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 website.
The first Science Express Report (that appeared in Science) giving details
of the study does indeed not state that patients were selected using the
However, in the second document entitled Supporting Online Material it does
clearly state that patients were selected using the Canadian Criteria and
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 Kupperveld 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, it was asserted that Kupperveld 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 Kupperveld et al couldn't be bothered to read all the detail of the
Lombardi et al study that they were supposed to be comparing their own study
with then it would seem to me that there was an element of incompetence on
the part of Kupperveld et al in not bothering to read what they should have
been reading. Further evidence of this assertion could be that the patients
selected for the Kupperveld et al study decided to use the "broad" Oxford
Kupperveld 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.
Kupperveld 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.
Kupperveld et al only carried out a non-validated PCR test using 25% of the
methodology employed by Lombardi et al in a study that took two and a half
years to complete.
In spite of all of this, there have been assertions that this study from
Kupperveld 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.
There have been assertions that reputable laboratories were used but this is
not the issue of concern.
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.
However, if there is an intention to bury any association between XMRV and CFS and ME 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
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.)
The simple fact is - thus far there is no emphatic evidence *anywhere* to
state 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
Yet all three studies obtained significant and totally co-ordinated 0%
outcomes and publicity across the International media 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.
Stephen Ralph DCR(D) Retired.
* * *
This was the problem 20 years ago with Elaine DeFreitas' virus -- the "replication" study was intentionally done wrong, repeatedly, because they didn't want to find anything to contradict Straus' stance that we're all depressed menopausal women.