I was asked to write an 'XMRV for Dummies' on another forum (i.e. a simple explanation of XMRV research to date)...
I thought it might also be helpful for some people on this forum, so here it is...
It's such a complex subject, and I've written a lot of it from memory so there maybe some errors... if anyone spots any errors, I'd be very grateful if you could let me know please, so I can correct them, thank you.
Summary of XMRV research.
XMRV is the third known human retrovirus.
The others being HIV and HTLV.
HTLV can cause cancer and is mainly found in Asia which is why people living in western countries don't hear much about it. I think it is a public health issue in Japan, for example.
XMRV is a human retrovirus, and it is not a mouse virus, nor has it ever been found in any mice.
XMRV is very similar to mouse viruses called MLV's, but it is genetically different.
Who has found it so far?
XMRV was first discovered in 2006 in prostate cancer patients.
Judy Mikovits working at the WPI, and her co workers, were the first to isolate XMRV in ME patients and published their paper in October 2009.
The WPI isolated the virus, photographed it, sequenced its genome, and demonstrated it infecting a new cell under a microscope. They also detected antibodies to it in their patient blood samples.
Their published paper has a 67% detection rate, but they have now found XMRV in 97% of their original patient samples.
They also detected the virus in 3.7% of their healthy control samples.
The WPI have now done an, as yet, unpublished follow-up study in a random selection of UK ME patients, using the Canadian diagnostic criteria which includes 'post exertional malaise' as a symptom, and it is reported that they have so far detected more than 80% positive in the first 50 patients. They are also detecting XMRV in the UK healthy control samples at 6 to 8%. http://www.cfids.org/xmrv/wrkshp-data-comparison.pdf
Since the original WPI study, there has only been one published positive study relating to ME patients. This is why the media has been so quiet about it so far... we need more studies giving even more definite answers before the media has anything sensational to grab onto. However, the second positive study was by Harvey Alter, who discovered Hep C, working for the FDA, so this has sent the scientific community into a spin, and they finally seem to be taking XMRV seriously, as no scientist is ever going dispute any of Alter's work as he has such a high status in the scientific community. Alter works for the FDA, and the US health departments finally appear to be taking this retrovirus seriously as well.
Alter actually found viruses which are very similar to XMRV but which are not genetically identical. He says that some genetic variability is to be expected, just as there is with the Hep C virus, and that his discovery confirms and builds upon the WPI's work. Alter named his virus discovery 'PMRV' and Judy Mikovits now seems to be unofficially calling all these types of virus 'HMRV' (Human - Murine Leukemia Virus - Related Virus). Alter found the virus in 86.5% of his ME patient samples, and in 6.8% of healthy control samples taken from the blood bank.
There have also been some other low-key, but significant, completed XMRV positive studies announced [in Japan, Germany, Norway, Belgium, Spain and in studies by Dr Cheney and Dr Bell] including a study in Japan which tested the blood bank in Japan at 1.7% positive for XMRV. But this Japanese study did not look for XMRV in ME patients. I am not sure if any of these studies have actually been published in scientific journals yet.
There have been quite a number of published negative studies relating to ME patients, including two high profile studies from the UK. All of these studies detected zero XMRV in ME patients and zero XMRV in the healthy control samples. [Some did result in some inconclusive positive readings, but the positive readings were dismissed by the researchers and explained as either contamination (e.g. Brigitte Huber), as non-specific results, as non-specific 'neutralising activity', or as non-specific antibodies (e.g. Groom, Stoye and Kerr.)] Some of the researchers of the 'zero' studies also failed to detect XMRV in positive control samples (i.e samples that were already known to be XMRV positive) sent from the WPI, although the researchers did not mention this small fact in their publications, but it was brought to light afterwards by others! These zero/zero results really give the impression that these researchers were just incapable of detecting the virus at all, rather than the virus not being present in the samples. All of these negative studies used methodology that is used for detecting other viruses, such as HIV, and it seems that these existing methodologies are not adequate for detecting XMRV. It seems that detection of XMRV needs some very specialised and specific methodology for successful results.
The fact that these scientists were unable to detect any XMRV at all suggests to me that these studies can safely be ignored as using inadequate methodology, especially as Judy Mikovits has now detected XMRV in UK ME patients and healthy control samples taken from UK blood donors, proving that XMRV does indeed exist in the general UK population, maybe at about 6 to 8% (the detection rate for the healthy blood donors).
There are now quite a large number of significant positive papers, either being completed or waiting to be published, and we should see some of these before Christmas.
Some of these are going to be really significant studies, including work by the US government's 'blood working group' which seems to be a well-funded government body working towards standardisation of the methodology for detecting XMRV. This is a very important step, because then all scientists will be able to work on XMRV without arguing about whether their methodology is adequate or not. This work will also expose the inadequacies of the 'zero/zero' studies which have already been published. Members of the blood working group have indicated that they think they now understand where these 'zero' studies are going wrong, and it is something to do with the methodology of collecting blood samples or processing them for storage... We expect to find out by the end of the year. Judy Mikovits is part of this working group and it seems to be taking the threat of XMRV in the blood banks very seriously.
Judy Mikovits is working on completing her very significant XMRV study in the UK and is reported to be detecting XMRV in UK ME patients at about 80%, and detecting XMRV in samples taken from UK blood donors at 6 to 8% (some reports say 6.8% and some say 6-8%, or 4% using a different methodology.) Judy has also carried out other unpublished research on families with XMRV, including family members with autism.
There are also a number of very significant studies being started in the USA, organised by the government health departments, and by some of the biggest names in virology. They seem to be taking it very seriously now. Harvey Alter, who discovered Hep C, and Ian Lipkin (who did internationally recognised important work on SARS and the west nile virus) are just a couple of big names who are leading US government studies. The director of the NIH, Francis Collins, also seems to have taken a personal interest in ME and was present at the 1st International XMRV conference. Not to forget the ongoing research being done by the original investigators such as Mikovits and the Ruscetti's of the National Cancer Institute (NCI). Sandra Ruscetti has moved way beyond many other researchers new to the field of XMRV and she is now looking at the effect that XMRV has on the immune system and looking at ways to disrupt the way the virus attacks the immune system. She is also looking at the toxicity of the viral envelope to see if it may cause some symptoms of ME. As you can see, she has moved way beyond discussions about contaminants.
Why the disagreement over whether it is there or not?
XMRV in ME patients was a controversial subject in the first place...
It was always going to put many noses out of joint... Many scientists have built a career on denying the reality of ME, and being able to persuade governments that ME was not infectious, but was just a female hysteria disease...
So many negative studies have now been published, that it has enabled many of the psychiatrists and other vested interests to propagate tales about contamination and other reasons why XMRV doesn't exist in ME patients.
For scientists, the negative studies placed a question mark over the whole subject for quite a while, especially as some of the negative studies have been carried out by established scientists who looked like they legitimately couldn't find the virus, using existing accepted technology and methodology for detecting other viruses such as HIV.
Luckily, the US government seems to have now risen above the arguments against XMRV, and are taking this retrovirus seriously because it is infecting so many Americans (3.7 to 8 percent of the population, based on the studies, including infection of the blood bank). I believe that they are not so much worried about ME as they are about the retrovirus, but this has had the added benefit of ME being taken seriously for the first time ever by many scientists... The status of ME research really does seem to be moving upwards in the US now.
What proportion of ME patients are testing positive?
Between 80% and 97%.
This detection rate will depend on the advancement of the methodology, and the types of patients tested, and also possibly the tissue sampled and the severity of illness in the patients sampled. There are a number of different diagnostic criteria for ME, and the official USA criteria are not solely being used for these research studies because it allows the inclusion of psychiatric patients who suffer from fatigue. The 'Canadian criteria' are being used for the studies because they exclude psychiatric illnesses and include 'post exertional malaise', which most of us recognise as being a fundamental feature of our illness, which is unique to ME.
What about family members?
Very little research has been done at all so far, but Judy Mikovits has looked at some families, and has found XMRV running through the families that she tested. Some XMRV-positive family members are without any symptoms, some have ME, some have autism, some have just psoriasis or gluten intolerance. Judy is also looking at atypical MS but hasn't indicated any results for this work yet.
What treatments are being considered for testing?
Anti-retrovirals seems the obvious way forwards, and GlaxoSmithKline have already funded some preliminary research, and the NIH (National Institute of health in the USA) have indicated that they maybe starting clinical trials soon. Some ME patient bloggers have already reported considerable success with individual trials of anti-retrovirals, but other individuals on ME forums have reported a lack success with anti-retrovirals, and even a worsening of symptoms. There are a number of anti-retrovirals that have already been found to be successful at inhibiting XMRV in test-tube studies and these drugs, including combinations of them, will surely be the first to be trialed on ME patients.
Reasons XMRV is not a contaminate
Genetic variability of the virus has been demonstrated which you are not likely to get if it's a contaminant. Blood antibodies have been detected and you don't get human antibodies to lab contaminants. Independent labs have got the same results as the WPI in their latest UK study meaning that their research has been independently verified by different labs. 70 strains of mice have been screened and no XMRV has ever been found in any mice.
Judy Mikovits isolated the virus, she photographed the virus, she sequenced the virus and she showed it infecting a new cell under a microscope.
Harvey Alter did everything possible to satisfy the journal in which he published his results, that this was a new human retrovirus. He did everything possible to guard against contaminants (and he knows what he's doing). He also tested for contaminants. The only thing that he didn't do was to see if the PMRV's that he discovered had inserted themselves into the DNA of the patients. This final step would demonstrate absolutely that these viruses are behaving exactly as one would expect a human retrovirus to behave, but this wasn't necessary at this stage in the research, to convince many scientists that we have a new human retrovirus here.
My opinion regarding contamination:
The only people who still seem to need convincing about this virus are Reeves (practically unemployed), Wessely (soon to be unemployed, hopefully) and McClure, a virologist in the UK (apparently with her own agenda)... But these scientists all have vested interests or careers/reputations at stake, and egos are at play... But these individuals have become irrelevant now anyway... How times have changed!
So what does all of this mean?
The evidence, from a number of studies, shows that XMRV is linked to ME but the exact association is not yet known.
The actions of other human retroviruses suggest that XMRV is a likely causative candidate for disease but there is no evidence yet that XMRV is the cause of ME.
We are still in the very early days of understanding the virus but research investigations are now ongoing into the action of XMRV and the resulting changes in the immune system and to see if XMRV actually causes ME, along with trials of antiretorviral drugs.
We now need more evidence from larger studies of ME patients, and we need to see the results of research into the role of XMRV and its effect on the immune system including whether or not XMRV causes ME. We also need to know the significance of the differences between Alter's PMRV and Mikovits' XMRV.
There is a considerable amount of very interesting research in the pipeline... see Cort's blogs for some of the details...
See Cort's blogs for more details on research to-date, and info on upcoming research:
Chart of published XMRV papers, on the CFIDS Association of America's website:
Chart of unpublished research presented at the 1st XMRV international conference:
XMRV - An explanation of XMRV research so far...
Blog entry posted by Bob, Oct 19, 2010.