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The point
that seems to be missing here is that the question, "Is XMRV the
cause
of CFS or M.E.?" is NOT primarily what scientists were interested in
with the
"Science" study.
They want to know what XMRV does, and that's a different question
entirely.
When you ask if something was wrong with the research, the answer
lies in the
lab, and specifically, whether the finding was a result of
contamination. (Answer:
No contamination - "Science" made them run specific tests to confirm
that).
Beyond that, collecting so many specimens that were positive is
going to be very
helpful in figuring out what this disease does - but while, for us,
the pressing
issue is "Does XMRV cause CFS or M.E.?" - for scientists, the
pressing questions
are "What does XMRV do to subjects who have it," and "How do we deal
with it?"
In the end, there is going to be a subset of patients who are really
XMRV
patients.
What percentage? Too early to tell.
We knew what AIDS was before HIV was discovered. What is the
equivalent for
XMRV? It will help greatly in answering that question to have a
ready-made data
set. CFS - or, rather, a major subset of CFS - appears from the
"Science" study
to be that short-cut.
Are any scientists seriously questioning the existence of XMRV?
None
of whom I
am aware.
The German study presented a conundrum, because they did not find
any XMRV at
all - not in the research subjects (men with prostate cancer), nor
in the
control group.
They should have found some.
Every prostate cancer study - except the one in Germany - has found
a consistent
level of XMRV in controls: 3-4% in the U.S., 1-2% in Japan.
The argument has been made that perhaps there are geographic
differences in the
prevalence of the disease. But I find it hard to believe that a
disease that
presumably has been around for 25 years has not found it's way from
the US to
GB, the Netherlands, or Germany.
So why the different results? In two cases there were glaring
differences in the
sample characteristics plus they did not use the same method; In the
third study
(Kerr), it's hard to say.
But absence of confirmation is not confirmation of absence -
particularly in
this case. Scientists had already moved on beyond "is there a newly
discovered
gamma retrovirus?"
The question now is "what does it mean?".
What did we learn from the studies that couldn't find XMRV anywhere,
including
the controls? Not much. The most we can do is ask what was different
about the
studies. Since they were not replications, there's a lot of
potential reasons
why the results were different.
If I want to learn what XMRV does, I need to find people who are
positive and
look at their characteristics. The Science study was helpful in that
regard.
The
four European studies, not so helpful. You can try to figure out
what was
different between the positive and negative studies - but it might
be more
fruitful to just move on from the Science study.
Every time the question has been, "Does virus A cause CFS?" a
negative study has
ended the conversation. [Even if it turns out that Virus A
identifies a subset
of CFS patients.]
We're all used to that. We're so used to it that some of us haven't
noticed that
THIS time it's different. It's different because it isn't about US.
So McClure-Wessely publish a quick and dirty study, and there's a
pause ...
Must
mean CFS doesn't have anything to do with XMRV, guess XMRV is going
away.
[Note:
the press is also off the mark here, for the same reason - they are
used to CFS
studies; they think they know this drill.]
But XMRV is not about CFS, and it most definitely is not going away.
We are not in sync with the scientific community, because the
question we're
real interested in is "Does XMRV cause CFS or M.E.?".
But the doubts raised by the European studies all come down to:
"Here's a group
of CFS patients. If they don't have XMRV, then XMRV has nothing to
do with CFS."
That leads us into the fuzzy world of "What is CFS?".
And (frankly) the young scientists interested in XMRV
internationally really
don't care what CFS is. They're trying to figure out what XMRV is.
So a study that finds XMRV in a clear subset of CFS is useful to the
scientist
working on XMRV - but a study that doesn't find it isn't all that
useful, unless
we try to focus on why there were different.
IT'S NOT ABOUT WHETHER OR NOT CFS IS CAUSED BY XMRV. IT'S ABOUT WHAT
CFS CAN
TEACH US ABOUT XMRV.
| Whatever you think of the answer to that question, understand that
this study
was not conducted by the Whittemore-Peterson Clinic acting alone.
It
was the
result of a COLLABORATION among the WPI, the NCI, and the Cleveland
Clinic. |
So be sure to include the National Cancer Institute in your
critique. As someone
who knows the researchers at WPI, I take exception to the accusation
that
there's something unethical or incompetent going on there..
Extend your assumptions to the National Cancer Institute - if you
think that's
appropriate.
The existence of XMRV is not being questioned by biologists - they
are all eager
to play with the third known HUMAN retrovirus. But again, let me
remind you how
many years it took to really nail HIV - and a vaccine continues to
elude us.
For a long time HTLV was the stepchild of retrovirus studies - what
did it do? -
but now we know it's connected to certain leukaemias.
Again - the REAL question is what does XMRV do?
We know it correlates with a virulent form of prostate cancer. Since
the other
two human retroviruses are associated with cancers, that makes some
sense.
But in matching XMRV to a data set that already has known
pathologies, we
suddenly have learned a lot more.
I think I was probably a fairly typical subject in the study - I am
positive for
some odd immune markers and have a trail of viruses that won't
behave, but there
is no good explanation of how that came to be.
What do we know, if I am a typical patient in that study? WE KNOW
NOTHING,
except it can be present in people who, biologically, can't get
prostate cancer.
But we can surmise.
We can suggest.
We can get a direction to move in.
I have the Rnase-L defect (similar to, but apparently not a perfect
match for,
the Rnase-L defect in that group of prostate cancer patients - mine
weighs
37kDa, theirs weighs a little more, I think). I also have a natural
killer cell
function of 2%.
We already knew that I had recurring EBV, plus active HHV-6 (Variant
A), HHV-7,
and cytomegalovirus (CMV). In the course of this disease I have
battled thrush,
do not seem to be digesting proteins, have had polio-like paralysis
of my left
leg with a dropped foot, significant myofascial pain; can't pass a
simple
Romberg test; score abysmally on just one day of VO2 MAX stress
tests (we've
done more than one since I lost Ampligen), suffered blackouts, and
been so
confused I once poured an entire pot of coffee into a silverware
drawer,
absolutely convinced it was a cup.
Did XMRV cause these things?
Did XMRV cause the immune defects which caused the viruses which
caused these
things?
WE DON'T KNOW YET.
So let's go back over how we got here:
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1. |
The
researchers working on the relationship between XMRV and
a particularly virulent strain of prostate cancer
noticed that every time they did a study, the prevalence
of XMRV among the study controls was higher than the
prevalence of
prostate cancer - it was consistently in the range of 3-4%.
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2. |
The
prostate cancer/XMRV researchers began to present papers
suggesting there must be a link between XMRV and some
other condition. They also noted that their XMRV
patients tested positive for a strange defect in the
2'5'A synthetate
antiviral pathway, producing Rnase-L that was basically half-sized.
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3. |
A
number of studies in the 1990s had found a similar link
between defective Rnase-L and CFS (Fukuda) - specifically, the Rnase-L weighed 37kDa,
roughly half
the size of normal 80kDa Rnase-L. (I had one of the first commercial
tests for
LMW Rnase-L and I was positive for the abnormal protein).
NOTE: When Reeves or Wessely says there were promising biomarkers
that turned
out to be immaterial, ONE of them was the Rnase-L defect.
Looks like it was useful after all.
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4. |
Judy
Mikovits of the WPI approached the Cleveland Clinic
about trying to see if CFS patients had XMRV, since so
many had the defective Rnase-L.
The Cleveland Clinic and the WPI were joined in this effort by the
National
Cancer Institute, the latter being alarmed by the implications of a
retrovirus
in 3-4% of the population.
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5. |
The
research took almost four years. Patients in the study
were tested using a number of different methods. THE
JOURNAL "SCIENCE" MADE THEM CHECK AND DOUBLE-CHECK THAT
THE SAMPLES WERE NOT CONTAMINATED.
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6. |
After
a rigorous process of ensuring the study met very strict
scientific standards, an article suggesting a link
between CFS and XMRV was published in "Science." Science
is about as "A" list a research pub as it gets, because
it encompasses ALL the sciences. (It outranks BMJ, Lancet, JAMA, and
the NEJM, for
example.)
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7. |
NIH, WPI, and groups in several other countries are really busy
trying to
find a relatively quick test for XMRV that is accurate and can be
performed by
lots of commercial labs.
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The urgent question in the scientific community is NOT whether XMRV
is the cause
or consequence of CFS and M.E.
The urgent question is how to get it out of the blood supply and how
to keep it
out of the blood supply. As usual, our story is, frankly, tangential
to what the
scientists are REALLY worried about - is 3.5% in the normal
population already
so high that it is too late to prevent the disease from becoming
endemic?
Finding it among patients in practices in the U.S. that already test
for a
number of biomarkers and viruses (and I do NOT know if this is the
case; I'm
operating on the assumption that they really did use the Canadian
definition) -
was helpful in suggesting what happens to patients with XMRV.
If we can use CFS patients as kind of a jumping off place for the
epidemiology,
in the context that, as it now stands, the method used in the
Science study was
very time and labour intensive -
We can get a rough picture of the syndrome that would correspond to
the disease.
For example, we already know that defective Rnase-L correlates with
XMRV. What,
then, about natural killer cell dysfunction? HHV-4, -5, -6, and -7?
Coxsackie B?
NMH/POTS? Hashimoto's? Hypocortisolism?
What about the CD4/CD8 ratio?
What about the "CFS" cancers? (Stem cell, Burkett's, other lymphomas
and
leukaemias) - plus prostate cancer?
The questions on the minds of scientists have to do with how quickly
this virus
binds with DNA; what would keep it from replicating; characteristics
(appears to
be carcinogenic and damaging to the immune system all by itself);
the envelope
discovery by the French; what drugs impact it (people are talking
about taking
AZT but we don't know how it would respond to AZT); why is there a
correlation
with defective Rnase-L?
We are just at the bare bones beginning.
But I do want to point out that many of the biomarkers and viruses
that were
supposedly disproved are now commonly diagnosed in CFS if you have a
cutting
edge doctor. I have immune defects and viruses galore, but the only
thing I have
that is recognized by CDC is cytomegalovirus (which was discovered
before AIDS,
which should give you a hint as to why the other ones remain
buried).
We are going to have to ask is M.E. really different from
"cluster-outbreak" CFS
(Tahoe-Truckee, Lyndonville NY, Rockville MD, and many, many more) -
because
obviously XMRV was not around in the 1950s; were there XMRV clusters
in the UK
in the 1980s? Is XMRV-CFS different from Ramsay-M.E.?
So - ultimately -
1. This is NOT about the Whittemore-Peterson Institute. They have
been in the
forefront of the news, but this was conducted in conjunction with
the Cleveland
Clinic and the National Cancer Institute, the part of NIH that
co-discovered HIV
all those years ago (and also where Ablashi was working when he
discovered HHV-6
and its two variants). If you're going to make accusations of shoddy
scientific
method, include all three groups.
2. We are, quite naturally, obsessed with whether XMRV causes or
even correlates
with CFS-Fukuda and M.E. But the scientific community as a whole is
not.
3. Personally, I wonder why we've found so many retroviruses in
other mammals,
but only 3 in humans - and they all showed up in the same decade.
Weird.
4. Keep in mind that retroviruses do not behave like other viruses -
they become
part of your DNA - so figuring out how to attack this thing is not
going to
happen overnight.
5. In testing CFS patients for XMRV, scientists were not unlike the
drunk
looking for his car keys under the street light. To the extent we
can find
links, that helps scientists draw a picture of what XMRV can do.
But
to
scientists, the question is precisely that:
"What does XMRV cause in patients?"
NOT
"Is XMRV the cause of CFS?"
Try to keep that in mind - this story is just beginning.
Mary Schweitzer
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