Judy Mikovits is playing whack-a-mole in her responses to the legion of anti-XMRV papers published to date:
She bitches about one thing, or another thing, as the papers are published, but she misses the big picture. Its not that there are moles randomly popping up. The problem is youre entire 3 acre lot is full of fucking moles. Its not one thing or another that is ‘the problem’. A negative paper here or there wouldnt be a problem. The problem is the implications of all the negative papers taken together in their entirety.
I really want to take a post to sum up everything that has happened thus far and put it together in a way that every damn one of you can understand (except Mikovits, who is apparently willfully or genetically incapable of understanding this information).
People all over the world cannot ‘find’ XMRV in CFS patients
Using the same, similar, or superior PCR protocols, investigators in the following countries cannot find XMRV in CFS samples or their healthy controls*:
- UK (>x2)
- USA (>x3)
This is not a matter of a lab here or there that cannot independently replicate Lombardi et al. It is a collection of laboratories from all over the US, and all over the world. To ‘believe’ in ‘XMRV–>CFS’, you have to believe that despite the collective experience of every investigator involved in these negative studies, they are incompetent. High school students do PCR in my lab. My undergrads this summer did it on day 2 in the lab. But everyone else in the world is incompetent, and physically unable to do what, apparently only Judy Mikovits and her laboratory can do. That is completely and utterly without precedent.
However, there is always the option that all of these labs are in cahoots in a conspiracy against CFS patients and Judy Mikovits, a hypothesis that Mikovits herself has encouraged since the day the first negative paper was published. This is also a conspiracy encouraged by HIV Deniers, and I have spoken about it frequently. My response to Mikovits and HIV Deniers is the same: 1) Where is the evidence? and 2) On what planet, in what dimension do you reside, where China would happily conspire with the US and UK?
* Minimum, I am sure I missed some
… or anyone else where we should ‘expect’ to find XMRV infection (‘expect’ via logic or assertions from Mikovits herself)
It is not just that other labs around the world cannot find XMRV in CFS patients. Labs all around the world cannot find XMRV in expected populations, or the places Mikovits herself has told labs to look (autism, MS, etc) The following countries cannot find XMRV in HIV+ patients, HCV+ patients, MS patients, Autistic patients, arthritis patients, transplant recipients, random sick children, or random sick adults*:
- France (x3)
- Italy (+2)
- US (+5)
In addition to all the labs that cannot find XMRV in CFS patients, all of the independent labs in these countries must also be a) incompetent, or b) in on the conspiracy.
That is ignoring the shocking finding that XMRV cannot be found in HIV-1 positive individuals not taking (or have ever taken) antiretrovirals– people who, as a whole, are populated with more viruses than HIV-1(-) controls. If XMRV were a real pathogen, even outside the context of CFS or prostate cancer, it should be found in HIV-1 positive individuals.
It is not.
* Minimum, I am sure I missed some
This lack of detection has nothing to do with ‘sequence diversity’ according to WPIs own reported sequences
A frequent excuse for why so many other labs cannot find XMRV via PCR is that there is ‘so much sequence diversity’ in XMRV, that other labs primers designed in-house cannot detect the variants in patients.
So… Judys lab, who just took a shot in the dark in 2009, could ‘find’ these wonderfully diverse XMRVs… while individuals actively setting out to find XMRV with primers and PCR technology that should be better (Real-Time >>>> nested standard PCR) cannot find it?
Furthermore, Levys group used Lombardi et als PCR conditions when looking at Group 1 patients, Lo et als in Group 2. Nothing.
And here is the bigger problem: There is no sequence diversity in the WPIs reported sequences. They are all the same relative to one another, and relative to a laboratory plasmid VP62 that everyone is using as positive controls in the negative studies. This is beyond obvious to even the most casual observers:
There is no excuse for why primers directed towards VP62 would not be able to detect the very sequences the Judy Mikovits herself as uploaded into GenBank. There is no diversity. The uploaded sequences of ‘XMRV from patients’ are VP62.
Here is a very quick-and-dirty phylogenetic tree:
The sequences of viruses found in different patients at different times from different parts of the country (world?) are virtually identical not only to one another, but a XMRV plasmid routinely used in labs.
Just to really drive home how absurd this is, here is an alignment made from the exact same region of XMRV in HIV-1, from only a small subset of HIV-1, Group M, Subtype C viruses found in different patients at different times from South Africa only:
In the WPIs liek, totally diverse sequences, there are only a handful of variations (strong majority of which are in one sequence, 1317, while others dont differ at all)– look for the black dots. Contrast that with the HIV sequences of the same region of gag– at almost every point, there is diversity in sequence. Think its a numbers game? Pick two HIV sequences at random– there is more diversity between those *two* sequences than there is in the entirety of WPIs ‘patient sequences’ and a laboratory clone.
If someone says other labs cannot ‘find’ XMRV via PCR because XMRV is ‘too diverse’, they are lying or stupid beyond repair.
The lab that could ‘replicate’ the WPIs findings didnt find XMRV
A paper was published by Lo et al ‘found’ MLV-like viruses in patients with Chronic Fatigue Syndrome. Not XMRV, MLV-like-thingies. Considering everything Ive written so far in this post, I guess WPI considered this a WIN!
Unfortunately, this paper would not have been published if the authors had simply run a BLAST search on their ‘sequences’ and noticed all they had done was discover mouse ERV contaminants. Or, if they were too busy to BLAST, if they had agreed to their reviewers request to map integration sites, they would have seen that they were mouse ERVs and contaminants (that has already happened with reported XMRV ‘sequences’ in prostate cancer when people take the time to map and pay attention to their results).
But they didnt. Probably going to end up retracting too. Good thing Randy Schekman isnt running a blog:
We’re publishing a science journal here. My strongest feeling is that the data that we publish, we want to be of the highest caliber. We’re not publishing a blog.
lol. Yes, youre publishing a journal that is too good for peer review (us plebeians have to abide) and too good for several XMRV negative papers also of high caliber science (not sensationalist enough for you). Yeah, no, you aint publishing a blog, I definitely agree with that.
WPI/VIPDx cannot detect XMRV in a logical manner using their own employees and their own reagents
Blood Working Group Phase IIb WPI results
Nested RT-PCR for MRV gag followed by sequencing of positive bands to confirm specificity
-RNA extracted directly from plasma
-Total nucleic acid extracted from PBMC and RT step performed
WB testing has not been completed (error discovered)
-For Day 0, Subject 1 and the pedigreed negative control were positive (note on slide: investigation following decoding of results determined that there was a procedural error during PBMC sample extraction involving reuse of needles, employed to lyse cells and shear DNA, on sequential PBMC cell pellets.)
-For Day 2 only, Subjects 1 and 4 were negative as well as the pedigreed negative control
-For Day 2 only, Subjects 2 and 3 were positive
Plasma results: All subjects and the control were negative for both days
After Judy boastfully accused a group in the Netherlands of fraud to the media (SHE could find XMRV in the samples they sent her, yet they still published their negative paper!), the authors published this in a letter:
At the moment you reported your findings on the Nijmegen samples, our paper was under consideration of the BMJ (after being rejected after a 5-week review process by the Lancet). Since our findings were based on solid, sensitive PCRs (described in detail in our paper) that efficiently detected XMRV in a cell line, as well as in positive samples that were provided to us by Dr. Judy Mikovits, we suspected contamination of our samples in your laboratory, the more so as XMRV was detected at a similar frequency in CFS patients (2 out of 7) and healthy controls (1 out of 3). Of note, the samples that you found positive were repeatedly negative upon retesting in our lab. Given the robustness of our paper, we considered it scientifically premature to report this finding before having settled the reason for the discrepancy. To solve the discrepancy, we proposed to exchange cohorts on February 9. Unfortunately, to date we have not received any response.
Sometimes the positives are positive. Sometimes the negatives are negative. Sometimes the positives are negative. Sometimes the negatives are positive. Errors abound.
That is not the kind of consistent, quality results I would expect from a laboratory telling other labs that they are incompetent. That is not the kind of consistent, quality results I would expect from a laboratory telling patients that they are infected with a pathogenic retrovirus.
WIP/VIPDx do not have their own house in order. They are in no position to be accusing other researchers of incompetence.
There is a logical explanation for why WPI/VIPDx ‘finds’ XMRV and others dont: Contamination
It is not just that others cannot find XMRV where WPI/VIPDx tell them it should be.
Sometimes researchers can find XMRV.
And it is the result of contamination via contaminated reagents and/or contaminated cells lines, and contaminating DNA via VP62 or other XMRV plasmids is always a possibility.
Furthermore, the natural history of the contaminating DNA has been determined– It was a chance mouse ERV recombination event in the early-med 1990s, long after many of the diseases ‘associated’ with XMRV existed. XMRV cannot be The Cause of many diseases it has been ‘associated’ with unless it is a time traveling virus.
And this is not a ‘hypothetical’ contaminant. It is real, we know where it is, we know where it came from, and we can find it if we do not take the necessary precautions.
When contamination is appropriately controlled for, ‘positive’ samples are suddenly negative, while positive controls remain unchanged. One might not necessarily fault the authors of Lombardi et al or the prostate cancer papers for not knowing all of this information about contamination before. But they do now. And Mikovits response is not to investigate the issue. It is to deny, deny, deny.
PCR is not the only non-reproducible experiment
Mikovits likes to focus on PCR. Acts like its some mystical magical potion she learned from Snape at Hogwarts, and no one else can do it right. Besides, she found XMRV lots of other ways too!
Minor problem: No one can replicate those findings either.
No one can find specific anti-XMRV antibodies in patients. Generic whore antibodies that will stick to any ol MLV-like-thing that walks by, and is non-neutralizing. Mindless complement. No anti-XMRV antibodies as we would know them.
No one can find XMRV virus, as assayed by direct RT-PCR, culturing for weeks and looking for numerous XMRV proteins or increases in RT activity or increases in XMRV RNA over time.
Granted, the one thing that other labs have not tried is to take an EM of XMRV budding off of infected patients cells. Well, if you want pictures of viruses– I can show you pictures of viruses. Treat cells with epigenetic modifying reagents like, say, 5-aza-2′-deoxycytidine, and youll get all kinds of viruses budding off to take pictures of. But they are ERVs. Not real infectious agents. You can get all kinds of crap coming out. But Mikovits knew that. She had done epigenetics research before.
What we did, after the paper was published, we went back and we looked with all four assays for evidence of XMRV in those PCR negatives. Because now we know that indeed those negative samples may have evidence of infection, and what we found was that 19 of the 33 had antibodies in the plasma. We found transmissible virus in the plasma of 33 of those people, and then we looked at that latent virus because the company I used to work at here in Santa Barbara was called Epigenics, and it was developing methylation-inhibitors for epigenetic silencing, and that’s what happens to viruses. So we used Decitabine, which is a demethylating agent that opens up the genome and turns on the virus and found that there was latent virus in 10 of those people. And when we summed it all up and tabled it out, 99 of the 101 patients in the Science paper had evidence of XMRV infection.
XMRV, ERVs, whatevs. lol.
There are numerous endogenous hurdles to XMRV infection of humans, assuming humans were ever genuinely exposed
Zoonotic events are not childs play. Turning a virus native to bats or fish or reptiles or crickets or tulips into a malicious pathogen infecting humans worldwide is no easy feat. Its not like we can shoot a vial of tobacco mosaic virus into your veins and alovasudden your leaves are wilty and discolored. Viruses are adapted for their hosts, and sometimes a virus just cant takeover a host no matter how hard it (or humans) try. A prime example of this is a problem we have in the HIV-1 research world– we have no small-animal model for HIV/AIDS. Our go-to animal friends, mice, cannot be infected with HIV-1, no matter how much virus we pump in their little veins. One of the many reasons why this happens, is because your (and mice, and every organism) has its own way with dealing with pathogens, and some pathogens just cannot handle it.
We know of at least three ways XMRV cannot handle humans:
- APOBEC – Retrovirus gets in, APOBEC stows away in babby viruses, lethally mutates babby viruses when they try to infect another cell
- Tetherin – Ties babby viruses to the surface of infected cells
- Complement – either antibody independent complement or complement mediated by generic V-D-J recombination neutralizes XMRV
Thats just what weve found so far.
XMRV is non-pathogenic in animal models
Pump a ton of XMRV into a macaque, absolutely nothing happens. No fever, no lethargy, and certainly none of them suddenly became obsessed with Simon Wessely. If you chop up these poor monkeys (and the poor control monkeys) for no goddamn reason and put their guts in a blender, you can kinda sorta find XMRV all over. Which makes sense because you just put a shitload of XMRV in the poor monkeys.
Minor problem: Just because you can infect some cells in a creature (Im granting that premise), that doesnt mean the virus is pathogenic. It also doesnt mean that your pseudo-infected macaque is capable of spreading that virus to anyone else, considering the fact that putting an obscene number of viruses in the monkey IV accomplished jack shit, and that kind of exposure would never, ever, ever happen in the real world. Which brings me to…
There is no epidemiology for XMRV infection
What the authors of the animal studies should have done, is jack-off/finger the monkeys. Cause XMRV proponents have another minor problem: Its not just all the negative papers coming up. Its also the lack of certain kinds of papers. Epidemiology papers. There are none.
Would someone please explain to me how children get ‘infected’ with XMRV? Their mothers vaginal fluids/blood during birth? Breast milk? Heroin? Taking spooge up the pooper? VACCINES???
Fine! Where is the evidence?
If XMRV is like a gazillion other pathogens, it is transmitted during sex, so why did no one jerk off the XMRV infected monkeys? Why did they grind up and slice up their prostates and *hypothesize* XMRV could be spread sexually, when it could have been answered loverly by looking in monkey sperm for XMRV?
Oh wait, people have already done that in humans. Sperm from HIV-1 positive patients. They had HIV-1 in their sperm, but no XMRV.
There is no logic for how a virus contaminating a culture in 1993-1996 escaped the lab, overcame humans innate defenses against XMRV, traveled across the world infecting humans in the 1980s or years earlier. Whats the vector? How is XMRV traveling through time? Can we harness this knowledge for our own purposes without accidentally having our mom fall in love with us and breaking up our teenage parents before the ‘Under the Sea’ dance??? Will we figure out how to go back in time fast enough to save Doc from being shot????
I had to get that out of my system. Ill go back and add links later.