Hoping that everyone can relax a little, here’s yesterday’s song that I couldn’t figure out how to post from my iPhone. We could use a little levity, I think.
When I started writing this blog, it was with a sense of astonishment that the physicians treating the patients, Lyme and CFS, didn’t seem to recognize that they had a new quiver for their arrows. The few that did were quickly censured, or swore a few patients to secrecy. I had been housebound, sometimes bedbound, for years and never expected to return to work, so I didn’t care who I pissed off. Anything was better than the isolation. The good thing about not caring was that I learned to write authentically.
During my 25 years in practice, I didn’t interface at all with the scientific community. Doctors only. I had no idea about the realities of this parallel universe that so impacts what clinical choices are open to us. I thought that the Science paper would be hailed as a great breakthough; scientists and doctors would come together, bringing different things to the table. The pace of progress would accelerate. If only that had happened!
The scientists that I’ve criticized by name were Coffin, Stoye and Racaniello. The first two put themselves out there very early on in a way that appeared designed to stop progress. They also have a long history of publishing things together that minimized the risk, so aren’t clean on the issue and their opinions shouldn’t carry much weight. Dr. Coffin also took it upon himself to try to limit treatment options, my pet peeve.
Professor Racaniello is a media figure, so fair game. I admit to being influenced by hurt feelings in his case, because I wrote to him when I started arv’s, in the midst of the first blush of excitement, wanting to have a discussion with him about the science and he shut me down, much the way Jason did. And to me, the tee-shirt still seems over the top thoughtless, though I think now that he probably didn’t understand what he was doing. There are signs that he is growing, e.g. publishing Dave Tuller’s important piece on his blog.
I was angry at Dr. Singh when she published her negative paper, for the reasons I expressed back then, but essentially the same thing again; scientists trying to call the clinical shots, though in this case I understand that she felt that her former paper was too strongly in favor. I sent her testimonials from patients improving on arv’s at that time. My understanding from Dr. Enlander is that she is back on the case. I thought her a lovely person when I met her and I am glad she is again working on our behalf. The Mt. Sinai initiative is very exciting. It is difficult not to fantasize about Dr.’s Shadt and Lipkin putting their heads together.
And Jason. Sorry Jason, I didn’t mean to hurt your feelings. I hope you learned something from our scuffle. No hard feelings on my end.
I hope I haven’t forgotten anyone. A virtual olive branch offered to all, even those most aghast at my choices…
Believe it or not, there are scientists that share with me, and I protect their privacy. I swear I’ll disavow knowledge of our friendship to my dying day if that’s what any scientist willing to share wants. At risk of scaring off the people we want to be here, there is a tracker on the blog, that allows me to see the IP address, location and the name of the server that loads each blog page, as well as how many prior visits from that address. Institutional servers give the name of the institution. There are at least a dozen readers at the NCI and another dozen who connect from NIH servers in a few different cities. A couple at the CDC in Atlanta. Readers at many universities and teaching hospitals, including a few at Columbia and Harvard. Cancer institutes around the country. Only a few of these people participate in the discussion. This is a potentially powerful thing. When I worked for the WPI, one of things I most wanted to do was establish lines of communication between physicians and scientists with all kinds of points of view. There is little to be learned from consensus when the truth isn’t even on the table. If there is a way to salvage some part of that dream, I’d like to.
Many of the scientists came to read about Dr. Mikovits’ travails, but I am asking them to think about the science with us. In particular, I’d like to know your reactions to Dr. Snyderman’s data. Please adopt a handle and share with us. Your secret is safe with me. I ask you for the sake of the patients that you are now beginning to know, be bold. I realize that you are constrained by the knowledge that a patient community can do what we did, but there are 17 million patients worldwide in the ME/CFS cohort alone, who need creative thinking from you. There is every indication that our disease is reversible until it is very advanced. The unclaimed talent in the patient community is staggering, if only the disease could be calmed, not even cured. Look at me. I am productive after years of being almost unable to care for myself, let alone anyone else.
I would like to put an end to the discussion about the lab science in the Science paper, the WPI, VIP Dx. Nobody knows the answers, including the protagonists. I certainly have no basis for evaluating any of it. I defer to the scientific community to figure it out; discussing it here is not productive. At this point, it is non-contributory and boring. Take it someplace else. This is also not the place to argue about whether Dr. Mikovits should be canonized or not, though she is my friend, and I am very sorry for what is happening to her. But from a clinical point of view it is irrelevant. This blog is about developing a model for treatment and how to best live with the disease.
Thank you to our mold warriors for giving it another shot here, and for keeping it appropriate this time. I for one, think that your experiences of improvement without medication are significant. I also understand why you feel the need to tell others in the hope of reducing their suffering, as well as your frustration when you feel you aren’t being heard. I have been interested in Ritchie Shoemaker’s pioneering work, since 2002 when we shared a couple of patients with Ciguatera poisoning.
And a big thank you to In Vitro Infidelium for the considered comment this morning. No invective or politics at all. Just a reply about the scientific discussion at hand. It was a breath of fresh air. Thank you for the excellent paper by Voisset et al. The quote you lifted in your comment is precisely the point. Although it clearly isn’t a simple, straight forward infection, there is epidemiological evidence that it is an emerging disease of very great proportions, not a stable situation. AIDS isn’t simple and straightforward either, without a test, in that infected people can remain apparently healthy for a long time, or even indefinitely. Only a small percentage of people with HTLV ever become clinically ill from it. Inbred sick mice don’t get sick from their MLV’s, but wild mice and some other rodents can. All I am asking for is that it be studied, not shut down if this attempt fails. Also, that our therapeutic options not be limited by how slow the science will be to unfold, even in a best case scenario in which Dr. Lipkin finds something.
My hat is off to Dr. Lipkin. His finely worded communication to the patient community brought tears to my eyes. The only thing I would take exception with at all was the use of the word definitive. If by some quirk of fate, this study is completely negative, we beg you, use those specimens to take the next step.
Today’s song: Learning to Fly: by Tom Petty
>"The Ruscetti's and Mikvoits never agreed to a retraction. "
The Science piece clearly states that Ruscetti was trying to coordinate a retraction. Therefore, he was in favor of some kind of retraction, even partial, unless of course you wish to claim that the Science piece is lying about this. Mikovits was obviously the only one holding out, which isn't much of a surprise these days.
>Looking in blood is not justified when gamma retroviruses are always near impossible to be found in blood. Hence why very few assays or assays that are very specific are needed. If you want to know how many people are really infected tissue studies need to be undertaken.
If MRVs behave like MLVs then the likely place to find them is inside B1 cells.
Unless the patient has some kind of infection/stress/inflammation you wont find these in the blood in any significant numbers. Somewhere less than 3% of peripheral blood B cells will be B1 cells.
>"The Science piece clearly states that Ruscetti was trying to coordinate a retraction. Therefore, he was in favor of some kind of retraction, even partial, unless of course you wish to claim that the Science piece is lying about this. Mikovits was obviously the only one holding out, which isn't much of a surprise these days."
The article is wrong as the Ruscetti's did not want the paper retracted. Ruscetti had explained to them that the viruses are polytropic.
>"The article is wrong as the Ruscetti's did not want the paper retracted. Ruscetti had explained to them that the viruses are polytropic."
How would you know, where's the evidence for this? Is your name Ruscetti?
>The civility of the dialog is appreciated AND so are the repetitive comments.
Thank you, Anon 7:16 & 8:46 for being willing to repeat the truth as many times as necessary.
If you allow lies to be expressed without challenging them, the falsehoods are accepted as truth.
Remember…
WMD's, WMD's, WMD's
Mushroom cloud, Mushroom cloud, Mushroom cloud
repeated regularly on the news before we invaded Iraq? And now in regard to Iran.
It's one trick of many in their propaganda bag of tricks, but it's not going to work here.
>I would like to know the erythrocyte sedimentation rate of the patients in the study.
This was the very first abnormality to show up in the 1985 Tahoe Mystery Illness (later renamed Raggedy Ann Disease, and then CFS) since this aberrant finding showed up on a standard blood test.
Dr Peterson told me, "Doctors are taught that 'The lower, the better', but a ZERO sed rate is too low… this is an abnormality!"
The odd thing about the misperception of CFS being from EBV is that this cannot possibly be attributed to the CDC's Holmes CFS definition, for this is clearly stated right up front as the reason why CEBV Syndrome had to be abandoned.
—————————————–
http://www.nightingale.ca/documents/GoteborgConference.pdf
Göteborg and Malmo, Sweden
M.E. Conferences: November 2009
Byron M. Hyde, M.D.
1B: PERCEPTION OF DISEASE BY DEFINITION: There is a bigger question than
the problems of defining M.E. and CFS that appears to have been totally missed by the
M.E. and CFS community. That question is “What is the average physician and
psychiatrist’s perception of what constitutes a CFS patient?” We all know that the
majority of non-M.E./CFS physicians and many patients still believe that CFS is caused
by Epstein Barr Virus although Holmes found in his 1987 paper that the 1984 Lake
Tahoe definition was not caused by EBV. Many newspapers still refer to CFS as EBV
disease.
Most chronic M.E. patients have 0 or low Sed Rates. This has caused some physicians to
state that there is no inflammation (or –itis), in M.E.
>"How would you know, where's the evidence for this? Is your name Ruscetti?"
He has said the viruses cannot possibly contamination and it is well known he tried to explain to the editors the viruses are polytropic. They know this because they sequenced the env region of the viruses again and put them in the genbank. They are PMRVs. He has been as clear as he can be. If this was HIV it is 1983 he said. You act now, not 10 years from now when god knows how far gone the viruses have spread.
Let me see if rewording it helps.
If you had Hepatitis C and then several labs tested you for Hep A and B, do you think you would be happy being told you are not infected with Hep C and that Hep C doesn't exist?
@Anon 11:03
Yes, that is exactly the game we are in. You can see the pattens so easily now. Notice how many times they have been trying to isolate Mikovits from all the other researchers and mentioning Wakefiled in as many articles as possible. Not that Wakefield is necessarily the Wakefield they have sold him to the public as. Global warming, phone masts, mobile phones, all the same. We all live under oppressive regimes because democracy is only the best of terrible forms of Government.
I don't particularly like knowing that the human race is colluding in a course of action that could lead to the end of the species. How can we survive if they are accidentally creating viruses that can infect humans without having the tools to detect them. It's one thing for evolution to adjust to naturally occurring viruses, but not multiple new ones that will recombinant and are designed to be in humans.
They should face up to it and deal with the problem. I don't believe most of them will manage to go through life as if this doesn't affect them. Pretending they are not moved by the suffering of others or that their families will remain safe won't last. The viruses cannot hide.
>The NIH study is only about retroviruses, so erythrocyte sedimentation rate won't be measured. It is also not the only test used for evidence of inflammation.
>There is a virologist at the University of Pittsburgh whom I contacted because the scientist had identified MLRVs in prostate disease. The scientist emailed me that fellow virologists had advised not to do this research and that no journal would be willing to publish positive results. Another prominent researcher who had early positive results with MLRVs confided to me that post-doc fellows were taken off any project related to MLRVs so as to protect their careers.
I find this very frightening for us, meaning people that probably have MLRV related disease. There are a only a very few brave scientists left like Dr. Lipkin willing to continue research to identify a virus.
Michael Snyderman, MD
>If a retrovirus fails to result in a zero ESD, then regardless of what it may cause, a retrovirus would still fail to explain the premier easily-testable blood abnormality in the illness that was called CFS.
(And, "ME")
>Erik,
Not all ME patients have low sed rates. There are patients with normal sed rates who unquestionably have the disease, no matter which doctor you ask, or which case definition you use. There is no marker for the disease, even if you look at only severe patients. That is precisely the problem. Until there is a specific test for what we have, we are stuck with case definitions. Absolutes never work with this illness. For anything one comes up with, there are patients for whom it simply isn't true, and not because they don't have "it".
Jamie
>"Not everyone has that" is sufficient reason to ignore the abnormalities in those that DO?
Shouldn't they at least try find out what it means?
>Jamie Deckoff-Jones MD said…
Absolutely. It's just that I don't like exclusionary criteria. It is very damaging to those excluded. I understand that we are still in the dark ages, trying to prove it is a serious illness, but to deny that the early stages are the same disease is to do a disservice to millions of people who are just starting to get sick.
Jamie
>http://niceguidelines.blogspot.com/2011/08/unusually-low-esr-in-only-five-diseases.html
An unusually low sedimentation rate of 3-mm/hr is common in M.E. ESR rates as low as 0 have been documented in M.E. patients, and levels of 1 and 2 are very common.
Dr Byron Hyde reported in 1989 that, "To my knowledge, there are only five diseases that have a pathological low sedimentation level: Myalgic Encephalomyelitis, sickle-cell anemia, hereditary sperocytosis, hyper-gammaglobulinemia and hyper-fibrogenemia.’
>@anon at 10:16 am New Year's Day
Assuming you are asking if studying retroviruses in a lab is dangerous, here the short answer. Yes, very dangerous, and I suspect this means we are likely to have many humans infected. Scientists who want to deny this are either living in la la land or very evil people. (Sorry to bring religious perspective into science, but I can't help myself.)
Retroviruses in labs are a biohazard. Here is the link and a short portion of the research.
(http://bit.ly/oONQ5N)
Human cultures derived after mouse xenografting frequently contain and release highly infectious xenotropic MLV viruses. Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially biohazardous human-tropic mouse viruses and their horizontal spread to other cultures.
>@ early bird anon at 6:45 am
Spect scan to rule out other diseases…hum, how about thyroid, Lyme, intracranial hypotension…you name it. There are many diseases that cannot be ruled out by spect scans yet these diseases might look like CFS. And any of the patients could have BOTH CFS and whatever. We simply do not have a definitive way to diagnose CFS, or FMS for that matter. If we can document retroviral involvement and IF we can improve the borrelia, babesia, bartonella and ehrlichia tests we might start to have some real disease groups. Or maybe not, but we have to start with the development of valid tests. I don't think that will be abnormal spect scans or, for that matter, sed rates which change in various diseases.
At the risk of getting tedious, IF there is an underlying retrovirus suppressing or altering immune system and hormonal system balance we could LOOK LIKE various disease states. Isn't that what we would see in HIV AIDS if we had never discovered HIV? And without a test for HIV it would continue to be total confusion.
>I beg to differ on lacking a definitive way to diagnose CFS.
Dr Peterson does this (very expensively) by ruling out a vast number of other illnesses, then places that "entity" in the context of ALL the immune abnormalities which embody the evidence-base which caused the CDC to create an "operational concept" to research it.
(Described in Osler's Web AND by Dr Hyde)
At the very least, whatever Dr Peterson diagnoses would be "commensurate" with the entity which received the term.
Yet Dr Peterson can go one better than that.
He still has a great number of the original cohort in his practice. There is no possible way for this original cohort to NOT be "CFS", for whatever this illness is.. it's the one which engendered the syndrome.
>Erik,
Beg to differ. It is still a diagnosis of exclusion. There is no testing that you could show Dr. Peterson that would allow him to diagnose definitively without history and his ability to recognize the symphony from hearing the notes. Any competent doctor who gave a damn could do that, in a sane world. We need a test that is idiot proof.
Jamie
>What a shame that we don't live in a sane world.
I don't think there ever will be any such test.
I'll let Dr Peterson speak for himself.
http://www.rme.nu/forskning-provtagning-och-behandling-av-mecfs-dr-dan-peterson-stockholm-6-okt-2011
>That was BAD, Erik. But good sense of humor. Got a link for those of us who only speak English, French, Latin and Greek?
>Erik@12;49pm that was a joke too eh. Why do you support CDC erasing ME and lumping us with CFS?
>Is CFS genetic? There seems to be more likelihood of getting it if you are a blood relative of a person who has it, but living in the same house but not a blood relative also increases your chances of getting CFS. Looks like it is contagious, but with other genetic or hormonal issues causing it to show up. Paula Carnes
http://www.cfids-cab.org/rc/Njoku-2.pdf
and this comment from my summary (Good Enough to Take to the Bedside) of work by Rosemary Underhill:
http://www.wicfs-me.org/Pdf%20Files/AACFS%202004%20Report_2.pdf
The next study presented by Rosemary Underhill, MB, presented a pilot study of the role of heredity and environment in CFS. A study involving 219 CFS patients revealed that 20.5% of the patients had family members with CFS. About twice as many were blood relatives. Secondary cases of CFS occurring in the genetically unrelated household members of CFS patients indicates that an infectious agent which can cause CFS may persist in at least some CFS patients and can be shed into the environment. The increased prevalence of CFS in non-household genetic relatives indicates that genetic factors may also be involved in a subgroup of patients.
>Re: patient selection for the 'Lipkin Study' as mentioned above.
There have now been at least two patients come forward on the forums – I see another this morning who do seem to imply that the selection and testing has been quite thorough, but of course (and as I have said above), we do not know for definite what criteria used have been used.
As Lo, Alter, Mikovits and Ruscetti – to name but a few – are actively engaged in this study I think it is reasonable to assume that they approve the selection process and indeed the freedoms they have been afforded (again) to test the samples provided.
To reiterate, I do not believe Lipkin or the sponsors of this study are obligated to announce the exact methods etc. prior to publication. V – have you contacted NIAIDS or Lipkin himself to ask? I am still waiting to hear from the former though I didn't write long before the holidays.
N.B. that was me at 5.03/5.14/5.37am yesterday – sorry I couldn't figure out how to register my name.
>Re: Lo et al retraction
Racaniello from Retraction Watch:
' [BWG] The Lo laboratory did not detect any positives by PCR, using the same nested assay that they had previously reported in their PNAS paper. The samples tested included 5 specimens that were positive in the Lo-Alter study. In other words, Lo-Alter could not detect retroviruses in the same samples in which they had previously detected them.'
http://retractionwatch.wordpress.com/2011/12/26/another-shoe-drops-as-authors-retract-pnas-chronic-fatigue-syndrome-virus-paper/
In their retraction notice Lo states:
'Although a more definitive, National Institute of Allergy and Infectious Diseases (NIAID)–sponsored, coded panel of samples from 150 well-characterized and geographically diverse CFS patients and controls is being assembled for further study, in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the association of murine gamma retroviruses with CFS has not withstood the test of time or of independent verification and that this association is now tenuous. Therefore, we retract the conclusions in our article'
The retraction itself also stated (amongst other things):
'Only one (1) of many laboratories has found a similar association between polytropic murine leukemia viruses (pMLV) and CFS and a careful study of 100 CFS patients (2), as well as a coded panel recently constructed by the National Heart, Lung, and Blood Institute (NHLBI) (3), have found no evidence for either xenotropic murine leukemia virus-related virus (XMRV) or pMLVs in CFS patient samples.'
Also important:
'Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.'
And they would appear to have accepted the findings of this paper also:
Katzourakis A, Hué S, Kellam P, Towers GJ (2011) Phylogenetic analysis of murine leukemia virus sequences from longitudinally sampled chronic fatigue syndrome patients suggests PCR contamination rather than viral evolution. J Virol 85: 10909–10913
http://www.pnas.org/cgi/doi/10.1073/pnas.1119641109
(1) That laboratory of course was Hanson's whose quote I provided above, and who is unable to determine if her results were indeed contamination and is also waiting the outcome of the 'Lipkin Study'.
Tuller reported in the NYT:
'Randy Schekman, the former editor in chief of PNAS, said the journal had been “encouraging” the authors to reconsider their findings in light of subsequent research…'
http://www.nytimes.com/2011/12/27/health/research/scholars-retract-another-study-linking-xmrv-to-chronic-fatigue-syndrome.html?_r=2
Of course you can make – and indeed have made – what you will from that 'encouragement', of course I don't and indeed I believe it was reported in WSJ that when they had reconsidered their paper they realised it amounted to a retraction:
http://blogs.wsj.com/health/2011/12/27/second-high-profile-xmrv-related-paper-retracted/
Now, I could be wrong – so do please provide an alternative – but the only place I have seen 'They said they remained confident in the integrity of their original work' was in the initial report from MedPage:
http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/30372 and it wasn't a quote it was an summation of the following from the retraction notice:
'Although our published findings were reproducible in our laboratory and while there has been no evidence of contamination using sensitive mouse mitochondrial DNA or IAP assays or in testing coded panels, we have the following concerns….'
But as I said I could be wrong and there could be a quote out there that I haven't read.
>@Paula Carnes
The SPECT scan would not be to rule out other diseases but to prove those included in a study have a neurological disease. Once all other causes are ruled and out and provided they fit the criteria then they should also be tested using a SPECT scan to see if they do have such signs. These are the patients that would be indicated to have a HGRV infection. Otherwise we continue to test humans on the basis of one symptom alone. Such an approach would not even have taken MS out of the fatigue category.
>I think we have confirmation now that the NGS study from Lipkin will indeed use those samples from the XMRV/MLV research as part of the CFS Initiative:
'In 2012: Samples collected for the XMRV/MLV “Lipkin” study will be evaluated by Lipkin’s team at Columbia’s Center for Infection and Immunity will be tested for known and novel pathogens using high-throughput molecular techniques.'
Again, details are sketchy.
Also something happening at NIH Clinical Centre involving patients who tested 'positive' for XMRV – don't know what that's about:
http://www.research1st.com/2012/01/01/2012-research/
>@Jack
We know nothing about the criteria for the NIH study. Patients being tested and having their blood drawn may not even be included in the final study and the clinicians providing patients are all known to select based on entirely different criteria. Some only select based on a person having fatigue.
" reasonable to assume that they approve the selection process"
They have agreed to take part, it doesn't mean they like the selection process. It doesn't mean the selection process won't be changed. When funding is being cut off to prevent research, there is little to do then take part.
"I do not believe Lipkin or the sponsors of this study are obligated to announce the exact methods etc."
There should be no benefit to keeping this a secret. Patients are entitled to know after the shenanigans that have taken place so far. If any of the labs are allowed to use VP62, they will be deliberately looking for a laboratory artefact and not the wild-type PMRVs that all 4 labs identified.
"The Lo laboratory did not detect any positives by PCR, using the same nested assay that they had previously reported in their PNAS paper. The samples tested included 5 specimens that were positive in the Lo-Alter study. In other words, Lo-Alter could not detect retroviruses in the same samples in which they had previously detected them.'"
That nested PCR detected no positive patients in the Lo et al paper. In other words the same assay that didn't find 5 patients positive in one study, didn't in another. The assay that did find those 5 positive was not used in the blood working group.
>", in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the association of murine gamma retroviruses with CFS has not withstood the test of time or of independent verification and that this association is now tenuous. Therefore, we retract the conclusions in our article'"
They have published no other data. If you now want to include other data than HGRVs have been shown to cause ME.
'Only one (1) of many laboratories has found a similar association between polytropic murine leukemia viruses (pMLV) and CFS and a careful study of 100 CFS patients (2), as well as a coded panel recently constructed by the National Heart, Lung, and Blood Institute (NHLBI) (3), have found no evidence for either xenotropic murine leukemia virus-related virus (XMRV) or pMLVs in CFS patient samples.'
Not true. Others have looked for the gag region of the virus, which is polytropic. They have reported this finding at conferences. They include Hanson, Cabrera, Beiger, De Meirlier, etc. It wasn't until the partial retraction of Silvermans work and the new genbank sequences that others knew Mikovits and Ruscetti had found polytropic MRVs. Other labs have only been looking for VP62 which is an XMRV. The NHLBI study only used assays optimised to VP62. Again, not using the proven assay from Lo et al.
"'Our attempts, through collaborations, to demonstrate antibody in affected patients, to isolate the virus by culture, or to show integration sites in the human genome have failed to support the initial findings.'"
Again this is not published, cannot be analysed and shows no evidence of replicating proven methodology. So do we now accept all the positive studies that are being prevented from being published?
"And they would appear to have accepted the findings of this paper also:"
Katzourakis et al applied a model of HIV to gamma retrovirus. It's laughable. They should have applied a model of HTLV another retrovirus with little sequence diversity. Gammas, delta's and Beta retroviruses preferentially propagate through clonal expansion. Lo and Alter clearly don't accept it as they stand by the integrity of their data.
Hanson should not be waiting for any study if she is finding positives with one PCR assay, negatives with another PCR and positives replicating the proven serology assay. Here is a quote from a person attending the Ottawa conference.
"Then she did antibody tests developed by the WPI – which do not have the contamination problems of PCR – and she found that antibody tests for XMRV were positive in half her CFS patients and in about 15% of healthy controls. She emphasized that this did not mean they had been exposed to XMRV (she never found XMRV). She suggested that people with ME/CFS could have a retrovirus other than XMRV and urged more work in this area."
>"'Randy Schekman, the former editor in chief of PNAS, said the journal had been “encouraging” the authors to reconsider their findings in light of subsequent research…'"
"encouraged" – nice word for it. Journals are not there to re-write history. At this rate all the negative studies will have no reason to exist. They will all be retracted. How long until all ME papers are retracted Jack? What would stop them doing that now that evidence that is undisputed can be removed from the record by those with vested interests? Data is never removed from the record because it is data. To do so is an attempted to hide the data.
" indeed I believe it was reported in WSJ that when they had reconsidered their paper they realised it amounted to a retraction:"
The article states it was the editors who decided that. Lo is taking part in the NIH study. Why? If they use the assays that have never detected a positive patient as they did in the blood study what is the point? If they use a proven assay they must think the viruses are there, or why take part?
Lo and Alter and HHS employees. Nice to know who is in control of them. They have never found contamination, they have not replicated, no other lab has replicated, they have published no further work, but they have been "encouraged" to drop it. It is impossible to scientifically dispute a finding this way.
>Have a listen to TWiV: http://www.virology.ws/2012/01/01/twiv-164-six-steps-forward-four-steps-back/
It might help to hear this and other interpretations – then again you may well disagree with them too I suppose. Free world.
>@Jack
Lipkin is not doing any NGS for the NIH multi lab study. He is not doing any of the testing for that study.
'In 2012: Samples collected for the XMRV/MLV “Lipkin” study will be evaluated by Lipkin’s team at Columbia’s Center for Infection and Immunity will be tested for known and novel pathogens using high-throughput molecular techniques.'
Do you still think people buy a ready made test and just use it? Immediately it will matter whether for this study he is using sequence independent deep sequencing and it will matter what level of coverage he uses. No study is definitive.
>@Jack
There is nothing to be gained from listening to TWiV. If you have a point to raise then name it.
>They were actually agreeing with you I believe about the need in this case i.e. 'Lipkins Study' to have released details particularly of the selection of patients. Though such releases are perhaps still not an obligation. But if you don't want to listen then that is your prerogative of course.
>Oh sorry. No you banana the NGS is being done post-'Lipkin Study' as part of another study using the same patient samples – as per the extract I gave. Do try and keep up. Details are scarce but some are now being released…
>@Jack/Russell
Patients still have a right to know and currently there is no guarantee they are not studying fatigued people. The NGS is still not a part of the NIH study and patient criteria is still a problem.
Details should be released in full including who is responsible for blinding, coding and decoding.
>Well, unfortunately, I am totally not joking about this being an insane world.
The entire CFS debacle has been PURE insanity.
Nor do I think that any unequivocal and foolproof test can be devised, for there will always be fools who would muck it up, somehow.
I promised myself that I would tell the truth about the weird flue that the CDC called "CFS".
The way the flu-like illness moved was exactly as Dr Hyde describes… which strongly indicates that "CFS" is NOT as OTHERS would have it.
Regardless of a retroviral involvement, the theory still has to fit ALL the facts.
————————————
http://www.nightingale.ca/documents/GoteborgConference.pdf
Göteborg and Malmo, Sweden
M.E. Conferences: November 2009
Byron M. Hyde, M.D.
3: The Whittemore Peterson Institute CFS – Retrovirus
Announcement
The Cause of CFS is a Retrovirus: In 2009, Dr Peterson, is probably one of the nicest
and learned colleagues in the field of CFS, recently from the brand new, just opened,
multi-million dollar Whittemore Peterson Institute in Reno Nevada, announced
overwhelming evidence that the cause of M.E. or CFS, is XMRV retrovirus. The XMRV
mouse retrovirus occurred in 68% of the CFS patient’s blood samples and only 4% of
non-CFS patients. Pretty convincing!
This retrovirus theory comes with a history: It was first raised as a possibility by the gay
community at a symposium I attended in San Francisco in 1987 and again by Florida
based researcher Dr DeFreitas in the early 1990s. Dr DeFreitas discussed this retrovirus
theory in our textbook, The Clinical and Scientific Basis of M.E. /CFS.
At the very least, this retrovirus discovery is great free advertising for the Whittemore
Peterson Institute. It will possibly bring them in many millions of dollars from, patients
willing to be separated from their assets, generous charities and governments before the
retrovirus theory is once again thrown into the garbage bin. I should add that incubation
period of XMRV is up to 21 days which makes it impossible to cause an epidemic illness.
>With regard to the criteria.
I think we're talking about two different things here, and so we need to be clear.
The first is whether we can come up with test panel results that would allow a primary care physician to state confidently that someone with exhaustion actually does have ME/CFS.
The second is whether we can come up with test panel results that would allow a primary care physician to state confidently that someone with exhaustion does NOT have ME/CFS.
Focusing just on the first goal, without worrying about the second one for the moment, seems an appropriate step at this point.
I interact most frequently with extremely ill patients (e.g. those who are bedridden or housebound). I have yet to see any who do not have a very specific group of lab results: low NKC function, elevated Rnase-L and LMW Rnase-L, skewed cytokine profile, low suppressor T cells (and thus abnormal suppressor/helper cell ratio), reactivated EBV and HHV6 (when not entirely negative for those viruses), abnormal methylation pathways test.
When these patients check, they nearly always have missing fingerprints and crimson crescents. Sed rate very frequently is low.
Here, Kenny de Meirleir lists some other tests that I've not seen as often but that also seem associated with the illness: a) elastase expression assay (a measure of inflammation); b) CD57+/CD3- Absolute Cell Count (a subset of NKC's); 3) soluble CD14 (a substance involved in the recognition of bacteria in the body); and 4) C4a.
http://www.redlabs.be/red-labs/our-tests/immune-function-assays.php
Figuring out which criteria are specific to the severe form of this illness is my point in proposing a study of just bedridden patients. Unless I am totally wrong, this will provide clear evidence that people who are at that level of illness DO have specific biomarkers that can allow them to be objectively diagnosed.
If we could get that sort of finding into the literature, the whole game would change. No one would be able to make any sort of case that this is a psychological illness any more, if particularly ill sufferers all have the same specific medical abnormalities. (To my understanding, the likelihood that someone who was healthy would come up with this particular set of abnormalities is zero, and it doesn't correspond to other known diseases either.)
Thus, this would allow a huge step forward into getting the illness recognized as legitimate, and allowing those people who suffer from the most severe form of it to get benefits.
However, doing this sort of study would NOT mean that someone who does not qualify for a diagnosis based on these markers does not have the illness. It still would be possible that they have a less severe form, are still at the early stages, or have an atypical case.
Anecdotally, if folks know of severely ill or bedridden ME/CFS patients who do not present with any of the markers listed above, I'd like to hear about that in the hope of starting a discussion.
>The only additional detail I found after listening to TWiV was here:
http://projectreporter.nih.gov/project_info_description.cfm?aid=8263583&icde=10870370
The XMRV/MLV study is under 'sub projects' and budgeted at $1.043m.
Lots of love Jack/Russell/Firestormm x
>Steve and/or V et al :)
'Patients still have a right to know and currently there is no guarantee they are not studying fatigued people. The NGS is still not a part of the NIH study and patient criteria is still a problem.
Details should be released in full including who is responsible for blinding, coding and decoding.'
I don't disagree. As it is an NIH grant then more detail should perhaps have been released. But – and do let me know if I am wrong here – they are clearly under no obligation to do this. Else surely they would have done by now. Anyway, like I said if you listen to TWiV the panel would also agree with you – well on this at least ;)
>My understanding is that doctors who treat CFS patients are the ones who have selected them for blood testing for the current study which at last mention had 123 samples of CFS sufferers and
was aiming for 150.
I agree that diagnosing by exclusion is not a great idea. There seem to be many biomarkers being found for CFS. Many use exercise and then testing for genetic expression, brain changes via an EEG, etc.
This is a problem for those of us who can't exercise, can't travel to appointments, and have low stamina and energy.
If there were a blood test (or other objective test), diagnosis would be much easier and less wear and tear on CFS sufferers.
Someone on the CFS blogosphere seems to have suffered a bad relapse after a few days of testing which included exercises.
>Staci Stevens (of the Pacific Fatigue Study Lab) states forthrightly that patients can relapse for long periods of time (sometimes months) after getting the exercise stress test. She says that these patients often still express gratitude for receiving the proof that their illness is "real," though.
Of course, it's hard to separate out here how much of these relapses are related to the exercise itself vs. to the effort expended getting to Stockton vs. possible environmental exposures encountered during the trip vs. random declines. Not everyone relapses for an extended period of time, and it's unclear what makes the difference.
Regardless, forcing people to do _anything_ that would give them a relapse in order to get evidence that they have a "real disease" is unfair. That's one reason why we need blood tests (and government funding to get people to come to the homes of those who are bedridden to draw the blood).
>@anon 5:21 am
But, but, but…what about passing out on a tilt table test? How about nystagmus? How about simply not being able to walk a straight line across the doctor's office? I've had all of the above with completely normal spect scans for years. What about constant enlarged lymph nodes for months to years? Yes, I know that is not neurological, but it fits the original list of symptoms for getting a label of CFS. I wish we had a simple test that either put you in or out of the CFS category. Maybe in my lifetime? I don't know. I am getting old.
>What needs investigating is why any retrovirologist would think that one genetic sequence could be representative of a retrovirus population. This would have been unique in the history of retroviruses. Why did they test for HIV DNA when it took the best part of 25 years for a commercial test for HIV to be reliable enough to be granted a liscence. Why did they then use PCR cycling conditions which could only detect one nucleotide sequence and only that sequence. Why has no one attempted to repeat the Lombardi experiments or the Lo experiments.
>" I've had all of the above with completely normal spect scans for years."
For research purposes it would allow them to uncover abnormalities that are present because they would be studying the sickest patients, i.e. those with abnormal SPECT scans. FMRI would also work. It is well known that they are found and are ignored simply because the doctor is trained to dismiss when they are found in ME. It doesn't matter to me whether I end up in the study or in the group that are then defined by the abnormality because it will move things forward.
It is catch 22 to require abnormalities be found in all patients, when all patients are defined by a symptom that all people have.
>@Jack Russell
The link to the NIH funding details does not even begin to explain how the study is designed.
"they are clearly under no obligation to do this. "
Why ever not?
Lets see if one important piece of information can be explained to you. Detecting a synthetic plasmid called VP62 is not the same as the conditions needed to detect a wild-type virus. The conditions do have to be exact for many viruses, which makes replication incredibly important. This link illustrates that very well. Under "Annealing Temperature and Primer Design".
"Plasmid and biopsy sample DNA templates were amplified at different annealing temperatures as shown: note that while plasmid is amplified from 37 to 55oC, HPV DNA is only specifically amplified at 50oC."
http://www.mcb.uct.ac.za/Manual/pcroptim.htm#Annealing
>There needs to be a simple blood or other objective test developed. Although the exercise stress test or a test of post-exertional genetic expression change or changes in the brain, some people just can't do this test.
Some people can't leave home, can't bathe themselves, can't go up or down stairs. How could they even take a car trip somewhere? Or endure any exercise?
And some people who are partially mobile can't travel for any distance and can't exercise for long anyway.
So even though finding all these objective findings and biomarkers still won't help to diagnose a lot of people with CFS if it's reliant on travel and exercise. Then, on some tests, re-exercising a second day. Some people would be too ill from the first exercise to repeat it. (This disease does get worse after exercising, after all.)
>The research and diagnoses need separating. If you always include everyone but those who cannot leave their homes, no bio markers will ever be accepted for diagnosis. You have to find a way to admit very sick people into studies, though this is likely to always miss the really ill, but using objective measures. Subjective self reports have no scientific basis and will never achieve anything for patients. If you keep insisting people are missed out, then what disease are you diagnosing? Research must be the priority. Even now when vested interests have reduced everything to one subjective symptom it can take years to get a diagnosis, but a few years of solid criteria applied to those selected for research would get bio markers through. Some of those bio markers will have already been identified, they are not used only because Wesselly school researchers and their supporters can put anyone into their studies, making the biomarkers disappear.
>@Michael Snyderman, MD
"There is a virologist at the University of Pittsburgh whom I contacted because the scientist had identified MLRVs in prostate disease. The scientist emailed me that fellow virologists had advised not to do this research and that no journal would be willing to publish positive results. Another prominent researcher who had early positive results with MLRVs confided to me that post-doc fellows were taken off any project related to MLRVs so as to protect their careers."
This is so chilling. Humanity at its best, hey.
>'The link to the NIH funding details does not even begin to explain how the study is designed.
"they are clearly under no obligation to do this. "
Why ever not?'
It doesn't no. And that is frustrating. That they are under no obligation to do this is my assumption based on the fact that they haven't and neither – but again, again, do please correct me – have other studies funded by NIH (although at the point of application there is usually more information granted – but this was indeed a 'special' case by all accounts). And that link did confirm the funding allocated $1.043m I believe.
You make another point:
'Lets see if one important piece of information can be explained to you. Detecting a synthetic plasmid called VP62 is not the same as the conditions needed to detect a wild-type virus. The conditions do have to be exact for many viruses, which makes replication incredibly important.'
The thing is you are assuming that they 'found' something other than a contaminating XMRV/VP62 and also repeating this meme about how that was all 'they' ever looked for or were capable of looking for. And I am afraid I don't agree. Those sequences? All were effectively the same. All represented contamination. No evidence of a human pathogen. And the burden of proof is on the authors – is it not? I mean do please correct me on this because I am – clearly – not a scientist.
This was always about the claims made in Lombardi – and to a lesser extent Lo – that 'XMRV' was found in human blood. It was about the paper(s) themselves but the authors were unable to 'find' was it was they 'found' when their samples were blinded. There conclusions were erroneous – they didn't stand up – even to themselves.
The XMRV/MLV study of Lipkin's will enable those same authors to apply their methodologies to 'find' what it was they think they 'found' in – and even outside of those papers – yet again.
Any other retroviral association with my condition will require new research and new publications. It isn't the 'end' for such associations – if indeed they can be established – but it is the second (and much larger and probably more rigorously controlled) chance to prove/disprove the XMRV/MLV hypothesis tentatively established by the authors of Lombardi and Lo and yes even Hanson. Although it should of course be noted that not only have those papers been retracted – but that also not all the original authors are participating in this Lipkin venture.
In terms of new research post-Lipkin into XMRV/MLV associations specifically I would imagine that funding would be hard to come by and perhaps this is what Dr Snyderman's contact was referring to? Or perhaps it is an impression that after the XMRV story in the last 2 years – funding bodies are – I don't know – 'nervous' 'sceptical'? I mean don't you have to have some evidence before applying for funding? Maybe Lipkin's work on this will indeed spawn new avenues of retroviral work?
>We were talking above – or I was – about the 'integrity' and reasons given/interpretations for the Lo et al. retraction. There is another interpretation of this of course and it was raised as well on TWiV:
'…the statements that they are making [in the Lo retraction] are just emphasising the point that this was not anybody’s fault. There are people who’s careers are riding on this. Retracting a paper is a horrible thing to have to do I’m sure. So they’re making the point that you know, nobody faked anything, we don’t have any evidence that anything was messed with, we just don’t have enough sample to get other people to confirm this, we can’t confirm it and we didn’t find contamination but we can’t be sure and so we’re pulling out of the conclusions – we don’t believe this anymore…'
Of course it would be nice to hear specifically from Lo and Alter, just as it would from other authors connected to all of this who seem to refrain from interviews. I don't know but maybe Ruscetti, Lombardi, more from Hanson perhaps… Maybe someone will one day write a feature about all of this and get some decent input from the 'players'? It would make interesting reading I am sure.