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The Race to Retract Lombardi 2009...

jace

Off the fence
Messages
856
Location
England
With Silvermans retraction of his sequences from the Lombardi 2009 Science paper, the people running the 0/0 studies have huge problems.

The VP-62 sequence is now known not to correspond to the gammaretroviruses detected by Lombardi et al. It is also known that Silverman's primers are capable of detecting the VP-62 plasmid and NOT capable of detecting the gammaretroviruses which exist in the Lombardi CFS patients.

The WPI and NCI tried to use Silverman's primers on the patients who tested positive for their nested PCRs, but could detect nothing. A great number of the 0/0 studies used Silverman's primers alone or in combination and thus their negative findings are invalid.

The slide being so viciously attacked demonstrates that the viruses are normally in a latent state which is maintained by methylation of the provirus. If one removes the methyl groups as shown by the experiment in the slide and the virus becomes active.

So what, says a chorus of voices - well, the virus or viruses are integrated into G-C rich areas called CpG islands. These are extremely difficult if not impossible to amplify using standard PCR approaches.

Any PCR which has been adjusted to detect the VP-62 clone in a spiked sample would not have a prayer of detecting a human MLV related gammaretrovirus integrated into such a region even if the virus did have the same sequence as VP-62 which it or they do not.

Thus the combination of Silvermans retraction and the discovery that demethylation can activate the virus or viruses in question completely invalidates ALL the negative 0/0 studies

Stoye, Coffin and ERV and their ilk must get Lombardi retracted at all costs before the scientific community as a whole realize that.
 

Kate_UK

Senior Member
Messages
258
Are you saying that if Lombardi is retracted, then it's as if it never happened, and no-one has to follow up on the viruses he found, even though the negative studies that we have already are not valid because they could not have found anything using their methods?
 
Messages
13,774
Hopefully Mikovits/WPI/Ruscetti will get another shot with the Lipkin study (I don't know what's happening with Mikovits and the WPI though). If they still cannot confirm their results under independently blinded conditions, then they should acknowledge that their initial paper was in error.

We don't know what the slide being so viciously attacked demonstrates, as the labelling of it was not clear - which is why it's being attacked!

We've had a number of negative studies since the Lo/Alter finding, which made everyone aware of the possibility of the virus being quite different to what was reported, and even some of the studies before that should have been able to detect the viruses found by Lo/Alter (remember that Lo/Alter were looking for XMRV). We've also had the negative BWG result, in which Lo/Alter, Ruscetti and Mikovits were able to do their own testing - and they were unable to distinguish between samples from patients previously found positive and healthy controls.

It doesn't look good for XMRV/HGRV/WPIRV, and the evidence against association is not all invalidated by the fact that the Lombardi paper included now retracted errors, and may have omitted important information.

I think that the retraction of the Science paper prior to the Lipkin study being carried out would be a mistake, and hopefully that will not happen. However, it seems like most of the scientific community are already assuming that the XMRV/CFS paper was in error, and only if Mikovits/Ruscetti release some really compelling new data will that change. Whether the paper is retracted or not is of almost no importance in that regard.

There's still a tiny chance that all the evidence against HGRV/WPIRV and CFS is the results of a bizarre series of coincidences and mistake - but it's looking increasingly unlikely.

I don't know if the above comes from the same source, but a couple of patients have tried to represent themselves as experts on these matters, and have made very bold and confident claims which have then been circulated around the internet. We need to remember that these assertions come from people who, just last week, announced that in their expert opinion two identical images were not the same, and that the claim that the same results had been used twice by Mikovits was the result of a conspiracy against her. Everyone could see that they were wrong for themselves, and that alone should have undermined people's willingness to trust the claims of virological expertise which are emanating from certain quarters. When some patients sound very sure of themselves

edit: I seem to have ended half sentence. Whoops.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
I don't know if the above comes from the same source, but a couple of patients have tried to represent themselves as experts on these matters, and have made very bold and confident claims which have then been circulated around the internet. We need to remember that these assertion come from people who, just last week, announced that in their expert opinion two identical images were not the same, and that the claim that the same results had been used twice by Mikovits was the result of a conspiracy against her. Everyone could see that they were wrong for themselves, and that alone should have undermined people's willingness to trust the claims of virological expertise which are emanating from certain quarters. When some patients sound very sure of themselves

Who are you talking about Esther?

Also, you sometimes come across as very sure of yourself. Does this mean I should not trust you?
 
Messages
13,774
Who are you talking about Esther?

I'm not entirely sure. **********

**********





Moderator: text removed.

Esther 12 edit: You what? I need to find a less inflammatory term for 'nonsense'? I think that some of V99/Gerwyn's claims about XMRV are utterly without merit, and reflections of only their own confusion. There's no kind way of saying that, but it needs to be said. I am sympathetic towards them as individuals, as I know how confusing and difficult it is to live with CFS and the prejudices that surround it, but we need to be able to point out when other people are posting things which are just *******. What term should I use?

I know mods are understaffed right now, but I thought people were pm'd prior to being edited?

I don't remember there being anything wrong about UKXMRV's post either (which was presumably attacking me, if anyone). I'd much rather be able to see others criticism of me than be protected from it.
 

ukxmrv

Senior Member
Messages
4,413
Location
London
********** It's just all opinion.

*********** As we are all equal as patients and entitled to our own opinions obviously that is fine. **********



Moderator: text removed.
 
Messages
13,774
Maybe I am wrong. Maybe Gerwyn/V99's virological expertise allowed them to see differences in those images that none of us could detect, and now Mikovits is in error claiming that they were the same. Anything's possible.

However, that some people trusted V99/Gerwyn over their own eyes was worrying. A lot of the technicalities are over our heads, so it can be tempting to just trust someone who sounds confident, especially if they are fellow patient - but Gerwn/V99 has shown that they are not a suitable guide for these matters.

There were actually some science arguments in my last reply - but it doesn't really matter. Either the Lipkin study will show that CFS patients are positive for 'something' at a greater rate than healthy controls, or it will not. Based on what we've seen so far, I think it is unlikely that Mikovits/Ruscetti/Lo/Alter will be able to distinguish between samples from patients and healthy controls under properly blinded conditions - although I'll be very pleased if I'm wrong (very, very).

If they cannot, and the Lipkin study ends without significant differences in rates of positives between those with and without CFS, then we should all accept that the Science paper was in error. I do not think that V99/Gerwyn would, and worry that their misplaced confidence could mislead others too.
 

currer

Senior Member
Messages
1,409
The hypothesis of a retroviral association with ME is an hypothesis with great explanatory power which merits full and careful investigation.

The rush to retract suggests to me that there is fear of the consequences of this hypothesis being true.

The value of this hypothesis is that it integrates several disparate observations.

The observation that rates of certain cancers have been rising in the last 30 years.
Breast 50% rise, prostate cancer tripled in all age groups, lymphoma has doubled.
Noone knows how to account for this. In the case of lymphoma, it has long been suggested that there are unknown viruses underlying this rise in cases,because the B cells are immyne system cells, but the viruses have not been found.
XMRV is responsive to androgens and oestrogens, and is found in the B cells.

The observation that autism and ME are more common in certain families.
Retroviruses which lie dormant in the immune system can reactivate following immunisation. Apparently HIV does this.
This provides a possible mechanism to account for the association of vaccination with autism.

The observation that there are abnormalities in the immune system of people with ME, that many viruses are found in patients, that there is no mechanism to explain why the body cannot rid itself of these viruses in the normanl way.

This is a valuable hypothesis which brings together observations fron different medical disciplines and unifies them into a whole.

The thinking cannot be retracted, even if the paper is attacked. Too late!
 

currer

Senior Member
Messages
1,409
Hypothesies differ in power. This one appeals to me.
Research cannot proceed without a theoretical basis for interpreting the meaning of that research.

I think Mikovits hypothesis is the best we have seen - as the one that best accounts for the known facts, that draws in observations that do not only relate to ME.

Before Judy Mikovits came along, there was no testable hypothesis for causation, almost no research, and unconvincing, conventional and unprovable theorising with no deeper analysis of the evidence.

Her work is attacked because her scientific hypothesis is set up in such a way that it is capable of being tested and proved.
In controversial areas of research we increasingly seem to see more and more research being funded which looks only at minor details, is insignificant in relation to the larger questions, and which is so badly planned that the conclusions are not really testable.

This is why we are seeing calls for the premature retraction of her paper.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
...The rush to retract suggests to me that there is fear of the consequences of this hypothesis being true.

...This is a valuable hypothesis which brings together observations fron different medical disciplines and unifies them into a whole.

The thinking cannot be retracted, even if the paper is attacked. Too late!

Jace posted the original comment that I believe originated with Gerwyn (at least that is what she said on Foggy Friends). I do not believe there is a 'rush to retract' if anything Science have taken a long time considering all of this and recent events (the contamination and retraction from Silverman) may only have served to compound their concerns. Remember they requested a voluntary full retraction before Silverman discovered the contamination and contamination questions remain unanswered.

What I have read in the past few days are excuses being banded around for why 'XMRV' was not found in the BWG study, along with the theory that it wasn't 'XMRV' at all (even after Mikovits and everyone else had been telling us all it was and Lombardi provided 'evidence' of a strong 'association' with CFS patients and even in healthy controls).

Here is one (in part) that seems to be offered up as reasons for the BWG failure:

http://www.twiv.tv/2011/10/02/twiv-1...ment-325127347

From 'Fry':

'Sorry Professor, but patients know that the WPI and NCI discovered HGRVs. XMRV was the wrong name, although of the human gammaretroviruses they discovered some will have a xenotropic host range.

As all the negative papers, including the blood group, used assays that had only been shown capable of detecting VP62, which does not exist in nature, and not theses viruses, everything is explained.

The WPI and NCI assays of course do not count in this instance as there was no Trizol used with the PBMCs and culture times that those assays do require was not given by the blood group. After all they were trying to protect the blood supply with a fast high throughput assay, not a reliable test for positives that takes times and it seems Trizol.

The CFIDS Ass have less than 1% of patients as members in the US, so they cannot claim to represent patients on any scale and even now have claimed they are switching to research, but how can they when the definitions they use for the disease don't require any symptoms, signs, or more importantly objective measures.

Most experienced ME scientists would also say this disease is not complicated at all. The WPI and NCI/Ruscetii are however making incredible steps forward, as their research has been confirmed by Lo et al. and Hanson.

It is interesting that you mention Lipkin is now doing deep sequencing for XMRV, will that include the human gammaretroviruses the WPI and NCI discovered? However, this really puts Lipkin is a new light, as if he is doing his own research he now has a conflict of interest regarding the multi lab study.

Really he should not be heading that up with this conflict and the Chronic fatigue initiative conflict of interest.'

Professor Racaniello:

'Your comments should be deleted because they don't contain a shred of truth. Your query "It is interesting that you mention Lipkin is now doing deep sequencing for XMRV, will that include the human ammaretroviruses the WPI and NCI discovered?" reveals that you don't understand the basis of deep sequencing. However I'm leaving the comment here so that others can see the misinformation that pervades discussion of CFS. '

The Hypotheses that HRGVs are in some way responsible for my condition, pain and suffering are simply that - theories. What you have said above might just as well apply to everything and anything. If/when Lombardi is retracted in full - what will there be to support the theory that it wasn't 'XMRV' it was 'HGRVs'? And what is there to support any theory relating to retroviruses and my condition?

If there is merit in the things people are posting by way of explanations for the 'failing' of the BWG and the 'failing' of those advancing 'XMRV' as the culprit - then we will once again have to wait for someone somewhere to publish a paper about it and for it to be subjected to scrutiny. I do not adhere to the theory that retroviral associations are being 'buried'. That notion is ridiculous. How many billions of $ have drug companies made from HIV alone? You think there is no incentive to investigate any of what you and others are advancing? If indeed what is being advanced on patient forums is even worth investigating.

I was listening to a recording of a 2010 talk from Annette Whittemore yesterday, who was speaking about 'XMRV' and what it could mean and the preventative actions to be taken by patients etc. One of the things she said was how much interest there was from drug companies since the Lombardi paper and how they were working collectively with WPI. I was left wondering where they are now. As well as wondering how this about change to 'HGRVs' suddenly suggests an 'aerosol' infectious route (Ottawa) when in that presentation Annette was saying 'XMRV' was not airborne? (http://vimeo.com/9004628 It says Mikovits but it is Annette). These are all theories and I would suggest dangerous ones to be airing (no pun intended) without anything - like a published paper - to back them up.

I would suggest that what you need is for someone who promised new research was going to be published - to publish it instead of talking about their theories and making even more claims that patients take on board because they follow the scientist/expert and not the science. Personally, I think if someone is expert in their subject that they should be able to explain it simply to their audience but this seldom happens on forums when someone (without an identity or acknowledged credentials) advances theories they claim have validity. Further, even when a science paper is published it is often the interpretation of it and the incitement that can follow that causes the dissent and the lack of understanding.

I am a patient Currer and I am not a scientist and I do not understand half of what is posted by patient/experts as fact - but I am most pleased when they do their best to explain things to me - then I can seek another opinion or three and make my own mind up and ask questions along the way. Not that it really matters - because I am a patient - these things will happen with or without me but I do find it all quite interesting as and when I am able to try and understand. However, when I read/hear of patients claiming that 'science' is wrong and they have an alternate opinion that provides a better explanation that they are happy to expound with complete confidence - I am duly skeptical and try to seek answers (if I need/want them) elsewhere.

O dear. Probably gone off on one now. Should have waited until the morning - doh! :cool:
 
Messages
10,157
I know ERV ain't always someone people read but I do and have for a while now. Anyway, she did post a reply to it. Perhaps predicable enough although maybe she will do a separate thread now? Someone did ask her too...

http://scienceblogs.com/erv/2011/09/xmrv_and_chronic_fatigue_syndr_29.php

Post number 875

Somebody actually answered the query.

... Anybody who works in molecular biology can tell in a second that those guys are simply making stuff up. For a start they seem to be promoting as idea that XMRV integrates into a GC rich region of the genome and becomes hypermethylated which will then make PCR difficult.
That statement alone shows them to know zero about molecular biology.
Methylation has no effect on genomic PCR.
GC rich regions themselves (with or without hypermethylation) can be a little difficult (but certainly not impossible) to amplify by PCR - but that is besides the point - the integrated sequence will have exactly the same sequence whether it integrates into a GC rich or a GC poor genomic location and will amplify just as easily in either location...
QUOTE]
 

SilverbladeTE

Senior Member
Messages
3,043
Location
Somewhere near Glasgow, Scotland
Once is an accident, twice is probably coincidence, but three times is deliberate!

In otherwords, yes there is a conspiracy to bury this whole damn issue, because again and again, any effort to help or deal with this illness gets torpedoed, backstabbed or run off the road (literally, even)
Note the crap Mikovitz got long before this, she had a bullseye painted on her back soon as she dared challenge the Wall of Silence and Vested Interests.

Again, very simply, go and look at the videos of the CROI coference, look at the attitudes, look how things were handled, who was allowed to attend and who wasn't...

Those who think all is rosy, this is normal fair Science in action, that no conspiracies occur, that the Weasels are only trying to help us poor ungrateful loonies...yeah keep drinking the Korporate Kool Aid, Komrades! :p
We'll, you'll never see any damn treatment in this generation, either, so kiss your ass (or rather, a chance at a healthy life) goodbye. Wake up!


Fear
Uncertainty
Doubt
And *poof!*, the threat to the Established Order goes away, again....
"Nothing to see here, folks! Just another hysterical female not knowing her place and being stupid, hope you didn't fall for her con? Only an moron would believe that retrovirus crap, you're not that stupid, are ya, citizen?"
ah huh.... (last line was ironic sarcasm condensing my point into a simple, enlightening bit of typical manipulative spiel, in case folk misread it)
 

jace

Off the fence
Messages
856
Location
England
There has been a concerted effort to disprove the 2009 Science paper ever since it was published. The first one, by McClure and Wessely, spent just a few weeks in the lab and four days in peer review. They are becoming more sophisticated in their attacks, but then, so are we in our rebuttals.

Why is no such effort evident with the Enteroviral hypothesis, the EBV hypothesis, the HHV6 hypothesis? Hmm.

I reworded Gerwyns' email to me a tad, to improve readability. I have checked on many of his statements, they have always held up so far.

Re CROI, it was funny at the end to see how worried researchers were about the infectivity of HGRV's, to the point that they were regularly testing themselves.

Dr Yes talks about the BWG and the slide issues here

The comment from ERV's blog, posted above, that included

That statement alone shows them to know zero about molecular biology.
Methylation has no effect on genomic PCR.

is presumably from another anonymous "expert". Keep trying to push it down, if you like, but the cat is out of the bag and all over the internet now. This is not 1991.

A PS from Gerwyn to the OP:

G-C pairs in the helix are held together by 3 hydrogen bonds as opposed to two with A-T opposing pairs.

C-G rich regions can cause the polymerase to stall.

The other problem is that the two strands tend to re-anneal quickly once denatured and need a longer denaturating time in the first place.

Annealing has to be quick and polymerisation rapid before the strands re-anneal. This means that the magnesium coenzyme needs to be reoptimised to maximise the performance of the enzyme via active site modification and the salt and buffer concentrations also need to be optimised to maximally stabilize the primer template dimer.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
Somebody actually answered the query.

... Anybody who works in molecular biology can tell in a second that those guys are simply making stuff up. For a start they seem to be promoting as idea that XMRV integrates into a GC rich region of the genome and becomes hypermethylated which will then make PCR difficult.
That statement alone shows them to know zero about molecular biology.
Methylation has no effect on genomic PCR.
GC rich regions themselves (with or without hypermethylation) can be a little difficult (but certainly not impossible) to amplify by PCR - but that is besides the point - the integrated sequence will have exactly the same sequence whether it integrates into a GC rich or a GC poor genomic location and will amplify just as easily in either location...
QUOTE]

R-i-g-h-t. The old 'anyone who is... can tell these guys (other scientists) are making things up'?

Well - if Abbie Smith says so, then it must be true... or not.

Watch the value statement nestled in the jargon people... Very few of you here can judge whether (or not) she is technically correct (and no shame in that whatsoever. Don't let the jargon spouters convince you otherwise).

But you certainly can see the lack of logic in the value judgements anyone makes, even super-duper bloggers.
 
Messages
13,774
I think that there's been some unnecessary moderation in this thread. It never seemed terribly heated. Is there a sub-forum I'm meant to mention this in?

As regards this thread : if what little remains of Lombardi et al is retracted, it will be for 100% scientific reasons.

No conspiracies. No politics. Just data.

Just to unnecessarily complicate this thread further - I don't think that politics can be so easily separated from any potential decision to retract or not. eg: A lot of people are unsettled by Mikovits's statements/behaviour, and this could well mean Science are keener to retract. The worry about CFS patients taking unnecessary ARVs might mean that the CFS paper would be more likely to be retracted than the PC papers. Politics/society often interacts and affects the way science progresses - more than some scientists like to admit.

In political terms, I think it would be a mistake to retract the paper prior to the results from Lipkin.

@ jace - I don't mean to come across as condemning of you for posting what you believe to be valuable information, but I really don't understand how you can say that Gerwyn's statements have always held up so far. What about the claims that were being put forth about the identical images Mikovits used to illustrate different results?
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
Why anyone would listen to people who were claiming the slides were not the same, despite now having this confirmed by Drs Mikovits and Ruscetti, is totally beyond me.

"Credibility" is not easily won in science. That's why it's not a good idea to listen to non-scientists who have clearly been shown to be talking utter nonsense about the work of actual professional scientists.

There are few skills more valuable than being able to spot an apparently convincing BS artist. Unfortunately, the ME/CFS arena has quite a few of them.

As regards this thread : if what little remains of Lombardi et al is retracted, it will be for 100% scientific reasons.

No conspiracies. No politics. Just data.

Um- some people were acknowledging the slides were the same, the kind of people I think you are talking about! Others - like me- for example- thought they looked different but acknowledged they could be wrong. That's what I did.

So because someone was wrong in their qualified guess makes them wholly unreliable for ever more? And people who were right on this one thing must be listened to for ever more? That makes no sense.

I think it's quite obvious that your 100% figure does not allow margin for error. By your own logic that makes you unreliable for ever, (anonymous) non-scientist yourself.

Because the evidence shows there clearly IS political, non-scientific factors at play, including Abbie Smith's potty-mouthed hatred of Judy Mikovits. It is just not rational to refuse to acknowledge what political factors are in play here, and it's an attempt to close down debate, a strategy that never works in the ME community, thankfully.
 
Messages
10,157
Somebody actually answered the query.



R-i-g-h-t. The old 'anyone who is... can tell these guys (other scientists) are making things up'?

Well - if Abbie Smith says so, then it must be true... or not.

Watch the value statement nestled in the jargon people... Very few of you here can judge whether (or not) she is technically correct (and no shame in that whatsoever. Don't let the jargon spouters convince you otherwise).

But you certainly can see the lack of logic in the value judgements anyone makes, even super-duper bloggers.

The quote I supplied was not written by Abbie Smith. There has been independent support on different websites that what Gerwyn has stated is erroneous.