Sunday, February 28, 2010

More anti-XMRV *spin* and another attempt to damage Lombardi et al


Comment on the latest anti-XMRV "spin" surrounding the 3rd 0% positive XMRV study from The Netherlands

Stephen Ralph DCR(D) retired

26th February 2010

As many of you here will know, when Lombardi et al was published in Science back in October 2009, two documents were published widely on the Internet simultaneously and are available via the Action for ME web site and various web sites around the Internet.

The first Science Express Report (that appeared in Science) giving details of the study does indeed fail to state that patients were selected using the Canadian Criteria.

However, in the second document entitled Supporting Online Material it does clearly state that patients were selected using the Canadian Criteria and Fukuda.

Taken from the Lombardi et al supporting materials document….


Patient samples. Banked samples were selected for this study from patients fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome (S1) and the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) and presenting with severe disability. Samples were selected from several regions of the United States where outbreaks of CFS had been documented (S2). These are patients that have been seen in private medical practices, and their diagnosis of CFS is based upon prolonged disabling fatigue and the presence of cognitive deficits and reproducible immunological abnormalities. These included but were not limited to perturbations of the 2-5A synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as measured by standard diagnostic assays), and elevated cytokines particularly interleukin-6 and interleukin-8. In addition to these immunological abnormalities, the patients characteristically demonstrated impaired exercise performance with extremely low VO2 max measured on stress testing. The patients had been seen over a prolonged period of time and multiple longitudinal observations of the clinical and laboratory abnormalities had been documented.


The Kuppeveld et al study failed to give this sort of detailed outline of the patients they chose to use samples from.

In a Statement published today from Dr Charles Shepherd, it was asserted that Kuppeveld et al appeared not to know about the use of the Canadian Criteria because it probably wasn't mentioned in the paper that appeared in Science.

Well, if Kuppeveld et al couldn't be bothered to read all the relevant detail from the Lombardi et al paper including the background information - text that they were supposed to be fully aware of when comparing with their own study; then it would seem to me that there was an element of incompetence on the part of Kuppeveld et al for simply not bothering to read what should have been mandatory reading for the sake of fully understanding the subject..

Further evidence of this assertion could be made because Kuppeveld et al decided not to even bother with selecting their patients using Fukuda et al as per Lombardi et al and instead decided through their own apparent convenience to use the often criticised and even broader UK Oxford Criteria instead.

Over the years it has been pointed out that the Oxford criteria excludes people with ICD-10 G93.3 Myalgic Encephalomyelitis.

From their study, Kuppeveld et al did not validate their test against samples from CFS patients known to be XMRV positive.

This was in spite of the fact that the WPI and Judy Mikovits have been offering to share their work with anyone interested in replication research.

Kuppeveld et al did not carry out their study using at least 100 patients defined using both Fukuda and the Canadian criteria for all their subjects.

A number of 100 patients or more is usually the accepted minimum for decent competent research and anyone with an "A" level in Psychology or indeed an "A" level in any real hard scientific discipline will recognise this as necessary.

Kuppeveld et al only carried out a non-validated PCR test using 25% of the methodology employed by Lombardi et al. The Lombardi et al study took two and a half years to complete as opposed to all three of the recent studies that took just a matter of weeks from start to finish.

In spite of all of this, there have been assertions from the same source (Dr Charles Shepherd at the ME Association) in the same piece that this study from Kuppeveld et al together with the two other UK studies that also had multiple and similarly significant flaws, constitutes the casting of yet more serious doubt on the original Lombardi et al paper.

To reinforce this anti-XMRV "spin" there have have also been assertions that reputable laboratories were used but this curiously is not the issue of concern at all.

What matters is what brief these laboratories were given i.e. not to bother with replication – not to bother with validation of their test via the sharing of samples from the initial Lombardi et al study and not bothering with testing *any* *sample* by *any* *other* method than basic PCR – a testing method that Judy Mikovits has already stated in various lectures and web casts is potentially unreliable in relation to finding XMRV in patients with CFS and ME.

Click here for Dr Judy MIkovit's detailed XMRV presentation and Q &A Webcast from January 22nd, 2010

However, if there is an intention to bury any association between XMRV and CFS and ME as appears to be the case then the best way to bury that association would be to "crush" it under multiple "quick and dirty" non-replication research studies that do not bother *in* *any* *way* to even try to replicate Lombardi et al i.e. to look at the samples as closely and as hard and with the care and precision as the original scientists did – scientists who spent two and a half years on their work to make the pioneering findings that they did in three centres of reputed excellence across the USA.

So in closing, we have now had three "post Lombardi et al" studies – 2 in the UK and one in the Netherlands.

None of them bothered at all to replicate Lombardi et al.

None of the three studies used Fukuda *and* Canadian criteria to specifically select *all* their patients using the detailed outline of patient selection given in the Lombardi et al paper (see above).

None of the three null studies validated their test against samples from CFS patients already known to be XMRV positive.

None of these three studies even conceded that there is a growing population of CFS XMRV positive patients across the world including in the United Kingdom.

None of these three studies made any attempt to carry out the full range of testing methods specifically used by the Lombardi et al research i.e.

a) PCR on nucleic acids from un-stimulated and stimulated white blood cells;
b) XMRV protein expression from stimulated white blood cells;
c) Virus isolation on the LNCaP cell line; and
d) A specific antibody response to XMRV.

(Note: It should be emphasised that all four methods were needed for very good reasons and not just for the sake of wasting time and money. You can find out why by reading the Lombardi et al papers cited in this article.)

The simple fact is – thus far there is no emphatic or supportable evidence *anywhere* to state that there is no association between XMRV and CFS and ME.

On the other hand there is emphatic evidence of three "quick and dirty" non-replication studies from teams who decided for whatever reasons not obtain any samples  from the Whittemore Peterson Institute from known XMRV positive CFS patients meeting both the Fukuda and Canadian criteria.

All three studies did no precise replication any of the Lombardi et al study.

Yet all three studies obtained significant and totally coordinated 0% outcomes and accompanying publicity across the International media within minutes of publication and with the sole intention of casting "serious doubt" on the original study published in Science during October 2009.

Those in the profession of liaison psychiatry and Governments pursuing CBT/GET agendas (i.e. the PACE Trial in the UK) with vested interests in finding a 0% association between XMRV and CFS are the only people currently benefiting from "quick and dirty" 0% non-replication findings.

The jury is therefore still well and truly out.

For details from the Whittemore Peterson Institute concerning XMRV and CFS and ME go here.....

For all the XMRV News surrounding the October 2009 Lombardi et al Science article visit here.....


Stephen Ralph DCR(D) Retired.

* * *
Thank you, Dr. Ralph.
As another patient put it so bluntly, those doing the recent research "failed to do their homework".
As someone else said, "follow the money".  The first published refutation had Wessely's name on it.  Did you really think he'd cooperate in a study that was going to prove he's been wrong all these years in his assertions that CFS is just bad thinking on the patients' part?  He has a vested interest in proving there's no XMRV -- if CFS=XMRV, he loses his career, his income, his reputation, and will have to flee to some uninhabited place.
When Elaine DeFreitas found a virus in CFS patients' blood, she sent her own blood samples to CDC for the replication studies and they claimed they couldn't find it.  She sent her own samples and her own pre-mixed solutions and they claimed they couldn't find it.  She offered to come in person and show them how she did it, and they turned her down.  Then she called one day to check that another batch of samples had arrived and was told "yes, they're in the freezer".  She had specifically told them the virus would be destroyed by freezing ... and it became apparent "they didn't WANT to find anything".  Again, to find a virus would destroy the reputation and ego of Straus, who'd banked his career on "depressed menopausal women" and didn't want to see anything to prove him wrong, not even the 1/3 of patients who are male.
Eventually, XMRV will be accepted and those who refuted it will be laughed at as much as those who think the Sun revolves around the earth, and those who think that the earth is flat. We have been patient for a quarter-century waiting for XMRV to be found; let's have a little more patience waiting for it to be accepted as patently obvious.



oerganix said...

XMRV hasn't yet been proven to cause CFS/ME but, as demonstrated in this post, it certainly has not been disproven either despite the 'valiant' attempts by the psych lobby. Too bad the media are not paying attention...yet.

Thanks for this blog. Keep up the good work.

peterpan said...

dr. mikovits and dr. lombardi continue to find the virus. they are working with the CDC and HHS.

i cannot wait to see the lawsuits start pouring in. all people seem to understand is money. thankfully, the WPI researchers don't have to worry about stepping on any toes because they are working with private money.

personally, i think this whole thing will lead to them finding that retroviruses are the culprit in ALS, some forms of MS, autism, and perhaps a multitude of other diseases. this could lead to a revolution in medicine.

even mrs. whittemore, when she started this, could not have foreseen the massive implications of this discovery.

one individual really can change the world.