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Mikovits radio interview Oct 7: XMRV, WPI, accusation of theft etc

Bob

Senior Member
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England (south coast)
So.... it is worth me listening to this 2 hour interview or not? Only there seems to have been very little reaction to what she had to say. Thanks.

It's really difficult to listen to, because of the sound quality and the density of the content, and the length of the broadcast.
So far, I've only listened to the first half hour, or so, twice. (I fell asleep to the hypnotic tones of Judy Mikovits last night!)
It's very interesting.

I'll post some of my initial impressions in my next post, but they are a rather muddled, and I need to relisten to make sure I haven't made mistakes.
 

Bob

Senior Member
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England (south coast)
My notes on the radio interview, in case helpful for anyone.

The future possibilities and hypotheses that she explores were the most interesting to me.

Mikovits once refers to XMRV as "XMRV Silverman", and it seems she considers the Lipkin study only to have totally ruled out that specific strain of XMRV as having anything to do with CFS, humans or animals.

She is adamant that the Lipkin study is solid, and "definitive", and that her original study was contaminated with the Silverman clone (At least, I think, she means that it was Silverman's clone.)
She explores some of the previous unknowns re XMRV that led to contamination, such as it being air-borne. (I can't remember all details.)

She discusses HERVs, which is of particular interest to me.
She discussed HERVs with reference to immune compromised patients.
This is interesting to me, because it could potentially be an exact fit with the Rituximab research.
(One theory behind Rituximab is that Herpes viruses (e.g. EBV) infect B-cells, which cause HERVs to be reactivated in the B cells.)
Judy raises HERVs as a hypothesis, in relation to both the serology results, and the PCR gag-sequences. (She says she only detected gag sequences, so this suggests the possibility of HERVs) [My comment - If I remember correctly - HERVs don't have ENV (envelope) sequences, as they are not full viruses.]
She says that humans do have HERVs similar to gamma retroviruses (which I think I didn't know, so that's interesting), so maybe these are what she was detecting.

She is of opinion that the presence of XMRV contamination has not made her research worthless, it just changes the interpretation.
And it seems that she is still interested in exploring her previous research, with the new knowledge about the nature of, and behaviour of, retroviruses/XMRV.
She seems to want to continue exploring her previous results, possibly doing some research with Lipkin, Ruscetti and others.
(I can't remember everything she referred to, with respect to how her previous results could potentially be interpreted, or what hypotheses they could lead to, but it was interesting.)

She mentioned anti-retrovirals, and explains how/why they could hypothetically be beneficial to people with ME. I can't remember details, except that she said that AZT helps people with HTLV, but it does not reduce their viral load - it has some other action that could potentially and hypothetically help people with ME.

I think she said that she has tested 'tics' for XMRV. They were negative. She says that no human or animal is infected with XMRV, as far anyone knows. She's even tested herself for XMRV, and was negative, luckily, she says, considering her handling of it, and its air-borne nature.

She seems keen on using her past results to investigate for biomarkers, whether the previous results end up being related to HERVs or whatever.

She is still open to the possibility of retroviruses, but she doesn't seem convinced to me.
I think she's open to the possibility that it could have been the case that she did detect legitimate human retroviral gag-sequences, but then isolated/sequenced only the contamination. She didn't offer satisfactory evidence for this, as far as I am aware, or if she did, I didn't grasp it.

She discussed the methodology of the Lipkin study, and said that all the individual sample results have been published in the supplementary material. She discussed why she/they only decided that a sample was positive only if more than one sample was positive, when unblinded. She said that a positive result had to be replicated in more than one sample from the same aliquot, otherwise it is meaningless, and only a result of contamination. (An 'aliquot' is a number of samples extracted from a single patient blood draw.) It wasn't clear how she came to this conclusion re methodology.

The positive serology results for patients have not been made worthless, by the Lipkin study, she says, because they may relate to HERVs, or other proteins or pathogens.

It seems that... what's the word... coincidence, luck, or serendipity... could have been at play if there are no retroviruses but that the serology, results, or PCR gag sequences, end up being used as a biomarker. I can't remember how it all began now... What made Judy look at XMRV for CFS patients in the first place?

Was it related to an RNAse-L gene? Is RNAse-L related to HERVs in any way, or to autoimmunity, or to anti-retrovirals?

She and Ruscetti are investigating their assay that they used for the serology, and trying to define, exactly, what protein the serology results are related to.

I think she's also very interested in revisiting her immunological (cytokine) research.

I need to re-listen to make sure I've understood it correctly, and listen to the rest of it.
 

beaker

ME/cfs 1986
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773
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USA
is suggests the possibility of HERVs) [My comment - If I remember correctly - HERVs don't have ENV (envelope) sequences, as they are not full viruses.]



I can't remember how it all began now... What made Judy look at XMRV for CFS patients in the first place?

.


I believe she first was interested in Silverman's work bc she was looking at the patients with the high incident of lymphoma in incline village.

What I didn't get out of the talk( yet ? -- I fell asleep trying to get through it a couple times too )
Is where is she working? She hinted at working w/ lipkin. Has she been given lab space there beyond the xmrv study?
anybody know what her employment status is ?
 

snowathlete

Senior Member
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UK
Thank you for posting those summaries.
Good to see that she is still working and with Lipkin. Really this contamination thing could have ruined her and so I'm pleased to hear that she is continuing. I think she needs to work with others and publish with them in order to rebuild her reputation. Looks like lipkin and others are supporting her and that's nice to see. Hopefully she can still make a big finding in the future - she clearly has ideas. I like a lot of the avenues that she is talking about looking into.
 
Messages
95
I got to about 80 minutes, but I think the summary is better for me :D

Have to say, the way Mikovits is often portrayed, and the way she sounds in conversation - completely at odds. Seems pretty reasonable to me. XMRV stirred every nest I think, it stirred patients behind something that might show the world what we already know from the experience of our illness, but I think we also saw a genuine fear from some that ME was about to burn through the rug it had erstwhile been swept under.
 

currer

Senior Member
Messages
1,409
Hi
Im really busy atm, but I cant resist joining this conversation - even though I have not had time to listen to the Mikovits talk yet.

Dr Mikovits started looking at MRVs because the only virus that came up on the viral microarray tests was the MRV group when at the beginning of their study they originally screened the patient blood samples for all known viruses - MRVs consistently showed positive - wheras no other pathogen was consistently positive across all the samples.
It could be that the microarray was not picking up an MRV pathogen, but a similar reactivated HERV - but this finding was still very important.

I am glad she and Ruscetti are looking again at the serology test. Just assuming a non-specific reaction to this test and dismissing it is not enough - if all the samples show positive it is an important lead as to what is a common factor in all the ME samples.
I am glad this is being followed up.
 

currer

Senior Member
Messages
1,409
The human genome is composed of millions of fragmented contiguous viral DNA sequences, dating from the dawn of evolution and reflecting retroviral insertions over millions of years of coexistence. Herpes and other viral insertion points correspond to the locations of over 120 Alzheimer's disease susceptibility genes and to linkage hotspots. The greater the number of pathogen matches, the more important the gene. These DNA sequences are translated into short contiguous 5-12 amino acid stretches (vatches), identical in viruses and man, and in other pathogens implicated in Alzheimer's disease (Borrelia, Chlamydia, Helicobacter, C. Neoformans , P. Gingivalis). C. Neoformans, which has been associated with a rare but curable form of dementia, expresses the most number of hits to Alzheimer's disease proteins. Vatches are often immunogenic and antibodies to viral proteins may knock down their human counterparts or activate immune responses killing the cells containing their human homologues. This is supported by the presence of the complement membrane attack complex in Alzheimer's disease neurones and by the ability of tau antigens (homologous to pathogen proteins) to promote the formation of neurofibrillary tangles and Alzheimer's disease pathology in mice. Vatches may act as dummy ligands or decoy receptors and interfere with the interactome of their human counterparts. Alzheimer's disease is thus a "pathogenetic" disorder caused by pathogens but dependent on the genes that create these matching sequences. This scenario is relevant to many other, and perhaps most human disorders, given the massive genomic extent of viral coverage. The vatches in the human proteome, dictated by polymorphisms and mutations, may predict, from birth, the spectrum of pathogens that match our proteins and which pathogenetic disease we are likely to develop. These may all be preventable by vaccination, pathogen detection and elimination and curable by immunosuppressant approaches, perhaps with a unique, safe, and effective immunosuppressant panacea.

http://precedings.nature.com/documents/4765/version/1/html

This paper was found by GcMAF on this thread. http://forums.phoenixrising.me/inde...-retrovirus-in-patients-with-bph.18674/page-2
It links up autoimmunity and HERVs (and it could be that antiretrovirals have immunomodulatory effects)
 

Firestormm

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Cornwall England
Thanks Bob for your efforts. I might take another attempt at listening, can't say I'll absorb any of it, and I've had enough of the why's and wherefore's and speculation and hypothesising over something that wasn't anything but wasted so much time and sparked such consternation. What did she have to say about the accusations and sacking incidents? Thanks.
 

natasa778

Senior Member
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1,774
this conversation brings up the recent paper (Stoye coauthored)
Resurrection of endogenous retroviruses in antibody-deficient mice


Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic4 MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.


So bad gut flora (contributing to) = > suppressed immune system = > reduced antibody production/control of pathogens => resurrected frankenviruses ... It all links rather nicely.
 

currer

Senior Member
Messages
1,409
I am glad Dr Mikovits is continuing to pursue the leads that XMRV created.
We need to give the science time and allow for all the exploration of new hypotheses that will follow from these findings.
There are no dead ends in science. All knowledge is useful.
 

Bob

Senior Member
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England (south coast)
Thanks Bob for your efforts. I might take another attempt at listening, can't say I'll absorb any of it, and I've had enough of the why's and wherefore's and speculation and hypothesising over something that wasn't anything but wasted so much time and sparked such consternation. What did she have to say about the accusations and sacking incidents? Thanks.

The section that I listened to is purely a scientific discussion, Firestormm.
A very interesting exploration of scientific/medical possibilities. (Interesting for some, anyway.)
 

JAH

Senior Member
Messages
497
Location
Northern California
Thanks Bob for your efforts. I might take another attempt at listening, can't say I'll absorb any of it, and I've had enough of the why's and wherefore's and speculation and hypothesising over something that wasn't anything but wasted so much time and sparked such consternation. What did she have to say about the accusations and sacking incidents? Thanks.

She didn't speak much to the firing and subsequent trial. Was asked if she ever got her notebooks back, and she said "no". And that was about it.

I think it is worth listening to, really just about XMRV - her study and the Lipkin study. A lot of detail about both. Very specific questions, better if you are scientifically minded (which I am not, but still glad I heard it). If you are fascinated by GAG sequencing, HERVs or cohort selection, you will love it. Really, really puts to rest idea that XMRV the cause of CFS. I wish she had gotten into what she is working on now, and what Lipkin is up to, but unfortunately that was not addressed.
 

Firestormm

Senior Member
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Location
Cornwall England
She didn't speak much to the firing and subsequent trial. Was asked if she ever got her notebooks back, and she said "no". And that was about it.

I think it is worth listening to, really just about XMRV - her study and the Lipkin study. A lot of detail about both. Very specific questions, better if you are scientifically minded (which I am not, but still glad I heard it). If you are fascinated by GAG sequencing, HERVs or cohort selection, you will love it. Really, really puts to rest idea that XMRV the cause of CFS. I wish she had gotten into what she is working on now, and what Lipkin is up to, but unfortunately that was not addressed.

Thanks. Yes I had been reading the 'debate' on the other wee forum. Does anyone know if Mikovits has any actual employment that involves working on any 'retroviral' hypothesis? I believe she mentioned continuing to work with Ruscetti - but on what and who's paying the bills? If there is nothing really happening, then is she perhaps placating the much-reduced crowd (again). Thanks.
 

Bob

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England (south coast)
Further notes from the radio interview.

First of all, some of my own thoughts, after listening to most of the interview:

I found some of the answers a little inconsistent, incomplete, and sometimes contradictory.

Incomplete: Why exactly did Mikovits need to find two samples positive in each aliquot, in the Lipkin study, for it to be declared positive? Judy says that this is because that's what they did in the original study, and that this was a replication study, but I didn't think that this was what they did in the original study? Maybe I've got this wrong about the original study? She says if only one sample in an aliquot is found positive, then it must be contamination, and not a result of low copy numbers. I don't think this is a reasonable explanation, but she seems to be entirely convinced, for a number of other reasons that XMRV is purely a contaminant, originating in a cell line.

Inconsistent: Judy admits contamination, but stands by her gag sequences. This might not be inconsistent (she doesn't seem to think it is), but I don't understand it.

Contradictory: On the one hand she is saying that she may have been detecting HERVs, but on the other hand she is saying that she was only detecting contamination, in the Lipkin study, in the inconsistently positive aliquots, such that the results did not need to be followed up. But she didn't offer details of any evidence for contamination of the Lipkin study, that I'm aware of. (But I haven't read the Lipkin study.)

Listening to her answers, I wondered if maybe she is under a certain amount of pressure to conform in relation to 22RV1. (These are purely my own thoughts about it, trying to read between the lines, and it may well be completely wrong to think along these lines. There's no evidence that Judy is/was under any pressure to conform, that I'm aware of.) But it also seems that she might have come to her own independent conclusion that XMRV 22RV1 was a contaminant, before the Lipkin study was completed, based on various factors. (I can't remember all the details re contamination.)

In any case, she seems thoroughly convinced that 22RV1 is purely a cell line contaminant, and clearly wishes to move forwards.


Now back to the notes:

It's an interesting, and in depth interview.

Here are some more snippets, in which I'm paraphrasing Judy, except where in "quotes":

@31mins. Positive readings whilst working at the WPI are unlikely to be a gammaretrovirus, because she hasn't 'isolated' a gammaretrovirus from "a single human yet".

@45 mins. Our current research doesn't rule out infection by RNA viruses including a retrovirus, but we don't have any data for a retrovirus, apart from the footprint from the abnormal cytokine response and the antibodies. (And later mentions the gag sequences again.) But these only suggest a possible association, nothing more. The only virus we (includes Ruscetti) have 'isolated' from 350 samples is 22rv1.

@48 mins. All Ashford 50 samples were contaminated by a patient cell line culture that was being grown in lab, which had become contaminated with XMRV 22RV1.

@59 mins. We're now doing NGS technology. (Mentions possibility of working with Lipkin, a few times during interview, but nothing specific.)

@61 mins. She stands by her gag sequences, and seems to be saying these are not due to contamination, despite contamination of the original study. (I don't understand this.)

@69 mins. The Lipkin study used Judy's own chosen cohort type.

@73 mins. Judy, Frank, and Lipkin have received "hate" mail. Distressing for all of them.

@80 mins. Disappointed that unable to 'isolate' any gammaretroviruses (other than 22rv1). Says will continue to try with Lipkin's ("unbiased") (NGS) technology. (But will also pursue other leads, such as HERVs and the cytokine research.)

@87 mins. Repeatedly refers to CFS/ME as "non-HIV AIDS". (i.e. in Judy's opinion, it's an Acquired Immune Deficiency.)
 

Enid

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Thanks Bob - I particularly like Acquired Immune Deficiency, non-HIV Aids. It just fits the bill for self and brother as various latent viruses appeared over the worst times.

Sorry to hear of "hate" mail and hope someone will monitor and remove for them.
 

justinreilly

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I haven't followed the XMRV/HGRV debate for a long while now and I am not a science person, but I do recommend the podcast. It was quite interesting to me.

I applaud her use of non-HIV AIDS! That is much more appropriate than "CFS". Although she didn't like to use ME and her reasoning didn't make sense to me, especially since she was a coauthor of the ME ICC (which she mentioned) and used the ME/CFS CCC in the Lombardi study. She implied she was leaving the terminology up to the clinicians. Anyway...

She did seem to think it probably wasn't a gamma retrovirus, but that anything was possible, that she will be (or is?) doing the "unbiased" Next generation sequencing with Lipkin.

Pretty sure I remember her saying that she and Ruscetti have been sequencing whatever she found in the Lombardi study and they've been doing that or attempting to do that in the lab "all along" (I think were her words, I took that to mean ever since the Science paper, but don't know). And she and Ruscetti are still doing that and will be doing that.

On LinkedIn she has her employment as Mikovits Consulting. I guess she is getting hired as a lab worker, investigator, contract employee or whatever by Lipkin and Ruscetti.

When asked why some people improved on ARVs, she gave the reasoning that was presented above in other posts. Plus she said that neither Michael Snyderman nor Jamie Deckoff Jones had been diagnosed with "CFS". I was pretty sure he was saying he did have ME in addition to CLL. I know Jamie's main diagnosis was Lyme, but I also thought she has said she has ME.

I don't know any statistics, so I can't really evaluate what she was saying about the following. She said that XMRV IS NOT A HUMAN INFECTION. She also said at least that it hasn't been found in other animals, and I think I remember her also saying XMRV does not infect other animals either. the evidence she gave for this statement were the facts that only six or so was it, of the samples were positive in the Lipkin study and that in each case the two other samples from each person were both negative. there were over 300 people in the study. And that she is XMRV negative.

I don't know how she can go from that evidence to flatly saying XMRV does not infect humans. There were 300 people in the study yes, and she, one lab worker is negative.

However, XMRV from an infected human cell line can blow through the air and land on a bleached surface (i think she implied also that the surface could then be bleached AGAIN) and the XMRV could remain viable several days and then infect another human cell line. And there are a huge number of people that work in labs that probably inhaled XMRV. How do we KNOW for sure that no one has ever been infected? This just strikes me as the sort of overreaching conclusions that Judy's detractors have always spouted.

Does any one have any thoughts on this?
 

Bob

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Does any one have any thoughts on this?

I think you've summed it up really well, Justin. That exactly matches my own interpretation of the podcast.

Maybe Judy has been advised to keep a low profile in relation to retroviruses for a while, and to let the dust settle?
She clearly hasn't completely abandoned them, and she says she is doing NGS with Lipkin.

Judy and Frank are trying to find out exactly what proteins the serology assays are detecting, she says, which will be interesting.
 

Ecoclimber

Senior Member
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I haven't followed the XMRV/HGRV debate for a long while now and I am not a science person, but I do recommend the podcast. It was quite interesting to me.

When asked why some people improved on ARVs, she gave the reasoning that was presented above in other posts. Plus she said that neither Michael Snyderman nor Jamie Deckoff Jones had been diagnosed with "CFS". I was pretty sure he was saying he did have ME in addition to CLL. I know Jamie's main diagnosis was Lyme, but I also thought she has said she has ME.

I don't know any statistics, so I can't really evaluate what she was saying about the following. She said that XMRV IS NOT A HUMAN INFECTION. She also said at least that it hasn't been found in other animals, and I think I remember her also saying XMRV does not infect other animals either. /
Interesting as I didn't read the transcript or listen to the broadcast but curious about your quote of Mikovits. Dr. Snyderman is an oncologist and hematologist and Dr. Jamie was ER director ...I believe. These two people are both clinicians and if anyone who could assess a condition of ME/CFS would be those two and not a researcher. Big difference between the two professions. Besides Lyme disease is associated with a bacteria infection which ART would be ineffective. Since there are no definitive bio markers for this illness, even Mikovits cohort could be suspect!

Don't understand Mikovits comments on animals as there were studies with infected with xmrv rhesus macaques and pigtailed macaques although one study showed antibody production to neutralize xmrv.

http://www.retrovirology.com/content/8/S1/A219

http://jvi.asm.org/content/early/2011/02/16/JVI.02411-10.abstract

Curious

Eco