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.”  

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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.