Wednesday, June 30, 2010


On April 15, 2010, a government source told CFS Central that a soon-to-be-published CDC study hadn’t found the retrovirus XMRV in CFS patients but that another government agency had.  The agency that found XMRV in CFS patients—and up to 7 percent of the blood supply—turned out to be two agencies: the National Institutes of Health (NIH) and the FDA, as was leaked last week

Today the Wall Street Journal is reporting that the CDC paper, which was accepted at the journal Retrovirology, has been put on hold, as has the FDA/NIH paper, which was accepted at the Proceedings of the National Academy of Sciences.  The reason?  According to the Wall Street Journal, it’s because “senior public-health officials wanted to see consensus—or at least an explanation of how and why the papers reached different conclusions.”  In addition, the Wall Street Journal also reported that a spokesman for the Department of Health and Human Services said the research was being reviewed to ensure “accuracy” and “relevancy of the scientific information.”

Some insiders say that this is a face-saving move to come up with a plausible explanation for the disparate XMRV findings and to present a united front so as not to confuse the public about blood safety.

The CDC has had a problematic year where CFS is concerned.  The long-time CDC principal investigator for CFS research Dr. William Reeves was reassigned on February 14, which many critics believe was because the scientist was embarrassing the agency.  After Dr. Judy Mikovits's paper linking XMRV to Chronic Fatigue Syndrome was published in Science in October, Reeves told the New York Times:  “We and others are looking at our own specimens and trying to confirm it.  If we validate it, great.  My expectation is that we will not.”  Reeves also told the Times that the culprits behind CFS were more likely sexual and emotional abuse and an inability to handle stress.

Privately, insiders have told CFS Central that they did not expect the CDC to find the retrovirus because the agency’s CFS definition has been watered down from one neuroimmune disease to five different combinations of depression, insomnia, obesity and “metabolic strain,” as Reeves himself explained in a 2009 paper.  In a 2008 CDC paper, “An extended concept of altered self,” Dr. Jim Jones argued that illnesses such as CFS are “illness states” rather than “true diseases.”  A CDC paper from 2006 on coping styles found CFS patients guilty of “maladaptive coping” and “escape-avoiding behavior.” 

If the CDC had found the retrovirus, it would have negated its 20-year affair with CFS as a psychological problem.  Now that two other government agencies have found XMRV and other studies due out this summer have also found the retrovirus, critics point out that the CDC is in a no-win situation and beginning to look like the odd man out.

Monday, June 28, 2010


One concern during antiretroviral treatment is drug resistance. That’s why HIV patients are usually on a three-drug cocktail, known as HAART, which stands for Highly Active Antiretroviral Therapy.  HIV is a lively, rapidly replicating retrovirus, leading to a high mutation rate:  As in most arenas, mistakes occur more commonly in haste.  The more mutations, the greater the risk of a favorable mutation popping up that confers drug resistance.

But XMRV replicates slowly and doesn’t appear to mutate much.  If XMRV proves to be the cause of ME/CFS and patients begin antiretroviral therapy, will patients still require a triple cocktail?

At present, only three FDA-approved HIV drugs have been shown to have efficacy against XMRV in vitro (in the test tube): AZT, tenofovir and raltegravir.  One possible way to determine whether CFS patients need all three would be for researchers to conduct retrospective longitudinal studies.  Examining the banked blood of HIV patients who’ve been followed for years, they would locate the positive XMRV samples.

Even if HIV patients aren’t infected with XMRV in large numbers, there may be a background rate of 3 to 7 percent, as per the findings of the soon-to-be-published FDA and NIH study, or the more conservative 3.7 percent background rate found in a study by Dr. Judy Mikovits, published in Science in October.

While the HIV patients have been on any one of the three antiretrovirals that appear to be effective for XMRV, has XMRV mutated?  If XMRV hasn’t mutated over several years, a single drug might be sufficient.  If it has mutated, researchers could examine the mutation rates of patients on two of the drugs that appear to be active against XMRV, and so on.

It would also be helpful to examine the banked blood of ME/CFS patients who’ve been followed over many years to determine the natural XMRV mutation rate over time. Researchers may also discover that some strains of XMRV are less likely to mutate than others.

It would be risky for patients to go on monotherapy until more is known about drug resistance and XMRV.  Because once you developed resistance, the drug is essentially useless.

Thursday, June 24, 2010


Directed by British filmmaker Geoffrey Smith for release in 2011, the documentary What About ME? chronicles the plight of ME/CFS patients in Great Britain and the United States.

The trailers (one for the U.K, one for the U.S.) feature interviews with ME/CFS physicians Sarah Myhill in the U.K. and Daniel Peterson in the U.S.; advocates, including biochemist Malcolm Hooper and Whittemore Peterson Institute president Annette Whittemore, who funded the first XMRV study in patients with Chronic Fatigue Syndrome; and patients, among them Whittemore’s daughter, Andrea Whittemore Goad, who talks about the worst aspect of the disease for many patients:  not being believed.

The production values in What About ME? are lush; this is a first-rate operation.  And the trailers convey an eerie, disquieting mood, underlined by the plaintive musical score.  They’re reminiscent of such memorable documentaries as Under Our Skin, Andy Abrahams Wilson’s film about the Lyme disease epidemic; and The Thin Blue Line, Errol Morris’s explosive movie about a man unjustly found guilty of murder.

One exquisitely painful sequence in the U.S. trailer of What About Me? has you gazing at photos of ME/CFS sufferers before they became ill alongside photos of them afterward.  It’s like the before-and-after pics of a beauty makeover—except reversed.  Beneath the placidity of the day-to-day lives of ME/CFS patients—many of whom are bed-bound or house-bound with no good treatments and little hope of getting well—brews the perfect storm. 

The saga makes for great drama even as it’s shattering lives.  On one side are more than a million sick patients in Great Britain and the United States, with few beleaguered physicians willing to treat them and, up until the XMRV study, poorly funded researchers looking into a viral etiology.  On the other is an army of well-funded psychological researchers in government agencies and at universities churning out studies on depression and early childhood trauma in ME/CFS. 

The trailers aren’t all sturm und drang, however.  There are laugh-out-loud moments. One British mother of a daughter sick with ME/CFS explains how she was told by various doctors that the disease doesn’t exist in children but that in any event her daughter would recover within two years.  “That’s quite a common thing they tell parents,” she says matter-of-factly.   “Which is an interesting one because if you don’t believe in something anyway, why do you believe there’s a time limit on it?”

Given that the filmmakers fall squarely on the side of the patients, it’s not surprising that none of the psychological or psychobiosocial proponents—some of whom have been outspoken critics of the Whittemore Peterson Institute XMRV study and have come out with studies refuting its findings—have to date agreed to be interviewed.  As a friend of mine always says:  The more open the marriage, the more private the divorce.

Geoffrey Smith, the film’s director, is best known for his award-winning documentary The English Surgeon, which New York Times critic Manohla Dargis cited as one of her favorite films of 2009.  Smith trailed prominent London neurosurgeon Henry Marsh on his latest mission to bring state-of-the-art surgery to the primitive medical conditions in Ukraine.

Shepherding What About ME? is Susan Douglas, who produced the 2009 documentary Who Killed Nancy? directed by British filmmaker and author Alan G. Parker.  Stabbed to death in the fall of 1978, Nancy Spungen was the girlfriend of Sex Pistols bassist Sid Vicious.  Widely believed—perhaps erroneously—to have been responsible for her murder, Vicious died of a heroin overdose four months after Spungen’s death.

In an email, Douglas said she conceived What About ME? two years ago, after an illuminating conversation with the mother of a young man with ME/CFS, which his mother believes he contracted after crop spraying near his home.  “That got my attention,” Douglas wrote.  “I have since realized what a massive, multi-layered subject it is.”

At present, filming is planned only in the U.K. and U.S. but, Douglas said, “As you know, the nature of the beast can change according to breaking stories, so if there is anything elsewhere and the budget allows we could possibly shoot outside of this premise.”

Douglas’s production company is Double D—and no, it has nothing to do with bra size.  It stands for Digital Documentaries, as the company specializes in online distribution.  “The name,” Douglas concedes, “makes it more memorable.”  Douglas is aiming for a multi-platform release—theatrical, online and television.  “We really intend to get this to the planet, not just the ME community.”

Monday, June 21, 2010


ME/CFS patients do hard time in
mental wards and foster care

In the fall of 1986, a young British boy named Ean Proctor became ill on a school trip to Wales.  Once home on the Isle of Man, his decline continued, and a neurologist diagnosed him with Myalgic Encephalomyelitis (ME), known in the U.S. as Chronic Fatigue Syndrome (CFS).  There had been an outbreak of the disease in Wales when the boy was visiting.

His case proved severe, and by 1988 12-year-old Ean was confined to a wheelchair and could no longer speak.  Ean’s neurologist suggested the Proctors consult ME/CFS researcher Dr. Simon Wessely but were not told, according to Ean’s father, Robin Proctor, that Wessely was a psychiatrist. 

At the hospital, “Wessely pinched his skin a bit and looked at him from the foot of his bed,” Ean’s mother Barbara Proctor recalls. “Then he took us to another room and told us that Ean didn’t have ME and that children don’t get it.”  When the Proctors told him that they believed he did have the disease, Barbara Proctor says, “Wessely accused us of playing doctor.”

Soon after, in response to a request from lawyers for the child care department, Simon Wessely issued a report [click on the blue type to view the report] obtained by CFS Central in which he attributed Ean’s symptoms to psychogenic causes and explained why he favored placing Ean in a mental ward. “Not withstanding the absence of severe depression or psychoses, Ean has a primary psychological illness causing him to become mute and immobile,” Wessely wrote.  Below Wessely’s signature were the typed words “Approved under Section 12, Mental Health Act, 1983”.  Section 12 enables authorities to consign patients with psychiatric disorders to mental hospitals against their wishes and is referred to colloquially as “sectioning.” 

Despite the Proctors’ ardent protests, Ean ended up in a psych ward for mentally ill children for several months. A doctor and two social workers escorted Ean there by ambulance while the boy cried.  Several years later, according to an interview with Dr. Anne McIntyre, herself an ME/CFS sufferer, Ean said that one of the social workers told him they were taking him away because his parents were letting him die. 

In the ward, “One of the children was screaming, ripping the rooms apart, turning the beds upside down,” Barbara Proctor remembers.  The doctors and nurses, she says, believed Ean was faking his illness and forced him to feed himself, which took hours because his arms were so weak.  He sat in soiled clothing because the nurses wouldn’t take him to the bathroom.

The staff, Barbara Proctor says, observed their interactions with Ean through a one-way mirror and disapproved of them helping their son. “They thought we were making him ill.  Ean was in a wheelchair, he couldn’t speak, his hands were in tight fists.  He was all skin and bones—he looked like something out of Belsen [concentration camp].  How could he do anything?” his mother asks rhetorically.  Ean communicated with his parents by nodding to letters of the alphabet.  To compel him to move, the staff placed Ean facedown in a swimming pool without water wings.  Too weak to dogpaddle, he sank underwater and had to be rescued.  “It was out of the dark ages, the way Ean was treated,” Barbara Proctor laments.

Five months later, after a protracted court battle that nearly bankrupted the Proctors, Ean was finally released into the care of his parents and ME physicians. “We often say if we hadn’t gotten Ean out of there, he wouldn’t have come out alive,” his mother says.  One of his new doctors had treated several children during the Welsh ME/CFS outbreak; Ean also saw a local homeopath. Only 4 to 8 percent of ME/CFS patients recover, but, astonishingly, Ean was one of the lucky ones.  In the reverse order in which they began, his symptoms slowly resolved, until he was well.

Recounting his ordeal on camera with Dr. Anne McIntyre, Ean said he was “very bitter” about the way he was treated.  “Most of the doctors,” he said evenly,  “didn’t really want to understand what the illness was about.”

Wessely's reports 
Ean Proctor declined to be interviewed for this article.  “We’re a small island,” Barbara Proctor explains.  “He doesn’t want anything plastered in the papers again.”  However, Ean gave me written authorization to publish some of his medical records, which his parents obtained legally during their court case.  In a June 3, 1988, letter to a social worker about Ean [click on the blue type to view the letter], Wessely wrote,  “I have absolutely no doubt that the primary problem was psychiatric.  My initial impression was that Ean’s condition was a form of hysteria, in other words, his apparent illness was out of all proportion to the original cause.”

The psychiatrist went on to write, “Ean’s parents are well meaning, but are very over involved in his care, and are certainly seriously over committed to one particular diagnosis.  I have considerable experience in the subject of ‘myalgic encephalomyelitis,’ and am absolutely certain that whatever the status of that diagnosis, it did not apply to Ean.  I feel that Ean needs a long period of rehabilitation, part of which will involve very skilled management of separation from his parents, and the restoring of his independence, and providing an escape from his ‘ill’ world.  For this reason, I support the application made by your department for wardship.”

Two months later, Wessely wrote in another medical report [click on the blue type to read the report], “What is wrong with Ean?  The symptom that is most distressing to Ean, his parents and medical advisers is that Ean is mute…. I have considerable experience of both the post-viral fatigue syndrome and child and adult psychiatry, and would submit that mutism does not, and cannot, occur in a true chronic fatiguing illness, but can, and does occur, in psychological illnesses.” 

Today, Simon Wessely won’t discuss Ean Proctor.  “I’m not going to talk about individual cases,” Wessely says.  “I’m a psychiatrist.  And you’re talking about events that took place 25 years ago now, aren’t you?  You can interpret that as you wish.  It’s not right for me to talk about individual patients.  I’ve read some of the ludicrous conspiracy theories about many many things, and I’d just like to say that I do not recognize myself in any of those things, to be honest with you.”

XMRV study
More than 20 years after Ean Proctor’s sectioning, Wessely remains a major player in ME/CFS research.  Critics cite that as a longtime proponent of the disease as a psychological or biopsychosocial malady in which a person’s negative “illness beliefs” cause physical symptoms, Wessely was not the ideal person to supply the patients for the retroviral XMRV PLoS One study published in January that failed to yield any positives in 187 ME/CFS patients.  An earlier Science study conducted by U.S. researchers found the newly discovered retrovirus in 67 percent of 101 patients, and more sophisticated testing later showed that 98 percent of patients were infected.  (Read “Blood Feud” Part 1 and Part 2 for more information on these studies.)

As for Ean Proctor, he is now 35, engaged to be married and working full time.  An avid mountain biker and hiker, he has defied the odds and remained healthy.  He emerged from his ordeal with his sense of humor intact, the Proctors say.  The old adage that what doesn’t kill you makes you stronger appears true in his case.  According to Barbara Proctor, during his stay in the psychiatric ward, a physician told Ean that he wouldn’t be coming home ever again and would, instead, be sent from the Isle of Man to mainland England to be adopted.  “That is mental cruelty to me,” Barbara Proctor says.  “But Ean only told us that story a few years ago.  I asked him, ‘Why didn’t you tell us then?’  And he said, ‘You had enough to worry about.’ ”

Sophia Mirza
The sectioning of children and adults diagnosed with ME/CFS still occurs in England.  According to Criona Wilson, in 2003 after daughter Sophia Mirza declined treatment of her ME/CFS with cognitive behavioral therapy (CBT) and graduated exercise therapy (GET), the 30-year-old woman was sectioned.  (GET, many ME/CFS physicians believe, can be injurious to patients, and CBT is often of limited benefit.)  A police officer broke down her front door, and a psychiatrist and social worker hauled her away for a two-week stint in a mental ward where, according to her mother, her fragile health deteriorated, and she never recovered.

Mirza died in 2005; her autopsy revealed spinal cord inflammation and kidney failure.  Neurologist Abhijit Chaudhurit told the British news show Meridian Tonight that the autopsy concluded that 75 percent of the sensory cells in Mirza’s spinal cord were significantly abnormal.  “She deserved,” he said, “to have been seen by a neurologist and managed by a multi-disciplinary team rather than be left in a psychiatric hospital.”  Criona Wilson told Sophia’s powerful story on camera.

Ryan Baldwin
Because ME/CFS is still so misunderstood, social services in the U.S. occasionally places children with the disease in foster care while the parents are charged with medical neglect and investigated for factitious disorder by proxy.  Better known by its defunct moniker Munchausen’s by proxy, it’s a severe psychiatric disturbance in which parents—usually mothers—make their children ill as a way to bring attention to themselves. 

Such was the case of North Carolina boy Ryan Baldwin, who was pulled from his home in January 2009 when he was 16, placed in a series of foster homes, made to exercise though it made him sicker and allowed no contact with his parents except in court.  It took nearly a year before his parents were cleared.  Ryan made it home in time for Thanksgiving.  In January, according to a local newspaper account, Ryan told the court that his time in foster care had been “a living hell.”


This article, “Hard Cell,” is copyright © CFS Central 2010.  All rights reserved.   You may quote up to two paragraphs from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is from CFS Central.

The three documents Ean Proctor authorized me to post on this site are copyright © CFS Central 2010.  You may not reprint these letters or forward them.  Instead, forward CFS Central’s URL to share the material.  

Coming up: An examination of ART (anti-retroviral therapy) in the treatment of HIV and ME/CFS.

Thursday, June 17, 2010


In my interviews with Dr. Myra McClure (principal investigator of the first British ME/CFS XMRV study) and Dr. Kate Bishop (principal investigator of the second British ME/CFS XMRV study), both acknowledged that their studies were not replications of Dr. Judy Mikovits's XMRV study.  (See their comments in the BLOOD FEUD: Part 2 post.)  However, most of the media has mislabeled their studies as replications.  
A friend sent this page from his daughter’s ninth-grade biology textbook, Biology, by Stephen Nowicki, published by McDougal Littell, 2008.  According to Nowicki, to be considered a replication:

"Scientists repeating another person’s experiment must be able to follow the procedures exactly and obtain the same results in order for the experiment to be valid. Valid experiments must have

• a testable hypothesis
• a control group and an experimental group
• defined independent and dependent variables
• all other conditions held constant
• repeated trials"

McClure's study didn't use controls, and the methods she used to test for XMRV were different from Mikovits's methods.  While Bishop included controls, like McClure she used different methods to test for the retrovirus.

Why isn't the media picking up on this?  One reason is that many reporters don't have time to read the actual studies, especially in this dried-up journalism climate, where newspapers and magazines are cutting back staff and coverage or going under.  Reporter Nick Davies terms much of today's journalism "churnalism."  Whether from overwork, disinterest or blind trust, some reporters simply scan a study's abstract, plug in perky quotes from the study's authors, and call it a day. 


Next week:  "HARD CELL."  ME/CFS patients do hard time in mental wards and foster care.

Monday, June 14, 2010


The Chronic Fatigue Syndrome XMRV controversy heats up with the second British XMRV study, the Dutch study and the unpublished CDC study 

This is Part 2 of an article on the newly discovered retrovirus XMRV in patients with Chronic Fatigue Syndrome (CFS).  Part 1 can be read here.

Last fall, a group of American researchers published a study in Science that offered hope to the 17 million Chronic Fatigue Syndrome (CFS) sufferers worldwide, most of whom are women.  Identifying what may turn out to be an important clue to the illness, the researchers found that 67 percent of 101 CFS patients were infected with the retrovirus XMRV.  More sophisticated testing later showed that 98 percent of patients were infected.

But in January, British XMRV researchers published a study that didn’t find the retrovirus in even one of 186 CFS patients.  Each XMRV camp blamed the other for flaws in methodology, and the exchanges between principal investigator Dr. Judy Mikovits of the U.S. cohort and Dr. Myra McClure of the British cohort quickly became testy.  Many patients were incensed that another of the British study authors, psychiatrist Simon Wessely, has been a 20-year proponent of the disease as a psychological malady.

British study #2
Just when the transatlantic bickering was beginning to abate, a second British CFS study published in Retrovirology on February 15th didn’t find any firm evidence of XMRV either, sending some patients into a tailspin.  Blogged one:  “If anyone can put a positive spin on this then please post now.  I sense defeat (in myself).  And another 13 yrs (to life) in the wilderness.”

From a group of 170 patients and 395 controls, these British researchers found that 26 exhibited antibodies to XMRV.  The surprise came when the scientists unblinded the study and discovered that 25 of the 26 were controls.  “I was quite shocked,” divulges principal investigator Dr. Kate Bishop, who expected that most of the 25 would be patients.  However, Bishop isn’t convinced that the antibodies were caused by XMRV.  That’s because the antibodies of all but three controls and one patient weren't specific for XMRV and neutralized other viruses as well as XMRV.

While the media has categorized the two British studies as replications, both McClure and Bishop acknowledge that they’re not. 

Bishop's group and the U.S. group have remained civil.  One reason beyond the obvious—that scientists don’t usually insult one another, at least publicly—may be that Mikovits and Dr. Jonathan Kerr—a Retrovirology author who has published papers linking CFS to genetic mutations—share a $1.6 million five-year NIH grant to decipher the cause of CFS.  While the media has categorized the two British studies as replications, both McClure and Bishop acknowledge that they’re not.  For her part, Bishop says one of the reasons her cohort didn’t adhere to the U.S. protocol is that she believes it’s tougher to get a paper published when the experiment is conducted in exactly the same way as the original study.

As for McClure, her study “was never designed to replicate [the U.S.] study or to say, ‘Look how clever we are, and they’re wrong,’ she says.  “It was simply an investigation to see if we in this country could detect this virus in our CFS patients that were homegrown here.”

Critics caution, however, that it’s essential to follow the identical protocol of the original study to validate or disprove it, and if the researchers don’t, they’re in essence comparing apples to oranges.  Interestingly, one of the authors of the second British study was an investigator on a study that failed to replicate the retroviral CFS research of Dr. Elaine DeFreitas at University of Pennsylvania’s Wistar Institute 20 years ago.   Back then, that scientist didn’t follow DeFreitas’s protocol either, and the media mislabeled the study a replication as well.  Given that back story, some patients and long-time researchers have categorized the current crop of British studies as déjà vu all over again.  Others call it a coda to And The Band Played On.

The negative findings in the British studies don’t faze Judy Mikovits, who says other studies due out in the next six months will confirm her study.  She believes that neither group of British researchers could confirm the U.S. findings because neither followed her protocol.

The Aha moment?
But perhaps there is another reason. A week after Bishop’s study came out, researchers at Emory University’s primate lab who injected XMRV into macaques reported that even when the virus was undetectable in the blood, it thrived in the reproductive organs as well as the spleen, gut, bladder, lung, liver and lymph nodes.  It’s possible the British studies couldn’t find XMRV in the blood because it’s not where the retrovirus likes to hang out. In addition, a German study published June 16 found XMRV in the respiratory tracts of 2 to 3 percent of 168 healthy controls and 10 percent of 161 patients with compromised immune systems, lending credence to the hypothesis that the retrovirus flourishes in areas other than the blood.

One government source says that the yet-unpublished XMRV study by the CDC didn't find the virus—though another government agency has.

More studies in the works
Retrovirologists at the University of Utah, Tufts, Stanford, Cornell and Columbia universities, and in Canada, Sweden, Russia, Spain, Australia and China are at work on XMRV studies.  The German researchers who found no association with XMRV and prostate cancer are now repeating their study using the methods of the U.S. cohort, which did.

The CDC also completed and is due to publish an XMRV study shortly.  One highly placed government source says that the CDC’s study didn’t find the virus—though, the source says, another unnamed government agency has.  In the fall, the CDC and NIH predicted it would take six months for the government to complete its studies, but there have been delays.  At the Chronic Fatigue Syndrome Advisory Committee meeting held at the CDC on May 10, Dr. Jerry Holmberg of the Department of Health and Human Services’s Office of Public Health and Safety apparently tipped his hand when he remarked that part of the holdup was determining the patient-notification policy on the positive XMRV patients from the 25 Whittemore-Peterson CFS samples.

Patients, meanwhile, have been fretting over the CDC’s XMRV study for months because of the agency’s longstanding position that CFS is largely a psychiatric problem.  More than a decade ago, the government agency began watering down the already trifling name of Chronic Fatigue Syndrome to “chronic fatigue,” “fatigue” and “unwellness,” largely due to the philosophy of its longstanding principal investigator, Dr. William Reeves. 

In recent months, the agency seems to be sending out mixed signals about its stance toward CFS.  On the one hand, Reeves was reassigned to a new CDC post in Mental Health Surveillance on February 14.  Some observers read this as a possible shift in the agency’s philosophy.

On the other hand, Dr. Steve Monroe, Reeves’s old boss and the agency’s director of the division of viral and rickettsial disease, where, oddly, most of the CFS psychological research has been carried out, applauds the British research.  “I respect the scientific credentials of the people who did the testing,” says Monroe, a careful speaker with a fondness for qualifiers.  He reasons that since the initial U.S. study found the virus in 67 percent and the first British study didn’t find it at all, “XMRV is not universally present in the majority of CFS patients.  Based on the U.K. results, it’s not universally true that XMRV is associated with the majority—more than half—of CFS patients.  Of course, there could be regional differences.” 

The tipping point
Everyone with a stake in Chronic Fatigue Syndrome has a point of view and something to prove, and it may take a year or more before science yields a verdict on XMRV’s place in the disease.  XMRV may turn out to be the tipping point that changes the game and the players in CFS.  Or it may turn out to be an inconsequential finding or collateral damage from a weakened immune system.  One argument against causality is that HIV and HTLV—the two other known human retroviruses—are transmitted solely through blood or sexual contact, which may be difficult to reconcile with the occurrence of several cluster outbreaks of CFS in the U.S. and England, including an outbreak among schoolchildren in Lyndonville, New York, in the 1980s.

Eminent Tufts University retrovirologist Dr. John Coffin, who’s working on an XMRV replication study, put the uncertainty into perspective at a retrovirology conference in February, reminding scientists of the confusion back in 1983 in the early days of HIV and affirming, “There’s no question that the virus is real and that the virus is infecting some number of people.”  An earthy, measured optimist, which makes him a big hit at conferences, Coffin remarked that it takes a long time to “grind the sausage” and come to a consensus about a big finding like XMRV, and that “although it’s annoying and confusing, it’s really very exciting at the same time.” 

Then again, a February 25 editorial in the British Medical Journal by Drs. Simon Wessely and Myra McClure categorized the research community as “underwhelmed” by the XMRV link to CFS.  The editorial accompanied a small Dutch study that didn’t find XMRV in any of its 32 patient blood samples frozen in 1991 and 1992.  Two of the study’s scientists are psychiatric CFS proponents and have co-authored more than 50 papers on the disease, including the 2008 “Guided self-instructions for people with Chronic Fatigue Syndrome,” which combined cognitive therapy with “email contact.”

Until the dust settles, the uncertainty and media frenzy over whom to believe is bound to continue, prompting Science’s Sam Kean to comment that the search for the cause of CFS, which “seemed to be gaining traction, now seems likely to descend into the same confusion and acrimony that characterized it for years, as a supposed viral link to CFS published just last autumn might be unraveling.”

Longtime patient Pat Fero, who tested positive for XMRV and whose son, Casey, came down with CFS at the age of 9, hopes it does not unravel.  She lived through the fallout from Dr. Elaine DeFreitas’s study 20 years ago and now hopes that the XMRV discovery leads to new treatments, “so that those young adults with CFS can look forward to a better life and experience a childhood they never had.”  Casey died in his sleep from the disease in 2005 at the age of 23.  His autopsy revealed viral myocarditisan infection of the heartand old scarring, but doctors never took his health complaints seriously.  “I’m hopeful,” she says wistfully, “that many sick children may soon wake up.”

This article, “Blood Feud,” Part 2 is copyright © CFS Central 2010.  All rights reserved.   You may quote up to two paragraphs from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by from CFS Central.  

Coming up:  CFS patients do hard time in mental wards and foster care.

Thursday, June 10, 2010


A transatlantic battle rages over the role of a
newly discovered retrovirus in patients
with Chronic Fatigue Syndrome

Last fall, a group of American researchers published a study in Science that offered hope to the 17 million patients with Chronic Fatigue Syndrome (CFS) worldwide.  Identifying what may turn out to be an important clue to the illness, the researchers found that 67 percent of 101 patients were infected with a newly discovered retrovirus called XMRV.  More sophisticated testing later showed that 98 percent were infected.

The XMRV study has already had global consequences.  Concerned that the retrovirus may contaminate the blood supply, health officials in Australia, Canada and New Zealand announced new policies banning patients with CFS from giving blood.  The U.S. government has stopped short of prohibition, but the National Cancer Institute has advised CFS patients against blood donation.

Despite these significant actions worldwide, XMRV’s role in CFS is still very much in question.  In fact, the New Year ushered in a severe blow to patients when British XMRV researchers published a study that didn’t find the retrovirus in even one of 186 CFS patients—and the XMRV momentum was stopped dead, if temporarily, in its tracks.

Each XMRV camp blamed the other for flaws in methodology.  Pundits took potshots at CFS patients for defending the U.S. findings.  In Psychology Today, rheumatologist Mark Borigini christened CFS patients “terrorists of health, in full jihadist mode.”  More than a hundred patients fired back comments, several asking Psychology Today editors to delete his article (they did not) and one comparing Borigini to Nazi physician Josef Mengele.  But most responses were like this one:  “Please, please tell me you did not actually compare legitimately chronically ill patients, desperate to find relief from their pain and disability, to violent radical extremists?”

Clearly, this is no run-of-the-mill scientific dispute.  These new studies are just the latest twist in a quarter-century saga of backbiting and infighting, politics and money, accusations of flawed studies and covert alliances, allegations of patient abuse and blood-supply contamination, charges of paternalism and sexism, culminating in two XMRV studies that pit a longstanding cohort of British psychiatrists endorsing a psychological cause for the disease against a longstanding cohort of American researchers endorsing a physiological one.  The antagonists include the parents of an adult daughter seriously ill with CFS facing off against an influential British psychiatrist and medal recipient from the Royal College of Physicians, who has long been a bête noire  of the CFS community.

The feud between the physical and psychological camps simmered in the 1980s and ignited in 1991, when a young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas discovered a retrovirus in the blood of CFS patients.  Whether XMRV and DeFreitas’s retrovirus are one and the same is not known with certainty, though preliminary evidence indicates that they are not.  Twenty years ago, newspapers and TV news shows latched onto DeFreitas’s finding, spreading the word that the cause of the debilitating disease had, perhaps, been found.

The jubilant atmosphere was short-lived.  The Centers for Disease Control (CDC) failed to find DeFreitas’s retrovirus in patients and controls (without using DeFreitas’s protocol) and British researchers found the retrovirus in all the controls and the patients—again without using her protocol.  Given the diametrically opposed findings, DeFreitas reasoned the problem was rooted in the methods.  But by that time, retroviral disbelievers outnumbered believers, media interest flagged and the CDC took the unusual step of publicly chastising DeFreitas.  Tangling with the U.S. government proved costly to the researcher, which scared off likeminded scientists for nearly 20 years, silenced patients and split the research community into two nonintersecting camps.

Over the years, their disparate positions have only become more entrenched, evidenced by the inevitable exclamatory XMRV headline posted on one patient forum: “The fight is on!”

Contaminated blood supply
XMRV—which stands for xenotropic murine leukemia virus-related virus—is the human version of a mouse gammaretrovirus.  The last retrovirus to jump species was HIV—from monkeys to humans.  XMRV could impact us all. In the U.S. study, 3.7 percent of a control group of healthy subjects tested positive for the retrovirus.  If those numbers hold up on subsequent studies, that will translate to 10 million people in the U.S.—nearly 10 times the number living with HIV/AIDS.  How many may become ill as a result, no one yet knows.  But since the host’s DNA becomes inextricably intertwined with the retrovirus, an XMRV infection lasts for life.

How did so many people become infected?  Although the mode of transmission has not been established, the Japanese Red Cross issued a disturbing report that XMRV has been detected in nearly 2 percent of Japan’s blood supply.  In the U.S., the National Institutes of Health (NIH) is investigating the blood supply; results are expected by the fall.

In animals, XMRV can cause serious neuroimmune problems as well as blood cancers, which afflict CFS patients as well.  Few are aware of the seriousness of CFS, though the severe abnormalities it causes—including seizures, heart failure and serious infections from a damaged immune system—have been documented in two thousand Medline articles.  That’s partly due to the disease’s trivial name, coined by the CDC.

U.S. studies: XMRV link
The first report of an association of XMRV with human disease came in 2006—from U.S. researchers studying a virulent form of prostate cancer, not CFS.  But then a German study found no such association, echoing the conflicting findings of the CFS studies.

Three years later, Dr. Judy Mikovits of the Whittemore-Peterson Institute in Reno, Nevada, led the U.S. group that connected XMRV to CFS.  The National Cancer Institute and the Cleveland Clinic replicated the study before the troika published in the prestigious journal Science.

Harvey and Annette Whittemore co-founded the Whittemore-Peterson Institute and funded the study in support of their daughter, who has CFS.  The other name on the Institute’s shingle is Dr. Daniel Peterson who, along with then-partner Dr. Paul Cheney, was the first to contact the Centers for Disease Control (CDC) about a CFS outbreak in the tony resort town of Incline Village on Lake Tahoe, Nevada, in 1984.

The Whittemores and Peterson have a lot on the line:  The Whittemores want to help patients, including their 31-year-old daughter, who’s had the disease for 20 years and requires supplemental oxygen and experiences seizures; Peterson wants to find the cause of CFS and get down to the business of researching treatments.

It’s a position endorsed by CFS sufferers, who also want to put an end to the anemic name and the 25 years of ridicule by many doctors, researchers and government agencies that treat CFS as an inconsequential affliction of whiners, hysterics and depressives.  “As a longstanding patient, a parent of a son who died of CFS and an advocate who in 20 plus years has spoken to hundreds if not thousands of patients, I want the bias aired, the bigotry gone and our stories told,” CFS patient Pat Fero says.  “To be the subject of laughter and the butt of a joke because of an illness I have no control over is a disgrace.”

British study:  No XMRV
British psychiatrist Simon Wessely and two of his colleagues in the psychiatry department at King’s College London, along with virologists at Imperial College London, conducted the British study, which didn’t find XMRV in any patients.  Wessely’s psychiatry unit supplied the blood samples.  Critics question the patient group for two reasons:  First, the psychiatrist bills CFS as a biosocial disorder, in which a person’s negative “illness beliefs” cause physical symptoms. And second, his studies often lump CFS in with “chronic fatigue,” “fatigue”  and, most recently,  “burnout,” which are entirely different entities. 

On the heels of the British study’s publication came a statement from the Whittemore-Peterson Institute questioning whether the patients in the British study actually had CFS:  “Significant and critical questions remain as to the status of patient samples used in the U.K. study as those samples may have been confused with fatigued psychiatric patients, since the U.K. has relegated ‘CFS’ patients to psychiatric care and not traditional medical practices.”

Former Villanova University professor and patient advocate Dr. Mary Schweitzer, who’s had severe CFS for 15 years and is XMRV positive, puts it more directly: “There’s an old saying in computerized statistics:  GIGO—garbage in, garbage out.  The study is only as good as the data set.”

Wessely, however, maintains that the patients in his study “fulfill the international criteria for this illness, are quite disabled and most of them aren’t working.  It has been said in some quarters,” he adds, “that the reason we did not find XMRV is because the patients at King’s College London did not really have CFS but instead had mental disorders, psychiatric illness, whatever.  On the record, I do not mind people insulting me, but I dramatically and vehemently object to them insulting our patients, and you can take it from me—and every one else on this service—that whatever CFS is, these patients have it.”

Fresh blood
Columbia University virologists Dr. Stephen Goff and Dr. Vincent Racaniello have suggested that one way to solve the XMRV puzzle is for researchers to exchange samples.  “I would be reluctant to do this,” says Dr. Myra McClure, one of the retrovirologists on the British study, a hint of a Scottish lilt in her voice.  She believes contamination of the samples could result, potentially leading to false positives.  “Please believe me, I’m not accusing [the U.S.] lab of contamination or anything like that.  I’m sure they’re very careful workers.  The way to do this cleanly, so that there’s no ambiguity, is to take fresh blood from CFS patients.  And to send one part to one lab, one part to an independent lab and one part to my lab and see what results you get.”

Dr. Judy Mikovits, the U.S. study’s principal investigator, agrees that procedure would have been ideal. The problem, she says, is that the British cohort never requested fresh blood—“or anything else”—from her lab.  In fact, maintains Mikovits, her lab has sent fresh blood to researchers around the world and would gladly have supplied it to the British.  All they had to do, she says, was ask.

Swimming to England
Both women sport impressive resumes:  McClure trained at the Institute for Cancer Research in London under Dr. Robin Weiss, a top retrovirologist in England; Mikovits trained at the National Cancer Institute under Dr. Frank Ruscetti, the co-discoverer of the first known human retrovirus, HTLV-1, and a co-author on the U.S. XMRV study.

McClure and Mikovits have been butting heads since the British group published. “Mikovits has been critical of us publishing so quickly,” McClure says, to which Mikovits responds, “McClure is the one who said we rushed to judgment.” Besides, Mikovits adds, “We didn’t judge anything.  We isolated a retrovirus.”

The British study was published after only three days of review in PLoS One, in contrast to the Science study, which was published after a six-month peer review.  In addition, the Cleveland Clinic and the National Cancer Institute replicated the Mikovits findings before the U.S. results were published, whereas the British researchers didn’t use outside labs to confirm.  The U.S. group looked for the virus with a technique called polymerase chain reaction (PCR), as well as culture and antibody testing because, says Mikovits, XMRV is difficult to detect through PCR alone.  In contrast, the British researchers used only PCR.  And unlike the U.S. study, the British study didn’t include healthy controls.

“If we had found one positive, we would have had to go for controls,” McClure explains.  “It was because we didn’t find any that there was no need.”  To which Mikovits responds:  “That is unscientific and not worthy of comment.”

McClure says the British scientists published swiftly because they “wanted to put a stop to this stampede of patients who were demanding antiretroviral therapy.”  Despite its speed, McClure is confident of the study’s conclusions.

Still, given that the U.S. and Japan have found XMRV, it seems odd that the British researchers didn’t find the retrovirus in even a few patients.  Certainly the numbers in England could be far lower than in the U.S., but zero?

“We wondered about that, too,” McClure admits. And she and Wessely concede a XMRV background rate of about 1 to 1.5 percent is possible.  “Our study doesn’t mean XMRV doesn’t exist in Britain,” Wessely acknowledges.  “It might.  But clearly our study would be incompatible—if our study is correct—with a high prevalence in this country.”

Using the U.S. study’s assays, the Nevada-based lab VIP Dx has already found, in a different cohort, XMRV in eight out of 20 British CFS patients, triggering one CFS blogger to quip: “Apparently XMRV can swim!”

Fainting couches and hate mail
Far more heated than the Mikovits-McClure face-off is Simon Wessely’s roiling feud with CFS patients that’s finally reached boiling point.

“I’m aware that some people feel that because I am by background a psychiatrist that these patients [in his XMRV study] therefore suffer from imaginary psychiatric conditions and not Chronic Fatigue Syndrome,” Wessely says.  “That is a disgraceful and disgusting suggestion, which I find insulting on behalf of our patients who have Chronic Fatigue Syndrome.  And you can quote me on that.”

Wessely’s critics point to the more than one hundred CFS papers he’s written over the course of 20 years as evidence of his underlying beliefs about the illness.  In 1989, he gave six books a mostly thumbs-down review because instead of focusing on psychological problems, they chronicled neurological and immune dysfunction in CFS—or ME, short for the malignant-sounding Myalgic Encephalomyelitis, as it was known in England for 40 years until Simon Wessely and England’s Royal Colleges of Physicians, Psychiatrists and General Practitioners favored a name change to the benign-sounding CFS a decade ago.  In his review, Wessely maintained that the disease is an updated name for neurasthenia, a 19th century affliction of hysterical women swooning on fainting couches, clasped hand to furrowed brow.

The Golden Girls
In another article that same year, Wessely takes issue with the conclusion of a two-part Golden Girls episode in which a doctor gives a relieved Dorothy (Bea Arthur) a CFS diagnosis—after two other physicians write her off as lonely or in need of a change in hair color and suggest she visit a psychiatrist.  “Most of us believe it’s a virus, it just has not been identified yet,” the third doctor tells her.  At the heart of the CFS “movement,” Wessely asserts in his paper, “is the rejection of any form of psychological causation or treatment.”  Patients say it’s articles like these that cause the CFS community—two-thirds of whom are women—to label Wessely as sexist and paternalistic.

In more recent years, The Lancet published Wessely’s “Functional somatic syndromes:  One or many?” on CFS, irritable bowel syndrome and other poorly understood illnesses. “Functional somatic” is a clinical term for physical manifestations of psychiatric disorders.  In another Wessely study, 72 percent of his CFS patients by the study authors’ own description “were cases of psychiatric disorder.”

Critics also note Wessely’s uncanny ability to affirm both sides—or neither side—of a debate, sometimes in the same maddening sentence, as if he’s Lewis Carroll and they’ve tumbled down the rabbit hole:  “What lies behind CFS is neither a virus nor psychiatry, but our idea of what constitutes a real illness, what doesn’t, and what we do to make something real,” Wessely told The Independent in 1997.

Penned British investigative journalist Martin Walker in Cultural Dwarfs and Junk Journalism, “Professor Wessely should be granted a dictionary of his own, so far has he stretched the meaning of the English language while attempting to explain that ME although a ‘real’ illness, is often first imagined.” 

Wessely gets his share of hate mail, and, in turn, his quarrel with the CFS community sometimes seems curiously personal.  “If one reads the angry responses to any article that mentions Chronic Fatigue Syndrome and psychiatry in the same breath, it is clear that the drive to find a somatic biomarker for Chronic Fatigue Syndrome is driven not so much by a dispassionate thirst for knowledge but more by an overwhelming desire to get rid of the psychiatrists,” Wessely wrote in 2009.

Offering counsel to me a few weeks after publishing the XMRV study, Wessely suggests, “My advice to you—which of course you will not take—is to wait a little [before publishing].  I think your piece might be more informative in the coming weeks as other groups begin to publish.” 

This article, “Blood Feud,” Part 1 is copyright © CFS Central 2010.  All rights reserved.   You may quote up to two paragraphs from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is from CFS Central.

Next week:  BLOOD FEUD, Part 2.  As Dr. Simon Wessely forecasted, a second group of British CFS researchers weighed in within weeks with a study that didn’t find any firm evidence of XMRV in CFS patients.