Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale 23 November 2011 by David Tuller Note: This account dr aws from int erviews, a close read ing of a fr action of t he 4608 epidemiologic studies that pop up (as of today; yesterday it was 4606) on a PubMed search for “chronic fatigue s yndrome,” and a review of many pages of government documents –in particular the minut es and test imony from meetings of the Chronic Fatigue S yndrome Advisory Committee t o the U.S. Department o f Health and Human Serv ices, one of many such panels est ablished t o provide guidance t o federal h ealth offic ials. Not much here will be a surprise to anyone who has read the better ME/CFS blogs, or Hillary Johnson’s auth oritative and prodigiously researched 1996 account, Osler’s Web: Inside the Labyrinth of the Chronic Fatigue Syndrome Epidemic. Some readers might know that I have written a number ofarticles on chronic fatigue syndrome as a freelance contributor to The New York Times, so Iwant to be clear: The Times has nothing to do with this piece. I want to thank ProfessorRacaniell o for letti ng me inva de his spac e to post this very long story. David Tuller is coordinator of a new concurrent masters degree in public health and journalismat UC Berkeley. He was a guest onTWiV 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 n erve 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
Note: This account draws from interviews, a close reading of a fraction of the 4608
epidemiologic 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: I nside the Labyrinth of the ChronicFatigue Syndrome Epidemic. Some readers might know that I have written a number of
articles on chronic fatigue syndrome as a freelance contributor to The New York Times, so I
want to be clear: The Times has nothing to do with this piece. 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 nearPhiladelphia, suffered through successive bouts of sickness — mononucleosis associated withEpstein-Barr virus, a stomach parasite, repeated episodes of bronchitis. One day, whilereviewing student exams in her office, she slumped over and blacked out. Not long after, shereceived a diagnosis of chronic fatigue syndrome.
In written testimony to a federal advisory committee a few years ago, Dr. Schweitzerdescribed how disabled she eventually became: ―On a bad day, I would never get up at all, orwould lie in bed curled up under the covers…I experienced pain behind my eyes and in theback 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 pl iers.‖
Over the years, Dr. Schweitzer has tested positive for multiple viruses. She experiences severelapses in memory, concentration and other cognitive skills. She suffers from ―neurallymediated hypotension,‖ a form of low blood pressure arising from nerve dysfunction, whichcauses nausea, loss of balance, and fainting. Her muscle and joint pain can be intense, and shefrequently requires a wheelchair. Her white blood cell counts have been way off; her immunesystem is often out of whack. She left her position at Villanova because of disability and hasbeen unable to work most of the years since.
Like others with chronic fatigue syndrome, Dr. Schweitzer is used to having her illnessignored, mocked or treated as a manifestation of trauma, depression or hypochondria — notonly 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 lastyear 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‘sperspective –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 researchcommunity involved with the illness, those two studies symbolize much of what has gonewrong with the agency‘s research program on chronic fatigue syndrome. As the country‘sleading public health organization, the CDC has enjoyed remarkable success in the fightagainst 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 somebehavior that we can change and miraculously be well. None of us want to be sick or aredoing 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 tothe public, policy-makers, health care providers and other audiences. Given those variedresponsibilities, the CDC‘s pronouncements about any topic— in this case, chronic fatiguesyndrome – exert an enormous impact on policy, clinical care, insurance reimbursement andpublic attitudes. Advocates say that when the agency reports that people with CFS suffer fromparanoid 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 theLake Tahoe area in the mid-1980s, the agency‘s CFS program has been marked by financialscandal, an epidemiologic strategy rejected as fatally flawed by the top researchers in thefield, and the kind of toxic relationship with much of the patient community that canundermine the trust and cooperation needed for effective policy-making and public healthstrategies. On a more substantive level, over the past quarter-century, the CDC‘s researchprogram has yielded little or no actionable information about causes, biomarkers, diagnostictests, 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 thewrong places. Starting with its 1988 report on the illness, they say, the agency hasdownplayed 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 thefrequent presence of multiple viral infections. Instead, say the critics, the agency has focusedmajor resources on investigating proposed psychiatric and trauma-related factors andassociations – the personality disorder and trauma studies were published, respectively, in the
journals Psychotherapy and Psychosomatics and Archives of General Psychiatry – even thoughstress 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 claimsfor tests ordered by doctors. (After years of complaints from patients and doctors, a paragraphthat dismissed the usefulness of many tests, including those for various infectious agents, wasfinally 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 abehavioral form of treatment —a gradual increase in exercise, known as ―graded exercisethera py‖– that is widely discredited in the CFS community. Patient surveys and anecdotaltestimony, as well as an increasingly robust body of research, suggest that the therapy mightcause 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 andhas never recovered his health. ―They pay lip service to it being a serious physical illness, butin 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. WilliamReeves, an epidemiologist and architect of the CFS research program from 1989 until hisabrupt move last year to another division of the agency. With his gruff and sometimesdismissive manner, Dr. Reeves was never popular with the patient community, which came toview 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 agencyhad been diverting funds designated for CFS to other programs and then lying to Congressabout it, Dr. Reeves — who was in charge of the program while the financial irregularitieswere 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 aggressivelypromoted in a public awareness campaign the agency launched in the mid-2000s. Patients saythe 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-dayversion 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 illnessthat 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 forchampioning 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 LauraHillenbrand (Seabiscuit , Unbroken), who has lived with CFS for decades, called the name of the illness ―condescending‖ and ―so grossly misleading.‖ She added: ―The average personwho has this disease, before they got it, we were not lazy people; it‘s very typical that peoplewere Type A and hard, hard workers… Fatigue is what we experience, but it is what a matchis 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 — aremarkable ten-fold increase over the previous CDC estimate in 2003. Other expertsdismissed this dramatic rise as an artifact of the agency‘s poor epidemiology. Subsequentresearch reported that the new CDC approach misclassified people with primary depression as
having chronic fatigue syndrome, when they did not; that kind of misclassification couldeasily 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 anincreasingly public revolt against Dr. Reeves‘ leadership. In January of 2010, the CDCabruptly appointed him as senior advisor for mental health surveillance in another part of theagency. 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 syndromeprogram.
Now, almost two years after Dr. Reeves‘ departure, advocates and researchers say they haveseen a shift in tone — some believe it is genuine, others not – but so far little change insubstance. (Requests to interview both Dr. Reeves and Dr. Unger, conveyed through the CDCmedia office, were declined; however, with a press officer acting as intermediary, Dr. Ungerresponded to questions via e-mail.)
―I‘m committed to continuing an aggressive program to address the needs of CFS patients andfamilies 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 formedical and health care professionals, and has contracted for studies that will help clarifyquestions about how to identify the illness.
Dr. Unger has made a point of meeting with patient, advocacy and scientific organizations. Incontrast to her predecessor, she has impressed some advocates and researchers with herwillingness to listen to their concerns and seek out joint initiatives. But reflecting awidespread view, one activist (who preferred to remain anonymous) said that ―overall, I donot 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 similarassessment, 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 oldestorganization on the illness, said she believes Dr. Unger ―is trying to restore some credibility tothe 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
Although Dr. Reeves‘ departure received little public notice, it was a watershed event forpatients and advocates, many of whom blame the agency for the prolonged lack of significantprogress in CFS research. (They also blame years of inadequate funding from the NationalInstitutes of Health, but that‘s another long story; it is worth noting, however, that the NIHonline 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 withsimilar levels of morbidity. While the roles of the CDC and NIH can overlap significantly, theNIH generally focuses more on basic research into disease processes than on epidemiologyand 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 toXMRV, a poorly understood mouse leukemia retrovirus. The finding thrilled the patientcommunity because it appeared to offer a plausible explanation for the disease and to suggesttreatment 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 mostresearchers 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 XMRVissue, although not the issue of whether another retrovirus might eventually be linked to casesof CFS.
(In the meantime, in a bizarre and unsettling turn of events, the senior author of the originalXMRV 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 inReno. The institute sponsored the XMRV research but has accused Dr. Mikovits, its erstwhilestar 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 earlierthis 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 asa ―fugitive from justice‖ and spent the weekend in jail; she was released on bail after ahearing on Tuesday.)
Nevertheless, the heightened focus on CFS during the past couple of years has brought theillness greater attention from a larger group of scientists, including many infectious diseaseexperts 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 likelythe 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, theywould 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 firingalmost constantly.‖
According to this view, the revved up immune system is actually much less effective atcontrolling other infections, and studies have found associations between CFS and a grab-bagof 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 peoplewith 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; astudy last year in the journal PLoS One found that people with CFS and a form of Lymedisease have patterns of proteins in their cerebrospinal fluid that clearly distinguish them fromeach other as well as from healthy controls.
In many cases, additional research has failed to confirm associations from prior studies. Yetthere is a reasonable epidemiologic explanation for such divergent results: Most expertsbelieve 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 suchdistinctions —and most haven‘t– are much less likely to reach consistent results aboutcausation or treatment. Moreover, different research groups have used different methods of
identifying people with chronic fatigue syndrome, making it even harder to compare findingsacross 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 biologicalcause,‖ wrote Leonard Jason, a professor of community psychology at DePaul University inChicago 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, toreplicate findings from one lab to another. And when consistent biological findings do notemerge, 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 theCDC or NIH but at academic medical centers; much of the new work is being funded byprivate donors who have family members with CFS. Researchers from Stanford, Harvard,University of Miami, Columbia, and other leading institutions are all engaged in innovativeefforts focused on pathogenesis, diagnosis and treatment, and in particular on such issues asinfectious triggers, biological markers, and medical therapies.
Dr. Derek Enlander, a longtime CFS clinician in New York, recently helped to launch anME/CFS research and treatment center at Mt. Sinai Hospital; his highly regarded team hopesto 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 fundingallows the group the freedom to pursue promising avenues of investigation. ―I believe that anindependent organization such as ours, which is not funded by the government or answerableto 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. Thesymptoms 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 Lymedisease, Gulf War syndrome, fibromyalgia, and multiple chemical sensitivity.
These conditions are characterized by shifting patterns of symptoms, a lack of agreed-uponbiological markers and diagnostic tests, arguments over the interpretation of evidence, and
competing claims of scientific authority. Patients presenting with these illnesses can bedevildoctors, who want to help but have few proven tools at their disposal. They might or mightnot be willing to try unorthodox strategies; some doctors clearly take advantage of patientswho are desperate for relief. Such contested illnesses impact millions of people and theirfamilies, cost the U.S. billions in lost productivity, and consume a significant chunk of healthcare resources — and yet remain poorly understood. With so much at stake, they often emergeas societal and legal battlegrounds, with patients, clinicians, researchers, insurers, healthofficials and government bureaucrats all seeking to influence and control dialogue, debate andpolicy.
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 whohave a condition and screens out all those who don‘t. Creating a case definition is easiestwhen a definitive laboratory test exists, as with HIV or hepatitis C. With an illness like CFSthat is identified through symptoms, devising a completely accurate case definition is almostimpossible; some people with the illness will always fall outside the parameters of the casedefinition, and some who have some other condition, or nothing at all, will bemisdiagnosed — or will self-diagnose – as having CFS. Yet without a case definition that is asaccurate 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, SanFrancisco, and an early AIDS investigator, told me for an article I wrote about case definitionsearlier 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 difficultto figure out what‘s going on.‖
Non-CDC researchers say the problem with the agency‘s 2005 method for identifying CFScases is that it mistakenly classifies people with primary depression as having chronic fatiguesyndrome instead. Depression and CFS can resemble, overlap and interact with each other inmultiple ways; patients with CFS may get very depressed about their situation, and depressionoften causes fatigue, as can many other ailments. So distinguishing chronic fatigue syndrome
from primary depression — in other words, depression that preceded and perhaps caused thefatigue — is important but tricky, and requires nuanced instruments. In epidemiologic studiesthat conflate the two, treatments that are known to be effective for depression could appear tobe 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 exercisethat has been promoted for CFS patients by the British psychiatric, medical, and insuranceestablishments; it is also highlighted as a treatment option on the CDC‘s website andeducational 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 acomplete misnomer; post-exertional malaise is much closer to a serious crash or relapse than aVictorian fainting spell.) An emerging field of research — much of it taking place at theUniversity of Utah and University of the Pacific in Stockton, California – indicates that peoplewith 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 manycases to a prolonged resurgence of their symptoms rather than the improvement predicted byproponents of graded exercise therapy.
Patients with CFS are very familiar with post-exertional malaise. Many report havingrecovered for a period of time, then pushing themselves too hard and suffering a devastatingset-back, repeating the cycle multiple times before learning to adjust their pace. When MarySchweitzer experiences post-exertional malaise, she said, she loses her formidablecommunications 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, butit‘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 toharness their energy by recognizing their limits, and not pushing beyond them. That approachis essentially the antithesis of graded exercise therapy.
―You learn what will bring on a crash– sitting upright at a restaurant, for example – and you justdon‘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 herdoctoral research at Johns Hopkins, Custom and Contract: Household, Government, and the
Economy in Colonial Pennsylvania, has undoubtedly never reached Seabiscuit -y heights inAmazon‘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 inan economics course she as an undergraduate at Duke); and was teaching, conductingresearch, 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 anddevotion 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 thatappears 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 ongoingclinical trial. She travels twice a week from her home in Delaware to her doctor‘s office inManhattan for infusions of Ampligen; unlike in most clinical trials, she has to pay for thedrug, which costs her $16,000 a year.
When off Ampligen, she has suffered major crashes; at one point several years ago, she testedpositive for four herpesviruses — Epstein-Barr, cytomegalovirus, HHV-6A, and HHV-7 — andCoxsackie B, an enterovirus. Whenever she can, she addresses public forums, in particular thetwice-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 advisorycommittee, 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 crashedone glass against another…It made no difference that now I knew the names of the varioussymptoms – ataxia, expressive aphasia, short-term memory loss, central auditory processingdysfunction, etc. My brain had disappeared.‖
A Bit of History
The conflict over the nature and definition of CFS – between the CDC and the patientcommunity, as well as between the agency and other researchers – dates back to the initialinvestigations of an outbreak in Incline Village, Nevada, near Lake Tahoe, of a mysteriousillness, 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 ―chronicmononucleosis.‖ (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-Barrhypothesis and rechristened the phenomenon ―chronic fatigue syndrome‖ to discourageunproven assumptions about viral origins. (Ironically, because CFS began as a suspected viralillness, 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, pluseither six of eleven ―symptom criteria‖ (mild fever, sore throat, painful lymph nodes, muscleweakness, muscle pain, prolonged fatigue post-exercise, headaches, joint pain,neuropsychological complaints, sleep disturbances, and sudden onset of the illness) and twoof 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 symptomcriteria, without the physical criteria.
In retrospect, for many patients the CDC‘s first big blunder was in not calling the Tahoeillness myalgic encephalomyelitis in the first place. Benign myalgic encephalomyelitis haslong been recognized by the World Health Organization as a synonym for ―postviral fatiguesyndrome,‖ 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 sincedropped 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 receivedhis B.A. in 1965 from the University of California, Berkeley, where his father was arenowned 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 amasters in epidemiology at the University of Washington, and worked at a major medicalresearch 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, hadabnormal 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, theywrote, was likely a ―chronic, immunologically mediated inflammatory process of the centralnervous 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 inunusually blunt terms. ―We conclude that the disease…described is not the chronic fatiguesyndrome or any other clinical entity and that they showed no association with active HHV-6replication,‖ 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 aretroviral link to chronic fatigue syndrome. These and other contradictory results gave rise onboth sides to claims and counter-claims and counter-counter-claims (etc.) of methodologicalflaws, 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 publisheda 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, alongwith at least four of eight other symptoms: impaired memory or concentration, disordered orunrestful sleep, muscle pain, joint pain, headache, tender lymph nodes, sore throat, and post-exertional malaise. Although the definition relied on self-reported symptoms rather thanbiological tests or standardized instruments to measure levels of fatigue and disability, it soonbecame 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 strongreviews. The book documented how the CDC routinely diverted money slated for CFSresearch to other projects because of lack of concern about the illness. (The CDC did notofficially comment on the book at the time, according to a CDC spokeswoman.) Two yearslater, Dr. Reeves leveled similar charges against his superiors, noting that the CDC lied toCongress 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 forlaboratory equipment and supplies for measles and polio and charged it to the CFS account. In1995, 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 goingpublic.
―I believe that CDC has intentionally misrepresented monies allocated to CFS research and Icannot ethically support this,‖ wrote Dr. Reeves in his public statement. ―Themisrepresentations involve systematically charging between $400,000 and $2 million incurredby 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 CFSresearch.‖
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 theillness. 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, CDCofficials 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 todetermine whether they were used to support CFS research or not. Even as the CDCshortchanged the CFS program, the report noted, it disregarded Congressional requests tosupport important research initiatives. As an example, the report noted that Congress hadurged the CDC to expand its surveillance of CFS among adolescents and to hire aneuroendocrinologist ―to enable expansion of its research efforts and pursue promisingfindings from other Federal agencies and the private sector.‖
At the time of the inspector general‘s report, however, the CDC had halted an ongoingadolescent study and had not hired an endocrinologist —even as allocated money wasn‘t beingspent. 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 beenheld in reserve by the Division Director during the year, and were not released until after thedeadline for obligations had passed. Thus, while important enhancements were not beingimplemented, more than $850,000 of FY 1998 budgeted funds were never made available tothe program.‖
In the wake of the scandal, Dr. Reeves‘ boss left his position; the agen cy agreed to reform itsaccounting practices and restore more than $12 million to the CFS program over the nextseveral years. Although Dr. Reeves‘ whistleblower status effectively solidified his position atthe CDC, his statement didn‘t answer all outstanding questions. Given the revelations fromOsler’s Web in 1996, it seemed unlikely to many patients and advocates that key officials atthe agency could have been unaware of accounting irregularities – especially since theyapparently continued through 1998, according to the federal investigators.
A subsequent investigation in 2000 from the U.S. General Accounting Office (now called theGovernment Accountability Office) found that communication between the CDC and the NIHabout CFS research programs and priorities was poor. The limited coordination, as well as theCDC misspending, had hampered progress in the search for answers to the illness, theinvestigators 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 chronicfatigue 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 235per 100,000 percent of the adult population, or about 400,000 overall in the U.S. That figurewas below the generally accepted estimate of one million sufferers, derived from acommunity- based study in the Chicago area by Dr. Jason‘s research group at DePaulUniversity. 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; thatresearch had been criticized for relying on doctors‘ reports of patients with CFS, a far lesseffective 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 CFSlost an average $20,000 annually in earnings.
Also praised was the CDC‘s partnership with Australian researchers on a study reporting thatmore 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 CDCpublished — with great fanfare – a set of 14 studies in the journal Pharmacogenetics, whichfound significant variations in CFS patients of gene expression and activity related to how thebody handles and adapts to physical and emotional challenges and stress.
Much of the research focused on genes associated with the hypothalamic-pituitary-adrenalaxis, which regulates the body‘s stress responses, among other functions. At a pressconference introducing the studies, Dr. Reeves outlined his understanding of the illness: ―Theworking hypothesis is that the HPA axis and the brain is a plastic organ which changes itsactual physical architecture depending on stresses accumulated over the lifetime,‖ heexplained. ―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 howyou are going to react to them, they determine how your allostatic load [a stress-relatedindicator] may accumulate, and more importantly, they actually determine your subsequentreaction 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 andexpressed empathy for patients. ―People with CFS are as sick and as functionally impaired assomeone with AIDS, with breast cancer, with chronic obstructive pulmonary disease,‖ he toldme 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 Pharmacogenetics papers reported that other scientists had raised seriousmethodological questions about the CDC‘s approach, with one prominent researcher callingthe new findings ―meaningless.‖ Others in the CFS community feared that the focus on stressand 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 andtreatments — and they note the recent personality disorder and childhood abuse studies asproof of their concerns.
The Rejected Empiric Criteria
Other CDC efforts, such as the multi-million-dollar public awareness campaign to brand thename ―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 highlycontroversial move, Dr. Reeves spearheaded in 2005 the creation of the new, purportedlymore precise method of identifying patients; critics feared the approach would wreak havocwith epidemiologic studies by mixing a lot of people with depression but not CFS intosamples of people all presumed to have chronic fatigue syndrome.
During the 2000s, researchers — including many clinicians who actually treated patients andunderstood 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, thedefinition 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 mostpatients, and one that clearly helped distinguish CFS from primary depression, as well asother chronic illnesses. The CDC definition also allowed for but did not require the presenceof 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 compareresults. The ―Oxford criteria‖ developed in Great Britain required only the presence of sixmonths of disabling fatigue; that single-symptom criterion was criticized as so broad that itwas likely to identify many people with primary depression rather than CFS. A more detailed2003 case definition developed in Canada focused on post-exertional malaise as a cardinalsymptom 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 andautonomic nervous systems.
Earlier this year, a team of top researchers — not surprisingly, without any participation fromthe CDC –published a new ―international consensus‖ case definition, which adopted the namemyalgic encephalomyelitis and abandoned chronic fatigue syndrome altogether. Using theCanadian definition as a jumping-off point, the new international definition also dropped theconstruct of ―fatigue‖ in favor of requiring post-exertional malaise, which they renamed―post-exertional neuroimmune exhaustion.‖ Other required symptoms include neurologicaland energy production impairments.
In contrast, the 2005 effort by the CDC to ―operationalize‖ the earlier 1994 case definition – byintroducing standardized questionnaires and measurement scales to assess levels of fatigueand functional impairment — has found no support outside the CDC itself. In suggestingspecific instruments and scales, Dr. Reeves and his research team proposed cut-off points torepresent sufficient grounds for identifying CFS.
Yet when the CDC researchers applied these new ―empiric‖ criteria, as they called them, to apopulation 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 theCDC estimate from its Wichita research just four years earlier, and four times the widelyaccepted figure of about one million — had the illness. Dr. Reeves and his co-authors defendedthe new numbers, attributing the increased prevalence estimates to a broad sampling strategyand ―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 theempiric criteria, like the Oxford criteria but unlike the 2003 Canadian case definition, blurredand expanded rather than clarified the disease boundaries. While some advocates believed theincreased estimates would focus more attention on the illness and should therefore beembraced, many others — including leading epidemiologists – believed that the expandedcategory could make it harder to isolate physiological correlates; that failure, in turn, wouldmake 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 byadvocates, 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 thenew 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 bewidely used by investigators and clinicians,‖ wrote Dr. Jason and his co-authors. ―This mightresult in the erroneous inclusion of people with primary psychiatric conditions in CFSsamples, with detrimental consequences for the interpretation of epidemiologic, etiologic, andtreatment efficacy findings for people with CFS.‖ The authors also noted pointedly that thepopulation prevalence for CFS calculated using the empiric definition was close to that formajor depressive disorders.
Although the empiric case definition was published six years ago, it has not found any favoroutside the CDC, raising questions about the comparability of CDC data derived from its useto 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 startedapplying case definitions using instruments as tools, recognizing the improved ability to getconsistent 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 empiriccriteria, 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 prevalenceestimates of CFS based on the Georgia surveillance study are subject to the limitations of thestudy design. However, the Georgia study, along with those from other investigators, doesdemonstrate 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 instrumentsand methods to best characterize and stratify CFS patients.‖ The agency is also launchingstudies with several investigators to enroll and characterize patients from seven clinicalpractices headed by leading CFS physicians to help clarify issues involving the case definitionas 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 proposedInternational ME definition,‖ she wrote. ―We anticipate that this data will assist researchersand clinicians in considering further refinements of the case definition.‖ With regar ds to thename of the illness, she wrote: ―Opinions of advocates, clinicians and researchers remaindivided about whether CFS and ME are the same or different entities. However, we arefollowing 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 toidentify 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), orcell marker tests (e.g., CD25 or CD16), have ever been shown to have value for diagnosingCFS. Other tests that must be regarded as experimental for making the diagnosis of CFSinclude the tilt table test for NMH, and imaging techniques such as MRI, PET-scan, orSPECT-scan.‖
Advocates and patients appealed to the CDC many times over the years to remove thelanguage. They acknowledged that these and other tests were not diagnostic for CFS butinsisted that wasn‘t the point; even though the tests couldn‘t be used to confirm that a patienthad CFS, they were important weapons for disease management. Experienced clinicians, likeDr. 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 treatmentstrategies, given their patients‘ histories of immune dysregulation and viral infections. Yetclinicians report that they have received letters from insurance companies citing thatparagraph in rejecting claims for tests they have ordered, in some cases as recently as lastsummer.
The agency finally removed that language this month, after an advisory group reviewed thewebsite and requested a host of changes. ―They [the reviewers] provided useful feedback inearly October and CDC is incorporating this feedback into our ongoing efforts to improve theCFS website,‖ wrote Dr. Unger. Replacing the old language is a new passage that suggeststhat some of the same tests once disallowed for diagnosis of CFS can be useful for diseasemanagement — 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 claimshad 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 therapyand cognitive behavior therapy. In the U.K, mental health professionals have dominatedresearch 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 casedefinition 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 outsidethe CDC‘s immediate orbit, generally believe that the U.K. case definition—like the CDC‘sempiric 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 probablydoesn‘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 prolongedfatigue 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 maintainingit is that you have some sort of phobic avoidance of activity. The idea is your bone andmuscle mass decrease, you become weak. So if you can get a person to slowly increase theamount of activity that they do, they will break this phobic avoidance.‖
In the U.K. framework, graded exercise therapy is often paired with cognitive behaviortherapy in the treatment protocol for CFS. Cognitive behavior therapy is a treatment modalitywith widespread application, and is likely to be useful to many people undergoing majorstresses – whether from cancer, a back injury, an existential crisis, fear of sex, migraines, a baddivorce, or cognitive fatigue syndrome. However, the kind of cognitive behavior therapyprescribed in Great Britain to treat people with CFS — as Dr. Jason and other researchers haverepeatedly noted – is largely geared toward convincing patients to overcome their avoidancephobia and increase activity levels; in other words, to encourage them to participate insomething very much like graded exercise therapy.
But for people who experience post-exertional relapses of their symptoms, graded exercisetherapy 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 unhappinessand increased morbidity among those who have been through a course of graded exercisetherapy. And, say critics, cognitive behavior therapy could also be harmful, if the goal is toconvince 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 includinginformation on graded exercise therapy and cognitive behavior therapy on the website, andthat the agency was reviewing those sections. The goal of the information, she wrote, was tolet 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 literaturefrom the U.K. that actually reported the modest benefits from these therapies, noting that ―as arule, 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 late2000s of the Chronic Fatigue Syndrome Advisory Committee of the Department of Healthand Human Services. The mandate of the committee, with a rotating membership of clinicians, researchers, patients and advocates, is to offer guidance and recommendations tothe department. In 2007, the committee requested financial records from the CDC‘s CFSprogram. Dr. Jason, a member of the CFSAC, and Dr. Reeves, an ex officio member as theCDC‘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 asthe CDC‘s ex officio member (although he retained his CDC position). Another CDC officialat the meeting said he hoped the change would help ―to leave behind past tensions to make a
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 thecommittee had sought, suffered from ―shameful scientific leadership, zero accountability,invisible outcomes and millions and millions of dollars stuck in suspended animation, if notwasted…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 privateresearch organization, Abt Associates in Cambridge, Massachusetts, in sole-source or no-bidcontracts 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 butremaining unspent — and work on other projects was proceeding slowly and at great cost, shetestified. The financial mismanagement, testified McCleary, ―has resulted in programmanagement coming often to this committee and telling other investigators that no funds areavailable for new projects or collaborations.‖
(The CFIDS Association of America had been criticized by some other advocates over theyears for its previous close association with Dr. Reeves. The organization had providedessential public support for Dr. Reeves during the accounting scandal in the late 1990s; in themid-to-late 2000s it implemented the agency‘s controversial multi-million-dollar CFS publicawareness 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 significantblow to the CFS program and found a welcome audience.)
McCleary‘s report further shredded support for Dr. Reeves among committee members; somewere researchers struggling with their own funding issues. The financial accounting appearedto confirm a frequently heard complaint about the CDC and Dr. Reeves — that they were nottaking full advantage of opportunities to collaborate with outside scientists at academicresearch 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 ona shoe string budget, when I start to look at some of these numbers, I was somewhatappalled… It just does not seem to be the best use of the funds. The thing that we asked for ata couple of previous meetings was for the CDC to consider more collaboration with outsideentities. We meant people who work a lot cheaper. It would seem that there are people outthere 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 ona study comparing people with CFS and Gulf War illness, and that the agency had failed tofinish its testing on samples, citing funding problems. She also unleashed another commoncharge: that the CDC was simply not interested in the role of pathogens. According to theminutes, ―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 pursuingidentification of pathogens and that CDC should be embarrassed not to be looking for them aswell…despite the evidence, the CDC is still saying that viruses don‘t matter in the illnesseven 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 ―progressiveleadership‖ for the CFS program; although the recommendation, in an apparent nod todecorum, did not cite Dr. Reeves by name, the intent was clear. The request for a toppersonnel change — essentially a vote of no-confidence in the current leadership – wasconsidered an aggressive move for this kind of federal advisory committee. At the same
meeting, the International Association for CFS/ME, a leading scientific and researchorganization, endorsed the call for new leadership.
In October of 2009, Dr. Reeves committed what many in the CFS world regarded as a majorpublic gaffe: an off-hand remark to a New York Times reporter (not this one) about the mouseretrovirus research that had just sparked a wave of excitement. In the interview, whichoccurred shortly after the publication of the Science paper reporting the link between XMRVand CFS, Dr. Reeves said his research team would look for the retrovirus but that they wereunlikely to find anything. He told the Times: ―If we validate it, great. My expectation is thatwe will not.‖
For a scientist to predict his team‘s outcomes in a contested field of research during a highlypublic 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 hisouster from almost every corner.
At the CFSAC meeting later that month, the committee again approved a recommendation fornew leadership and emphasized the urgency of the issue. According to the minutes: ―CFSACconsiders that recommendation important and would like to get some feedback, includingwhether or not the recommendation is being considered. This has become more importantbecause of certain quotes that have been made in The New York Times concerning theretrovirus 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 toarrive at a consensus definition of CFS that is accurate, standardized, and reflective of the truedisease.‖
Within months, Dr. Reeves was gone from his position, although no public explanation for themove was offered. For the most part, the elements of the CFS program that Dr. Reeveschampioned — 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 theresearch community express optimism about being able to develop, with Dr. Unger, the kindof 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. Ungerwas ―way more responsive‖ than Dr. Reeves, noting that she had attended the association‘sannual conference this fall in Ottawa.
―We reached out to her and she has been very accommodating and engaged in conversation totalk 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.‖
Tagged as: CDC, centers for disease control, CFS, chronic fatigue syndrome, david tuller, elizabeth unger, myalgic encephalitis, william reeves
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Anne Boyd 2 hours ago
Many, many thanks to Mr. Tuller for writing this piece and to Dr. Racaniello for publishing it on his widely-readblog.
I think it is EXTREMELY important for those in the science community to know this story, whether or not they have aspecific interest in ME/CFS. There are, unfortunately, many occasions when science fails to live up to its own ideals of disinterested pursuit of the truth. Young scientists, or those without political experience, should be aware of the enormousrole played by public agencies and institutions in determining which scientific problems get studied and which do not. Thisgoes beyond "merely" providing or withholding resources for research. The actions and policy statements of public agenciesplay an enormous role in creating the "reality" in which "everybody knows" something - for instance, that a serious, painful,debilitating disease that can strike anyone without warning "doesn‘t exist, it isn‘t a real disease."
ME/CFS patients often wonder why it is that their disease has been singled out for such special disdain and neglect. Certainlythere is a social/cultural/economic component to this attitude: a disease of "fatigue" is a disease of unproductivity, so thestigma and contempt attached to it is not terribly surprising in our socioeconomic environment. Most people rightly fear theloss of their wage-earning ability, not just because it would destroy their livelihoods (especially because our social safety netfor the disabled is horrendously inadequate), but because such a loss would profoundly damage their sense of self.Scapegoating and blaming those who fall victim to a disease like ME/CFS (and other "contested diseases") can be seen a
defense mechanism against that intolerable threat.
But the majority of individuals (including individual scientists and individual doctors) can only comfort themselves by
brushing off the reality of a disease like ME/CFS when the larger institutional framework in which they operate allows themto do so. In the case of ME/CFS, US public health and scientific agencies have not just tolerated or supported such a view,but encouraged it. In recent years, it *seems* there has been a shift in public rhetoric by these agencies; but as long as thisrhetoric is not supported by significant financial commitments, it will ring rather hollow.
This rhetorical shift is echoed in miniature in the consulting rooms of doctors. It seems to me that doctors are somewhat lesslikely than in the past to dismiss the 'reality' of the disease, at least to patients' faces (although they still do so in inexcusably
large numbers). However, I do not see much increased willingness on the part of doctors (and health insurance providers) toactually *behave* as though the disease is a serious one - for instance, by becoming informed about it, and exercisingwhatever due diligence is currently possible in properly treating it. Where is the accountability? Right back where we started- the standard of care cannot improve until public agencies take their leadership role seriously, and disseminate updateddiagnosis and treatment guidelines that are science-based rather than assumption-based. The CDC's "guidelines" on ME/CFS,to the extent that they have been based on unprovable negatives, can hardly be said to be science-based.
A thousand thanks again to David Tuller for this important article.
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Anna 4 hours ago
Mr Tuller, forgive me for being so blunt: But I think I love you!Thank you, thank you, thank you for this fantastic piece that I'm sure took you many hours to research. You covered everysingle important point and got it all completely right.
I have to say my faith in Dr. Unger is limited, so far I have only seen her defending the useless CDC definition. It would takea complete about-face to make up for decades of neglect and harm.
Thank you, too, Dr. Racaniello, for providing this opportunity to Mr. Tuller, it is very much appreciated.
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Christopher Messina 2 hours ago
Thank you David for increasing awareness about the core issues surrounding this disease.
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anciendaze 4 hours ago
One small correction: the CDC first investigated a non-resolving, flu-like illness in Punta Gorda Florida in 1956.Poskanzer and Henderson published an account in the NEJM in 1957. Henderson and Shelokov published a review of suchoutbreaks later. The diagnostic similarities were so pronounced that Henderson and Shelokov took part in discussions aboutnaming the disease after those outbreaks described above took place. Both objected to the name CFS. Henderson has aremarkably good reputation in public health, due to his work on smallpox. Poskanzer taught neurology at Harvard MedicalSchool. These are not people easily fooled by hysterical women or hypochondriacs.
Hope to read this later. In the meantime, there is a petition against the empiric criteria at:http://www.ipetitions.com/peti... . It has over 2500 signatures. There is some extra information in the blog section.
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Keith 58 minutes ago
I'm a physician who treats people with ME/CFS. A patient referred me to this post. What a delight to find such agreat piece of journalism - and such a great virology resource! I hope Mr. Tuller will continue to track developments inME/CFS with his top-notch journalism skills.
Let's close the curtains on the CDC/Oxford Follies and open them to a coherent and rigorous effort to solve this systemsbiology puzzle.
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HR 1 hour ago
Thank you David Tuller and Dr Vincent Racaniello for this article. Please keep up the good work!!
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kellylatta 1 hour ago
At the November 8th, 2011 HHS CFS Advisory Committee meeting, Dr. Nancy Lee told committee members theyshouldn't expect anything but virological studies from a research group in the Division of High Consequence Pathogens andPathology.
As Dr. Nancy Klimas, who has been researching CFS since the early 90s and who even did a sabbatical with the CDC,replied - that that's just it - they don't do research on pathogens.
