Discussion in 'General ME/CFS News' started by Gerwyn, Mar 21, 2010.
You sure about that?
Gerwyn, I apologize if I mis-read your motives
Thankyou for your apology I appreciate how much brain fog can affect comprehension and expression
I should repeat the point just to be clear Dr vernon knows about problems inherent in trying to compare results in different trials in the area of CFS.She has however been entirely silent regarding the matter irrespective of which european study she has commented on.
Anyway, my comments about degrees and studies becoming obsolete are certainly correct in the sense that the information in those degrees and papers becomes obsolete
I agree that some information obtained while obtaining a degree can become obsolete.That is not what you originally said however.I quote the following
because our degrees would be obsolete in just a few years.
As to information in papers becoming obsolete .Sometimes the information is rebutted,built upon or of course confirmed.Whether the scientific elements contained in a paper become obsolete with time is therefore highly variable
My own background was also in a behavioral field, my specialization was technology design.
It didn,t know you were a psychology graduate .Behavioursim has been marginalised in European psychology and superceded by the neurocognitive approach as that is considered to be more consistent with the processes underlying brain function and the construction of the mind.I dont know about the situation in the USA
I also have a degree in Chemistry and Medical Microbiology .I spent a number of years working in the latter field.This is why I know so many Doctors who have been kind enough to impart their knowledge in many areas of the discipline
I just noticed from reading your profile that you are a doctoral student in psychology, is that correct? If so then I can understand that you may feel really angry about the treatment of ME in the UK as a psychological disorder, given that you of all people know what ME is like and realize it is not a psychological disorder. Even the CDC has acknowledge CFS as a biological disorder, and I just looked at the position of the NHS on CFS and that is horrible. Is that situation what is behind your continued support for XMRV? Do you think that XMRV would change the NHS position, if it were proven to be causal for CFS?
Yes the situation in the Uk is horrible even though the UK government accept the classification of the WHO.My view re XMRV as a causative ageant is based on my knowlege of retroviruses which were the subject of my final year paper.I have maintained that interest ever since.
I have worked alongside a number of psychiatrists and know too well the political manouverings some are capable of.
s problems I know many other labs are having replicating and validating the WPI finding.
The problems the other labs are having replicating the WPI results is because they are not attempting to.As Rich would say largely due to ego, stupidity amd blind faith in their methodology which is entirely untested in this area
The reason I challenge XMRV is because it just does not seem like the right biological explanation for all of CFS.
As a microbiologist the connection between a retrvovirus and the symptom complex of ME is clear enough.It is however possible that ME and CFS are quite seperate diseases.
I am collaborating with others with a scientific background to produce a theoretical model connecting a retroviral infection with the observations made regarding people with the illness.This is highly unlikely to be complete.It should be ready in about two weeks perhaps i could post that asa foundation for a debate
XMRV and Culturing, HERV's and more
because of high possibility of false negatives, and because xmrv-specific antibody testing would be more reliable, quicker, simpler (see Gerwyn's explanation on complexity of PCR testing for latent retrovirus) and cheaper.
By the way ask yourself what the standard HIV test is and why.
My training included both behavioral and neuro-cognitive psychology, and also general systems theory, but as I stated, my research area was applied, use of technology for advanced military training systems. But what is relevant here is that I worked enough on medical projects to understand the research paradigms, and ran enough studies myself to know how to read the papers, etc. Anyway, the point is that I also have access to medical experts and there is clearly some new and powerful information now about CFS that should be leading to new theoretical models soon.
If ME has exogenous retroviral cause then I suspect you are right that it would be very different from CFS. Particularly given the epidemiology of CFS. But there is RT in CFS and that suggests to me an endogenous retrovirus is possible. So some of the breakthroughs I am studying right now are about the interaction between HHV and HERVs, mostly this is being pursued in MS research, but also one team is studying HERVs in CFS (B.Huber, at Tufts).
Yes, you are correct that researchers in the field know about HERVs, but I take the opposing view with regard to XMRV, their knowledge that HERVs have confounded many prior efforts to connect retroviral infection with disease should give them great pause regarding XMRV in CFS. Particularly given the non-specificity of antibody studies using MuLV, and the reliance on that test by WPI. Also, I am surprised at your statement of PCR having poor resolution for low-count virus, which type of PCR are you referring to? Real-time methods can detect single viral copies, and that is pretty good resolution.
Anyway, please do post any new theories, maybe we should have a section for theory discussion on the forum.
Culturing XMRV: Questions
I read the WPI Science supplement and did not see any culturing process for their PCR. There is a section where they discussed the process of isolation and extraction of the nucleic acids prior to PCR, is that what you are referring to? Their culture study was separate, so they did not overcome any PCR sensitivity issue, they reported that they ran PCR on normal samples and had that high rate of positives (67%). Nobody since has repeated that PCR result, apparently including VIP. Doesn't that make you even a little suspicious?
As for the culture/serology testing, there are some possible problems with that if you look critically and think about HERV activation. If CFS samples have HERV activation, then if a viral protein is activating those HERVs it would likely be in the blood fraction used in the transfection. And since WPI was infecting prostate cancer cell lines, it seems very possible that the viral protein then also transferred over, activating the same HERVs in the prostate cell line. Then in the final step, the MuLV antibodies might get hits on the activated HERVs in the new cell line. I am not claiming this happened, just pointing out that there is an alternative explanation that must be ruled out.
Anyway, if the serology is getting this type of cross-reactive false positives it certainly is not overcoming problems with the standard PCR test used by WPI.
I would love a theory discussion section. I don't think I'd be able to contribute to it, but I would love reading it.
The amplification processes and activation are the issue kurt I,m genuinely sorry that you dont appear to be able to grasp that .You would not find a latent virus using PCR without that.The rest is speculation without any fact to back it up.The issue about herv activation is not an issue it has been dealt with by experts and put to bed. The issue with PCR is false negatives and that is why it is not considered reliable enough to confirm or more importantly dismiss a hiv infection.
If CFS samples have HERV activation, then if a viral protein is activating those HERVs it would likely be in the blood fraction used in the transfection. And since WPI was infecting prostate cancer cell lines, it seems very possible that the viral protein then also transferred over, activating the same HERVs in the prostate cell line. Then in the final step, the MuLV antibodies might get hits on the activated HERVs in the new cell line. I am not claiming this happened, just pointing out that there is an alternative explanation that must be ruled out.
If , would be likely it seems very possible might science does not deal with speculation kurt but objective observations.If any of this had been observed then it would of course have to be accounted for. If it is mere speculation however it is irrelevant
I am very suprised that you are not suspicious of 3 studies rushed out in 51 days by psychiatrists who's carreers are heavily dependant on portraying CFS as a psychological illness
Anyway, if the serology is getting this type of cross-reactive false positives it certainly is not overcoming problems with the standard PCR test used by WPI.
Another IF Kurt
Yes, you are correct that researchers in the field know about HERVs, but I take the opposing view with regard to XMRV
Are you seriously saying that your view as a lay person is anywhere near the same importance or value as a proffessional retrovirologist
yes we have discussed Hubers in vitro work before
I am familiar with the work in MS and Herv activity they are also heavily expressed in patients suffering from several other diseases and in pregnancy.The patients in the control group of the groom study all had conditions where Hervs are heavily expressed--I,m sure it was a coincidence of course
Also, I am surprised at your statement of PCR having poor resolution for low-count virus, which type of PCR are you referring to? Real-time methods can detect single viral copies, and that is pretty good resolution
yes Kurt any PCR method can detect "copies" of viral nucleic acid .to get copies of course the virus needs to be replicating
But there is RT in CFS and that suggests to me an endogenous retrovirus is possible.
I,m suprised that you think that the presence of RT activity in CFS suggests the presence of an endogenous retrovirus.To a virologist RT activity would suggest the presence of an exogenous retrovirus.while it has been possible to clone a herve and induce RT activity experimentally it has never been observed in vivo.
I am not clear one one point however did you say you were a psychology graduate or didn't you
I look forward to your new and powerful information
Yes, real-time PCR can produce false negatives, that might have been a problem with the UK and Dutch studies. But standard PCR can produce false positives, and the WPI might also have that problem. Validation by outside studies with a valid cohort would help illuminate that issue.
HERV activation was not seriously dealt with in the Science article and it remains a significant possible confound for the antibody and culture portions of the WPI study given the cross-reactivity of MuLV antibodies. WPI does not have any XMRV antibodies, nobody has discovered them yet, at least that is reported.
Speculation? What was observed during the WPI transfection study could be explained by other than the proposed hypothesis that they saw XMRV infecting new cells. WPI has hypothesized that their process proves XMRV is infecting, but they have not to my knowledge ruled out the alternative hypothesis that they created HERV activation transfer. Their final antibody test also does not rule out HERVs, in fact MuLV antibody is one possible test for HERV activation. All that was objectively observed was that at the end of the transfection process the MuLV antibodies got hits.
I don't have a suspicion like you might have in the UK of the motives of those researchers, but I do understand why you would be suspicious. I am FAR more suspicious of activities and claims of private companies like VIP/WPI, given how things often work here in the US. But yes, those tests were rushed, I agree that is a risk, they ran convenient samples using existing PCR techniques readily available. This rushing does not by itself prove anything, but it casts doubt. And suggests that they do not value the CFS population enough to run a fresh study using carefully designed testing procedures and new samples from a strong cohort. Sad state of affairs.
The cohort of the Dutch study certain is questionable as you pointed out in another thread, which is too bad because that was probably the strongest assay yet in a follow-on study. So at this point my only conclusion about those 3 rushed studies would be that they are weak, and certainly insufficient evidence to draw any global conclusions. I hope we get better studies by summer. Anyway, I don't need to do the dirt digging there, others here already have.
There is still a possibility that the tested cohorts in those three studies simply had no XMRV. We really need to see some stronger studies though to get a better sense of how widespread the virus really is. IF XMRV is a false finding for CFS, then whether or not the UK and Dutch studies were adequate will become a moot point.
Yes I graduated, my field was an integrated discipline similar to what you might call I/O psychology (industrial/organizational), although mine was a Systems focused program, more technology. So that included psychology, technology and systems, educational/training research methods, things like that. Then worked for a few years as a research psychologist, a post-doc at a US military research lab. Then later worked as a systems designer for MD training project (Cardiology), then worked for a private military research company, where CFS totally wrecked my career. Anyway all that really transfers from that experience to CFS is that I learned how to read research, and having authored studies and been a peer reviewer I realize the limitations of published research reports.
So you said you had a degree in chem/medical, were you a microbiologist, a lab technologist or med tech?
New and powerful information ... would be nice. I believe that can come from connecting all the many pieces of the puzzle we have now in front of us. The role of HHV, HERV K18, enterovirus, other co-infections, glutathione depletion, methylation problems with SNP expression, mitochondria malfunction, cytokines, NK problems, pain/fatigue receptor over-expression (PEM), and problems from resulting neuroendocrine over-stimulation all need to be connected together. What could cause all of these to express together as they do in CFS? That is a theory I would like to see, using a systems biology approach. I have talked with other researchers, including biomedical, but have found nothing concrete, no workable systems model that could include all this. Maybe all these clues ARE the model for CFS, who knows.
I am still not clear as to whether you are psychology graduate Kurt.A yes or no would be fine. Are you saying you have a phd in psychology again a Yes or no answer will be fine
you may have been talking to the wrong researcher before
By the way I am a Microbiology Graduate just for the purposes of clarification. I know brainfog can make life very difficult. I practised as a medical microbiologist for three years untill I had itchy feet.I did indeed engage in Microbiology at the coal face.That is why i am so acutely aware of methodological issues and problems that a microbiologist who spent the main part of their working lives in a managerial role would not be.
You said that new and powerful information is on the way . Now you talk about a mere belief. A systems model would not reveal anything in this branch of science would it? I,m suprised that biomedical researchers know anything about this method at all
what could cause all the abnormalities you mentioned by the way?. What is systems biology exactly?
As you can read research then you must be acutely aware of the methodological problems with the European studies but you appear to be silent on those .You also appear to be at odds with world renowned retrovirologists regarding your aasessment of the WPI methodology oh and the peer reviewers of the science journal.Perhaps you should inform them of your superior reading ability.
I may have misunderstood you though because reading clinical papers and critically evaluating them are two seperate things of course
There is still a possibility that the tested cohorts in those three studies simply had no XMRV.
Yes anything is possible given that the cohorts in the European studies in general and the Dutch study in particular contained few if any patients with CFS You are correct the cohorts did not have XMRV and nor would they be expected to!
And suggests that they do not value the CFS population enough to run a fresh study using carefully designed testing procedures and new samples from a strong cohort. Sad state of affairs.
Precisely Kurt they did not do what the WPI did in any way shape of form--i am glad that you see that now.
What was observed during the WPI transfection study
Hervs are activated in transfected cells kurt If they were not the cell lines would not be permissive for an infecting ageant.There is of course a reason why they are defined as Hervs what do you think that reason is I wonder?
No for the degree but yes for the post-doc. As I said earlier I was in a multi-disciplinary doctoral program that included a heavy psychology component, similar to I/O Psych. The PhD degree was in Systems. However, my post-doc (3 years) was as a military research psychologist where I trained in additional areas and worked in an experimental cognitive and educational psychology group. Then later I worked in industry as a systems designer & researcher, basically applied systems science using cognitive psychology heavily. Most of my research studies and publications are related to modeling expert cognitive models in software-based training systems. And I do have some experience in the medical field, mostly consulting on projects, including one for training doctors in basic Cardiology principles, and help with one clinical medical study. The interesting part of my work with clients is that I have to learn many new fields quickly, then work with the real subject-matter experts, applying psychology, design and systems principles, helping them improve processes and practices, building training programs, etc. But I don't do much consulting now, just small projects, as I am disabled by CFS. So the past five years I have been studying the biology of CFS when I had a clear head. Also, my wife has helped me with some concepts, she has a similar biology background to yours, with a degree in Medical Technology and Chemistry. She worked in a local hospital lab for some years, I used to go spend time there, have watched how tests are run, etc. Every little bit of understanding helps, right? This CFS mess really forces us to learn for ourselves. Not what I had planned to do with my life...
Thanks, now I understand better some of the things you have said. I do appreciate micro is a tough area, my wife never like working in micro, takes a certain type of detail mindset I think. She preferred work in hematology and had one stint at a University research hospital in virology. So sometimes she adds something to help when I am studying these issues.
Well, this all explains alot. I think I'll listen to the likes of Gerwyn more on the WPI's studies.
The posts regarding culturing, HERV's and all and XMRV have been moved to a new thread in the XMRV Research and Replication Forum here: http://www.forums.aboutmecfs.org/showthread.php?3917-XMRV-and-Culturing-HERV-s-and-more
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