronic fatigue syndrome or any other clinical entity and that they showed no association with active HHV-6 replication,â€ 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 Oslerâ€™s Web, the CDC failed to confirm other researchersâ€™ 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, Oslerâ€™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 â€œattempted to rectify this within CDCâ€ before going public.
â€œI believe that CDC has intentionally misrepresented monies allocated to CFS research and I cannot ethically support this,â€ wrote Dr. Reeves in his public statement. â€œThe 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.â€
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: â€œCDC 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.â€
The inspector generalâ€™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 â€œto enable expansion of its research efforts and pursue promising findings from other Federal agencies and the private sector.â€
At the time of the inspector generalâ€™s report, however, the CDC had halted an ongoing adolescent study and had not hired an endocrinologistâ€”even as allocated money wasnâ€™t being spent. The report noted: â€œInternal correspondenceâ€¦ indicated that delays were forced due to a â€˜lack of available funds.â€™ 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.â€
In the wake of the scandal, Dr. Reevesâ€™ 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. Reevesâ€™ whistleblower status effectively solidified his position at the CDC, his statement didnâ€™t answer all outstanding questions. Given the revelations from Oslerâ€™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 CDCâ€™s work in chronic fatigue syndromeâ€”funded by the millions restored to the budget–received praise.
In 2003, Dr. Reevesâ€™ 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. Jasonâ€™s research group at DePaul University. Yet the new figure was accepted as far more accurate than the agencyâ€™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 doctorsâ€™ 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 CDCâ€™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 agencyâ€™s few successful efforts to document viral links. And in 2006, the CDC publishedâ€”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 bodyâ€™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,â€ he explained. â€œSo 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.â€
Dr. Reeves himself declared the illness to be a matter of great public health concern and expressed empathy for patients. â€œPeople with CFS are as sick and as functionally impaired as someone with AIDS, with breast cancer, with chronic obstructive pulmonary disease,â€ 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 patientsâ€™ imaginations. But a news article in Science about the PharmacogenomicsÂ papers reported that other scientists had raised serious methodological questions about the CDCâ€™s approach, with one prominent researcher calling the new findings â€œmeaningless.â€ 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 treatmentsâ€”and they note the recent personality disorder and childhood abuse studies as proof of their concerns.
Â The Rejected Empiric Criteria
Other CDC efforts, such as the multi-million-dollar public awareness campaign to brand the name â€œchronic fatigue syndrome,â€ 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, researchersâ€”including many clinicians who actually treated patients and understood how seriously ill they could beâ€”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 â€œrelapseâ€ or â€œcrash,â€ rather than â€œmalaiseâ€). 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 â€œOxford criteriaâ€ 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 researchersâ€”not surprisingly, without any participation from the CDC–published a new â€œinternational consensusâ€ 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 â€œfatigueâ€ in favor of requiring post-exertional malaise, which they renamed â€œpost-exertional neuroimmune exhaustion.â€ Other required symptoms include neurological and energy production impairments.
In contrast, the 2005 effort by the CDC to â€œoperationalizeâ€ the earlier 1994 case definition–by introducing standardized questionnaires and measurement scales to assess levels of fatigue and functional impairmentâ€”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 â€œempiricâ€ 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 peopleâ€”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 millionâ€”had the illness. Dr. Reeves and his co-authors defended the new numbers, attributing the increased prevalence estimates to a broad sampling strategy and â€œapplication of more sensitive and specific measures of the CFS diagnostic parameters.â€
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 othersâ€”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. Jasonâ€™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.
â€œGiven the CDCâ€™s stature and respect in the scientific world, this new definition might be widely used by investigators and clinicians,â€ wrote Dr. Jason and his co-authors. â€œThis 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.â€ 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 â€œothers have started applying case definitions using instruments as tools, recognizing the improved ability to get consistent results.â€ 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. â€œNo single study or approach can be considered sufficient to determine the true population prevalence of an illness as complex as CFS,â€ she wrote. â€œLike 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.â€
Dr. Unger indicated that the agency â€œis in dialogue with other investigators about instruments and methods to best characterize and stratify CFS patients.â€ 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.
â€œWe 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,â€ she wrote. â€œWe anticipate that this data will assist researchers and clinicians in considering further refinements of the case definition.â€ With regards to the name of the illness, she wrote: â€œOpinions 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.â€
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: â€œNo 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.â€
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 wasnâ€™t the point; even though the tests couldnâ€™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 patientsâ€™ 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. â€œThey [the reviewers] provided useful feedback in early October and CDC is incorporating this feedback into our ongoing efforts to improve the CFS website,â€ 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 managementâ€”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 agencyâ€™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 CDCâ€™s immediate orbit, generally believe that the U.K. case definitionâ€”like the CDCâ€™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 doesnâ€™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 patientâ€™s inability or unwillingness to maintain an active lifestyleâ€”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.
â€œItâ€™s a psychological model,â€ said Dr. Jason of DePaul University, of the British view of CFS. â€œItâ€™s an illness that might be caused by some kind of virus or trauma, but whatâ€™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.â€
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 CFSâ€”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. â€œThough these approaches may not work for everyone, the scientific literature shows that they provide some benefit to some patients,â€ 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 â€œas a rule, CDC doesnâ€™t comment on research not conducted by CDC.â€
The View from the Chronic Fatigue Syndrome Advisory Committee
The growing dismay about Dr. Reevesâ€™ leadership and the agencyâ€™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 CDCâ€™s CFS program. Dr. Jason, a member of the CFSAC, and Dr. Reeves, an ex officio member as the CDCâ€™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 CDCâ€™s ex officio member (although he retained his CDC position). Another CDC official at the meeting said he hoped the change would help â€œto leave behind past tensions to make a fresh start.â€
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 â€œshameful scientific leadership, zero accountability, invisible outcomes and millions and millions of dollars stuck in suspended animation, if not wastedâ€¦Only the government contractors seem to be benefiting from millions spent for which there are no worthwhile outcomes for American taxpayers, or CFS patients.â€
The largest chunk of the programâ€™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 â€œin limboâ€–obligated to specific projects but remaining unspentâ€”and work on other projects was proceeding slowly and at great cost, she testified. The financial mismanagement, testified McCleary, â€œhas resulted in program management coming often to this committee and telling other investigators that no funds are available for new projects or collaborations.â€
(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 agencyâ€™s controversial multi-million-dollar CFS public awareness campaign at a time when others were seeking to change the disease name. McClearyâ€™s public rebuke of Dr. Reevesâ€™ leadership, therefore, was viewed as a significant blow to the CFS program and found a welcome audience.)
McClearyâ€™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. Reevesâ€”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: â€œAs somebody who works on a shoe string budget, when I start to look at some of these numbers, I was somewhat appalledâ€¦ 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.â€
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, â€œDr. 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 wellâ€¦despite the evidence, the CDC is still saying that viruses donâ€™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 CDCâ€™s recommended behavioral treatment and exercise.â€
At its meeting in May 2009, the committee unanimously voted to recommend â€œprogressive leadershipâ€ 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 changeâ€”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: â€œIf we validate it, great. My expectation is that we will not.â€
For a scientist to predict his teamâ€™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: â€œCFSAC 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.â€
The committee also formally rejected the CDCâ€™s empiric case definitionâ€”the centerpiece of Dr. Reevesâ€™ epidemiologic approachâ€”and recommended support for â€œa national effort to arrive at a consensus definition of CFS that is accurate, standardized, and reflective of the true disease.â€
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 championedâ€”the empiric criteria, the name of the illness, (most of) the disputed website information, etc.â€”remain in place under Dr. Unger.
Reaction to Dr. Ungerâ€™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 â€œway more responsiveâ€ than Dr. Reeves, noting that she had attended the associationâ€™s annual conference this fall in Ottawa.
â€œWe reached out to her and she has been very accommodating and engaged in conversation to talk about some joint efforts,â€ said Dr. Friedberg, a professor of psychology at Stony Brook University Medical Center. â€œIt remains to be seen what goals sheâ€™s going to set up and what kind of studies sheâ€™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, thereâ€™s an opening.â€
Loree Rudin says
This disease has been neglected for many years, and I don’t know why? I came down with CFS in 1985 and I can function, but not like a normal person. I lost my youth to CFS. It is very sad.
Having read Osler’s Web a fewÂ yearsÂ ago, I want to thank Â Mr. Tuller and Dr.Â
RacanielloÂ forÂ picking up the story where Ms. Johnson left off.Â
I have had CFS since the early 1980’s after vacationing at Incline Village where IÂ contractedÂ pleurisyÂ after rafting on the American River. Â I went to the Incline Village hospital was diagnosed and given antibiotic for the pleurisy and have never felt healthy since.
I’m not all that hopeful thatÂ treatmentsÂ orÂ curesÂ will be found any time soon. Â The CDC will still very slowly drive the engine that defines this condition.
cfs boston says
“A disturbing announcement was made at the July 1992 international AIDS conference held in Amsterdam: Several people with symptoms of AIDS, but who had no evidence of infection with either HIV-1 or HIV-2 (the viruses generally believed, at the time, to cause AIDS), had been identified by the U.S. CDC.
A few weeks laterâ€¦Newsweek made an even more shocking announcement: that CFS researcher Dr. Paul Cheney had in his practice 20 CFS patients who had the same immune system deficiencies as the non-HIV AIDS cases revealed at the Amsterdam conference.”
More on ICL:http://www.autoimmune.com/Non-HIVAIDSGen.html
Where are you located? I’ve been suffering since my pre-teens and am now 47. I have been on full disability since 07.Â I suspect my 20 year old daughter has it too, and my father may have also. My anti-bodies for CMV are through the roof.
I live near Madison WI from June to December and then liveÂ near SAcramento CAÂ from December to May.
Do you have any good recommendations for treatment and doctors you would recommend? At this point I believe I need intravenous viral treatments as I can’t find a venue to pursue this. Also I’ve already spent over 100k so don’t want to go down the same road again with same treatments.
HI: i too have chronic fatigue. i am a nurse practitioner with a past history of 20 years of a well established private practice employing 45 practitioners. I had chronicÂ EpsteinÂ BarrÂ tittersÂ for years, but in 2008 my business partner and best friend of 25 years embezzled funds from the company. I had treated many many clients over the years with fibromyalgia and chronic fatigue syndrome and it was one of my own clients who had noticed my failing health, pain, fatigue and brain fog getting worse over the course of a year who recognized what was wrong with me.Â
I was devastated since all of my clients I had helped with disability claims, and their life was forever changed: so needless to say i did not want to accept this.Â
I have been struggling with this ever since, but i do what alot of people do, i have a good couple of days and think i am all better. Then i crash. Its hard when you have always been a type A personality and then have to learn to think about conducting your life in a whole new way.Â
thank you for taking the time to help focus on this research.
PS; i have been trying to watch your documentary but MUBI keeps blocking it out.. just thought you should know. Deb
If people believe that HIV causes AIDS, and that CFIDS could be caused by a retrovirus, why not consider that CFIDS could be caused by an undiagnosed strain of HIV.Â Let’s just take the $3.1Billion (of our tax money) that currently fuels the AIDS establishment (per annum) and research CFIDS/AIDS collectively.
7 Step Plan to resolving our Worldâ€™s catastrophic public health disaster:
1. Demand research funding parity for CFIDS with AIDS.2. Suggest that CFIDS & AIDS be researched together by scientists rather than as separate entities.3. Urge the CDC to move their AIDS division under the CFS/ME umbrella so they research all the infections that AIDS and CFIDS have in common.4. Urge that AIDS organizations (like AmfAR) include CFS under their umbrellas so that CFS advocates donâ€™t have to reinvent the wheel.5. Demand that the White House, 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, CFIDS/ME is just as serious a public health problem as AIDS.6. Request that an annual international joint CFIDS/AIDS conference be held by the World Health Organization.7. Suggest that next December 1st be declared the first â€œWorld CFIDS/AIDS Day.â€www.cfsstraighttalk.blogspot.com
All the patient testimony from theÂ June 13-14, 2012Â CFS Advisory Committee Meeting in Washington, DCÂ was published here:Â http://forums.phoenixrising.me/index.php?threads/cfsac-june-2012-patient-similar-testimony-oral-written.17920/
This article is just brilliant in every aspect. Dr Tuller and everyone else associated with this web page gets a BIG thank you and many hugs from me and the CFS community. It has been exactly 4 years today since I started experiencing the debilitating symptoms of CFS.
You are a true humanitarian Dr Tuller! It’s so hard to imagine a non-CFS sufferer advocating so much for the disease! At least these is someone out there, who doesn’t think that it’s a phantom disease!
Can you talk at all about the relationship between glutamateric excess and nitrosative dysfunction in the brain?Â
Also, I have been hypothesizing for some time that the ciguatera epitope (discovered in ME/CFS) plays some role in either causing or maintaining nitrosative micro-circulatory dysfunction in the muscles of ME/CFS and FM patients (the lack of iNOS where micro-capillaries junction to the muscle cell) and have found evidence that ciguatera toxin can cause nitrosative dysfunction.Â So I am wondering if it’s possible thatÂ the combination of diastolic dysfunction and nitrosative micro-circulatory dysfunction end up causing such metabolic over-reliance on glycolytic/anaerobic energy sources (when blood flow to the muscles declines with activity) that we in essence “bonk” when we experience the “raggedy ann/andy fatigue” with drop out in blood pressure; which then allows transient ischemia in the spinal cord/brain and which causes excitotoxic brain damage with glutamatergic excess and further nitrosative dysfunction.Â In other words, do we have “bottom up” nitrosative dysfunction feedback looping with “top down” nitrosative dysfunction?Â Thoughts?Â Thanks.
Â I call it “Professional Personality Disorder.”Â In other words, the tendency to cling to personal hypotheses and beliefs regarding a scientific ideas despite copious and massive amounts of evidence that one is incorrect.Â
Additionally, the fact that health insurance and disability insurance companies benefit greatly from the “conservative” approach to the diagnosis, treatment, and research of this illness cannot be ignored; esp. when one looks at the situation in the UK in which nearly all the main players in the ME/CFS field are psychiatrists who have especially close ties with the disability insurance industry.Â There is a vested interest in keeping ME/CFS controversial since disability insureres are only required to pay out 2 years of benefits for psych illnesses.Â While in many ways the situation can be seen as a “conspiracy of dunces,” (esp. in the US) that isn’t the whole story by a long shot.Â
One cannot help but notice that when Simon Wessely (the British psychiatrist) makes statements about the adoption of the term “Myalgic Encephalomyelitis” being recent and somehow due to patient and advocate pressure, he is trying to revise history since he cannot possibly NOT know that the term originated in 1956 and was formally adopted by the WHO ICD in 1969 (considering he lobbied to become the medical director of the ME/CFS advocacy agency started by Melvin Ramsey, the originator of the name “M.E.”; to which Ramsey said “over my dead body!” BTW.)Â He HAS to be lying through his teeth; there’s no other explanation!
Â Studies have found a correlation between activity and long term prognosis so it would make sense that taking it easy early on would make it more possible to recover.Â Ramsey and Richardson both noted that enforced rest improved outcomes and the discovery that diastolic heart dysfunction plays a major role in the illness for a majority of sufferers would tend to back up the idea that exercise just worsens the situation for most.
Â It’s a typo.Â I don’t think there is a such diagnostic moniker.
Spinal proteins.Â Look it up.
Please.Â It’s Chronic Fatigue SYNDROME, not chronic fatigue.Â If you are going to use the “fatigue” name instead of Myalgic Encephalomyelitis, please use the full name as it confuses it with fatigue from other illnesses.Â Thanks.Â Sorry to hear about your loss of the practice; that’s a blow for many people besides yourself.Â Bummer!Â Wish you good health.
Jill McLaughlin says
There is no such Â recognized diagnostic entity as ME/CFS. There is no WHO recognition or ICD code. It is not opinion; ME case definitions are distinct as stated by CDC and select very different patient cohorts. We (ME patients) cannot play the “CFS is not chronic fatigue games.” Fatigue is NOT an illness, it is a symptom of many illnesses both physical and psychological as well as a normal physiological state and has NO basis as the definition of a serious neurological disease such as ME. ME and CFS are in different Chapters of the US ICD. Fact: they are not the same.Â
The case definition of ME is fine; CFS should not apply.Â It is the conflation of the two and the misdiagnosis of ME as CFS that has caused the problems, abuse and neglect of ME patients. You do not solve problems at the same level which created them. [The Canadian “ME/CFS” Case definition is not strictly an ME definition but was a combination of both. It was published nearly 10 years ago in a Journal that is no longer in existence and is not routinely used or recognized. The majority of the original authors of the Canadian ME/CFS definition have abandoned and eschewed it for a strictly ME basis.]Â
Confederacy of DuncesIt is the US patient groups that make up stories about “ME AKA CFS = ME/CFS” and promote the mythical, unscientific ME/CFS, ban and censor the truth, and use PR and political agendas to flood the media with ME/CFS “stories” and misinformation.Â Â
Currently the CFSAC has grossly overstepped its authority in trying to add or incorporate ME and create the bogus, unscientific ME/CFS construct rather than stick within the taxonomic, diagnostic and scientific boundaries. An advisory committee should not change or make up terminology to change the name of the committee or illness (cheap political power grabs by this committee to usurp another illness to expand its scope should not be tolerated). ME patients should continue to write HHS (and cc Congress); otherwise, the federal officer should be removed or the committee should be abolished if it cannot abide by HHS policy, WHO convention and its own mandate.Â
A more Â thorough and accurate article would be appreciated as these ME/CFS/”CFIDS” groups and advocates do NOT represent ME.Â
Â Like many who became ill, I was an athlete (an elite mountain bike racer in Alaska) and when I attempted to exercise my way out of the illness, I just got worse.Â It’s known that elite endurance athletes in general are more susceptible to the illness and studies have confirmed that the worst prognosis occurs with those who try to exercise the most after becoming ill (and considering the research indicating that we have diastolic dysfunction [i.e., heart failure], micro-circulatory dysfunction with resulting metabolic dysfunction in the muscles, an abnormally extended muscle recovery that is 15-60X that of a normal person [incl. people who are deconditioned], the poor prognosis shouldn’t be surprising.Â
The idea that we just need to “just get up and move” is a lovely hypothesis but doesn’t accord with reality but unfortunately, the “experts” who have developed this idea have created an entire paradigm in which they can logically connect all the dots; but the “dots” are chimeric and unsubstantiated.Â
For instance, they assume that we are motivated by secondary gain but that assumption is never tested or proven in ANY way.Â Â There is NO secondary gain, only primary and secondary loss.Â It’s hard to understand how we can gain anything from the “sick role” when the propaganda has been so effective at painting us as malingerers that family, friends, and medical professionals withhold assistance and support on a regular basis.Â Talk about a catch 22!
The “psych-neurotic” paradigm is a house of cards built on poor reasoning, no evidence, and a flat refusal for it’s adherents to actually critically review and self reflexively challenge their own ideas and there is abundant evidence that almost every aspect of their program fails to meet any standards of scientific rigor.Â Imagine if you had to teach a course in ethical practices in science and you needed examples by which to teach.Â Normally, one would have to find examples of each different kind of unethical practice from multiple different fields and different specific scientific endeavors.Â But in this case, you could find practically every single unethical practice evidenced in this one situation and with one small group of people involved with the research of this disease.Â Publication bias, lack of specificity in diagnostic parameters, un-empirical and un-validated scientific measurements, reporting of others’ research as supporting their views when the research actually supports the opposite view, serious financial conflicts of interest (most of the researchers involved have close ties to the insurance industry,) undue control of research funding mechanisms (which they use to great effect to limit research supporting the biomedical hypotheses,) unsubstantiated claims of persecution (i.e., death threats) by patients and advocacy agencies, and a whole host other egregious activities that would barr any researcher from their fields in a heart beat.Â
It’s really one of the greatest scientific scandals in the history of medicine.
Non HIV AIDS Now Confirmed in Asia: Is All AIDS Non HIV Caused?
or simply google “NON HIV AIDS”
Patricia Fero says
Holly. Please look at the WI ME CFS WEBSITE to find our info and my phone number. Pat Fero. we do not publish MD names. In Madison we have 1 10+ MD, PhD and a researcher who is working on PENE.
OR you can e mail me on FB
This Dr. should be tested for lyme disease by a Western blot. She has all the symptoms of CFS/Lyme Disease. If she only knew that the lyme disease tests are faulty and the CDC covers that up too. Like it quotes her in the article “something is making her sick,very sick from something” That something could very well be lyme disease or some other tick or mosquito borne disease. I have lyme disease and was fortunate to get a positive test even though that doesn’t happen in many cases. I had the same exact symptoms….severe eye pain as if someone was pulling my eyes out and severe pain at the back of my head. Hmm what a coincidence. But don’t look to the CDC to get accurate information about Lyme Disease either. They are too busy pretending it is nothing to be concerned about.