1. This is not approved by the author, but was translated by Monique Drost and edited by Heidi Bauer. All effort has been made to stay true to the intention of the author while making sentences grammatically correct in English.
2. Ms. Drost changed the name of the place Nijmegen into UMC St. Radboud (the hospital that facilitated this research), because she would have to use Dutch conjugations like Nijmeegs, Nijmeegse and Nijmegen, and she felt that would be a bit confusing for readers.
- Orthomolecular magazine
Ortho no. 2, sent today to subscribers, contains once again an article on the retrovirus XMRV and the relationship to ME/CFS. However, recent developments couldn't be included in the article, hence this web publication.
By Toine de Graaf
Latest news – 'UMC St. Radboud's' blood XMRV-positive after all
Gendringen, the Netherlands – April 16th, 2010. Researchers from the UMC St. Radboud announced in February that they didn't find the XMRV virus in the blood of Dutch Chronic Fatigue Syndrome (ME/CFS) patients. However, they left out that American researchers did find the XMRV virus in blood samples, taken from the same patients.
This is concluded from a letter that Annette Whittemore, director from the Whittemore-Peterson Institute (WPI) in Reno, sent on Monday, April 12, to Dr. Myra McClure (1). Dr. McClure is a professor in retrovirology at the Imperial College, London, and one of the authors of the first negative "replication study" for XMRV contamination with ME/CFS (2). In her letter, Whittemore invited McClure to co-operate with the WPI to research XMRV. She also reveals some information on the other two negative replication studies that have been produced so far, including the UMC St. Radboud study.
The experimental virologist Dr. Frank van Kuppeveld from UMC St. Radboud and internist doctor Jos van der Meer didn't find a trace of XMRV in the frozen blood of 32 Dutch CFS patients, taken in 1991 and 1992. Also, in the blood of 43 healthy control subjects they didn't find the retrovirus. They published their findings online in the British Medical Journal (3), late January.
However, in her letter, Whittemore points out that the WPI, at the request of van Kuppeveld, has tested some blood samples from the Dutch research cohort before the study at UMC St. Radboud was completed. The WPI found traces of XMRV in those blood samples. Whittemore claims she possesses over email correspondence, which proves that van Kuppeveld was informed about these WPI research results before he published his negative study. However, in his scientific publication, no word is spoken about the co-operation with WPI (3). The redaction at Ortho has requested a copy of the email correspondence with UMC St. Radboud from Annette Whittemore, but this request has not (yet) been honoured.
Furthermore, Whittemore writes in her letter that van Kuppeveld has asked WPI for the reagents and a positive blood sample to determine if his test procedure was able to detect XMRV in positive blood. The WPI met that request. In her letter, Annette Whittemore questions why he didn't use these materials in his research.
Annette Whittemore's letter raises a lot of questions concerning the UMC St. Radboud XMRV study. The most pressing question is whether Van Kuppeveld can confirm WPI's findings. And if so, how many blood samples were sent from the Dutch research cohort to Reno, and how many positive samples did WPI find? And last, but not least, why did the UMC St. Radboud researchers keep silent about all of this in and around their research publication in the British Medical Journal?
Last Wednesday, the redaction of Ortho called virologist van Kuppeveld after emailing him Annette Whittemore's letter. During the call, he declared he had never seen that letter before. Van Kuppeveld also said he wasn't able to respond on such short notice. "I will first have to study the letter, and at least discuss this with my colleagues, who might be out of the country right now," he said.
However, after some urging, van Kuppeveld confirmed Whittemore's findings. He says that the case is slightly more complicated then the letter assumes. According to him, one or more of the 43 healthy control subjects from the UMC St. Radboud cohort has been positively tested on XMRV by the WPI. In conjunction with the findings of van Kuppeveld, this has raised some questions concerning the reliability of the WPI methods. Besides this, he has also stated that he had requested more samples from WPI, but has never received more than one XMRV positive sample.
Seven blood samples
Searching for answers, we contacted Dr. Judy Mikovits yesterday. She is the research director for WPI and leader of the XMRV research. She gave us several answers during a telephone interview. "Frank Van Kuppeveld has sent us seven samples", Mikovits said. "They were numbered 1 to 7. It was about cDNA, that he had made out of RNA".
WPI tested these seven samples with advanced PCR techniques in a closed system, so that contamination was impossible. Three samples appeared to be positive. After they reported the positive numbers to UMC St. Radboud, a message was returned, saying it concerned 2 patients and one control subject. For Mikovits, this result was expected. "We never were informed how many control persons there were on those seven samples, but two positives in seven is approximately what I expected. I didn't count on a 100% score, especially not with PCR.
That one control subject has been found positive by WPI was no surprise to Mikovits. "It totally depends on where you get the blood." At BMJ the UMC St. Radboud researchers have declared that the control samples were taken from people from the same environment as the patients. "The positive control subject is no surprise if it concerns family or a care taker. Control subjects that come with the patients to give blood we call contact-controls. Some of these people might be infected."
It is a fact that XMRV has been discovered with healthy persons. With WPI's own Science Research, in a group of 218 healthy control persons, showed that 8 people had a positive XMRV test (3.7%) (4).
Judy Mikovits and her colleagues are disappointed that the UMC St. Radboud research group has stated nothing about the co-operation with WPI in the BMJ publication. "During a month, we contacted each other at least every 3 or 4 days,' she said. "Material went back and forth, including co-operation agreements, signatures." She felt van Kuppeveld was keeping her on her toes. "He was very strenuous and kept asking whether I had received, tested or looked at stuff."
About a week before the BMJ published the UMC St. Radboud online, the communication fell silent. "That was after I had sent the positive results," said Mikovits. "I considered it to be good news. You've got something to work with. But Van Kuppeveld didn't consider it good news, because they didn't find anything. His message was, on your side, there must have been contamination. Even though I got his material, I was speechless. That was the end of our contact. A week later their publication followed."
Mikovits finds it unbelievable that the UMC St. Radboud researchers haven't used the material they got from WPI in any way. They did claim to have done a replication study. "We sent them antibodies, positive serum and positive DNA," said Mikovits. "Van Kuppeveld could have cultivated his samples, just like we did in our Science study. They could have tested their plasma for antibodies and they could have used our reagents to search for proteins and that kind of stuff. But they didn't, and have also mentioned nothing about the possibilities to do it. We would have wanted Van Kuppeveld to report all the data. If there is a difference in opinion or a misinterpretation, you can look at it together. They could have adjourned the samples, and worked together with us. But you can't just create the appearance to the outside world that nothing happened."
In retrospect, van Kuppeveld and his colleagues only were interested in the PCR technique, while Mikovits assumed that at the UMC St. Radboud the entire Science study would be replicated. "I had no idea he didn't want to do the rest of the research. That totally surprised me."
The WPI kept silent until the beginning of this week. Mikovits suspects that Annette Whittemore was triggered by the statements Dr. Myra McClure recently made on television, where the British retrovirologist disregarded the meaning of XMRV with ME/CFS. After this, Whittemore decided to enter the arena with this letter. "For a long time we thought the best way to deal with this was to continue with the research and forget about the lies. What else can you do? We got seven samples, we did our jobs and reported honestly what we found."
Mikovits confirmed that van Kuppeveld requested more samples. "I wanted to send him more, but what would he have done with it? Find out they were negative and say bad things about it? Mikovits is determined to walk the XMRV-route further, and she sounds more motivated than ever. "We've isolated a virus, and we displayed from a hundred people how their immune system is reacting. Did you know that there is no immune response to a contaminant? The patients obviously are infected with a virus."
Mikovits isn't the only one that takes XMRV seriously. Previously this month it was announced that in Canada people with ME/CFS aren't allowed to donate blood. Canada is the first country in the world that has taken this precaution.
1. Whittemore A, Dear Dr. McClure, April 12th 2010 (www.wpinstitute.org)
2. Erlwein ), Kaye S, [..], Cleare A. Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS ONE 2010; 1e8519
3. Van Kuppeveld FJ, de Jong AS, [..] van der Meer JWM. Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort. BMJ 2010 340:c1018
Lombardi VC, Ruscetti FW, [..]. Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with