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

 

Even though Wessely and White have been cited as examples. And again in any case there's the casual incorrect premise: that Dr Mikovits science is being "discredited because of social skills" although as so often it's not clear who exactly you're saying, or implying, is doing this.

I believe you just called Weesely and White brilliant scientists!


I would like to point out, yet again, for something like the 100th time, that I have not attacked Cort. I have attempted to explain why people are frustrated with him. Given the large number of people who have left this forum because of this frustration, I would think he, and you, would be interested in understanding why. Instead of reacting to what my comment was (an explanation), a bunch of people reacted, for pages and pages, to what it was not (an accusation of sexism) which, as anyone would have done in light of a similar misrepresentation, I contested. I was then accused of dragging it out. It was not me who dragged it out, it was the people who kept misrepresenting what I said and forcing me to repeat myself.

As for the comment about a swarm of men, they all, except one, have male usernames, so unless these are false identities these are men. I did not say they were sexist either this is simply a fact.

If you would like to accuse me of not backing up my comments, fine, I was in fact at the beginning doing my best to keep my responses brief and get back on topic. However you can not accuse me of this without providing any backup of your own. Find me Cort's supportive comments for Mikovits (the WPI does not count). Deny and prove that he did not favour Racy's responses over hers (despite the fact that he was ill-informed, and it was her science they were discussing) when he interviewed the two of them. Explain to me why he chose to feature, and thus to propagate Trine Tsouderos's vitrolic attack on Mikovits through this site, if not to help Trine undermine her: Is he truly not aware of that woman's long, dubious history on autism coverage and anything that even remotely resembles validation of the claim by some parents that their kids got sick after vaccines?

And when you are done with that, find me an article of his where he opens the CAA up for any sort of questioning.

 

the way the words are actually used does not make sense - and sometimes they are used in a scientifically technically inaccurate way - so awol is in a way right and one can say "well we call HIV the HIV virus - or indeed the AIDS virus - when there are lots of strains" - but that is a shorthand, and no such term exists at present - certainly not 'XMRV' which falsely implies xenotropism, and who knows whether we will eventually call it, in common language, the HGRV virus, or something similar. For now though, it's a family of gammaretroviruses.

... I think this whole confusion is artificially created, and this confusion was immediately what I saw when I read the press release, which disappointed me for that reason because these complexities and arguments were immediately foreseeable. It was immediately obvious that this was a confirmation and extension of the WPI's work that had issues of detail that would dress the whole thing up as less important than it is. .. which just happens to downplay the story in the public spotlight in just the way one would predict that information with such massive implications would be handled.

It has been a very trying and disconcerting week for us in some ways.

I think we can all agree what most of us were expecting to see in the Alter/Lo report, namely:

Yes, we also found XMRV (pure and simple), yes, we confirm the WPI's findings they were right all along, yes its a retrovirus pure and simple, yes its in the blood supply, yes, this is what is causing these patients to be so ill and yes this is quite clearly a biomedical illness no doubt about it.

ie Good clean clear statements - roll in the big bucks and anti retrovirals ...

But that is not exactly what we were given - although in a way we were - although it came with a lot of additional brain-addling, MLV, scientific jargon, semantics, malarky.

Mark is right in my view, in that it seems to be what we ordered, but upon closer inspection isn't entirely what we ordered, so we have got what we wanted, but in a confusing way that isn't entirely satisfying, when it could all have been so much more simple.
This has caused predictably, exactly this kind of debate (not just amongst ourselves but the other scientists too) and effectively takes the extreme heat off the big organisations - just for the moment anyway- until they find a way to standardise testing procedures, clean up the blood supply, and work out their long term public policy and how they are going to categorise this illness from now on - no small task.

I think also Mark's 'shorthand' comment is spot on. I've seen numerous reports - medical and media - referring to 'viruses' as shorthand for 'retroviruses'. HIV for eg is also a retrovirus, but it only gets a 'V' for virus, as mentioned above.

Also, yes, we are still only largely dealing with the published information made available to us, pieces of the puzzle. The WPI clearly have a few more pieces in hand that they have not yet discussed/published and these will hopefully bring the desired illumination (or maybe muddy the puddle further!)

Anyway, the expectation is, more of these pieces will hopefully be revealed in just 9 days time - and counting - at the Bethesda XMRV Conference.

Sorry - that would be the "XMRV and MLV related-viruses Conference".

 

Maybe y'all could take this argument off the public forum, e-mail privately back and forth or something? I'm looking for useful, hopefully uplifting information about my illness, and the interpersonal vitriol is stressing me and making me feel worse. Surely the crimes of simplification and misinterpretation committed in the press far outweigh what you are arguing about here?

Please? :worried:

 

I see you're still pumping out the falsehoods thick and fast, so I'll make this the last batch I'll respond to for now.

The attacks in the article to which I refer are when he claimed that if the results conflict, the WPI must be wrong, the refusal to use Mikovits' own words as a credible source, etc.

As always, you exaggerate everything into a falsehood - "refusal to use Mikovits' word as a credible source" - refusal? - I don't even know but knowing your pattern my guess is because there wasn't a Mikovits quote in the article, maybe?

The title is simply a factual error. Alter also called Hep C and HIV "families of viruses". This does not change the fact that we still understand them and refer to them as single viruses when we speak of them.

Pure insanity. "Four viruses?" is now a factual error. Unbelievable.

"When we speak of them", "we still understand" all the members of these families to be a single virus. Even though they aren't. This is your argument? That it is "a factual error" to use the word "viruses" here because most people don't even know or care that HIV is a family of viruses?

The science is simply not there yet to declare these to be anything except variants. While words are not perfect, this is what we have to represent ideas. When we talk about having a virus, we say we have a certain one. Scientists can talk all they want about families of viruses and variants and strains etc. That does not change the fact that the title seems, because of the way we non-scientists use language, to be talking about big differences, like Hep C versus HIV versus H1N1, when really we are talking about minute differences that normally would have no role in popular perceptions of their virus. That is why the title is inaccurate and misleading.

"4 viruses?"

"Inaccurate and misleading?"

For introducing the issues discussed in depth in the article, by posing the question "4 viruses?" about the 4 viruses described in the papers?

Inaccurate, because the "4 viruses" bit doesn't expand to "a family of 4 gammaretroviruses" ?

Misleading, because the non-scientific reader prefers to call this family one virus? Even at a point in time when its latest proposed name has only recently been unofficially leaked?

Ah no, but I get it. It's a subtlety of language, a PR thing - Cort is failing to do the optimal advertising job to the man in the street reading Phoenix Rising to help him decide whether this virus really causes CFS; in the blogosphere his mention of these other 3 viruses is spreading doubt in people's minds...

Yeah, damn that Cort. What has he ever done to help publicise XMRV, or the WPI, or ME/CFS? A paltry contribution compared to your own, I'm sure.

 

Sorry - that would be the "XMRV and MLV related-viruses Conference".

Ha!! So true.

 

Maybe y'all could take this argument off the public forum, e-mail privately back and forth or something? I'm looking for useful, hopefully uplifting information about my illness, and the interpersonal vitriol is stressing me and making me feel worse. Surely the crimes of simplification and misinterpretation committed in the press far outweigh what you are arguing about here?

Please? :worried:

I would be glad to. However as I have been falsely accused of saying things I did not say in public, my refutation of these claims would serve no purpose in private.

 

http://www.pnas.org/content/early/2010/08/16/1007944107.full.pdf+html

May I point to the editorial by Valerie Courgnauda, Jean-Luc Battinia, Marc Sitbona, and Andrew L. Mason

In Fig 1 XMRV is depicted as a hybride.

They write: Indeed, XMRV genomes (1, 2) are actually hybrids between polytropic endogenous MLV sequences for their 5′ half up to approximately the middle of pol and xenotropic MLV for their 3′ half that harbors env. The glycogag leader of XMRV matches 100% of a polytropic endogenous sequence of the 129 1/SvJ laboratory mouse strain (accession no. AAHY01591888.1), a commonly used strain for gene knock-outs in embryonic stem cells. However, the glycogag/gag sequences reported by Lo et al. (6) best match endogenous polytropic sequences of the C57BL/6J laboratory strain of Mus musculus, with 99% nucleotide homology, and the env sequences share 97% homology with similar endogenous polytropic MLV and mink cell focus-forming viruses. Env cross-dressing between different MLV, known as pseudotyping, is a common feature in dually infected hosts (19),allowing MLV to extend their original tropism. Indeed, the multiple origins of these xenotropic sequences, the hybrid nature of the XMRV genome, and the occlusion of the otherwise necessary glycogag ORF underscore the potential complementation and recombinational events that may lead to their transmission into humans.

The current data suggest that a variety of xenotropic and polytropic MLV can be found in North Americans with and without disease. To add to this bewilderment, it is likely that more than one environmental agent impacts on the development of both CFS and prostate cancer.

 

I believe you just called Weesely and White brilliant scientists!

Hah! Well obviously not deliberately.

I would like to point out, yet again, for something like the 100th time, that I have not attacked Cort. I have attempted to explain why people are frustrated with him.

So whereas Cort, when he expresses frustration with Dr Mikovits' PR in an article, is "attacking" her,
you, when you come on to his forum to explain the detail of why people are frustrated by Cort are not "attacking" him.

If you attempted to explain why people are frustrated with Cort, you succeeding only in explaining to me why people are frustrated with you.

I won't be digging around for all these counter-examples to your false premises; in fact the onus remains on you to do the reverse. Come up with legitimate examples of Cort's supposed attacks on the WPI etc - better quality examples than the manipulative use of the words "4 viruses" please - and there would be a case to answer. "You have done so numerous times" I'm sure you'll reply - but sadly not once has one of these examples been convincing of anything other than your own misunderstanding.

 

I would be glad to. However as I have been falsely accused of saying things I did not say in public, my refutation of these claims would serve no purpose in private.

No you haven't, and you provide no evidence.

 

The evidence on both counts is all over this forum, and this thread. But if you cannot be bothered to prove your point, you cannot blame me for not wanting to spend hours digging up all of the proof for mine. I only take this argument as seriously as you do, which is to say, not very seriously at all. Ask yourself if it was me who blew my comments out of proportion and turned them into something else, or if it was the posse of attack characters that seem to pop out all the time here.

The only person whose points against mine were the least bit considered was Dolphin, but at the end with the McCarthyism comment he totally lost me.

I cry for a world that is so black and white that we cannot acknowledge that sexism is part of all of our behaviour, and that it hurts people. I cry for a world where it is not possible to talk about, and therefore hope to address the patterns of behaviour where it is represented.

 

I think that would be an amazing finding - to go from 85% with MLV's to none - that would REALLY say something.

What the heck does this mean?

It means that it makes a big statement about how different the cohorts are. Lo/Alter find 85% (really 86% but let's not quibble) in the Komaroff et al samples but 0% in the CDC samples - suggests the CDC are picking different sorts of "CFS" patients.

 

Additionally, the CDC laboratory provided 82 samples from their published negative study to FDA, who tested the samples blindly. Initial analysis shows that the FDA test results are generally consistent with CDC, with no XMRV-positive results in the CFS samples CDC provided (34 samples were tested, 31 were negative, 3 were indeterminate)

He said:

The primer sets we used for studying CDC samples were the same ones published in our paper. The primer sets should amplify both XMRV and MLV-related virus gene sequences we identified in our PNAS study.

That is so close! Does he actually say there were no MLV's in the population? Can you try to pin him down one more time specifically on the MLV's.

I think that would be an amazing finding - to go from 85% with MLV's to none - that would REALLY say something.

I'm afraid I wrote to him again and said:

Dear Dr. Lo,

Thank you for your reply.

I will not take up any more of your time to ask you more questions.

In case you're interested, I'm attaching a letter I had published in
Psychosomatic Medicine challenging the method the CDC are using to
pick their CFS patients.

Further information on the problems with the defintion have been
published by Prof. Leonard Jason and team since I wrote that.

Also, even before this empiric criteria (that was used to chose the
patients in the Switzer study), their community sampling were picking
out high functioning, not very ill patients e.g.
http://www.hqlo.com/content/1/1/48 (despite the name, these aren't the
same patients used in the Switzer study - it's a long story).

Also, the exclusions they use such as the Romberg test, may actually
exclude some of the "proper" CFS patients particularly the more ill
patients.

so I don't want to write to him again.

I think my initial question was quite straightforward - see response above:

Dear Dr. Lo,

Just a moment of your time please.

I believe that the CDC are not choosing their CFS patients in a good
way but like to have my facts straight.

I posted the comment below on the Switzer et al paper based on my
initial reading of the information on the FDA website.

However one person has pointed out that maybe you only tested for XMRV
and not the MLVs you found in the paper?

I don't expect a long answer as I'm sure you're a busy man.

 

http://www.pnas.org/content/early/2010/08/16/1007944107.full.pdf+html

May I point to the editorial by Valerie Courgnauda, Jean-Luc Battinia, Marc Sitbona, and Andrew L. Mason

In Fig 1 XMRV is depicted as a hybride.

They write: Indeed, XMRV genomes (1, 2) are actually hybrids between polytropic endogenous MLV sequences for their 5′ half up to approximately the middle of pol and xenotropic MLV for their 3′ half that harbors env. The glycogag leader of XMRV matches 100% of a polytropic endogenous sequence of the 129 1/SvJ laboratory mouse strain (accession no. AAHY01591888.1), a commonly used strain for gene knock-outs in embryonic stem cells. However, the glycogag/gag sequences reported by Lo et al. (6) best match endogenous polytropic sequences of the C57BL/6J laboratory strain of Mus musculus, with 99% nucleotide homology, and the env sequences share 97% homology with similar endogenous polytropic MLV and mink cell focus-forming viruses. Env cross-dressing between different MLV, known as pseudotyping, is a common feature in dually infected hosts (19),allowing MLV to extend their original tropism. Indeed, the multiple origins of these xenotropic sequences, the hybrid nature of the XMRV genome, and the occlusion of the otherwise necessary glycogag ORF underscore the potential complementation and recombinational events that may lead to their transmission into humans.

The current data suggest that a variety of xenotropic and polytropic MLV can be found in North Americans with and without disease. To add to this bewilderment, it is likely that more than one environmental agent impacts on the development of both CFS and prostate cancer.

Thank you for this brilliant paper.

 

I've written a post elsewhere on this forum about the possibility that other factors have to bring down our immune systems to enable XMRV (or closely related MLV-related viruses) to infect en replicate in humans. After infection has firmly settled within the host, this virus could be able to cause immune dysfunction on its own, without the initial (environmental?) factors (which could also include infections with other pathogens that temporarily disable the immune system from clearing MLV-related viruses)
http://www.forums.aboutmecfs.org/sh...Dr.-Alter-Out!&p=117077&viewfull=1#post117077

 

CDC's 0% study of XMRV in CFS was designed to fail, the CAA agree also. It's invalid.

It means that it makes a big statement about how different the cohorts are. Lo/Alter find 85% (really 86% but let's not quibble) in the Komaroff et al samples but 0% in the CDC samples - suggests the CDC are picking different sorts of "CFS" patients.

Hi Dolphin. Now about the negative CDC XMRV paper, anyone who has read it and analyzed it knows it's a joke. I can see you haven't read it or you'd know. Their test didn't work. They found zero percent in non CFS as well as CFS. A bizarre finding as other XMRV studies around the world have always found XMRV in healthy controls, irrespective of CFS.

But for today, lets stick to XMRV in CFS..........

If I am trying to detect XMRV in a certain group of sick people (CFS), and someone asks me, can you prove your test is actually capable of detecting XMRV *at all*, and my answer is no. What does this mean? It means my test does not work. The CDC could not detect XMRV *at all*! This makes me a poor scientist who doesn't follow basic protocols. We'll let that slide and really I should not bother to be involved in something as important as a severe chronic disease as it's too dangerous for sufferers if I screw my work up.

In addition what if I also then refuse to use XMRV+ control sample from CFS patients that is proven to be there (sent from WPI to CDC), and still claim I cannot detect XMRV in my CFS patients despite knowing my test doesn't work as the positive spiked XMRV sample sent from the WPI was refused to be used.

Then we're in a whole new ball game now. Then I am a fraud if I don't make this information public. The CDC did not make this information public. Finally, what if I then go and print my 0% finding of XMRV in a journal when millions of people are waiting for medical help, fully aware that I don't know what I'm doing and my work is going to harm CFS patients globally. Then I am corrupt and a liar.

The CDC has done all those things in their CFS sample. But wait, I could be biased here and be talking garbage because I have an agenda. Lets hear from someone who knows way more than me....

The CAA's scientific director, Suzanne Vernon wrote an article trashing the CDC 0% finding of XMRV in CFS. I suggest you read it as otherwise you are falling for the assumption that the CDC assay was capable of detecting XMRV *at all* which they never proved, never mind finding XMRV in CFS patients! Meaning the CDC 0% finding in CFS was irrelevent. Same goes for the other studies that found no XMRV in CFS. All of this science is meaningless if I cannot show first of all I know what I am comparing my findings against. To do this I need a known positive sample of XMRV+ in CFS. The CDC refused the offer of that. No explanation but needing the study to fail, would be the reason.

Check this out........

Blood from a Stone
http://www.cfids.org/xmrv/070110study.asp

''Further, the samples from these three study cohorts were collected using different types of tubes, each of which has a distinct way of being processed. As if this werent bad enough, none of the blood tubes used were of the same type used in the Lombardi study. (They used tubes containing sodium heparin that are intended for use with virus isolation). The blood tubes from the 18 Georgia registry patients are designed to collect whole blood and preserve nucleic acid; it is not clear where the plasma came from for these subjects since plasma cannot be obtained using these blood tube types. So the explanation for not finding XMRV in these samples is simple this was a study designed to not detect XMRV using a hodge-podge sample set.''

If you don't believe the CFIDS Association of America's scientific director this is your choice, I'm not forcing you. Just trying to give you a heads up the CDC's XMRV study of CFS patients was worthless and shouldn't be taken seriously.

 

Originally Posted by Cort

Based on her testing Dr. Mikovits believes two of them are strains and two are actually very close but different viruses.

Cort, where does she say this?

I emailed her asking her to look at the XMRV article I wrote and we talked and she told me that. That is based on their antibody results I believe. If I have this right the antibody results pick up all four strains but differentiate only two. My understanding is that antibodies respond to antigens on proteins. This suggests that two of the strains have synonymous amino acid substitutions; ie while their genome is slightly different they produce the same proteins and they have the same functionaility. The other two are different viruses or variants - I'm not sure the technical term - but my guess, based on all of this, is that they produce slightly different proteins - which different antibodies respond to. I'm just trying to piece this together - I hope its correct.

 

I emailed her asking her to look at the XMRV article I wrote and we talked and she told me that.

ok, well this is good to hear Cort. Still it would be nice to hear it directly from her or someone else involved with these papers at some point. The picture right now is ridiculously blurry!

 

Thanks. It sounds like he said they did. I emailed Dr. Alter about it but he hasn't answered me.

 

Hi Dolphin. Now about the negative CDC XMRV paper, anyone who has read it and analyzed it knows it's a joke. I can see you haven't read it or you'd know.

I think you have missed the point I was making.
It was not just the CDC who couldn't detect XMRV or whatever. Dr. Lo has also tested those samples and said the following:
http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm223232.htm

Additionally, the CDC laboratory provided 82 samples from their published negative study to FDA, who tested the samples blindly. Initial analysis shows that the FDA test results are generally consistent with CDC, with no XMRV-positive results in the CFS samples CDC provided (34 samples were tested, 31 were negative, 3 were indeterminate).

When we just had the data from the Switzer et al. first came out, CDC's testing ability was the leading candidate.

However, we now have information that the CDC *may* be not terrible at testing for XMRV: http://www.fda.gov/AdvisoryCommitte.../BloodProductsAdvisoryCommittee/ucm221857.htm

Combine this with the fact that Alter/Lo team didn't find any positives for XMRV and MLVs in the 34 samples they got from the Switzer et al. study and it now appears that a likely reason is because they didn't use proper CFS patients.

There could be other reasons.

None of my previous posts were praising the Switzer et al. study.
And none of this is saying that there is 0% XMRV/MLVs in "proper" ME/CFS patients.

As I pointed out, if there was a test which should find something in 1% of samples (p=0.01), if one runs it 104 times, there is a 35% chance it will find 0 positives. That doesn't prove the test is flawed. As Mark pointed out, if the CDC's test only had a 50% sensitivity, if XMRV/MLV occured in 2% of cases, there would be a 35% chance it would find 0 cases if 104 samples were run. A bit like if you flip a coin 4 times, there's a 12.5% chance you will get all heads or all tails but if one gets all heads or all tails, one hasn't proven the coin is biased.

 

Thanks. It sounds like he said they did. I emailed Dr. Alter about it but he hasn't answered me.

The more natural thing to assume I think is that they were doing the same testing, not XMRV-specific testing.