Article: Four Viruses! Alter Paper Confirms Retroviral Findings in CFS

You can view the page at http://www.forums.aboutmecfs.org/content.php?213-Four-Viruses-The-Alter-XMRV-Paper-Arrives

 

Clearly you haven't read the paper. What's with the bit about 'write the paper'

If you have so many problems about my paper - calling it 'nonsense' and stating you can't read any further because its so bad and stating I'm missleading people and ' haven't even read the paper (for God's sake) and doing so in such a negative tone as to imply that I'm willfully misleading people - it sounds like you know alot more about this than I.

Hence this

Again my comments are about you leaving out important information. As you have read.

You seem to know it all. I suggest that you start writing - write the paper you want to see and send it out. In fact after all these comments I challenge you to do that. You have very aggressive posts - you seem to think that you are telling like it is - you don't even try to be polite - its apparently so simple to you - I challenge you to put something on the matt instead of chiming in from the sidelines. How about it?

 

If something has a 1% chance of happening, the chances of it not happening in 104 goes is (.99)^104=0.3516.

If something has a 2% chance of happening, the chances of it not happening in 104 goes is (.98)^104=0.1223.

True again, but Gerwyn's rebutal made some very important points.

1) Other studies of gamma retroviruses have also been unable to detect the virus by unstimmulated PCR, in hosts known to be infected.
2) PCR fails very easily if you are looking for the wrong sequence. All it takes is an extremely tiny variation, and variation is extremely common, geographically, person to person, and even within a single host.
3) Neither their PCR nor their serology assays had established diagnostic sensitivity. In fact, they were unable to detect the virus in infected samples that the WPI sent them.

 

Journalists sometimes get things wrong particularly about science - it is not like a peer reviewed article where one may take weeks to write it. It doesn't mean we should stop them writing. Cort has comment facilities at the bottom if people think there are mistakes. I think his articles are useful. If people think they can do better than Cort, they are welcome to write pieces.

 

While the WPI’s overall thesis was confirmed we still have two disparate findings; the WPI found XMRV and no other MLV’s while the Lo/Alter group found no XMRV and several other MLV’s. Researchers abhor impasses like this and they must eventually be cleared up. That the virus is exceedingly tricky is clear.

It’s possible but hardly likely that both findings are correct. It’s more likely, I would guess, based on the ‘swarm’ thesis, that the problem lies with the WPI findings rather than Dr. Alter’s.

You are intentionally saying that these two studies come into conflict, they do not. Both findings can still be correct.

I think you're uncomfortable with subtleties

What does that even mean? It's a nonsense statement.

I noted very clearly that the Alter paper and Harvey Alter himself stated that his findings validated the general findings of the Science paper. Did you miss this?

Which I have been pointing out to you, but somehow you still think that it's 'hardly likely that both findings are correct'.

They obviously did not confirm the presence of XMRV....If they didn't do that do you suggest that I act as if they did?

What you don't do is pretend that one of the studies has to be wrong. They can still both be right.

 

People will usually participate in constructive debate if done with respect. I see no reason feedback and debate on this article has to become hostile. Everyone wants to get the science right and appreciates it being interpreted correctly, but negative energy ruins it for some of us.

Intellect and knowledge are fine as long they are accompanied by humility and care for one another....otherwise, it's just mental masturbation.

 

If you have so many problems about my paper - calling it 'nonsense' and stating you can't read any further because its so bad and stating I'm missleading people and ' haven't even read the paper (for God's sake) and doing so in such a negative tone as to imply that I'm willfully misleading people - it sounds like you know alot more about this than I.

Hence this

You seem to know it all. I suggest that you start writing - write the paper you want to see and send it out. In fact after all these comments I challenge you to do that. You have very aggressive posts - you seem to think that you are telling like it is - you don't even try to be polite - you seem to think its so simple - you seem to have no recognition of how difficult it is - I challenge you to put something on the matt instead of harping from the sidelines.

I would never do such a ridiculous thing, because it would be misleading people, just like you are doing now. Its great that you write blogs Cort, keep doing it. But when you delve into technical details, you don't check your facts. It's not worth it. We need solid science right now, nothing else. We get the else from the other side.

 

True again, but Gerwyn's rebutal made some very important points.

1) Other studies of gamma retroviruses have also been unable to detect the virus by unstimmulated PCR, in hosts known to be infected.
2) PCR fails very easily if you are looking for the wrong sequence. All it takes is an extremely tiny variation, and variation is extremely common, geographically, person to person, and even within a single host.
3) Neither their PCR nor their serology assays had established diagnostic sensitivity. In fact, they were unable to detect the virus in infected samples that the WPI sent them.

There could be lots of reasons. But given we have learned this week that Lo et al couldn't find them in the CDC samples they tested, the cohort issue seems a leading candidate.

Hopefully more swaping of samples will go on in the future. This would seem a more straightforward issue than most research issues in CFS.

 

Lo still has a few more samples to test form the CDC.

 

I would never do such a ridiculous thing, because it would be misleading people, just like you are doing now. Its great that you write blogs Cort, keep doing it. But when you delve into technical details, you don't check your facts. It's not worth it. We need solid science right now, nothing else. We get the else from the other side.

Cort is trying his best to present the material to those who could not possibly understand the technical paper. I'm sure there are a few errors since even the scientists don't know that much--I found it interesting and thoughtful. Respectful debate would be appropriate if one disagrees. I find that Cort's analysis, while it necessarily contains speculation, contains less (and a lot more respectful thought) than your posts regarding it.

 

Yes, I am absolutely trying to stamp out misinformation. I completely realise the implications that such a thing has right now. I will not take my time in writing comments on this, because to be frank, the more everyone here misunderstands the worse off we will be. I agree my posts have been blunt. But I have not had time to compose them. It's fair enough to say that he is trying his best, but you are not aware of the mistakes that are appearing. You think they are minor, but they are echoing the comments made by people like Myra McClure. We don't have the time to leave things hanging for more patients to read and misunderstand. The WPI are still regarded as producing an outstanding paper, the PNAS study supports that. We don't want them to stop research at this point.

 

I would never do such a ridiculous thing, because it would be misleading people, just like you are doing now. Its great that you write blogs Cort, keep doing it. But when you delve into technical details, you don't check your facts. It's not worth it. We need solid science right now, nothing else. We get the else from the other side.

Believe me V99 I am checking my facts right now. This entire sequence of events, I assure you, the writing the paper, getting comments on it, correcting whatever needs to be corrected will illuminate this topic far more than if the paper had never been written. I promise you that.

It would be great at some point if you comment in less than such final terms such as 'you don't check your checks'; while I do miss a few I do check my facts and I do go to the original articles. Obviously I will make mistakes at times. Suggesting that I provide is what you get 'from the other source' is just so unfair and uncalled. Its clear who you are talking about - I am not them...I am not them - however much you desire to make me out to be.

I would also note that I'm sure I make mistakes on both sides..that if people with certain persuasions were to read them they would, at times, be able to rip the pro-XMRV side to shreds.

 

...3) Neither their PCR nor their serology assays had established diagnostic sensitivity. In fact, they were unable to detect the virus in infected samples that the WPI sent them.

While other points may seem to be narrow technical arguments, this is a fundamental weakness in design and conception of the negative studies. They tried to substitute artificial samples for clinical samples from infected humans to validate their assays. This is a major logical fallacy, forced by the belief that no infected humans exist. Since there are healthy people with infections, this does not require acceptance of anything concerning CFS.

As for the samples WPI sent to the CDC, those were split. We haven't heard officially from the others in that investigation. Stay tuned!

-----

There appear to be many afraid the CDC will get off the hook on this one. I ask you to note who was at the press conference: not Reeves, not Switzer, not Ungar, but Steve Munroe, director of the division of high consequence pathogens. When things blow up four or five levels in a hierarchy, and someone from mahogany row has to take a public drubbing, you can be pretty sure the organization is aware that someone screwed up.

Considering the number of nasty surprises for the CDC group looming in the near future, it will be very interesting to watch the fancy footwork from here on.

 

Can I then ask, with all respect Cort that you do the checking first. Then post.

Suggesting that I provide is what you get 'from the other source' is just so unfair and uncalled for in my opinion.

I'm not sure what you mean by this? Are you talking about references? I do think you should start to provide them, especially when you post about technical details.

I am not Wessely...I am not them - however much you desire to make me out to be them when I make a mistake.

I may be being harsh, but it's not about you. I have no reason to think of you in any particular way.

I would also note that I'm sure I make mistakes on both sides..that if people with certain persuasions were to read them they would, at times, be able to rip the pro-XMRV side to shreds.

The only persuasion I have is about getting good biomedical research for this disease. Nothing more or less. XMRV and other MLV's should be research to the bitter or happy end. It makes no difference. We cannot be cured, if the path is wrong. I'm sure you are not suggesting that you are anti-XMRV.

 

The WPI are still regarded as producing an outstanding paper, the PNAS study supports that. We don't want them to stop research at this point.

Here you go again - these kind of innuendo's that creep into your comments all the time....The WPI is still regarded as producing an outstanding paper. WHO SAID THEY DIDN'T?

Who is saying stop research at this point? You are implying that my paper says stop the research! Where in the world does it say that?

Here I stated Dr. Mikovits views: DId you miss that? Did Dr. McClure, whose comments I have not read, reference that?

Off on the Wrong Foot? - In a video Dr. Mikovits reported that the negative studies were due to researchers using a clone that was not representative of the variability found in the range of MLV’s present in ME/CFS. These clones, to my knowledge, are used in some studies to determine the sensitivity and specificity of the assays. Up until recently researchers were using what they had which were clones that referenced the original prostate cancer XMRV tissues. (See A New Kind of XMRV for more). Dr. Mikovits reported that the DHHS group is incorporating more variability into their search XMRV.

Or this?

the Alter study provided a strong boost to the WPI’s finding of retroviral infection in ME/CFS. Many questions remain to be resolved including what types of MLV’s are present in ME/CFS and in what types of patients and all the researchers agreed that the Alter/Lo study indicated the need for much more extensive research. All looked to the DHHS Blood Working Group to resolve the essential questions about the virus

 

Yes, I am absolutely trying to stamp out misinformation. I completely realise the implications that such a thing has right now. I will not take my time in writing comments on this, because to be frank, the more everyone here misunderstands the worse off we will be. I agree my posts have been blunt. But I have not had time to compose them. It's fair enough to say that he is trying his best, but you are not aware of the mistakes that are appearing. You think they are minor, but they are echoing the comments made by people like Myra McClure. We don't have the time to leave things hanging for more patients to read and misunderstand. The WPI are still regarded as producing an outstanding paper, the PNAS study supports that. We don't want them to stop research at this point.

And you believe that the scientists working on this are going to base their work on this forum? Do you think an experienced scientist with the credentials of Alter and Lo care about what Cort or you think? I don't think you know as much as you pretend so you don't know the "mistakes" either. I'm done with this.

 

Well said anciendaze

 

And you believe that the scientists working on this are going to base their work on this forum? Do you think an experienced scientist with the credentials of Alter and Lo care about what Cort or you think? I don't think you know as much as you pretend so you don't know the "mistakes" either. I'm done with this.

No, but patients base their hopes on forums like this, and the media will use information here, so too will any health organisation that wants to say that the patients are not seeing these problems, so they don't have to do anything. Which mistakes?

 

Yes, but you said the problem was not the methods.

And the problem WAS in large part the methods because if their methods had been good, they would not have found NOTHING.

I invite you to carefully read Gerwyn and company's rebuttal in Retrovirology, to understand, once and for all, why NONE of the negative studies are worth the paper they are written on, because their methods were bad.

I have entered the following search terms in pubmed to find this article:
("Retrovirology"[Journal]) AND Gerwyn
("Retrovirology"[Journal]) AND Gerwyn[Author]
this search gives me no results. Can you give an accurate reference to this paper; date of publication, volume, issue, authors?
Thanks a lot!

 

Here is how I have altered one section of the paper. V99 pointed this out and it made the paper stronger.

The other factor the FDA response cited was differences in sample preparation. Since that's all they stated they stated its difficult to know what they were referring to. The Alter/Lo group found that testing plasma cut their positive rates in half compared to whole blood. The CDC used plasma - but so did the WPI in the original Science paper - and they, of course, had results similar to the Alter/Lo study. The FDA response did not, interestingly, suggest that they believed other problems with methodology played a role. However, the Alter/Lo paper in PNAS discussed primer problems which may be similar to those Dr. Mikovits referred to in her video.

Here is the major correction - its all about learning about the intricacies of nested PCR

BIG CORRECTION! -the groups did use the same primers for the first round of the nested PCR but they used different primers for the second round of the PCR. Because the second round basically zeroes in on the genetic sequences in question, using incorrect second round sequences will nullify whatever positive results were present in the first round. The Alter study used sequences the WPI used for its second round; the other studies used other sequences. More on this later.

 

I have entered the following search terms in pubmed to find this article:
("Retrovirology"[Journal]) AND Gerwyn
("Retrovirology"[Journal]) AND Gerwyn[Author]
this search gives me no results. Can you give an accurate reference to this paper; date of publication, volume, issue, authors?
Thanks a lot!

(Comment was directed at me but I thought I'd speed things up)
You are right it isn't a published response. It doesn't have the status of something that comes up in PubMed.
But it was accepted by the editor as a comment. It can be found along with other comments at: http://www.retrovirology.com/content/7/1/57/comments