learning process. Positive or negative, the results can serve as a
springboard for where to put research dollars next. While support for
specific scientists on a personal level is most likely welcomed by the
scientist receiving it, the scientific process itself requires input
from many different scientists as noted by Dr. Racaniello whose award
winning blog focuses not on personalities, but the peer-reviewed
process of science itself.
Virology Blog
Trust science, not scientists
27 SEPTEMBER 2011
Whether or not the retrovirus XMRV is a human pathogen has been
debated since the virus was first described in 2006. The answer is now
clear: the results of Blood XMRV Scientific Research Group, along with
a partial retraction of the 2009 Science paper describing
identification of the retrovirus in patients with chronic fatigue
syndrome (CFS) show that detection of XMRV in patient samples is a
result of contamination.
The Blood XMRV group obtained new blood samples from 15 individuals
previously shown to be positive for XMRV (Lombardi et al., 2009) or
MLV (Lo et al., 2010) ; 14 of these were from CFS patients. Fifteen
blood samples were also obtained from healthy donors. The samples were
coded and sent to 9 laboratories for analysis. These laboratories
(Abbott Molecular, Abbott Diagnostics, CDC, FDA/Lo, FDA/Hewlett,
Gen-Probe, NCI/DRP, and WPI) conducted validated assays for viral
nucleic acid, viral replication, or viral antibodies. Positive control
samples were also included that were =91spiked=92 with XMRV, in the form
of cell culture fluids from the cell line 22Rv1. Each laboratory was
at liberty to choose which assays to carry out.
Two laboratories reported evidence of XMRV in the coded samples. Only
WPI identified positive specimens by PCR: two from negative controls,
and one from a CFS patient. The FDA/Lo laboratory did not detect any
positives by PCR, using the same nested assay that they had previously
reported in their published study. The samples tested included 5
specimens that were positive in the Lo et al. study.
Lombardi and colleagues have previously concluded that viral culture
is the most sensitive method for detecting XMRV; however the
FDA/Hewlett laboratory failed to culture virus from CFS samples. This
laboratory did culture virus from positive control specimens,
demonstrating the sensitivity of their methods. The FDA/Ruscetti
laboratory recovered virus from 3/15 CFS samples but also from 6/15
negative control specimens. WPI did not carry out viral culture assays
due to contamination of their cell lines with mycoplasma.
Four laboratories tested the samples for the presence of antibodies
that react with XMRV proteins. Only WPI and NCI/Ruscetti detected
reactive antibodies, both in CFS specimens and negative controls.
There was no statistically significant difference in the rates of
positivity between the positive and negative controls, nor in the
identity of the positive samples between the two laboratories.
These results demonstrate that XMRV or antibodies to the virus are not
present in clinical specimens. Detection of XMRV nucleic acid by WPI
is likely a consequence of contamination. The positive serology
reported by WPI and NCI/Ruscetti laboratories remained unexplained,
but are most likely the result of the presence of cross-reactive
epitopes. The authors of the study conclude that =91routine blood
screening for XMRV/P-MLV is not warranted at this time=92.
One of the authors on Lombardi et al., Robert Silverman, decided to
reexamine some of the DNA preparations from CFS patients that were
originally used to detect XMRV DNA by PCR. He found that all the
positive specimens from CFS patients were contaminated with XMRV
plasmid DNA. Therefore the authors of the original study have
retracted Figure 1 (single-round PCR detection of XMRV in CFS PBMC
DNA); table S1, XMRV sequences, and figure S2, phylogenetic analysis
of XMRV sequences.
A puzzling aspect of Silverman=92s results is that XMRV plasmid DNA was
detected only in samples from CFS patients, not healthy controls. This
pattern would not be expected if the specimens were properly blinded,
that is, coded so that the investigators did not know which were
controls and which were from CFS patients. The authors offer no
explanation of these findings.
The paper reporting contamination of samples with XMRV is entitled
=91Partial Retraction=91. It=92s not clear to me why the entire paper has
not been retracted. After removing the PCR and nucleic acid sequencing
results, there is no evidence indicating the presence of XMRV in the
patient samples. The remaining experiments show detection of a
retrovirus by cell culture experiments, and the presence of viral
proteins or antibodies to the virus in clinical specimens. None of
these findings prove that what is being studied is XMRV. The title of
the original paper =91Detection of an infectious retrovirus=92, XMRV, in
blood cells of patients with chronic fatigue syndrome=91, is
unsupported.
In an accompanying article on the XMRV story entitled =91False
Positive=91, Judy Mikovits of WPI notes that =93Anyone who says this is a
lab contaminant has drawn the wrong conclusion and has done a
disservice to the public=94. She goes on to imply that a gammaretrovirus
is likely involved in CFS. On the contrary, pursuing the
CFS-gammaretrovirus hypothesis is a disservice to those with CFS, and
detracts from efforts to solve the disease. There are no data to
support such an association, and to suggest that a lab contaminant,
XMRV, has pointed the way to a bona fide etiologic agent seems
implausible.
XMRV does not cause CFS. The virus arose in mice between 1993-96, and
its detection in patient samples is clearly a result of contamination.
Reaching these conclusions has required a long and often contentious
journey that has highlighted the best and worst aspects of scientific
research. There are many lessons to be learned from XMRV, but an
important one is that science progresses not from the work of a single
investigator, but from the collective efforts of many laboratories.
XMRV reminds us to trust science, not scientists.
http://www.virology.ws/2011/09/27/trust-science-not-scientists/
---------------------------------------------
Send posts to CO-CURE@listserv.nodak.edu
Unsubscribe at http://www.co-cure.org/unsub.htm
Too much mail? Try a digest version. See http://www.co-cure.org/digest.htm
---------------------------------------------
Co-Cure's purpose is to provide information from across the spectrum of
opinion concerning medical, research and political aspects of ME/CFS and/or
FMS. We take no position on the validity of any specific scientific or
political opinion expressed in Co-Cure posts, and we urge readers to
research the various opinions available before assuming any one
interpretation is definitive. The Co-Cure website <www.co-cure.org> has a
link to our complete archive of posts as well as articles of central
importance to the issues of our community.
---------------------------------------------
