Late last year virologist Ian Lipkin was asked by National Institute of Allergy and Infectious Diseases head Anthony Fauci to coordinate a multi-center study of CFS patients. Newly drawn blood samples from 100 CFS patients and 100 healthy controls from around the US will be blinded and sent to three groups – FDA, CDC and the Whittemore Peterson Institute – and assayed for the presence of XMRV. After the recent publication by Ila Singh on XMRV in CFS patients, Dr. Lipkin sent me the following note:
Dear Vince-
We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we don’t have evidence that they have. Absent an appropriately powered study representing blinded analyses by Mikovitz and Lo/Alter of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion.
I remain agnostic. We won’t have answers until the end of 2011.
The NIH will post something on our study today.
Ian
Seeing how I have just explained that Lipkin’s methodology (which consists of NOT using clinical samples to calibrate assays and NOT demand exact replication from the CDC or any other laboratory) is perfectly consistent with my posts and contradicts your circular and unprecedented methodology, please go right ahead.
Also, seeing as you fail to address any of my valid questions and arguments and instead posts quotes that don’t even support your illogical assertions, I will in turn just refer you to John Coffin’s quote from the Science article which really does support my position:
“Singh bent over backward to try to use the same assays as published, allowing her to knock down what I consider to be a real straw man but that nonetheless was out there,”
But of course, you don’t think Coffin is a world class retrovirologist anymore with good knowlegde about what’s needed for replication studies, since you don’t like some of his latest results? You refer to him and his “followers” as “the Coffin Cabal” on the forums, I even noticed?
QUOTE – profvrr”- he is merely stating that no number of studies will convince non-scientists that the Mikovits study was incorrect.”
I dont think it is safe to assume that this ideation is the inspiration behind Ian Lipkin’s words @profvrr:disqus. My interpretation would be that he is saying, in the absence of precisely replicated experiments, the scientific community need to test Mikovits and Lo/Alter labs+methods+reagents using a blinded protocol to discover the cause of the anomalous results. That would seem to be the appropriate scientific procedure.
QUOTE – Ian Lipkin “We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we don’t have evidence that they have.”
That is not at all what Lipkin states. Literally quoted from his comment (caps for emphasis and I cut out a bit for clarity):
“Absent an appropriately powered study representing blinded analyses BY MIKOVITZ [sic] AND LO/ALTER of samples […] all we have is more confusion.”
Thus, Lipkin believes that not even a true, perfect and unprecedented replication study would not satisfy the XMRV proponents. He says that MIKOVITS AND LO/ALTER must retest (blindly) THEMSELVES.
Therefore, it is evident that Lipkin is not at all criticising Singh’s or any other’s methodology. He is just promoting his study by saying that it will settle the debate once and for all. Which, for the wackos, it won’t, by the way.
Sorry for the double negative…. 🙁
It should read “Thus, Lipkin believes that not even a true, perfect and unprecedented replication study would satisfy the XMRV proponents.”
Ask Lipkin, he will correct you.
This is what Lipkin said in the quote above
“Dear Vince-
We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we don’t have evidence that they have. Absent an appropriately powered study representing blinded analyses by Mikovitz and Lo/Alter of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion.I remain agnostic. We won’t have answers until the end of 2011.The NIH will post something on our study today.”
Instead of conceding that you didn’t understand his quote and thank to my post you now do (but don’t like it), you simply requote his full comment, somehow *mysteriously* implying that I misquoted him without actually providing arguments for said suggestion.
I’ll requote the important bit, without cutting out the bit for clarity:”Absent an appropriately powered study representing blinded analyses BY MIKOVITZ AND ALTER/LO of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion”
Do you know the meaning of the word “by”?
If so, do you agree with me that Lipkin states that he think only a blinded retesting by the original investigators will bring clarity or do you cling to the unsubstantiated belief that he is somehow mysteriously implying that Singh’s methodology is wrong?
Is XMRV a laboratory contaminant?
“These four papers are probably the beginning of the end of XMRV and CFS,”
https://virology.ws/2010/12/21/is-xmrv-a-laboratory-contaminant/The retractionXMRV and CFS – It’s not the endhttps://virology.ws/2010/12/22/xmrv-and-cfs-its-not-the-end/
Shin et al
“Here the results are overwhelmingly convincing that XMRV is not there. …This study trumps Mikovits’ because it is more convincing in its methodology.â€
“There is an initial finding, others try to replicate it but fail,†he said. “So along comes another independent scientist, with no interest except to get the story straight. That scientist carefully plans all the right experiments, and even gets blood from some of the original patients, and finds nothing. It is done in a way that all scientists can completely believe.â€
http://www.chicagotribune.com/health/la-heb-xmrv-chronic-fatigue-20110506,0,7721861.storyShin et al was not a replication study.
They were not the same assays as those used in Shin et al.
Yes, HGRV’s have been validated by Lo et al also. Lo et al did lower the stringency of the primers though, which none of the negative studies have tried.
There are several assays that can detect HGRVs in blood provided by Lombardi et al and Lo et al. The issue is whether the original findings are in question, not that there are others methods validated to detect HGRV’s in blood. You cannot disprove that the findings are wrong if you do not apply the same methodology.
The Lipkin study will be using the same methodology as Lombardi et al or validating their assays with known clinical positives. That is what the WPI and NCI will be doing.
Sufferer,
Thanks for replying. Whilst I am afraid I do not share your opinions I really do and have been very aware of the potentially devasting impact that research as thorough as this – not to mention all the other negative papers that are splashed across the headlines – must have on those who have ‘tested positive’ for ‘XMRV’.
In many respects this has been the reason why I have passively sat by and let some posters bombard scientists with their desperation-induced diatribes and pet theories and beliefs.
Watching from the sidelines the impression that such attacks are giving to the scientific, medical, and outside world, is that this is the ‘majority’ opinion – and I do not believe that it is – but what I do believe is that this impression is becoming very damaging. I actually shivered when they posted that advert comparing those with CFS who might have ‘XMRV’ with those who had HIV and AIDS. What a statement to make when so little was really known. What propaganda.
Nobody should claim to be an ‘advocate’ unless identifying who exactly they are representing. I hear words like ‘most’ and ‘many’ and ‘majority’, being banded about – and you know what – when was the last time you heard of a single organisation actually representing more than a few thousand members? Where is the true representation? In the UK the numbers are ESTIMATED at 250,000, in the US what 1-4 million – where is the organisation representing those sort of numbers?
Speak for oneself – fine – have suspicions that others share your views on something; but don’t presume the many share all your opinions or are supportive of everything you say. And the same goes for scientists and medical professionals.
I ‘like’ something someone says or does or a particularly well researched endevour – for sure. It doesn’t mean I ‘like’ everything that person or organisation does – I am not in the business of being led with a blindfold over my eyes – thankfully.
These scientists and medical professionals who are prepared to open up their time on places like this, giving we laypeople as well as other professionals a chance to ask questions, are to be commended – not attacked – just because they happen not to share you view. And yes, the same applies to all of them – included Dr Mikovits – although in that respect I don’t feel the critique of her work has been anything like as hostile as that of others whose work seems to generate such animosity among those most active.
I think the word ‘debate’ has dropped by the wayside in so many respects on forums and in places where a difference of opinion seems to mean a declaration of war. Cripes in some places to ask a question about ‘XMRV’ or the WPI – just to gain a better perspective and understanding, can be enough to generate such hostility from the few with the loudest ‘voices’ – that one has to ask is it any wonder people tend to just read and ‘like’ rather than seemingly post a comment?
When a paper is published or a comment is made, that requires later clarification or apology; than is it not to be commended that mistakes have been recognised and addressed? That understanding has been improved?
Nobody is infallable. Dr Mikovits, the WPI, Prof Racaniello, Prof Singh, Dr Lipkin, Dr Coffin, nobody – as sure as eggs is eggs the same goes to ‘advocates’ as well as pseudo-scientists on the internet.
If people don’t share the same opinion or have a different interpretation, why has it become necessary to ridicule? On and on and on…
And don’t get me started on what has become known as ‘politics’ amongst the ‘advocate’ community. You want to rant against the system, and blame someone else, claim conspiracy; then fine. Just don’t expect me to join the gang – at least not without trying to assess the facts first and getting other opinions, and asking questions.
Jack
(Time taken to post – 2.5 hours: am off back to rest now :))
Please quote Coffin.
“Coffin emphasized once again that doing a replication study implies that it is performed in exactly the same way.”
http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind1005a&L=co-cure&T=0&F=&S=&P=1724
Hi Flex,
Thanks for replying. Sorry I don’t have the energy to respond directly, but maybe refer to my above attempt?
I was sorry to read of MECFS Forums that you feel your efforts ‘to defend’ were not receiving the wholesale support you felt they deserved.
It is a tough compromise isn’t it – our health and believing that our efforts in posting and campaigning are worth the sacrifice?
I am afraid I don’t like aggressive posting, but as I said I have tried to recognise what it must be like to have been told you are ‘postive’ for a ‘human retrovirus’ and then feel compelled to confront what you see as attempts to belittle that finding.
I do wish you well, as I do everyone affected by this illness termed ‘CFS’.
Jack.
In my comment, I was not speculating on what I ‘thought’ Dr. Lipkin meant by his comments. I spoke with him after he sent the email to make it clear what he meant, and I based my comment here on that conversation. Whatever you choose to believe, the study that he is coordinating is exactly the kind of study that he believes will resolve the situation. Note that he says that the results won’t be available until the end of 2011.
I have no problem stating that I ‘liked’ your comment LJ. Thanks. And I see 36 people before me did too.
I guess you suspect ‘most patients…’ 🙂
Sorry Karen I didn’t – I just ‘liked’ LJ’s comment – with the caveat about using ‘most’ references of course 🙂
Is it necessary to do background checks on posters now? Jees. You guys work for the CIA or something? You know their opinions can be just as wrong too sometimes.
I just wanted to thank you Bookkeepchick for taking the time to answer in such a way that even I could understand without needing to resort to dictionary or search engine 🙂
I very much appreciate it.
Jack
Thanks also to you Gob for your reply.
Jack
Doesn’t any scientist in charge of a research project have to weigh all of these points up on an almost daily basis, though Gob?
I mean I used to in my humble role as an Investment Manager as part of a six man team with several billion under my control. It’s what one does – though maybe one would not want it expressed in the way that Alan Dove chose to 😉
BTW I have ‘liked’ both your and Alan Dove’s comment, oh and RRM’s too.
Jack.
They were close enough. The PCR clearly amplifies. The degree of difference in the PCR method (doubling the Taqman concentration and using dUTP instead of dTTP) is nothing like enough to make 14 positive samples go completely negative. If you made that degree of variation in, say, an HIV assay, you wouldn’t get 68% positive dropping to 0% positive. There are lots of different molecular assays out there with much more variation than that. When you get to immunological assays the variation can be even greater.
What would the numbers be like with a hate button? What about the other 16,999,962 and other scientists?
Ask Lipkin, he will correct you.
I will quote the important bit
“Dear Vince-We have a plethora of explanations for how CFS/XMRV/MLV studies could go awry. However, we don’t have evidence that they have. Absent an appropriately powered study representing blinded analyses by Mikovitz and Lo/Alter of samples from well characterized subjects using their reagents, protocols and people, all we have is more confusion.I remain agnostic. We won’t have answers until the end of 2011.The NIH will post something on our study today.”
Close enough is not replication. They did not use clinically positive samples, but a clone. The assays are not validated. Nested PCR is not Nested RT-PCR.
Lipkin also has a responsibility to state when research has been shown to be incorrect and know when funding is being wasted. He has not said that this is the case.
You are placing your own interpretation on the communication. He is very clear that nothing has been presented that suggests the results of Lombardi et al or Lo et al are incorrect.
You want your comment to say something that it doesn’t say. Instead of arguing, you just repeat this quote, which doesn’t say what you want it to say. It’s pretty sad really.
Can you repeat it just one more time, because then it might become true?
“I remain agnostic”
Why is it important to note that the results won’t be available until the end of 2011?
Thanks
But John Coffin said at the NIH ME/CFS State of the Knowledge Workshop a couple of weeks ago, that he thinks XMRV should be left behind. I don’t know if he only meant in ME/CFS, but i think this was a doubtful comment, given that even in the eyes of many non-believers of the association with ME/CFS the link between XMRV and prostate cancer is not disproven. The paper by the CDC’s Bill Switzer published some days ago found XMRV in prostate cancer patients.
And how can Coffin’s hypothesis regarding the creation of XMRV (in the lab, during xenografting) be correct, if XMRV is in prostate cancer patients? Does that mean it was created in a lab, escaped, and is now out there in the population?
This is what I thought…that you (VR) had more info from Dr. Lipkin than just the note posted….since your interpretation of the note is so different from how most people who read the note would interpret it.
so now we are left, once again, with CONFUSION…Dr. Lipkin’s note implies one thing and you provide an entirely different meaning based on a private conversation with him.
the patients are left scrambling in the dark with bits and pieces of information, struggling to remain hopeful.
i personally feel it was more damaging to the patient community for you (VR) to post a note from Dr. Lipkin that implied one thing, when in reality he may have meant something completely different (based on your conversation with him).
Seeing how Science works (over the past 18 months)…. I must say I am quite disappointed…it appears to be a murky, snarky, competitive world with very little empathy or sympathy for the sick people hanging on every word the scientist say.
Before this personal journey thru illness, I thought science and medicine were noble and pure professions, but each day I learn how naieve I was. This a blanket generalization and there are some caring dr’s and scientists, but far too many heartless, uncaring ones. it is a pity that these professionals have so much power and ability to do good in the world and instead they squander and misuse it.
This is my opinion….of course many will disagree…..but from the view of a person whose entire life was robbed by this disease, this is the way things look : (
And?
I openly declare that I hate all your comments. I also start to hate your attitude.
“It seems that you are an hilariously ironic self-styled connoisseur of the “scientific method” yourself.”
Nice turn of phrase! Oops…apologies, those are actually my words.
“Please point me to a proper replication study then, Steve. It shouldn’t be hard.”
This is such a weak argument, I’m surprised you keep returning to it. It is a fallacious appeal to history.
Furthermore, it clearly implies two rather unsavory things about your scientific idols:
1) If, as you imply, there are no “true replication” studies in the history of virology, then you are essentially damning an entire field of scientific inquiry for their historical inability to understand and adhere to basic scientific protocol. Perhaps this might explain their persistent failure to get to the bottom of this.
2) Buying into this line of argument (you, as well as, apparently Dr. Coffin and others) belies a strong aversion to experimental rigor. You are essentially admitting that proper science has not been conducted and then trying to justify that fact bye saying “but we’ve never done proper science.”
But you remain annoying.
I am sure that many do. Usually that is the case when sticking to the facts.
Lipkin would not use unvalidated assays.
Not sure yet, will have to wait and see what happens next.
No, I meant how is that a reply to what I said? You just copy pasted some stuff.
Says the person who didn’t realise that Shin et al did not replicate and used qPCR and Nested PCR, not Nested RT-PCR.
I agree with you ME sufferer re “so now we are left, once
again, with CONFUSION…Dr. Lipkin’s note implies one thing and you provide an
entirely different meaning based on a private conversation with him.â€
This is quite unsettling!! Dr Lipkin is someone in charge of coordinating a
large multi-centre study, yet appears to be an appalling communicator.
One
minute he is saying that he himself is an agnostic, the next minute he is
“merely stating that no number of studies will convince non-scientists that the
Mikovits study was incorrectâ€.
If his only concern now is about non-scientists not accepting that Mikovits
study was incorrect, why agnosticm on his part?
This is the second time I’ve heard him describe himself as an agnostic.
Either A) he does not agree that Singh’s study is the final word in XMRV
research, or B) he has no clue about the meaning of the word ‘agnostic’, yet uses it repeatedly.
“Usually that is the case when sticking to the facts”
It’s funny you say that, since you never do it.
you’re making a mistake by trying to attack me. I’m not responsible for what happens after this.
Nested RT-PCR
I should have expected you not to read it.
Do you think, you’re sticking to the facts by stating the name of a molecular biology technique? I can do it too: Yeast two hybrid.
I already expected you not to comprehend what you copy pasted, and I was right.
That is what Lombardi et al used and what Shin et al did not use. That is from the published research. Perhaps you would have done better to read the paper before claiming differently.