Test Your Knowledge – The Phoenix Rising XMRV Quiz (January 2009) by Cort Johnson
Who said this? “And suddenly I could see myself 20 years
from now, when I'm a high school biology teacher and someone calls
and says, ‘Hey, they just found a retrovirus in CFS’.
And maybe that's how it will happen. And I know how I'll feel - it'll feel
great”
Elaine DeFreitas, the researcher who made the first retrovirus claim in this disorder in the early 1990's. She said this
after talking to another woman who's pathogen discovery hadn't worked out either and was working in a completely different field
but whose work was ultimately validated by a later research team (which, of course, took credit for her finding :)). The moral of that story
was that inertia in the research community can kill an idea fast.
After a car accident in the early 1990's Dr. DeFreitas slowly came down with a disorder
called reflex sympathetic dystrophy (RSD). By the mid 1990's with her retrovirus discovery in
tatters and in considerable pain and confined to a wheelchair, Dr. DeFreitas was forced to give
up her position at the University of Miami and stop working.
What in the Science paper suggested that the WPI was still quite a ways developing
the definitive blood test for XMRV?
Dr. Klimas noted that when they took the serum - the non-cellular material in the blood -
from 33 patients who did NOT test positive and introduced it to an uninfected cell line that the cells in that cell line
became infected in 30 of the cases. This indicated that even the patients that didn't test positive for the virus
were still carrying it - and carrying it in its active, infective form. This suggested that almost all the CFS patients
in the Science study, in fact, had an active infection - and that the WPI needs to refine their PCR test a bit more.
Its often said that its better to be lucky than good. Why was the WPI team both
lucky and good?
The WPI team was good because when no one else did they put the pieces
together regarding RNase L and XMRV. They were lucky because it turned out the pieces didn't
fit together at all.
When prostate cancer patients with a genetic abnormality in an immune enzyme
called RNase L were found to have an increased risk of XMRV infection Dr. Mikovits pricked up her ears;
many ME/CFS patients had an RNaseL abnormality as well - could they have XMRV too? Subsequent
research suggested that RNase L problems have no effect on XMRV infection in either disease making
the ME/CFS community(for once) possibly very lucky; if the research indicating that RNase L was a false lead had
come out any earlier the WPI wouldn't have gone after it - and the XMRV probably would have
remained hidden for decades.
How this virus is transmitted from person-to-person is one of the major
questions facing researchers particularly since the Science paper suggested that 4% of Americans may be carrying it.
We know that XMRV is not transmitted through the air but
it could be transmitted via the blood or through other bodily fluids
such as saliva and semen. There is at least one more mode of transmission that we haven't mentioned. What is it?
Dr. Klimas talked about the possibility that the virus could be transmitted from generation to generation
in the DNA that, it could, in fact, hang out there without causing problems until some event (another infection?) somehow
turned it on. Interestingly XMRV is transmitted in mice that way
The Mommy Factor - The greatest risk factor a recent
study found was having a mother with the disorder.
Since mothers (but not fathers) pass a set of their mitochondrial DNA to their children the study
suggests that genetic factors associated with mitochondrial DNA could play a role.
The Co-Factor Question Dr. Klimas's idea of a
necessary co-factor makes sense since we know that most people who carry this virus are not ill; if this virus does contribute to or
cause ME/CFS and other diseases, researchers are need to find some trigger that activates. The idea of a trigger or underlying
factor, actually not uncommon in retroviruses. Yes,
most people infected with HIV do come down with the disease but a small subset do not and
only a subset of patients infected with an infectious HTLV retrovirus come down with cancer - co-factors definitely play a role
in how retrovirus's express themselves in the body.
XMRV stands for Xenotropic Murine Leukemia Virus-Related Virus. The 'xenotropic' part of the name is what makes this virus so enticing. Why is
it so important that the virus be xenotropic?
Xenotropic means 'acquired' i.e. that the patient acquired this virus from somewhere else. This is what retrovirus hunters
hunters are looking for. Their bane, on the other hand, is an 'endogenous' retrovirus - a retrovirus that humans already carry
within their DNA. In fact,
a significant part
part of our genome is composed of old retroviruses; ie. 'junk DNA'. Because we carry so much retroviral DNA
its easy to find pieces of endogenous retrovirus's floating around in our system. (Both the CDC and the Gow research team
concluded that Dr. DeFreitas retrovirus
in the early 1990s was an endogenous retrovirus.
Oddly enough, XMRV appears to be very closely related
to an endogenous retrovirus that's carried by laboratory mice. Because of this one of the first things the WPI needed to do, therefore, was to convince
the research community that they hadn't simply picked up a piece of endogenous mice retroviral RNA in their samples. They did that by
fully sequencing several of the viral samples and demonstrating they came from XMRV - not a piece of 'junk DNA'.
What got Dr. Mikovits, the Research Director of the WPI interested in this field
?
Dr. Mikovits worked for many years in the National Cancer Institute with Dr. Ruscetti. At some point
she left the Institute and settled in Santa Barbara where she worked for a pharmaceutical firm.
The firm failed but Kirsten Loomis, a cofounder of the HHV-6 foundation, (also based in Santa
Barbara), invited Dr. Mickovits to attend an HHV-6
conference in Spain. Most of the conference was uninteresting to her but Dr. Peterson's presentation on a lymphoma subset
of patients caught her
attention.
'That's a virus" she said. She talked with Dr. Peterson and later
Annette Whittemore hired her to head
the
fledgling and still unformed Whittemore Peterson Institute's research program. That cancer
cluster got her entrée to National Cancer Institute technology. At one point
she decided to pursue the
RNase L/XMRV connection, and the rest they say, is history.
The last retroviral discovery in chronic fatigue syndrome (ME/CFS) occurred in the
early 1990's when Dr. DeFreitas of the Wistar Institute announced the finding of a HTLV-2 like virus
in several sets of patients. Beyond the fact that both that and the XMRV discovery were associated with
prestigious institutions (National Cancer Institute, Cleveland Clinic) few parallels between the two
discoveries can be drawn. For instance, Dr. DeFreitas was only able to isolate the genetic sequences of the virus;
the Whittemore Peterson Institute has been able to do that and capture the virus,
recreate its full sequence, demonstrate the immune system is reacting to the virus,
that it is infective, etc.)
The CDC's last collaborative effort with Dr. DeFreitas ended when she was unable to pick out CFS patients
from the healthy controls in a set of blinded samples they'd provided her. She argued that the CDC
was overlooking a critical issue that could have effected the results. Interestingly, the same
issue is at play today. What is it?
The patients being tested. The CDC, following standard research protocols, gave her their 'purest' CFS patients - those
without psychiatric disorders. Dr. Cheney, on the other hand, was possibly providing her with just that set
of patients. One of the retroviruses perculiarities was that it was not showing up in
your typical, fluey patients - it was showing up patients with neurocognitive
and neurological problems - possibly just the type of patients
CDC removed from the test. Dr. DeFreitas argued that she should be given the 'psychiatric patients' to test. The CDC refused.
Now the question of what patient cohort is being tested is again possibly a critical factor. The first study
contained a rather specific subset of patient; lthey were disabled patients with immunological abnormalities and metabolic
dysfunction - a perhaps somewhat select group. (Dr. Bateman estimated that 10% of her patients were that ill.)
The CDC's groups of patients couldn't be more different; one group (Georgia) meets the criteria for the Empirical Definition and
the most of the other group (Wichita) didn't even meet the 1994 criteria for CFS. The WPI group, on the other hand,
met both the 1994 and the Canadian Consensus Criteria. (The CDC is asking for other more 'CFS-like' samples to test).
The first replication attempt contained patients from Dr. Wessely's practice - which reassured no one.
The differing patient groups present
will make it more difficult to interpret the XMRV studies coming out and suggests it may take quite
awhile to understand just what role XMRV plays in this disorder.
Why could XMRV almost be called the 'anti-AIDS' retrovirus?
Dr. Coffin explained that XMRV is about as different from HIV as a retrovirus
can be. HIV replicates and mutates rapidly, a factor pharmaceutical companies have used to attack it.
Because HIV mutates so quickly, however,
its difficult to build a vaccine that will stop it.
XMRV appears, on the other hand, to replicate and mutate very very slowly. In fact, Dr. Coffin
noted that HIV will undergo more mutation in a person's body in a couple of weeks than was
seen in all the samples of XMRV from across the country. Because XMRV's slow replication/mutation rate
gives researchers less of a window to knock it out treatment options may be more difficult to come by.
On the other hand XMRV's low mutation rate
suggests it might be easier to develop a vaccine for it
Even so, why are we in much better shape treatment wise than AIDS patients were when HIV was first discovered?
Because we have a huge community of retrovirologists available now that can quickly study this virus (and
are apparently getting a little bored with HIV) and because Dr. Klimas
stated there are literally thousands of anti-retroviral substances on the pharmaceutical
firms shelves that simply never made it the market for HIV. Indeed, Annette Whittemore reported that pharmaceutical
firms are already starting
to test drugs for XMRV, as is the WPI. Interestingly, AZT appears to be able to knock
down XMRV in some patient samples but not others.
We're in the midst of 'Retroviral mania'. We've identified 15 studies/groups
actively engaged in XMRV research and surely some have been missed. Retroviral
mania also occurred in the first retroviral discovery in ME/CFS. The CDC got the
lions share of attention but other groups were involved. How many groups do we
now know were looking for a retrovirus back then?
Osler's Web and a PubMed search indicate at least nine groups took a stab
at finding a retrovirus - none, unfortunately, with success.
The Herst
Labs reported high accuracy rates for about a year and then failed to distinguish the virus in a
the blinded CDC test. The Chiron Labs partnered with Wistar for about 9 months before they had
technical problems and backed out. The Gow team from Scotland failed to find the virus. The CDC actually appeared
to find the virus at first but then failed to do so later and eventually backed out. The Gallo labs, which had recently isolated HHV-6 for the first time from CFS patients
failed to find any retroviruses. Dr. Levy and Dr. Grossberg's labs failed to
find retroviruses and Dr. Martin findings were controversial. A later CDC study of all
known retroviruses failed to find any in CFS and a Japanese
team failed to find any evidence of HTLV-type viruses in the disease.
At one time or another studies have uncovered a variety of
pathogens in chronic fatigue syndrome (ME/CFS) patients yet research into them has been spotty.
Thats clearly not been so with XMRV; the federal
government has created a special task force, the CDC began testing samples the
day after the Science paper came out and the research community is basically
falling all over itself to study this pathogen. What is the difference?
Most of the pathogens found thus far in
chronic fatigue syndrome are
opportunistic viruses from the herpesvirus family that everyone, even healthy people, carry in their body.
The theory regarding these viruses is that they're under control in healthy people but reactivated
in CFS. A significant amount of research into herpesviruses in the 1990's suggested this theory
was wrong. Since then evidence has emerged that it may be right after all but lingering questions about
diagnosis and testing have thwarted the theories acceptance in the research community at large. Conclusion: herpesviruses
are difficult to study - which is bad news for such a controversial disease
XMRV, on the other hand, may be the first virus that, if it is not uniquely found in ME/CFS patients, appears,
at least to be concentrated in them. XMRV's biggest boost, however, came from
the depth of the Science paper. Essentially the WPI answered alot
of questions about XMRV before the scientific community had a chance to ask
them. First they isolated the virus, then
they examined it genetically, then they compared it to several other viruses,
then they showed that the patients immune system were reacting to it, then they
showed that the virus could jump from one cell to another. They even showed XMRV
was found in a 20 year old blood sample. It helped a great deal that the
Cleveland Clinic validated several key components. Since the WPI was able to successful
surmount so many key hurdles the scientific community was ready to jump on XMRV
once the paper was published and they have (See XMRV Studies). Conclusion: compared to herpesviruses XMRV
is a walk in the park.
Given the Science paper was so fantastic why are so many groups
urging caution?
Because the biggest hurdle in any discovery is
replicating it and ME/CFS history is full of 'false starts' with regards to pathogens.
To be sure no pathogen discovery has come close to XMRV in the amount of expertise and the
sheer depth of research that the WPI, the Cleveland Clinic and the National Cancer
Institute have provided. But Elaine DeFreitas retrovirus discovery in the early 1990's was backed by
the prestigious Wistar Institute and by Hillary Koprowski, one of the most hallowed figures in retrovirology. Because the first Science paper found XMRV in 2/3rds of a quite ill subset of patients
its also still unclear how it will translate to other patients. Plus, there's the hurdle of showing that
XMRV is a cause of CFS and not another opportunistic virus that has taken advantage of a
depleted immune system. The WPI made a great start with this virus but we still have a ways to go.
Test Your Knowledge – The Winter 2009 Phoenix
Rising ME/CFS Quiz by Cort Johnson
1. Researchers in a small lab in California believe
they have found a test that could quickly legitimize ME/CFS, document - for the first time
- the exertional problems in the disease, get patients over the disability hurdle and alter
how this diseae is defined. In short this test could revolutionize the medical communities understanding of chronic fatigue syndrome.
What is it?
The Stevens Protocol developed by Staci Stevens (a person with
ME/CFS) at the University of the Pacific's Fatigue Lab has uncovered
startling metabolic abnormalities in a high percentage of chronic fatigue
syndrome patients when they participate in standard exercise tests for two
days in a row.These types of abnormalities appear to be unique to ME/CFS
patients. For more on this potentially revolutionary finding read "Cracking the Foundation: the Pacific
Fatigue Lab and ME/CFS" (and sign up for the newsletter!)
2. In upcoming interview Dr. Friedberg, a psychologist who has ME/CFS asserts that with regards to activity,
most chronic fatigue syndrome
patients are doing
- too little
- about the right amount
- too much
Dr. Friedberg believes that most chronic fatigue syndrome patients are doing too
much. He asserts that in most cases patients that cut back on their activities
and engage in stress reduction exercises can greatly increase their quality of
life and even health.
3. In the harshest language they’ve used in a decade the CFIDS Association of America slammed the largest federal ME/CFS
research program for what?
At a federal advisory meeting on chronic fatigue syndrome (ME/CFS) the CAA’s president Kim McCleary slammed the Centers
of Disease Control for ‘Zero accountability’, squandering funds, and funneling large amounts
of precious research dollars to a firm that essentially had no use for them.
Read more about
it
4. What has it been suggested that you not tell you attending physician if you happen to end up in the emergency room?
That you have chronic fatigue syndrome. Several ME/CFS physicians and patients have related stories of patients receiving substandard care once doctors learned they had ‘CFS’.
3. Which recovered chronic fatigue syndrome (ME/CFS) patient developed his own therapy for the disease
using neurolinguistic reprogramming, meditation and other techniques that he asserts has high improvement rates.
Ashok Gupta asserts that the organ in the brain that governs the ‘fear reaction’, the amygdala,
has been chronically turned on in ME/CFS. His amygdala retraining therapy uses techniques to turn the activity of that organ down.
Check out reports from patients trying
his technique. Go to the Amygdala Retraining website.
4. A Centers For Disease Control study found that to its surprise that a significant percentage of people who met
the International criteria for chronic fatigue syndrome not only had ME/CFS but evidence of what else?
Almost 50% of the people who met the criteria for ME/CFS
over the phone during a random sampling survey were later found to have undiagnosed (and mostly treatable) medical or psychiatric problems.
5. What do Dr. Lappe and Dr. Cheney believe is the best ‘activity’ for ME/CFS patients?
Hydrotherapy – light workouts in the pool appear to work for several reasons; they keep the body cool and the waters buoyancy appears to stimulate the lymphatic system and it may stop blood from pooling in the extremities.
6. If you’re a chronic fatigue syndrome (ME/CFS) patient with this problem you should avoid:
- Sitting in place for long periods
- Hot tubs, saunas and lying on the beach
- Other hot environments and hot showers
- Eating large meals
- Drinking alcohol
-
Sitting in high chairs
What problem do you have?
Orthostatic intolerance or OI. OI results when problems with the circulatory system make it difficult to maintain adequate blood flows to the heart and brain when one stands. Check out
The Perils of Standing for more information on OI and how to treat it.
7. A Freedom of Information Act (FOIA) found that over the past
five years chronic fatigue syndrome researchers have had what percent chance of
getting their research grants funded at the NIH using the only funding mechanism
(Program Announcement) the ME/CFS research program sponsors.
8% Check out the results of the FOIA here
8. Dr. Peterson, the head of the clinical arm of the Whittemore-Peterson Neuro-Immune Institute believes that about 20% of chronic fatigue syndrome (ME/CFS) patients are radically different from the rest of the group. How?
Dr. Peterson believes that about 20% of ME/CFS patients have a viral induced disease.
This group does not respond to the standard therapies given to ME/CFS patients but can respond to anti-viral therapies.
Check out more on the Whittemore-Peterson Institute's new take on ME/CFS in "Coming Out of the Closet: the WPI and ME/CFS" Also check out an overview of
Dr. Peterson’s presentation at the Symposium On Viruses in CFS
Links Wrap Up
Test Your Knowledge – The Second Phoenix
Rising ME/CFS Quiz (March, 2008) by Cort Johnson
1. The orthomolecular specialist Dr. Murphee wrote that
‘increasing X levels is beneficial for 95% of my patients”. What was he
referring to?
2. What do Dr. Bateman, Dr. Bested and Dr. Klimas all agree is the most
essential symptom to treat in chronic fatigue syndrome (ME/CFS)?
3. In From Fatigued to Fantastic, Dr. Teitelbaum, a well known chronic
fatigue syndrome (ME/CFS) physician states that at times he uses small doses
of up to how many different prescription drugs in order to get his patients
to sleep?
4. Who is the one patient advocate on the CFS Federal Advisory Committee and
which group does she come from?
5. Which of these prominent chronic fatigue syndrome (ME/CFS) physicians
does not a have personal connection to ME/CFS? Dr. Teitelbaum/Dr.
Bateman/Dr. Chia/Dr. Friedberg
6. The Whittemore-Peterson Neuro-immune Institute is the first private/state
research/education CFS institute in the U.S. Harvey and Annette Whittemore
make up the Whittemore part; who does Peterson refer to?
7. Which dynamic new ME/CFS Support group got Senator Orrin Hatch to open
and close one of their conferences?
8. “I Had a Mind Like a Steel Trap, and I Ended Up With a Colander for a
Brain" – What CFS-like disease was this person referring to?
9. What national leader not only works on ME/CFS but also married the son of
a prominent ME/CFS patient?
To go to the
Answers Click Here.
PHOENIX RISING QUIZ #1 (October, 2007)
(1) To what were Dr. Leonard and Jason Dr. Nancy
Klimas referring to when he said "
If we had twenty sites like this it
would make a big difference" and she said that it was something
"that
absolutely has to be done?"
(2) Dr. Reeves of the CDC recently said that ME/CFS is not a disease.
What did he say it was?
(3) In a remarkably direct statement which NIH official told the CFSAC
that "You still have to convince the institutions of the (NIH of the)
importance of this fight".
(4) Which ME/CFS website has a cat on its front page?
(5) Which co-founders of this prominent advocacy/support organization
didn’t meet in person until three years after they formed the
organization.
(6) What prominent ME/CFS physician has a book coming out this month?
(7) What was this prominent doctor referring to when he said "all
things considered, it is the most effective treatment for severe ME/CFS that
I have found in my 21 years of looking. But it has serious drawbacks and
risks"
(8) What did Dr. John of the Veterans Administration’s report he says
when faced with colleagues who say ‘CFS is not a disease"?
(9) What is this?
(10) When was the last time a CFS patient was on Oprah?
To go to the
Answers Click Here.