Just days after the retraction of a paper in Science that had claimed a link between chronic fatigue syndrome (CFS) and the virus XMRV, the authors of a similar paper in the Proceedings of the National Academy of Sciences (PNAS) have retracted theirs.
The PNAS paper, “Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors,” was published online on August 23, 2010 by Shyh-Ching Lo, Harvey Alter, and colleagues. Here’s the notice, which PNAS says will be available on its site sometime this week:
The authors wish to note the following: “Although our published findings were reproducible in our laboratory and while there has been no evidence of contamination using sensitive mouse mitochondrial DNA or IAP assays or in testing coded panels, we have the following concerns:
1. The original chronic fatigue syndrome (CFS) patient samples were of insufficient volume to distribute to other laboratories for independent confirmation.
2. Only one (1) of many laboratories has found a similar association between polytropic murine leukemia viruses (pMLV) and CFS and a careful study of 100 CFS patients (2), as well as a coded panel recently constructed by the National Heart, Lung, and Blood Institute (NHLBI) (3), have found no evidence for either xenotropic murine leukemia virus-related virus (XMRV) or pMLVs in CFS patient samples.
3. Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.
4. While recall of eight patients from the original cohort 15 y later showed pMLV gag sequences in seven, the copy number was very low and phylogenetic analysis showed these sequences were not direct descendents of the original dominant strains (4). Still later samples from four of these patients tested negative in the NHLBI panel. While this result could be explained by viral clearance over time, it fails to support a sustained retroviral infection in human cells.
The notice refers to an ongoing study led by Ian Lipkin:
Although a more definitive, National Institute of Allergy and Infectious Diseases (NIAID)–sponsored, coded panel of samples from 150 well-characterized and geographically diverse CFS patients and controls is being assembled for further study, in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the association of murine gamma retroviruses with CFS has not withstood the test of time or of independent verification and that this association is now tenuous. Therefore, we retract the conclusions in our article.”
We asked Columbia University virologist Vincent Racaniello, who has been following the CFS-XMRV story for years as part of his This Week in Virology podcast, to explain what the original paper found, and what the retraction meant:
…in 2009 Lombardi et al published a Science report indicating they had detected the new retrovirus XMRV – first detected a few years earlier in prostate tumors – in the blood of a high proportion of patients with chronic fatigue syndrome. Many other laboratories tried to reproduce this finding, but none found XMRV in CFS patients.
In 2010 Alter and colleagues reported finding retroviral sequences in blood from a substantial number of CFS patients. No viruses were isolated in this study; only viral sequences were obtained by PCR. These sequences were not XMRV, but rather were closely related to endogenous retroviruses of mice called polytropic murine leukemia viruses. (Polytropic means the viruses can infect many species, including mice; xenotropic means the viruses, though originating in mice, only infect non-mouse species).
As to the retraction notice itself:
Curiously, they begin the retraction by writing that they could not detect contaminating mouse DNA in their samples – which was most certainly present and lead to their detection of MLV-like sequences in the first place. This failure remains puzzling and unexplained; but as they report in the next paragraph, they appear to have run out of material to distribute to other laboratories for ‘independent confirmation’. This is just as well: it’s better not to waste more time on what clearly is a case of contamination.
Lo et al provide three additional reasons why they are retracting this paper. They note that no one has been able to reproduce their findings, including the Blood Working Group as discussed above. They have not been able to find (along with collaborators) anti-XMRV antibody, XMRV virus, or viral integration sites in patient samples. It sounds as though they have done quite a number of experiments with others using their precious samples – so it’s not clear why their collaborators could not also look for contaminating mouse DNA (see previous paragraph). Finally, they mention their finding from the PNAS paper that a second set of samples taken 15 years later from the same CFS patients also were positive for MLV-like viruses. They write that phylogenetic analyses revealed that these sequences were clearly not descendants of the original strains. The sequence data used to make this conclusion were available at the time of the PNAS publication, so it is not clear why this evolutionary incompatibility was not noted at the time.
The authors made the link between their paper and the now-retracted Science paper clear in their original paper’s conclusion:
Although we find evidence of a broader group of MLV-related viruses, rather than just XMRV, in patients with CFS and healthy blood donors, our results clearly support the central argument by Lombardi et al. (3) that MLV-related viruses are associated with CFS and are present in some blood donors.
But that wasn’t the case, says Racianello:
The Lo-Alter finding was viewed by many as supporting the findings of Lombardi et al; but in truth they only confused the matter. The viruses pinpointed by Lo-Alter in CFS patients were not XMRV, and it made no sense that CFS would be caused by such a diverse range of viruses. A second report in 2011 reported MLV-like sequences in a CFS cohort but many other studies failed to find any kind of retrovirus in the blood of CFS patients.
Just this year it became clear that XMRV is a laboratory-generated recombinant virus: it arose during the passage of a prostate tumor in nude mice in the early 1990s. This made it highly unlikely that it could be associated with human disease. Lombardi et al retracted a part of the 2009 Science paper that reported nucleic acid sequence; they noted that their samples were contaminated with XMRV plasmids. What remained of the paper were serological and virus culture experiments that were not specific for XMRV. Last week the remainder of this paper was editorially retracted by Science. What that meant is that there is no longer any confidence that XMRV, or any related retrovirus, causes XMRV.
So what’s happened to the XMRV-CFS hypothesis since Lo and Alter published their paper?
The first blow was the finding in several laboratories that reagents used to carry out PCR are often contaminated with mouse DNA. The presence of this adventitious DNA can lead to detection of MLV-like sequences that resemble those found in the Lo-Alter study. The implication was clear: the Lo-Alter findings were wrong, a result of contamination of PCR reagents with mouse DNA.
The next blow was a report of the Blood XMRV Scientific Working Group, which was assembled to determine if XMRV constituted a threat to the blood supply. In this study, sets of coded samples previously shown to be XMRV positive, as well as samples from healthy controls, were blinded and provided to 9 laboratories for analysis by PCR, virus culture, and serology. Two laboratories reported evidence of XMRV in the coded samples. Only WPI identified positive specimens by PCR: two from negative controls, and one from a CFS patient. The Lo laboratory did not detect any positives by PCR, using the same nested assay that they had previously reported in their PNAS paper. The samples tested included 5 specimens that were positive in the Lo-Alter study. In other words, Lo-Alter could not detect retroviruses in the same samples in which they had previously detected them.
And what’s next? Does the retrovirus-CFS story have a future?
With the retraction of the Lombardi et al and Lo-Alter papers, this brings to an end any hope that there might be a retrovirus associated with CFS. Many (including Lipkin) have suggested that a related human gammaretrovirus might be involved in CFS. But I don’t see how a lab contaminant can point you in the direction of a bona fide etiologic agent. Contaminants just cloud our vision, they don’t improve it.
As for the Lipkin study – the more I think about it, the less compelling it seems. Many laboratories have failed to find any retrovirus in CFS patients. The story is over. Why do we think that the results from one laboratory will clear the matter up further? On the contrary – if the Lipkin study is positive, I would not believe it, in the face of all the other negative results we have seen. As I always say, trust science, not scientists.
The paper, which has been cited 76 times, according to Thomson Scientific’s Web of Knowledge, was subject to a minor correction of GenBank accession numbers.
The timing of the two retractions — bookending a holiday weekend — appears to be coincidental. We asked Science last week whether they had tried to coordinate publication with PNAS, and the journal told us they weren’t aware of the PNAS retraction.
The announcements themselves marked a bit of a switch; typically PNAS has not included retraction notices in its press materials, while Science has, as our sister blog Embargo Watch noted last week. The opposite was true this time. We’ve urged journals that use press releases to to press-release retractions whenever they appear.
The assertion that they and their collaborators were unable to “demonstrate antibody in affected patients” and “to isolate the virus by culture” is rather interesting.
Although there was not enough left of the original samples for further testing, there was (naturally) enough material taken from the 9 patients that were “revisited” in 2010. Dr. Lo did send material from these 9 patients to the Ruscetti lab at NCI. Mikovits reported in December of 2010 that:
“It’s not part of the publication, but Frank Ruscetti – Harvey [Alter] asked Frank if he would isolate the virus from these patients. He did so and he detected XMRV, suggesting that our cell line preferentially replicates XMRV. Importantly, Rachel Bagni also showed an immune response in these 9 samples 15 years later.”
http://www.youtube.com/watch?v=MpUbbRX3als
Did Mikovits made this up out of thin air (well, it was mostly a lay audience and we know how she likes to ‘simplify’ things for them), or do they really know that these methods are flawed and/or their lab was contaminated?
Apologies for the multiple posts, but two more things:
1. I’d like to retract the isolation part of my previous post, as Ruscetti naturally isolated XMRV and not the viruses that Lo had detected.
2. Professor Racaniello notes that “the sequence data used to make this conclusion were available at the time of the PNAS publication, so it is not clear why this evolutionary incompatibility was not noted at the time.”
Although it certainly is no excuse, the rather controversial and highly publicized hold up of the study (as well as the Switzer et al. study) is the reason, I guess. After all, the re-analysis of the 9 patients was not part of the original publication (and thus only the originally found sequenes were subjected to a phylogentic analysis). After Lo/Alter found out about the Switzer et al. study (which directly contradicted their own results) they decided to perform the additional experiment of re-testing some of thier patients. Unfortunately, after they again found these 9 patients to be positive (with no mentioning of using controls let alone blinding of samples by the way), they didn’t redo their phylogenetic analysis as well.
I can really only imagine that the pressure to publish the paper was the reason for this, although it is of course never an excuse for sloppy science.
“3. Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.”
Should this not have been done PRIOR to the PNAS publication? Once again the failure of peer review, the rush ro publish high profile results and the ambitions of a famous journal have played a significant role here. This is an embarassing episode for science.
This was actually discussed before publication, but it appeared PNAS made the wrong decision. The following is all IIRC:
As you may know, this paper was a so-called “track 1” paper, which means that the NAS member (Harvey Alter) responsible for its submission could choose his own (two) reviewers.
After the paper had already been approved by Alter’s reviewers, the authors asked PNAS to delay publication (because of the CDC study contradicted it). When (then-) PNAS Editor-in-Chief Randy Shekman became aware of this, he asked another independent expert to review the paper. This independent reviewer actually asked of the authors to show human integration sites. However, Alter declined doing this and explained this by saying that their data was already strong enough and that holding it up any further would be a disservice to the public.
Shekman then consulted yet another independent expert who basically agreed with Alter. PNAS then decided to publish the paper.
Ah thanks for the info. This makes things a little clearer.
The full text of this retraction hasn’t been published, but from the excerpts posted here on retraction watch, it looks like they probably only retracted their conclusion, not the rest of the paper.
Prof. Racaniello was quoted in retraction watch as saying “With the retraction of the Lombardi et al and Lo-Alter papers, this brings to an end any hope that there might be a retrovirus associated with CFS.” You were also quoted in the Washington Post as saying “There’s no evidence at the moment that any virus is associated with chronic fatigue syndrome.”
I hope these were misquotes or taken out of context since he says on his latest post on his blog that it is theoretically possible that ME has a retroviral cause. btw, it is completely accepted by science that ME is strongly associated with a number of opportunistic viruses such as all or almost all herpes viruses, mycoplasma fermentans, echovirus, enteroviruses, parvovirus and virally-associated blood and lymph cancers.
I’d guess they retracted the paper as a whole if they believe their results to be the product of contamination.
“ME is strongly associated with a number of opportunistic viruses such as all or almost all herpes viruses, mycoplasma fermentans…”
When did mycoplasmas become viral?
The timing of the two retractions — bookending a holiday weekend — appears to be coincidental. We asked Science last week whether they had tried to coordinate publication with PNAS, and the journal told us they weren’t aware of the PNAS retraction.
yeah right and pigs might fly
I have to agree with Polly. Since the Lombardi paper was first published, there has been a concerted, sustained attempt to ‘shut the door’ on possible retrovirus-ME/CFS link research. The constant fallacious claims that the ‘science is done’, ‘the link is dead’ ‘the science is finished’ are shocking, coming as they do from people claiming scientific expertise. ‘Scientists’ show no concern or curiosity whatsoever, preferring to follow the line of least resistance, and just sit, slack-jawed, accepting the exhortations to ‘look away’, while sneering with contempt at patients’ justifiable concerns, and ignoring the pernicious effects on the scientific process. In this context, claiming that two major retractions on the same subject, occurring during the Christmas holidays when they are least likely to be fully responded to, ‘just happened by coincidence’ appears either absurdly naive or disingenuous. Retraction Watch – are you not even curious about the oddities and discrepancies in this whole saga? Even if they are only being raised by the wretched patients and their supporters?
I think the timing has more to do with journals HATING to publish retractions – especially high impact journals retracting high impact papers. It does NOT have to do with people / patients wanting to ‘retract the retraction’ because that isn’t how science works. The papers were flawed. Period. Whether CFS is caused by a retrovirus or not will NOT be understood by these papers because they were flawed. Seriously flawed. Even the authors acknowledge these serious flaws. And future investigations will probably look into the possibility of data manipulation in one of these studies! Ack!!! Completely new studies will be needed to address any possible connection between CFS and retroviruses.
The link IS dead. There may be another virus(es) that trigger CFS, but the link with XMRV/PLV, ect… is dead. Lab contamination is a bear to avoid and it seems that this whole saga will serve as nothing more than a lesson to future scientists about what to be very careful to avoid doing. Sorry, Angela. I suppose you can always try to find comfort in the fact that with every failed hypothesis, scientists eventually narrow down the possibilities.
For science: Please show me the evidence for integration into human genome. You claim scientists don’t care about science, but do you? Provide evidence that these are actual human pathogens. Retroviruses integrate into the genome. If the genome arround the retrovirus genome is human genome, it is a human pathogen. If the genome around the retrovirus is mouse genome, then it is a contaminant. Simple test. So please, show me the evidence for integration into human genome.
For the record: This was a reply to “Angela Kennedy” and “polly”.
@ Tony Mach I dont know who you are but you appear to be stalking me wherever I comment why is that exactly ?
Im ill and im sorry but I have a right to an opinion just like everybody else , I made a simple comment ‘yeah right and pigs might fly’ your reply to be fair has nothing to do with the comment I made .
I agree with Tony Mach and RRM regarding your and Angela’s comment.
Why do you choose see conspiracy when there isn’t one?
polly: I am not stalking you, but you choose to go everywhere and spread your BS, and I call out that. I don’t care if your name is “polly”, “gerwyn”, “V99” or whatever. Post BS? Get called out.
And no, what you state is not a “opinion”, what you do is to try to pass of your BS as *fact* – I take offense at that and I ask you and anybody else, again and again, to supply evidence for your assertions or STFU. Science is not a matter of opinion.
And what scoundrel participates in a discussion of scientific topic, and when asked to supply evidence retreats to a “I have a right to an opinion just like everybody else” position. If your point was to say “pigs could fly”, UFOs could exist and this year we could see the mayan apocalypse, then better keep this “opinion” to yourself and stop polluting science blogs.
I don’t see how any more shoes can be left to drop now with the XMRV linkage to CFS.
@Tony…I don’t think it’s that simple. Sure, if it’s a retrovirus, it can integrate into the genome, but that’s not the point. I believe in the Science paper the authors showed that part of the vector ( I THINK some sort of resistance gene) to clone XMRV was integrated into the patient samples, and this signifies contamination (as a non-cloned virus shouldn’t have that resistance gene provided by the cloning vector). I don’t think it matters if mouse DNA is between human or vice-verse, but more so if parts of a cloning vector integrated into the patient samples (and even the controls).
But I could be absolutely incorrect; I am no virologist (nor do I wish to be one), but this is what I remember reading from the partial retraction to the Lombardi et al. in Science.
I think you may have misunderstood slightly. The PCR by Silverman’s group using primers in the virus and in a resistance gene, present in the plasmid but not the virus, was expressly intended to show whether there samples contained the plasmid. They did. The resistance gene was never in the patients or the virus, the plasmid somehow (hard to prove but many cynics could suggest how this might have happened) contaminated the patient samples, in all probability before they reached Silverman.
Oops “their samples” or possibly “the samples” but definitely not “there samples”, sorry, I should sleep!
Why are only the CFS papers being retracted when the Prostate cancer papers especially Urisman et al.(2006) are equally suspect?
Bias and stigma anyone?
Excuse my ignorance, but can you elaborate why Urisman et al.(2006) is equally suspect?
In brief – the results from the CFS studies have shown that XMRV is a lab artefact and all results indicating that it (or any other murine retorvirus) infects people are most likely explained by contamination of the lab and/or the reagents used. If XMRV doesn’t infect people then it can no more cause prostate cancer than it can CFS, so the prostate cancer results must also the result of contamination.
As for why there isn’t such a fuss about retracting the prostate cancer papers, it is probably because no one has been advocating whole sale changes to the diagnosis and treatment of prostate cancer neither did they propose scare stories about the risks to the blood supply or the entire human population from a novel retrovirus. Which isn’t to say that Urisman et al. doesn’t deserve to be retracted, just that it requires a fair amount of effort to get a paper retracted and most of the time erroneous papers are quietly forgotten rather than publicly retracted. It’s not a perfect system – I’ve had a student who was astonished to learn that findings in a published paper are not always reliable and I’m sure he isn’t the only one.
Ah, I should have focused my question on Andrew’s supposed “bias and stigma”.
Thanks for replying Perplexed. I agree with your explanation for why one was retracted and the other wasn’t.
In the prostate paper, there were legitimate previous research result(s) that highlighted the elevated prevalence of prostate cancer in patients harboring the RNASEL mutation, and the paper sought to provide a possible candidate for the cause of elevated prevalence to the XMRV found in patient samples. It was an attractive proposition, XMRV-prostate paper itself was cautious to make the link, and it was just like any other SNP follow up study that have failed to provide a definitive answer. Think about how many SNP follow up studies have garnered spotlight only to stall (or for that matter GWAS)?
What distinguishes CFS paper from the prostate paper has been the lack of previous findings that could plausibly lead one to consider the etiology of CFS to be XMRV. If anything there has been plenty of discussion if CFS is psychological or not. (Is that the bias and stigma you are talking about Andrew?)
I don’t think there is any outright bias in the way one was retracted and the other wasn’t. One set out a greater claim and was therefore more scrutinized, period.
The etiology of CFS has long been linked with viral involvement. Likewise, a high ratio of low molecular weight RNASE L has been proposed as a potential biomarker for CFS in a variety of papers. If you remembered the papers in question, you would know this.
There are also a variety of papers that have found that CFS is more common in families, though whether this is a genetic risk or an environmental (including viral) risk is not fully explained yet.
There have been similar failures to replicate the prostate cancer XMRV link or a strong RNASE L SNP association.
The fact is that the ‘association’ of XMRV and prostate cancer is just as likely to be due to contamination. The genomic integration evidence for example has been discredited in two later papers for example.
What message does it send to patients if XMRV if those papers are not put under the same scrutiny?
If we want CFS patients to move on, then those papers need to be put under the same scrutiny to show patients that the retractions aren’t due to bias and social stigma, but rather simply the normal functioning of the scientific process.
The Lombardi et al paper certainly attracted more media attention, if this is considered a reason, then all this suggests is that the practice science of is influenced by the media.
Perplexed – Given that another name for CFS is post-viral fatigue syndrome, how is a new viral association, for a subset of patients a whole sale change to diagnosis or treatment?
There were responses to the Urisman et al. paper that suggested changes to the diagnosis of prostate cancer and treatment, given the findings. Likewise, there were papers discussing the risk of spreading XMRV before the Lombardi et al study was published.
??? your comments left me scratching my head a bit.
virus-CFS link has been thrown around, but no link has ever been established. As far as I know, it was always “there may be a viral link, we don’t know yet.” Plus, there were many other possible culprits that were bandied about, immunological, neurological, etc. Given that there were no known credible etiology of CFS to rely on for a treatment strategy, a claim that there is a XMRV-CFS link was worth a lot more scrutiny than XMRV-prostate link. XMRV-prostate link was admittedly interesting, but hardly paradigm altering in terms of treatment for prostate cancer.
As for the low molecular RnaseL evidence, I’ve never heard of that being seriously considered an appropriate biomarker for diagnosis of CFS. Evidence of elevated protease activity is hardly an appropriate biomarker when the protein itself is not implicated in the disease. Was it something you heard at a conference somewhere? I’ve never encountered it from the conferences that I’ve participated.
Maybe you can tell me some papers that show RnaseL involvement in CFS?
“There have been similar failures to replicate the prostate cancer XMRV link or a strong RNASE L SNP association.”
>> It’s true that XMRV-prostate link is tenuous at the moment, given that samples from Europe, East Asia, etc. have been tested that didn’t show any evidence of XMRV. But whether or not the SNP found in Rnase L that are overrepresented in prostate cancer samples are important for the occurrence of prostate cancer is still open to interpretation.
“What message does it send to patients if XMRV-prostate papers are not put under the same scrutiny?
If we want CFS patients to move on, then those papers need to be put under the same scrutiny to show patients that the retractions aren’t due to bias and social stigma, but rather simply the normal functioning of the scientific process.”
>> See, this is what I was getting at in the first place. You are advocating retraction of Urisman et al. to somehow placate patients who think it’s some bias and political wrangling that’s causing retractions of XMRV-CFS papers. Such is precisely the WRONG reason to retract a paper. Now you’ve really shown your colors.
@ LNV, your comment about ‘that’s how science works’ is problematic. Any student of the sociology of science (and indeed the philosophy), indeed anyone who has read and understood Thomas Kuhn, will understand there can be no rational appeal to any ‘invisible hand’ in science (nor indeed economics- sorry any Adam Smith fans out there). There are massive discrepancies in how the possible retroviral link to ME/CFS has been handled by those claiming scientific authority in various ways. There are many, MANY scientific papers with flaws (serious ones) that do not get retracted – including the negative studies, by the way! The discrepancy in the way THESE papers have been treated (the retractions), within a political context of widespread and prolonged denial of the serious effects of THIS disease. You may not be aware of these. But the people who are concerned about the discrepancies are, with very good reason. I don’t want to be turning this particular comments thread into a long-winded shouting match (because this inevitably happens – anonymous ‘scientists’ attack patients and their supporters as being ignorant, irrational hostile recalcitrants as soon as they DARE pipe up, and the actual facts-arguments become very quickly lost), so I’m asking readers of this blog who are GENUINELY interested in the scientific process to put their critical faculties into gear and not accept these two retractions as mere ‘science in progress’ at face value.
@ Tony Mach. Good grief man. You’ve answered me with a number of fallacies there. I can’t ‘show’ you evidence because (a) I’m not a retrovirologist and don’t do that kind of research and (b) that’s exactly the problem – the search for ‘evidence’ isn’t over yet! Or at least, it shouldn’t be. There is enough evidence that MORE RESEARCH needs to be done- but the language used around these retractions (and a long time before that) is that the door has to be shut on research on retroviral links with ME/CFS. That’s clearly what my original post is about. Plus- I never said ‘scientists don’t care about science’ – your paraphrasing is wholly inaccurate. ‘Simple test’? Please. That way of false choice thinking is one of the major fallacies of reasoning that is making a mockery of ‘science’ in this whole arena. Also – me (or anyone) not being a retrovirologist is irrelevant to the issues of scientific principle and process, or logical reasoning. Let’s get that old canard out of the way sharpish.
If you read the retraction by Lo et al where they state that “Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.”, you’ll notice that they apparently did check for insertion sites. The problem is that the data simply does not support your claim. More research does not seem necessary in this line anymore. What needs to be done is to move on to new avenues of research to find what is actually causing CFS.
@ poodle stomper – there is no comfort to be found in claiming the link is dead when it is being strangled at birth, frankly. Your comment sadly has illustrated the problems I raised in my original post. The problem as identified by a patient advocate, Khaly Castle, still stands: “”Patients are not pushing for a favorite pathogen. Patients are pushing for real science to occur and to take its course before the door gets slammed on ANY potential avenue of study. Patients are not stupid and are tired of being treated as such. Patients are particularly irked that they point out the discrepancies in scientists’and government’s claims, and said scientists and government continue to push the mistruths forward as if by saying it loud enough and long enough, it will be true.”
With the number of published studies on a possible XMRV-link to CFS/ME we can hardly still claim that the issue is being “strangled at birth”…
As you have declared to be a follower of Kuhn and make several references to qualitative sciences I can’t help but wonder what your position on Popper is? Or the discrepancies between qualitative and quantitative sciences? As a more or less lifelong scientist in clinical evaluation I know that the worst question of all to pose to patients is “Did this intervention/answer/evaluation/diagnosis/etc make you feel better/more seen/understood/compensated/etc” – as this question never answers inquiries into cause-and-effect. And strangely (with time) it is only patients, and their “advocates”, that seem to push for possible leads from retracted papers…
As others have mentioned, this has most certainly not been strangled at birth. Many labs have tried to reproduce the findings using a variety of techniques available. Mikovits’ own assays have proven unreliable under blinded conditions. The problem is that a small group of people are so emotionally vested in this hypothesis that they claim conspiracy and politics rather than look at the science. I’d suggest that perhaps you should look elsewhere than your forum for scientific information. The link to XMRV is, for all intents and purposes, dead. That doesn’t mean that the cause isn’t out there. It doesn’t mean that the cause won’t be found. It also doesn’t mean that the cause isn’t viral. It simply means that, as so often happens in science, a hypothesis is tested for reproducibility, fails and is discarded to be replaced by a better fitting hypothesis. The patients can be “particularly irked” if they wish but that is irrelevant when it comes to data. XMRV is no more supported as cause of CFS as “chronic lyme”. That won’t stop some nutters from holding on to it for dear life, though.
I think it is also worth mentioning that if you read the full retraction of the Lo et. al paper, that the authors also agree saying:
Although a more definitive, National Institute of Allergy and
Infectious Diseases (NIAID)–sponsored, coded panel of samples
from 150 well-characterized and geographically diverse CFS
patients and controls is being assembled for further study, in
consideration of the aggregate data from our own laboratory
and that of others, it is our current view that the association
of murine gamma retroviruses with CFS has not withstood the
test of time or of independent verification and that this association
is now tenuous. Therefore, we retract the conclusions in
our article.”
There is no claim that the attempts to reproduce their work is flawed, or that there is a conspiracy, or anything sinister. Independent verification has failed to confirm the hypothesis. It’s been given more than its fair chance. The link to CFS is dead and we now get to go back to work trying to find the real cause. Hang in there.
@Angela Kennedy
To put it this way: if in the future scientists discover that XMRV (and/or MLV-related viruses) are associated with ME/CFS/PC after all, it would probably be unprecendented in the sense that no other scientific finding in the history of peer reviewed research publication would then have had so many experiments going against it before it turned out to be true after all. Of course, nothing in science is ever absolutely proven (I take it you know the saying that proof is reserved for math and whiskey), but this hypothesis is about as dead as dead can be in science – there will always be some people that argue it is just pining for the fjords though.
Another problem is that people are actively “debunking” all of the negative studies on the forums you frequently visit. While patients are certainly not stupid, it would be a stupid choice to rely on an “analysis” from one or two patients that really have no relevant background in the matter but who are just slightly more knowledgeable (and better at googling stuff) than the avarage forum member. For instance, the idea that VP62-studies are without merit or that assays should be “clincally validated” are faulty arguments that subsequently act as some sort of straw man mechanism, in order to easily reject studies that don’t meet this “standard” of not using VP62 or “clinically validated” assays. Fact is there is little wrong with all those cohorts and all those assays and all those phylogenetic analyses of all those negative studies, and together they paint a very convincing picture of who is right and who’s wrong.
As to your agreement with Polly regarding the notion that the timing of the retractions was not a coincidence, remember that it was the publication of the BWG paper (9/22) that really started a critical re-examination by the authors and/or journal editors. Through the BWG paper it turned out that all of the labs involved in the original studies (Mikovits, Rusectti and Lo – admittedly not Silverman but he retracted his part of the study on 9/22 anyway) labs were totally unable to replicate their earlier findings on samples taken from the very same “positive” subject. Besides, you must think the people involved are very stupid themselves if you think the ‘chosen’ timing is proof of some hidden concerted effort in itself.