Take three. Western blot gel April 09 (top) shows the original number of patients and the use of 5-azacytidine, but the numbers were changed and the chemical was not mentioned in the October 09 science paper (middle), who became
science Lombardi et al; Judy Mikovits
Judy Mikovits had some rough weeks. September 22, Scienc he posted online a new laboratory study widely considered the last blow to the theory, defended by Mikovits and colleagues in 09 Science paper October, which recently detected mouse retrovirus might play a causal role in chronic fatigue syndrome (CFS). A letter in the same issue of Science of one of the laboratories contributing to the 09 report revealed that the contamination had marred his contribution detection-PCR and sequencing mouse virus, dubbed XMRV. Mikovits and colleagues have defended the validity of the remainder of the study, known as the Lombardi et al ., Which detected the virus by several other methods, so Science has issued a rare partial withdrawal of the original article.
Then on September 29, Mikovits was fired from his post as research director of the Whittemore Peterson Institute for Neuro-Immune Disease (WPI), a private organization in Reno, Nevada, dedicated to research and the treatment of CFS. Both Mikovits and CEO of WPI, Annette Whittemore, say the shooting was not related to the disappearance of the theory of XMRV.
The next day a graduate student who wrote a sarcastic blog that was critical of Mikovits and XMRV theory raised questions about whether a figure in Lombardi et al . had been distorted. Science Editor Monica Bradford said in a statement that the review examines the allegation. "As our policy in cases of alleged manipulation figure, we follow with the authors of the research from our own review of the claim is over," said Bradford. " Science takes these matters seriously and seeks to answer fully and effectively."
Fury turns around an image of the lower half of Figure 2C in Lombardi et al .- shows that XMRV proteins CFS patients but not healthy controls . In known as VRE (endogenous retroviruses) blog, Abbie Smith September 30 noted the striking similarities between 2C and Mikovits slide presented at a meeting of the CSA in Ottawa, Canada, September 23. Smith, who is working on his doctoral thesis at the University of Oklahoma, Oklahoma City, and HIV studies, wrote an anonymous informant had reported to her that the two identical pictures looked, but had a different number of patients and experimental conditions. Smith asked if this was a simple mistake or an attempt to recycle the old data to a new argument.
The slide Ottawa supports the thesis that although Mikovits XMRV could not be detected in CFS patients, and others roamed gammaretroviruses their chromosomes. Mikovits describes how it treated cells two CFS patients with chemical 5-azacytidine, which takes methyl groups of the DNA. This procedure prods cells that harbor latent versions of retroviruses to produce them, and the image on the slide shows the protein resulting in what is known as a Western blot gel. In Lombardi et al . what appears to be the same image shows "XMRV protein" and makes no mention of 5-azacytidine use.
Mikovits collaborator, Francis Ruscetti of the National Cancer Institute (NCI) in Frederick, Maryland, who ran all Western blots, confirmed that the slide Ottawa uses the same image that appears in Lombardi et al . Ruscetti and Mikovits, in a joint email to Science for this article, said many patients and their doctors, Daniel Peterson (who has since had a falling out with WPI), knew the original coded numbers so the researchers changed them for publication science "to protect patient privacy." Ruscetti said it was a mistake for Mikovits have used the codes from the original patients in Ottawa. " We were under so much pressure, we missed, "said Ruscetti.
regarding the use of 5-azacytidine, and Ruscetti Mikovits said in their email that" there was no attempt in the original document to hide anything. " They say the purpose of Lombardi et al , the use of 5-azacytidine was not germane. They were simply trying to show that CFS patients had viral proteins not seen in controls. At the time of the Ottawa meeting, they say they have realized that this experience does not actually show XMRV proteins but a larger family gammaretroviruses.
After Lombardi et al . appeared, several laboratories have reported that they could not detect XMRV in CFS patients. But Ruscetti Mikovits and noted that most of these studies relied polymerase chain reaction, which used DNA sequences of XMRV to fish pieces of the virus from blood samples. These tests, they point out, have missed other gammaretroviruses with different sequences. The Western blot test they used in Lombardi et al . so happened to cast a wider net that discovered the protein of any member of the family gammaretrovirus. Moreover, they say, the use of 5-azacytidine said these infections would be missed in routine testing, because these viruses often exist in a latent state.
On the blog of VRE, Smith and others have also argued that the study lacked appropriate controls: healthy controls in this experiment are not 5-azacytidine added to their samples. "My [principal investigator] say," Why did you run this gel? if I gave him, "wrote Smith.
Vinay Pathak, a retrovirologist the NCI who earlier damaged the XMRV theory / CFS with a study published in Science who documented how the virus was created accidentally in experiments laboratory, said he was "perplexed" by Ruscetti of and explanations about Mikovits Figure 2C. "If [5-azacytidine] was used in the original experiment, it is clearly wrong to leave him out of the Science paper, "says Pathak. "It makes a difference how I interpret the results."
Jonathan Stoye, a retrovirologist who once supported the XMRV / CFS hypothesis, but then changed his mind after his own studies have failed to replicate the finding, said its time to retract Lombardi et al . in its entirety. "I think there is a point where Science has to say, there is no substance to this document," said Stoye. "It was published with a message, and that message is party. "
neither Lombardi et al . or questions on the slides were mentioned in September 30 letter from Whittemore end formally the contract Mikovits, sent the day after the two had a heated telephone conversation. In this letter, Whittemore asked its high profile researcher to be "insubordinate and insolent." Mikovits was immediately locked out of his laboratory.
Three letters between Whittemore and Mikovits say the articulated shooting that Mikovits spend on a cell line that was sent to Vincent Lombardi, the first author of 09 Science paper in October that directs UNEVX (formerly known as VIPDx), a diagnostic laboratory belonging to WPI. Until recently, the laboratory has sold a test for XMRV and related viruses.
In a written response to October 1 Whittemore, Mikovits argued that it was "entirely appropriate" for her as director of research, not to Lombardi cell line. The line cell was not linked to studies on gammaretroviruses but Lombardi wanted to use for experiments related to a grant Mikovits had obtained US National Institutes of Health to study the possible causes of CFS. Mikovits argued that Lombardi " would not take my direction "and should not be undertaken a new project," while neglecting other duties. "She also questioned its ability to carry out this experiment.
Annette Whittemore issued a statement Science in which it strongly defended the performance of Lombardi. "Dr. Lombardi is a valuable and important part of our team, and conducts research accordingly, "says Whittemore." While personnel matters are generally confidential, statements made by Judy Mikovits are false, baseless and those of a disgruntled former employee. "
in an interview with Science Mikovits argued that his shot was also linked to a long battle of the decision WPI sell by VIPDx / UNEVX, a test for human gammaretroviruses. the laboratory began offering the tests, which cost about $ 500, soon after Lombardi et al . reported a link between XMRV and CFS. Some patients tested positive continued to take antiretroviral drugs, "I said," No, no, no, no. "says test Mikovits" I asked them for the better part of two years to show me that what we have in Lombardi. et al . The same thing they sell to patients. "
The issue came to a head with the recent publication by Science study of new laboratory. The Working Group blood is called, which included laboratories managed by Mikovits and Ruscetti, failed to find XMRV reliably or other gammaretroviruses in blind samples from people who had previously tested positive for the virus. both Mikovits Ruscetti and co-author of the paper, which invalidated their own tests for XMRV. WPI said UNEVX stopped offering diagnostic tests, but did not give details on the timing or the reasons.
Whittemore, which refers to CFS as myalgic encephalomyelitis (ME) -a common name for CSA in Europe stressed that the Institute remains dedicated to human gammaretroviruses study "ME and related diseases" and that person there "would never put personal interest before the search or find the causes of ME."
Mikovits, who said she currently does not have access to his laboratory notebooks, is looking for another institution to continue its work.
With reporting by Martin Enserink .
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