FDA/NIH STUDY UPDATE

Dr. Randy Schekman, editor-in-chief of the Proceedings of the National Academy of Sciences (PNAS), where the FDA/NIH XMRV ME/CFS paper had been accepted, gave CFS Central an update.  The NIH's Dr. Harvey Alter, one of the authors of the study, told Schekman that he'll be returning the paper to the journal "within weeks."  After that, the PNAS editorial board will consider the paper, which, Schekman says, is "standard procedure."  The FDA/NIH study found the retrovirus XMRV in the majority of ME/CFS patients that it tested.

COWARDLY ACTS and EVERYDAY REBELLIONS

The Old Guard versus the Crackbrained 
and big news at the end of this post

“When a true genius appears in this world, you may know him by this sign, that the dunces are all in confederacy against him,” wrote Jonathan Swift in 1706.  With that one sentence, Swift deliciously summed up the abuse the gifted suffer at the hands of the ordinary and provided the prophetic title for John Kennedy Toole’s 1980 best-selling novel, A Confederacy of Dunces.  

That manuscript’s first editor wanted the book reworked to make it more marketable, but after much dickering Toole refused, sank into a warren of depression and paranoia, and committed suicide.  Toole’s tormented mother spent a decade fielding rejection notices from publishers before the book was finally published—and won the Pulitzer Prize.

When 17^th century British physician William Harvey argued that the heart was not a spiritual entity but rather just a pump that circulated blood, he was dismissed as “crackbrained.”  Harvey’s theory flew in the face of the 1,400-year-old widely held “fact” that blood originated in the liver, snaked through the heart and drained into the tissues.

Change may be inevitable, but it isn’t measured or fair.  It’s bitter and bloody with the old guard on tenterhooks, fighting to the death to stave off its own obsolescence.  “Unrewarded

genius is almost a proverb,” remarked Calvin Coolidge in 1914.  “Yes,” bemoaned playwright Oscar Wilde, “the public is wonderfully tolerant.  It forgives everything except genius.”

Cowardly acts
Institutions—entrenched in the status quo, jealous guardians of their turf—stomp out creativity and color inside the lines.  The result is that throughout history many brilliant, defiant minds have lived haunted lives of ridicule and disaster, while their sheep-like counterparts prosper.  The abuse the gifted suffer from those who are not is, like all cowardly acts, based on fear.

That is why French chemist Louis Pasteur, who had already created in 1885 the first therapeutic vaccine (for rabies) and who would go on to invent pasteurization and prove that microbes caused infectious disease and fermentation, was nonetheless denied admittance to the prestigious Academy of Sciences, in Paris.  According to biographer Patrice Debré, Pasteur wrote a prophetic letter to his wife about it:  “Everyone knows that I am the valid candidate…. But they are afraid (at least many of them are) of chemistry.  They are saying that chemistry wants to take over everything.”  Pasteur was not surprised when the Academy rejected him.

Pasteur’s germ theory built on the work of Hungarian obstetrician Ignaz Semmelweis, who was ridiculed for his seemingly modest request that in the interim between doing autopsies and delivering babies, physicians wash their hands.  Semmelweis reasoned deductively that the high postpartum mortality rate among new mothers following delivery by male physicians, as opposed to the low mortality rate by female midwives, was due to infection from a “poisoned” cadaverous substance, inadvertently passed on by physicians who went directly from autopsy room to delivery room. 

The midwives, however, didn’t conduct autopsies, so their hands were, relatively speaking, clean. Now known as sepsis, in Semmelweis’s time the infection was called childbed or puerperal fever.  But Semmelweis’s theory was dismissed, and his distress over thousands of women needlessly dying landed him in a mental institution, where he spent the remainder of his life.

Now even kindergartners know to wash their hands when they’re dirty.

Emergence versus acceptance
The late physicist and science historian Thomas Kuhn, who authored the groundbreaking book The Structure of Scientific Revolutions in 1962, believed the lag between the emergence and acceptance of new ideas is natural and inevitable.  Change, he postulated, can come about only after long periods of stasis because “frameworks must be lived with and explored before they can be broken.” 

Compounding the inertia, and contrary to popular belief, Kuhn held that most scientists are not objective and independent thinkers.  Rather they are conservatives who do their best to implement exactly what they've been taught.  While Kuhn addressed the scientific process, this rigidity is characteristic of all disciplines and is longstanding.  “Inventions have long since reached their limit, and I see no hope for further development,” claimed a blasé Julius Sextus Fontinus, a Roman engineer, in the first century after Christ. 

Nearly two thousand years later, in 1943, an equally blinkered Thomas Watson, then chairman of IBM, declared:  “I think there’s a world market for maybe five computers."
   
Abram Hoffer and Linus Pauling
In the 1950s, the great Canadian psychiatrist Abram Hoffer, an early proponent of vitamin therapy, and two of his colleagues discovered that high-dose niacin lowered bad cholesterol and raised good cholesterol. Later, Hoffer joined Nobel laureate Dr. Linus Pauling to test out Pauling’s theory that Vitamin C was an effective adjunct therapy for cancer patients.  The duo found that the vitamin prolonged the length and the quality of life, and in some cases, particularly in lung cancer, effected long remissions. 

In response to both findings, the medical establishment vilified them.  The bruised Pauling was offended that no one would listen.  But the circumspect Hoffer reasoned that it can take two generations—forty years—for new ideas to be accepted.  With all the speed of a glacier melting (in pre-global-warming time), scientific derision morphed into doubt and, finally, acceptance of niacin as a cholesterol remedy.  While vitamin C hasn’t exactly been embraced as a cancer treatment, in the past few years researchers at the NIH and elsewhere have found it to be effective.  
  
Paul Cheney and Daniel Peterson
In 1984, Dr. Paul Cheney and Dr. Daniel Peterson contacted the CDC about an outbreak of a debilitating illness afflicting the residents of Incline Village, Nevada. As chronicled by Hillary Johnson in her book Osler's Web, epidemiologists Jon Kaplan and Gary Holmes arrived at the tony resort town, saw about 10 ME/CFS patients, then went gambling and skiing.  Twenty-six years later, not much has changed as far as the government response to ME/CFS is concerned.  As a result, many physicians, researchers and citizens still don't understand that it's a grave and sometimes fatal neuroimmune illness. Some continue to debate its existence, as if the disease were a matter of theology, not science. 

Was Abram Hoffer right?  Will it take another 14 years before the government stops shrinking back and dismissing the collection of scientific data, if by their denial they could make fact fiction and alter the grim misadventure this disease has become?  Or, perhaps the fed-up patients will push through and the FDA/NIH XMRV Chronic Fatigue Syndrome study will be published intact in the Proceedings of the National Academy of Sciences, and, like the flip of a switch, the energy changes.

 ***

Apparently, at least for today, it's the latter.  The news from the CFIDS Association this morning:  "The [FDA/NIH] researchers have conducted additional experiments as requested by the reviewers, and their paper is expected to be published in the Proceedings of the National Academy of Sciences within weeks."  Sources to CFS Central say that the researchers' conclusions have not changed.  PNAS Editor Dr. Randy Schekman is on vacation and could not be reached for comment.
 

This article, “Cowardly Acts and Everyday Rebellions,” is copyright CFS Central 2010.  All Rights Reserved. You may quote up to 150 words 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 Mindy Kitei for CFS Central.  You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue.  Instead, refer readers to this blog to read the article.

"Dear Sirs: I am SICK"

As many of you know, in 1996, the publisher and a reporter at the New York Native newspaper contacted New York Congressman Jerrold Nadler about the CDC’s financial improprieties where ME/CFS was concerned.  Their action  led to a congressional investigation that proved that CDC scientists siphoned millions of Congress-appropriated ME/CFS dollars to what then-CDC director Jeffrey Koplan told the Washington Post were "more important" maladies, including measles and polio. 

The New York Native learned about these abuses by reading Osler's Web, Hillary Johnson's landmark book about years of governmental neglect and abuse of ME/CFS patients.  Dismissing the disease as a trivial and psychogenic problem, the CDC had such disdain for patients that it even concocted, Hillary Johnson wrote, a letter from a phony patient "I. M. Zappode," which began, "Dear Sirs: I am SICK.... I am so tired it took me 6 days to dictate this letter to my secretary. Please send me all available information and I mean ALL about CEBV, CMV, HSV, VZV, HPV, HTLV III/LAV/HIV, RSV, HAV, HBV, SV40...." The bogus letter went on like that.

Nadler still represents New York, but if enough patients write in, what senator or congressman wouldn't be interested in the safety of the blood supply?

FDA/NIH PAPER IN LIMBO; PATIENTS UNITE

CFS Central has learned that it was the CDC that made the initial request to pull the FDA/NIH XMRV paper after the Proceedings of the National Academy of Sciences (PNAS) accepted it. Sources have told CFS Central that higher-ups in the Department of Health and Human Services (HHS) made the ultimate decision to hold up the study.  In addition, insiders said that HHS can keep any government study from being published—no matter how solid—and that it is anyone’s guess whether the FDA/NIH paper will eventually be published.

The FDA/NIH study found the newly discovered retrovirus XMRV in most ME/CFS patients in a New England cohort that it tested, as well as in up to 7 percent of healthy controls.  That 7 percent would translate into nearly 20 million people in the United States and signals concerns for the safety of the blood supply.  As a comparison, 1 million Americans are living with another retrovirus, HIV/AIDS.  The Japanese Red Cross issued a disturbing report that XMRV has been detected in nearly 2 percent of Japan’s blood supply.  This year, Canada, Australia and New Zealand banned patients with CFS from donating blood due to the concern about blood safety.

Another government XMRV paper, this one by the CDC, failed to find any evidence of the retrovirus in patients or healthy controls and was published in Retrovirology July 1. The Wall Street Journal had reported on Wednesday, June 30 that both the CDC and the FDA/NIH papers would be put on hold until a consensus could be reached—or until it became clear how the agencies reached opposite conclusions.  But in an abrupt about-face, the CDC ended up publishing its paper on Friday, whereas the FDA/NIH paper remains in limbo.  CFS Central sources said that some scientists attempted to halt the release of the CDC XMRV paper to no avail.

On Friday, I asked the CDC's Dr. Steve Monroe, director of the agency's division of high consequence pathogens and pathology, why the CDC requested that the FDA/NIH study be held, and he replied in an email, "When CDC, FDA, and NIH learned that separate studies had been conducted with differing results, a collective decision was made to try and account for these differences.”

PNAS paper already in galleys

Highly placed insiders tell CFS Central that PNAS had not only accepted the FDA/NIH paper, it was in galley proofs when it was pulled.  After a manuscript is accepted and edited, it goes into galleys for review by authors and editors before being published.

Dr. Randy Schekman, the editor-in-chief of PNAS and professor of cell and developmental biology at the University of California at Berkeley, told CFS Central that he couldn’t comment specifically on any unpublished paper.  He advised talking to the NIH’s Dr. Harvey Alter, the principal investigator of the FDA/NIH study. Alter is best known for pioneering work in "non-A, non-B hepatitis," now known as hepatitis C.  Responding through a press officer, Alter said that the XMRV research data can’t be discussed until it’s published.

Randy Schekman said, however, that putting a hold on a paper is unusual and has occurred only one other time that he knows of in his nearly four-year tenure as PNAS editor-in-chief.  In that case, Schekman himself held up the paper, which was eventually published.  Precise in the way that scientists usually are, Schekman qualified, “But there may have been other examples handled by the staff that never rose to the level of urgency that required my attention.  A common example where I would not have gotten involved is when the author holds off in the interests of coordinating his or her paper with someone else’s paper, in the spirit of cooperation.”

Dr. Judy Mikovits

Dr. Judy Mikovits of the Whittemore Peterson Institute (WPI) in Reno, Nevada, was the principal investigator of the XMRV October 2009 Science study that found the retrovirus in 67 percent of 101 ME/CFS patients and 3.7 percent of controls. A July 2 WPI press release noted, “The methodology used by the CDC was not the same as that used in the WPI study nor was the patient selection criteria.  In September 2009, WPI sent the CDC 20 confirmed positive samples and the appropriate methodology to help them develop a clinically validated test.  However, this team chose not to do this.” 

Mikovits told CFS Central that the CDC wouldn't be able to find virus in the samples her lab sent.  “The CDC assays [chemicals used to do experiments] as published in Retrovirology would absolutely not detect XMRV in a human sample,” Mikovits explained.  “Switzer [Bill Switzer, the principal investigator of the CDC study] said in his paper that if XMRV were there, his assays would have detected it, but this is not the case.  There is a difference in the analytical sensitivity and the clinical sensitivity of an assay.  The simple fact is that the CDC’s assays have never detected XMRV in a confirmed positive clinical sample.  It does not matter the population, they could not detect XMRV if it was there.”

As reported on this blog, on Friday I asked the CDC’s Switzer in an email if he had tested the confirmed positive samples sent to the CDC, and, if so, did he find XMRV in them or not?  Switzer sidestepped the questions with this reply:  “As reported in Retrovirology, this study used and tested samples that were collected in CDC-sponsored studies of CFS, as well a set of healthy blood donors.  Continued efforts are underway to learn more about XMRV, including work with other HHS [Health and Human Services] agencies and non-governmental organizations to standardize testing methods across all XMRV studies.”

In his study, Switzer did not include that Mikovits sent positive XMRV samples to the CDC.  CFS Central has learned that two other labs have confirmed the samples sent to the CDC as XMRV positive.  In addition, CFS Central has learned that another lab sent the CDC blood samples that were positive for XMRV as well. 

Dr. William Reeves

Another of the CDC’s study authors is Dr. William Reeves.  After Judy Mikovits’s study was published in October, the then-head of CFS research at the CDC 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 likely culprits behind CFS were sexual and emotional abuse and an inability to handle stress.  During his two-decade tenure as the chief of CFS research, Reeves focused on psychiatric research into CFS, including his 2006 paper on CFS coping styles, which found patients guilty of “maladaptive coping” and “escape-avoiding behavior.” Reeves was transferred out of the department on February 14.

Dr. Walid Heneine

Still another of the CDC XMRV study authors is Dr. Walid Heneine.  Back in 1993, Heneine served as one of the CDC researchers conducting the study that attempted to corroborate the first paper to link CFS to a retrovirus. In 1991, Dr. Elaine DeFreitas of the Wistar Institute at the University of Pennsylvania wrote that paper that linked ME/CFS to a novel retrovirus, which was, ironically, published in PNAS.  (It’s not clear whether XMRV and DeFreitas’s retrovirus are the same, though preliminary evaluation indicates that they are not.) 

Twenty years ago, the CDC researchers weren’t able to replicate DeFreitas’s work and, as with the current study, they didn’t use the same methods and assays, prompting many patients, physicians and researchers familiar with the events of the past to feel a sense of déjà vu. 

In addition, the current batch of CDC scientists sent XMRV samples to the Robert Koch Institute in Germany for outside confirmation.  The Koch Institute didn’t find XMRV either, though some researchers believe that was to be expected since the Institute didn’t find XMRV in a 2009 prostate cancer study.  (XMRV was first detected in a virulent form of prostate cancer by American researchers back in 2006.)

Patients unite

Many patients report being appalled with the events of last week.  “The scientists at NIH and CDC are supposed to be just that:  scientists,” said patient advocate Dr. Mary Schweitzer, who has ME/CFS and is XMRV positive.  “In all avenues of scholarship, medical science included, disagreement is an expected part of the process—particularly in a new avenue of research. There should be nothing wrong with conflicting results from dispassionate scientists working on the same problem.  But the patients… are used to seeing politics, not science, from our public health agencies.

“After AIDS was recognized, American insurance companies took a serious hit because they had not prepared for the contingency that a new, deadly disease could emerge.  With CFS, they were facing the same thing—if the disease was recognized for what it really was.  We’ve had evidence of biomarkers, immune defects and active viruses in subsets of patients with CFS for two decades.  Each time, the CDC has done a quick study, declared that “Agent X” is not “The Cause” of CFS, and that was the end of funding, the end of publication, the end of the research.

“The CDC's website on CFS insists there is no relationship between CFS and abnormal Rnase-L [an antiviral pathway], chronic EBV [Epstein Barr Virus, which causes mono], abnormal natural killer cell function [immune cells that, as their name suggests kill pathogens], abnormal brain scans, and other tests and biomarkers that could have been used to identify subgroups of patients within the larger group of one million or more adults estimated to have CFS.  Why would that have made a difference? Because there were therapies and treatments that then could have been used to help those patients.

“Of course, private insurance companies, Social Security disability, and Medicare would have had to pay to take care of so many sick people, and they would have had to pay for their treatment. In place of a serious effort to define and treat subgroups of CFS patients, the CDC adopted the approach of British psychiatrists—indeed, CDC's website steers medical professionals to the UK for instructions on how to treat CFS.  Cognitive behavior therapy [a type of psychotherapy], graded exercise, and perhaps some antidepressants.  That’s it.

“This strategy perhaps made financial sense in the short run.  If XMRV does turn out to be a factor in even half the cases of CFS, that would be about as many people as have MS.  Again, if XMRV proves significant, it’s a little late to worry about getting it out of the blood supply:  That horse left the barn 25 years ago when the disease exploded in cluster outbreaks across the country.  But the CDC did nothing.

“And what about those of us who do have HHV-6 Variant A? What about those of us with the 37kDa Rnase-L defect?  That’s where former CDC colleague Suzanne Vernon’s comments
make one wonder.  According to Vernon, the samples used by the CDC team when searching for XMRV were stored in such a way that viral evidence would have been destroyed. They needed samples in green-topped, sodium heparin tubes. They were stored in something else.  That strategy, which would have ensured no virus was found, would have worked to ‘disprove’ the existence of defective Rnase-L and HHV-6, too.  Unless the samples were stored with a sodium heparin solution, the samples would have been useless.

“The longer the CDC insists that there are no tests or treatments for CFS, the sicker the patients get.  Some have already died of heart disease or rare cancers. The longer the CDC is permitted to pretend CFS is due to an abnormal stress response, the more people become infected with the underlying causes of the disease.  It is a remedy that is short-run smart, long-run stupid. After 25 years, the long run is here.”

Blood-bank demonstration

Some ME/CFS patients are demoralized over the FDA/NIH paper being pulled and the CDC paper being published.  Some are angry.  But there’s something new:  The birth of a powerful, organized, articulate, mad-as-hell-and-not-going-to-take-this-anymore brand of advocacy unleashed by the Internet.  Patients from all over the world are connecting in patient forums and on blogs, private messaging each other, planning their next moves.

One of those patients is W.L. Karns.  “Even after all the CDC has done over the years to suppress the seriousness of our illness, it’s still numbing to see them continue to spread disinformation disguised as research,” explained Karns, who’s had ME/CFS for 23 years. “The CDC ministers of propaganda who wrote the XMRV study are cunning.  They even released the study before a holiday, hoping to minimize the backlash they knew would follow.  I can’t tell you the anger I feel about the CDC’s continuous abuse and contempt for the people they’re supposed to be helping.

“Twenty-five years of willful inaction by the government when it comes to this illness have convinced me that patients must empower themselves like the AIDS patients did. Twenty years ago [AIDS activist] Larry Kramer and ACT UP [AIDS Coalition to Unleash Power] became fed up with the AIDS response by the government and conservative advocacy groups—including the Gay Men’s Health Crisis, which Kramer himself started.  They just weren’t getting anything done, and people were dying, like today.  The leading advocacy groups were too cozy with the government, and they cared more about their own welfare than the patients.  Then, ACT UP came up with an incredibly effective slogan:  Silence = Death.

“I propose we start a worksheet on [the patient forum] Phoenix Rising Wiki pages to plan, ask for volunteers and track demonstrations to increase public awareness of the situation.  Patients who aren’t bed-bound or house-bound can congregate outside the busiest blood banks and disseminate information to inform people that researchers have found a new retrovirus in people with ME/CFS, and that the blood supply is contaminated—but that the government is suppressing the information. 

“I believe we need to act quickly, before the FDA/NIH paper is killed.  Those of us who are too sick to go to the blood banks could get a family or friend to stand in their place.  For maximum exposure, we’d alert the media and hand out leaflets.  We could record the demonstrations and put them on Youtube, Twitter and Facebook.  That’s something ACT UP couldn’t do 20 years ago.  Let the message go viral—pun intended.  Surely the million of us in the United States and a quarter million in the UK and elsewhere can unleash the power of the media and the Internet to change things so the public and the government will finally hear us.  I’m tired of being barely alive, I’m tired of being invisible, and I’m tired of being silent.”  

###

To understand more about the CDC’s complicated ME/CFS history and XMRV research, see “Blood Feud” Part 1 and Part 2.  To read the CFS Central interview with CDC scientists on their XMRV study, see “Q and A with CDC Scientists.”

This article, “FDA/NIH Paper in Limbo; Patients Unite” is copyright CFS Central 2010.  All Rights Reserved. You may quote up to 150 words 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.  You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue.  Instead, refer readers to this blog to read the article.

THE CASE OF JOAN IRVINE

California resident Joan Irvine came down with ME/CFS the day after a blood transfusion during surgery to repair a shattered hip and thigh in 1987.  She sought treatment with Dr. Daniel Peterson.  Seeking answers, she wrote in 1992 to Dr. William Reeves, who was already heading up research into this disease at the CDC, as well as Dr. George Rutherford, then chief of the infectious disease branch of the California Department of Health.  Both men advised against donating blood. 

Two readers sent in Irvine's letters to Reeves and Rutherford today, as well as her synopsis of the events.  You can read them here: http://www.cfs-news.org/joan.htm

Irvine’s ME/CFS case was virulent, and she committed suicide in 1996.

NEXT:  What happened with the FDA/NIH study, and patients' call to action.

Q and A with CDC SCIENTISTS

Through emails, CDC scientists Bill Switzer, lead investigator of the CDC XMRV study, and Dr. Steve Monroe, director of the CDC’s division of High Consequence Pathogens and Pathology, discussed the agency's XMRV study, published in Retrovirology July 1.  The study found no evidence of the retrovirus in the CDC's Chronic Fatigue Syndrome patients and controls.

I also asked Switzer and Monroe questions about the FDA/NIH XMRV study, which found the virus in CFS patients and had been accepted by Proceedings of the National Academy of Sciences only to be put on hold, which was reported June 30 in the Wall Street Journal.

A CDC press officer emailed Switzer’s and Monroe’s replies on Friday at 5:10 p.m.  Monroe had already left for the day; Switzer for a week’s vacation. Thus, there could be no timely follow-up.

CFS Central:

“My sources tell me that there were at least 20 XMRV samples confirmed to be positive from several other labs that were sent to you for the CDC study.  Did you test these samples, and what were your results when you tested the samples? Did you find XMRV or not?”

Bill Switzer MPH, lead investigator of the CDC XMRV study:
“As reported in Retrovirology, this study used and tested samples that were collected in CDC-sponsored studies of CFS, as well a set of healthy blood donors.  Continued efforts are underway to learn more about XMRV, including work with other HHS [Health and Human Services] agencies and non-governmental organizations to standardize testing methods across all XMRV studies.”

CFS Central:

“Why did the CDC request the FDA/NIH study be put on hold pending more research?”

Dr. Steve Monroe, director of CDC’s division of High Consequence Pathogens and Pathology:
“When CDC, FDA, and NIH learned that separate studies had been conducted with differing results, a collective decision was made to try and account for these differences.”

CFS Central:

“Why couldn’t both the CDC and the FDA/NIH papers be published and then the agencies do follow-up research to resolve the differences in your findings?”

Monroe:
“Timely discussion among researchers regarding the specifics of scientific studies is common and can help them more readily account for the direction of further research.  Future research will benefit from the knowledge gained from the Retrovirology study and other studies that have attempted to learn more about this novel retrovirus.”
 
CFS Central:

“Why didn’t the CDC try to culture XMRV?  (That’s what the Lombardi study did.)” [Published in Science in October 2009, that study found XMRV in 67 percent of 101 CFS patients.]

Switzer:

“It is unclear whether or not performing culture on all samples would have improved the ability to detect XMRV. The CDC Retrovirology study used the same PCR testing methods of a previously published study that found an association between XMRV and CFS. While CDC could not confirm an association between XMRV and CFS, the method utilized in the study provided the best means of detecting XMRV if it was present.”

CFS Central:

“Why didn’t the CDC use blood tubes intended for use with virus isolation as the Lombardi study did?”

Switzer:
“Many blood collection tubes with a variety of anticoagulants can be used for virus isolation. The archived specimens we used were collected with anticoagulants that are not known to interfere with either PCR testing or virus isolation.”

CFS Central:

“According to your paper, the CDC used the ‘revised Fukuda’ AKA Empirical definition of CFS…. The CDC study cohort, as defined by the Empirical definition, includes many people who are simply depressed and tired but do not have Chronic Fatigue Syndrome. How can this CDC cohort be valid if it includes people who are just tired and depressed?”

Monroe:
“All subjects in the study met the 1994 International Research Case Definition for CFS. One aspect of the definition is its ability to distinguish between subjects who may suffer from CFS symptoms, such as tiredness or depression, but do not have CFS.  CDC used samples from CFS subjects who fully met the 1994 case definition and healthy controls that were collected from two previous population-based studies in Wichita, Kansas and metropolitan, urban and rural populations in Georgia. In addition, CFS patients from the CDC Health Care Provider-based Registry of Unexplained Fatiguing Illnesses and CFS were included.

“Thus, CDC used population-based and clinic referral samples. This enabled us to examine sudden onset cases and those that develop gradually. The use of both types of samples in this study helped us to more precisely examine whether or not infection, such as through XMRV, might have played a role in the onset of symptoms.”

***

Having had none of my questions answered by the CDC, I turned to other sources.

Coming up:  THE FDA/NIH XMRV PAPER—and ME/CFS PATIENTS—IN LIMBO.  Plus, one patient’s solution:  A united demonstration of solidarity at blood banks in every city, in every country, and on every continent to inform the public that Health and Human Services is withholding the publication of the FDA/NIH XMRV study and that the newly discovered retrovirus may be contaminating the blood supply and infecting millions of people.


This article, "Q and A with CDC Scientists," is copyright CFS Central 2010.  All Rights Reserved. You may quote up to 150 words 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 Mindy Kitei for CFS Central.  You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article.

CDC and FDA/NIH STUDIES ON HOLD

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.

 

DETERMINING XMRV'S MUTATION RATE

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.

NEW ME/CFS DOCUMENTARY

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.”

What About Me? Trailer - UK from Double D Productions on Vimeo.

What About Me? Trailer - USA from Double D Productions on Vimeo.

You can find out more about the film here: http://www.whataboutme.biz/

HARD CELL

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.

ARE YOU SMARTER THAN A 9th GRADER?

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.

BLOOD FEUD: Part 2

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 15^th 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 myocarditis—an infection of the heart—and 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.