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
>I have read a lot on this blog that is dumb
the only way of disproving the results of the lombardi experiments is to repeat the lombardi experiments and see whether the results were the same or not
what we have seen is people repeating a different protocol a dozen times and then stating that the gammaretrovirus does not exist. That might be the idea of science within the retrovirology club but it is total nonsence
we then have the spectacle of a guy that qualified in 1956 in an entirely different field forcibly retracting a paper containing experiments that no one has attempted to repeat
from an advocacy perspective that cannot be repeated too often.To accept this travesty is dumb
It is also dumb to accept the words of plausible establishment spokesmen as if they were in any sense true
I know judy does not know everything but she does know that the core of the scientific method is reproducibility
If an experiment is repeated by independent workers and the results are the same then the work is deemed reproducible and hence validated.
At no time in the history of science has any paper containing experiments which have never been repeated been retracted
A blogger who allows people who very plausibly make absurd claims such as being able to induce an antibody response by spikin blood samples with viral antigens is dumb especially when such a claim libels judy
repeating an experiment means leaving all the independent variables involved in the original experiment unchanged and not as is the custom within a retrovirology clique changing them all
A clever blogger who is not familiar with the science would check facts before allowing establishment spokesmen to cause patients reading undue distress
There is a difference between an olive branch and a white flag
Not knowing the difference is dumb
acting as if born with a dominant niavety gene is also dumb
If lipkin is serious about finding MRvs then he will look in lymph nodes and tonsilluar tissue where MLV viruses exist in very high numbers
none of the people involved in the study have an assay capable of reliably detecting MRVs in blood. It is a simple matter to detect MLV viruses in lymphoid tissue .Mrvs have already been detected in lung tissue
Onmaloon et al and qui et al have already demonstrated that xmrv is only detectable in blood by PCR after the acute period but is thereafter readily detectable in tissues.In similar vein due to the infection of FDCs the antibody response disappears.This is typical of the behavior of the murine aids virus Lp-BM5.Readily detectable by PCR in lymphoid tissues but has yet to be detected by PCR in naturally infected mice
this needs to be continually pointed out otherwise all we will get from Lipkin is a false negative.should you require references for the points I,ve made they can be readily supplied
Retrovirologists have already been responsible for allowing one human retrovirus to create a plauge by denying its existence for thirty years
Accepting that a consensus within retrovirology is in any sense objective fact is totally dumb given their track record
>PS the authors did not conclude that the antibody reaction was XMRV specific but that it was specific to a MLV class gammaretrovirus. HERV-W has the most complete env sequence but that would have given a reaction in controls as well as people with ME
everyone is entitled to their own opinions but not to their own facts
>". I chose this as a juxtaposition against the anon poster who keeps making claims that are not based in real science "
I am basing my posts on science, I only asked where you have seen this. You then referenced a study that did not show that and all we then have is your word as a anonymous person. That is fair enough wouldn't you say?
"XMRV that originally came from 293T cells and a VP62 plasmid:"
For the umpteenth time you said you have seen virions to VP62. The link you give does not show virions to VP62 pumping out of 293T cells. Jamie ask him to explain the details of where the 293T cells are in that figure with virions of VP62 pumping out of it.
The entire issue this is to do with is the data from Lombardi et al. But the samples from that study have been independently tested as being free of the VP62 plasmid and they never had the VP62 plasmid in their labs. So how can you explain the results with VP62?
"Mouse made because the virus recombined in a mouse and infected the prostate cancer."
There is no evidence to prove that. We don't know when VP42 or the polytropic sequences were born. VP62 was a laboratory artefact that made from 3 patients are some filing by Silverman in 2006.
"So blood samples by themselves can't produce antibodies. Only B-cells found in lymph nodes are capable of such feats. However, they can be found in plasma, and this is what Mikovits tested."
You cannot spike a blood sample and get an immune response in the plasma. So you agree the serology results cannot be explained using VP62?
"This protein very similar to XMRV Env so they assumed that if patients had a signal then it would indeed be from XMRV."
The antibody to the SFFV will identify xenotropic and polytropic viruses.
"That Env protein is also similar to other Env proteins from other retroviruses. The possibility of cross-reactivity is definitely there. This is all the more possible when endogenous retrovirus litter the human genome (they make up close to 8% of our genome). Is it possible that in CFS patient sera, the SFFV env protein cross-reacted with something else we have, that we don't even know about? Yes. At least this is my opinion. In my opinion, it was wrong for authors to conclude that those anitbodies and XMRV antibodies since the experiment itself is not very specific."
What env protein or something else are you saying has cross reacted with this assay? If no published research can show it can react with anything but the SU protein of a MuLV, which at this time is true, then the findings cannot be refuted. The SFFV has never in decades of research ever been found to have cross reacted with any ERV or anything else. To say it is not specific after decades of research into that antibody is not logical. It lowers the probability that there is a cross reaction considerably and this is the cornerstone of science. The weight of probability. If it was a human ERV every sample would have been positive, so that is also illogical. A scientist would test this is the lab and produce a paper showing if anything could be found. There has been no such paper published.
>Mikovits had this to say on this very issue.
"Neither 22Rv1 nor any of the cell lines reported to be contaminated with XMRV or cell lines growing the VP62 infectious molecularly cloned virus was in the laboratories where the patient cells were isolated. This can also not in any way explain the Env antibodies demonstrated in patient plasma in Lombardi et al. The reactivity demonstrated to Spleen Focus Forming Virus (SFFV) Env was competed by the rat monoclonal antibody which detects all known xenotropic, polytropic and ecotropic MLVs. This again suggests that we have, in fact, detected more than one strain of human gamma retroviruses in these patient samples. Clearly data presented in Lombardi et al. where samples were PCR negative but Western blot positive, using the 7C10 antibody, further support the notion of a family of gammaretroviruses. These data must be appreciated as a complete body of evidence and not in the context of individual pieces, such as PCR amplification using primers designed to an arbitrary reference strain."
http://www.wpinstitute.org/news/docs/FinalreplytoScienceWPI.pdf
>Thank you, NotBilly,
You are a breath of fresh air.
Jamie
>@Jamie
Could you tell me where you see the use of 293T cells in the link NotBilly provided?
It's a honest question.
>Anon 2:26 PM,
The real answer is, I haven't looked. I am between patient calls and short on time. I couldn't care less about making NotBilly wrong. I have no intention of trying to second guess the lab science. I have never done the testing in question myself. I suspect, neither have you, so your persistence in trying to make real scientists wrong at their own game is completely bizarre to me. I shouldn't say this, but I don't have the ability to block a single reader without moderating the whole blog, and I am not going to do that, so we will persist. At least have the decency to sign something, so everyone can put your comments in context, and skip them if desired. You don't have to sign in to call yourself something, anything, identifiable.
I am interested in concepts, not minutia. I invite the scientists reading to engage the real questions with us, even speculate, as NotBilly did with Paula. I also invite you to ignore the crazies.
Jamie
>@Jamie
It isn't a trick question, there is no evidence of VP62 virions pumping out of 293T cells in that paper. I didn't make anyone make a claim about that paper that is not true and I cannot therefore be held responsible if you think that ruined their credibility. You are asking me to say nothing when others are wrong and asking me to pretend I am wrong. It is bizarre to persistently try to that when you haven't looked, but I accept you may not wish to look or it is not an area you are familiar with.
"I invite the scientists reading to engage the real questions with us, even speculate,"
That does require discussing the details. So far you are only assuming who is a scientist and putting a lot of faith in them, whilst at the time you are berating me for doing the same as they are. Why do I deserve no less respect.
Diego
>Diego,
In the first paragraph of the results section. It says that the virus was produced by transfecting 293T cells with the xmrv plasmid. The virus was detected as reverse transcriptase in the supernatant. The virus in the supernatant was then used to infect the LNCAP cells, as shown in the figure shown in NotBilly's link.
Sinbad
>It does not say that virions of VP62 were observed coming from transfected 293T cells. This was not an observation recorded in Schlaberg et al.
Diego
>Here is the paper that should be quoted. Hohn et al. 2009.
http://www.retrovirology.com/content/6/1/92/figure/F4
Diego
>Diego,
It doesn't say they were "observed." It says they were produced, detected as RT activity, and then used to infect the prostate cancer cells. It's very hard to "observe" a virus. They are very small. I don't think NotBilly saw the viruses come out of the cells with his naked eyes. But it is clear that live viruses came out of the cells. One infers they came out by budding, because that is how this sort of virus comes out.
Diego
>Sorry,
My pseudonym is Sinbad (at 4:36 PM)
Sinbad
>Sinbad, it does not say VP62 virions were produced from 293T cells in Schlaberg et al.
Hohn et al. had no trouble observing them using electron microscopy.
>"pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection (Fig. 1A), indicating the release of viral particles. These were inoculated onto naive 293T cells and LNCaP cells, a human prostate cancer cell line (American Type Culture Collection CRL-1740). Viral release from infected LNCaP cells was first seen on day 7 postinoculation and peaked at day 12."
Diego,
This says that the virus was produced from 293T cells, even if it wasn't "observed". But if you accept that virus was photographed coming out 293T cells, I guess we both agree with NotBilly's claim that it does so.
Time to go home. I'll leave you to argue with NotBilly's antagonists. Goodnight.
Sinbad
>Diego,
What's your point? I didn't mean that the details don't matter, If they prove something meaningful to the discussion; and I didn't mean to be mean, only to break it up. A very large percentage of the comments on this blog are you trying to prove something, again and again, in a very irritating way. What is it that you would like to say? Say it. Not hinging on any one particular detail. What is it you are trying to tell us? In concept. Also, tell us something about yourself that would allow us to put it in context. You seem to have an agenda. What is it? It's OK if you are a sick patient with no scientific background that reads a lot, but say so, please. What are your intentions?
Jamie
>Dear Genius-oids. When you "Select profile" from the drop down box… there are several selections other than "Anonymous".
If you choose Name/URL, you can type in a name (I.E. "Diego" or "Sinbad") and, if desired,
a URL.
It takes no more time than signing within the comment window, and replaces "Anonymous" with the name of your choice.
Thank you.
>@Jamie
I only ask earlier, "Have whole virions been found in 293T cells and did they have that in the lab. January 5, 2012 10:18 AM"
The question wasn't answered with a paper that showed that. I said it wasn't. Then we got sucked into a back and forth as I know the paper they showed does not show that. Eventually I had a search and found a paper that does present this information, Hohn et al. That's it. It wasn't about LNCaP cells, or reverse transcriptase. They have presented a very large percentage of the comments on this blog trying to prove something that isn't true. Schlaberg et al. never made this observation. I agree it is very irritating and they should have just admitted their mistake and move on. It was only a point raised around the issue that an immune response cannot be produced by VP62 unless you infect a person. My agenda was only to say they were wrong and that I wasn't lying. My intentions are to discuss the merits of the research and to talk about the evidence and what is hypothetical. What is wrong with that?
@Sinbad
" But if you accept that virus was photographed coming out 293T cells, I guess we both agree with NotBilly's claim that it does so."
Yes, but I asked had this happened. I would have hoped for a real reference. Instead I provided it.
Diego.
>Yes, Diego, but readers are glazing over. So what does it accomplish? What is your point? It's my blog, and I don't really know, other than that you want to defend the Science paper to the death? And say that the work of Mikovits and Ruscetti was flawless? That's no better than the folks who want to say, we can't find XMRV in patients, so let's get back to the real work of retrovirology. Why do you feel you must behave like a pitbull with respect to this particular detail, pray tell? At risk of shutting down the discussion, or is that what you wanted?
Jamie
>@Jamie
If someone said you were lying you would defend yourself wouldn't you?
"defend the Science paper to the death? And say that the work of Mikovits and Ruscetti was flawless?"
I have not done that. Evidence needs to be presented to suggest there is something wrong with the experiments. What research are you saying did that?
"Why do you feel you must behave like a pitbull with respect to this particular detail, pray tell? "
Because you are accusing me of lying.
"At risk of shutting down the discussion,"
Shut down the blog????? Jamie, that doesn't make any sense.
Diego
>"The question wasn't answered with a paper that showed that. I said it wasn't. Then we got sucked into a back and forth as I know the paper they showed does not show that. Eventually I had a search and found a paper that does present this information, Hohn et al. That's it. It wasn't about LNCaP cells, or reverse transcriptase. They have presented a very large percentage of the comments on this blog trying to prove something that isn't true. Schlaberg et al. never made this observation. I agree it is very irritating and they should have just admitted their mistake and move on. It was only a point raised around the issue that an immune response cannot be produced by VP62 unless you infect a person. My agenda was only to say they were wrong and that I wasn't lying. My intentions are to discuss the merits of the research and to talk about the evidence and what is hypothetical. What is wrong with that?"
Why on earth would admit something is a lie that I did for 2 months straight?
I don't know how else to explain it to you. You transfect ANY cell line, LNCAP, 293T, 293A, 2fTGH, DU145, HeLa, etc…, some amount of virus is going to come on out those cells.
How on earth do you think all of the XMRV papers were able to study the virus? How do you think they made the virus? Answer me that question? Out of thin air?
Your direct quote: "Sinbad, it does not say VP62 virions were produced from 293T cells in Schlaberg et al."
Here is the Schalberg quote again:
"pXMRV1 was transfected into 293T cells. Reverse transcriptase (RT) activity was detected in the supernatant within 1–2 days of transfection (Fig. 1A), indicating the release of viral particles. "
Again, I really have no idea how toy still argue this. "indicating release of viral particles"
Please tell me how I'm lying to you. PLEASE.
As for your Hohn et al. reference – you are absolutely correct! Good job! Now please realize that this can be done not only with 293T cells but with other cells as well. Not every EM image on this planet gets published.
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Dr. Snyderman, I'll get back to you later tonight after I get home from work.
>@ErikMoldWarrior
Thank you Erik, I didn't know that.
>@NotBilly
You said they showed this in Schlaberg. They didn't, Hohn did. Schlaberg's research only indicated they might be present, it did not show they were as reverse transcriptase is not a virion. I asked you where you saw this, all you could say was you had. Many papers used lots of other cell lines for research. The issue was where this was published for 293T cells and where you had seen it happen. Once you use a reference that doesn't back up your statement just admit it and move on. It would have been simpler if you had looked for a paper that did and found Hohn et al. You are accusing me of lying when you don't do that. If research is not published in the paper it does not officially exist and has not been through peer review. Is that not true? Look I don't want to drive everyone crazy, I'm sure you don't.
>@NotBilly
Lets use this to discuss previous findings. If you think that reverse transcriptase (which is an enzyme) means virions must be present how would you explain these findings?
Immunocytology and in vitro reverse-transcriptase activity in CFS
AuthorsM.I. Holmes, R. Easingwood, J. Cross, and J. Faed
Objective: This paper describes two blind clinical trials of paired, age, sex and ethnically matched patients with CFS; 24 pairs of patients and controls in the first, and 18 in the second. In the first, the range of duration of symptoms was 1 to 3.5 (mean 1.5) years and in the second 1 to 5 (mean 1.7) years. Peripheral blood lymphocyte (PBL) cultures were assayed in triplicate for reverse-tran scriptase (RT) activity, and examined by EM for the presence of virus-like structures at days 0 and 12 and CD2, 3, 4, 8, 16, 20, and 31, and B1 phenotypes were counted at day 0 by FACScan.
Methods: A single dose of 1 µg ml-¹Concanavilin A (Con A) was given to all cultures at day 0. At days 4, 8 and 10 they were given 4.5 ng ml-¹ human recombinant IL-2. Cells were harvested at day 12 for EM studies, and ultracentrifuged supernatants and cells for RT assay using a poly rA:oligo dT template-primer and measuring RT activity by uptake of tritiated thymidine triphosphate.
Results: In Trial 1, RT activity up to 3 times background was observed in 9, and virus-like structures in 7 of 24 patients, and not in controls. Group means showed a significant CD4 cytopenia. In Trial 2, RT activity at levels of 2 to 4 times background were observed in 5 patients, and virus-like structures were observed in 4 of these, and not in controls. Group means showed significantly reduced CD4/CD8 ratios and an NK cytopenia. RT activity and EM virus-like structures were seen almost exclusively in the cohort of patients who identified the onset of their condition with a non-specific, acute febrile illness and whose duration of symptoms was 2 years or less.
Conclusion: These studies suggest the in vitro RT activity and the presence of virus-like structures in PBLs may correlate in CFS with patients who relate the onset of their condition to a non-specific, acute febrile illness.
http://www.cfids-me.org/aacfs/poster3.html
>Hey Not Billy, (a good southern name)
You wrote:
"But just to be clear, there are no runaway infections going on. Just enough so we can study XMRV."
Yes, I get it that you are not currently letting this stuff out the lab door and you are protecting your workers in your lab. But isn't it highly likely that retroviruses contagious to humans have accidentally been let loose from previous work such as vaccines grown in mouse tissue and then injected into humans? How about cancer research and hep C research in central Africa which may have accidentally produced a retrovirus which started infecting humans? This fits the picture with the three cities where gay people were given hepatitis vaccines just prior to the outbreak we now know as HIV AIDS. So this latest finding of whatever retrovirus in CFS is disturbing as is the "outbreak" of autism.
You wrote:
"Is it possible that in CFS patient sera, the SFFV env protein cross-reacted with something else we have, that we don't even know about? Yes. At least this is my opinion. In my opinion, it was wrong for authors to conclude that those anitbodies and XMRV antibodies since the experiment itself is not very specific."
Yes, disturbing. Forget about what the retrovirus may be. The evidence seems to be that patients who had antibodies to something were very sick patients. I know personally one such patient. She is very much sicker than I. I tested negative, period. And, assuming there was some validity to Mikovits' original study, the CFS patients were definitely sick and positive for something??? at much higher levels than healthy folks tested.
So we have to keep looking. I sure wish Gilead would get on this. They stand to make a LOT of money off us sickies. If I heard they were researching this I would buy their expensive (relatively speaking) stock.
>"Schlaberg's research only indicated they might be present, it did not show they were as reverse transcriptase is not a virion."
I hate to burst your bubble on what you think science is, but EVERY retrovirology lab, including mine, uses RT activity as measure of active virions. When a retrovirus buds from a cell, an active virus must have reverse transcriptase. This is science fact since 1975. Unless you want to argue with David Baltimore who won a Nobel prize for discovering RT of retroviruses. You don't need an EM image in every paper to show that one can make virus. All you need is the enzyme activity associated with RT.
" Once you use a reference that doesn't back up your statement just admit it and move on."
It did. Do you want me to quote the paper again??? For the 30th time now?
"It would have been simpler if you had looked for a paper that did and found Hohn et al."
Didn"t need to since this is common knowledge in the materials and methods section of almost every paper that makes XMRV to study.
"You are accusing me of lying when you don't do that."
EXACTLY correct. I'm accusing you of lying when I don't do that. In essence I'm accusing you of ignorance and then lying. Actually, more to the point, lying to promote your agenda of attacking any scientist that reasonably comes on thsi blog.
As for your other reference, I refuse to debate you to no end about a poster that was presented in 1998. A poster that has no data. A poster that was not peer-reviewed and published in a respected journal.
>For those of us with CFS, this discussion has gone off the radar screen, over the waterfall, beyond the pale. Why is everyone repeating and beating everything to death? It's giving us headaches.
Points were made over and over again. Why? Our eyes are glazing over and we can't keep reading the same thing, so we're skipping the posts.
One point though: Someone, perhaps one of the many anonymi, said that people can't have CFS and cancer, that cancer cancels out the CFS. Well, Drs. Mella and Fluge in Norway gave Rituximab to people who have lymphoma and CFS, and for some the CFS symptoms abated. Thus, we're now hearing about their studies about Rituximab and CFS. Their findings may help us, their studies of B cell dysfunction, relationship to CFS, etc.
I'm not cheering for Rituximab, but saying their research may be helpful overall, and to say that some people have CFS and cancer. I'm concerned about the relationship of CFS to lymphatic cancers and would like to know more.
The only thing that jumps out at me to question here is it true that lymphatic tissue must be tested for MLV's, and not blood samples? Am curious about this.
Meanwhile, can't folks just move on? We've seen this movie 100 times and want to move on.
No one is keeping score on who is right and who is wrong, and since so many are anonymous, no one is getting demerits. However, this is too much. Let's go on to other points, which are revelatory and interesting.
Meanwhile, I fainted today at home and am more concerned about why and what's going on here, than I am about the continuing argument. Let's contribute to the discussion, not continue the competition. This isn't a race or a contest.
>To understand "CFS confusion", and to see where the bizarre notion came from, that a cancer diagnosis could even possibly exclude someone from the "CFS category", one has to read page 275 of Osler's Web.
>Thank God for Diego. I lost my rather lengthy response as to why Diego has done many people on here a service – but will have to write something similar another time.
In the meantime – while the comment about the pitbull was meant (fallaciously) as an insult, anyone who knows about these animals will know that it actually is a compliment. These are loyal, intelligent, focused canines, both cruelly victimised and falsely demonized by humans. Diego's focused behaviour is cutting through unsubstantiated claims and irrational appeals to authority and mystique here. While it is easier to take the line of least resistance, shooting the messenger here is not the best way forward.
>PS, unlike some here, I can substantiate my comments about pitbulls with solid empirical evidence. There are a number of sources of quantitative evidence available which I'll put up only if people are interested.
I say this because empirical adequacy, coherence and compreheniveness have been sadly missing from those claiming scientific authority and mystique, and some patients here need to understand that complexity (and the drive to understand that) needs to be engaged with, otherwise you are just allowing what is often complete BS to flourish without challenge. Diego has taken up the gauntlet where others (including myself) are unable. I'm very grateful for that.
>@NotBilly
You cannot say not all EMs are published and then refuse to discuss a poster. I can provide published papers if you wish? RT activity in people with ME is not new.
Again you are making false claims about Schlaberg. Reverse transcriptase could be found and be associated with any retrovirus. It does not mean VP62 virions were observed and they were not recorded in the paper. Reverse transcriptase is not a virion.
>Re the cancer/ME/cfs business, am I right when I say that of the 300 strong Incline Village outbreak cohort of CFS, 77 were found to have contracted Mantle Cell Leukemia? And that the normal population prevalence of MCL is 0.015%?
I too am grateful to NotBilly, and am tired of being preached to by alleged scientists, who fail to engage directly with arguments and throw insults about.
I am a patient patient.
>>I am interested in concepts, not minutia.
I agree 100% Jamie. Too many here (on both sides) are interested in ego, points-scoring and "being right" for the sake of being right. This approach has accomplished nothing except to turn the debate into a slanging match.
I think a debate can either be about the big picture, or it can be about minutia, but it cannot be about both.
>What concepts are people wanting to discuss?
Here is a paper that found MRVs in ME patients in 1989, with the paper being published in 1997. We know this was an MRV because a sequence was recently added to the Genbank.
http://www.ncbi.nlm.nih.gov/m/pubmed/9201810/
A human B-lymphoblastoid cell line constitutively producing Epstein-Barr herpesvirus and JHK retrovirus.
>PC@ January 6, 2012 12:06 PM wrote: “What matters is what we find in vitro, not the labels we currently have. If we knew what caused autoimmune diseases, autism or myalgic encephalomyalitis then we could group ourselves. Right now we cannot form such groups, so we group as best we can and test for things.”
There are two diametrically opposed problems with this statement, and the failure to distinguish between these is fundamental to the difficulty faced by JDJ in her appeal to have scientists join a discourse with her and others who share her perspective. Firstly there is the ever confounding position held by a large proportion of M.E/CFS commentators (patients and carers) who demand that only by a proper definition of the ‘true’ disease can patient selection be adequate for the needs of proper scientific study. Secondly there is the practical position of researchers who have to be able to select patients for study in a meaningful way.
Of course if there is indeed valid science that shows a common disease process irrespective of current labelling, then that would allow research to proceed on the basis of what was found ‘in vitro’. But there is none in respect of XMRV (the named subject of this blog) and (other than challenging poor apprehension as attempted by NotBilly) there is now no basis for scientists to engage in a discourse located in a proposition of a relationship between XMRV and M.E/CFS.
If there is some other locus for discourse that is seen to be valid, that needs to be clearly specified. It remains my question to JDJ – what is “it” ? Science needs ‘definition’, and faced with an amorphous mass the scientific process demands taking a guess and posing an hypothesis, defining terms and then testing to destruction. Mmuch of the time the choice of hypothesis will be ‘the wrong one’ but it is the only basis on which scientific discourse can be founded. More than one hypothesis may well be part of a wider discourse but each needs to be specified, and no hypothesis should be reliant on another. This may all seem over restrictive but it is what is required if one wants serious contribution from scientists. If that’s not what is required then of course people are free to expound as they wish, but that shouldn’t be confused with anything that is more than ranting, gossiping and story telling – these are all fine in themselves and scientists as much as anybody else indulge in them, but ranting, gossiping and story telling are not part of a scientific discourse.
If science is what is wanted, and M.E/CFS is to be part of the discourse, then an acceptance of agreed illness definition (CDC/NICE) is requisite because that is the basis on which science is currently proceeding. Counter hypotheses (eg CCC) can of course be entertained but if those are seen as being exclusively the basis for discourse, then the engagement of scientists will necessarily be limited to those who consider current reserch to be misdirected and are themselves not engaged in active studies.
>@EMW January 7, 2012 12:03 AM
Osler's Web is not a scentific reference. You may not like the scientifically agreed criteria for M.E/CFS diagnosis and may consider yourself an eminent authority but JDJ has made a direct appeal (the subject of the current blog post) for scientists to engage in discourse. It may be that making cancer an exclusionary diagnsis in M.E/CFS is wrong, but the current scientifically accepted position is that a diagnosis of cancer excludes a diagnosis of M.E/CFS. Where someone contends that they have both conditions concurrently, some explantion of why and how the accepted scientific position is wrong, is required if they are to be taken seriously in a scientific context.
>@IVI, your demand that the illness definition for research that has to be agreed is CDC/NICE is untenable, and saying that does not render me against science. To imply such (as you are doing) is a fallacious rhetorical device.
The CDC and NICE definitions are diagnosis of exclusion. They are based upon the notion of 'medically unexplained' illness, and as soon as signs of organic illness are detected, it renders a patient NOT a CFS or ME sufferer, according to their own (flawed) logic. This is in conflict with the WHO's categorisation of ME (whether or not you personally agree) and certainly with a large body of research (even where, for example, the CDC criteria have been used incorrectly – NOT excluding people with organic signs of illness where by the rubric of Fukuda/Reeves/Reeve, they should! Check out the papers directly- that's what is required). Newton et al found a large amount of people being referred to 'CFS' clinics basically had other conditions! The potential for confusion due to the use of confused criteria designed to promote psychogenic explanations is huge. And this has borne out in actuality, from that first negative paper by Erlwein et al.
There is no good reason why those two criteria are to be 'requisite'in 'science' or having ME/CFS as part 'of the discourse', and strong reasons against such an opinionated demand on your part. The whole issue of the criteria is a mess, parsimony is urgently necessary (meaning stringent definitions in this context in order to prevent the confusion that has reigned over this illness for so long from continuing), and you in affect are arguing against that- one of the more important tenets of scientific process.
Despite your authoritative pronouncements, this patient community is not powerless and pathetically dependent on the paternalistic patronage of 'scientists', and can engage with scientists and demand that they – well – pull their fingers out and practise correct science. They are not the only patient community to do this of course. I think your above comments if addressed to the AIDS community in the 1980's would be laughed at. The time of kow-towing to irrational appeals to authority as a matter of course are over, especially when they come from anonymous posters claiming scientific expertise they may not have.
>"In the meantime – while the comment about the pitbull was meant (fallaciously) as an insult, anyone who knows about these animals will know that it actually is a compliment. These are loyal, intelligent, focused canines, both cruelly victimised and falsely demonized by humans. Diego's focused behaviour is cutting through unsubstantiated claims and irrational appeals to authority and mystique here. While it is easier to take the line of least resistance, shooting the messenger here is not the best way forward."
Well Angela, as a scientist who has handled XMRV with my own hands and has done 6 years of schooling for a Ph.D. along with 6 years of post-doctoral work, Diego is not what he says he is. He has no experience in research – this is plain to see.
He makes claims as if he knows the science but is completely misleading to you and other readers. Please take caution in reading what he states. Its often wrong.
>Diego,
What's your point? What are you trying to accomplish? Why would you keep repeating yourself in a way that seems meant to obfuscate? Why are you afraid to tell us something about yourself? It is most peculiar behavior. I am again asking you to stop.
Angela,
What gauntlet? Do you know what Diego's point is? Diego has yet to make a point of substance, other than blind defense of the first round of an experiment.
I was wrong to malign pitbulls, but I was an ER doctor and one of the most horrible cases of my career was a 2 year old mauled by a pitbull. But you are correct, pitbulls don't bite any harder than other dogs. They do however appeal to certain kinds of people who train them to bite and fight; but you are correct, it is the people, not the dogs who are the problem.
Jamie
>"I defer to the scientific community to figure it out; discussing it here is not productive."
Dr DJ, this has been my position for a long time on this particular subject. I appreciate this blog post very much. I've been ill for many years. I've never been depressed, although there have been a few low moments, usually concerning missed family events. The lowest I've ever felt however, has been as a result of my fellow "patients" in the last several months, and their totally irrational and destructive behaviour. We need all the sensible voices we can get, and all the help we can get from good quality scientists. I've said this over and over for several years : the ONLY route out of this illness for all of us is via honest, good quality scientific research.
Thank you.
>"You cannot say not all EMs are published and then refuse to discuss a poster. I can provide published papers if you wish? RT activity in people with ME is not new.
Again you are making false claims about Schlaberg. Reverse transcriptase could be found and be associated with any retrovirus. It does not mean VP62 virions were observed and they were not recorded in the paper. Reverse transcriptase is not a virion."
Sure I can. Not all EMs are published. Sorry, but your wrong. Not everything is published. For example Diego, this month alone I produced 27 western blots for various experiments with my project. Only one will *maybe* be published. If peer-reviewers accept my story.
And sorry but I speak the truth. The virions (any retrovirus) have reverse transcriptase that can be tested in the lab. This corresponds to active virus.
Another example for you. In this case they transfected LNCaP cells with XMRV and made virus. But I'm lying yo you again huh?
Rodriguez et al.:
"XMRV virus particles were generated by transfecting LNCaP cells with 5 μg of proviral DNAs."
and
"The relative concentration of XMRV in supernatants was determined by measuring the reverse transcriptase (RT) activity in the cell culture media of harvested stocks "
I'm not making this up!
>@ NotBilly. Can you not see the comic irony in what you have just written? You are an anon making appeals to authority and mystique. You have not substantiated your claims despite repeated appeals from Diego to do so. I have NO way of knowing whether your claims to expertise are true, CERTAINLY not whether you are indeed a 'scientist' with all this alleged experience, nor what you claim to have 'seen with you very own eyes!'By your own logic if you claimed to be abducted by aliens you would expect us all to act with slack-jawed credulity, all because you claim to be a 'scientist', yet refuse to use your own name!
Yet you are attempting to persuade me to believe YOU over the poster (Diego) who has at least written with logic, has made no claims to eminence or authority or mystique, and is relying on the substantive points on their critique and questioning. Now you're trying to construct a straw man (Diego is not what he says he is? He hasn't said he is anything! He's made no such claim to experience in research!)
Your erroneous rhetorical devices here render you an unreliable narrator. If you don't see that – then it makes your claim to know science even dodgier than at present.
>@ in vitro
International experts have put their names to the ICC and agreed that strict criteria should be used for a disease that is listed as neurological.
Choosing to study all people and look for abnormalities has never worked in defining a disease scientifically because there is nothing grouping all people but the fact they are human.
You comment on XMRV. What about the polytropic sequences identified by all four labs? And what about the JHK paper I posted earlier that found a xenotropic MRV in ME patients before the claimed creation of 22Rv1. An X-MRV variant different to other known strains.
Sorry Jamie, but part of my response earlier was not included as to why the evidence shows VP62 plasmid cannot have produced the EM of budding virions. Independent testing of samples from both lab could not detect the plasmid, which is easily identified from wild-type viruses.
>@Billy
This is my last comment about Schlaberg and the claims made about VP62 virions and 293T cells in that paper.
VP62 virions were not observed coming from transfected 293T cells in that papers. RT activity was, but that could be any retrovirus. If they had recorded the event for the paper it would be named in the paper. It is normal practice to say the image or figure is not shown. That is not in the paper either.
You claimed it was in the paper, it is not. That's your choice of reference not mine. As you have made this comment, I think you will agree unpublished data cannot be assumed to have occurred or it did not get through the peer review. If we cannot debate unpublished material and not even a poster exists on that finding in this paper it cannot be duscussed.
"As for your other reference, I refuse to debate you to no end about a poster that was presented in 1998. A poster that has no data. A poster that was not peer-reviewed and published in a respected journal."
>Angela,
NotBilly is writing to us from an institutional server, as was Sinbad last night (different city). Their comments have the ring of authenticity to me. Diego, OTOH, seems to me to be the one claiming "authority or mystique", but engaging in sophistry.
We can argue about the fine points of the literature 24/7, but the real answers for us aren't in the literature. NotBilly, Sinbad, other scientists reading, how would you go about the next round of testing for a retroviral etiology of ME/CFS (and ASD), since we have learned some things despite the fiasco?
Scientists, since you use RT assays routinely, can you tell us why we don't have an RT assay for clinical use? Why is there not a test for generic retroviruses?
Jamie
>@AK – Well as always you know best. My appeals to authority are (as always before) 'irrational' while as always yours are 'rational'. And of course your 'science as a consumer choice' approach which treats scientists like 'supermarkets' (customer service is poor – must do better) has drawn engagement with scientists to an unprecidented level. Glad to see your priority here has been to match your usual ad hominem proseology with PR for the pitbull canine community. Truly your commitment to the advancement of medical science is astounding. Two questions though – is JDJ's request for engagment with researchers a rational or irrational appeal ? And if M.E/CFS sufferers stop believing in your sub Socialist Workers Party 'politics of conflict' doctrine of illness, do you disappear like Tinkerbell ?
>@ Jamie.
Diego's point, as far as I can see, is that some of the claims being made here are unsafe/wrong. That's a perfectly fair position to be taking.
You surely must be aware that there is an awful lot of polemic (as opposed to careful discussion) going on in responses to this blog. There is so much of it (mostly of the "oh those stupid evil patients" kind) that it is becoming hard for actual patients to sift through it all to establish facts and logical argument. Some give up. This has been a constant in the way outside forces of power (government, 'scientists', the medical establishment) have addressed this patient community and their supporters.
I'm not intending to make an irrational appeal to authority here, but I will make a claim to expertise: I am a sociologist (including the sociology of science) and a research methodologist. I have been trained to analyse texts of many kinds for instances of exercising of power, ideology, polemic, assumptions caused by hegemonic social structures, and logical fallacies (including the two biggies for the purposes of my research – ad hominem and appeals to authority for polemic effect). It's not really relevant, if I had not been trained to find these, but was self-taught after being laid off as a construction worker, it would not render my identifying of the above implausible per se. That would be irrational The only factor I can rely on is whether my argument is correct at any one time, or whether my concerns are plausible, and THAT IS THE CASE FOR EVERYONE HERE – AND FOR THOSE TAKING PART IN THE WHOLE DISCOURSE ON ME/CFS.
But what has happened in that discourse has been an onslaught of hostility to ME/CFS patients (and their supporters), reams and reams of authoritative-sounding but ultimately unsafe assertions, all used for polemic effect (shut the door on research into the possible link of ME/CFS with retroviruses, sometimes together with psychogenic explanations for the illness). This community, for its own safety, does need to learn to distinguish plausible argument from polemic, but that is very difficult due to the amount of polemic thrown at it, neurocognitive difficulties, exhaustion, life adversity and having to cope with it, etc. etc. (even though the fittest and healthiest humans appear to have the same problems).
I'm asking you to think carefully about the way you have become so polite and accomodating to the more 'aggy' anons on here claiming scientific authority without back-up, against someone who has never claimed scientific authority, but has relied on substantive points. NotBilly has repeated him/herself repeatedly but is not being subject to the opprobrium you are reserving for Diego. Your blog has become an important area to discuss vital issues – but currently you have become a bit cowed to those claiming scientific authority here (I'm not saying this with any prejudice, and forgive me for being blunt). You are in danger of alienating patients and rendering them powerless when you attack them while allowing anons clearly not patients or supporters to carry on with polemic regardless.
>@jamie
Anyone can post from an institution. That they have still not given any suggestion on how to further the science does nothing to argue they are scientists. I suggest tissue studies for starters.
@Invitro
Do you have any response to Jamie's request?
>@ Ah, in vitro – the 'tu quoque' argument I have come to expect from you on a regular basis, and the eventual resort to multiple ad hominem to hide the fact you cannot answer my comments to you in a rational fashion. Your tendency to the polemic, no matter how eloquent and authoritative you sound, cannot disguise the flaws in your argument.
>@ In Vitro Infidelium,
I agree with most of what you've written this morning. I was struck by this though: "..faced with an amorphous mass the scientific process demands taking a guess and posing an hypothesis, defining terms and then testing to destruction." Why not test to construction? The rigidity in your logic leaves us with nowhere to go until "it" is solved. It's like building a stairway without seeing the landing.
The problem with the case discussion arguments is that the needs of the research are completely divergent with the needs of the patient group. Clinically, it is essential to use a very broad case definition. If you then want to define a subset of the sickest patients for study, fine. I agree that the sickest patients should be studied.
Jamie