Nature: Integrity Issue Follows Fired Researcher

[Firestormm]

5 October 2011: http://www.nature.com/news/2011/111005/full/news.2011.574.html

 

[Esther12]

I think nature were unfair to focus solely on Mikovits, and not mention Ruscetti at all.

We're getting more of an explanation now. She says that the IACFS/ME slide was deliberately mislabelled, with the healthy controls being presented as CFS patient samples for illustrative purposes only, and that this was appropriate for a talk before a patient audience. That sounds plausible to me... although a bit of a risky move when you're already under such pressure.

She says that the AZA-5 was not mentioned specifically in Science, but that activation was. She wasn't clear over whether all samples were treated the same and with AZA-5 (which is the vital point!! Why is no-one asking her this!?!).

Also, I get a sense that other scientists would be a bit pissed if AZA-5 was vital, wasn't mentioned in the Science article, or in their follow up article on methods.

If AZA-5 was used with all samples, then the trouble related to those results could be explained by a few errors, and a bit of a lack of clarity in the Science paper. But we're still not exactly clear with what happened, and even those errors were pretty silly and costly.

I'm getting off-line to listen to some Miles Davis and get ready for bed. Thanks for the article Fire. Take care all.

 

[currer]

What can I say?

This is a show trial.

We patients are done for.

 

[ukxmrv]

Mikovits says that the Science paper didn't mention the azacytidine treatment because that detail was not necessary for the publication. Instead, the authors referred to the samples as being 'activated'. But for her presentation, she wanted to emphasize that the addition of methyl groups to viral nucleic acids may have prevented the virus from being detected using standard assays. Azacytidine strips off those methyl groups and, Mikovits argues, can boost viral gene expression.

If I were a researcher, I'd be pissed that they left this vital detail out of the original Science article.

Hindsight is a wonderful thing Ecoclimber,

When the original Science paper was published Dr Mikovits et al obviously didn't know that replication attempts would be so bad.

You are nitpicking here

 

[justinreilly]

Mikovits says that the Science paper didn't mention the azacytidine treatment because that detail was not necessary for the publication. Instead, the authors referred to the samples as being 'activated'. But for her presentation, she wanted to emphasize that the addition of methyl groups to viral nucleic acids may have prevented the virus from being detected using standard assays. Azacytidine strips off those methyl groups and, Mikovits argues, can boost viral gene expression.

If I were a researcher, I'd be pissed that they left this vital detail out of the original Science article. There is more to it then that as well where Patient sample 2905 in lane 3 and patient sample 1674 in lane 6 are treated with 5-azacytidine in the original experiment. This is not disclosed in the Science paper.

B. At the Ottawa talk
Lane 1 (T cells in the original experiment) is described as Normal PBMC
Lane 2 (T cells in the original experiment) is described as 2905 PBMC
- In other words a non patient control sample is being described as a patient sample in the talk.
Lane 5(PBMC4/10 in the original experiment) is described as patient 1674
- Again, describing a non patient control as a patient sample.

OK, I'm out of my depth here, but may be she felt that saying it was "activated" was enough; either that any 'activation' substance would be ok or that if someone wanted to do a replication, they could contact her since she wasn't allowed the space to include everything. I guess that leaves the question of why she didn't specify aza in the follow up methods paper. Did she still think it wasn't needed? Maybe she hadn't realized yet how crucial it was to emphasize the aza. Just speculating. Curious what people's thoughts are who know something about this type of thing.

I'm not a scientist, but i'm underwhelmed by the 'charges.' She was a little lazy or rushed and it was more efficient to do it this way than to do some more editing. It seems like quibbling to me. doesn't seem to me to deserve the tag that nature gave it of "scientific misconduct" (check out the upper left hand corner of the page).

All this from a very mentally unstable person, ERV. Does it really deserve this attention? not really, but we have Trine to thank for what seems to be nitpicking. If I were a reporter, my reaction would be 'ehhh (shrug); what else you got?' Keep in mind these are reporters who are supposedly too busy to look into trifles like decades-long standard operating procedures of patent fraud in "science" publishing by Wessely, BMJ etc, etc.

 

[Lee]

From the Nature article:
"Mikovits says that the Science paper didn't mention the azacytidine treatment because that detail was not necessary for the publication. Instead, the authors referred to the samples as being 'activated'. But for her presentation, she wanted to emphasize that the addition of methyl groups to viral nucleic acids may have prevented the virus from being detected using standard assays. Azacytidine strips off those methyl groups and, Mikovits argues, can boost viral gene expression."
-----------------------

In immunology, 'activation" means something very specific - essentially, turning on the immune functions of the cells.

In Figure 2A, they describe how they activated the cells (this seems important enough to describe):
"PBMCs were activated with phytohemagglutinin and interleukin-2..."

In Figure 2C, they say:
"Lysates of activated PBMCs from healthy donors (lanes 1, 2, 4, 5, and 7) or from CFS patients (lanes 3 and 6) "
Activated PBMCs.

Nothing about 5AZA.

When JM implies that describing the cells as 'activated' covers the 5AZA treatment - she is not being truthful.
Remember, Ruscetti says that the Ottowa labels were correct, and from Ottowa we know that only the patient samples were treated with 5AZA.All the samples were activated. Activation does not mean 5AZA.
------------------------


JM argues that mentioning the 5AZA treatment was not necessary for publication.
She also says that treatment with 5AZA boosts virus production.
So, by her own words, they boosted virus production in patient samples, did not do so in controls. They saw virus in patient but not controls - they showed us this, in the WB. They used this difference to claim that patients have virus, but controls do not.

But they didn't feel it was necessary to mention that they had boosted virus production in patient samples but not controls?

It's a ludicrous claim.

 

[justinreilly]

so if they only used 5aza on the patient samples in the study then then the study wasn't blinded? i'm confuse...

From the Nature article:
"Mikovits says that the Science paper didn't mention the azacytidine treatment because that detail was not necessary for the publication. Instead, the authors referred to the samples as being 'activated'. But for her presentation, she wanted to emphasize that the addition of methyl groups to viral nucleic acids may have prevented the virus from being detected using standard assays. Azacytidine strips off those methyl groups and, Mikovits argues, can boost viral gene expression."
-----------------------

In immunology, 'activation" means something very specific - essentially, turning on the immune functions of the cells.

In Figure 2A, they describe how they activated the cells (this seems important enough to describe):
"PBMCs were activated with phytohemagglutinin and interleukin-2..."

In Figure 2C, they say:
"Lysates of activated PBMCs from healthy donors (lanes 1, 2, 4, 5, and 7) or from CFS patients (lanes 3 and 6) "
Activated PBMCs.

Nothing about 5AZA.

When JM implies that describing the cells as 'activated' covers the 5AZA treatment - she is not being truthful.
Remember, Ruscetti says that the Ottowa labels were correct, and from Ottowa we know that only the patient samples were treated with 5AZA.All the samples were activated. Activation does not mean 5AZA.
------------------------


JM argues that mentioning the 5AZA treatment was not necessary for publication.
She also says that treatment with 5AZA boosts virus production.
So, by her own words, they boosted virus production in patient samples, did not do so in controls. They saw virus in patient but not controls - they showed us this, in the WB. They used this difference to claim that patients have virus, but controls do not.

But they didn't feel it was necessary to mention that they had boosted virus production in patient samples but not controls?

It's a ludicrous claim.

 

[Esther12]

But they didn't feel it was necessary to mention that they had boosted virus production in patient samples but not controls?

Has it been clearly stated that this is what happened anywhere yet?

From the look of the slides, it does seem that this is the case... but surely this is the key point? Why didn't the Science or Nature articles confirm it one way or the other with Mikovits/Ruscetti? If it is the case, then the claim that it was not worth mentioning in the Science paper does seem bizarre.

 

[oceanblue]

(@Lee "But they didn't feel it was necessary to mention that they had boosted virus production in patient samples but not controls?")

Has it been clearly stated that this is what happened anywhere yet?

From the look of the slides, it does seem that this is the case... but surely this is the key point? Why didn't the Science or Nature articles confirm it one way or the other with Mikovits/Ruscetti? If it is the case, then the claim that it was not worth mentioning in the Science paper does seem bizarre.

Yes, weird it hasn't been clarified. You'd think Mikovits/Ruscetti would have been keen to spell out that all samples (patients and controls) were treated with 5-aza if that was really the case, and that the Ottawa slide was wrongly labelled in that resepct. The fact this wasn't spelled out by them makes me very suspicious, but I agree Science and Nature should have explicitly clarified this (not least because it's the main story).

 

[redo]

There are thousands of members on these boards, so it's not easy to keep track. So there's no need to get in defence position. I've got some normal questions. I saw how the other thread turned out, and I was sorry to see that.

[...]If I were a researcher, I'd be pissed that they left this vital detail out of the original Science article. There is more to it then that as well where Patient sample 2905 in lane 3 and patient sample 1674 in lane 6 are treated with 5-azacytidine in the original experiment. This is not disclosed in the Science paper.

I was under the impression that you where a researcher and a CFS patient. Correct me if I am wrong. Or a researcher and a person whom had a loved one with CFS.

Just to forewarn the patient community, things are going to get really ugly in the near distant future. But remember this point, there are still many dedicated scientific researchers conducting scientific experiments to find the cause and cure for this illness. The media might have a field day but remember this. NEVER, EVER LOSE HOPE!

Eco

About this quote. Is it the things going down now you where talking about?

I very much welcome that you've shared information, and I am certainly not out to "get" anyone, just to make that clear.

 

[redo]

I understand your question and your frustration but at this time I feel that it serves no purpose to reveal anymore additional information. If you want to get some related background information you can always Google Miller Ecoclimber.

There is going to be further information coming out in the way of explanation on the slides and labeling and how it effects the claims made in the Science paper today. There will be further official investigations which will result in revealing information on whether any criminal or civil charges will be forthcoming. The future of ME/CFS research at the WPI is still up in the air. Normally, NIH grants stay with the institution. There will be a legal battles, lawsuits filed concerning patents and intellectual property...claims and counterclaims being made. There is also the issue on accountability of funds collected from various groups for various projects and whether those funds were used properly. There will be issues concerning the testing protocol or the test kits that patients paid for. The legality of promising that these tests could detect XMRV within the blood has been refuted by the BWG group. Science is still considering on whether to retract the Lombardi et al. paper and the ramification from that decision if it is retracted will be severe in regards to future research and funding. So in answer to your questions, yes, there is still a lot that will be coming out in the days and months ahead unfortunately.

Eco

There's no frustration here ecoclimber :Retro wink: I was curious if the cat was out of the bag or not, according to the quote above ("Just to forewarn the patient community, things are going to get [...]"). Or if there where more to come on top of what you've already mentioned (and what came out just recently).

(I googled some eco, and for what it's worth I think the ethics comitee treated you very unethically ;-) I really thought I'd PM, but as it's shut off I just posted here. You've got my full support on the activites you are doing for all of us.

 

[Firestormm]

There is going to be further information coming out in the way of explanation on the slides and labeling and how it effects the claims made in the Science paper today.

There will be further official investigations which will result in revealing information on whether any criminal or civil charges will be forthcoming. The future of ME/CFS research at the WPI is still up in the air.

Normally, NIH grants stay with the institution. There will be a legal battles, lawsuits filed concerning patents and intellectual property...claims and counterclaims being made.

There is also the issue on accountability of funds collected from various groups for various projects and whether those funds were used properly. There will be issues concerning the testing protocol or the test kits that patients paid for.

The legality of promising that these tests could detect XMRV within the blood has been refuted by the BWG group. Science is still considering on whether to retract the Lombardi et al. paper and the ramification from that decision if it is retracted will be severe in regards to future research and funding.

So in answer to your questions, yes, there is still a lot that will be coming out in the days and months ahead unfortunately.

Eco

Hi Eco,

I don't have subscription to Science but there was something about Mikovits up for 7 October in Newsmakers; although I don't think it was what you are suggesting. Perhaps you have access and can repost?

On a previous thread - now closed - you mentioned trying to upload something. Would you PM me perhaps? Only I can't seem to PM you.

Re: retraction I tend to agree - Science have been reviewing Lombardi since before Silverman's partial retraction and have said this WB analysis is also being investigated. I also think contamination concerns will be a feature if they even publish their full rationale.

Fire