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

[Bob]

And here we go again. Bob made some good points about XMRV but this is still a layman discussion. I don't know if his 7 arguments are valid and neither do most other people here. I would do anything to have some comments on these arguments from a virologist or people like RRM and drosha who seem to have a scientific background. This is the only way we can advance.

But like I said earlier, if you ask 100 virologists, you will get 100 different answers, and they won't be any more informed answers than the information that is available on this forum.

If you ask Coffin, he will say forget about XMRV, it doesn't exist (well, not in ME patients anyway), move on.
If you ask Singh, she will say XMRV exists in prostate cancer, but there is no XMRV association with ME/CFS.
If you ask Mikovits then she will say that she is very confident about her results.
If you ask Lo, he will say that his research is still valid.
If you ask Switzer, he will say that he is unable to detect XMRV in the blood, but that it is a human virus that needs further investigation.
Some scientists might tell you that XMRV doesn't exist at all, or that it is purely a mouse virus, although I can't think of any who still have this view.
etc etc etc

There are not any definite answers right now, but only conflicting research studies. So the research continues.

Until we have further and more solid evidence then things are just going to carry on as they are right now, with everybody arguing about what the facts are. At the moments the facts are often a matter of personal bias because there is conflicting evidence.

Each of the seven points that I made in my earlier post was based on the evidence that is available to all of us.
A virologist would base their opinions on the same evidence that I have based my information on. e.g. the published research papers, and related information. There is no other evidence available.
I made my points as simple as possible, but if you want me to, I can point you towards the evidence that I based my points on, or I can explain my points in more detail.

It seems to me that you want an authoritative voice to tell you what the facts are.
But that's not going to happen any more than it happens on this forum.

 

[ukxmrv]

Thanks Jemal, but unless the posts are made openly there is no way we can all benefit from this process. Hope it can be made public.

Wave runner started this thread with a proposal and that doesn't help if things hidden.

 

[Jemal]

Thanks Jemal, but unless the posts are made openly there is no way we can all benefit from this process. Hope it can be made public.

Wave runner started this thread with a proposal and that doesn't help if things hidden.

I don't want to hide things ukxmrv. I just think the person messaging me has a valid point and I would be interested in seeing him/her post the message. But if he/she doesn't want to, I will certainly post myself.

 

[ukxmrv]

Jemal, I certainly don't think that you were trying to hide things. Sorry if my post give that impression. I do understand that it was a private message and of course you would respect that.

 

[Waverunner]

But like I said earlier, if you ask 100 virologists, you will get 100 different answers, and they won't be any more informed answers than the information that is available on this forum.

It seems to me that you want an authoritative voice to tell you what the facts are.
But that's not going to happen any more than it happens on this forum.

I don't know much detail about XMRV but I know that 100 virologists will not have a 100 different opinions. Well, of course their opinion will differ the more we go into detail but the main question is if they believe that XMRV is a pathogenic virus with causes harm to us humans and has a connection to CFS. In my eyes and what I conclude from the latest news about XMRV, probably 90 will be contra.

I don't want an authoritative voice to tell me what the facts are. I want a science based discussion. Someone just wrote me a long message with counter points /the longest counter point was about the Alter/Lo study which according to many scientists and recent research is NO replication study) to every single of the 7 pro XMRV arguments, which Bob made. I don't know if people are scared to start a public discussion here but in my eyes there are not many contra XMRV people here who speak out publicly. I would love to hear RRM or drosha say their opinion about it.

 

[ukxmrv]

Then why not ask you to post it so it can benefit us all Waverunner?

There is no reason why people would want actual arguments to remain hidden. They themselves may want to remain behind the scenes for a variety of reasons including the fact that they simply cannot type much, handle stress or follow a thread.

 

[Bob]

I don't know much detail about XMRV but I know that 100 virologists will not have a 100 different opinions. Well, of course their opinion will differ the more we go into detail but the main question is if they believe that XMRV is a pathogenic virus with causes harm to us humans and has a connection to CFS. In my eyes and what I conclude from the latest news about XMRV, probably 90 will be contra.

I don't want an authoritative voice to tell me what the facts are. I want a science based discussion. Someone just wrote me a long message with counter points /the longest counter point was about the Alter/Lo study which according to many scientists and recent research is NO replication study) to every single of the 7 pro XMRV arguments, which Bob made. I don't know if people are scared to start a public discussion here but in my eyes there are not many contra XMRV people here who speak out publicly. I would love to hear RRM or drosha say their opinion about it.

Waverunner, there are no answers yet. It's as simple as that.

All I want is for the research to continue.

What annoys me about people making statements that XMRV is a contaminant, is that that there is no conclusive evidence for this.

However, there is evidence that XMRV is a real human virus, and that it might be associated with ME.
There must be about 20 to 40 published papers now that provide evidence towards the XMRV being a human virus.

Even if Alter's research does not confirm the WPI's research (which isn't Alter's opinion), then we still need to investigate the association between PMRV's and ME. So far we have a study that says that XMRV is associated with ME, and a study that says very similar MLV-related viruses are associated with ME. I don't see how we can separate the two.

And our knowledge about XMRV is growing and evolving every day/week/month/year.

 

[Bob]

I don't want an authoritative voice to tell me what the facts are. I want a science based discussion.

Well, what do you think is going on here then?

Like I said, I'm happy to give you references to the published research that I've based all of my statements on.

I think what you probably need is for the whole XMRV story to be presented to you in a balanced and accessible way.

 

[Bob]

Someone just wrote me a long message with counter points /the longest counter point was about the Alter/Lo study which according to many scientists and recent research is NO replication study) to every single of the 7 pro XMRV arguments, which Bob made. I don't know if people are scared to start a public discussion here but in my eyes there are not many contra XMRV people here who speak out publicly. I would love to hear RRM or drosha say their opinion about it.

I would like someone to please provide me with one single piece of conclusive evidence that XMRV is contamination.

One piece?

 

[jace]

Bob, that piece you quote is from Waverunner, isn't it?

You won't find one piece of evidence that HGRV was contamination in Lombardi or Lo, because there isn't any. There's guesswork and conjecture (is that tortology?) and assumptions, but there is no proof. Both the Mikovits lab and the Lo lab have stated categorically that they take and have always taken extraordinary measures to prevent contamination. Mikovits has never had the 22rv1 cell line in her lab.

Similarly, there is no hard evidence that XMRV is a recombinant from a lab event in 1992. Again, there is conjecture, phylogenic trees drawn with imagination, hunts for MLV's with partial sequences that match parts of the XMRV virus, and the assumption that they combined, without even the knowledge of which mouse strain was used in the hypothetical event in the unnamed lab.

Re the quote from Waverunner, personally I have no desire to see RRM or Drosha posting more of their dogma here. They do enough of that elsewhere on the web.

Annette Whittemore stated in Invest in ME Conference that the WPI has an open mind about the causation of ME, and so do I. However, I find that the science is more rigorous and believable on the HGRV positive side.

 

[Bob]

Bob, that piece you quote is from Waverunner, isn't it?

Yes, thanks for pointing that out jace, I've corrected my post now.

You won't find one piece of evidence that HGRV was contamination in Lombardi or Lo, because there isn't any.

Thank you jace... That's precisely the point that I was making... Thank you for the interesting answer.

 

[Cort]

@Kurt: What does auto-immune mean though? The concept is advanced in order to explain ideopathic states in which the immune system appears to be chronically activated, apparently inappropriately activated, and attacking various parts of the body. But what is causing the immune system to be activated? Once I start to think about this, informed by the possibilities that XMRV highlights, it occurs to me, at least, that this idea that the immune system is misrecognising part of the body as an enemy to be attacked could be quite wrong. It seems at least as likely that some unknown, persistent, near-impossible-to-kill pathogen is the cause of the chronic immune activation - and the attack on the body itself is just a byproduct of this chronic activation. Maybe the body is doing the best it can in the face of something it can't kill, and can just barely keep in check; the collateral damage can't be helped, it's the lesser of two evils. I realise this is a very informal argument but as soon as I entertained the idea, it kind of leaps off the page to me that the "auto-immune" concept is based on the assumption that there's no unknown pathogen provoking the immune response.

Both are right. Infections do seem to be able to spur auto-immune responses - that is not in doubt. It could be that a antigen in the pathogen looks very much like a protein in the human body - causing the immune system to mount an attack against both. I think its also possible that an infection starts some sort of immune cascade that goes berserk so to speak; the immune system knows its under attack but is not sure from where and starts attacking back in all sorts of different directions - sometimes hitting the body. I think there is some suggestion of this with NK cells and NK cell exhaustion.

 

[Cort]

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.

Getting expert advice is difficult but more would be very valuable. I've talked to a couple of researchers but only a couple. Dr. Satterfield, for instance, has a history with CFS and in conversation is very balanced - so I've used him. Dr. Mikovits has, at times, replied to emails. Dr. Racaniello has at times...and has Dr. Miller....but the pool is not a large one

I wish I had, from the beginning, tried to hunt up some retrovirologists who have no skin in the game who would've followed along this issue with us..

 

[Jemal]

I have not heard back from the person who sent me a private message, so I will just post this myself.

I said that there were no studies that directly address the Lo/Alter study. That's not true as there's now at least one study that addresses the Lo/Alter study:

The exact variety and nature of our sequences show very close parallels to those reported by Lo and colleagues from patients with CFS [5] especially in the set of samples from recent repeat isolations. They argue that the recent sequences (MLV001MLV006; HQ60195762) show evidence of viral evolution from an earlier sequence (assumed here to be cfs1 since this was identified in 18/21 sequences). However such evolution would be predicted to show monophylogeny. Our maximum likelihood analysis of these sequences is clearly inconsistent with such a prediction (Figure 2). In particular we see no obvious explanation for a sequence of the modified polytropic cfs1 type evolving into a polytropic sequence like MLV002 or MLV006 (Figure 3), Similarly it seems implausible that MLV001, which shares with 9C a deletion encoding 15 amino acids of matrix (MA), presumably precluding virus replication, could evolve from cfs1. In the absence of evidence for replication competent MLV in the samples reported by Lo and colleagues, we believe that the finding of a population of gag sequences in the reagents, as well as the coincidence of a virtually identical replication incompetent MLV in our study and that of Lo and colleagues, must call into question the biological provenance of these sequences and therefore any conclusions drawn [5] concerning their relationship to CFS.

We suggest that contamination may complicate studies of XMRV in multiple ways depending on the source of the adventitious nucleic acid. Presence of material (RNA or DNA) from 22Rv1 cells would result in sequences identical or nearly identical to XMRV. Alternatively, mouse DNA could be the problem in other studies, when a variety of endogenous MLV will be amplified resulting in a range of related sequences as seen in this study. In particular we caution that the reagents used to detect MLV-like sequences may themselves have been contaminated with murine DNA. Although we do not suggest that this is the primary source of the XMRV/pMLV sequences observed in previous studies, it could well represent a confounding factor and note that the original detection of XMRV gag sequences by Urisman and colleagues used Invitrogen Taq and Lo and colleagues used IPT reagents. Finally we believe we would be wise to remember the classical warning Caveat Emptor.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019953

If I understand correctly, they are not definitely saying the Lo/Alter study is about contamination, but they say it's a possibility and they give a warning that reagants might be contaminated.

This study popped up in pubmed this week.

As a layman I have no idea what worth this study has, I just wanted to correct something I said.

 

[Sam Carter]

...

With regards to the addendum, Judy has always said that PCR is the least effective method to detect XMRV.

...

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.

...

It's only by using further techniques, such as nested PCR, ...


...

"""""""""""
Science. 2009 Oct 23;326(5952):585-9. Epub 2009 Oct 8.

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.

Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA.

Using the Whittemore Peterson Institutes (WPI) national tissue repository, which contains samples from well-characterized cohorts of CFS, we isolated nucleic acids from PBMCs and assayed the samples for XMRV gag sequences by nested PCR (5, 6). Of the 101 CFS samples analyzed, 68 (67%) contained XMRV gag sequence.
""""""""""""

 

[Bob]

"""""""""""
Science. 2009 Oct 23;326(5952):585-9. Epub 2009 Oct 8.

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.

Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA.

Using the Whittemore Peterson Institutes (WPI) national tissue repository, which contains samples from well-characterized cohorts of CFS, we isolated nucleic acids from PBMCs and assayed the samples for XMRV gag sequences by nested PCR (5, 6). Of the 101 CFS samples analyzed, 68 (67%) contained XMRV gag sequence.
""""""""""""

I can't work out what the message is in that post Sam?

 

[Sam Carter]

I can't work out what the message is in that post Sam?

Hi Bob,

Yeah, I'm in a kinda elliptical mood tonight ...

In post 54 of the thread you appeared to be arguing that PCR lacked the sensitivity to detect the presence of XMRV in a person's blood, yet that was exactly the technique used by Dr. M in the Lombardi paper.

Sam

 

[Bob]

Hi Bob,

Yeah, I'm in a kinda elliptical mood tonight ...

In post 54 of the thread you appeared to be arguing that PCR lacked the sensitivity to detect the presence of XMRV in a person's blood, yet that was exactly the technique used by Dr. M in the Lombardi paper.

Sam

I hope you enjoy your elliptical mood Sam!

It's all explained in my post. Lombardi et al did not use single round PCR for the main part of their study. The used nested PCR along with other methodologies.

 

[Sam Carter]

I hope you enjoy your elliptical mood Sam!

It's all explained in my post. Lombardi et al did not use single round PCR for the main part of their study. The used nested PCR along with other methodologies.

(Continuing in an elliptical spirit ...

)

That's my point -- Erlwein, Switzer, Satterfield, Furuta, Shin and Knox also used nested PCR and found nothing.

 

[Bob]

That's my point -- Erlwein, Switzer, Satterfield, Furuta, Shin and Knox also used nested PCR and found nothing.

I was replying to a specific point raised in a previous post, and it looks like I over-simplified my discussion.

To answer your point, I'll refer to you Annette Whittemore's list of differences in the methodologies:
http://treatingxmrv.blogspot.com/2011/06/comparison-of-methods-for-detection-and.html