Life is full of misery, loneliness, and suffering – and it’s all over much too soon.
~ Woody Allen
Every time I write a blog I feel like it might be my last. How could I have anything left to say? Then the next one appears in my head, generally pretty much fully formed, and I need to write it. It’s a strange process to reveal one’s personal journey so publicly. But your letters have made it well worth putting up with the unpleasantness and infighting. The feedback that my writing has helped someone’s isolation, or helped medically in some way, means everything to me. One of the worst things about getting sick for me was being unable to be of service.
Writing this blog has required a willingness to be wrong. As I’ve said repeatedly, I could be wrong about anything, though it seems unlikely that I’m wrong about everything. If I am, I figure I can still become Jamie Jones and move someplace where there is no internet:). There must be somewhere on earth one could still go and live completely unplugged:). There are inconsistencies inherent in blogging, writing on different days from different moods. When I sit down to write, I try to center myself so I can find what is true for me at that moment. It isn’t about building a flawless argument over time. It is a moving target. I have made being honest more important than being perfectly consistent, but there isn’t much I’ve written that I’d retract. I’m not as angry now as I was when I wrote certain things, so I might be gentler if I wrote some of it today, but not so different in substance.
I received a lot of mail today concerned that I sounded depressed and hopeless yesterday. I am neither. I am sad and, unfortunately, somewhat sicker than I was a couple of months ago. And really tired of this fight, because absence of proof is not proof of absence and we’ve got something serious, most likely of retroviral origin. Something I now have to treat, with or without all the answers. Like all of us, I hope that the BWG and Lipkin are positive studies. But if they aren’t, it doesn’t change a thing for me, except for the timeframe in which I can reasonably expect help and change. As Karina so eloquently said in the comments of the last post:
I have accepted that I have to live with this disease and I will most probably die from it too. As ridiculous as it sounds accepting that is somehow giving me some peace of mind.
I am no longer trying to reach for the stars but try to reach for the possible.
I worry less…..
But I still worry for our children
and for our children we must continue to fight….
I took a big emotional hit in early July, and my declines are always a month or two after a major physical or emotional stressor, so right on time. I am sorry that arv’s didn’t protect me. Until now, it has seemed to me that I was more resilient than expected. But I am not depressed and I certainly still have hope. My coping mechanism is always to look for meaning in my predicament. However, I am getting real about what I can expect, personally and professionally. Baby steps. I’ve put a lot of energy into understanding the unfolding science. The heady days of discovery seem to have wound down to this period of uncertainty. My focus has turned to the clinical now. I have a limited bag of tricks at my disposal, but not an empty one. I don’t feel in any way powerless. The patients I’m seeing have some maneuvering room and we will work with what we have.
>Well, you have made wonderful, positive impact on my life. Thank you. That quote from Karina sure sums it up for me too. I have come across so many references of receiving peace during tribulations within the last 30 minutes. Think God's trying to get His message deeper into our hearts. — Tracey, dancingstarheart
>Please keep on blogging Dr Jamie.
Your contribution to the worldwide debate about M.E. is too valuable and to too many people, for you to end now.
To me, you are the clear voice of reason and sanity in a bitter, corrupt and twisted world.
>"Conflict is the primary engine of creativity and innovation.” – Ronald Heifetz
I just thought that this quote fits really well with our issues in our community and in the politics of our disease. It gives me hope for the future that we can get there despite the differences.
Thank you for contributing to our community Jamie and for being so honest.
>Dr. Jamie, if XMRV causes this disease, why do you think you are you still so sick?
I understand that there are not yet drugs to control all parts of the virus's growth, but AIDS patients got lots better just from AZT.
>HGRV are slow replicating retroviruses. They will not be as smple to treat as HIV as viral replication or stopping Viral replication will not help as much. Immune modulators and other agents may be needed. This is more like HTLV than HIV. IMHO
>Dr. Jamie, what do you make of Dr. Bridgitte Huber at Tufts work, showing re-activation of the human endogenous retrovirus, HERV-K18, in ME/CFS patients? Caused by EBV infection and other viruses. It seems to me like a model that fits ME/CFS very well, with the multiple triggers.
She presented her findings at the Invest in ME conference in London last year, but it largely got overlooked with all that was happening with XMRV, including her own study in which controls tested positive, but patients did not, that highlighted the importance of having "real" controls, where samples have been taken at the same time, using the same methods, apparatus and storage procedures. As wasn't the case either with Lombardi et al. or Lo et al, unfortunately.
I hope she hasn't abandoned her work with ME/CFS, as a result of the abuse leveled at her from patients.
>Ed, no one's abusing anyone, except patients being abused by the government. Stop with the nonsense please.
>The one thing that does reactive an endogenous retrovirus is an exogenous one. Again, Huber's work points to this being caused by HGRVs.
Huber presented her data on HERVs after only studying about 4 patients. Normally she would have been rejected by everyone for doing this.
>my thinking until a few days ago seemed to always run "when i'm treated and feeling better i need to …". it suddenly dawned on me this disease (me/cfs) IS my life, and whatever i need to do, i'm probably not going to get the chance. i'm not depressed (at least not any MORE depressed) but have had an epiphany concerning being sick and trying to function in a world that seems to have tilted permanently off-kilter. there is likely no way a comprehensive study/research into this disease will happen, and accepting the facts is far better for me in the long-run than opening my life-link laptop each day hoping for the miracle. we can all hope i'm wrong, but it sounds to me like many of you have come to the same sorry conclusion. just sayin…
>Chris, nobody's abusing anyone? Check out a post from XMRV Global Action's Facebook page yesterday where Prof. Myra McClure is called both a "fuckwit" and a "halfwit", just because she uncovered sources of mouse contamination whilst testing prostate cancer samples.
http://www.facebook.com/pages/XMRV-Global-Action/216740433250
It's nonsense not to see the craziness of some of the far-fetched paranoid conspiracy theories that get thrown around and the unjustified trashing of experienced and respected scientists. I can understand some of the reasons behind it, but that doesn't excuse it.
>Hey Dr. Deckoff-Jones, have you ever considered that a large part of your argument against XMRV and other MLV's being contaminants relies on the assumption that XMRV and MLV's are ubiquitous contaminants? Kind of funny how that works out, don't you think? :)
>Hey Anon 11:41,
It's been a while since I've discounted the lab contamination issues. Zhang/Gazdar established what a difficult problem it is, even in a clean lab. We can't know how it will all play out yet. However, contamination can't explain away serological response in some patients.
Jamie
>Myra McClure changed every variable in the Lombardi paper. Do you think she was avoiding asking if people were infected? IS it any wonder people have no respect for her.
To anon above. What is your scientific argument?
>Here is another argument. If Coffin believes his assumption (not science) that one variant called VP62 was created in a lab accident, and two he wants us to believe contamination is everywhere al the time. Then that variant did get out.
Now what about the polytropic and modified polytropic variants and the other XMRVs?
>Anon @ 11:52, you don't seem to understand the issue fully as there is not just one source of contamination, there are many many potential sources of contamination.
Yes XMRV was created as a result of the 22rv1 cell line and therefore is in all 22rv1 cell lines around the world, with the 22rv1 cell line being a common cell line in many labs, therefore of course the contamination 'got out'. Also, a recent paper of Dusty Miller's showed that another cell line called NIH3T3 contained one 'half' of XMRV, therefore any contamination from this cell line in studies which searched for this 'half' of XMRV would also report positive results.
Then there is the issue of other MLV's, which could come from mouse DNA itself which could insert itself at really any time point in the manufacturing, processing, shipping, etc. of any of the materials, supplies, reagents, etc. used in such studies, MLV sequences have also been shown to already be in many of the actual reagents used in such studies, which would mean that IAP/mouse mito DNA tests might or might not pick up the contamination. These are just a few of the potentials for contamination with there being many many more and I think it would be interesting to see them all collated. I had a few sips of beer last night (literally) and am not thinking the sharpest today so I can't even remember all of the potential routes of contamination, but from what I remember remembering, there are quite a lot of them.
As for 'other XMRVs', I don't think that they are truly XMRVs, but rather are distinct recombinant viruses produced in distinct recombinant events and are simply being mistakenly called 'XMRV', similarly to how all of these endogenous MLV sequences and/or recombinant XMLV viruses are mistakenly being called 'HGRVs' by some. At least one of them, I think the Lithuanian one, actually did not share a distinctive hallmark of XMRV, namely the gag-leader deletion, and I question whether the authors will be allowed to call them 'XMRV' in any published papers.
>Prof. McClure used the assays that she had already spent a long time developing to detect XMRV, as was logical. She was not involved in patient selection. She was just approached and asked to test some samples, which she did. I'm sure she wishes she hadn't bothered now.
>Jamie, just an fyi, if you find your song on youtube, you will see the possibility of embedding it. You simply copy and paste the long string of code into your blog before you post, and the youtube video will show up, and people can just click play and listen to it while they read.
Are you going to use the chamber for you and Ali and for your patients? I'm very curious.
Jill Neimark
>There is a dance with this illness (well, with anything chronic, I suspect) where I find myself bouncing between what I call my higher truth and my deeper truth.
My higher truth is where I have something of an overview of things, like sitting on top of a mountain, seeing the big picture and feeling more connected with everything – like that wonderful feeling you get when flying somewhere: not here or there and yet above it all. That's a pretty heady feeling, one that gets a lot more cultural support than what follows, the deeper truth.
What I call my deeper truth is where I'm fully in my body with all of her pain and fear and frustration. Where the boundaries and walls comprised of what I can't do make themselves so manifest and concrete that I can't ignore them or explain them away or push past. They push back. There is the bitter truth of my physical limitations in my face and the boundaries feel like a prison. It's a place where I'm shocked and horrified at how desperately ill I truly am, every day.
The higher truth and deeper truth are the endpoints of a polarity and my daily reality lives somewhere in the continuum between the two.
I have had this illness long enough to know that even if the endpoints feel so absolute there is always, always movement and flow. So patience, humor (when possible, not always so available to me) and reaching for serenity smooth things out. There is also room for rage and despair as long as I can express and keep things moving and flowing.
The bottom line is that I must find my way to who I am outside of this dance as well, the being that encompasses the paradox, and much more besides. Then there's room for the whole thing and I'm not flung against all those walls and boundaries as hard when I can really know it. This is some of what having this illness has taught me. I expect I have much more to learn!
I too had great hopes that finding a pathogen would speed up progress to treatment at last. The descent into infighting and politics could make me bitter, if I allowed it. But, like the quote above, I know now that there is no getting "back" to normal. I don't want to go backwards, if that means losing all I've gained in every other arena. I would, of course, welcome more functionality, less pain, as well as sane and respectful treatment by medicine and society at large. Staying in the fight helps preserve my sense of dignity and looking to the future to help prevent such suffering for the next generation is crucial.
I do know this, no matter where I am in the dance: I am bigger than all this, I'm bigger even than what the prospect of living with and ultimately dying from this portends. We all are.
>wow, kkrizani. thank you for sharing that.
jamie
>@Ed
"Prof. McClure used the assays that she had already spent a long time developing to detect XMRV, as was logical. She was not involved in patient selection. She was just approached and asked to test some samples, which she did. I'm sure she wishes she hadn't bothered now."
Developing to do what Ed? They have never been shown capable of detecting a positive sample!
The patients were not ME/cfs patients and the assay was completely different to anything that had ever worked.
>@Ed
You do realise that if McClure had used that kind of PCR to detect HIV she would now be in jail? It is illegal to use an assay unless its diagnostic sensitivity has been demonstrated!
>Jamie,
Your candor is nothing short of courageous and continues to build profound trust. I especially appreciate the lack of sugar-coating regarding difficult issues.
>@Anon, August 20, 2011 12:23 PM
I will go easy as you are new.
There is no proof the XMRV variant was created in the parental cell line called 22Rv1. That hypothesis was not tested in Coffin's paper. It is not based on empirical observation. That cell lines has not been in the NCI labs, the Lo or Alter Lab, or the WPI lab. It was frozen in the Silverman lab. Therefore the patient can still have been infected with that variant before the tissue sample was taken.
With the 3T3 cells only half the virus was cloned. The rest may be XMRV. Which would mean that patient was also infected.
As for mouse viruses. The Lo et al. and the Lombardi et al. findings have never been found in mice.
The immune response has never been challenged and the polytropic and modified polytropic variants from the WPI/NCI and Lo et al have never been challenged.
>The lithuanian isolate is obviously an ancestor of the polytropic xenotropic hybrid discovered by Silverman. Frameshift deletions would create frameshift mutations.
>Anon, the assays had been developed to detect XMRV in prostate cancer samples, which she had already been working on.
"It is illegal to use an assay unless its diagnostic sensitivity has been demonstrated!"
If that were the case then every researcher that has been involved with XMRV testing, including the WPI, would have broken the law, as there are no clinically approved diagnostic tests for XMRV. It's research!
>@Ed
McClure has never shown any of her assays to have any diagnostic sensitivity. Therefore scientifically she cannot say whether a virus is there or not.
The point was that if it were HIV she would be in jail.
>An editor of journal of virology, Jeffrey M. Bergelson, has gone on record as saying that three clones of lp-bm5 def with 18 nt difference, proves a virus has sequence diversity.
The difference between the HGRV clones from patient VP62 and Vp42 is 25nt. This is no contaminant,
>Coffin and Stoye admit lack of sequence variation normal for XMLVs (Mouse viruses).
"The Xmvs differed on average by 1.8% (0.3%–5.9%) from the group consensus (estimated from the alignment used for Figure 1 and extreme values excluded), compared to differences of 0.18% (0%–0.5%) and 0.21% (0.1%–0.3%) for Pmv and Mpmv from their respective consensuses. Between the groups, consensus sequences differed by 2.3% comparing Pmv to Mpmv, and 5.2% and 5.1%, respectively, comparing either to Xmv."
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.0030183#pgen-0030183-g005
>@ Ed
How many blood samples did McClure test? Is it correct that she only tested 4 samples? Did she actually find XMRV in the samples who were healthy controls? Please look this up and let me know, as I find this bizarre.
I am reminded of a twins study of fms patients done years ago. One of the twins in the study told me, off record, that her blood and her twin sister's sample were confused in the study, so that the results were totally meaningless. One has to wonder if this has happened once again.
Can you investigate my two questions? I have other fish to fry.
>does anybody know if there is any relationship between xmrv and the mmrv that has been associated with breast carcinoma?
>Singh has reported in a patent she holds on XMRV for ME/cfs and prostate cancer that she has found the virus in 25% of patients.
>The XMRV variant of HGRV is a recombinant of 3 types of MLV according to the CDC
https://www.facebook.com/notes/xmrv-global-advocacy/the-xmrv-variant-of-hgrv-is-a-recombinant-of-3-types-of-mlv-according-to-the-cdc/208343822556977
Mattia C F Prosperi1*, William M Switzer2, Walid Heneine2, Marco Salemi1 1Department of Pathology, Immunology and Laboratory Medicine, Emerging Pathogens Institute, College of Medicine, University of Florida, Gainesville, Florida, USA; 2Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA
E-mail: m.prosperi@epi.ufl.edu Retrovirology 2011, 8(Suppl 1):A235
Background: Murine leukemia viruses (MuLV) are classified into three groups by host tropism correlating with viral receptor sequences present in the surface protein of env. Ecotropic MuLV are found only in mice, xenotropic replicate in non-mouse cells, and polytropic in mouse and non- mouse hosts. Xenotropic MuLV-related viruses (XMRV) and polytropic MuLV have been found in humans and reported in different diseases, including prostate cancer and chronic fatigue syndrome. Classification of MuLV tropism is typically done using small portions of gag/pol, however, this may be complicated by viral recombination. Methods and results: Eight eco/poly/xenotropic MulV complete genomes were selected from GenBank, plus an XMRV sequence. The dataset showed strong phylogenetic signal. By tropism-group analysis using SimPlot software, XMRV was detected as a mosaic recombinant form of all three groups. Using more sensitive analyses, we found evidence of inter-tropic recombination, especially outside of env. Different procedures for recombination analysis (SimPlot/TOPALi2), applied to the whole dataset independently from the tropism, inferred discordant break-points.
Conclusions: Given the evidence of inter-tropic recombination in MuLV, detection and classification of recombination in XMRV using different MuLV tropism prototypes should be interpreted with caution. Despite using a small dataset, a strong phylogenetic signal in the alignments and highly resolved phylogenies inferred both by full-length and sliding- window approaches, different recombination programs reported conflicting results. These results suggest that identification of parental strains of the potential recombinants is difficult and that recombination in the highly genetically related MuLV have been occurring for some time.
http://www.biomedcentral.com/content/files/pdf/1742-4690-8-S1-full.pdf
It is now known that xeno's infect mice too. So the host range thing is nonsense. Really what this shows is that they have all found the same virus in humans.
It is only bad assays that miss the virus.
XMRV is a recombinant of 3 types of MLV, which totally contradict Coffins idea about the origin of the variant.
>Anon @ 1:38- It does not matter that the 22rv1 cell line has never been in the Lo lab as the Lo lab did not report finding XMRV. As for the 22rv1 being or not being in the NCI lab or the WPI lab, that does not matter either as Silverman sent Mikovits (and presumably Ruscetti) the VP-62 clone to work with. From what I understand, the VP-62 clone is considered the standard reference for XMRV and is an infectious clone, which needs to be propogated in order to be used for research. The propogation of VP-62 in the WPI and NCI labs could easily have resulted in both of these labs being contaminated with XMRV. For that matter, XMRV from the 22rv1 cell line could have hitched a ride on the VP-62 sample and contaminated things in the same manner.
Also, although it is often (incorrectly, as shown above) stated that the WPI and NCI labs have never housed XMRV, either the WPI and/or the NCI labs do indeed have patient cell cultures expressing what is essentially the same virus as XMRV. These labs would probably claim something along the lines of "of course they have XMRV as it came from the patients", however this infectious virus is a perfect source of contamination and goes against the claim that either/both of these labs do not/have not contain(ed) XMRV in cell culture.
As for the virus in the NIH3T3 cells being only half cloned, the paper states the following- "We determined the complete sequence of the XMRV-like mouse endogenous virus in the NIH/3T3 cells (GenBank accession JF714652.1)". So while only the left half was cloned, the full virus was sequenced and therefore it is able to be ascertained that it is not, in fact, XMRV.
The paper also states the following-
"The use of highly sensitive PCR techniques to identify XMRV sequences in human samples have been performed using primers designed to amplify sections of the XMRV genome that were believed to be absent from the mouse genome. However, all primers used to amplify gag region sequences perfectly align with the mERV-XL sequence and amplify regions of mERV-XL that are 100% identical to XMRV (Fig. 1). Even some of the env primers align well with mERV-XL and could amplify products with the same size as those expected from XMRV. Because NIH/3T3 cells are in such widespread use, DNA from these cells is an obvious source of contamination that could lead to false positive detection of XMRV." I would advise you to be wary of information from certain sources as these sources are known (by me, at least) as reading (or more likely misreading) a single line in a paper and drawing all further conclusions from the single misread line, as demonstrated above. This happens over and over and over again in the XMRV debate.
>Cont'd. *sorry for the lack of paragraph breaks in the post above*
As for the Lombardi findings never being found in mice, I direct you again to the NIH3T3 paper, which states the following- "We were unsuccessful in identifying a full-length copy or the right half of XMRV in the mouse strains we examined. A very recent publication also reports an inability to find an intact XMRV provirus in a wide range of mouse strains, but these authors were able to find two mERV in nude mice that can generate XMRV following six recombination events. One of these proviruses, PreXMRV-2 (GenBank FR871850), is 99.9% identical to mERV-XL, and the other, PreXMRV-1 (GenBank FR871849), exhibits high similarity to the right half of XMRV. Thus, it is clear that XMRV is not as distant from known mouse viruses as previously believed, but has clear roots in endogenous retroviruses of mice."
As for the Lo findings never being found in mice, I question that assertion- the recent Cingoz and Coffin paper 'Endogenous Murine Leukemia Viruses: Relationship to XMRV and MLVs' shows that phylogenetic analysis of the Alter/Lo findings was indistinguishable from direct and purposeful contamination with mouse DNA. The Cingoz/Coffin paper also states the following- "XMRV is not found as a single endogenous provirus in any mouse strain tested, whereas the partial sequences detected by Lo et
al. are very close or identical to proviruses found in mice." (before anyone goes on about XMRV not being found in a single endogenous provirus in mice, that is well known since it was basically shown that XMRV is the result of recombination of two endogenous proviruses found in mice) There was also a recent paper by Stoye called 'Caveat Emptor' which discussed the similarity and/or identicalness of the Alter/Lo findings with murine ERVs. While I basically support throwing out research by the psychosocial lobby in CFS due to poor patient selection, poor methodologies, etc., one cannot do the same with XMRV research.
As for the polytropic and modified polytropic variants from the WPI/NCI never being challenged, they have also never been published, so go fish.
>@August 20, 2011 4:31 PM
Lo et al did not report not finding XMRV. XMRV is only a variant. HIV-1 has variants too. What Lo reported was polytropic and modified polytropic sequences. As XMRV is a poly, xeno and eco, it cannot be said to be a different variant. The new variants in the GenBank from the WPI are also polytropic and modified polytropic.
VP62 by your beliefs could also explain the cell line 22Rv1. That could have become contaminated with the clone. That should be investigated. Where your argument fails is that the diversity of HGRVs is too large to be from a single cell line.
Another point your argument fails on is that the CDC retested 20 samples from the WPI that were positive. The CDC could detect nothing. Which means its the assays that do not work.
As for the virus in NIH/3T3 cells being only half cloned. That is what the paper says in the text. Perhaps you should read it. They did not clone the other half.
We should now investigate labs that have been using mouse viruses for the last 30 to 40 years to see whether they have created some of these viruses.
Also the JHK variant of XMRV, that was first detected in 1989. Tissue for 22Rv1 was not taken from the patient until 1992 and Coffin has the hypothetical recombinant of 2 variants, not 3 like the CDC says, as being 1993 to 1996.
>Anon @ 4:10- XMRV is not a recombinant of 3 types of MLV's, XMRV is a recombinant of 2 mouse ERV's. However one of these mouse ERV's is itself a recombinant, which would make a total of 3. Therefore Coffin's conclusions are not disputed.
>Sorry but xenotropic mouse viruses can infect mice too, so even if XMRV was found in a mouse, it would still not point to contamination.
Coffin's paper is built on sand. There is no data in it.
As for scientific evidence of contamination, non has been published. So go fish.
>@August 20, 2011 4:44 PM
According to the CDC it is a recombinant of 3 viruses.
" XMRV was detected as a mosaic recombinant form of all three groups. "
>Anon @ 4:42, your argument is mistaken. All of the viruses in question are distinct viruses in and of themselves and are not simply variants of one single virus.
VP-62 could not have infected 22rv1, as VP-62 was only created a few years ago, whereas 22rv1 was created in the mid-nineties. Furthermore, all cultures of 22rv1 all over the world contain XMRV. Where your argument fails is that you are calling the entire family of MLV's, with each one of these viruses being a distinct virus, simply variants of a hypothesized 'HGRV'. This is incorrect.
That the CDC could not detect XMRV could just as well indicate that the contamination occured somewhere downstream in the WPI's testing process.
As for NIH3T3 being only half cloned, yes this is indeed what the paper says, however what the paper also says is that the entire virus was sequenced, which shows that it cannot be the same virus as XMRV. Perhaps you should read the paper.
As for the JHK 'variant' of XMRV, as I stated in my post, I do not believe this to be a variant of XMRV but rather a distinct recombinant virus, and therefore not evidence of sequence variation in XMRV nor evidence which indicates Coffin's conclusions are wrong.
>RE: your arguments are mistaken"
Who do you think you are and why don't you start by standing behind your arguments and stating who you areand what are your credentials?
M.P.
>@August 20, 2011 4:55 PM
As opposed to MP. Your arguments will remain mistakes whether I am alive tomorrow or not.
These arguments are from scientists.
Did you know John Coffin tried to claim that HTLV was a contaminant when Ruscetti discovered that. He does have a habit of crying wolf.
>@4:53
Where is the evidence that XMRV was created in a cell line? Where is the evidence it is not VP62 that has contaminated that cell line? As the line line was only thought to be infected since 2009, after VP62's creation. It.can be VP62. Now as that virus in the cell line does not behave like those in humans it is very likely to be the clone.
As the WPI had completed their testing on those 20 samples that were given to the CDC there was no more downstream testing. The only conclusion is that the assays don't work.
NIH/3T3 cells contain other viruses. As only half was cloned it is not possible to say that the other half is not from a different virus. Or more accurately parts of the other half from multiple viruses.
JHK Is XMRV if you compare it to known sequences of XMRV. Therefore it is, along with the Lithuania variant and polytropic and modified polytropic variants proof that Coffin is once again wrong. As he was about HTLV.
>Is anyone else besides me getting CFS-brain death from trying to figure out which argument is from which anonymous poster? Really. Could it hurt to put a name to your posts? I don't care which side of which issue you are on.
michael a.
>Coffin's recombination argument is based on a one in ten to the twelfth chance. Which is more likely, that pre-existing XMRV contaminated the cell line or that it was created by recombination? The probability calculation actually works against the recombination argument. What the recombination argument does show is that the origin of XMRV is probably recombination of MLVs, which is not a surprise. It does not show when this happened. If cultures can be so easily contaminated, the sudden appearance of XMRV is probably not from recombination in the 90s. alex3619
>Alex Young- I think you have misunderstood what the probability calculation actually attempted to calculate. It wasn't necessarily that the chances of XMRV being formed to begin with were one in ten to the twelfth chance, the calculation was in regards to the exact same virus occuring twice in two independant recombination events was calculated as being one in ten to the twelfth. So you could get the virus known as XMRV once, but the authors calculated it being one in ten to the twelfth that the exact same virus would happen again in a seperate recombination event.
>Hi anonymous, you are possibly correct, and I think also in error. It doesn't really matter ultimately. I did a rough calculation of how many recombination events probably occur with MLVs in nature over a century, and came out with what I consider a conservative figure of 10^18. That would imply that XMRV has been recreated many times. Even if my figures are out by orders of magnitude, this is still the case. Furthermore, if you are right about the probability calculation, and I have not gone back to recheck it, it makes their theory orders of magnitude more untenable than I was claiming.
However, each recombination event should have the same probabliity of the same sequences recombining in the same way under the same conditions. So I still think, if their calculations are correct, that my interpretation is correct.
The so-called recombination event was most likely contamination. They did not control for this, they had no way to do so it was a retrospective analysis, unlike many of the studies on XMRV that were done in the last few years.
Part Two follows.
>Part Two
I also don't think recombination is entirely random. It is likely to be pseudo-random governed by principles involving the specific genetic sequences as well as by chance. These viruses probably have evolved to recombine all the time, if for no other reason it is a way to evade the immune system.
One of the disturbing issues that the contamination claim has raised is what this does to outcomes of positive XMRV studies. The small (4-7%) rate of detection in controls might be due to contamination. In CCC CFS patients its up to 98% detection of XMRV. Even if you presume that the controls are all contamination, which is unlikely, and subtract 5% from 98%, you get 93%, which is still nearly a perfect number, and now its 93% infected patients, 0% infected controls. If you allow for a reasonable bias of increased contamination of patient samples, say 25%, you still get a 73% prevalence, still very good.
To decide that all patient samples are contamination, is to decide the only explanation is poor lab technique at some times and not others. This might be so, but where is the evidence?
The only really confounding issue in my view is causation. It is reasonably plausible that we have HGRVs due to a defective immune system, which is why we also have high rates of other infections. The causation issue will only be strongly addressed however once we can strongly show the association or non-association of HGRVs with CCC CFS or ME.
Bye
Alex
>@Paula,
You're confusing Myra McClure with Bridgitte Huber and XMRV with HERV-K18. McClure tested about 150 patients and 150 controls and found all to be negative. Huber showed that 4 patients had re-activated HERV-K18 in her preliminary evidence. In her XMRV/MLV study, she tested 112 patients and 36 healthy controls. 1.8% of patients tested positive, compared to 47.2% of controls. All those that tested positive, were also positive for contaminating mouse DNA.
http://www.retrovirology.com/content/pdf/1742-4690-7-109.pdf
Try not frying fish at the same time as reading, as it seems to effect your concentration ;)
>Huber's pol assay had already been shown incapable of detecting positives as Danielson et al. had shown. And the nested assay was not XMRV specific and could detect MLVs.
>@Anon
Lombardi et al. and Lo et al.'s assays were not XMRV specific either. In fact Lo et al. could not even find XMRV.