XMRV and chronic fatigue syndrome: “Ours are the wings of hope.”

I finally understand, Whittemore Peterson Institute. I get it. You exist to torment me. (video NSFW if you will get in trouble for throwing up at your desk)

There are a couple things people have been asking me to write about re: WPI & XMRV.

1– The new paper
The lead PI on the “XMRV–>CFS” paper is a woman named Judy Mikovits. She is a nutbar. Everyone is out to get her, everyone is part of conspiracies to discredit her research, she consorts with anti-vaxers and snake-oil peddlers– aka, nutbar. One of her many claims of persecution was that she has allllllllll these papers written but no one will ‘let’ her publish. Well, they have finally published their sequel to the “XMRV–>CFS” paper, and like all non-’Empire Strikes Back’ sequels, it sucks. If this paper is representative of what they have been submitting to journals/meetings, it is painfully obvious why they are not being accepted, and it has nothing to do with the *DRAMA!!!!* (jazzhands) of XMRV. But at least she has to stop bitching about how no one will let her publish. So, theres a win after reading a shit paper:

Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome Reveals a Distinct Inflammatory Signature

They looked at cytokine profiles of people who had CFS and people who didnt have CFS. They were different. Therefore, the differences were due to XMRV, to the point where you can use the phrase “XMRV/CFS”, you know, like “HIV/AIDS”, LOL. *blink*

This paper would be rejected, universally, from normal journals for numerous reasons. The most obvious, is that the conclusions (even the title) grossly overstretch the actual data presented. They cannot make the conclusions (even the title) they made from what is in that paper. Let me make this clear: They could have gotten the data they needed to investigate what they said they investigated in this paper (but didnt). They did not. Your guess is as good as mine as to why they chose not to. What they need are the following patient populations:
1– CFS, XMRV+
2– CFS, XMRV-
3– Healthy, XMRV+
4– Healthy, XMRV-

Theyve got a ‘test’ for XMRV, right? Super awesome test no one else can do but them? So they could have gotten these four populations, easy. Then you get all four groups cytokine profiles, compare em, and you have a ‘Journal of Immunology’ paper or higher.

They did not do that.

They declared they had a cytokine profile associated with ‘XMRV/CFS’ anyway (even though they didnt test their healthy controls for XMRV, LOL. *blink*) and published in ‘in vivo’.

The *data* contained within the paper, if addressed critically and honestly, could have been accepted into a normal journal. Similar data has been accepted before (impact factor 5 vs ‘in vivos’ 1). But they overstretched and made asses of themselves, because they just had to connect it to XMRV, even though they had no reason to (the whole paper could have been written without mentioning XMRV once. they mentioned it ~50 times).

Let me give you an example, from my own work:
I have isolated viruses from a patient at various time points. I have done lots of biochemical assays to measure this, that, the other. What I cannot do is say “I STUDIED THESE 20 VIRUSES AND THEY DID X SO ALL HIV DOES X!” or “I SAW X IN THIS PATIENT SO X IN ALL HIV PATIENTS!”. What I can do is say “While we have a limited sample set, we did observe X, and can explain Observation X with Data A, B, C. While Observation X might not hold true within the entirety of HIV-1, other labs have also made Observation X within their own limited sampling, with different cohorts of patients with different Subtypes of HIV-1. Furthermore, Data A, B, and C could putatively biochemically explain Observation X, something no one has investigated before.” You explain your data, you explain someone elses data, you say something new. This is how the field moves forward.

If I am being generous, I would say that they did not start with the right populations of patients and grossly overstated their data because they are mind blowingly incompetent.

On the other end of the spectrum is the assumption that they know damn well what they are doing, and just wanted to publish ‘something’ to justify selling CFS patients another expensive-say-nothing ‘diagnostic test’. They mentioned in the paper they wanted to use this ‘cytokine test’ to assess whether antiretrovirals are working. So they could sell this test to a CFS patient, 2, 3, 4, more times a year? If I were evil, thats how I would do it.

*blink*

2– The new sequences
I have no idea what the hell they think they are doing. They uploaded 11 sequences. Guess what these ‘totally new clearly unique’ sequences are.

Guess.

Youll never guess.

VP62

SURPRISE!!!!

They isolated VP62 over and over and over and over and over! HURRAY!!!!

…

……

*blink*

You want a conspiracy? These people only exist to torment *me*.

Comments

#1 minimalist
May 17, 2011

Whittemore :Headdesk: Pads. Now with wings.
#2 Jack
May 17, 2011

Meh Cytokines Smitocykines…
This one generated so much ‘feel good’ factor amongst the faithful, I was hoping for more analysis ERV.
BUT… I canne blame you at all. Maybe there was no need to analyse
#3 virologystudent
May 17, 2011

erv regardless of your personal views re xmrv etc, I have to play devils advocate here becuase you claim the “impact factor” of the journal against the current paper, but were very much behind the very swiftly published negative papers, you didnt note then that plosOne has a low impact factor, and plosOne is where a lot of the swift barrage of negative xmrv papers were published rather amazingly fast so soon after the original Science paper, if baffled me how fast they managed to crank out those early studies, and Science of course is a very high impact factor. I currerntly remain open to the possibility of xmrv playing a factor in human disease but I await more papers
#4 ERV
May 17, 2011

Sorry, Jack! There isnt much you can say from the data they presented except “CFS patients immune systems are jacked up”, and you might not even be able to say “CFS patients” with their data. You might only be able to say “these CFS patients”, because of the unique characteristics of the CFS patients they chose for this analysis.

Thats it.

And, though I dont know much about the topic, I believe “CFS patients immune systems are jacked up” was already known.

Not much in that paper. Not even a reference to the paper I linked to on cytokine abnormalities in CFS patients… Crappy paper, man. Sorry!
#5 ERV
May 17, 2011

virologystudent– A normal journal (PLOS One, Journal of Immunology, Retrovirology– all with impact factors around 4) would have accepted that paper if they were honest and critical of their own data. If they designed the experiment well, it could have been higher. They chose to do neither, so they published a substandard article in an extraordinarily low tier journal.

That was their choice. If thats what they sent to ‘Journal of Immunology’ or god help them, ‘Science’, then they deserved to be rejected. It wasnt conspiracy.

I currerntly remain open to the possibility of xmrv playing a factor in human disease…

Then you better learn how to BLAST fast, honey child! Mikovits might be too dumb to do it, but I assure you that your professors and future reviewers will not be.
#6 Jack
May 17, 2011

ERV – T’was British sarcasm on my part I am afraid – you have nought to apologise for
#7 Asparagusofficinalus
May 17, 2011

I sometimes read comments on CFS blogs. Commenters often seem compelled to list their diagnoses and self diagnoses in addition to CFS and provide an exhaustive description of their current symptoms. Like establishing bona fides I guess. Any human being with half of these problems, probably any human who thinks they have half of these problems, would have a jacked up (insert name of whatever system here). Hell, just lying in bed more than normal can change your cytokine profile or your CSF protein profile. No need for an imaginary infection.
#8 Jason Dick
May 17, 2011

The Dunning-Kruger affect strikes again!
#9 LJ
May 18, 2011

Hey ERV, do you mind running through the steps to run BLAST on the WPI sequences vs VP62. Obviously I will not be able to draw any conclusions from my limited understanding but the picture you posted sure does not look like any significant variability.

The VIPdx currently offers tests to patients for measuring their cytokines profiles: http://www.vipdx.com/docs/TEST_RQN_Aug_2010.pdf I do not know what to think about this anymore. It is a conflict of interest but it seems many researchers profit from testing they have created and used in studies. I would have no problem with them making money off their XMRV and other tests if researchers were validating the results and the WPI were making reasonable claims; after all they need money to maintain their research efforts. The sloppiness of this paper, the overreaching conclusions from the data presented, the endless excuses for why others are not finding the same results, and the personal attacks on other researchers is what really bothers me and raises red flags not that the WPI is making money of tests.
#10 justawriter
May 18, 2011

Oh come on, ERV, the nutbar aspect of this whole schlmozzle must have really thrown you off your game. The first author was Vince Lombardi and you couldn’t find it in you to throw out one little football joke?
#11 The Analyst
May 18, 2011

I personally think this is an important paper, but I agree XMRV didn’t need to appear in it.

Retrovirology fast-tracked 5 or so negative XMRV papers on the same day. It smelled like rotten eggs to me, so I waited for more research.

So, the current XMRV research does not look very promising. I agree.

However, if you are still convinced that XMRV and related MLVs are not human infections, I would have to disagree with you there based on recent research and research that is about to surface. But I will agree with you that the XMRV/CFS evidence is by no means strong.

It looks like there may be some good info coming from the 15th International Conference on Human Retroviruses, so I will patiently wait for the information. From what I’ve heard, the researchers seem quite enthusiastic now actually, and this conference doesn’t appear to be loaded with the negativity that was evident at CROI.

I am a patient, and even if there is no connection between XMRV and CFS I hope the disease receives funding and research. I am afraid that if there is no association, the funding and research will dry up like it did in the past. That’s my biggest fear.

But I am not going to rule XMRV in or out until the dust has settled – and no it has not settled yet. We must stick to proper scientific method to rules things out, and the BWG/Lipkin study will be important in this regard.

I understand that Mikovits (and Coffin for that matter) have an ego complex, but they are both accomplished researchers (and yes, I know you’d rather refer to Mikovits with fancy words such as nutbar). It’s sad to me that they couldn’t communicate with eachother in an effective way, and it was Dr. Alter had to moderate the two at the NIH State of the Knowledge Conference like children. I must say that I was impressed by Dr. Alter and how well he adhered to the scientific method while other researchers were more interested in interjecting their opinions all the time.

What I don’t understand is why Mikovits would go so far if there was no connection. You can say follow the money, but that really doesn’t make sense to me either, because if she is completely wrong about everything, she is essentially committing career suicide (and she knows that and has stated that several times).

If I am being generous, I would say that they did not start with the right populations of patients

I am sorry, but I do not know what you mean by this, or why you assume this. They use extremely well selected cohorts. If you wanted to say they were good at one thing and shitty at everything else, I would think you would say they have excellent, well-defined cohorts – but whatever you say.
#12 The Analyst
May 18, 2011

Nevermind, I think I understand what you meant:

What they need are the following patient populations:
1– CFS, XMRV+
2– CFS, XMRV-
3– Healthy, XMRV+
4– Healthy, XMRV-

Sorry about that.
#13 The Analyst
May 18, 2011

Random snippet:

Our lab is recognized for our research on a similar gammaretrovirus isolated from nonhuman primates, gibbon ape leukemia virus (GALV). GALV is the only gammaretrovirus other than XMRV found in primates. In collaboration with Frank Ruscetti at the NCI, Bill Switzer at the CDC and Suzan Winfield and Jessica Siegal-Willcot at the National Zoo, we are investigating the source animal for XMRV, and screening gibbon apes in US zoos for the presence of GALV and XMRV. We have obtained samples from the CDC and the Biological Research Steering Committee that provide us with materials permitting us to determine that many gibbon apes at various zoos have been infected with an XMRV-like virus. We have determined the cell tropism of XMRV using an engineered biologically active XMRV virus with a GFP reporter gene and are identifying cellular factors that restrict XMRV infection of receptor bearing cells. These factors that can restrict XMRV infection will be used as a means of developing XMRV antiviral drugs. In addition to being a horizontally transmitted infectious agent, XMRV is a threat to the human genome. We are in the process of isolating rat germ line cells and exposing these cells to engineered biologically active XMRV virus with a GFP reporter. Sperm obtained from these cells are being assessed. Positive results of sperm expressing GFP indicate that XMRV can be transmitted from infected individuals horizontally (i.e., to offspring as a mendelian trait) as well as vertically through the more traditionally route of viral infection. We used cysteine scanning mutagenesis (SCAM) methods to assess the topology of the GALV receptor and intend to identify extracellular domains of the XMRV receptor using similar methods. These studies will lead to the identification of the XMRV-binding domain. Finally the spread of most retroviruses is mediated not by direct virus infection but by cell-cell transmission from an infected cell to an uninfected cell. We have developed a model system to assess blocks to cell-cell virus transmission using spinning-disc confocal microscopy to visualized individual budding of fluorescently labeled virus particles into adjacent cells in three dimensional space over time.

VIRAL AND CELLULAR FACTORS GOVERNING EFFICIENT GENE DELIVERY

http://projectreporter.nih.gov/project_info_description.cfm?aid=8158079&icde=8151490

You might be more interested in all the technical therapeautic gene delivery stuff I left out.
#14 SAWells
May 18, 2011

I think I see how this works. Ahem. Activating woomeister mode:

Abby is clearly wrong to ask us for a cohort of Healthy XMRV+ individuals because XMRV causes CFS so XMRV+ people aren’t healthy!

Abby is clearly wrong to ask us for a cohort of CFS XMRV- individuals because XMRV causes CFS so CFS people are XMRV+!

Buy our XMRV test kits! Guaranteed to always find XMRV!

Deactivating. Deactivating. Oh god. Brain hurty.
#15 Corkscrew
May 18, 2011

To use BLAST:

1) Follow the link to the sequences. Click “FASTA”. Copy the CCAGCG… data in the results.

2) Go to http://blast.ncbi.nlm.nih.gov and click “Nucleotide BLAST” under the “Basic BLAST” heading. Paste the FASTA data into the “Query Sequence” box. Under “Database” select “Others” and then “Nucleotide Collection” from the dropdown list. In the “Organism” box type “Xenotropic MuLV-related virus VP62″. Hit the BLAST button.

3) Wait.

4) Note that there are matches to the reference sequences that have 99% fidelity.

The point here, if I understand correctly, is that this particular chunk of XMLV (fyi it’s a plasmid) has been pretty conclusively shown to be laboratory contamination.

IANACB (I am not a computational biologist) so anyone who is, feel free to explain what I’m doing wrong.
#16 SAWells
May 18, 2011

Suggest new slogan for ERV. “Yours are the wings of hope: ours are the surface-to-air missiles of facts.”
#17 daedalus2u
May 18, 2011

Analyst, whether this will hurt or help CFS funding depends on how long it goes on and how much dead horse beating there is. Those who fund research really don’t like to see money wasted. They really don’t want to see research money spent on funding the ego trips of PIs unless that ego trip includes an answer. They really don’t want to see the kind of “competition” that wastes resources and holds the field back. There are no shortages of fields where more money will lead to productive research and progress.

If the CFS field can’t self-regulate itself via peer review of publications and peer review of research proposals such that there is the perception of lots of wasted money and pursuit of useless dead ends, then research funding for CFS will dry up.

When good researchers are vilified simply for wanting good and rigorous research, then good researchers are being driven from the field. A field that has good researchers leaving it because of back-biting and harassment is not a field where more funding would be productive.

Not a threat, a prediction.
#18 John
May 18, 2011

There’s a great slide from John Coffin’s presentation at the NIH ME/CFS State of the Knowledge Workshop. It’s pretty illuminating about the Alter/Lo MLV findings which the WPI are claiming provide evidence for ‘sequence diversity’.

(unofficial excerpt from Coffin’s presentation)- “So if we go back to our phylogenetic tree now and we put in these green dots- the samples that the Huber study found, we find that they just sort of plop all over this tree, more or less randomly- there may be a little concentration here but more or less randomly distributed across the tree. Here are all of the XMRV sequences for reference, here by the way. These again are quite similar, not identical but very similar to one another.

If we now look at Mary Kearney, a colleague at NCI Frederick, she did an experiment where she deliberatly took very very small amounts of DNA, she took 1/30th of a cell and distributed 1/30th of a cell over a lot of wells, amplified the DNA that was in there, sequenced those amplification products and so this is what you’d find from low level, deliberate contamination with mouse DNA. You tell me if that looks different, really different in any significant way from this (referring to slide). And this for comparison (slide) is what was in the Lo et al study, again I don’t see any difference between any of these and I just can’t come up with any explanation for this pattern of sequences unless it really is due to that.”

The accompanying slide that Dr. Coffin refers to shows the Huber MLV sequences, the deliberate PCR contamination he talks about above and the Alter/Lo sequences. All of them appear to be basically identical on a phylogenetic tree and give a good graphical depiction of what is being discussed. Actually his whole presentation is a fairly good education on the contamination discussion.

Coffin NIH SoK XMRV/MLV presentation slide- http://i56.tinypic.com/2mqp3le.jpg

http://videocast.nih.gov/Summary.asp?File=16575 (Coffin presentation starts at 154:00)
#19 ERV
May 18, 2011

*laugh*

You know how Creationists know everything? They have a degree in math, and they know biochemistry better than a biochemist? They have a degree in philosophy and they know physics better than physicists? A very special kind of arrogance that only wooers possess?

Here is Sir Gerwyns response to the screen-cap I took from Sequencher:

this makes it a bit easier to see

181 ccacggacac ccggatcagg tcccatatat cgtcacctgg gaggcacttg cctatgaccc

181 acggacaccc ggaccaggtc ccatatatcg tcacctggga ggcacttgcc tatgaccccc

That is not how you do sequence alignments. You dont align 1-10 with 1-10, because sometimes one sequencing run started getting good sequence at -5, and one didnt get good sequence until 20. Figuring out how to align 200 sequences that all have different start points would be maddening. Thats why we have programs like Sequencher. [mockingly]This makes it a bit easier to see:

181 ccacggacac ccggatcagg tcccatatat cgtcacctgg gaggcacttg cctatgaccc

181 acggacaccc ggaccaggtc ccatatatcg tcacctggga ggcacttgcc tatgaccccc

becomes:

183 acggacac ccggatcagg tcccatatat cgtcacctgg gaggcacttg cctatgaccc

181 acggacac ccggaCcagg tcccatatat cgtcacctgg gaggcacttg cctatgaccccc

Tah dah.

And then we get this from a different credulous, arrogant asshole:

Isn’t it interesting that those letter combinations don’t appear in the pretty picture for sequences 1301 and 1302

Yes, they do. I couldnt fit everything into one screen shot, but that particular sequence is ~840-890, with the C I emphasized above clearly visible at 846. Its the only difference between VP62 and the 11 ‘new’ sequences in that region. lol.

I wonder if Mikovits is stupid enough to think the same thing about these sequences as Geryyyyyyyyyn does…
#20 Kemanorel
May 18, 2011

@15

As someone who just this past weekend finished a Master’s Degree in CS with a concentration in Bioinformatics from Johns Hopkins, I can say that you are correct, assuming that you are correct in the statement “this particular chunk of XMLV (fyi it’s a plasmid) has been pretty conclusively shown to be laboratory contamination.”

BTW, the e-value gives you an actual “by chance” sort of measurement. I.e. The chance of two given sequences happening by chance is 1 in million/billions/etc. The fidelity is a good measurement, but the e-value is the actual computation.

I can’t give you the direct numbers because I don’t have the information to do the computations by hand, but I can say that with 300-400bp, that the XMRV sequence is the same as a known laboratory contaminant happened by chance is ridiculously small.

So, long story short, if what it matched to is a known laboratory contaminant, chances are the original sequence is a contaminant as well.
#21 daedalus2u
May 18, 2011

Kemanorel, and that is for a “one-of”. If you have 11 (supposedly independent) sequences that match a known laboratory contaminant, the likelihood that all of them are not contamination is calculated by multiplying together their individual likelihoods (if they are independent, that is what you have to do). It becomes:

(1/(millions*billions*ect))^11

sort of fitting that 11 comes into play, 11 being the little bit extra umph that Spinal Tap paid extra to have put in their custom amplifiers (generic amplifiers only going to 10).
#22 Kemanorel
May 18, 2011

That’s true, daedalus2u, but all they really need is for one of them to not be a contaminant, so we can keep each of them as an independant test. The problem is demonstrating that they aren’t contaminants, which by what has been shown is by far the most likely situation.

Where the principle you demonstrated can really come into play nicely is for evolution when talking about ERVs. To have happened by chance, it is 1 in billions just by their placement in the genome, then you have to add in the chance at the sequences match, and then it’s to a power of (IIRC) 9000 or so.
#23 Kemanorel
May 18, 2011

BTW, daedalus, that’s funny that you brought up the Spinal Tap reference. I wouldn’t have gotten that just a couple weeks ago because I’d never seen it before. Woohoo for Netflix.
#24 The Analyst
May 18, 2011

I currerntly remain open to the possibility of xmrv playing a factor in human disease…

Then you better learn how to BLAST fast, honey child! Mikovits might be too dumb to do it, but I assure you that your professors and future reviewers will not be.

What about prostate cancer? You got proof that’s all contamination too?

Scientist, you are. A blogger one, that is. A skeptic, you are not.

:blink:
#25 Kemanorel
May 18, 2011

What about prostate cancer? You got proof that’s all contamination too?

Scientist, you are. A blogger one, that is. A skeptic, you are not.

:blink:

WTF are you talking about?
#26 ERV
May 18, 2011

I echo Kemanorels ‘lol wat?’. If you want to know what I think about XMRV and prostate cancer, there is a search bar in the upper left powered by Google. Im assuming I dont need to give you instructions on how to Google, but Ill make things easy for you: XMRV = Lab contaminant.
#27 jemal
May 18, 2011

Contamination?

“In collaboration with Frank Ruscetti at the NCI, Bill Switzer at the CDC and Suzan Winfield and Jessica Siegal-Willcot at the National Zoo, we are investigating the source animal for XMRV, and screening gibbon apes in US zoos for the presence of GALV and XMRV. We have obtained samples from the CDC and the Biological Research Steering Committee that provide us with materials permitting us to determine that many gibbon apes at various zoos have been infected with an XMRV-like virus. We have determined the cell tropism of XMRV using an engineered biologically active XMRV virus with a GFP reporter gene and are identifying cellular factors that restrict XMRV infection of receptor bearing cells. These factors that can restrict XMRV infection will be used as a means of developing XMRV antiviral drugs. In addition to being a horizontally transmitted infectious agent, XMRV is a threat to the human genome.”

http://projectreporter.nih.gov/project_info_description.cfm?aid=8158079&icde=8151490
#28 JohnV
May 18, 2011

21 papers off of that grant and 0 are titled “xmrv is bringing upon us the zombie apocalypse”
#29 Dave
May 18, 2011

As someone who just this past weekend finished a Master’s Degree in CS with a concentration in Bioinformatics from Johns Hopkins

Dancing Rodents to you. How is ole Johnny U these days?
#30 The Analyst
May 18, 2011

I strongly disagree that XMRV in all cases is a lab contaminant. Lots of new research is about to be published real soon, and we’ll see where that heads.

I agree that the evidence at the moment is heavily against the association of XMRV/CFS.

However, you know those pretty cytokine/chemokine profiles present in the study? Well, I have contact with people that have tried or are on anti-retrovirals.

While my impression is that the patients do not benefit from these drugs, some strange things happen.

Certain cytokines will go to normal levels. Ok, they may be acting on other viruses, etc. Right. I get it.

However, what I don’t get is that when certain cytokines go from extremely elevated to normal, other cytokines that were previously normal will spike extremely high. However, from my observation, even the patient shows little signs of improvement, but their symptoms may change (perhaps something like an increase in cognitive symptoms and a decrease in physical symptoms).

Can you please explain why this weird shift happens like a seesaw effect? Do you think it could be another retrovirus (not XMRV related) that current antiretrovirals are not highly active against? Thank you.
#31 Kemanorel
May 18, 2011

Dancing Rodents to you. How is ole Johnny U these days?

Thanks. It’s fantastic. There’s some new buildings go up at the satellite campus in Rockville, which looks like it’s quickly growing because of the bioinformatics/biotechnology growth in Rockville and Bethesda.

As far as classes and everything, I had absolutely fantastic teachers who were experts that were actually in the field they were teaching, so they not only knew what they were talking about, but also provided real-world information, in addition to simply being enthusiastic about the subject. In particular, Systems Biology and Biological Databases & Tools were just fantastic for everything I learned in them. (Not to discount any of the classes but those two stand out).

What’s really cool is that to get a concentration, you only need a minimum number of classes, but you can actually take as many as you want. So, out of 11 classes, 7 of them were bioinformatics related, which provided a great opportunity to push my expertise into biology from a computer science background.

And now the bioinformatics background may very well get me into the Master’s in Biotechnology program and then a PhD program, so attending JHU is easily one of the best opportunities I’ve ever had the privilege of getting.
#32 Mary
May 18, 2011

IMHO, I did not think that there was another group that could frustrate me as much as the IDiots do..

@The Analyst and Jermal..I’m sorry you guys are stuck with this shitty condition…but moving the goal posts and cherry picking the data isn’t helping..(and I’m not accusing either of you of personally doing this…but that is what seems to be happening with the xmrv debate..)..

I would be somewhat worried about future funding as my experience with MS research is that whenever there was a “dust up” ..it seemed that funding got harder, esp. from the private sector..However, I don’t have any data to support this…JMO.

and I don’t know why..but I was actually a little embarrassed for Judy bacause in my little section of the lab world, people actually LOL at the methodology in this paper…
#33 Kemanorel
May 18, 2011

I strongly disagree that XMRV in all cases is a lab contaminant.

You realize that your “strong disagreement” is about as convincing as someone who is “strongly convinced” they’re going to win mega-super-awesome-powerball-jackpot thing several weeks in a row, right?

However, what I don’t get is that when certain cytokines go from extremely elevated to normal, other cytokines that were previously normal will spike extremely high.

TL;DR version: Drugs affect way more than just the intended target.

Long (and still simplistic) version: Because this is how gene networks work. There’s lots of proteins that work together in all sorts of ways. Some inhibit gene expression, some promote it, some have direct effects, some increase/decrease the production of proteins that do have direct effects… it is an extremely complex system that had a ridiculously large number of variables, including every single individuals genome.

Whenever you put a drug into someone’s system, you have to deal with ADME-tox. i.e. How your body deals with it.

There’s really no such thing as a drug without side effects because even the best ones will effect more than just the intended target. And you’re wondering why after taking a drug meant to affect the immune system there are effects on cytokines, a part of the immune system?

I would be surprised if there WEREN’T effects on parts of the immune system, as well as several side effects.
#34 The Analyst
May 19, 2011

I blasted all the published sequences, and it all looks like a bunch of VP62.

However, I am wondering what the expected variation would typically be if it was a true human infection.
#35 Jack
May 19, 2011

@John V.

Hmm… I see what you mean: http://www.cfscentral.com/

CDC Press bloke posts sommit ‘funny’ on CDC blog. Some feel whether in irony or in reality (hard to tell these days), that the tale of Resident Evil is the tale of XMRV and its’ associations: ‘Sounds Like ME/CFS to Me’

Some think – hey what was that guy doing posting this shite on the CDC blog? Research ME/CFS you muppet.

I think he was having a laugh – so I laughed too. Ooopppsss…

Any Zombie Apocolypse and I am blaming ERV for not spilling about her secret underground experiments
#36 Smurfette
May 19, 2011

They know damn well what they are doing. They know what they are selling and they are a marketing machine. People don’t become billionaires by accident. Do cranks/quacks become cranks/quacks by accident (unless they really are insane)?

Like any quack, they are selling false hope. Only, to the patients, it is real hope. They don’t know that the people selling it to them know it is false hope. In order to sell false hope, they have to convincingly sell it as real hope and even delude themselves.

They don’t have real hope that a cure or treatment will reach these patients during their lifetime. Thus they sell them false hope to get them through their lifetime.
#37 Jack
May 19, 2011

Smurf, I know where you are coming from, but I can’t help laughing out loud about all this.

I mean don’t these ‘offended’ peeps as well as the ‘OMG they are talking XMRV/CFS aren’t they! OMG! OMG!’ not find it really, really funny?

This origining (I believe) cartoon series had me in bits – then I am British and well… you know…

http://theoatmeal.com/comics/zombie_how
#38 jemal
May 19, 2011

@Mary

Thanks for you kind reply. Most patients are not worried by the impact on the funding, because funding is very little at the moment, almost none. Personally I don’t think the situation can get any worse… but I might be wrong.

XMRV is still very exciting for many patients as it offers the opportunity for funding and maybe even treatment. I personally don’t think XMRV is contamination, but I admit I graduated at Google University. Also I am not making claims that the virus causes disease, just saying I think it will turn out to be a real virus. In june there’s another retrovirology conference and many presentations will be given on XMRV. Let’s see what happens.

And I loved that Zombie cartoon!
#39 Jack
May 19, 2011

Hey Jemal what’s with the ‘most patients’ ‘many patients’ malarky – you speaking on our behalf or what?

I am concerned very much so with the WPI and Mikerknickers and the effect this might have on funding, more so on the effect their dalliances will have on serious folk taking an interest in the future.

XMRV has remained exciting only for those who have been coerced into thinking they carry an infectious human retrovirus (sorry gammaretrovirus) that is responsible for their suffering; and a whole lot more dangerous stuff besides – including the ARVs are cool business.

Some sufferers who are ‘positive’ are misrepresenting the greater population – that’s my suspicion and not a generalisation. And their persistent harrasment is not doing ‘us’ any favours – not any more.

Most and many I am afraid don’t cut it with me. Too many people seem content to give the impression that significant numbers of their fellow sufferers (but only really those they deem worthy of that title) share their fervour and belief in the ‘holy grail’.

Probably an oversight on your part – but it bugs me is all.
#40 jemal
May 19, 2011

Lets be honest Jack, not many honest folk were interested in ME/CFS even before the XMRV controversy. I don’t think we have much to lose and we might even gain a lot.

I guess I should not speak about “many” or “most” as like you I have no idea how many patients have their hopes riding on this XMRV thing. I understand I have given you some offense, so I apologize for that.

We will see how it all turns out. I believe times are changing and in a good way.
#41 Dr Speedy
May 19, 2011

Hi ERV,
CDC will now look for XMRV and MLV in their own lab workers !

[spam removed by ERV]
#42 Jack
May 19, 2011

@Jemal

No offence taken – like I said it is just a bug-bear of mine. You know all these estimates flying around and being quoted in association with ‘epidemics’ and HIV/AIDS… etc. etc. it just gets me sometimes – who is actually representing anyone anymore?
#43 Kiwi
May 19, 2011

You know how Creationists know everything? They have a degree in math, and they know biochemistry better than a biochemist? They have a degree in philosophy and they know physics better than physicists? A very special kind of arrogance that only wooers possess?

To be fair to him I think he only has degrees in everything almost relevant to whatever he talks about, not in everything. He’s only a microbiologist or a psychologist, depending on whether he’s complaining about virologists or psychiatrists at the time. I guess that lets him pretend to any complete laymen that he’ll know better than them, but gives him a chance to pretend it’s just that he doesn’t know all the right terminology any time anyone that actually knows what the hell they’re talking about can’t even work out what he’s trying to say.
#44 In Vitro Infidelium
May 19, 2011

@ Smurfette #36
The WPI dynamic is somewhat more complex than you suggest. There are quacks that cynically exploit the vulnerability of others, and there are quacks who sincerely believe their own quackery, and from that adopt an authority to involve others in their ‘truth’. The problems with the WPI come from its lack of scientific cogency which is in turn the result of its foundation upon an a priori proposition of illness character, and the complete absence of any disinterested scientific presence in its governing process. There can be no doubt that the Whittemore family ‘believe’ in M.E/CFS as a ‘real’ disease, however I’m not sure that the ‘hope’ that WPI is selling has been the source of any delusions for the Whittemores. The WPI is constructed in a way that maximises ‘confirmation bias’ so that any ‘positive’ result is treated without scepticism, and any ‘negative’, including external ctiticism, is treated as a ‘fault’ which needs to be corrected. It is this confirmation bias and the lack of any internal challenge to it that produces a corporate delusionalism within the WPI. In my view the WPI situation raises concerns about the role of private tax advantaged Institutions involved in medical research, that goes far beyond the M.E/CFS or XMRV issues. WPI has been able to garner over $1million in Federal funds to support a research programme that is predicated upon a dubious notion of illnss character – neuroimmune disease, without a single scientifically competent person holding a position on the WPI board.
#45 ERV
May 19, 2011

Kemanorel– My immediate thought, for an example, are the anti-inflammatory properties of antibiotics, a side-effect capitalized on by Chronic Lyme Woo. Especially considering how cozy WPI has gotten with Chronic Lyme Woo, I am sure they are aware of this.

IVI– Where do you put Andrew Wakefield? The similarities see between him and the WPI are legion, and the list is only getting longer.

Dr. Speedy– Are you ever going to contribute to discussions here, or are you going to spam links to your blog and run?
#46 Kemanorel
May 19, 2011

My immediate thought, for an example, are the anti-inflammatory properties of antibiotics, a side-effect capitalized on by Chronic Lyme Woo. Especially considering how cozy WPI has gotten with Chronic Lyme Woo, I am sure they are aware of this.

That sort of cross-over between CFS and Chronic Lyme really wouldn’t surprise me at all.
#47 daedalus2u
May 19, 2011

I think the “anti-inflammatory” effects of antibiotics are (mostly) mediated through the Jarisch-Herxheimer reaction. Cytokines are what cause sickness behaviors including things like the fatigue of sickness.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740752/

Sickness behaviors are triggered and regulated responses to sickness. That triggering and regulation is mediated through pro-inflammatory and anti-inflammatory cytokines. There needs to be a “balance” between the pro- and anti-inflammatory cytokines or you get multiple organ failure or insufficient immune system activation. The major anti-inflammatory compound is nitric oxide, which inhibits NFkB. One of the things that robustly “turns on” the immune response is the inflammation of the respiratory burst. That produces a local lowering of NO, which upregulates NFkB, which then causes the expression of many pro- and anti-inflammatory cytokines (but in differential amounts).

My hypothesis of CFS is that it is the ultimate consequence of what I call the “low NO ratchet”, where immune system stimulation under conditions of low NO (i.e. high stress) potentiates the NFkB response which increases expression of iNOS which increases NO levels during the acute phase of the immune response (as in sepsis). This high NO level then causes feedback inhibition of constitutive expression of nNOS and eNOS, which results in a lower basal NO level following the decay of iNOS (iNOS expression is transient, so the NO it produces is transient too). That reduction in constitutive eNOS and nNOS is part of the normal regulation of physiology, the “auto-tuning”, one of the mechanisms by which automatic gain control is instantiated. The reduced expression of eNOS and nNOS lowers the basal NO level and reduces the threshold for activation of NFkB the next time.

Chronic antibiotic use only kills non-resistant bacteria in the gut, the antigens from those dead bacteria trigger the immune response, trigger the respiratory burst, trigger NFkB activity, trigger iNOS expression and cause a transient increase in NO levels (until the iNOS gets cleared). That cycle activates the “low NO ratchet” and makes CFS (and chronic Lyme) worse in the long term, even as it resolves symptoms temporarily.
#48 anonymouse
May 19, 2011

ERV — please clarify. Our favourite armchair retrovirologist has stated this “The env region is the most hypervariable some of theGAG isolates have a 2% max identity variation from VP62 in a 300 base sequence from an 8 kilobase genome this may not be apparent at first but a PCR based on vp62 using high stringency primers would easily miss these sequences.” So he is saying the wpi sequence results using BLAST that show they are all VP62 etc is not correct. Please explain why he is incorrect. Thanks so much.
#49 ERV
May 19, 2011

You can look at the Sequencher alignment I did and plainly see they are all VP62. No one even needs to BLAST those sequences– I did the alignment of VP62 to the 11 sequences for you. I only posted the majority of the 5′ end, but I can upload the last bit of the 3′ end if you like?

Re: Morons comments– I have no idea what he thinks hes saying. Env has nothing to do with anything, as the sequences the WPI just uploaded are not env.
#50 The Analyst
May 19, 2011

My immediate thought, for an example, are the anti-inflammatory properties of antibiotics, a side-effect capitalized on by Chronic Lyme Woo.

Interesting. An anti-inflammatory that initially exacerbates symptoms to the point where I end up in the ER getting radiated by CT scans.

I couldn’t even tolerate doxycycline, but now that it’s decreased symptoms, I can’t get off of it without symptoms returning.

Mmmm… anti-inflammatory. It’s fun assuming. Please direct me to an anti-inflammatory that actually works without destroying all the “good” bacteria in my gut.

If such a thing existed, I’d be on it. However, I think I tried every single one on the market to the point where I had internal bleeding.
#51 The Analyst
May 19, 2011

And if you don’t think it’s infections, the NO hypothesis from whoever he was makes a lot more logical sense to me than anti-inflammatory effects guess.
#52 In Vitro Infidelium
May 19, 2011

IVI– Where do you put Andrew Wakefield? The similarities see between him and the WPI are legion, and the list is only getting longer.

I’m not sure there is any direct equivalence between Wakefield and the WPI, and importantly science isn’t going to give the “XMRV = new Aids = screen every blood product or we’ll all die” meme the same run that “MMR = autism” got; by mid 2012 XMRV will either be shown to be significant or the Lombardi et al study will be dead. That will not stop the fanatics of course but there’s not going to be the undue validity give to WPI that many clinicians and researchers gave to Wakefield’s work for several years after it was published. That aside there’s a huge difference between WPI and Wakefield, as generators of ‘illness theory’. The WPI was from the outset a highly ‘bureaucratised’ and formalised entity – the science(such as it is) has followed upon the bureaucratisation process, where as in Wakefield’s case the science(albeit fraudulent) is what allowed the production of the Wakefield personality.

In Wakefield’s case as soon as the science started to unravel his only route was to ‘formalise’ himself, firstly into a firebrand preacher and then as head of his own bureaucracy, though ironically that bureaucracy expelled him in the end. The WPI is something more resilient and actually at this stage is probably capable of recasting itself as a respectable science based institution. Even if the Lipkin and BWG studies rip the 2009 Lombardi study to pieces, there’s still a chance that the WPI will put their hands up and say, we misjudged our results, mea culpa (or whatever the plural is), science moves on and so are we. There will probably have to be a one two sacrificial victims but as an entity the WPI could continue, though it would very likely need to ‘re- present’ its nutty neuro-immune disease proposition as something less contentious. The WPI has been very closely linked to Nevada politics and a sustained poor public image of the WPI could impact on any future electoral candidates who had supported the WPI or were connected to the Whittemore family. That political connection would be a strong driver for change should the WPI become an electoral issue; the alternative would be for the WPI to be aggressive in its defence but it’s difficult to see the University of Nevada being happy being at the centre of the kind viciousness that would likely be entail.
#53 The Analyst
May 19, 2011

Hold on a second there ERV!

From the original Science paper.

Both gag and env products obtained from either single-round or nested PCR were sequenced and shown to be 99% identical to XMRV VP62.

And…

The env sequences amplified from LNCaP cells infected by patient PBMCs exhibit less similarity to mouse genomic DNA than to XMRV VP62, further indicating the presence of XMRV infection rather than mouse genomic DNA contamination.

Perhaps you are not as clever as you may think you are.
#54 RRM
May 19, 2011

As it takes one to know one, I believe the moron is actually referring to the new env sequences uploaded by Switzer.

Of course, it still doesn’t make sense, but I am sure the argument reduced the cognitive dissonance caused by those new WPI sequences to tolerable levels.
#55 RRM
May 19, 2011

@The Analyst

You seem to be the “not so clever one” as ERV was not talking about the Lombardi paper but about the new sequences uploaded by WPI, which are only gag sequences.

Short summary as I understand it:

WPI: “your PCR for gag may miss ‘wild’ sequences because we are now finding much more variance tan originally reported in the gag sequences we detect.”

WPI: *upload new gag sequences that all those PCR tets should have detected*

Moron et al.: “env!!11!”

amidoinitrite?
#56 Stephen Wells
May 19, 2011

Daedalus, for the love of mercy, write your thing about NO on a web page somewhere and stop writing it out over and over again on erv. It’s a waste of bandwidth unless and until anybody finds some evidence.
#57 cynical1
May 19, 2011

Hey, I just wanted to send out a message to those people who are buying into the XMRV hype. First, let’s assume that everyone agrees that XMRV is linked to CFS. What scientific data do you have that would even hint that an active lytic replication inhibitor (which is what all those loonies are taking) would do jack shit to effect the disease course of a neuroimmune condition? Autoimmunity is not HIV. Relatively speaking, linking HIV to AIDS was a cake walk compared to understanding how a virus induces an autoimmune reaction. Why does measles only cause subacute sclerosing pan encephalitis in 1/100,000 and takes place years after infection? Hell if I know. Why do literally millions of people harbor HTLV-1 but only a tiny fraction develop TSP/HAM or HTLV-1 associated lymphoma. Why do 50% of people exposed to EBV post-puberty develop mononucleosis and the other 50% are asymptomatic? Why do many mono patients develop autoimmune hepatitis and others do not? Riddle me that. (And BTW, antiherpetics don’t do shit for mono either.)

There are autoimmune diseases whose association with viruses are essentially unequivocal at this point. And they’ve tried lytic inhibitors which knock down the virus but they haven’t had any effect on disease course. Ever heard of latency?

So, even IF XMRV causes CFS, the likelihood that an antiretroviral would affect disease course is remote. You’re hopelessly naive if you think that there’s a drug on the shelf that would magically cure you if everyone would only listen to what the loonies at the WPI are saying. That’s not the way it works!

Get a clue. And stop thinking that because you have every hour of your day to play on the internet that you really know what the hell you’re talking about. Do you want to help patients with CFS? Use your energy trying to raise money/awareness for your disease rather than playing armchair scientist on some blog. Many of us work in a lab everyday doing research on many different types of diseases and any honest one of us would tell you that we basically don’t know what the hell we’re doing. Any one of us who tells you that they have it all figured out is completely and utterly full of shit. But the good ones will admit that and back down when all the data tells them their hypothesis was crap. The bad ones call Jenny McCarthy.

Oh yeah, and don’t think that people like me are just insensitve bastards. My wife has MS and she shits and pisses herself regularly. She can’t walk. She can’t drive. She can’t move from her wheelchair to the toilet without help. She has a hard time talking. She’s broken her arms five times from falls and steroid induced osteoporsis. She can’t feel her hands and persistent tremor keeps her from writing. She has difficulty swallowing and her cognitive function is clearly deteriorated augmented by high dose narcotics to treat neuropathic pain. Oh, and yeah, she’s really tired too. And every last dollar I make goes to paying for her medical care. So piss off if you think I can’t possibly understand how hard it is.

Forgive my language but I’m in a pissy mood today and needed to vent. ERV isn’t the only one whos gets to throw a hissy fit at stupidity.
#58 The Analyst
May 19, 2011

Perhaps there may be a strategic reason they only uploaded those sequences so far, and I’m sure they will discuss it in detail at the upcoming conference.

I do not think Mikovits is a moron, but I do know the evidence is against XMRV/CFS connection. I felt like the WPI shot themselves in the head after I performed a blast on the sequences.

However, I will say it again, I think there is a reason these sequences were uploaded and I will await the upcoming reasoning. They aren’t as huge of a surprise as I initially thought they were.
#59 RRM
May 19, 2011

@The Analyst

C’mon. There’s always some new, yet to be published finding that will ‘make the poltics go away shortly’.

There is one even more damning circumstance that hasn’t been addressed: by their own admission, the WPI will sequence every gag product they detect. These 11 sequences are therefore not some set of random sequences that they have found and uploaded, but are in fact chosen by WPI because these were the “most diverse” sequences out of all those hundereds of gag sequences that they have found thus far. Thus, all those other sequences that they have found are even closer to VP62 than these sequences.

But no, it must be that Mikovits works in mysterious ways. I’m sure I’ve heard that before.
#60 Smurfette
May 19, 2011

IVI – I see the things you are saying. I don’t think my comment excluded the complexity, but I wasn’t going into it, and personally I was looking more at the psychological motivations rather than the bureaucracy. There’s no doubt they believe in CFS as a real disease, but I do have doubt they believe in the science and treatments they are promoting, even though one of the hope-sellers is also a patient. Now that is a strange position to be in. A mother will do anything for her child.
#61 Jack
May 19, 2011

‘A mother will do anything for her child’…

Insert parliamentary representative and constituent and here come the Brits:

http://www.meassociation.org.uk/?p=6129

Straight into welcoming arms of the WPI and Miss Knickerfits.

Invest in ME conference:

http://www.investinme.org/IIME%20Conference%202010/IIME%202010%20International%20ME%20Conference%20Agenda.htm

and then playing Belfast to a full house…

http://www.meassociation.org.uk/?p=6263

Well that’s some promotional whistle-stop!
#62 Smurfette
May 19, 2011

Use your energy trying to raise money/awareness for your disease rather than playing armchair scientist on some blog.

Good point.

By the way, if anyone wants to help raise free money up to $500,000 for CFS research, not at WPI, please use 1 of your 5 votes for the CFIDS Association in Chase Community Giving on FaceBook.

http://bit.ly/kQkWKR

They have recently funded researchers at Cornell, NYU, and other universities, and are currently seeking applications for a new round. $500,000 could add another 5 research grants to the 6 they are planning to fund.
http://cfids.org/research/current-grants.asp
#63 The Analyst
May 20, 2011

Use your energy trying to raise money/awareness for your disease rather than playing armchair scientist on some blog.

I actually do believe it or not. Since I have a background in web development, a team of us have created a rapidly growing social network for young people afflicted with chronic illness of many types.

Site was launched a week or so ago. We have about 150 members so far, and we currently have about +/- 3-10 active members (pretty diverse) at any given time, which really isn’t bad. So the good news is, people are using the site.

Tonight we hosted a special web event and had about 15 or so members show up.

Pretty good for one week, eh?

Oh, and my energy? It’s pretty darn good since starting back on doxy! Days are still unpredictable, so I really can’t work for anyone but myself.

I’ve been up since 9 AM. It is nearly 2:30 AM now, and I still have energy to comment after working on some site content and bugs – but CFS truly isn’t about being fatigued anyway. Many, if not most of us get spurts of energy as it gets very late. Why this is, I don’t know. Mornings are probably the worst part of the day for most.

And you be surprised, we have many with ME/CFS and nobody has mentioned XMRV. While I don’t think it’s game over for XMRV, I think you guys would be proud.

The focus of the site isn’t really illness. It’s more about meeting people you can relate to (or people near you), and having fun even if you can’t get out of the house. It’s a very positive vibe even though we have quite a few members that are bed bound. We also have members with last names you would recognize. And they are very great people.

I’m doing a more boring corporate free lance job as well for an engineering firm.

I may not drive a car, and I may not get out a lot, but I think it’s fair to say I am doing a lot with my time considering my circumstances.
#64 anonymouse
May 20, 2011

ERV — sorry to be a pest but what the heck is crazylegs going on about here?

http://www.mecfsforums.com/index.php/topic,7419.0/topicseen.html
#65 ztuire1
May 20, 2011

Some lay advice for people who don’t feel well even though doctors can’t find anything wrong with you:
1. Follow a regular sleep schedule, don’t give in to “bursts of energy” at 1AM or staying in bed until noon.
2. Talk to people, face to face, in real life.
3. Get a regular job and work hard.
4. Get off the internet and go outside, get some sun.
5. Get some exercise.
They once called this “mental hygiene.” I’m no doctor, but I think it would work better than ARVs, antibiotics, vitamins, transfusions, Internet groups, and research funding to help “CFS” patients like The Analyst get their cytokine profiles and CFS proteomes and maybe their lives back to normal.
#66 Kiwi
May 20, 2011

I’m no doctor, but I think it would work better than ARVs, antibiotics, vitamins, transfusions, Internet groups, and research funding to help “CFS” patients like The Analyst get their cytokine profiles and CFS proteomes and maybe their lives back to normal.

But that’s because you’re a fucking idiot.

Evidence? We don’t need no stinkin’ evidence! It’s got a silly name. That’s all the proof we need that nothing’s there. Well done.
#67 The Analyst
May 21, 2011

I’m looking forward to ERV ripping Dr. Coffin’s paper on the origin of XMRV apart.

Oh that paper is not out yet? Ya, I’m probably just making stuff up.
#68 The Analyst
May 21, 2011

Some lay advice for people who don’t feel well even though doctors can’t find anything wrong with you

My lab tests look like an 80 year old. Guess you are talking to someone else.
#69 Adeeno Viruss
May 21, 2011

I’ve been checkin’ out this Chase Giving thing, since WPI is floating near the top of the crop. I know they have added benefit of marketing their “wings of hope” to autism, FM, MS and nearly every other mystery illness under the sun. That boosts their numbers. But I wonder if the people know about the possible mar on their name/contest if XMRV goes down in flames as predicted? The posted rules exclude charities involved in any kind of scandal. The Levy-Peterson study is still pending and sounds like Coffin has damning evidence on the way. The Chase folks ought to know they’re sitting on a landmine. I submitted the links to the Nature and Chicago Trib articles using the “Concerns?” form from the WPIs Chase page (http://bit.ly/lgSzGG). No financial institution wants to be burdened with scandal when there are 99 other charities to give money to. Later. Deeno.
#70 Adeeno Viruss
May 21, 2011

The more I look into this WPI, the more I see a real Greg Mortensen/Three Cups of Tea brewin’. They con the state govt to put up $75 million for a glistening new building. In the meantime, their medical director-the P in WPI-comes to his senses and realizes he’s better off in private practice on the other side of a mountain range. They get the place open, but have nobody to see patients. That was in August of 2010? Even with all this “success” and pent up demand for service, they can’t find a doc to open the clinic. The pamphlet they posted up showed the handsomely decorated treatment and infusion rooms, but the place looks as hollow as their souls. Just like Greg Mortensen’s schools in Pakistan.

The three doctor gals they have enlisted make quite a team of Harvey’s angels – Dr. Judy, Dr. Donnica and Dr. Jamie. Dr. Judy has had as many titles for her job as she’s had papers with original data. Oh yeh. Just two. Dr. Donnica parachutes in every 6 months to share her wisdom with Dr. Oz or some other crackpot tv doc. And blogger-extraordinaire Dr. Jamie decided herself she’s a contractor with no intention of ever seeing patients. Just tidying up the place for whoever comes next, announcing unpopular reimbursement policies via her blog and suggesting her daughter’s tapping therapy might be a useful adjunct to ARVs while she vacations in Hawaii.

Yep. The place is a real asset to the patients. As it sits there empty.
#71 Smurfette
May 21, 2011

AV – It’s cheap PR and advertising for these charity contest companies. They don’t respond to e-mails. The way their contests are structured kind of shows they don’t really care who gets their funding. But yeah, try anyway. While you’re at it, how about contacting the Vivint Gives Back folks too. They are going to win that one too. You can also vote for the 4 orgs placing under them. I think it’s cool that CFIDS Association just got a vote from TWiV. Guess who he didn’t vote for.
#72 Jack
May 22, 2011

I so love it when ‘Drs’ start bloggin their own perscriptions:

http://treatingxmrv.blogspot.com/

Gives me that warm glow and a need to ‘replicate’. Off now to the chemist and find all those lovely drugs
#73 Kiwi
May 22, 2011

Look who they’ve got backing them in the Chase Giving thing now. We’re all rescued.

They’re comparing WPI to Wakefield in the comments now too.
#74 Smurfette
May 22, 2011

What would it take for Dr. Treating XMRV’s medical license to be revoked or at least investigated?

Maybe the more they compare WPI to Wakefield, the better the case for being disqualified, except it’s not an official association. They’re on track to get nearly $500,000 between Chase and Vivint. Yuck.
#75 In Vitro Infidelium
May 22, 2011

@ AV #70
They con the state govt to put up $75 million for a glistening new building.

The WPI only occupies part of the Center for Molecular Medicine, although the CMM itself was ‘seeded’ by a ‘pledge’ of $5 million from Harvey Whittemore of which only just over $1 million was called for by the University of Nevada. There are no public details of the occupancy relationship between the U of N and the WPI but it’s possible that WPI is paying a market rate. Whether the Nevada politicians think they got a good deal probably depends on Party affiliation rather than concern for the academic good standing of the U of N. The idea that the WPI was ever going to be clinical centre was always hype over reality although Peterson’s involvement made it a theoretical possibility. It seems likely that the everyone at WPI got to believe their own propaganda and actually thought they were going to be curing the (non existent) XMRV disease with patients flocking from across the US to Reno for private consults and treatment.
#76 XMRV Positive UK
May 22, 2011

I think it is very wrong of you to write such un kind words about WPI.

No one knows how the end picture will look on ME CFS XMRV, no one.

The FDA, NIH, CDC, NCI and a blood working group are all looking into this.

Thankyou for taking the time to read my message.

Kate.
#77 XMRV Positive UK
May 22, 2011

I have a twitter page where update the latest news on xmrv.

http://twitter.com/#!/XMRVpositive_UK
#78 John
May 22, 2011

Smurfette, where do you see that TWiV voted for the CAA in the Chase contest? Thanks.
#79 Smurfette
May 22, 2011

John, I happened to check the voting page right after he voted so I saw his profile picture linked on the featured recent voters. Also says so on the Facebook page: http://www.facebook.com/thisweekinvirology
#80 Adeeno Viruss
May 22, 2011

#71/#75 – You’re probably right. I used to work for banks in “loss prevention” (aka fraud) and it all comes down to behavior. Something just ain’t right about this outfit. But like you said, there’s probably little chance anyone will stand in the way of them winnin’ money to grease their slick test-for-nuthin’ operation with a fancy clinic to feed the cash cow lab. At the banks, they were more worried about how many lollipops or dog biscuits the moms cruising the drive up tellers could request then they were the real sources of loss and fraud. Answers just won’t come from any group that likens themself to Wakefield and teams up with Age of Autism and wooers. Erv’s got it right. Later, Deeno.
#81 wise observer
May 24, 2011

You’re gonna love this:

http://www.freepatentsonline.com/y2011/0117056.html

(suggest dose of anti-emetic and activate torment-deflection shield)
#82 Jack
May 24, 2011

Yes Wise I see what you mean. Listing ARVs (and specific ones at that) as ‘treatments’ when causation is merely speculative at best… Words are failing me right now… but will not prevent others of that I am certain:

http://www.mecfsforums.com/index.php/topic,7463.0/topicseen.html
#83 Kemanorel
May 24, 2011

I think it is very wrong of you to write such un kind words about WPI.

No one knows how the end picture will look on ME CFS XMRV, no one.

I think it’s wrong of you to continue to think WPI has any kind of answer dispite all the problems.

But it’s true that we don’t know the end answer, but we do know it’s not XMRV.
#84 John
May 24, 2011

A question for those knowledgable about BLAST-

On a certain forum someone stated the following in regards to a BLAST query for two sequences (one sequence being a recent WPI upload and the other being VP-62) which had 100% identity with 88% query coverage- “Blast selects for matches and discards non matched areas hence for example with an 88% query coverage there is no reference match for 12% of the sequence under investigation but 88% of the remaining sequence is 100% homologous to VP-62″ and followed with “…in 12% there is no match on the database so that gives you the variation”.

So basically this individual is saying that since there is only 88% query coverage, with 100% matching in the sequences compared, that this means that there is a full 12% variation between the sequences under comparison. Are the above statements a correct assessment of this particular situation or of BLAST in general? Thanks a bunch for any help.
#85 Jack
May 25, 2011

Morning ERV,

I have been – for my sins – rereading a little of your blog following the publication of Lomabardi et al in 2009, and came across this article – among many referenced:

http://www.sciencebasedmedicine.org/index.php/neurosciencemental-health/cfs-viral-vs-somatization/

…which was followed up by this one from the same publication in January 2011.

Anyway, it got me to thinking – again (I know dangerous habit for a non-professional like me ), IS replication even possible? I mean enough to be of significance to ‘science’?

Sorry – probably old ground raked over and all… but… (yeah always buts in this jolly old life eh ).
#86 jack
May 25, 2011

Apols the link to the January article is:

http://www.sciencebasedmedicine.org/index.php/basic-science/followup-more-evidence-against-the-xmrv-virus-as-a-cause-of-chronic-fatigue-syndrome/#more-9461
#87 The Analyst
May 25, 2011

It’s clear from reading the article and title from post 85 that the author knew nothing about CFS is probably mislead by the misinformation the CDC perpetuated all these years.

It’s unfortunate that there is STILL huge misunderstanding by many in the medical professional, but I guess we can’t expect everyone to be perfect.

In terms of contamination and XMRV, perhaps his theory will be proven right, but other than that, there is an abundance of factual errors throughout the post.

If you know nothing about CFS, don’t write an article pretending that you do, especially on a blog called Scienced-Based Medicine.
#88 virologystudent
May 26, 2011

erv stated that XMRV=contaminant
could somebody please detail how this could be a contaminant?
http://www.hindawi.com/journals/av/aip/965689/
#89 ERV
May 26, 2011

virologystudent–

I dont know on what planet you normally reside, where someone who displays such a lack of basic knowledge (BLAST) and basic logic can pass as a ‘virologystudent’, but Im going to humor you and assume you are some kid who took a class in micro which had a module of virology, so you fancy yourself a ‘virologystudent’. Not an asshole using the handle ‘virologystudent’ in a transparent attempt to gain some sort of unearned ethos on this topic.

So Ill give you some Pro-Tips so you dont make an ass of youself if you do one day decide to become a graduate student in virology:
1– If, through direct intervention by some deity, another lab determines XMRV is actually a real pathogen, that has *zero* impact on the fact Mikovits and Alters papers are clearly the result of contamination. For example, just because scientists could find what Hwang Woo-suk proclaimed he found, it doesnt mean Hwang Woo-suks work was not fraudulent.

2– That paper is in a journal that does not have an impact factor. It doesnt have one. Which tells me either their work is beyond ‘controversial’ (doubt it, the data this paper is derived from was published in a normal journal), or the paper sucks (could be any number of reasons). It doesnt have an impact factor. I mean for fucks sake.

3– I have stated this before on ERV. Amazing how much you can post here when you cant be bothered to fucking read, ‘student’. Infecting macaques was not magic. This paper is derivative of a previously published paper where they gave macaques a putative lethal challenge of XMRV, and nothing happened. So good for them, they found XMRV somewhere. Considering the difficulty they had getting any kind of infection via IV, that the virus can successfully mediate infection via sexual intercourse is beyond doubtful, and not something they established in that publication. There is *nothing* impressive about that publication. And just to make this 100% clear, here: three animals died for this shit. Our cousins died for a shit publication in a shit journal. I ashamed for my field.

If you are planning on actually becoming a virology student ‘virologystudent’, you need to fucking learn how to think, and to think for yourself. Rely on someone like me to think for you, all your grants will fail, and all your papers will be rejected. Or published in a journal with literally no impact factor.
#90 virologystudent
May 26, 2011

hello ERV, the fact you get so worked up so easily is rather amusing although I do worry about your blood pressure. That can be really bad for you…..

anyway…I find it funny you lecture me about how to think when you yourself cant have a debate with anyone without ranting and trying to band around accusations.

My original point is that YOU said XMRV=contamination, my point is it infected the monkeys in those tissues and the paper actually states why it cant be contamination. Regardless of Lombardi et al and Lo et al, the fact is XMRV is unlikely to be an contaminant, but wierdly you seem obsessed with “impact factors” kinda very old fashioned idea that really. I prefer to stick to the science itself and the quality of the scientists doing the science.

by the way you didnt explain how the monkey study test results could be a result of contamination you instead ranted until you got to point three then misunderstood my question. No one knows whether it is or isnt sexually transmitted and I didnt even ask about that…I repeat…how can this study be a result of contamination? explain to me how their testing methods are just showing a contaminant?….
#91 RRM
May 26, 2011

Virologystudent, you are not an actual virology student, as even I can understand ERV’s argument. The idea that ‘XMRV is a contaminant’ is not disproven or even attacked when you infect monkeys with large doses of XMRV and then detect XMRV as a ‘non-contaminant’.

Think about it. Using the ‘logic’ of your argument, no contaminant could ever be a contaminant. The source of the contaminant would be ‘proof’ that it is was really not a contaminant.

The circularity of your argument boggles the mind. I take it that you also believe that ‘known WPI positives’ should be used in XMRV/CFS validation studies?
#92 anonymouse
May 26, 2011

@Virologystudent

The research you referenced has to do with monkeys that were infected with XMRV that was grown in the lab. So the monkeys were actually infected with XMRV. This has nothing to do with the Mikovits study — there is no proof that anybody was infected with XMRV as in the monkey study.

Further testing of patients with symptoms have been mostly negative for XMRV infection. The macaque study has nothing to do with ME/CFS — you can’t draw any conclusions at all about the role of XMRV in humans from this study as the presence of XMRV in humans has yet to be shown by replicated studies. Even if you find that XMRV infects humans — you then have to study how the infection manifests and how the immune system deals with said infection. Then you have to determine whether or not XMRV actually has any connection with ME/CFS. I am not a scientist, I have a few University level biology courses so maybe I have no clue of what I am saying. The study on the macaques has nothing to do with contamination — if the monkeys were injected with real live cultured XMRV then they were infected with real live XMRV — this is miles away from the Mikovits study.

So at this point in time, whether or not XMRV can be possibly sexually transmitted is a moot point.
If you are a virology student, what kind of piss poor education are you receiving? Are you one of those people diagnosed with ME/CFS who fancy that they know everything about virology because they know how to type “XMRV” into a google search?

I rather enjoy ERV’s rants. BTW, the bastards also sacrificed the control monkeys.
#93 The Analyst
May 26, 2011

BTW, the bastards also sacrificed the control monkeys.

I know this is sad they sacrificed them so soon. They could have at least infected them with arsenic, mercury, Stachybotrys, monkey EBV?, Enteroviruses, Lyme disease, Toxoplasma gondii, and perhaps something like Coccidiodes immitis.

They could have at least tried to get the damn thing to replicate before sacrificing the poor monkeys.

Well, they used immunizations and that got it to replicate in a monkey, but why did they stop there?
#94 ERV
May 26, 2011

The Twisted Piece of Shit– I know this is sad they sacrificed them so soon. They could have at least infected them with arsenic, mercury, Stachybotrys, monkey EBV?, Enteroviruses, Lyme disease, Toxoplasma gondii, and perhaps something like Coccidiodes immitis.

Well, you always have the option of an heroing and donating your otherwise worthless carcass to science, you repulsive psycho bitch.
#95 anonymouse
May 26, 2011

Gerwyn and is band of lunatic fringies are now stating ME/CFS is AIDS as suggested by Saint Mikovits herself.

Unless the diagnostic guidelines have changed, AIDS is caused by HIV. How many people of died of AIDS == well in 2009, approximately 1.8 million died of AIDs. How many people died of CFS/ME? The only casualities of real XMRV infection happen to be some poor murdered macaque monkeys — it wasn’t even the virus that killed them.

What will it take for people to accept the truth.
#96 daedalus2u
May 26, 2011

An actual treatment for CFS that is better than placebo. So far they don’t have one. Hyperventilating about XMRV is only going to slow down the process of finding the real cause and real treatments.
#97 virologystudent
May 26, 2011

hello
people on here seem obsessed with Mikovits! I actually didnt mention Mikovits! Get over it people. I didnt even mention her…..move along now….

in the macaque paper it states “Though some recent reports have suggested XMRV detection using RT-PCR in specimens collected from human patients may be the result of laboratory contamination [10-13], the data generated in our study did not rely on amplification techniques involving PCR.
The techniques used here (IHC and FISH) were not susceptible to contamination errors, our laboratory does not work with rodent tissues and while tissue collections from each animal were done at different times, embedding and slides preparation were processed as a batch”

why would they bother stating this then if they were not worried about contamination in their testing products…isnt that one of the issues debated in relation to the Lombardi and Lo papers?

Therefore it would appear this latest paper is interesting in the fact they are finding it in certain tissues, therefore it cant just all be contamination as Erv stated. I belive she phrased it xmrv=contamination…kinda sweeping statement there really. I have no idea who these other people you mention from forums are and I was talking XRMV in general not in any particular disease. I think people around here need to calm down…I guess Erv understands things better if its littered with childish swear words or speaking like a child in Lolspeak

Also its totally obvious they were deliberately infected and also there wasnt any particular symptom the point is their test found it….and found it in certain places and their testing wasnt related to contaminated testing products.

its a shame discussion here has to be filtered through a verbal shitstorm…and btw I guess the authors of that paper would love you all to write to them and tell them how wrong they are and how more superior you all are at scince…guess they wasted all those years in science school eh
#98 anonymouse
May 26, 2011

@virologystudent

You are missing the point. IF you infect monkeys with XMRV, then you would expect to find XMRV. Contamination really isn’t an issue here. They used a specific cultured strain of XMRV and if they were finding different strains, then it would be an issue. The point is that Mikovits stated she found XMRV in a large percentage of people with CFS and a small number of healthy controls — ERV is stating that contamination occurred in the study performed by Mikovits. You can’t begin to compare the Macaque study with Mikovits — two different animals.

By the way, the OP by ERV is about the WPI — who researches for the WPI — Mikovits — which is why people are discussing Mikovits.

Does ERV have to spell it out to you because you seem to be a moron — XMRV=contamination unless it’s not contamination because there is a real documented infection with XMRV as in the macaque study. You should go join the mecfsforums, they would love your brand of crapitude.
#99 The Analyst
May 27, 2011

An actual treatment for CFS that is better than placebo.

I can name several. Hypermethylating vitamins and B12 (methyl and/or hydroxy) injections and sublinguals being the most powerful (given the patient can tolerate this type of treatment as some cannot). The effects are profound for me.

In terms of medical journals. You aren’t going find one that will satisfy the skeptics, but I can almost guarantee science will follow my (and many other patients) footsteps. I’m ahead of science.

B12 injections help me when pain medicine and other controlled substances can’t. It’s also the best sleep aid. They help me go to sleep and stay asleep. They help me get up in the morning. I got rid of my beta blockers because B12 does the work. Given that B12 is just a stinkin vitamin, I think that is profound.

Not a miracle cure, but they can make me completely non functional to functional in the matter of minutes to hours.
#100 Jack
May 27, 2011

@87 The Analyst

Yeah what you say is of course true and perhaps more relevant to the time, but I was asking about his other ‘prediction’ – not that it is exclusively his or anything:

‘I’m betting that either the work WILL NOT BE REPLICATED, or that some other innocent explanation such as an artifact of lab technique accounting for viral presence will be found. I estimate the odds at 80:20 (4 to 1.)’

My question was – and again this may not be what he meant exactly – but is it possible in science to replicate a study such as the Lombardi one?

I am guessing it will not be – to the complete satisfaction of those who have been told they are ‘positive’ or who believe they might be ‘carriers’ of something that has been dangerously speculated upon by those who should know better – you see that patent application or the ‘sexually transmitted’ rubbish or the lectures that demonstrate how ARVs can erradicate ‘XMRV’ – all implying (but not specifically saying of course), that ‘XMRV’ is the cause of their own and my illness?

But is replication at all possible or even necessary in the world of medical science? These ‘negative’ studies (whatever the heck that means), that are accused by some of being of little consequence because they are not true replications; do they represent the ‘norm’ – the way in which progress is actually made?

I suspect they are – but ‘the much anticipated’ Lipkin and BWG studies are hyped as being replications – yet I wonder if they are likely to be in the true sense of the word and if this is really all that important anyway, to the scientific medical community?