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virology.ws - XMRV contamination now more likely

guest

Guest
Messages
320
http://www.virology.ws/2011/03/02/authenticity-of-xmrv-integration-sites/#comments

These observations do not directly impugn the veracity of the other 12 XMRV integration sites identified in prostate tumor DNA. However, when DNA contamination occurs it is often ubiquitous. Hence the authors write:

Whilst it is conceivable that the other 12 integration sites apparently derived from prostatic tumor tissues are genuine patient-derived sequences, we suspect that some or all of them may also be the result of contamination with DNA from experimentally infected DU145 cells.

This possibility can and must be addressed experimentally.
 

LJS

Luke
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213
Location
East Coast, USA
I am happy to see we are getting closer to getting an answer if XMRV is a real human pathogen no matter if the news is considered negative, it helps piece the puzzle together.
 

eric_s

Senior Member
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1,925
Location
Switzerland/Spain (Valencia)
Let's wait until we hear the "defendants". They are not some beginners, i'm sure they will have something to say. Before that, i don't feel like i'm able to know what to make of this.

If the contamination hypothesis really were to turn out to be correct, then i find it very hard to imagine how all of this could have happened. How can people like Ruscetti, Mikovits, Alter, Lo and others have contamination in their samples and not find out about it for such a long time. And have an antibody assay that would somehow produce so many false positives. I find it very hard to imagine how this could have happened without it having been done deliberately, which i absolutely don't think was the case. So it just doesn't seem very plausible to me. On the other hand the evidence against XMRV can't be dismissed either. So it's really high time for some reactions.
 

heapsreal

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What about the different immune abnormalities that WPI are finding in xmrv+ as well as other cfsers, this isnt explained by contamination theory.

cheers!!!
 

LJS

Luke
Messages
213
Location
East Coast, USA
What about the different immune abnormalities that WPI are finding in xmrv+ as well as other cfsers, this isnt explained by contamination theory.

cheers!!!

Most if not all CFS patients have immune adnormalities, the cause of these adnormalities has not been found so there is not really any data to say they are caused by XMRV.
 

heapsreal

iherb 10% discount code OPA989,
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Most if not all CFS patients have immune adnormalities, the cause of these adnormalities has not been found so there is not really any data to say they are caused by XMRV.

I know but its still helps with those bozzos who think its psychological and also make them look further into it or else prozac will be the main treatment with CBT again. All of us with cfs know theres something infectious going on in us or some type of immuno defiency.

cheers!!!
 

SilverbladeTE

Senior Member
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3,043
Location
Somewhere near Glasgow, Scotland
as said there's huge vested interest in making this (XMRV <--> ME/CFS) go away

so you'll get a LOT more studies being green lighted or backed that will tend ot be negative rather than positive (not saying the researchers are necessarily factually wrong or have ill intentions...but those who have very long strings ot pull and deep purses can easily manipulate things in very crafty ways merely by "suggesting" who gets funding etc)

AND

in science, it works by DISPROVING things, so you'll always get lets of "nay" work until hm, how would you put it...you work out the better routes to the facts, by figuring out what is wrong way to go about it.
ie sorting out what may cause too many negatives because of a peculiarity of the item you research that will only be uncovered by further research.
Because "science" does not know everything, not even remotely close.
Takes years of hard bloody work to chip chip chip away at such subjects.
And unlike HIV, which had terrible bigotry but the sheer death toll broke through that in the end, we sitll have this huge vested interest against us.

BUT

worst of all, no one has done exact REPLICATION WORK of the WPI!! (that I know of) Argggggggggh!!!
QED, when did that fly out the damn window, eh? :/

So alas it will take time.
 

LJS

Luke
Messages
213
Location
East Coast, USA
as said there's huge vested interest in making this (XMRV <--> ME/CFS) go away
Who does it benefit for the XMRV CFS connection to go away??? This is not some conspiracy to get rid of XMRV it is just science working the problem. The pharmaceuticals stand to make a ton of money off it, the testing companies will make money. The government stands to gain from less people off social security disability and more working people generating tax revenue. The only people that may lose out is the insurance companies and there is no way they are some how influencing every one of these studies. This studies are finding legitimate problems with the CFS and prostate cancer XMRV papers..
 

Snow Leopard

Hibernating
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5,902
Location
South Australia
Let's wait until we hear the "defendants". They are not some beginners, i'm sure they will have something to say. Before that, i don't feel like i'm able to know what to make of this.

I agree. But I can't say I'm confident about it.

The weird VipDX results don't fill me with that much confidence either. (eg positive on antibodies but not culture and vice versa!?!)
 

Deatheye

Senior Member
Messages
161
I agree. But I can't say I'm confident about it.

The weird VipDX results don't fill me with that much confidence either. (eg positive on antibodies but not culture and vice versa!?!)

Diddn't more then one person say that it seems like worser cases are antibodies negative cause theyr immunsystems seems to fail to produce antibodys against it anymore?
 

toddm1960

Senior Member
Messages
155
Location
Rochester, New York
worst of all, no one has done exact REPLICATION WORK of the WPI!! (that I know of) Argggggggggh!!!
QED, when did that fly out the damn window, eh? :/

So alas it will take time.[/QUOTE]

I agree 100%, WPI's testing is different than how viruses have been found in the past. Why hasn't anyone repeated their process exactly? It's no different than WPI finding the virus with an MRI, but all follow up studies just took x-rays!?!? Of course you won't get the same results. We also can't exclude the cohort problems of some of these zero/zero studies.

Cort have you heard of any reason why someone hasn't repeated WPI process and samples exactly?
 

August59

Daughters High School Graduation
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1,617
Location
Upstate SC, USA
worst of all, no one has done exact REPLICATION WORK of the WPI!! (that I know of) Argggggggggh!!!
QED, when did that fly out the damn window, eh? :/

So alas it will take time.

I agree 100%, WPI's testing is different than how viruses have been found in the past. Why hasn't anyone repeated their process exactly? It's no different than WPI finding the virus with an MRI, but all follow up studies just took x-rays!?!? Of course you won't get the same results. We also can't exclude the cohort problems of some of these zero/zero studies.

Cort have you heard of any reason why someone hasn't repeated WPI process and samples exactly?[/QUOTE]

It almost appears as if their "ego" is preventing this. Its as if they are thinking well if they can find it, I can find it my way cause I'm smarter than they are. I certainly understand researchers trying it different ways, but at least repeat what was originally done, Hell, their PCR machine might have a glitch in it. Who knows???!!
 

alex3619

Senior Member
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13,810
Location
Logan, Queensland, Australia
Diddn't more then one person say that it seems like worser cases are antibodies negative cause theyr immunsystems seems to fail to produce antibodys against it anymore?

Hi, while not published, in one recent video Judy Mikovits stated that one of the problems is that most of the antibody is bound up with XMRV in some patients, which means that you are no longer looking for the antibody but antibody-XMRV complexes. This may mean that searching for antibodies will fail. Bye, Alex
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Unless you have demonstratable immunodeficiency, that argument doesn't really make much sense.

Hi Snow Leopard, again unpublished research from the WPI shows an assortment of immunodeficiency issues. Some of those have been shown also by other groups. Expect many publications on this in the next several years. One of the WPI claimed deficiencies is a severe deficit of mature B cells. These are the ones that make antibodies. Bye, Alex
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
Who does it benefit for the XMRV CFS connection to go away??? This is not some conspiracy to get rid of XMRV it is just science working the problem. The pharmaceuticals stand to make a ton of money off it, the testing companies will make money. The government stands to gain from less people off social security disability and more working people generating tax revenue. The only people that may lose out is the insurance companies and there is no way they are some how influencing every one of these studies. This studies are finding legitimate problems with the CFS and prostate cancer XMRV papers..

ah, sorry but research even honest research, CAN be warped as I've said before, statiscally (by altering funding/support to favour studies you believe will be negative) and in other ways

http://www.meactionuk.org.uk/Wesselys_Way.htm

Studies using nonspecific definitions of Gulf War neurological syndrome are biased toward finding negative results. Early in the history of Gulf War illness research, around 1993, a decision was made in the government to the effect that ‘there is no Gulf War syndrome’, and this led to pressure on researchers who wanted government funding not to use a case definition of the illness in their research. Without at least a provisional case definition, however, it is virtually impossible to design studies that will elucidate the nature of the illness, or illnesses, and connect them with causes.



“The most important example of the unproductive use of a nonspecific case definition concocted was the series of studies from the Kings College London group. In place of a case definition describing the disease that veterans were complaining of, they defined Gulf War illness as having a score of greater than 72.2 on the SF-36 questionnaire, which measures functional impairment regardless of the cause. This case definition essentially counted veterans as having Gulf War illness if they had any condition that caused them to feel bad. Consequently, many veterans with diseases other than Gulf War neurological syndrome that made them feel bad were mistakenly counted as cases, and conversely, many with typical symptoms of Gulf War neurological syndrome but who were not very ill with it were not counted as cases. This severe degree of bidirectional misclassification has caused all studies from the Kings College London group to reach spuriously negative conclusions”.



Professor Haley also provided evidence (against Professor Wessely’s studies) that: “Studies using nonspecific measures of nerve agent exposure are biased toward finding negative results”.



Wessely told the Inquiry: “The Gulf war syndrome debate is really just of academic importance” but Lord Lloyd (a former law lord) said there was “every reason” to accept the existence of a “Gulf War Syndrome” (The Independent Public Inquiry on Gulf War Illness. Report published on 17th November 2004).



In March 2008, The US National Academy of Sciences published another report by Dr Beatrice Golomb (of the University of California, San Diego, and Chief Scientist to the US Congress-appointed Committee on Gulf War Illnesses); this report found evidence linking the symptoms experienced by the Gulf War Veterans – including muscle and joint pain, rashes and breathing problems – to a particular class of chemicals, specifically to the anti-nerve gas agent given to the troops, to the pesticides used to control sand-flies, and to the nerve gas sarin. Dr Golomb told Reuters that: “Convergent evidence now strongly links a class of chemicals – acetylcholinesterase inhibitors – to illness in Gulf War veterans”. She said that a lot of attention had been given to psychological factors, but that “psychological stressors are inadequate to account for the excess illness seen” ( http://www.bbc.co.uk/1/hi/health/7288902.stm ). The Proceedings of the National Academy of Sciences is specific: “Increasing evidence suggests excessive illness in Persian Gulf War veterans can be explained partly by exposure to organophosphate and carbamate acetylcholinesterase inhibitors, including pyridostigmine bromide (PB), pesticides and nerve agents (and) this exposure may be causally linked to excess health problems in Gulf War veterans” (Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0711986105).



This study was reported in The Economist (War of nerves. 13th March 2008), which also reported Professor Wessely’s comments about these irrefutable findings: “This may encourage sick veterans that a cause of their suffering could finally be found, but Simon Wessely, a professor at the Institute of Psychiatry’s centre for military health research, is sceptical. He says that the review is ‘an opinion piece that continues a line of argument Dr Golomb has put forwards for some time’”.



In a response to The Economist, Malcolm Hooper (Emeritus Professor of Medicinal Chemistry and Chief Scientific Adviser to the UK Gulf War Veterans) wrote: “The casual and dismissive comments by Professor Simon Wessely about the recent review by Professor Beatrice Golomb that makes clear the link with chemicals used in the first Gulf War are unacceptable. (They are) indicative of the resistance to extensive American research studies that have identified serious damage to the brains of sick soldiers, major heart and cardiovascular disorders, as well as immune, respiratory and neuromuscular disorders, including an excess of motor neurone disease. Despite no official funding, UK research has found excess osteoporosis and severe endocrine damage in UK veterans. The neglect of these veterans is shameful. Golomb’s paper challenges us to seek and speak the truth and to act accordingly”.



It seems strange that Professor Wessely should reject the science reported in the Proceedings of the New York Academy of Sciences (which has an impressive impact factor rating) in favour of his own speculation.



Moreover, it seems that he fails to see that he is doing exactly that of which he accuses Dr Golomb – i.e. his own view is nothing more than “an opinion piece that continues a line of argument” that he has “put forward for some time”. The big difference that Professor Wessely seems to have missed -- either by accident or by design -- is that Dr Golomb has got actual evidence to support her findings, whereas he has none.
 

kurt

Senior Member
Messages
1,186
Location
USA
worst of all, no one has done exact REPLICATION WORK of the WPI!! (that I know of) Argggggggggh!!!
QED, when did that fly out the damn window, eh? :/

So alas it will take time.

I agree 100%, WPI's testing is different than how viruses have been found in the past. Why hasn't anyone repeated their process exactly? It's no different than WPI finding the virus with an MRI, but all follow up studies just took x-rays!?!? Of course you won't get the same results. We also can't exclude the cohort problems of some of these zero/zero studies.

The critical part of the WPI process HAS been precisely replicated, by every one of the negative studies, that is calibration of the PCR to VP62. As to why they don't replicate the actual probe/master mix chemistry, that is not considered to be required to validate a finding. What counts is whether you can calibrate.

Another probable reason for lack of precise replication is intellectual property rights. More than likely WPI will not give out all the details to anyone but a close confederate lab. I have not heard WPI complaining about lack of precise replication recently (although I believe Mikovits did say something like that originally), that seems to now be coming mostly from CFS patients who are not PCR experts. In fact, Mikovits gave several reasons she believed there were differences between the studies in her 1/17/11 presentation, and lack of precise replication was not one of them. Rather, she said something to the effect that her test design picks up a wider range of strains, which is not supported by any data I can find (still looking for that).
 

Cort

Phoenix Rising Founder
I agree 100%, WPI's testing is different than how viruses have been found in the past. Why hasn't anyone repeated their process exactly? It's no different than WPI finding the virus with an MRI, but all follow up studies just took x-rays!?!? Of course you won't get the same results. We also can't exclude the cohort problems of some of these zero/zero studies.

Cort have you heard of any reason why someone hasn't repeated WPI process and samples exactly?

I actually think the PCR portion of the paper has been replicated and the antibody portion has as well. The antibody portion shouldn't have been difficult - they simply looked for an MLV protein that they believed was present in CFS. Ditto with the PCR - they simply looked for a few sequences.

Culturing is the one that has not been replicated, and it seems for a couple of reasons; one is, apparently, that its not done that much anymore. Its quite time consuming and from I read somewhere it's more complex...and PCR has taken over the field; it was pointed out to me that people are sentenced to death based on PCR evidence. I think the prevailing view is that PCR and antibodies are the two keys to diagnosis.

Culturing does involve PCR - its just that most PCR guys don't think you need to culture - ie prompt the virus to replicate first - in order to find it. They think they should be able to find anything that's in those blood samples. One study did culture but not for as long as the WPI does. Nobody has come close to culturing for 42 days.

I think culturing will take place in the BWG tests.

The WPI has two problems right now....Not only are most other researhers not able to find the virus but the CROI conference and some other findings suggest that even if they do - the research world is just going to think its a contaminant that somehow got in their blood samples.

That's why they need to show that it's integrated into human DNA - that would apparently indicate that it has infected human cells. We've heard that Silverman is working on that and I would imagine that Dr. Mikovits and Dr. Ruscetti are as well.

The BWG test will be the one, though...if they can pick out the positives from the negatives that means they really know how to find XMRV and no one else does. It would also suggest that XMRV is not a contaminant - because it would be found preferentially in CFS patients.
 

leaves

Senior Member
Messages
1,193
Ugh. :(
I just feel, intuitively, that xmrv must be it. It just makes perfect sense. It explains why I've been Having weird symptoms since birth, having chronic shingles as a small kid, why my mother is Ill why my father died of cancer, why her mother had lupus, why her father died from a fungal infection etc etc. It must be a retrovirus.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
Kurt,

Do you have any evidence to support this? i.e. can you prove that the WPI or anyone else consider this an adequate replication. It comes across as your opinion that way you wrote it and I am just wondering if it shared by any of the researchers and if so, whom.

(The critical part of the WPI process HAS been precisely replicated, by every one of the negative studies, that is calibration of the PCR to VP62. As to why they don't replicate the actual probe/master mix chemistry, that is not considered to be required to validate a finding. What counts is whether you can calibrate)