Proposition to put the XMRV discussion here on a more profound and scientific basis

[Bob]

Ok, I can't help myself anymore. Everytime I see that quote, I want to start singing.

"The chances of anything coming from mars are a million to one. But still they come."

[video=youtube;lqvwxvCOSH4]http://www.youtube.com/watch?v=lqvwxvCOSH4[/video]

It was a scientist as well saying the first part

hehe, thank you for the musical interlude Jemal

(I like having the slightly over-dramatic background mood-music to this discussion thread.)

 

[Wayne]

I'm not saying that all scientists can't be trusted. Far from it. I'm just saying that they are not necessarily more objective or better informed than well informed 'expert patients'. Some scientists are not particularly objective, not particularly trustworthy and not particularly well informed, especially when it comes to ME and XMRV.

Hi Bob,

Nice treatise. I agree with your above comments (and your whole post). Although most scientists think they are being totally logical, honest, and objective, they have clearly shown in the XMRV debate they are not. If they kept their biases to themselves, that would be one thing. But when they trumpet them to the unquestioning mainstream press, then that's another thing, and is detrimental to us and the entire scientific community.

Various comments have been made about "subjective" takes. Well, here's a subjective take on my part. Whether XMRV proves to be associated with ME or not, I have found Judy Mikovitz and WPI to be credible and trustworthy, much more so than many in the scientific community who have been far too quick to discredit their work. They seem to be genuinely working on our behalves and I don't believe would be publishing their results unless they absolutely felt it was in our interests to do so. I can't say that for some of their critics.

Subjectively Yours,

Wayne

 

[Jemal]

hehe, thank you for the musical interlude Jemal

The really good part starts around 6:17.

 

[Bob]

The really good part starts around 6:17.

Now, every time I see 'a trillion to one' quoted, I'll think of you bursting into song "The chances of anything coming from Mars are a million to one he said... The chances of anything coming from Mars are a million to one... But still they come!" (I might even join you!) (But I can't sing, so I'd get thrown off the forum if I did it too often!)

 

[Jemal]

Now, every time I see 'a trillion to one' quoted, I'll think of you bursting into song "The chances of anything coming from Mars are a million to one he said... The chances of anything coming from Mars are a million to one... But still they come!" (I might even join you!) (But I can't sing, so I'd get thrown off the forum if I did it too often!)

Hehe. It's just that I get mighty suspicious when people are throwing around such numbers when it does not concern something mathematical.

 

[currer]

Hi kjm,
I feel I owe you an apology - my post was a bit abrupt. I have seen your posts up for a while and I always assumed you were some kind of medic - yes, I know you say you were a nurse, maybe that is why. I felt rather threatened by your post because I felt you had some kind of authority over patients you were trying to assert as a professional and not as a patient.
I did not realise you were a patient like us, too.

 

[Undisclosed]

KJM,
Your post assumes that we see a fair scientific debate going forward about XMRV.
I do not see a fair debate. I live in the UK and the Alter paper, for example, is not acknowledged by our government. I do not expect the other positive XMRV papers to be acknowledged here either - the Bieger or Hanson papers.
What I do see happening, is two narratives developing, one for informed insiders - scientists, government health employees, the odd patient who is able to keep up, and another totally spurious one for public consumption about contamination.

If you follow the research at the retroviral conference going on now, there is ample evidence that XMRV is being taken very seriously indeed. But that is not what gets into the press releases.

How are we to hold our public servants and governments to account for the decisions they make on our behalf if such a double standard is allowed to continue without protest?

You seem very unperceptive about these obviously fraudulent proceedings. You cannot however require that everyone else be as unsuspecting as you, especially when as patients we are always the ones to pay for the political shenannegans that go on around CFS/ME (a chronic tiredness which somehow kills the odd unlucky patient)

Currer, I wasn't actually alluding to any debate but the research studies themselves. I concur that many of the debates are one-sided and not fair. I never said people were not taking the research seriously, I know it is being taken seriously. I take anything written by the popular press as usually being crap because it's easy for people to contact the media and get a story written -- and usually it's about one side or the other, there are very few balanced articles out there.

I guess I shouldn't have said anything, this is very stressful for me because I can't even produce a coherent sentence without really struggling and it's seems what I am trying to say is not coming across well at all. There was no intent of anything really.

Oops just saw your most recent post. I lost the ability to practice nursing years ago, it was a huge blow to me. I am just like everybody else here. Looking for an answer.

 

[currer]

Dont be upset. It is easy for misunderstandings to occur on forums. We are all really talking to ourselves here, in a way.
I think Cort is quite correct in keeping PR carefully moderated. It would be a shame to allow the bullying here that goes on on the other forum. That is why I do not go there.
If I thought you were a patient I would have been more careful in what I said.

 

[currer]

When I attended the Invest in ME conference last month I met many of the researchers whose work we discuss endlessly here, including JM and AW.

It made me realise that these forums are a way of compensating for our isolation from what is really going on. None of the people I met seemed harmed by the politics around ME.
Judy Mikovits looked as if she was completely fulfilled and having a great time - probably every virologists dream to do what she is doing.

No, it is us who are unhappy about what is going on, and that is because we are ill.
The researchers are much tougher than we give them credit for - they are healthy and robust.
On these forums you can see such pain, and that is why we can attack each other.
You can see it especially on the other forum.

 

[Waverunner]

It's a difficult situation, a very emotional situation at that. I have chosen to divest myself of the emotions and look at the research and frankly it's not looking good for XMRV at this point but I am waiting for Lipkin to publish his research. I do think some people have gone way too far in that anybody who is not "for" XMRV has been demonized. Is it possible to hate somebody you don't even know, you can dislike the results of their research but to post diatribe after diatribe about different researchers on a forum is a bit much (not talking about this forum). I contacted a virologist a while back to ask a few questions about XMRV, the answer I got was we are not going to respond due to prior replies to interested patients being posted on forums with the information twisted into something we didn't actually say (not this forum). I can see their point. I have seen virologists trying to post information about the state of the research and being called troll and baby killer and all sorts of unkind things -- just for trying to post how the testing actually works or why people may be misinformed about something etc. This is damaging to the community because rather than using the knowledge of somebody positively, they get insulted and has a group we miss out on puzzle pieces.

I am not for or against XMRV, I am for continuing research.

When looking at the comments on twiv.tv I see a debate pro vs contra XMRV. In my eyes the contra XMRV side is more trustworthy as well as scientific. I give you one example where the pro XMRV side makes a bad stand:

RRM: "The CC "confirmed" 7 out of 101 samples. Great confirmation."

Gob: "They only tested 11."

RRM: "No, they tested all 101 using that same assay. It's in the addendum to the Science paper: "The remaining 90 samples described in the paper exhibited very few XMRV-gag specific PCR products and no env specific PCR products following single round DNA PCR of DNA of unstimulated PBMCs."And thus:"only 7% of our 101 patients PBMCs exhibit products upon DNA PCR."

Gob: ""XMRV gag sequence. Detection of XMRV was confirmed in 7 of 11 WPI CFS samples at the Cleveland Clinic""

RRM: "Yes. It was confirmed in 7 out of 11 "highly viremic" patients. The other 90 patients were negative, as you can clearly conclude from the quote I've provided.
You understand the addendum is a clarification, right?"

Gob: "They did not test the remaining patients with that assay in Lombardi et al."

Instead of admitting that she (Gob) was wrong with the numbers she switches topic!

RRM: "Who cares if they did it before or after? Fact is that all patients were tested and a whopping 7% was found to be positive using that assay."

And this goes on and on and on. RRM and drosha as far as I can judge this, always win the discussions and they don't seem biased to me.

 

[ukxmrv]

I'd like to suggest another way for patients to consider this ongoing saga.

Even if you are more comfortable sitting on the fence or even if you find the science baffling and want to sit and wait for the experts to sort this out.

Please remember not to be quiet and passive about ensuring that XMRV and the MLV's are thoroughly investigated and this path taken to it's logical conclusions (whatever they may be).

If you don't feel comfortable about XMRV, please still support us patients who do want the research to continue until we get an adequate answer.

 

[Angela Kennedy]

I'd like to suggest another way for patients to consider this ongoing saga.

Even if you are more comfortable sitting on the fence or even if you find the science baffling and want to sit and wait for the experts to sort this out.

Please remember not to be quiet and passive about ensuring that XMRV and the MLV's are thoroughly investigated and this path taken to it's logical conclusions (whatever they may be).

If you don't feel comfortable about XMRV, please still support us patients who do want the research to continue until we get an adequate answer.

Beautifully put ukxmrv!

 

[Bob]

When looking at the comments on twiv.tv I see a debate pro vs contra XMRV. In my eyes the contra XMRV side is more trustworthy as well as scientific. I give you one example where the pro XMRV side makes a bad stand:

RRM: "The CC "confirmed" 7 out of 101 samples. Great confirmation."

Gob: "They only tested 11."

RRM: "No, they tested all 101 using that same assay. It's in the addendum to the Science paper: "The remaining 90 samples described in the paper exhibited very few XMRV-gag specific PCR products and no env specific PCR products following single round DNA PCR of DNA of unstimulated PBMCs."And thus:"only 7% of our 101 patients PBMCs exhibit products upon DNA PCR."

Gob: ""XMRV gag sequence. Detection of XMRV was confirmed in 7 of 11 WPI CFS samples at the Cleveland Clinic""

RRM: "Yes. It was confirmed in 7 out of 11 "highly viremic" patients. The other 90 patients were negative, as you can clearly conclude from the quote I've provided.
You understand the addendum is a clarification, right?"

Gob: "They did not test the remaining patients with that assay in Lombardi et al."

Instead of admitting that he (Gob) was wrong with the numbers he switches topic!

RRM: "Who cares if they did it before or after? Fact is that all patients were tested and a whopping 7% was found to be positive using that assay."

And this goes on and on and on. RRM and drosha as far as I can judge this, always win the discussions and they don't seem biased to me.

Some XMRV/PMRV studies have been positive and some have been negative, and researchers are currently looking for more evidence. There is a scientific debate going on about the subject, and it's going to be a long process.

The only reason I get frustrated about the issue is because I read about people saying that XMRV is just contamination, or that XMRV is not a real virus, or that it's a lab artifact, or that there is no association between XMRV and ME, or that XMRV research is not looking good, or that we should forget about XMRV and not worry ourselves about it.

All of these opinions are just unscientific opinions. There is so much that we don't know about XMRV that it is far too early to draw any conclusions from the tiny bit of research that has been carried out so far.

So it would be very nice if we could be allowed to watch the research unfolding without feeling like we are under attack all of the time from people who seem to wish to close down the subject. Maybe that's not what they are doing, but that's certainly my interpretation, from the strange comments that people like Coffin and Stoye persistently make.


With regards to the addendum, Judy has always said that PCR is the least effective method to detect XMRV. In the addendum the authors state clearly that they used 5 different methods, and that single-round PCR was the least sensitive of the methods used, possibly because of the very low copy numbers of the virus in the blood. So they selected a small cohort of 11 patients to test using this method, who they had observed to have persistent viremia (viremia = virus in the blood), and 7 out of 11 tested positive for gag and env XMRV sequences.

"We included this figure to demonstrate that nested PCR, which inevitably raises questions of contamination, is not essential to detect XMRV in highly viremic ME/CFS patients."

"The remaining 90 samples described in the paper exhibited very few XMRV-gag specific PCR products and no env specific PCR products following single round DNA PCR of DNA of unstimulated PBMCs."

"In contrast, when cDNA was prepared from PBMCs, 67% of the samples exhibited gag products upon nested PCR, though PCR with nested env primers did not result in detectable products from these samples."

"Of the 34 patients whose PBMCs were negative for XMRV by DNA or cDNA PCR, 17 were positive for infectious virus when co-cultured with the LNCaP indicator cell line, as XMRV gag and env PCR products were detected in the cell line following their infection with XMRV from the patient PBMCs"


So when the authors of the negative (zero/zero) studies say they can't detect XMRV by PCR, then it's not really a surprise. Judy Mikovits couldn't either, except for 7 out of the 11 carefully selected patients who were probably extremely ill, and showing signs of viremina. (I don't know the details about the signs.)

It's only by using further techniques, such as nested PCR, stimulated PBMCs, and by culturing the samples, that Judy was able to detect XMRV in most patients.

When the authors of the negative studies say that they did exactly what Judy did, her methodology was very complex and they haven't followed it exactly, and some not even closely.

Here's what the authors of the addendum say about the UK zero/zero studies: "...very few, if any, of the samples would be expected to be positive by DNA PCR..."

So, unstimulated single round PCR (gag) detected 7% positive XMRV DNA.
Unstimulated nested PCR (gag) detected 21% DNA and 54% cDNA.
Stimulated nested PCR (gag) detected 72% cDNA.
Cultured LNCaP nested (gag) detected 89% cDNA.


I think it's a shame that the addendum wasn't added to the original paper, because I think most XMRV researchers don't seem to have read it, probably because they think they already know how to detect a retrovirus, so why would they need any advice?


Here's the addendum:
http://www.landesbioscience.com/journals/virulence/MikovitisVIRU1-5.pdf

 

[Bob]

If WPI have data to suggest why a large number of virologists are wrong we need to see it. Soon.

I don't see why that burden should be placed solely onto the WPI. That's rather a heavy demand you are placing on them.

I would place that burden on the whole scientific community.

But the WPI have already released a lot of data, and they have more that they are working on.

The WPI have now released a comprehensive list of the differences in the methodologies in the various studies, and they have published a whole load of new gene sequences to genbank. And this is all from private funding, as nearly all of their grant applications have been rejected.

I don't understand why you need more data KFG. The research is already out there if you look for it, or if you ask about it.
For example, Coffin's study has now been rebutted and superseded by the CDC's research, and by the new gene sequences published in genbank.

XMRV research has not been static for the past year... It's been dynamic and ever evolving, although you wouldn't know about this from the media reports. If you only look at the highest profile studies, then you are missing a lot of very interesting research.

 

[Bob]

John Coffin and Illa Singh went from being strongly pro-XMRV at the beginning to being strongly anti-XMRV now. Why ? Because the weight of scientific evidence has led them there.

I disagree with this. There isn't a weight of evidence behind them at all. I believe that it is Coffin's personal biases that led him to his opinions, and the results of Singh's personal research that led her to her opinions re the XMRV association with ME. This doesn't make their conclusions correct. They do seem to be very premature to me.

Singh is not anti-XMRV. She detected XMRV in prostate cancer patients

 

[Jemal]

Singh is not anti-XMRV. She detected XMRV in prostate cancer patients

Yes, and she stated after her CFS research, she still believed in her prostate cancer research (XMRV). She has taken a very weird position, but there you have it.

 

[Bob]

Bob,

Those are excellent points. I'd like to add another factor. Diagnostic criteria ( my favourite subject....not ). How many people in the negative studies had what we would consider to be "proper" CFS ?

It's the ultimate question, in my view. Of course some people would counter that out of all the negative studies at least some of those patients must have been suffering from "proper" CFS. Still, not a good basis for detecting the elusive XMRV....

Diagnostic criteria is the most important issue in CFS research. It renders all the debate on lab techniques substantially meaningless.

I agree that 'diagnostic criteria' is an important issue, but in my opinion, it is not the most important issue with most of the negative XMRV studies. The negative studies simply have not replicated the WPI's extremely complex methodologies in order to attempt to detect an extremely elusive novel virus, which Judy Mikovits has stated will not be likely to be detected using simple PCR, based on her own results which I outlined earlier.

 

[ukxmrv]

John Coffin and Illa Singh went from being strongly pro-XMRV at the beginning to being strongly anti-XMRV now. Why ? Because the weight of scientific evidence has led them there.

KGF, can you please so me a really big favour and show me where the weight of scientific evidence is that Coffin supposedly has? Yes, he does have a theory on contamination but this has already been rebutted and argued against. It's not "scientific evidence" just another unproven and maybe totally wrong theory.

I've read the papers he refers to, the recent Tufts uni piece, watched him at the recent conference (CFS SoTS) and I can't see the scientific evidence.

The reason I am posting this is that I also want my life back. It's too important to miss any facts.

Really sorry if you are feeling badgered and please feel free to ignore this post if you can't face this thread again.

 

[Dainty]

Thread cleaned up and re-opened. :Retro smile:

 

[omerbasket]

I've been following the forums and especially the XMRV discussion for a year now. We have many people outside this forum who are contra "XMRV" and neglect any connection to CFS. On the other side we have many people here who support WPI and see the XMRV discussion far from over.

The great problem and biggest chance for progress in this field in my eyes is the fact that currently there is no interchange between these two opposing sides. Both sides are convinced that they are right and members of both sides try to convince other group members that their side is right.

We have many intelligent people here who read the studies. They make very interesting arguments which all seem valid and scientific. The other side does the same and the other side has many studies on their side. The problem and this is the only point I want to make, as long as both sides don't talk to each other, progress will be very slow. Most people here are layman regarding virology. Maybe it would be better if people who have arguments that speak for WPI or XMRV confront virologists with their questions.

Vincent Racaniello has a geat site and the comment section offers a great possibility to discuss XMRV but many questions stay unanswered as as long as Gerwyn keeps his troll like behavior it will be very hard to have a solid discussion. So my thought is that in case of valid questions/arguments pro XMRV it would be very good to speak to real virologists and maybe post the answer here, instead of keeping the discussion to mainly PWCs only who do not have a virologist background. Most of us are layman so we cannot counter any pro/contra XMRV arguments even if they are completely false. Putting the discussion on a more profound and scientific basis would be a very good thing in my eyes.

The problem is that those "real virologists" also have their opinions. Racaniello thinks that there is no connection between XMRV and ME/CFS. Other scientists, at least as good as he is, think otherwise (for example: Mikovits, Ruscetti, Lo, Hanson etc.), and others, probably with the same kind of record, would agree with him (like Coffin, Stoye, Singh etc.).
As long as there are not definitive facts, there are just opinions. And if we are talking about an opinion, it's possible that a total layman would have the opinion that would eventually be proven to be the right one, while an experienced virologist would have the opinion that eventually would be proven to be the wrong one.