Talk:Xenotropic murine leukemia virus–related virus/Archive 3
This is an archive of past discussions about Xenotropic murine leukemia virus–related virus. Do not edit the contents of this page. If you wish to start a new discussion or revive an old one, please do so on the current talk page. |
Archive 1 | Archive 2 | Archive 3 |
Some comments on recent changes
I am uncomfortable about the weight of detail in the intro para. There are two main scoping themes for XMRV: prostate cancer and CFS. In the first case we have a qualitative description with the quantitative details in the body, whilst with CFS we quote lots of figures and percentages that are also repeated in the body. My view is that the article would be easier to understand for most readers if we left the quantitative detail in both cases to the body and kept the intro short. So what I have done is to remove the "N out of M" details as I see little point in this duplication here.
Likewise, the Alter paper is primary research which is only indirectly related to XMRV yet has the most detailed coverage of any paper referenced in the page. Given the controversy over the presence of MLVs in CFS patients, perhaps there is an argument for including such details somewhere in WP, but surely not here. I have edited out some redundant detail, but, I still think that somewhere in the CFS article hierarchy might be better though at the moment this only touched on it Chronic fatigue syndrome#XMRV and not at all in Controversies related to chronic fatigue syndrome. I would suggest that everything in the Alter paragraph from "Seven of 8 patients ..." is really out of scope for this page.
I also feel that the paragraph "At the 1st International Workshop on XMRV..." also has undue weight and the article would be more balanced without it, or certain the reported opinion "Lipkin has suggested that ...". We should wait until results are published. -- TerryE (talk) 12:09, 3 October 2010 (UTC)
- Yes, I agree - far too many unnecessary details. How about we just remove the entire CFS section from the lede and just replace "Several reports have associated the virus with familial and sporadic prostate cancer,[2][3] but other reports do not find a link." with something like "Several reports have associated the virus with prostate cancer and CFS, but other reports do not find a link". --sciencewatcher (talk) 18:37, 16 October 2010 (UTC)
- I just made this change. --sciencewatcher (talk) 20:26, 25 October 2010 (UTC)
- The recent reversions, particularly the removal from the lede of summary results of the FDA/NIH joint study under Harvey Alter, indicate strong editor bias. This now represents a pattern of bias. The campaign to remove any indication that XMRV-related viruses are associated with CFS appears intentional. Studies which are utterly unable to detect XMRV in both patient and control populations should be grouped by their protocol and detection method failures, and summarized accordingly. Frankly, these non-protocol studies carry vastly less weight than the FDA/NIH Alter study, and its removal goes to motive, demonstrating the assertion of intentional editor bias against the possibility of any XMRV or XMRV-related viral etiology pathways CFS. I disagree with what has amounted to a full reversion of the lede after numerous talk discussions in favor of adding the new FDA/NIH findings, and I seek additional comments from other editors on the subject. I propose the consensus edits made in September be re-instated, and if necessary, a broader editor bias review be initiated. —Preceding unsigned comment added by HealthandScience (talk • contribs) 22:57, 11 November 2010 (UTC)
- The study hasn't been removed, it has been summarised (that is what the lede is meant to be - a summary. It definitely should not give detailed info about ANY study!) And please assume good faith. If you have a better suggestion for a summary, go ahead and improve it. --sciencewatcher (talk) 00:32, 12 November 2010 (UTC)
- Looking at the changes to the lead since the end of September, I see nothing particularly problematic, provided that the details are covered in the article. In fact, I'd be tempted to move the second paragraph to the article body. The lead isn't the place for intricate details—it's supposed to be a summary.
- To quote WP:LEAD (give or take some formatting and commentary): "The lead should be able to stand alone as a concise overview of the article. It should:
- define the topic (first sentence),
- establish context (third sentence),
- explain why the subject is interesting or notable (third sentence again), and
- summarize the most important points—including any notable controversies (third sentence yet again...it's a good sentence!)."
- Based on that, we could move or remove the second sentence and the entire second paragraph. Yes, the second paragraph covers conflicting studies, but the fact that studies have conflicted has already been mentioned—specifics should go into the article body. —RobinHood70 (talk • contribs) 21:48, 12 November 2010 (UTC)
- Agreed, though I think the second sentence could be retained given the current interest in this topic. The second paragraph is inappropriately detailed for a lead paragraph. -- Scray (talk) 03:47, 13 November 2010 (UTC)
- I think that SW has done a very good job on the lead. If you read the article that was present at the end of September it was rather a convoluted first paragraph to wade through. Another step in the right direction would be, as RH has suggested, to move the second paragraph away from the lead to the main body of the article.StevieNic (talk) 09:21, 13 November 2010 (UTC)
Yes, I agree about the second paragraph. --sciencewatcher (talk) 17:11, 13 November 2010 (UTC)
- I may have overreacted when I saw that most of the edits made to the lede in September appeared to have been reverted to pre-September wording, even though ample discussion had occurred prior to their application. The idea of removing the second sentence and second paragraphs seems a calmer, more rational approach. What troubles me is the slant created by stacking failure-to-detect studies in the reference tags of the second sentence, giving the appearance that XMRV and related viruses are all just red herrings. This is tantamount to arguing the controversy in a weighted and one-sided fashion in the lede. All of the failure-to-detect studies have one thing in common: no XRMV or related viruses found in neither patient nor control populations. That is a valid grouping and should be included in any sentence intended to establish their plethora as a cohesive indicator. The more likely indicator, as argued by Dr. Alter, is the lack of protocol, which has been argued by others on this page for nearly a year. That argument now carries significant weight and should be given its due deference. HealthandScience (talk) 16:26, 15 November 2010 (UTC)
You're lucky HealthandScience. When I tried to add that study (without percentages or details), they just removed it without any explanation. Click. Delete. Nothing. A handful of editors have taken a position and are defending it. If they were being reasonable, they would have added that study to the top themselves. Talk about interesting and notable. Harvey Alter is world-class. He's moved mountains of attention and funding onto the area, organized an international conference on it, launched a new study with tons of funding, and triggered countless other studies. And yet, deleted it remains from the top paragraph. Instead, these guys collect peanut gallery studies that demonstrate how someone can't find bread in a toaster. Seriously, not a single detection in any patients or control populations? And yet they keep collecting and adding the negative studies but somehow accidentally miss the positive ones? It's blatant. I vote someone summarize or mention the FDA study at the very top. It is *by* *far* the most notable and interesting thing to happen on this topic. And for pete's sake, fix the area that says XMRV is not infectious. I don't know how to do those formatting things, but someone please look at this and add it: ( http://www.retroconference.org/2010/Abstracts/39393.htm ). Those old rushed studies are dangerous in their faulty conclusions. People may be reading the first few lines on this page and walking away thinking XRMV probably does nothing and there's no need to worry about intercourse or blood transfusions. Mgladden2 (talk) 04:52, 15 November 2010 (UTC)
- Nice find on the macaque study. We'll include it. HealthandScience (talk) 16:26, 15 November 2010 (UTC)
- @Mgladden2, the Alter study is referenced in the lead paragraph. If you search Pubmed for XMRV and have a scan, then the basic reporting in the lead is correct and balanced: some studies report an association. OK the score count is a little out of date, but more do not, and the results are still inconsistent. It isn't our job to weight or rank the interpretation of references: that's the job of field experts in secondary reviews, and when these are published then we can reference them. If one does and emphasises the importance of specific primary findings, then fair enough, but none of the contributing editors should try to bias the article with their own opinions -- which in WP terms are not expert. IMHO, the lead is balanced, and appropriately short. -- TerryE (talk) 01:07, 16 November 2010 (UTC)
While the fourth sentence of the lede ("It has not yet been established whether XMRV is a cause of disease.") is in itself correct, the source for it seems outdated to me: it is from February of 2010, long before for instance the Switzer and Lo papers were published. I suggest adding/substituting this paper as a source, which was written by scientists "on both sides", so to speak, and published online ahead of print on 12/22/2010: http://www.retrovirology.com/content/pdf/1742-4690-7-113.pdf. It states (page 3): "...,the research community has failed to reach consensus on the origin of this virus, its causative (or passenger) role in disease pathology, and the extent to which it is prevalent in the human population." I would also suggest to rephrase the fourth sentence of the lede to at least include the "prevalation information" from the Retrovirology paper. — Preceding unsigned comment added by Griek1 (talk • contribs) 15:12, 18 January 2011 (UTC)
4 new studies point to XMRV just being contamination
this needs to be added to the article (with the proper refs). --sciencewatcher (talk) 16:29, 21 December 2010 (UTC)
- Here is a secondary source peer reviewed opinion of the 4 new studies that is better than the newspaper article for medrs purposes. Unfortunately it doesn't seem raise to the level of a review since it is called a viewpoint. I was waiting for Pubmed to categorize it. Ward20 (talk) 04:22, 22 December 2010 (UTC)
- Alternatively we could just reference the 4 studies ourselves like we've been doing with the XMRV studies themselves. I haven't had time to look at any of this yet myself. --sciencewatcher (talk) 14:46, 22 December 2010 (UTC)
- Why reinvent the wheel with primary sources when we have a secondary source? I would be inclined to go with the retroviroloy article conclusions by Smith [1]. It doesn't seem like he has any conflicts of interest and he summarizes the contamination issues neutrally. It seems to me to be the best MEDRS source available at this time. Ward20 (talk) 21:30, 22 December 2010 (UTC)
- remember that already a nuber of doctors and researchers have come forward with good arguments and statements why the contaimaination papers conclusions are false....we need that for balance217.39.36.241 (talk) 14:38, 24 December 2010 (UTC)
- Possibly true, but we can only use those if published, and reliable per WP:MEDRS. — Arthur Rubin (talk) 15:09, 24 December 2010 (UTC)
- This link is an opinion piece by a virology professor, so not suitable for inclusion, but it may help summarize what the four new studies are saying for those of us not so well-versed in virology terms. It also includes a number of other links about the studies and related information. – RobinHood70 talk 00:16, 29 December 2010 (UTC)
- If you see anything that is wrong or unclear in my recent changes please don't be shy to correct them. Thanks. Ward20 (talk) 00:22, 29 December 2010 (UTC)
- Lombardi et al, the authors of the paper published in "Science" (Oct 09), which originally linked XMRV to ME-cfs, have issued a statement http://www.wpinstitute.org/news/docs/WPIResponseToRetrovirology122010.pdf refuting the suggestion that contamination affected their results. It stresses that unlike their critics, the methodology they used was not reliant on PCR evidence alone and took rigorous precautions against contamination. They also discovered an antibody response to the virus in patient samples, which cannot be explained by laboratory contamination. The God of Pleasure (talk) 05:43, 31 December 2010 (UTC)
- One of the negative studies found an antibody response in 24 controls and 1 patient, concluding that the response was nothing to do with the XMRV virus. They also said "Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses." See here. --sciencewatcher (talk) 14:39, 31 December 2010 (UTC)
- 22Rv1 is the standard positive control for XMRV.
A quick google search shows taht 22Rv1 is a human prostate carcinoma cell line. What is your point? Also please sign your posts when posting to talk pages. --sciencewatcher (talk) 17:35, 7 January 2011 (UTC)
- The WPI now have a longer press release and there is a recent Science magazine news article (unofficial full text for those without access: http://www.meassociation.org.uk/?p=3737) which states: "Moreover, the lead author of the Science paper on CFS and XMRV, Judy Mikovits of the Whittemore Peterson Institute (WPI) in Reno, Nevada, points out that PCR wasn’t the only test her studies used: For example, Mikovits’s team also showed that XMRV-positive patients make antibodies to the virus and that XMRV isolated from their blood can infect cultured human cells. Mikovits said in a statement, “Nothing that has been published to date refutes our data.”" Also included is Racaniello's retraction. Other scientists are quoted too, and the take home message is: Care needs to be taken as contamination is possible, but the situation has been overhyped and the data does not support the sweeping statements that have been parroted in the news. Finally, much of the text on contamination in this Wikipedia article looks like it was simply copied and pasted from the LA Times article but only cites the primary research. - Tekaphor (TALK) 02:40, 8 January 2011 (UTC)
- I believe the contamination material is derived from the Retrovirology viewpoint article by Smith as edited by sciencewatcher and myself. If I had a better MEDRS source I would use it, but I don't know of any. Ward20 (talk) 08:47, 8 January 2011 (UTC)
- I made a mistake. IP:67.110.177.226 added this text on the 27th December 2010 and cited a medpagetoday.com article dated 21st December 2010. Under the "Contamination issues" section of the XMRV article, the 1st sentence still remains verbatim, the 2nd has been slightly altered, the 3rd has been altered more and a 4th has been added.
- I notice that the Smith paper currently has 0 such citations on Google Scholar. Having seen papers often rejected by Sciencewatcher on the basis of lacking such citations but then routinely adding "XMRV negative" studies to Wikipedia whenever they are published, should I take this to mean that when a paper receives some news media attention the "Google Scholar argument" is invalid? - Tekaphor (TALK) 10:41, 8 January 2011 (UTC)
- I stand corrected then about exactly who added the material. The questions now become: is the material supported by the reference, is the reference WP:MEDRS, and is the material worthy of inclusion? A previous argument about including similar XMRV material in the main Chronic Fatigue Syndrome article was that with all the publicity of the studies, readers would expect some coverage in the WP article. It would seem a difficult question that will have to be reached by editor consensus. Perhaps an RFC to draw some more editors in would be in order? Ward20 (talk) 22:15, 8 January 2011 (UTC)
- I just changed the ref from the news article to the review - I didn't change the text. If it is verbatim then it will need rewritten. Oh, and obviously new studies will always have zero citations. Remove it if you like. --sciencewatcher (talk) 00:22, 9 January 2011 (UTC)
- Looking at PubMed, as far as I can see none of the commentary / the four articles cites the paper that Racaniello notes in a recent post: "Kim, S., Kim, N., Dong, B., Boren, D., Lee, S., Das Gupta, J., Gaughan, C., Klein, E., Lee, C., Silverman, R., & Chow, S. (2008). Integration Site Preference of Xenotropic Murine Leukemia Virus-Related Virus, a New Human Retrovirus Associated with Prostate Cancer Journal of Virology, 82 (20), 9964-9977 DOI: 10.1128/JVI.01299-08, PMID 18684813". Whilst these "contamination" papers provide good explanations for possible contamination, none provides a sufficient explanation for provirus integration into human chromosomal DNA. Surely we should not present inferences beyond the MEDRS evidence. -- TerryE (talk) 00:55, 9 January 2011 (UTC)
- Thanks Sciencewatcher for the clarification. I don't seek removal of the paper, I can be regarded as an inclusionist with emphasis on context. But as Ward20 points out, it is difficult finding additional MEDRS sources for further commentary on the recent "contamination" claim, so a RfC may be in order. For some reason the controversial aspect of XMRV research has always been limited to the WPI article but it now seems clear the "controversy" goes beyond the WPI and I think this warrants a similar section in this XMRV article which allows RS news sources because the issue is not strictly MEDRS. The entire issue could then be concisely addressed with current sources: the original science, the claims in the press release, the news media parroting, commentary from other researchers about how the evidence has been overstated etc. Terry, I read rumors about XMRV researchers working on an official reply publication, which should include such points you presented. - Tekaphor (TALK) 03:18, 9 January 2011 (UTC)
- Sounds reasonable. I wouldn't have any objection as long as it is done carefully. --sciencewatcher (talk) 16:14, 9 January 2011 (UTC)
- Much has been written elsewhere about the issue over the last 16 months. Is it time for a separate Wikipedia article? - Tekaphor (TALK) 03:08, 17 January 2011 (UTC)
- I agree. The controversies around XMRV are better grouped under their own article, suborned to XMRV. The WPI article should be limited to WPI related facts and issues. One area that should be kept in the WPI article is the VIP Dx controversy, though this might be worth repeating in both. -- TerryE (talk) 11:54, 21 January 2011 (UTC)
Full text here. What is the consensus for the proper WP:MEDRS weight to give this publication? Ward20 (talk) 19:13, 20 January 2011 (UTC)
- It seems to be a comprehensive review, but without evidence of formal peer review, I would have thought it WP:RS rather than WP:MEDRS. However, in respect of recommendations in the context of the blood supply in the US, it is a reliable and authoritative document. We don't need MEDRS here. Therefore we should consider including précised recommendations from the sections "XMRV and Blood Transfusion" and "Further AABB Actions". They should be clearly attributed as recommendations from the AABB Interorganizational Task Force on XMRV. -- TerryE (talk) 11:41, 21 January 2011 (UTC)
No Xenotropic Murine Leukemia Virus-related Virus Detected in Fibromyalgia Patients
This is a letter (not peer reviewed so not WP:MEDRS), and used 15 Fibro patients not CFS patients. I don't think this should be in the article. Ward20 (talk) 15:57, 7 February 2011 (UTC)
- You're right, it shouldn't be here. Also I notice that I incorrectly referenced that fibromyalgia letter in the main text instead of the newly added study. Oops - now fixed. We should perhaps mention somewhere that this new study is different from the others in that it looked at the cerebrospinal fluid. --sciencewatcher (talk) 16:32, 7 February 2011 (UTC)
- Yes, that they used cerebrospinal fluid would be worthy to mention I believe. Ward20 (talk) 18:57, 7 February 2011 (UTC)
- I added it but forgot to put on an edit summary. I did some minor ce also. Ward20 (talk) 20:07, 7 February 2011 (UTC)
Restructuring
I wade back into this discussion with trepidation and without any firm editing intentions, but I would caution the users that Robin Weiss's editorial review should, first of all, be included here, prominently, and secondly be given more weight than about 90% of the current sources for this article. Not least because his editorial but nonetheless secondary "cautionary tale", which resembles what I and others have been writing here since the CFS report, is ringing truer by the day. Of course, we have to wait for the papers currently in press, but all of us--Ward, Terry, Sciencewatcher, presumably anyone who's following the buzz--now know that multiple independent and thoroughly respected groups are finding that XMRV is purely a laboratory artifact. Not only contamination, but laboratory recombination of MLV contaminants. It's probably not transmissible in the least (unless you inject yourself with a trillion virions), it doesn't replicate to speak of in vivo, and when it replicates at all, the resulting sequences are more divergent than the entire lot of sequences purportedly amplified from human samples. In light of all of this, which you all must be aware of unless you've been off-line for the past month and more, I'm bemused by the current state of the article, mostly ignoring the now quite well-supported rumour virus hypothesis.
A restructuring will be needed in short order, and we all know that. Why not start making some necessary changes now? Starting with inclusion of the insightful if uncomfortable Weiss review. Keepcalmandcarryon (talk) 04:44, 2 March 2011 (UTC)
- Can you please provide a link to the Weiss paper? Also, as far as I've seen, the primary objections to the negative studies (patient selection, detection methods) have yet to be addressed. I could be wrong on that, but that was the last I heard.
- The studies suggesting lab contamination were also very careful to state that they were only showing how contamination could happen, and that there were numerous methods of proving whether or not it actually had, some of which the WPI had already used to prove that contamination wasn't the problem. At least, that's my understanding of where the science is at. Honestly, I think it could go either way at this point, and pretty much everybody seems to agree that more research is required.
- I see no particular need to jump the gun, and even if the editorial qualifies as MEDRS, which it might assuming it's in a peer-reviewed journal, you've said yourself that it's a "cautionary tale", not a proof or conclusion. – RobinHood70 talk 06:30, 2 March 2011 (UTC)
- I'm pretty sure KCCO is referring to Robin Weiss's BMC Biology editorial (same as PMID 20920148) from a few months ago, which does seem quite relevant, even though it's largely a well-referenced opinion piece. The study chartered by Collins and led by Fauci should be definitive, but it will take awhile - until then, this is likely to remain controversial. -- Scray (talk) 12:49, 2 March 2011 (UTC)
- Thank you, Scray. I should have linked the Weiss article and apologise for not doing so.
- I would have agreed with RobinHood on at least the possibility of going either way until I had a look at the CROI 2011 information. The abstracts and presentations include some very strong statements on contamination and how it explains the XMRV results. I was quite surprised that several researchers suggest that the contamination problem extends even to the prostate cancer side of things. Just a selection of what one can glean:
- Scientists reported that the WPI primers amplify sequences from MLV contaminants, not XMRV exclusively. That is, they are not specific. Different and truly XMRV-specific primers give different results and turn false positives into negatives.
- There are two papers from scientists including John Coffin, whom I'm sure we can all agree has been even-handed to a fault during the unfolding controversy, that suggest that the advent of XMRV itself is a recent laboratory accident in which two MLV contaminants recombined in a prostate cancer xenograft. The authors consider the probability that XMRV arose any other way to be vanishingly small.
- Other scientists report that XMRV does not replicate in vivo, and as stated before any minimal levels of brief replication produce greater genomic diversity than has been reported even in geographically distinct human populations including individuals who have been living with putative XMRV infection for several decades. Contamination is the obvious (and given) explanation.
- Study after study reports no XMRV in patient or general populations, especially when multiple detection techniques are used. The few positives are sometimes unmasked as genomic or unrelated sequences by sequencing (e.g. in at least one of the CROI presentations).
- Again, I'm not sure that any of this should be included in the article prior to publication, per our policies on sources for medicine-related topics. However, the article currently cites multiple news sources, websites and controversial primary sources, and I would rate CROI reliability (there's actually a detailed methodological description of abstract peer-review/selection in the CROI literature) at least as highly as any of these. In light of this, the new information and the trajectory of the conclusions suggest that our XMRV article give more voice to the contamination, artifact and "rumour virus" theories and include the Weiss article. Weiss, I would note, is probably the world's leading authority and most prolific writer on proposed but unproven viral causes of disease.
- The multi-centre patient study has entered its final phase, and the rumblings are...well, there's much more to say, but the talk page is not the place for whispered rumours. There's enough publicly available evidence now, though, to make some alterations to the current version. Keepcalmandcarryon (talk) 23:07, 3 March 2011 (UTC)
- There is also http://preview.retrovirology.com/content/pdf/1742-4690-8-13.pdf which points to contamination in the prostate cancer studies. It looks like it hasn't quite been published yet. --sciencewatcher (talk) 23:31, 3 March 2011 (UTC)
- How does this piece account for the presence of antibodies?
I agree that the entire article will most likely need to be revamped in the manner described, but I question whether we should do so in the absence of peer-reviewed published articles and reviews, which will most likely happen soon enough. One reason behind this is that at CROI last year CDC made a presentation along the lines of 'more diversity occuring in XMRV than previously reported' due to a couple positives (most likely false when weighed against the current crop of findings) out of a hundred or so samples which diverged from the nearly identical sequences which had been reported in the then published studies (I can't find a way to make that sentence work, sorry), yet this finding was never published and most likely won't be judging by the latest reports. Maybe just include the currently published papers in the 'contamination issues' sub-heading, with this sub-heading most likely expanding until it is the dominant section.
For instance the recent Towers insertion site paper(1) would be a good one to include, and there was an NCI study last year(2) which examined prostate cancer samples and didn't find anything via a couple different methods and as a result questioned whether XMRV was a genuine human pathogen, the Abbott/rhesus macaque antibody study(3) which only found XMRV antibodies in like three of a thousand-plus samples which the authors excluded from the results due to them considering the samples in question to be false positives, etc.
1. Analysis of XMRV integration sites from human prostate cancer tissues suggests PCR contamination rather than genuine human infection http://www.retrovirology.com/content/8/1/13
2. XMRV: a new virus in prostate cancer? http://www.ncbi.nlm.nih.gov/pubmed/20966126
3. Characterization of antibodies elicited by XMRV infection and development of immunoassays useful for epidemiologic studies http://preview.retrovirology.com/content/7/1/68 —Preceding unsigned comment added by 74.51.82.193 (talk) 06:28, 4 March 2011 (UTC)
- I believe the antibodies are addressed in http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839973/?tool=pmcentrez where they were found to be mostly false positives. This should perhaps be mentioned in the article. --sciencewatcher (talk) 15:40, 4 March 2011 (UTC)
- Those are two different studies- the Groom paper studied neutralizing antibodies in CFS patients and controls, with the controls having the vast majority of 'positives', indicating that the antibodies in question were not specific for XMRV. The Qiu study is also known as the 'Emory/Yerkses/rhesus macaque study' where they infected rhesus macaques with XMRV in order to characterize XMRV-specific antibodies and then tested something like a thousand-plus healthy blood donors for these XMRV-specific antibodies and only found I think three equivocal 'positives' which they ended up discarding from being included in the analysis due to them being deemed false positives. —Preceding unsigned comment added by 74.51.82.193 (talk) 02:04, 5 March 2011 (UTC)
- I don't disagree that the article needs updating to reflect new information, but care should be taken in the "restructuring" not to impose an alleged inevitability of the demise of XMRV when such has not been properly established, at least in print. Even if it were to appear to be over for XMRV, Wikipedia is not a crystal ball, and I agree with RobinHood70 that fundamental questions remain to be answered. These papers may remain unpublished rumour papers for some time yet, or be subject to shameless hype like the Wellcome Trust press release was and end up in more mea culpas like Racaniello's.
- Keepcalmandcarryon claims "the article currently cites multiple news sources, websites and controversial primary sources"
and uses this for an argument to add conference abstracts. I'm guessing "controversial primary sources" is a reference to Lombardi et al and Lo et al? Anyway as far as I can tell, no news sources or websites are actually being used in this article to make scientific claims about XMRV itself,which is what Keepcalmandcarryon wants to do by lowering the standards of MEDRS so we can include rumour abstracts from a conference to support the notion that it is basically over for XMRV. But this goes both ways; do we then start including abstracts from other conferences and discussions from the BWG meetings which support the "pro-XMRV/MLV" side of the argument? - Considering that Keepcalmandcarryon has from the very beginning been somewhat antagonistic towards XMRV, going beyond mere "caution" with the WPI, and clashing with several Wikipedians who questioned the twisting of sources used in this article, I must say I am surprised at the recent statement that "I would have agreed with RobinHood on at least the possibility of going either way until I had a look at the CROI 2011 information."
- _Tekaphor (TALK) 02:54, 6 March 2011 (UTC)
- I think if we all just wait a little while, we will have all the info published in MEDRS sources. At some point we will also have the new NIH/FDA study published which will (in theory) sort out this mess once and for all. --sciencewatcher (talk) 15:51, 6 March 2011 (UTC)
- I'm not asking editors to look into a crystal ball, and I did not advocate citation of conference abstracts. It's just that, in my opinion, a peer-reviewed abstract from John Coffin, presented at the leading scientific meeting on retroviruses where half of all abstracts are rejected, is at least as reliable as some of the sources presently cited. That's an argument to give less weight to those sources, not to cite abstracts.
- No study has yet replicated WPI's results; even Lo et al. was negative re: XMRV; and a host of published studies, plus a growing list of peer-reviewed conference abstracts, have come up negative. Add to this the cautionary pieces from leading virologists, some involved in the research and some watching from a distance, and there is more than enough, RS-wise, to make more clear in the article that pretty much no one is still arguing that XMRV is associated with CFS and that the prostate cancer link is becoming rather controversial, too. Keepcalmandcarryon (talk) 17:03, 8 March 2011 (UTC)
- I made a few changes. We must be careful not to place too much emphasis on primary sources. An entire paragraph for the XMRV-negative Lo et al. study is, for example, quite inappropriate. We should plan to cite Weiss in the article and to balance the entirely primary drug study information with the cautionary writing of Maldarelli and others. Keepcalmandcarryon (talk) 17:33, 8 March 2011 (UTC)
- And one more point. The WPI results were not endorsed by the National Cancer Institute or the Cleveland Clinic. That one or two researchers from these institutions have their names on the Science paper does not justify associating the results with their organisations. In contrast, WPI is associated with the results. Keepcalmandcarryon (talk) 17:40, 8 March 2011 (UTC)
this just came out today. It looks like the writing is on the wall for XMRV. --sciencewatcher (talk) 16:28, 9 March 2011 (UTC)
- Suggestions:
- Place greater emphasis on contamination in the lede.
- Change the "disease association" section title, perhaps to "disease association controversy" or "proposed disease associations and contamination", as no disease associations have been established. An introductory sentence or two should summarise the history and the contamination/rumour virus theory, followed by subsections on prostate cancer, CFS, other conditions (combined into one paragraph), and contamination.
- Move or remove the "Transmission" section, which in any case is currently misplaced. This is all or mostly speculation, and the recent findings would suggest that we de-emphasise transmission.
- Some of the transmission information could be included in a new and brief section on the sociological dimensions of the CFS controversy and the actions of WPI/Mikovits/others in commenting about blood supply, speculated disease associations and appropriateness of antiviral treatments.
- The "drug studies" section should removed or at least changed to "in vitro XMRV research", which would also include other XMRV investigations. There should be no implication that antiviral treatment of purported XMRV infection in humans is currently sanctioned or justified according to any reliable source. Keepcalmandcarryon (talk) 18:41, 9 March 2011 (UTC)
- You may be right, SW. What they're talking about certainly seems plausible. At the same time, though, I've seen other pre-release info that makes some of the XMRV contamination theories implausible. As always, I think we're in limbo until there's more evidence as to precisely what's going on, and the reviews to back it up. For those of you with FB accounts (at least, I think you'll need one), this seems to very briefly summarize the back & forth. Strangely enough, Coffin is one of the ones in the "BWG" sections of that page, so he seems to be saying two different things simultaneously...that it's all contamination and that not all contamination can be explained away. I'm having difficulty reconciling the two, and much of the science is way beyond me. So...back to what I said about waiting for reviews. ;) – RobinHood70 talk 21:12, 9 March 2011 (UTC)
- Thanks for the link RobinHood70, which worked without a FB account. My understanding is similar to yours. For those who are keen, the recently published update discussed in the link is PMID 21366602 where results and plans are presented. Contamination is only given a single paragraph, the possibility is acknowledged and caution is advised, the 5 Retrovirology papers from late 2010 are cited, but not much weight is lended to the hypothesis itself. The Phase II results weren't as encouraging as some had hoped, but they are still moving forward. CROI 2011 was after this paper was authored so their position may be revised after the rumour papers get published as well.
- Keepcalmandcarryon, OK, I'll strike out that part of my comments. Both sides of a controversy need to be addressed, obviously according to appropriate weight. Unpublished abstracts from a conference are not "at least as reliable as" primary sources published in high ranking journals such as Science and PNAS, regardless of the rumours and "rumblings". Tekaphor (TALK) 02:25, 10 March 2011 (UTC)
- The lead currently states: "Initial reports associating the virus with prostate cancer[2][3] and chronic fatigue syndrome (CFS)[4] were followed by a large number of studies in which no association was found.[5][6][7][8][9][10][11][12][13][14][15]" Is it accepted practice to list a whole bunch of primary sources, basically every single published negative study, in the lead like that, just to demonstrate a point? - Tekaphor (TALK) 02:44, 10 March 2011 (UTC)
- There are several negative studies that have not yet been included in this list, but I do agree that it appears rather like a demonstration of a point. However, if we're going to include the unreplicated WPI study, it must be balanced by the many negative studies, not just one or two. My take on the lede is that it's unnecessary to cite any sources there, as everything in the lede should be expanded upon (and fully cited) later in the article. But that's just me, and others obviously disagree.
- On the other issue, I haven't advocated citing conference abstracts. But you must admit that the results of Coffin, Switzer, Pathak, Maldarelli, and many others are not just rumours and rumblings. They were accepted through peer review and presented at the world's leading conference on retroviral science. (If you would like to discuss rumours and rumblings, please send me an e-mail.) With the growing weight of evidence against the WPI hypothesis in the literature (and I emphasise once more that Lo et al was negative on the XMRV question), including the new results, reports and publications by members of the working group, there's no reason to continue presenting the XMRV subject as if there were an equally weighted scientific debate. Keepcalmandcarryon (talk) 03:06, 10 March 2011 (UTC)
KCCO, in case you have forgotten, I believe the issue of co-authors has been discussed before. The Science paper clearly states Vince Lombardi and Frank Ruscetti to be co-lead authors. "Vincent C. Lombardi* Francis W. Ruscetti*- *These authors contributed equally to this work." Jaydip Das Gupta of the Cleveland Clinic was second author. The NCI and Cleveland Clinic both issued press releases upon it's publication clearly stating their involvement in the study so your statement that the results were never 'endorsed' by the institutions in question is incorrect.
Consortium of Researchers Discover Retroviral Link to Chronic Fatigue Syndrome- NCI http://www.cancer.gov/newscenter/pressreleases/2009/cfsxmrv
Research Shows a Potential Retroviral Link Between XMRV and Chronic Fatigue Syndrome- Cleveland Clinic http://my.clevelandclinic.org/news/2009/research_showing_potential_retroviral_link_between_xmrv_and_cfs.aspx http://www.youtube.com/user/ClevelandClinic#p/search/1/gl35thTv_SQ http://www.youtube.com/user/ClevelandClinic#p/search/2/RWOWvdiXiSE —Preceding unsigned comment added by 74.51.82.193 (talk) 11:28, 12 March 2011 (UTC)
- There is one organisation that is synonymous with the putative XMRV-CFS link and is known for nothing else. That organisation is WPI, not the Cleveland Clinic or the National Cancer Insistute. Shall we write that the United States government found a link between XMRV and CFS, since NCI is a government entity?
- If there is one organisation that deserves mention in the article, that organisation is WPI. If Cleveland Clinic and NCI are added, we must also note that NCI researchers have been also had negative results, and, for weight, we should also list the affiliations of all researchers involved in the negative results. I don't think that's appropriate for a general encyclopaedia.
- Since there are too many names to mention and some editors don't want to see WPI named without the company of more established organisations, let's simply omit the organisation names. Keepcalmandcarryon (talk) 16:59, 14 March 2011 (UTC)
- That seems like a reasonable change, although it should probably be noted somewhere that WPI were the first to report a link. Either that could be added as its own factoid somewhere in the first paragraph, or perhaps just as a clause in the next paragraph where WPI is first mentioned. – RobinHood70 talk 23:33, 14 March 2011 (UTC)
10 million Americans ?
According to http://treatingxmrv.blogspot.com/ ,Lombardi et al demonstrated that this new human retrovirus is circulating in the blood of as many as 10 million Americans. : wouldn't it be usefull to check/quote/reference this ? Trente7cinq (talk) 13:22, 18 March 2011 (UTC)
- Sorry blogs aren't usually considered a reliable source for use in medical and science articles. Please see WP:SPS and WP:MEDRS. Ward20 (talk) 19:29, 18 March 2011 (UTC)
Drug studies
I have decided to remove the drug studies section in its entirety. A few primary in vitro studies seem a bit out of place in an article about what is almost surely a recombinant murine virus that hasn't been shown to be associated with, much less cause, disease. As stated previously, there may be a place for a brief mention, but it must be balanced with cautionary statements from the literature about the off-label use of these drugs. Keepcalmandcarryon (talk) 02:55, 22 March 2011 (UTC)
Conclusions
I removed the sentence, Reported detection of XMRV is widely thought to represent contamination of clinical specimens and laboratory reagents with mouse retroviruses or related nucleic acids[1][2] and has been called a "rumour virus". because it wasn't supported by the cited sources, or any other WP:MEDRS source I could find.
Smith in Contamination of clinical specimens with MLV encoding nucleic acids: implications for XMRV and other candidate human retroviruses (which is only a viewpoint article but seems to be the best secondary RS on the issue presently) states in the introduction: The underlying factors responsible for this discord are unclear; but from the beginning, researchers have repeatedly voiced concerns that at least some accounts of PCR-positive results are attributable to the inadvertent contamination of human specimens or reagents with mouse DNA. And in the conclusions: The reports discussed above [8-11] collectively identify three potential sources of contamination in PCR-based studies of XMRV:... Collectively, these results cast serious doubts on the PCR evidence used to support claims of MLV-related viruses in prostate cancer and CFS patients. Future assessments of the prevalence of XMRV should include more rigorous PCR and phylogenetic tests to exclude the possibility of contamination.
So the Smith viewpoint article supports the original wording which I reinserted.
The other source given was Garson, Analysis of XMRV integration sites from human prostate cancer tissues suggests PCR contamination rather than genuine human infection., which is a primary source from three researchers. They say: We propose that the patient-derived sites are the result of PCR contamination. And: In conclusion, we believe that our findings undermine a central component of the evidence for XMRV being a human pathogen.
So the primary source did not support the removed sentence either. Ward20 (talk) 08:16, 22 March 2011 (UTC)
- I'm afraid I don't follow this line of reasoning. At least five published studies propose that XMRV detection is the result of contamination of samples and/or laboratory reagents. Both PCR contamination and contamination of clinical samples by mouse viruses are identified as sources. This is precisely what was written (and sourced). The word "widely" is something we could discuss, but the evidence for contamination is presented in multiple published studies, secondary sources, presentations at the conference on retroviruses, and news reports (even in Science, which originally published the WPI paper and has been quite WPI-friendly throughout the controversy). This is balanced by press releases from WPI. Members of the scientific community are clearly concerned that XMRV is nothing more than a contaminant, and the article should reflect this concern, not simply repeat a technical phrase about PCR contamination. Keepcalmandcarryon (talk) 14:59, 22 March 2011 (UTC)
- As far as I know, there is no WP:MEDRS review source that supports, "Reported detection of XMRV is widely thought to represent contamination of clinical specimens and laboratory reagents with mouse retroviruses or related nucleic acids". If there is, please present the passages that support it. Studies are still being published that are finding XMRV[3]. I agree that some "Members of the scientific community are clearly concerned that XMRV is nothing more than a contaminant", but even that doesn't seem to have been published in a WP:MEDRS review. It is against policy for editors to survey multiple primary sources, news articles, and conference presentations to write a conclusion that hasn't been published. What is there now about contamination is only from a viewpoint article which arguably isn't MEDRS.
- The Science study wording is actually, "These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS". Using the word claim about a possibility
is just POV and poor writing.implies a bias. Ward20 (talk) 17:50, 22 March 2011 (UTC)
- The Science study wording is actually, "These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS". Using the word claim about a possibility
- Ward20, I appreciate the disappointment that the recently reported XMRV results have caused members of the CFS community, and I can certainly forgive the tendency to take it out on the messenger with accusations of poor writing and POV. However, the sources in the article now, as well as those you deleted, support "contamination of clinical specimens and laboratory reagents with mouse retroviruses or related nucleic acids". Which part of this is objectionable to you? Clinical specimens? Laboratory reagents? Mouse retroviruses? Mouse nucleic acids (endogenous viruses)? This is all in the sources. The first part of the sentence, "Reported detection of XMRV is widely thought to represent", is quite negotiable, as I stated earlier, and may very well be evidence of my notoriously execrable writing, but that's probably not a good reason to remove verifiable information and reliable sources. Keepcalmandcarryon (talk) 22:04, 22 March 2011 (UTC)
- Keepcalmandcarryon, I've asked you many times to talk about edits not editors. I don't appreciate it. Make that one more time.
- Reported detection of XMRV is widely thought to represent contamination of clinical specimens and laboratory reagents with mouse retroviruses or related nucleic acids. has two major problems:
- No MEDRS source has stated any consensus that reported detection of XMRV in studies is contamination.
- The primary sources discuss doubts on the PCR evidence, not the other methods of XMRV detection in the positive studies.
- A little perspective please.
I removed one sentence unsupported by the sources along with one primary source that didn't support the material and restored the previous material supported by a secondary source that you removed.(see below) Also, Keepcalmandcarryon removed a whole section along with a primary source that supported the material.
- A little perspective please.
- WP:CLAIM is in play here, there is no MEDRS stating any consensus on detection of XMRV and contamination in the Science study. Ward20 (talk) 07:41, 23 March 2011 (UTC)
- Per clarification requested by Keepcalmandcarryon, strike out sentence should read: I removed one sentence unsupported by the sources along with one primary source that didn't support the material and restored the previous material Keepcalmandcarryon replaced, supported by the Smith secondary source retained by Keepcalmandcarryon's edit.
- I apologize to Keepcalmandcarryon for the error in the strike out above. Ward20 (talk) 20:21, 23 March 2011 (UTC)
- The literature is quite clear on the point that concerns about contamination abound. I'm not sure why you're singling out the Science study. My sentence did not, as these concerns apply to all XMRV research. Take the secondary source from Smith (which I certainly did not remove). ...from the beginning, researchers have repeatedly voiced concerns that at least some accounts of PCR-positive results are attributable to the inadvertent contamination of human specimens or reagents with mouse DNA. Several paragraphs later, Smith refers to mouse genomic DNA and mouse viruses in a human cancer cell line as possible contaminants. These are precisely the elements in the sentence I wrote: human specimens; reagents; mouse DNA; mouse viruses. In addition, I provided another recent study on contamination that rendered the current language (four studies) out-of-date. There are yet more potential sources, Weiss, Shen, etc., which make the point about the rich history of retroviral "rumour viruses". Or we could simply quote John Coffin, who declared, "It's all contamination" (Science, 11 March 2011). "Widely suspected", "researchers suspect" "scientists have concerns"...I'm not sure what language would satisfy here, but the current version needs revision. Keepcalmandcarryon (talk) 19:08, 23 March 2011 (UTC)
- We already mention the 4 contamination studies in the lede, and expand on them in the article (we have an entire section). I think Ward20 is correct in saying that we need to be careful how we string together these primary sources. If you wanted to go further you would need to use a source such as the recent LA times article. However it might be more appropriate to add that info to the WPI article. Also, the WPI article is quite out of date on the research (it only lists 4 negative studies), so I'm thinking that people should maybe spend more time updating the WPI article and less time arguing here. --sciencewatcher (talk) 19:24, 23 March 2011 (UTC)
- Two points:
- There are at least five primary sources on contamination, so the current sentence is out-of-date.
- The update I added is from the secondary source accompanying the first four primary sources: ...from the beginning, researchers have repeatedly voiced concerns that at least some accounts of PCR-positive results are attributable to the inadvertent contamination of human specimens or reagents with mouse DNA. Keepcalmandcarryon (talk) 19:58, 23 March 2011 (UTC)
- Two points:
- @Keepcalmandcarryon, the Science article was singled out in my talk page edit concerning this sentence of the article, not other edits. I have no problem with the material in the latest revisions. They state the sources well. Thanks. I believe the Smith source alone without all the primary sources supports the sentence that starts," Numerous researchers", but it's not a big deal to me.
- @Science watcher, thanks for the suggestions and trying to moderate. Ward20 (talk) 20:56, 23 March 2011 (UTC)
- Thanks for striking. Keepcalmandcarryon (talk) 21:02, 23 March 2011 (UTC)
Reorganisation
Any thoughts on the following?
- Could we take the "Transmission" and "Contamination" subsections out of "Disease Associations", and if so, what would be an appropriate title for a new section?
- Would any editors object to removing the unsightly citation strings from the lede? I maintain that citations in the lede are unnecessary and distracting, especially in their current form.
- Revision of the drugs section.
Thank you . Keepcalmandcarryon (talk) 23:51, 23 March 2011 (UTC)
- What is the context for "Contamination" apart from the disease association studies? Since there is no scientific consensus that infection of humans has occurred, I'm not sure a "Transmission" section belongs in this article at all; that said, controversy regarding the blood supply would be a notable topic under which that existing content could be refined. Agree with removing citation strings from lede to other sections. -- Scray (talk) 00:05, 24 March 2011 (UTC)
- Thanks. I see your point on contamination. Keepcalmandcarryon (talk) 18:07, 24 March 2011 (UTC)
- The lede, and the page organization overall, is significantly improved. Nice work! Sorry I have not pitched in more (off-wiki life is currently more hectic than usual). -- Scray (talk) 19:25, 24 March 2011 (UTC)
- Thank you! Keepcalmandcarryon (talk) 16:18, 25 March 2011 (UTC)
- The lede, and the page organization overall, is significantly improved. Nice work! Sorry I have not pitched in more (off-wiki life is currently more hectic than usual). -- Scray (talk) 19:25, 24 March 2011 (UTC)
- Thanks. I see your point on contamination. Keepcalmandcarryon (talk) 18:07, 24 March 2011 (UTC)
Questions about contamination
In this edit I reverted the underlined insertion (emphasis is mine):
From the first reports of XMRV and disease associations, scientific researchers have been concerned that some of the positive PCR findings could be artifactual, the result of contamination with nucleic acids from mice or mouse viruses.[5]
The source cited PMID 21171980 has this sentence:
The underlying factors responsible for this discord are unclear; but from the beginning, researchers have repeatedly voiced concerns that at least some accounts of PCR-positive results are attributable to the inadvertent contamination of human specimens or reagents with mouse DNA.
The wording in the source would be consistent with researchers being concerned that anywhere from some to all (i.e. at least some of) of the reports of XMRV/MLV are due to contamination. If we retained the insertion "some of" in our statement, that would not reflect the source (because it would be limited to "some of", i.e. not all). We could use "at least some of", but that would be clumsy in the context of our current wording. Therefore, I reverted the insertion, because (as I said in my edit summary), the use of the subjective "could" in our sentence softens it in a manner that reflects the source accurately. -- Scray (talk) 03:39, 28 March 2011 (UTC)
- But the way it reads presently, "scientific researchers have been concerned that the positive PCR findings could be artifactual" states "the findings" (all), and doesn't represent some to all. Ward20 (talk) 04:58, 28 March 2011 (UTC)
- As Scray noted, the source says "at least some", presenting a possible range from two of the four or five positive studies to all of them, and the source says "are" not "could be". But let's not ignore the evidence by overexamining the exact language in only one source. Multiple reliable sources present the artifact worry. It is not restricted to PCR concerns. There are also concerns about the specificity of anti-XMRV antibodies, which we do not currently address. Keepcalmandcarryon (talk) 15:24, 28 March 2011 (UTC)
Glossary at end of article
Why do we have the "Glossary" link (to Oncology-related terms) at the end of this article? -- Scray (talk) 21:46, 28 March 2011 (UTC)
- It may relate to the XMRV prostate cancer studies. I'm not sure of the relevance. Ward20 (talk) 22:39, 28 March 2011 (UTC)
22Rv1 does not contain XMRV
"The authors conclude that XMRV contaminated 22Rv1 cell cultures, likely during passage in athymic mice." - That line is incorrect. 22Rv1 only contains a virus that is similar to XMRV, 22Rv1 has still not been fully sequenced.
"These results provide independent confirmation of retrovirus production by 22Rv1 cells and show that the virus produced by 22Rv1 cells is similar to XMRV over its entire length and not just over the gag region that we sequenced," [3] Knouf, 2009 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704771/ — Preceding unsigned comment added by [.Barny Toll (talk)• 12:56, 31 March 2011
- Yes, and what do you call a retrovirus that's similar to another retrovirus over its entire length? The same retrovirus. The authors started out with the knowledge that 22Rv1 makes a virus, which they called the 22Rv1 virus. By sequencing, they found that it was more-or-less identical to XMRV. That is, it was XMRV. From the Knouf/Miller paper: Here we describe the detection of multiple integrated copies and high-level production of XMRV from 22Rv1 prostate carcinoma cells. And From these data, we conclude that the 22Rv1 virus is XMRV and is not a mouse xenotropic virus acquired during passage of the cells in culture or in mice. Clearly, the authors of this 2009 article consider the 22Rv1 virus to be XMRV.
- In any case, the paper cited in our article is from late 2010. In it, we find this: We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result of PCR contamination with mouse DNA and that the described clones of XMRV arose from the tumour cell line 22Rv1, which was probably infected with XMRV during xenografting in mice. Keepcalmandcarryon (talk) 16:12, 31 March 2011 (UTC)
- No they have found it is "similar" not identical. It is only 30% homologous in the env region, and has not been fully sequenced as you have alluded to. They may have decided it might be XMRV, but the paper does not provide the necessary evidence and it is this which is relevant in science. If you start to claim a 30% difference is XMRV, then Lo et al certainly found XMRV. Which paper are you citing for 2010? 22Rv1 has not been fully sequenced, and as the Miller paper says " and 33% of the Env protein sequence. " It has not been fully sequenced, and no evidence exists for anyone to claim it is XMRV until it has.
- The statement about "identical XMRV integration sites were also found, a phenomenon never before reported for a retrovirus", is also incorrect. Integration has been shown to occur in hotspots as small as 10 base pairs. Really, if people here are going to claim to be accurate they should present all the relevant information instead of selectively editing based on emotions. — Preceding unsigned comment added by.Barny Toll (talk) 09:34, 1 April 2011
- The heading of this section is "22Rv1 does not contain XMRV". The paper you cited clearly states the opposite - it's the main point of the paper, and is accurately represented by the quote Keepcalmandcarryon cited above. We must not, as WP editors, re-interpret the data in a peer-reviewed article; rather, we can cite the article as supporting their main conclusions. They concluded that 22Rv1 contains XMRV (if you don't like that conclusion, find other MEDRS that refute it). -- Scray (talk) 12:39, 1 April 2011 (UTC)
- I would leave this note on the user talk page of an account editor, but as IP addresses can change, I will leave it here: If you have questions about a scientific source, please ask them at the reference desk or elsewhere to ensure you are not misrepresenting the source.
- I'm concerned that you have, several times now, taken short quotes out of context from a publication because of what I hope is just a misunderstanding of the science. Actually, your quotes are not from the publication itself, but from an addendum to the publication, in which Miller and colleagues describe recent proteomics work that also supported their assertion that the 22Rv1 virus is XMRV. Nowhere in the addendum or the paper do the authors state that the 22Rv1 virus and XMRV are "only 30% homologous in the env region". Instead, they state that proteomics results included exact peptide matches for "54% of the Gag, 47% of the Gag-Pro-Pol, and 33% of the Env protein sequence". This doesn't mean that the remainder of the Env sequence was different; rather, it means it was not detected. There are many technical reasons for this. In proteomics research, a protein is often unambiguously identified based on only two or three peptides; sometimes just one. Here, the virus is identified by many exact matches.
- Only infrequently am I accused of having emotions about retroviral integration sites. That said, if you have a reliable source that demonstrates identical but independent integration sites for other retroviruses, you're welcome to present it. We could note this beside the current statement. However, I'm not aware of any such sources. Keepcalmandcarryon (talk) 14:23, 1 April 2011 (UTC)
- I am concerned that you are not reading the paper in question and have misrepresented the data. The abstract clearly states that "Here we show that 22Rv1 prostate carcinoma cells produce high-titer virus that is nearly identical in properties and sequence to XMRV isolated by others". The data in this paper shows it has not been fully sequenced and is not considered to be identical to XMRV. If you cannot provide a source that shows it has been fully sequenced then you cannot state it is the same virus. Unless you want to claim sequences with less homology than those found in Lo et al are the same virus, and circumvent the scientific process due to emotions that are out of control. As you have shown with the quote above, 67% of the env sequence has not been sequenced, neither have large portions of the gag and pol. If there is no data, you cannot make such a statement. It is therefore on you to provide a source that shows differently. Either correct the line or remove it. Time to get those emotions in order. Barny Toll (talk) 22:19, 1 April 2011 (UTC)
- It is not our role to interpret the data; rather, we base our edits on main conclusions from cited sources (and find other relevant reliable sources when we can). It's up to the authors and peer reviewers to ensure that the results support the conclusions. The paper explicitly concludes that 22Rv1 contains XMRV. As previously pointed out by Keepcalmandcarryon, you (and the prior IP editor, if you are distinct) continue to misinterpret the addendum (added at the proof stage, btw) about the proteomics analysis (those statements do NOT indicate that 67% of the env region has not been sequenced). I won't belabor that point because rereading the response above should clarify. This seems to be devolving toward WP:IDHT. -- Scray (talk) 16:52, 2 April 2011 (UTC)
- I am concerned that you are not reading the paper in question and have misrepresented the data. The abstract clearly states that "Here we show that 22Rv1 prostate carcinoma cells produce high-titer virus that is nearly identical in properties and sequence to XMRV isolated by others". The data in this paper shows it has not been fully sequenced and is not considered to be identical to XMRV. If you cannot provide a source that shows it has been fully sequenced then you cannot state it is the same virus. Unless you want to claim sequences with less homology than those found in Lo et al are the same virus, and circumvent the scientific process due to emotions that are out of control. As you have shown with the quote above, 67% of the env sequence has not been sequenced, neither have large portions of the gag and pol. If there is no data, you cannot make such a statement. It is therefore on you to provide a source that shows differently. Either correct the line or remove it. Time to get those emotions in order. Barny Toll (talk) 22:19, 1 April 2011 (UTC)
- Then why are you interpreting the data? There is no source that shows the virus in 22rv1 to have been fully sequenced. The paper explicitly states that the virus is nearly identical, and the data reflects that. Only 33% has been sequenced. If you cannot read this I suggest you are out of your depth and should leave the editing to those who do have the necessary experience. This is the same old party line that a cabal here push, which has nothing to do with science and is only about an agenda and emotions. I am sure you will now call on your friends to help you out with larger numbers of deniers, who also cannot read the paper. It won't alter the facts. You have to present alternative ones if you want to claim differently. Barny Toll (talk) 18:15, 2 April 2011 (UTC)
- I am not interpreting, I am restating what was said explicitly in the paper: "...we conclude that the 22Rv1 virus is XMRV..." (snippet taken from Keepcalmandcarryon's quote above, for emphasis). Such an explicit statement always gets scrutinized by peer reviewers (so, it doesn't matter what evidence was presented in the paper - we're not here to synthesize new conclusions. Please stop attacking whatever you might infer of my credentials - this is about content, not editors. -- Scray (talk) 18:40, 2 April 2011 (UTC)
- Just out of curiosity (meaning, this is original research and therefore doesn't belong in article space) I took a look at the sequences of provirus from 22Rv1 reported in PMID 20335265 (Paprotka, NCI) and XMRV strain WPI-1178 reported in PMID 19815723 (Mikovitz, WPI). They differ at only 3 nucleotides (out of more than 8100) - essentially identical. I provide this to emphasize that (i) full sequences are available and (ii) they are nearly identical. This is consistent with the conclusions already attributed to cited references. You're simply misinterpreting the description of the proteomics data, as has been stated above. -- Scray (talk) 20:10, 2 April 2011 (UTC)
- Then why are you interpreting the data? There is no source that shows the virus in 22rv1 to have been fully sequenced. The paper explicitly states that the virus is nearly identical, and the data reflects that. Only 33% has been sequenced. If you cannot read this I suggest you are out of your depth and should leave the editing to those who do have the necessary experience. This is the same old party line that a cabal here push, which has nothing to do with science and is only about an agenda and emotions. I am sure you will now call on your friends to help you out with larger numbers of deniers, who also cannot read the paper. It won't alter the facts. You have to present alternative ones if you want to claim differently. Barny Toll (talk) 18:15, 2 April 2011 (UTC)
- Finally, you have bothered to find a source. Now shall we do this with the rest of the article? There are far too many claims on this page that are not supported with sources, yet I see you arguing about other points, when you have allowed others to post without a source. Either you stick to the guidelines, or you are only pushing an agenda. Get it now do we.Barny Toll (talk) 22:31, 2 April 2011 (UTC)
[Outdent]@Barny Toll, I want to support what Scray says on this point. The article -- or at least its current content relating to this point is not making claims about whether the virus in 22rv1 is identical to XMRV, per se. The statement is "The authors conclude that XMRV contaminated 22Rv1..." [my ital], and that content is an accurate reflection of a conclusion of the MEDRS primary paper. Even if you were right in your interpretation, it's not our job to interpret. We should leave this to MEDRS secondary reviews. -- TerryE (talk) 22:00, 2 April 2011 (UTC)
One other request on this topic. The wording "another article reported on the striking identity of XMRV genomic sequences ... " [my ital] is journalese. It doesn't make sense, and is not what the paper concludes. Identity surely means identity, and the reference doesn't even use the word "striking". What it states is that the XMRV sequences form a monophyletic clade with interspersed 22Rv1 clones. In layman's terms: you can't distinguish between the putative patient XMRV samples and those found in 22Rv1 (at a 0.99 confidence level). Perhaps "significant similarity" is better lay summary of this conclusion. -- TerryE (talk) 22:17, 2 April 2011 (UTC)
- Read above also. The paper I cited still does not provide the evidence. I want to see you all find it for once. Barny Toll (talk) 22:31, 2 April 2011 (UTC)
- Barny Toll: It does, you're just not paying attention. TerryE: you make a valid point - this is akin to "most unique", though as you know when molecular virologists speak of the degree of identity, what they mean is that many sites along the sequence are identical (thus, it's not an unreasonable construction). Whatever wording we choose must reflect the paper's conclusion, which was that the virus was XMRV. So, we could say that the virus sequences recovered from 22Rv1 were found to be consistent with XMRV. -- Scray (talk) 02:38, 3 April 2011 (UTC) -- Scray (talk) 02:38, 3 April 2011 (UTC)
- Unfortunately my academic background is maths and not biology :-) so I am a lot more comfortable with the concepts of distance measures and clustering than most. Scientific authors (and reviewers) tend to take great care in how they phrase their findings in the abstracts and conclusion content of their papers. The term monophyletic clade is well described in WP, and the conclusion that the 22Rv1 clones intersperse the clade form by the XMRV patient sample is such a case: it is a very compelling conclusion. The danger we face as editors lies in the two menings of "to interpret": (i) to translate, that is to convert [language] from a form understood by one population to that understood by another without the addition or changing of meaning; (ii) to add personal knowledge or experience and hence "enhance" the meaning in some way. To me, the first is entirely allowable under WP P&G, but the second is simply "under the radar" WP:OR and WP:SYNTH and should be avoided at all costs, as article content should accurately reflect MEDRS not "enhance" it.
- I may seem a little pedantic here, but my reason is that there is some scientific controversy around these contamination finding. Of course, no observer who believes in scientific method could rationally dispute such a body of finding: contamination is clearly a huge issue and provides plausible mechanisms to explain the findings of the minority papers. However, a number of field experts have also cautioned that it is a step-too-far to apply inductive reasoning here and state that they are currently sufficient to falsify the findings of Silver, Lombardi, et al, as some other experts are doing. I feel that this issue is too ill-defined and too recent to raise in the article itself, but we should take care not to imply one position as a fait accompli in our wording. -- TerryE (talk) 12:08, 3 April 2011 (UTC)
- I think you and I are in complete agreement on this point; for example, see my comments above under Restructuring where I emphasized the importance of the ongoing trial, that we all hope will be definitive, chartered by Collins and overseen by Fauci to investigate the concerns about contamination. This section here is about whether a specific cell line contains XMRV, and I'm dismayed by the amount of wasted "ink" for something that is well-established in cited references. -- Scray (talk) 15:39, 3 April 2011 (UTC)
- The authors of Knouf et al didn't take care though. Their conclusions didn't fit the data. But this is hardly the point in relation to having no source for the statement on the wikipedia page. Editors would of course be required to post accurate information. You cannot do that if you choose to follow a misleading conclusion that opposes the data presented. The scientific community is not immune to exaggerating results. Contamination may always be of concern, but without data to support that reasoning it is merely a belief. The Lipkin study wont't be considered to be definitive, as that is not how science tests a hypothesis. One study should not be overstated. We have multiple papers now that have used different methodology. If they had used a previously proven method or ensured their assays would work, the negative results would have likely have indicated a problem with the original study. Scray, you have wasted ink on the XMRV page by not providing sources, and making claims that are not supported by data. This is only one problem I will be raising. There are several more as I will highlight. Again, people have let their agenda's get away with them and provided sloppy editing. Barny Toll (talk) 16:40, 3 April 2011 (UTC)
- @Barny Toll, the issue here is about the accuracy and appropriateness of WP content based on MEDRS. If you want to criticise an accepted MEDRS, then please submit your comments to the appropriate journal. Yes, it is a primary source, but the point is quite subtle as we've talked about above, so I am not sure how we could precis it more than the current couple of sentences without losing clarity. I really think that we've just about done this one to death :-) -- TerryE (talk) 17:14, 3 April 2011 (UTC)
- The authors of Knouf et al didn't take care though. Their conclusions didn't fit the data. But this is hardly the point in relation to having no source for the statement on the wikipedia page. Editors would of course be required to post accurate information. You cannot do that if you choose to follow a misleading conclusion that opposes the data presented. The scientific community is not immune to exaggerating results. Contamination may always be of concern, but without data to support that reasoning it is merely a belief. The Lipkin study wont't be considered to be definitive, as that is not how science tests a hypothesis. One study should not be overstated. We have multiple papers now that have used different methodology. If they had used a previously proven method or ensured their assays would work, the negative results would have likely have indicated a problem with the original study. Scray, you have wasted ink on the XMRV page by not providing sources, and making claims that are not supported by data. This is only one problem I will be raising. There are several more as I will highlight. Again, people have let their agenda's get away with them and provided sloppy editing. Barny Toll (talk) 16:40, 3 April 2011 (UTC)
- Nothing subtle about it. There was no source provided and then you decided it was acceptable to use a source that presented apposing data. All to push an agenda. It's the same complaint about about most science pages on wikipedia. It is the individuals and cliques here that are choosing to present information as fact without data to support those conclusions. Yet, somehow you all believe you are providing a public service. Well who to? False and misleading information makes everyone look mentally challenged.Barny Toll (talk) 23:18, 4 April 2011 (UTC)
Paprotka et al sequenced the entire length of the 22rv1 virus and concluded it is XMRV- 'Inhibition of Xenotropic Murine Leukemia Virus-Related Virus by APOBEC3 Proteins and Antiviral Drugs' http://jvi.asm.org/cgi/content/short/84/11/5719
irish blood ban
will someone please add the fact that ireland has also banned blood donations from M.E patients due to possible xmrv transmission86.149.122.237 (talk) 20:54, 16 May 2011 (UTC)
http://nighearain.wordpress.com/2011/04/20/irish-blood-transfusion-board-bans-mecfs-patients-from-donating-blood/ 217.39.38.226 (talk) 12:10, 17 May 2011 (UTC)
Journal that published the original research has second thoughts regarding reliability.
[4] Doc James (talk · contribs · email) 20:24, 1 June 2011 (UTC)
- Doc James was referring to an article in Science. There have been subsequent reports that some previous studies were contaminated (see "Another Blow to Putative Cause Of Chronic Fatigue Syndrome" Science 13 May 2011:774), and Science has published an Editorial Expression of Concern regarding the 2009 Lombardi paper. It seems appropriate to review the recent literature and consider a major overhaul of this article. - J. Johnson (JJ) (talk) 22:15, 29 July 2011 (UTC)
Add HGRV as new acronym for XMRV
The WPI want to change (or already did) the acronym. — Preceding unsigned comment added by Bubbletruble (talk • contribs) 20:08, 5 August 2011
- While I know it's been suggested, and I've seen it used sometimes in the patient community, we need evidence of acceptance or endorsement of the term in medical or scientific circles before we would document it on Wikipedia. – RobinHood70 talk 20:59, 5 August 2011 (UTC)
Needs updating!
In light of the recent events – such as the new study that the original findings are not replicable, the partial retraction of the original paper, and the news that Mikovits has been fired; see also the "False Positive" article in Science and various commentary – this article needs some updating.
I also point out that the article could be modified to take the point of view of how this affair developed, as an illustration not that specific "science" is sometimes wrong, but how "science" (as process) and scientists resolve conflicting evidence. Do that well and this could be a GA. ~ J. Johnson (JJ) (talk) 21:31, 27 October 2011 (UTC)
- The 2006 paper has now been retracted, and new publications have been published.
A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus. Alter HJ, Mikovits JA, Switzer WM, Ruscetti FW, Lo SC, Klimas N, Komaroff AL, Montoya JG, Bateman L, Levine S, Peterson D, Levin B, Hanson MR, Genfi A, Bhat M, Zheng H, Wang R, Li B, Hung GC, Lee LL, Sameroff S, Heneine W, Coffin J, Hornig M, Lipkin WI. MBio. 2012 Sep 18;3(5). pii: e00266-12. doi: 10.1128/mBio.00266-12. Print 2012. PMID: 22991430
Infectious diseases. New XMRV studies bring closure--and fresh dispute. Enserink M. Science. 2012 Sep 21;337(6101):1441-2. No abstract available. PMID: 22997296
http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.0020025
user:Nocontroversytalk 18:45, 27 September 2012 (UTC)
- Also given the publication of the Lipkin findings this month, I think that the MEDRS consensus is strong enough to rewrite the article lead emphasising that XMRV is a purely laboratory artefact. I've crossed swords on this article too often to make the changes myself, but I just want to say that I would support anyone who talk this on. :-) -- TerryE (talk) 18:26, 9 October 2012 (UTC)
Out of date template
I've added a template in hopes of attracting editors to address the issues raised above. The article is indeed quite out of date. I plan to do some editing in the next few days. Keepcalmandcarryon (talk) 02:07, 30 May 2013 (UTC)
- The lead has now been worked over. As time permits, I plan to restructure the article to reflect the recent MEDRS and the weight of the RS overall. Possible sections are discovery; disease association and controversy; blood supply; Recombination and contamination; Retraction and misconduct allegations. Another possible section would cover the public and patient response to the story and its fallout, since there are clearly social implications and RS. Keepcalmandcarryon (talk) 14:59, 30 May 2013 (UTC)
- ^ Smith RA (2010). "Contamination of clinical specimens with MLV-encoding nucleic acids: implications for XMRV and other candidate human retroviruses" (PDF). Retrovirology. 7 (1): 112. doi:10.1186/1742-4690-7-112. PMID 21171980.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: unflagged free DOI (link) - ^ Garson, Jeremy A; Kellam, Paul; Towers, Greg J (2011). "Analysis of XMRV integration sites from human prostate cancer tissues suggests PCR contamination rather than genuine human infection". Retrovirology. 8: 13. doi:10.1186/1742-4690-8-13. PMC 3050814. PMID 21352548.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704771/