(This thread picked up from the "Dr. Vernon thread on the General News Forum": http://www.forums.aboutmecfs.org/sh...trists-from-the-Wesselly-school-as-Co-Authors) So you have no beliefs here? No speculation? I would say you have shown plenty of belief in your posts. I only say I believe something when I do not have the references handy to quote, but most of what I say I can back up with data. Just don't have the time to sort through it all continually, unless I am writing a paper. I could write out all the facts I am working from, probably have mentioned most of them already. But regarding current issues, the most important fact is that I know many people with CFS who are testing negative for XMRV, and they DO have CFS but do not have XMRV, including by WPI, and other outside labs that hopefully will eventually publish their studies. Yes, a systems model can really help in a complex situation like this. Systems biology is the study of interactions between parts of a biological pathology. Think of the 'sum of the parts being greater than the whole' but apply that to a disease model. I believe CFS is a perfect match-up with the systems biology paradigm. I believe there is a wiki entry on systems biology. [Gerwyn, an aside, you continue to use put-downs, and a condescending attitude in your posts. I can ignore this, and acknowledge that sometimes I may miss some things and over-react myself provoking that (blame the CFS), but I try to avoid direct put-downs and implied insults in disagreement. A disagreement is not an insult. I really think that given your background and working on a doctorate you should be above personal attacks. Can we stick to the discussion without all the insulting innuendo?] For the record, I think you are the one who is misreading a study here, namely the WPI study. I realize some parts of that are ambiguous, and some statements after publication about ongoing work with XMRV may be wrongly attributed to the original study. Anyway, what I am saying about HERVs and the WPI methodology is not just my own view, I am also getting this from other researchers back-channel. As I am sure you know, researchers get into factions over issues like this, and if you only talk to one side you only get half the story. So here are some of the points I suspect you may be either missing or ignoring: 1. WPI did not run any culture on samples prior to their PCR testing in the Science study, and they got positives from a very small blood amount. This has been confirmed by private emails from Mikovitz to outside researchers (I have not read those emails but my source is reliable). Also the order of presentation in the Science article implies they did not culture cells prior to PCR. The paper implies that the DNA was extracted directly from PBMC's for PCR. I realize the wording of the original study is a little difficult to interpret, I had to have some parts explained to me so I can not claim to understand this perfectly, but I believe what I have been told by outside experts. Am I talking with the wrong experts as you suggest? I have no way to know. But some statements WPI has made afterwards about culturing apparently apply to their ongoing work and not the Science article, although you and others on the forum seem to be interpreting those statements as meaning they pre-cultured prior to PCR and so must other labs. I have heard only the opposite from outside researchers. Other labs should not have to pre-culture PCR samples. WPI only cultured for antigen and infectivity tests and microscope images. IF WPI did pre-culture before PCR, then that is a major omission in their Science article that invalidates that article, and it should be amended or retracted. But of course that is not the case because as Mikovitz has apparently told people, they did NOT culture before PCR. 2. You raise a good point about the peer reviewers and the expert virologists who have made positive comments about the Science study. However, consider also that neither the peer reviewers nor the expert virologists, nor Judy Mikovitz claim to be experts in CFS. The peer reviewers and expert virologists might not have even known about the connection between CFS and HERVs. In fact the peer reviewers apparently wanted the paper to not even mention CFS. But we know that CFS has a host of very strange medical presentations in the brain, viral immune and detox systems, and that HERVs may be activated in CFS. So is it not possible that their assessment would apply more to ordinary retroviral patients and maybe they have not thought through all the special issues related to CFS in making those comments since they are unfamiliar with our disease? Also, if you are going to refer to experts, be sure to look at both sides. Not all experts are happy with the current XMRV testing and results. Dr Kerr for example has apparently believed at least his study and will not take further funding for XMRV research. 3. My opinion of the European studies is tempered by the fact that WPI did not pre-culture their PCR tests, and if there were ANY real CFS patients in the three cohorts used, then some of those studies should have had some positives. The fact that one UK study did include an antibody test and had some hits (more on the controls) suggests that the MuLV antibody study worked, as it hit something, such as an activated HERV perhaps, or some other antigen it cross-reacts with. If any significant number of those patients had XMRV, there would have been many, many more hits from the MuLV antibody. So why are these studies all negative? Either the cohorts were completely non-specific for CFS, in which case there should have been 2-4% positives, or the tests were incompetent, but they did get hits on control positives so even if they were diluted in strength there should have been some positives, or there was simply no XMRV in the patient population. Remember, WPI got hits on PCR without culturing. So that is why I am not making a big deal of the European studies except what I have already said, the UK studies had low sample volumes and one did not fraction out the Lymphocites further lowering the resolution, and the Dutch study may have had a very weak cohort (we can not know for certain without sample-by-sample background checks since in any study like this the samples may always exceed the diagnostic criteria). But some of those tests were RT-PCR and very sensitive and should have gotten some hits, even without culturing, given the WPI claims. 4. The situation in the UK is awful and I realize that XMRV, if it is true for CFS, could make some change happen there. That is great, but I don't think that issue has any place in the discussion of the science of XMRV. The lack of careful analysis of the WPI claims suggests to me that a bias is at work here on the forum. I want answers as much as anyone, but only correct answers. A false finding that is over-promoted could do tremendous harm to our cause, so I think it is best to wait for more studies before turning XMRV into an advocacy campaign, trying to force CAA to change their cautious stance towards XMRV, and raising patient hopes and expectations. Honestly I wish everyone would just wait, put this on hold, at least until after the CDC study and a few others are released (hopefully by mid summer). Anyway, CFS certainly DOES have a biological root cause, regardless of the outcome of XMRV, this is not the only angle for a solution to the political ME problem in the UK, I believe there is already more than enough evidence that CFS is biological, maybe the CDC and CAA should send a letter of protest to the NHS, and UK ME patients should find some way to have a voice. I would certainly sign on to any petition as a 'friend of the UK ME community' to advocate for change in the NHS position on ME, as I believe most here would, you really are among friends... You have to tackle political problems with better politics. 5. You say I speculate, and sometimes I do, just as you and many others here. So here is my connecting the dots, I think WPI may have inadvertently demonstrated the huge involvement of HERVs in CFS. After all, their 98% positive rate (or whatever it is) is using an antibody type (MuLV) that can sometimes be used to test the presence of HERV activation! That would be huge, and in a political sense would be better for us to have a HERV I think than an exogenous and communicable retrovirus (but that is a separate political issue, of course). 6. You have mentioned repeatedly that without culture the virus can not be found. I question that, particularly given one study that I quoted a few weeks ago that showed dozens of copies of XMRV in every infected cell (sorry have lost that ref, it is back on one of my prior posts). The virus should be found by PCR if it is present in the blood as WPI claims. Yes, that is an obvious problem with the 'quick and dirty' European studies (anyway that is what some researchers here call that type of study). It shows the low value of ME/CFS to those establishments. Regardless of my other views on the facts, this point is more clear now. To really check the XMRV results the outside labs need to take ME/CFS seriously. That means plan a clean study, carefully build a validation or replication assay and test it thoroughly before even collecting data, collect fresh blood samples, write a balanced report, draw only supportable conclusions, go through hostile peer review, and then give us something useful to talk about. (and yes, I do value hostile peer review, that is the best kind, a good scientist is as happy to be proven wrong as proven right, as both build knowledge, and anyway the important point is to get to the proof, not to be right). Sorry, I am missing your point here. HERVs are not completely understood yet, I know there is an issue with their being more active when methylation is failing, as LTR methylation is required to keep them dormant. Also, that HHV is known to activate them, but my point was that WPI used an MuLV antibody for the final step in this test, which is known to cross-react with some HERV classes. Therefore, the transfection may simply be movement of HERV activation triggers between the samples.