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
It certainly sounds like Alan Dove is making some kind of criticism of Lipkin. If he is saying Lipkin has ulterior motives, he should just spell it out. Making an innuendo like this against a respected scientist such as Dr. Lipkin and then showing no evidence would be beneath a real scientist.
Oh, and by the way, it is the correct scientific approach – to be agnostic about something before you know for sure what’s right and what’s wrong.
Many, perhaps most, of the scientists (including yourself), and also those who are not scientists, don’t do that. But it is still the right thing to do.
You can be a scientist when you have prejudice, but it is still an anti-scientific thing.
Yes but you dont!! Why dont you have a grant to study XMRV?
Not at all. Lipkin is an outstanding scientist, and I have enormous respect for him. I’m just pointing out that if someone asks him what he thinks of the XMRV/CFS hypothesis after Singh’s paper, he can’t possibly give any other answer. The NIH asked him to do this study, they moved a large sum of money from other places to fund it (generating some understandable complaints from other scientists), and now he’d damn well better finish it. Not only does he have to say that it’s still an open question, I imagine he has to believe it in order to get up in the morning and go to work.
It’s not the scientists’ failure that people like you can’t comprehend and don’t read peer reviewed research and just choose to believe or base their opinions on press releases or interviews. Those may give you an idea about the research but unless you go and read the peer reviewed article you will never get the full picture.
People like it because it was a good interpretation of what Dr Lipkin said and put an end (at least tried to) to your attack. Your and your pals’ approach to this reminds me of bunch of hooligans approaching a referee call in a soccer game. Inability to think objectively and misinterpreting quotes based on your personal agenda.
RRM thankyou for the laugh.
The point is that if Alter and WPI can consistently find blinded positives in the Lipkin study if all other collection methods etc are of good quality and the CDC produce another 0/0 study it will show how useless the CDC assay and all 0/0 assays are.
Your approach is becoming increasingly unscientific in more manners than one could even conceive to be possible and reeks of the desperation of a denialist desperate not to be proved wrong.
Your sentiments makes a mockery of science regardless of an “ultimate conclusion”.
1
jack
i am sorry you are so ill. so are many of us responding here. this is why we are fighting so hard for fair science to take place. Lombardi/Mikovits and Alter/Lo are the first real hope we have had in 25 years…how can we allow this hypothesis to be cast aside so casually when a true replication study to dispprove their findings has yet to be done.
there are no other hypothesis out here right now explaining why we are so sick….if XMRV does prove to be a red herring….we are at zero again. why would we throw away our only chance of understanding this disease so casually.
yes, u may not like the style of debate of some of these posters…but believe me, they are fighting for your life too…..would it not be nice to have non-shaking hands and a brain that works clearly again.
if u do not belief there are politics involved in this entire story you are very mistaken. until wpi came along, no one was doing any valid bio-physical studies on this disease. wpi kickstarted this movement and until they are disproven me/cfs patients should support them, since they are working to solve the disease that afflicts us.
do u think john coffin or VR or Alan Dove give a hoot about finding out the cause and treatments for ME/CFS….I don’t.
Because he’s a journalist.
Why don’t you?
….like a record baby right round…you spin me right round……..
It is, as a matter of science, unknown whether XMRV would cause any disease (ME/CFS, prostate cancer, breast cancer, or any other). You would need a prospective study, which would take a lot of time and a lot of money, to definitively prove that. You could also do a formal clinical trial with anti-retovirals to more quickly give a shortcut sort of answer.
As a matter of common sense, it would be pretty unusual for an exogenous retrovirus to not cause a disease. (An exogenous retrovirus is one not already in the genome [all one’s genes] but gotten through an infection of some kind; an endogenous retrovirus is one that is already in the genome which is presumed to have gotten there during a historical infection of one’s ancestors.) This would be the third human infectious exogenous retrovirus. The others are HIV, which along with an incidental infection causes AIDS, and HTLV, which causes cancer.
Keep in mind that the posters above do not speak for the entire patient population. Singh is well-respected in the ME/CFS community.
It is true that it is standard for science to expect replication studies, and that, speaking in general terms, only an exact replication can decide whether the issue is related to methods.
In the NIH study which Lipkin is heading, each lab is allowed to use their own protocol, so WPI will be using their own protocol and this should provide an answer to whether methodology is a factor.
The Lombardi study was elegant. The Lo study was fascinating. The Singh study I haven’t yet read but I trust that it’s excellent. (Most/all the other negative studies are not relevant because they were unable to perform differential diagnosis and some didn’t even bother to use any controls.) But the Singh study doesn’t explain everything away. The fact that Singh found contamination and couldn’t detect XMRV or any related virus with her slightly different assays, doesn’t necessarily mean that Lombardi and Lo were wrong. They could be wrong. Or they could be right. Or everyone could be partly wrong. We really don’t know for sure.
What we have is a conundrum.
I think Ian Lipkin indeed understands that he must keep an open mind, at least if he wants all objectives of his study to succeed. He stated the following in ‘Microbe hunting’ (
http://mmbr.asm.org/cgi/content/short/74/3/363
):
“There are three objectives in pursuing de-discovery projects. The first is to test, rigorously and objectively, a candidate hypothesis; the second is to persuade one’s peers that the first objective has been achieved; the third is to persuade an educated lay audience that you and your scientific peers have considered the hypothesis in a fair and balanced fashion. Many scientists fail in impact because they consider only themselves and their peers in the study design.”
Now I thought I was good at comedy Jev.
I suggest you contact Dr Lipkin. He will correct Dr Racaniello’s personal interpretation.
Mr Dove,
since you say you don’t think that Dr Lipkin is being insincere, are you saying thathe is instead delusional?
” … I imagine he has to believe it in order to get up in the morning and go to work.”
and that his work in this area is coloured by ‘false beliefs’?
Professor Racaniello, both you and
Alan Dove have committed the fallacy of substituting your
inferences for Ian Lipkin’s very straightforward statement about the necessity
of remaining open at this point because he wasn’t convinced by the
arguments.
No reasonable person
can see ambiguity in what he says.
Simply put, the enthusiastic desire that you and Alan Dove share to put
“another nail in the coffin†of XMRV puts your very obvious prejudices on how
you frame the problem, your mutual desire to short circuit the process on
prominent display.
Speaking of “coffinsâ€, Ian Lipkin basically echoed Harvey
Alter’s statement that while he appreciated John Coffin’s arguments,
finding them elegant and intellectually stimulating, there was still quite an
explanatory gap between the contaminationist views and the results found in
both the Lombardi group’s work and that of the Alter/Lo paper published in
PNAS.
While I’ve been uneasy about allowing the Lipkin project to
claim “definitiveness†because I don’t think that this is how science should
proceed, it is money well spent. Carping
about the fact that they had to round up the funds quickly is simply
complaining about the way emergency projects are often handled. And make no mistake there is a very
strong constituency that sees the presence and transmission of Human Gamma
Retroviruses as a health crisis.
My reading of Alan’s usual passive aggressive rant is that
he still cannot wrap his mind around the fact that anything associated with a
disease he believes is psychogenic in character can be associated with
infection.
” Because he is a journalist”
B I N G O ! ! !
However he appears to have a PHD in microbology so he should understand the scientific method better.
I dont have a grant to study XMRV because I am a patient but if I did have access to funds I would give it to a scientist not a journalist. Especially one who tells sick ME/CFS patients not to “step off any balconies”.
His comments sound like a troll’s not a journalist’s.
I have absolutely no “righteous” feelings about XMRV being wrong. I would have no problem with reassessing my opinion when new evidence comes available.
I am repeating my main arguments because they are valid but remain unanswered: -First, if you think this is not proper replication, one of you could provide me with a proper, or at least better replication study in this field. If you cannot come up with a proper replication study, it means that your definition of “replication” in this field is wrong. -Second, if you think that basing a validation study’s assays on the supposed positives of the original study is *normal* scientific methodology, you should be able to provide me with examples of this being done this way.You must thus see that I am not repeating hollow statements ad nauseum, but am supplying statements that should be very easily proved wrong (if untrue). The assertions of the “trolls and troublemakers” are circular and thus unverifiable. ‘Try getting this through regulators” is not a verifiable argument in support of using unprecedented methodology.And yes, the CDC will choose and use their own methodology for the Lipkin study. Mikovits will use hers and Lo will use his, and then Lipkin will see who gets consistent results on fresh samples that have been selected, collected and processed in a way that all parties agreed to beforehand. That is the simple but neat set up of the Lipkin study. Lipkin in no way demands that the CDC will calibrate their assay(s) against “known positives. On the contrary, like the Singh study (and many others), they will use non-wild-type samples as positive controls and no patients will be used from the Science study, if you look at previous, similar undertakings from Lipkin (see his paper ‘Microbe hunting for more information on his methodology: http://mmbr.asm.org/cgi/content/short/74/3/363
Presently no paper has directly tackled whether the virus is causative for any disease. However, these types of viruses only have to be present in the body to do so and they are notorious for causing cancer and neuroimmune disease in mice. Research into this is question is being conducted as we speak. The best place to find out about how these viruses cause disease is to look at the literature on MLVs, but bearing in mind what we already know about the underlying biology of ME/CFS.
Singh’s responses in the CFS Central item are circular and the answers change in later questions. Whereas in other responses she refutes the conclusions of her own paper. She has tied herself in knots trying to answer these questions and they do not always match the data in the paper. One must ask why was the paper so poorly written if her claims are true and how she can possibly believe her assays are validated, when they are anything but.
Anything that is too stupid to be spoken is sung.Voltaire
The WPI, Ruscetti at the NCI and Alter/Lo at the NIH and FDA respectively, have been doing what you suggest. Lipkin is not asking that they use a particular method though, but the one they feel is most superior. Each lab will make their choice.
Perhaps the CDC will once again use a new unvalidated assay that has never worked, as this was their approach in the blood working group. The data will reveal all.
You are right that this study is not the decision maker, as one study cannot decide anything. Perhaps you mean to say that further data needs to be presented. No doubt this will happen. The rest of your remark is lacking in data, as other strains of HGRV have been detected by the WPI and others. The four methods in Lombardi et al validated those positive samples. The immune response could have not have been to anything but an MLV virus such as XMRV (a Xenotropic and Polytropic hybrid), polytropic and modified Polytropic sequences. The rest of your remark can be summarised as worthless.
Lipkin can give an answer that the data supports. That would be entirely reasonable. If he felt that further research was unwarranted, or that any data had shown Lombardi et al to have been faulty in some way (which has not happened), he being an ”
outstanding scientist” would make that abundantly clear. As time and funding should really not be wasted on research that has led nowhere. But this is not what he has said at all. At this time little funding and resources have gone into this study, so it is illogical that you would suggest he is considering monetary issues over a scientific investigation of such importance when he is an “outstanding scientist”. Imagine the complaints that would be made if money were wasted in such a way. No Alan, you are quiet wrong. Please contact Dr Lipkin and he will put you right.
Yes, as the data does not support there being a problem with Lombardi or Lo et al.
You constantly ask for answers to questions that have not yet been tested as if they represent data. You ignore other data in order to present a hypothesis that you personally wish to convey to others. I’m not interested in your motivation for behaving in this way, perhaps you really don’t understand the basics. However, the answers to the questions we all want answered cannot be attained by refusing to try the methodology in Lombardi or Lo et al or refusing to validate assays. Scientists should attempt to end the debate in the lab.
Singh claims there are no controls and so uses clones (unvalidated assays). Later she says she also used patients positive for XMRV from her prostate cancer work. Yet, in other articles claims the virus in them is not XMRV.
Translation: I can’t give you the answers that would be very easy to give if I were right.
Just assume that I am not very bright if you haven’t already. Please enlighten me with an example of a single true replication attempt, or at least one that was more rigorous than Singh’s. That way, I can see the light and understand *true replication* the way it should be done.
Have you ever heard of the term “quote mining”?
It’s good to know that I at least can make you laugh a bit.
I take the rest of your post as a compliment. Not one of you have given me an example which, if it existed, could have easily proved me wrong.
Thus, Lipkin is not relying on “known positives” to calibrate to nor is he asking “exact replication”. Which precisely is the point…
And damn, is the following really worthless? Sorry for repeating:
“-First, if you think this is not proper replication, one of you could provide me with a proper, or at least better replication study in this field? If you cannot come up with a proper replication study, it means that your definition of “replication” in this field is wrong.
-Second, if you think that basing a validation study’s assays on the supposed positives of the original study is *normal* scientific methodology, you should be able to provide me with examples of this being done this way.”
I note that you have still not provided me with simple answers to these easy questions Gob, while you routinely assert that ‘this is the only way fow science to go’.
No RRM and I dont care what it means. I stick to the scientific method, – have you ever heard of that term?
Yes, I am actually quite well versed in it. If you ever don’t understand, just ask and I *will* answer.
i believe lipkin did not consider singh’s study a true replication….ergo his statement.
i am not a scientist, so i cannot your scientific questions. prior to becoming ill i worked in the fashion industry for 15+ years….so my comments have been about the right to argue your view point, the fact that i stand behind mik/lom and alter/lo until they are truly disproven, my dislike of the fact that ppl who stand up and fight for XMRV as a a viable hypothesis in ME/CFS are called trolls, trouble-makers, etc….and VR’s twisted interpretation of Lipkin’s stmt regarding study.
Finally, I find Alan Dove’s comments to patients highly distasteful and uncompassionate…if he does not give a SH_T abt ME/CFS pts and their suffering, he should refrain from commenting….since his comments only insult a group of people who suffer greatly on a daily basis…..I really have NO idea what his motivation is in these discussions….it appears to be to insult and make bad jokes at our expense. I’m sure he would argue this not to be true…but this is what his comments come off as.
VR is doing the patient community a service by discussing XMRV and allowing patients to comment and discuss the issue on his websitee, so i thank him for that….but i was highly disappointed by his interpretation of Dr. Lipkin’s stmt…it appeared to be very biased by his own views on XMRV.
RRM
Your so called scientific expertise has been reduced to making meaningless one line digs. Is this the level of faith you have in your previous illogical interpretations, that you cant be bothered to post them anymore?
I don’t need to ask you any questions about the scientific method I will just refer you to Lipkins note to Vincent form now on anytime you attempt to bury facts with circular reasoning.
No hard feelings RRM, hope you can swallow your pride and move on.
Ps keep your eyes and ears peeled in the coming weeks.
You present no data and I have constantly presented the data. Try reading.
Where is the data for:
– a “proper” replication study in the field of (retro)virology?
– a more compreshensive replication study than the one by Singh in the field of (retro)virology?
– a validation study which calibrated its assyays to the supposed positives of the study it was trying to validate?
Please do enlighten us with the data, Gobs.
@a2dc987c71224598a61d1888e27a0720:disqus it is amazing that you seem to know what “most CFS patients” believe. You must have quite the rolodex!
Please name
a study that has replicated results without replicating the methodology?
Singh’s study was not a replication study.
http://www.criticalthinking.org.uk/unit2/fundamentals/logicalfallacies/appealtohistory/
“The second type of appeal to history is committed when it is argued that
because something has been done a particular way in the past, it ought
to be done that way in the future.”
How do you know? Did you start lying on behalf of other people now?
We’ve yet to see this famous comedy of yours. Looking forward to laughing at you.
This answer is definitely to the point and related to the discussion made above. Excellent uneducated comment.
I find it very troubling that people in here are under the impression that dr Racaniello is prejudiced in the case of XMRV. Last week I went back and listened to all XMRV related TWIV episodes, and I can definitely say that he is staying objective and not rushing to any conclusions. The fact that he and Alan Dove are skeptical towards this seems to upset some people. I suggest you stop your personal attacks to my favorite podcasters, and keep the discussion to the science. The fact that you are this aggressive makes me feel that I made the right decision by choosing a career in science because I don’t have to deal with people like you in my everyday life.
Well, said. What’s even more insane is the brigade of hilariously ironic self-styled connoisseurs of the “scientific method” who are desperately trying to convince people that avoiding a true replication study is not only acceptable (because, you know, apparently retrovirologists have never heard of the idea before) but actually sensible.
It is inexcusable that a true replication has not been done. It is beyond inexcusable that actual scientists (forgive me if I’m using the word too loosely here) are condoning and promoting this state of affairs.
Everyone knows your an associate of Cort and he has a financial interests that do not include patients getting treatment if XMRV ends up being the cause.
That is not what he said at all and I don’t know how you interpreted it that way. He is saying there are a plethora of explanations for how CFS/XMRV/MLV studies could go awry. That in no way says nonscientists will not be convinced. He’s saying the verdict is still out and that a appropriately powered study still needs to be done. Way to try and blame it on the patients not believing what has not been proven yet. Haven’t we been blamed enough? We are sick, just as MS and Epilepsy patients were sick and finally let out of institutions for only being sick, when the medical test was finally found. Why were the assays changed? And why was she able to find 4% postiive in controls in the prostate study but none in this one with a different assay?
How many would you like? In fact, the WPI science study is a good example of that in itself, as the NCI and CC did not use the same methodology as the WPI to confirm their results.
But to keep the nuts close to us: Montagnier replicated Alter/Lo’s results isolating mycoplasmas from AIDS patients in 1993, using different methodology than Lo/Alter in 1986.
Please note that, while I at least have tried to answer your question without any of you answering mine, your question does not even address my argument at all.
That does not address my argument.
The assertion of Gob is not that this is new methodology, but that it is the normal and even only useful methodology. Asking for a historical example is then not a appeal to history fallacy.
Suppose I say that fortune-telling is the only way virologic findings have been confirmed ‘for thousand of years’. Should I then not be able to provide an example of this having happened in the past?
Please point me to a proper replication study then, Steve. It shouldn’t be hard.
It seems that you are an hilariously ironic self-styled connoisseur of the “scientific method” yourself.
If you read the Science article, you’ll note that Coffin himself notes that the call for exactly replicating WPI’s assays was a strawman argument in his eyes.