Unfinished Blog-Post: A Post-Mortem for Lombardi et al. 2009 - The Response to Comments

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

Unfinished Blog-Post: A Post-Mortem for Lombardi et al. 2009 - The Addendum

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

Unfinished Blog-Posts: Comparison between the results of Lombardi 2009 and the "Addendum"

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

Unfinished Blog-Post: A Post-Mortem for Lombardi et al. 2009 - Unanswered Questions

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

Unfinished Blog-Post: To Pull A Gallo

A long time ago I started some blog-posts, but never found the time nor energy to finish them. Now I have long lost interest in the matter and will publish them all "as is" – maybe someone will find these raw thoughts helpful.

BTW: It is this post I most regred not finishing – it is mainly missing one table in the middle, listing some parallels between the story of "Fictional Gallo" and those who brought us the XMRV fraud. However the so inclined readers might be able to find parallels by themselves.

Publish shoddy study in PNAS, dupe patients, get access to NIH-funds!

CFS Advisory Committee, October 3-4, 2012:
… Dr. Susan Maier (NIH) reported that several new members were added to the Trans-NIH ME/CFS Working Group, including Dr. Harvey Alter. It’s very good news that Dr. Alter is staying involved in CFS despite the end of XMRV. …
(via CO-CURE maillist)

Oh isn't it simply great news that our beloved Harvey Alter, after pushing the shoddy Lo/Alter/XMRV study into PNAS, gets money from the NIH to continue his fabulous work? Dandy, indeed. Simply splendid. A great scientific addition, indeed.

In that spirit, I nominate Marc Hauser, Scott Reuben and Diederik Stapel as new members for the Trans-NIH ME/CFS Working Group – with such outstanding scientists we will know for sure how the NIH-money will be accounted for!

Another "Oldies, but Goodies" episode

Thanks to RRM for bringing this to the attention of us all.

Patrick Moore
March 6, 2011, 9:05 pm

Occam’s Razor of Virology: When you find a virus that causes disease, the disease should be easier to understand and not harder.

If you have to come up with more explanations for the virus than you would without it, then you are wrong (e.g., XMRV infection is not a HERV and is restricted to a rare form of prostate cancer and CFS–diseases which share no apparent common features. Somehow, these prostate cancer and CFS patients have a common exposure to this virus as a risk factor despite there being no common epidemiologic patterns. Although XMRV is clearly a murine ERV, people with exposure to mice are not at noticeable risk for prostate cancer or CFS).

It makes more sense that XMRV is a murine ERV that jumped to a human prostate cancer cell line decades ago when it was passaged through a nude mouse as a xenograft (a common practice) as elegantly shown by the Hue et al Retrovirology article. It has since been detected as an intermittent PCR contaminant.

My advice, above all else, is to test samples blindly and randomly. If you have PCR contamination, your results will be “biased toward the mean” of no significant relationship. This is the easiest and least costly confirmation possible. When your postulated virus-disease relationship survives this stringent test, then you possibly have something. Then, the science begins. Randomized and blinded testing has saved me, on multiple occasions, from appearing to be a bigger idiot than my natural talents for idiocy allow.

For what it is worth, when the CFS-XMRV paper was first published, we had severe concerns about its methodology and conclusions, which was published in F1000 (subscription required so it is reprinted below). I think it it is still valid:

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome.
Lombardi VC, Ruscetti FW, …, Silverman RH, Mikovits JA
Science 2009 Oct 23 326(5952):585 -9 [abstract on PubMed] [full text]
DOI: 10.1126/science.1179052 PMID: 19815723
Competing interests: None declared

Comments

The discovery of the cause of chronic fatigue syndrome would be an extraordinary finding. Rather than providing extraordinary proof, this manuscript has flaws that leave the reader unsure of knowing precisely what was measured.

To detect the xenotropic murine leukemia-like virus (XMRV), the authors used nested-PCR on non-randomized and non-blinded samples, a recipe for uncontrolled PCR contamination. This technique re-amplifies previously cycled products and is inherently prone to intermittent false positivity that has occurred in our lab and many others (e.g. {1} and {2} on which I am the author). This is a concern in light of post-publication claims that XMRV detection rates among chronic fatigue syndrome (CFS) patients have climbed from 67% to 95%, and XMRV tests are now being sold and advertised on the internet at http://www.redlabsusa.com.

Southern blotting, which would allay this suspicion, was not done. Other results in the study also lack support. Flow cytometry and immunostaining with murine leukemia virus (MLV) antibodies were used to directly detect viral proteins in patient cells (see Figure 2A of the paper). The CFS peripheral blood cells have robust monotonic staining rather than the bimodal peaks that are expected from a mixture of infected and uninfected populations of peripheral blood cells. It is not certain whether this level of viremia for an exogenous retrovirus is medically possible. It may, perhaps, be possible but it seems improbable and is a pattern more consistent with a cross-reactive endogenous retroviral antigen.

To confirm this finding, CFS peripheral blood cells (without negative controls in Figure 2B) were immunoblotted using cross-reactive spleen focus-forming virus (SFFV) and MLV antibodies. XMRV gp70 and p30 proteins are found at higher levels in 2 out of 5 CFS peripheral blood samples (1150 and 1221) than in the positive control — HCD-57 cells directly infected with SFFV — a very remarkable result. Repetition with negative control samples (see Figure 2C of the paper) has the higher molecular weight bands cut from the photograph, thus we cannot interpret potential positivity for p30 gag precursor proteins among the control samples (see CFS samples 1199 and 1220 in Figure 2B).

Finally, the positive control HCD-57 cell lane in Figure 2C lane 8 has a completely different banding pattern from the very same control in Figure 2B lane 7 for the p30 gag protein. The elementary issue of whether the authors are measuring XMRV has to be clarified. The fundamental basis for the CFS case and control samples is also not defined at an appropriate level. The samples (supplementary online material) were “selected for this study from patients fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome (S1) and the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic encephalomyelitis (CFS/ME) and presenting with severe disability”. These are two separate definitions, the latter published in the “Journal of Chronic Fatigue Syndrome” (which is no longer in print). It is unclear how the samples were selected from these two criteria. No references or cut-offs are given for tests used to clinically define the CFS patients as cases so we are unable to interpret the essential basis for the study. In addition, no description is given to indicate that controls were tested in the same manner as CFS patients; in fact, there is no description for negative control samples at all. For a disease whose diagnosis is controversial, a clear statement of where and how the cases and controls were selected is a critical first step.

"XMRV has never replicated outside of the laboratory setting."

XMRV has never replicated outside of the laboratory setting.

The association of XMRV with prostate cancer has now been thoroughly refuted.

So Silvermann does the right thing and tells us that there isn't XMRV in prostate cancer either – so this case is closed as well.

XMRV was from the beginning an dead end – no matter how much misinformation Mikovits and her acolytes have spread, with daily changing sock-puppets. Don't expect an apology from Mikovits, or Gerwyn/V99 and his army of sockpuppets, for chasing the ME/CFS community down an dead end.

The one thing that remains lacking is an truthful explanation by Mikovits and Ruscetti as to their "amazing" lab-results – what has been presented so far in the way of explanations remains inadequate.

Is Ruscetti an clever Schweinehund or what?

Honestly:

There were some positive results returned by the NCI-Cornell-Mikovits team using another method that looked for antibody reactions to these agents. Dr. Francis Ruscetti’s NCI lab tested serum from the coded samples using a flow cytometry-based assay slightly modified from the one he reported in the original 2009 Science paper. The team detected antibodies in human serum but when the code was broken, it revealed equal numbers of CFS cases and healthy controls had these antibodies – nine in each group, or six percent of the subjects. The paper states, “The serology results are more difficult to address given that the assay cannot be validated with plasma from humans with confirmed [???] XMRV or MLV infection. We posit that positive results represent either nonspecific or cross-reactive binding and note that irrespective of explanation, a positive signal does not correlate with case status.”

So he claims to use a "slightly modified" assay.

And results are indistinguishable if he had thrown in randomly some positive results.

Mmmm. Hmmm. Right.

How convenient for our dear Dr. Ruscetti, how convenient indeed.

And I can see our dear Dr. Ruscetti played it much cooler than our dear Dr. Mikovits. He is a much much cooler customer. Much much cooler indeed.

Sir, you played that nice and safely – chapeau.

Small sample sizes for the serology done in his lab. Ambiguity about whether the tests were done blinded. A few "false" positives mixed in. A nice signal, but enough noise (with the small sample size) so he has his bases covered.

If there had been actually an virus involved in ME/CFS, he could have claimed "We found it first!" – even if it had been some completely different virus.

And now he say with a straight face: "My bad – sorry."

A cool customer indeed. Plausible deniability and exit strategy, played like the real pro he is.

One can see that Dr. Francis Ruscetti has learned from our dear Dr. Robert Gallo, a master in his field.

And I guess John Crewdson would fully agree. Science Fictions indeed, now in their (at least) third generation.

Only Mikovits overplayed her hand, quite a bit I'd say. Not everybody is an natural talent like Ruscetti. One can see what Gallo liked in Ruscetti. And why Gallo fired Ruscetti – Ruscetti is simply a much cooler customer than Gallo. Gallo likes to overplay his hand, he needs to make it big – Ruscetti plays it much safer.

No XMRV means no more money for Ruscetti to pocket. And no money for Ruscetti to pocket means no Ruscetti. I say good riddance, with people like Ruscetti helping us to relieve us from urgently needed research money, with people like him we will go under while he stuffs his pockets.

Ruscetti has his bases covered and other than that keeps his lips tight.

Lombardi is tight lipped as well.

But it's Mikovits who has put her head above the parapet – she could very easily play the fall gal. And rightfully so, I would like to add.

As she doesn't want to play the fall gal, I wouldn't be surprised if she goes into blame-mode again, trying to throw somebody under the bus. Either she plays it straight (and we know that is not her style) and tries to shifts blame to Lombardi. Or she will go to full-retard mode and attempt to throw Lipkin under the bus – which wouldn't surprise me. Or she has gained some sense and plays it cool, keeping her lips shut.

We'll see, we'll see.

We have lost three years to this shit.

Three years.

Thankfully there is other research going on. And Ian Lipkin looking for answers is an real plus, an real asset.

I for one am not thankful for what Mikovits, Ruscetti and Lombardi did – their selfish actions could have easily destroyed most possibilites for progress in ME/CFS for at least the next decade.

Let's hope for the best, and prepare for the worst.

The XMRV-fraud is over! No MLVs or other related viruses in humans! Is the work of Mikovits and Ruscetti only sham?

So the "Multicenter study" by Ian Lipkin has announced its results:

No XMRV/pMLV in CFS/ME

And:

[Mikovits and Ruscetti, among others] were wrong about a potential link between chronic fatigue syndrome and these viruses. 

I fully expect the Gerwyn/V99 sockpuppet army to ignore the findings by Ian Lipkin, and flood the comment sections to put their deluded and manipulative spin on things.

It's over. 

The XMRV-fraud is over! No MLVs or other related viruses could be found in humans.

There is no "HGRV", there is no XMRV infection in humans, there is not pMLV in humans, and there is certainly no MLV in humans.

You have been had.

The reported results from Mikovits and Ruscetti were riddled with inconsistencies and impossibilities. Whatever they reported, it was no real life process in humans.

It was not real, it was artificial.

The reported results were lab-artifacts, and furthermore lab-artifacts that can – in their total sum – rationally be only explained as intentional.

Mikovits was pushing a sham.

Everything Mikovits said had only one effect: To muddy the waters.

Not a single word written or uttered by Mikovits can be trusted.

It is sad that people fell for her and her deceptive words – we now have to move on from this mess created by Mikovits and Ruscetti.

Gerwyn/V99 and his sockpuppets are hacks.

I fully expect Gerwyn/V99 and all the other deluded acolytes to continue their self-deceptive promotion of BS instead of science.

Same as Mikovits, not a single word by this army of sockpuppets can trusted.

What will Mikovits say now?

I fully expect her to do some BS and try to throw someone under bus. What ever BS and sham was happening around her, she always blamed other people – I fully expect that pattern to continue.

Was it fraud by Mikovits and Ruscetti?

The legal definition of fraud is as follows:

A false representation of a matter of fact—whether by words or by conduct, by false or misleading allegations, or by concealment of what should have been disclosed—that deceives and is intended to deceive another so that the individual will act upon it to her or his legal injury.

We now know as an matter of fact that "XMRV/(p)MLV" are not involved in ME/CFE – claiming otherwise (as Mikovits did) was an false representation of an matter of fact.

The question whether Mikovits' behavior was fraudulent (or just plain stupid) rests on the question: Did Mikovits intend to deceive us?

It is always hard to look into brains of people – and especially with someone like Mikovits who muddies the water with every word she says.

But if pressed, I would say the actions and words of Judy Mikovits were intentional.

Vampire, meet Stake

The Lipkin study results will be announced soon. I dearly expect that Ian will drive a stake through the vampire-study, that study that has sucked out the blood from the ME/CFS community. And with all matters undead, if Ian does it not right, the Mikovits/Ruscetti-study will continue to haunt us.

And if Lipkin would actually find out something about ME/CFS – unlike the anti-science produced by the Ruscetti and Mikovits hacks – then that would be really dandy.

Lies, damned lies and Dr. Mikovits

In July, she says, she found it—an entry from March 2009 indicating that a culture of the XMRV virus had been placed into the same incubatorwith the rest of the lab’s blood samples.

http://www.thedailybeast.com/articles/2012/07/23/how-research-into-chronic-fatigue-syndrome-turned-into-an-ugly-fight.print.html

Oh, there was XMRV culture in the WPI-lab, while she did the Lombardi 2009 study? You don't say. That would mean that Gerwyn/V99/Flex (or however his sockpuppets call themselves) is a stupid lying cunt.

Mikovits says she was out of town the day this occurred. 

I am sure that's what she said. Its always the others. Always. A shitstorm of incompetence and conspiracy around her, and Saint Judy is the only person, I tell you, the only person in the world who is gifted and innocent. And it's always her who throws others under the bus speaks up about ethical breeches. Always her.

I still wonder how only the patient samples got contaminated, though. Wasn't it supposed to be a blind study? Or was that another lie by Gerwyn/V99/Flex?

And I deeply wonder why fabrication is the only reasonable explanation I can come up for the results Mikovits reported?

Is Dr. Ruscetti a Fraud?

The other thing I asked about recently (besides Dr. Mikovits) is whether the 100% peak shift was the result of falsification by Dr. Ruscetti. A nice anonymous commentator took issue:

And now you want to smear Ruscetti as well. Disgusting!

Oh dear, smearing Ruscetti? I just mused that the 100% peak shift was never the result of a process in the human body – which left for me the only option, that it looks like falsification to me.

The anonymous commentator claimed that "it has all been explained quite properly and clearly". So I guess there must be an "quite proper and clear" explanation for the 100% peak shift out there that does not involve 5AZA.

Dear anonymous commentator: Please set things straight, if you can! Please explain "quite proper and clear" the 100% peak shift, so nobody will ever dare to smear Ruscetti again! Please explain how a supposed infection with XMRV, with supposedly very low numbers of viruses, can lead to 100% of the white blood cells being infected.

I'm waiting.

Is Dr. Lombardi a Fraud?

I recently raised the question as to the possible falsification, fabrication and plagiarism in the works of the doctors Mikovits, Ruscetti and Lombardi.

There is one area that remains elusive for me so far: What role played Dr. Lombardi in this?

He has (supposedly) written the 2009 study ("Lombardi 2009") – but as we have seen already, the content from the WPI (the nested PCR) in this study is minimal.

There are some differences as who at the WPI has initiated the contact to Dr. Silverman, and who has requested the XMRV VP62 plasmid. At least it seems like it was Dr. Lombardi who had the contact to Dr. Silverman (through his prior work on RNASEL) – and not Dr. Mikovits.

But it seems like Dr. Mikovits has received the VP62 plasmid – and not Dr. Lombardi. The Addendum, with its infamous table 4, was written by Dr. Mikovits – and not Dr. Lombardi. The WPI research lab was run at that time by Dr. Mikovits – and not Dr. Lombardi.

From what I have seen, all the defenders of Judy Mikovits think that Silverman and Lombardi are the culprits. Silverman supposedly contaminated his samples, but we have already seen that Silverman was not involved in the sequences submitted by the WPI.

So what was Dr. Lombardi's role in this affair? Silent (and stupid?) bystander? Silent (and knowing) bystander? Active accomplice? Or might he have been the one contaminating the patient samples with VP62 and fooling everyone?

If there is evidence to the role of Lombardi in this affair, please point me to it!

Is Dr. Mikovits a Fraud?

As I mentioned before, table 4 from the "Addendum" looks to me like it was fabricated by Dr. Mikovits. Since Feburary I have been looking for an explanation – without luck so far. Yesterday a nice anonymous commentator has left this comment, trying to clear up some things:

It has all been explained quite properly and clearly. You just haven't been paying attention to anything that doesn't fit your preconceived notions. That twit, erv, made up the big lie and you didn't get it?

There was no falsification, fabrication or plagiarism. At worst there was a small mistake in labeling a slide and Silverman contaminated his own samples.

Have my "preconceived notions" lead my attention astray? Have I been had by "that twit"? Fallen in for "the big lie"? Oh my, better change that then.

So he(?) says that "it has all been explained quite properly and clearly". So please, tell me anonymous, were can I find this "quite proper and clear" explanation? So I can share it with the world – and hopefully change my preconceived notion that Dr. Mikovits is a fraud.

Or alternatively, please tell me were my "preconceived notions" lead my reading of table 4 astray – if you have read table 4 and can comment on it, that is.

And never mind that table 4 is not about slides and not about Silverman – if I were unkind, I would say this is an rather crude attempt to throw sand in my eyes.

(And by the way, the VP62 plasmid contamination happened at WPI, not at Silverman's lab)

Table 4: Mikovits Best Work – And Nobody Has Read It

What I find interesting is, that the best work that Dr. Judy Mikovits has published in her life – Table 4 from the Addendum – is being ignored both by her critics and her defenders. There are several statements from Dr. Mikovits that directly contradict the content of table 4 – one has just to take some time and look.

And the Addendum was written by Dr. Mikovits – not by Dr. Lombardi. And the best part: Dr. Silverman isn't even mentioned in the Addendum.

And mind you, you need to just gather statements and publications by only Dr. Mikovits. That fine reseacher can't make a factual statement without contradicting herself. To me, this looks like a web of lies – your milage may vary. And now my dear anoymice anonymouses, go and email this post to your best friends, and tell them I am smearing Mikovits again. And please don't read table 4 from the Addendum. Never ever do that – because you might end up smearing the fine Dr. Judy Mikovits.

XMRV: Falsification, Fabrication and Plagiarism – and nobody clears it up

What I find interesting in the context of the works of the doctors Mikovits, Lombardi and Ruscetti is that no scientist has tried to properly take their work apart. Not Abbie Smith of erv-blog fame, not Dusty Miller – certainly not Coffin, certainly not Racaniello and most certainly not Dr. Alberts from Science. Lipkin is positively oblivious to what Mikovits has done.

Passing off VP62 plasmid as one's own isolates is plagiarism.

The 100% peak shift is the result of falsification, not a process the human body.

Table 4 from the "addendum" can realistically only be explained by fabrication.

VP62 has been talked about. But are there any consequences? Except a retraction and Mikovits getting sacked? An inquiry that would clear things up? Find a verdict? What about Ruscetti? Or even Lombardi?

The 100% peak shift has been mentioned once in the comments of erv's blog. Once. In the comment section. I am deeply impressed by Abbie Smith's courage in going up against Dr. Ruscetti, while at the same time restraining herself from indulging herself with moronic ME/CFS-patients. It would be a lot easier for her to get into a bitch fight with some deluded patients and ignore the possible fraud of Dr. Ruscetti – thank GOD she is not doing that, and thank god she has her priorities set straight.

Table 4? Nobody cares. Nobody gives a fuck. Nobody has really looked at Lombardi 2009, Mikovits 2010 and everything they published in that context. There are most certainly more other clues to their fraud in there. Table 4 is easy. Really easy. Even I get it.

"The science will sort itself out!". Yet it's the 95% ignorant scientists who make the fraudulent 1% look good. The 4% who care are too chicken to really do anything.

I don't know what I want most: An apology? An explanation? Honest words? The declaration of all acts of falsification and fabrication? Justice and punishment? Quite frankly, punishment is not high on my list, I'd rather have honest words – but if there is not some form of light being shed on this affair by the major actors, I will quite gladly settle on punishment instead. It's a pipe dream. There will be no honest words. No explanation. No shedding of light. And no punishment. Most certainly no justice.

WPI back on track?

The WPI has published its new research program. From its website (highlights are mine):

[Whittemore Peterson Institute] Current Research Program
http://www.wpinstitute.org/research/research_basic.html
Friday March 25th 2012

1. Pathophysiology of chronic fatigue syndrome

This National Institutes of Health (NIH) funded study proposes to identify pathogens associated with chronic fatigue syndrome (CFS). Initially, this study relied upon microarray technology to detect viruses potentially associated with CFS. However, now, under the direction of Dr. Vincent Lombardi, this study will instead utilize unbiased next generation sequencing technology. This state-of-the-art method is not subject to the limitations of viral microarrays. Not only does this technology have the capacity to identify any viruses, it also has the ability to identify any pathogens, associated with CFS. Additionally, it will allow us to perform transcriptome analysis, which has the ability to identify differences in the immune system when compared to those who do not suffer from CFS. Therefore, all of the original specific aims of the grant will be addressed; however, transcriptome analysis may provide additional knowledge that could not be obtained using originally proposed methods. This study also proposes to investigate dysregulation in the interferon response associated with CFS.

[From the PDF]
New Strategies to Decipher the Pathophysiology of Chronic Fatigue Syndrome

The original Aims of the National Institutes of Health (NIH) RO1 grant were to identify both novel viral infections and genetic susceptibility factors in European and American cohorts of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients. The principal investigator (PI), Dr. Vincent Lombardi, will pursue these Aims using more advance technology in order to discover pathogens (known or unknown infectious agents) and their associated immune responses in ME/CFS.

The overall goal of this research project is to define viral and host parameters that correlate with distinct disease phenotypes in European and American cohorts of ME/CFS patients with diagnoses fulfilling the Center for Disease Control (CDC) definition and Canadian Consensus Criteria for ME/CFS. To do this, we will obtain blood samples from ME/CFS patients and healthy control subjects from specific medical practices, with the recent approval from the University of Nevada, Reno Biomedical Institutional Review Board (IRB). We will utilize next generation sequencing by synthesis (SBS) technology to detect novel virus mRNA and evaluate transcriptome differences between ME/CFS subjects and healthy control subjects. Any pathogen infection will be confirmed with a combination of quantitative PCR (QPCR) and culture methods. Additionally, we will evaluate serum chemokine and cytokine profiles using multiplex suspension antibody arrays on a Luminex platform. Finally, we will evaluate HLA and KIR genotypes and investigate possible defects in the type I interferon signaling pathway.

At the conclusion of this study, we anticipate identifying any pathogens uniquely associated with ME/CFS. We also anticipate identifying differences in the lymphocyte transcriptome as well as any differences in HLA, KIR and interferon immune parameters.

Some observations from this:

• They are still looking for "knowns and unknown" "pathogens uniquely associated with ME/CFS".
• They are switching from an microarray-assay to next generation sequencing (next generation "sequencing by synthesis – SBS").
• They are doing a transcriptome analysis
• They are still focusing for cytokine differences

Sure sounds partially promising.

The question is: Will this yield once again results that are not based in reality, unreproducible by anybody else? After all, Dr. Lombardi worked together with Dr. Mikovits on her seminal work, and he is quite firmly rooted in Woo-Land. We'll see.

2. Pathogen and biomarker discovery in Gulf War illness

This Department of Defense (DOD) sponsored project will utilize next generation sequencing technology in order to identify differentially transcribed genes associated with Gulf War illness (GWI). This information will be used to better understand the pathophysiology of GWI. Additionally, this information will be used to identify potential biomarkers for diagnostic purposes and evaluation of treatment progress.

From the PDF:
Pathogen and Biomarker Discovery in Gulf War Illness

The goal of this study is to identify potential biomarkers, including pathogens, associated with Gulf War illness (GWI), which in turn will afford physicians the necessary tools to make more accurate diagnoses. This study will be conducted under the direction of Dr. Vincent Lombardi as the principal investigator (PI).

GWI is a chronic multi-­‐symptom disorder affecting approximately one third of the veterans and civilians who served during the Persian Gulf War (Desert Storm 1990-­‐ 1991). It is a syndrome primarily described by a spectrum of symptoms, innate immune abnormalities and opportunistic infections. A wide range of acute and chronic physical symptoms are associated with GWI including fatigue, musculoskeletal pain, gastrointestinal dysfunction and cognitive problems. Unfortunately, diagnosis of GWI is difficult in that no discrete biomarkers or etiological agents have been identified. A greater understanding of the innate immune system and the associated opportunistic pathogens may provide insight into the pathophysiology of this disease.

In order to explore this issue, we will recruit subjects diagnosed with GWI who served during the Persian Gulf War, whether or not actually deployed to Iraq and surrounding areas, along with healthy control subjects, following approval of the University of Nevada, Reno Institutional Review Board (IRB). We will conduct lymphocyte transcriptome analysis of GWI subjects and compare the results to the same analysis of healthy control subjects. The transcriptome is reflective of the genes that are being actively expressed at any given time; therefore, the lymphocyte transcriptome represents a window into the innate immune system, potentially leading to an understanding of GWI pathogenesis. Transcriptome analysis also has the ability to identify any pathogens present in the immune cells, potentially identifying an etiological trigger.

We look forward to commencing this important study after obtaining IRB approval of the study protocol.


3. Cytokine dysregulation in chronic fatigue syndrome

Cytokine and chemokine dysregulation is one of the most consistently reported observations in individuals with ME/CFS; nevertheless, the mechanism of this dysregulation remains unknown. The acute onset and epidemiological patterns of ME/CFS etiopathology support the involvement of a pathogenic trigger. Consistent with this observation, is the fact that the innate immune system responds to infection by producing proinflammatory cytokines and chemokines. The microbial pattern recognition receptors, Toll-like receptors (TLRs) 3 and 4, are activated by pathogen-derived dsRNA and LPS, respectively, to produce these proinflammatory cytokines. This system is tightly regulated; however, in patients with ME/CFS, it is constitutively active. The focus of this research project is to better understand the mechanism of this dysregulation.


4. Biomarker discovery in neuro-immune and inflammatory diseases

Previously, we identified a cytokine/chemokine signature with high specificity and sensitivity in diagnosing ME/CFS patients. Our project will extend this signature to other inflammatory and neuro-immune diseases, providing physicians with necessary tools to delineate closely related neuro-immune and inflammatory diseases.

"In Vitro Infidelium" on the WPI-RED-VIPdx-Connection and Conflict of Interest

"In Vitro Infidelium" on the WPI-RED-VIPdx-Connection and Conflict of Interest.

This looks like a rats-nest to me.

Digging for Dirt in Nevada

More interesting dirt from WPI/VIPdx/UNEVX:

Further email exchanges confirmed that “…XMRV testing is for both the culture and the serology tests…” and that “…ALL of the tests we run are validated and inspected by the State of Nevada,”

I asked to see the “validation data”, requested details about “the State of Nevada” and reiterated my question about why a “clinically validated” test (or tests) was withdrawn.

VIPdx replied that “The State does not “hold” this information. It is a proprietary record of the laboratory. They inspect but do not keep our records. Our validation records and test protocols are proprietary intellectual property of the laboratory.”

This is interesting too:

During the ensuing correspondence, and contrary to VIPdx’s statement to me, it emerged that “Vincent Lombardi is not the laboratory director, nor has he served in that regulatory capacity” and “they took this off their website today, it is incorrect.”

[The regulatory Laboratory Director (i.e. the person who represents the lab for regulatory purposes) was/is Sanford Barsky who, in February 2012, CFS Chronicles found to be accused of scientific fraud.
http://www.cfschronicles.com/1/post/2012/02/vote-of-no-confidence.html]

While I am pleased to see them digging up dirt on the WPI, it saddens me to at the same time that they ignore the contributions of our fine researcher and heroine at large Dr. Judy Mikovits. Just to reiterate:

January 22, 2009, Santa Barbara XMRV Seminar by Whittemore Peterson Research Director Dr. Judy Mikovits

Dr. Mikovits:
…
So you can be infected with retroviruses and be carriers and not be sick. And that’s one reason to be tested. If there is a genetic susceptibility, which we’re looking to, maybe a reason, an immune defect that was unknown as to why some people get sick and others don’t. You certainly want to know where the virus is, so if you’re a carrier you can protect your family.

Question:
Do you know how many have tested with VIP-Dx, and how many are positive?

Dr. Mikovits:
I don’t work with the company. They only take samples two days a week because it takes three days to do that, so they’ve done hundreds of samples in the last couple of months, and at least half of them are positive. Or 40 percent. And again, their doctors are looking at, the doctors who are well versed with CFS, so they’re immediately sending off. Dr. Cheney, Dr. Klimas, a doctor in Canada, Ellie Stein, maybe even Susan Levine in New York. I’m not sure, because it’s illegal for me to know those data because there’s confidentiality between the patient and the physician. But quite a number and, yes, it’s there.

…

Annette Whittemore: Earlier you said that 40% were positive [by VIP Dx]. So describe the fact that if you’re positive, you’re positive. But if you’re negative, you’re not necessarily so?

Dr. Mikovits: Yes, that’s correct. I answered that question based on the samples that came through there. Everyone who is positive is definitely positive for having the virus. But we don’t know what the people are, what the doctor is sending in, so the people might not have that disease. So it could be a clearly, distinguishing delineating marker – biomarker – or diagnostic at that point for various diseases. So a doctor might see a spectrum and say “I don’t know, maybe I’d better check.” Because the earlier you catch it, just like cancer. Early detection. Make sure the reservoir is (inaudible), make sure you don’t have that virus multiplying, and you can live a normal life. Don’t let it get (inaudible). You know the commercial out right now is “HIV doesn’t have to equal AIDS”; well XMRV doesn’t have to equal disease. If we keep it down, we keep the immune system strong.

Question: So what you’re saying is you may test negative but not be negative?

Dr. Mikovits: That’s correct. If you do it by the PCR. If you do it by VIP-Dx, at least right now, it’s running along the lines of (inaudible). We’ve got the antibody, and we’ve got three of the four tests. We’ll license it to anyone. We’re a non-profit institute, so everybody pays the same royalty, so any diagnostic company could do the gold standard. But right now, if you test negative, you’re not necessarily negative, even at VIP-Dx. Because we want to go do that serology test. Maybe we can’t find evidence of the virus. But you’ve been exposed, which would be a good thing because your levels are theoretically low, and you’ve just now made the antibodies, so you can prevent disease, as we did with Magic Johnson. But we don’t know anything about the immune response to the virus.

And this email from Dr. Judy Mikovits:

Email from Dr. Judy Mikovits on XMRV and ME
Posted by Birgitte on 14/03/2010
http://www.me-nyheter.info/?p=1191
(copy here: http://esme-eu.com/news/email-fra-dr-judy-mikovits-ang-xmrv-og-me-article304-7.html )

Dr. Judy Mikovits writes:
Regarding the ramifications of being XMRV negative. First of all the current diagnostic testing will define with essentially 100% accuracy XMRV infected patients. The negatives are more difficult as there are additional tests that can only be done in the research lab at this time and not in a clinical setting such as VIPDx. The most important test is to check your blood for an antibody to the virus. If you are positive in the serology test and have an antibody to the virus, you have evidence of infection but at the time your blood was drawn the amount of virus in your blood was below the limit that could be detected by the most sensitive test currently available clinically, which is the the one done at VIPDx. that means while you tested XMRV negative..it could be a false negative. …
…
But by definition if you have ME you must have XMRV. [????]
…
We will test everyone that tested negative to see if we can find antibodies in your blood and look for that variant that we describe..that is evidence of XMRV infection. …