The findings by the NIH and FDA that XMRV is associated with chronic fatigue syndrome has been accepted for publication by the Proceedings of the National Academy of Sciences (PNAS). Release of the article has been blocked by PNAS due to work carried out by the US Centers for Disease Control and Prevention (CDC). That study, which was submitted to Retrovirology, failed to find a link between XMRV and CFS. Its publication has also been placed on hold. According to ScienceInsider:
The contradiction has caused “nervousness” both at PNAS and among senior officials within the Department of Health and Human Services, of which all three agencies are part, says one scientist with inside knowledge.
It is senseless to block publication because the two papers reach different conclusions. If both manuscripts were subjected to proper peer-review, and were deemed acceptable by the referees, then they should be published. The journal editorial offices must respect the opinions of the reviewers. By overriding their decisions, they have compromised the entire peer reviewer process.
Blocking publication also sends the wrong message to CFS patients, to the public, and scientists. Not only does this action raise suspicions about their motives – are they trying to publish only the result they believe is correct? – but it ignores the very important fact that science is self correcting. Scientists are humans, and they make mistakes. But eventually the right answer will come to the surface. And that is why PNAS and Retrovirology should respect peer review, publish the XMRV papers, and let science correct itself.
Update: As noted in the comments section, the results of the CDC study have been published in Retrovirology.
“…before we see suffering like in we have for people with neuropsychiatric disorders throughout history.”
Marie, it is far too late to have avoided this. People have been dying from ME for decades.
Research takes time – Agreed. BUT these people with CFS are so ill, this does have to be classed as an emergency and a race against the clock to find the answers.
Some cannot walk, Others haven't been out for years, Some cannot feed themselves.
They live a life simular to the elderly, 20 year olds with a worse quality of life then a 90 year old.
If there is the remote chance we have made a discovery as to why they are sick, we cannot wait years, we have to use all the money & resouces we have. These people have no quality of life and NO medication, No treatments, they are just stuck, they deserve the treatment that all other illnesses have.
It's time to end the mystery….do it for the 17 million who have CFS. We are all waiting to join the rest of you back in the world.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC287…
The above paper describes sick people who have CFS. It describes serious immune system dysfunction using bio markers that can be repeated by other researchers.
The CDC criteria does not:
(http://www.fatigueregistry.org/Sites/fatiguereg…) :
• Current severe fatigue persisiting for one month or longer
• One of the following for at least one month:
– Unrefreshing sleep,
– Problems with memory or concentration, or
– Unexplained joint or muscle pain in the lower extremities
• Age: 12 to 59, inclusive
• Body mass index (BMI) les than 40.0
CFS patients don't mean to push away researchers. They are just so tired, worried, sick and scared of being ignored again like they have been for the last 30 years.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC287…
The above paper describes sick people who have CFS. It describes serious immune system dysfunction using bio markers that can be repeated by other researchers.
The CDC criteria does not:
(http://www.fatigueregistry.org/Sites/fatiguereg…) :
• Current severe fatigue persisiting for one month or longer
• One of the following for at least one month:
– Unrefreshing sleep,
– Problems with memory or concentration, or
– Unexplained joint or muscle pain in the lower extremities
• Age: 12 to 59, inclusive
• Body mass index (BMI) les than 40.0
CFS patients don't mean to push away researchers. They are just so tired, worried, sick and scared of being ignored again like they have been for the last 30 years.
This is a science blog. While everyone's feelings and opinions are certainly valid this is not a patient discussion forum where anything goes.
I would like the echo the sentiments of my fellow-patient's posts and add that I highly doubt the leader in the discovery of hepatitis C, Dr. Alter, produced a questionable paper. I am sure you are used to open and transparent scientific debate which is what we, the very ill patients, deserve. We demand that the original Alter be published for an open and honest review.
We will accept a negative XMRV result, heck no one would WANT an retrovirus, but we have suffered long and hard and want honest, unbiased and thorough, science to be applied – to rule this in or out – so we can get on real treatments before it's too late for us and the next generation.
The stakes are very high, not just for ME/CFS, but for men at risk for prostate cancer, not to mention the blood supply.
Thank you.
Otis
Pete S: I've been sick for 16 years. The day I got sick I had been out on my bike for what was a normal 60 mile Saturday ride. The first sign was lymph node the size of a plum.
I now count the number of days a week I am able to shave, shower or leave the house so my doctor can track my “progress.”
I have a 75 year old neighbor who had quadruple by-pass surgery six weeks ago. He's FAR more active than I am. Another 65 year old neighbor was diagnosed with ALL (leukemia) four months ago. She's been through four rounds of chemo and she stops in to check on me and say to say hi while she's out on her walks; walks that I can't even dream of doing.
The CDC would never have included me in their recent study because of all the neurological problems I experience but they have absolutely no interest in what is causing my neural and immune systems to collapse. They have treated this with a gallingly cavalier attitude as millions more become ill with an illness they can't even be bothered to recognize because it threatens their proprietary notion of Chronic Fatigue Syndrome (the Canadian Consensus Dx Criteria has been available for 10 years).
I got sick when I was 31. I'm now 47.
Bill Reeves is betting the bank that there is no hell nor is there a vengeful God.
To the scientific community, the withdraw of a paper is an appalling aberration and an attack on the integrity of the institution of science.
To a CFS patient it just another day dealing with the government.
Sorry Guys, welcome to our world. Thirty plus years of the same BS and STILL counting.
On the CDC XMRV Update page they hide the fact that they are using Reeves Criteria and instead twice say they are using Fukuda!!! This goes beyond mere fudging. These are lies.
From CDC XMRV Update webpage:
“Patients from both groups had CFS that met the criteria of the 1994 International CFS Research Case Definition, which was established to help distinguish CFS from other illnesses that cause fatigue.
All CFS patients received a clinical assessment and had a diagnosis that met the criteria of the 1994 International CFS Research Case Definition. The use of specimens from two types of CFS study populations (population-based and physician referred) enabled the CDC study team to assess potentially different types of CFS illness. For example, the participants from population-based studies tend to have a more gradual onset of illness compared with physician-referred patients, who tend to have a more sudden onset of symptoms.
The study reported in Science tested samples from a repository containing specimens from CFS patients, but information about the repository and the CFS patients was insufficient to allow a meaningful comparison of groups evaluated by the two studies.”
As noted by others, Dr. Vernon said that the CDC study was trying NOT to find XMRV. That is extremely damning considering the source: Dr. Vernon worked for Reeves at the “CFS” program and is a co-author of the Reeves Criteria.
WTF? GTFO?
Reeves Criteria are NOT ME/CFIDS patients they are WTF & GTFO: Wichita Tired and Fatties and Georgia Tired and Fatties Only!!
This is like trying to pass off a study of tired people as a study on MS or Leukemia! Sure, fatigue is a very prominent symptom of these diseases, just as in ME/CFIDS, but that doesn't mean you can just study tired people and lie and claim you studied MS or Leukemia cohorts!
If anyone tried this they would be rightly run out of science. But Reeves , Heneine and co-conspirators have been persecuting us for a quarter century and they have no choice but to continue because if the truth gets out, they will go to prison. Please stand up for science! Please speak out against them or they will continue their war on science as long as they can! Thank you!
In these two articles published after your blog post, it sounds like it was the author's own decision to “pull it back” and conduct more experiments in response to reviewers' questions.
http://news.sciencemag.org/scienceinsider/2010/…
“UPDATE 2 July: The authors of the PNAS paper have decided it needs more work. Corresponding author Harvey Alter of the NIH Clinical Center, who is in Berlin this week, issued this statement on 30 June: 'Our paper has not yet been accepted for publication. My colleagues and I are conducting additional experiments to ensure that the data are accurate and complete. Our goal is not speed, but scientific accuracy.' NIH spokesperson John Burklow explained to Insider that the paper had been accepted, but Alter and his co-authors decided to 'pull it back' and revise it in response to questions raised by reviewers.”
http://blogs.wsj.com/health/2010/07/01/cdc-team…
“John T. Burklow, a spokesman for NIH, says the FDA-NIH paper has been accepted for publication but that the authors decided to pull it back to conduct additional experiments.”
KAL, this is Dr. Rancanciello's blog. If he decides any comments are inappropriate — i.e. a “patient discussion forum where anything goes” – it's certainly within his rights to remove it. Otherwise, who died and made you the blog police?
Oh and by the way, some of us are scientists who are affected by CFS. I'm sorry to inform you that the initials after your name do not protect you from CFS. I have 7 initials after my name and it didn't do anything for me.
Similarly for the other (CDC, Retrovirology) paper. It sounds like the block came from the Department of Health and Human Services, not the journals' editors.
http://online.wsj.com/article/SB100014240527487…
“Kuan-Teh Jeang, editor-in-chief of Retrovirology, said the Switzer paper went through peer review and was accepted for publication when he got a call from the authors earlier this month. They asked that the Retrovirology paper be held.
'My understanding was HHS [Department of Health and Human Services] wanted to get it straightened out. Both reports are from different branches of the government,' Dr. Jeang said.
In an email between scientists familiar with the situation, viewed by the Wall Street Journal, a researcher said the two teams were asked to put their papers on hold because senior public-health officials wanted to see consensus—or at least an explanation of how and why the papers reached different conclusions, said the people familiar with the situation.”
http://blogs.wsj.com/health/2010/07/01/cdc-team…
“Switzer says that after the FDA-NIH team submitted a paper with results different from their own, the CDC group decided to take a 'scientific pause' to look at both papers, compare study methods and do additional experiments. After this review, they decided to proceed with publication—and he says no changes were made to their original manuscript.”
Thank you for continuing to follow this story and supporting the need to have both papers published. Scientists need to see both “positive” and “negative” studies to learn from them and governmental interference sets a poor precedence for the free exchange of information and discussion that is needed to advance science. We need more people like you, Dr. Rancanciello, to speak up about such things. I know as a scientist with CFS, when I speak about it, other scientists are more willing to listen to what I say than to the average patient with CFS.
Scientists who have no interest in ME/CFS or XMRV should also take notice as this might also affect you in the future if your findings happens to contradict what the government finds “convenient.”
Absolutely, these papers should be published and without delay.
I still cannot believe what is going on here and what is done to science and all the sufferers. By using wrong diagnostic criteria (Reeves criteria!) which were made for diagnosing healthy or psychologically ill humans that suffer from fatigue for whatever non-somatic reason, the CDC is trying to disprove the existence of CFS and the connection to XMRV as a whole. This is the biggest scam for a long time and even I am a very calm person I want to walk up to whoever is repsonsible for this and tell him what a bastard he or she is.
Max Planck was completely right when he said:
““A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with itâ€
Your comments exactly echo those of my son's who has been ill now with ME/CFS for 5 years. No-one seems to care what becomes of him. He never leaves the house unless taken and that is to the doctor's surgery. The doctor doesn't understand the illness and therefore cannot hope to alleviate the symptoms let alone cure him. He saw the specialist at the hospital last autumn and his next appointment is in the Autumn of 2010. Whatever can they hope to do for a patient if they treat them in this callous way? He had a very good and interesting career before being afflicted and is only too keen to carry on interesting himself in the world around him when he is fit enough to do so. He is very keen to talk about the world news amongst many other topics and my daily 'phone call to him is taken up with current affairs, in which he would be so pleased to partake. It is all so infuriating when one reads the news that this terrible illness is 'make-believe'. There are so many intelligent, valuable, people out there being treated in this way because the powers that be see fit to ignore them. The sooner they get some acknowledgement and some research done the better.
WE MUST MARCH IN PROTEST!!
Calling all Chronic Fatigue Syndrome sufferers!
Those that can…..March in Protest!
Prof Racaniello,
A microbiologist posted this paper on an ME forum, which looks at successfully isolating a SFV from PBMC of a patient. It states:
J Virol. 1997 Jun;71(6):4821-4.
Simian foamy virus isolated from an accidentally infected human individual.
“For successful virus isolation, it was essential to stimulate the host lymphocytes by phytohemagglutinin and interleukin-2 for 2 weeks prior to cocultivation with permissive cells.”
So this microbiologist is saying that in the original Science XMRV/CFS paper, the researchers at WPI,NCI and Cleveland Clinic found it essential to use an amplification process to stimulate the PBMC so they could isolate XMRV.
However NONE of the negative XMRV/CFS papers, including this recent CDC paper, did this essential process.
So my question is, is this amplification process an accepted, normal step in such research for isolating various classes of retroviruses from PBMC?
And if so,how on earth did these papers pass peer review?
Even if it isn't normal procedure, but one sometimes known to be necessary, and since the Science paper had found it esential to do this, surely the researchers and the peer reviewers of these negative papers should have picked this up and required the researchers retest their samples with the addition of this amplification process?
Thanks Prof R for your writings on XMRV/CFS, please stick with us…
Prof Racaniello,
Here is Dr Suzanne Vernon's damning response to the CDC XMRV/CFS paper, “Blood from a Stone”, I've posted an exert below:
http://www.cfids.org/xmrv/070110study.asp
Blood from a Stone
Suzanne D. Vernon, PhD
Scientific Director
The CFIDS Association of America
“From what I can decipher, the samples were drawn from 18 people identified through a Georgia registry who met criteria described in the paper that is different from 1994 international CFS criteria. Eleven CFS cases and matched controls were identified from the Wichita studies, although it is not clear if these samples came from the longitudinal studies or the clinical study, and 22 CFS cases and controls from the Georgia community-based study. There is little indication that these three cohorts are comparable in regard to CFS definition, as each cohort was selected using different definition. The authors strenuously object to application of the Canadian case definition in other studies, stating that, “physical findings in persons meeting the Canadian definition may signal the presence of a neurological condition considered exclusionary for CFS.†Yet the physical findings listed are those commonly experienced by CFS patients, and one (tender lymphadenopathy) is a case-defining symptom of the 1994 criteria.
Further, the samples from these three study cohorts were collected using different types of tubes, each of which has a distinct way of being processed. As if this weren’t bad enough, none of the blood tubes used were of the same type used in the Lombardi study. (They used tubes containing sodium heparin that are intended for use with virus isolation). The blood tubes from the 18 Georgia registry patients are designed to collect whole blood and preserve nucleic acid; it is not clear where the plasma came from for these subjects since plasma cannot be obtained using these blood tube types. So the explanation for not finding XMRV in these samples is simple – this was a study designed to not detect XMRV using a hodge-podge sample set.”
The peer review process seems to be completely flawed when papers such as this CDC paper are allowed to be published.
Especially so when there has been so much controversy over this issue and one would have hoped that the peer reviewers and Retrovirology staff should have been hyper-vigilant to check everything was OK.
But look at the flaws Dr Vernon picks out, and I'm sure that is not all…..
The issue of tubes for storing blood, SURELY the peer reviewers should have spotted this?
And what about her comment about the 18 blood sample and how they could have got blood plasma?
And the issue of diagnostic criteria, this is a complete farce, but they manage to get this published.
I have a degree in Zoology. I used to have faith in science and peer review process but since having CFS (30 years, my husband and sister in law too)) and seeing what goes on in the name of science it is impossible to have any faith.
Either through monumental arrogance and incompetence, or design, the process is severely flawed and open to abuse at the expense of seriously ill patients and to the detriment of real scientists.
Why are real scientists not all standing up and exposing all this, defending the principles of their profession and defending patients?
PLEASE RELEASE FDA NIH PAPERS:
http://www.youtube.com/watch?v=PnWtTcCFlJY&feat…
PLEASE RELEASE FDA NIH PAPERS:
http://www.youtube.com/watch?v=PnWtTcCFlJY&feat…
Dr Racaniello,
Thank you again for keeping us up to date on XMRV. I would love to hear a podcast on this matter. Thank you for your time
You are all deluded. I know the real cause of CFS. It is a virus, brought to earth by beings from the Alpha Centauri system. This virus is indigenous to their home planets. They are using it to weed out the earthlings not capable of adapting to it. Thus, there will fewer humans to transport back to their home worlds to work as slaves, and they will be more resistant to falling sick once they arrive there. Dr. Reeves and the CDC are part of this plot. They are working with the beings trying to appease them, in hopes that they will be our overseers instead of slaves themselves. I was told all this by a high vibrational squirrel, in a local park, who has never lied to me in the past. I laugh in scorn at how little the rest of you truely know. Ha, ha, ha !
What's that ? You think I'm crazy ? Well, after 26 years of CFS, if I'm not crazy, I missed a really good opportunity !
Zippy
I guess the reply is that there are more appropriate forums for some of the comments. Like you, I'm entitled to my opinion and opinions are like belly buttons regardless of how many initials you have after your name.
The CDC has been very cunning in disassociating itself from the ME epidemics and inventing CFS which is afatigue definition without neurological signs or immunological abnormalities.
They do not claim to be studying ME but whatever they want CFS to be and therefore in their world they are correct in stating that neurological findings are exclusionary for CFS!
From the CDC website, Overview of CFS, they state:
http://www.cdc.gov/cfs/cme/wb3151/chapter1/over…
Various terms are often used interchangeably with CFS. CFS is the preferred term because it has an internationally accepted case definition that is used in research and clinical settings. The name chronic fatigue and immune dysfunction syndrome (CFIDS) was introduced soon after CFS was defined; there is no case definition for CFIDS, and the name implies an understanding about the pathophysiology of CFS that does not currently exist. Chronic active Epstein-Barr virus (EBV) infection (chronic mononucleosis) was thought to be the cause of CFS during the 1980s, and this association is now known to be rare. However, post-infection fatigue syndromes have been associated with EBV and other infectious agents. ***The name myalgic encephalomyelitis (ME) was coined in the 1950s to clarify well-documented outbreaks of disease; however, ME is accompanied by neurologic and muscular signs and has a case definition distinct from that of CFS.***
That is their get-out clause, they are not studying the neuro-immune disease ME and they can claim whatever they like about CFS. Time for patients to reclaim ME as their diagnosis?
The WPI apparently provided 20 XMRV +ve samples to the CDC in order to help them to validate their testing methodology and yet Switzer et al chose not to make any reference to that fact in their paper. Why ?
See WPI press statement : http://www.wpinstitute.org/news/docs/XMRV-CDC%2…
The big question is therefore – “Did they make use of those samples and if so, did their methodology manage to find the virus?” If they didn't, then why not?
Mindy Kitei offers an illuminating perspective on this in her CFS Central blog: http://www.cfscentral.com/?psinvite=ALRopfXnGE_…
Is it therefore any surprise that people who know these facts about what the CDC has done (or not done) are very angry and want to see the individuals responsible for distorting the sience, held to account.
27 here…. used to work out 3.5 hours a day, was in perfect physical condition. I worked as a community organizer 70+ hours a week. Degrees in physics, mathematics, and theology. I now have permanent flu like symptoms, neurological symptoms…i break out in rashes and get ulcers in my throat, i have tinnitus so bad sometimes i want to pop my ear drums. Post exertional malaise… just a long list of the same redundant symptoms.
… I have improved my diet, i take vitamins and herbal antivirals, i take amino acid supplements used for neuropathy in diabetes patients and i can still can't do day to day chores without help.
And the best part is… I'M UNINSURED. I don't need a treatment that makes me completely well… just something that could at least allow me to be healthy enough to get a part time job.
I can't tell if XMRV is a cause or not… enough descent studies haven't been done… it seems like there is at least a portion of the population that is healthy and has it, and if your studies aren't picking that up, it seems like you need to dig a little harder (IMHO). Either way, blocking the research findings is just ridiculous.
http://healthcare.change.org/petitions/view/xmr…
Jason you are so right. The two journals in question have brought their entire review process into question.
The truth is we do not know if the 'Science' paper is on the money. The only way we can start to get an answer to this question is though a replication study. All that patients want is the truth. Is XMRV associated or not. Not the continual smoke and mirrors that usually happen in CFS research. Unfortunately, the issues that have been raised around the 'Science' study and the negative studies, are indicative of this entire subject.
In the UK, it has been about ten years since the Medical Research Council funded biomedical research into CFS/ME, and the NICE guidelines only offer psychosocial support therapies (CBT and GET). The estimate on the number of patients in the UK is 250,000, and the Government accepts the WHO classification of CFS/ME as neurological. So why is it treated like an orphan disease, when clearly it is not.
Please stop SHOUTING.
Many of us are very interested – even those of us not currently studying viruses.
Maybe because the authors themselves want to be sure?
This will be tough to get past peer review.
Choose the best and the bravest journal you can find.
You may be venturing into rocky seas. A heads up .. you might want to leaf thru the book “Osler's Web” or just contact the MDs/PhDs that have been through this before. Also, the autism community is navigating rough seas, too.
I look forward to reading your papers.
Who is any legislative body, to tell Galileo that the earth doesn't revolve around the sun. Let the papers be published. Let science progress.
July 9, 2010 – Posted on CFIDS Assoc webpage (http://www.cfids.org/xmrv/default.asp):
The study pending from NIH/FDA attracted a lot of attention in June after news of its conclusions was leaked by a Netherlands news agency. The 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.
Speaking at a meeting at Tulane University on June 18, 2010*, Dr. Frank Ruscetti, one of the authors of the Science paper, listed the following “reasons for the lack of detection of XMRV” in his presentation:
* Greater sequence diversity than originally believed
* In vivo reservoir(s) of viral replication not identified
* World wide distribution scattered like HTLV-I
* Patient selection and methods applied vary widely
* PCR/other contamination.
*quoted with permission from Tulane University
it said they were already going to print… if he thought it was fine going to print… other sources said it was simply accepted, why did he suddenly change his mind? we don't have his direct statements as to why the study was pulled. we have statements from those in authority over him, but not from him directly… I.e. the NIH Public Relations office, CDC statements… but not from him. IF it was reported that the article was already accepted, then why did that suddenly change.
it is not clear… Maybe he did just want it to be certain… but how do we know, and why are we not being given a direct explanation?
that is not “more” … thats just another nebulous rumour, show me a link to the NIH statement on their press release feed and ill believe it. if the NIH says this, why don't they provide a physical reference…
we have alter's original conclusions. his staff verified the slides were authentic.
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So 1 month down the track, what has happened?
Apparently the Alter study will be published in PNAS this month.
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