Chronic fatigue syndrome: virus hypothesis collapses further, Forbes magazine ‘Fighting Pseudoscience' blog, 2 June 2011 (story by Steve Salzburg).
Two years ago, a team of scientists announced with great fanfare that they’d found the cause of chronic fatigue syndrome: a mouse retrovirus called XMRV. There were many media reports and much excitement, and at least a dozen studies were launched to look for this virus in more patients. Unfortunately for patients, the findings turned out to be seriously flawed.
New results published this week seem to be the final nail in the coffin for the XMRV hypothesis. The editors at Science have taken the unusual step of publicly asking the authors of the 2009 study to retract their findings. As reported in the Wall St. Journal, Science sent a letter to the authors stating:
“At this juncture, Science feels that it would be in the best interest of the scientific community” for the co-authors to retract the paper.”
In addition, the editors published an “expression of concern” this week, which is their way of warning everyone that the results are wrong. Judy Mikovits, the leader of the study, steadfastly insists that she is right and all the others are wrong.
Despite Mikovits’ claims, the evidence is very clear that she is wrong. Study after study has found no trace of the virus in CFS patients. Where Mikovits’ original study found 67% of the patients had XMRV, followup studies found 0%. A set of three papers in the journalRetrovirology, published in December, showed conclusively that the finding was due to laboratory contamination. The XMRV virus turned up as a contaminant in cancer cell lines that are widely used in laboratory research. As I wrote in January:
“It turns out that a common tumor cell line called 22Rv1 is infected with MLV-X. It also turns out that all the XMRV sequences from human patients are far more similar to the exact same strain of MLV-X that is in the mouse cell line. The tumor cell line was in the lab doing the experiments: ergo, it’s contamination. Elementary, my dear Watson.”
Two new papers in Science this week found the same thing. One of them, titled “No Evidence of Murine-Like Gammaretroviruses in CFS Patients Previously Identified as XMRV-Infected” looked at patients who had tested positive for the XMRV virus, and found that they didn’t have it all. The second study provides new detail on how the XMRV virus got into the cancer cell lines.
So why does Mikovits cling so fiercely to her claims? (She posted a long letter defending herself at the Whittemore Peterson Institute, where she works.) What she doesn’t say is that she has gone far beyond her original findings: she and her institute are actively promoting the use of anti-retroviral therapies for CFS patients. As Nature News reported in March,
“The WPI owns a company that charges patients up to $549 to be tested for XMRV, and Mikovits believes that patients who test positive should consult their doctors about getting antiretroviral drugs normally prescribed to those with HIV.”
This is a blatant conflict of interest, and it perhaps explains some of Mikovits’ stubbornness.
It gets worse. As Trine Tsouderos reported last summer in the Chicago Tribune, Mikovits claimed at the Autism One conference that XMRV also causes autism. She has no evidence to support this startling claim. Mikovits stated to the Tribune that “unless we do something now this (XMRV) could be the worst epidemic in U.S. history.”
Mikovits also believes there is a conspiracy against her. In March, she told Nature “I had no idea there was that much bias against this disease.” Nonsense. The collapse of the evidence about XMRV and chronic fatigue syndrome is just science doing what it is supposed to do: when a study cannot be replicated, then the hypothesis is abandoned and we move on.
This is a classic tale of a scientist gone bad. Unfortunately for CFS patients, Mikovits is distracting attention from efforts to find the real cause. By speaking at the Autism One conference, she has joined the ranks of pseudoscientists and anti-vaccinationists. It’s pretty clear now that she will never retract her findings, despite the pressure from the editors atScience. I can only hope that CFS patients, who are understandably desperate for a treatment, won’t be fooled into taking ineffective and possibly harmful therapies based on the failed XMRV hypothesis.
Bloomberg: Chronic Fatigue Study That Sparked Ban May Have Been Flawed, 31 May 2011 (story by Elizabeth Lapatto and Michelle Fay Cortez).
“Calls to retract the paper at this point are premature”, says Ian Lipkin, who is leading a major study.
A 2009 study on chronic fatigue syndrome that led to a ban on blood donations from sufferers of the disease may have been spoiled by laboratory mistakes, according to the science magazine that published the research.
While the study linked the syndrome to the mouse virus XMRV, at least 10 trials since then haven’t been able to duplicate the results, the journal Science said in an editorial published today. New research also indicates the blood samples used in 2009 likely were contaminated with the virus in the lab, Science said.
The study’s validity “is now seriously in question,” Bruce Alberts, editor-in-chief of Science, said in the editorial.
Science requested a voluntary retraction from the 2009 study’s authors, said spokeswoman Natasha Pinol in a telephone interview. Judy Mikovits, one of the study’s authors, contacted the journal on May 30 to inform them she disagreed with the editorial expression of concern, Pinol said.
“We feel this is an extremely premature action which is not in the best interest of the scientific community or human health,” Mikovits said in a letter to Science published on the website of the Whittemore Peterson Institute for Neuro-Immune Disease. “We respectfully request that you allow the scientific process to run its course unhindered by bias.”
A phone call to Mikovits’s office at the Whittemore Institute in Reno, Nevada, wasn’t returned. The trial was led by Vincent Lombardi of the institute and Francis Ruscetti, a National Cancer Institute scientist in Frederick, Maryland.
Extremely Disappointed
“We are extremely disappointed that the editor of Science has published an ‘editorial expression of concern,’” said Annette Whittemore, president of the Whittemore Institute, in an e-mail. “The authors of the Lombardi study believe that it is premature to conclude that the negative studies are accurate or change the conclusions of the original studies and we fully agree.”
The study led the American Red Cross, the largest U.S. supplier of blood products, to announce in December 2010 that it would no longer allow donors with chronic fatigue syndrome. The U.S. National Institutes of Health is sponsoring studies to determine if a link between XMRV and chronic fatigue syndrome can be confirmed.
Clinical Trial
The study of 150 patients with chronic fatigue syndrome and another 150 healthy volunteers should be complete by early 2012, said Ian Lipkin, a professor of epidemiology at Columbia University in New York, who is leading the effort. Until the research is complete, it’s too soon to know whether there is a link between a virus and chronic fatigue, he said.
“Calls to retract the paper at this point are premature,” said Lipkin, director of Columbia’s Center for Infection and Immunity, in a telephone interview. “We need to let this study take its course, look at the data in a coherent fashion and figure out what it tells us.” While interesting, “the publications don’t dissuade us from continuing our work.”
More than 1 million people in the U.S. have chronic fatigue syndrome, more than those with multiple sclerosis, lupus, or lung cancer, according to the Centers for Disease Control and Prevention in Atlanta. The condition, which saps people of energy for months or years, has no proven cause and mostly affects women ages 30 to 50, according to the National Institutes of Health. Women are four times more likely than men to develop the disease.
Original Conclusion
The study, published in October 2009, found XMRV in the blood of two-thirds of tissue samples taken from people with the condition and 3.7 percent of a group of healthy individuals.
Scientists led by Jay Levy, a professor of medicine at the University of California, San Francisco, said in a study today that the link was probably because chemicals and cell lines used in the lab where it was detected were contaminated with XMRV.
Levy’s group examined 61 patients with chronic fatigue syndrome, 43 of whom had been previously reported as infected with XMRV. Using a similar procedure to the original paper, the scientists tested the blood. They didn’t find any evidence of XMRV or any other mouse-related virus.
In addition, the Levy study demonstrated that human serum quickly kills the virus, making an infection unlikely.
‘Totally Surprised’
“When that paper came out I was totally surprised and suspicious,” Levy said today in a telephone interview. “Who knew there would be pressure on the government to do these expensive studies? I’ve never been around anything quite so dramatic and misleading and misunderstood for so long. There are financial ramifications, and medical and health ramifications.”
The Whittemore researchers didn’t claim the virus caused chronic fatigue syndrome. People with the condition may be more vulnerable to the virus or it may be a so-called passenger virus, one that shows up in diseased tissue without being a cause of the illness, the researchers said.
A second paper also published today by Science showed that XMRV was created by recombining two mouse leukemia viruses while scientists passed a human prostate tumor to mice. The cell line derived from that graft is the best explanation for the detection of XMRV in human samples.
“Taken together, these results close the door on XMRV as a cause of human disease,” John Coffin, a professor at Tufts University School of Medicine in Boston and a co-author of the paper, said in a statement.
To contact the reporters on this story: Elizabeth Lopatto in New York at elopatto@bloomberg.net; Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net.
New York Times: Studies Examine Syndrome of Fatigue, 1 June 2011 (story by David Tuller)
In a blow to patients with chronic fatigue syndrome, two new studies published on Tuesday raised serious doubts about earlier reports that the disabling disease is linked to infection with XMRV, a poorly understood retrovirus.
The new papers were posted online in the journal Science, which in October 2009 published the initial research linking XMRV to chronic fatigue syndrome. In an “editorial expression of concern” accompanying the two new studies, Bruce Alberts, editor in chief of the journal, declared that the earlier finding “is now seriously in question” and was most likely due to laboratory contamination.
Based on those earlier findings, some people with chronic fatigue syndrome tried to obtain access to antiretroviral drugs used to treat H.I.V., which had been shown in laboratory studies to inhibit the replication of XMRV.
But in one of the two new studies, researchers found no trace of XMRV or related viruses in the blood of 43 patients who had previously tested positive for XMRV. In the second study, scientists reported evidence that XMRV was likely a recombination of two mouse leukemia viruses created accidentally in laboratory experiments.
The new studies are the latest in a series of disappointments for people struggling with chronic fatigue syndrome. Other researchers have been unable to duplicate the original findings implicating XMRV, although none of their studies fully replicated the methods of the original research from the Cleveland Clinic, the National Cancer Institute and the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev.
Dr. Vincent Racaniello, a microbiology professor at Columbia University, said in an interview that it now appeared unlikely that XMRV infection is a cause of chronic fatigue syndrome. But it also would be wrong to conclude that chronic fatigue syndrome is not an infectious disease, he added.
“These patients have a lot of signs of hyper-immune activation, with their immune systems firing almost constantly,” he said.
Dr. Jay Levy, a professor of medicine at the University of California, San Francisco, and the senior author of one of the new studies, said he nonetheless believed that many or most people with chronic fatigue syndrome are suffering from a disease initiated by one or more viruses.
Many of the disease’s symptoms are likely caused by the immune systems’ response to an infection, rather than to the pathogens themselves, he said.
“The immune system pours out its toxins to stop this agent, and then the immune system doesn’t calm down,” he said, adding that environmental toxins could also play a role in the illness.
Last week, the editors of Science asked the authors of the original research if they would retract their paper in view of the new findings about to be published. The senior author, Dr. Judy Mikovits, research director at the Whittemore Peterson Institute, responded that such a step was “premature” and that she knew of other investigators planning to publish research backing the original findings.
Some patients reacted angrily to the news that Science had asked for a retraction. “The patient community is shocked,” Rivka Solomon, a largely homebound Boston-area writer with chronic fatigue syndrome, said in an e-mail. “Most of us feel that the scientific inquiry necessary to bring this to conclusion has not yet been played out.”
Ms. Solomon recently organized small demonstrations in Washington, D.C., and San Francisco to focus attention on the small amount of financing the government has allocated to the disease in recent years. If the XMRV association does not pan out, she wrote, patients like her “worry that we will once again be abandoned.”
The government is supporting additional studies to determine whether XMRV plays any role in chronic fatigue syndrome at all. The retrovirus had also been linked to prostate cancer, an association also challenged by the research published on Tuesday.
CBS News: Scientists now doubt studies linking chronic fatigue syndrome to mouse virus, 31 May 2011
(CBS/AP) Doctors who continue to believe that chronic fatigue syndrome is caused by a mysterious mouse virus may need to wake up and smell the coffee. New studies suggest that previous research purporting such a link was a false alarm.
In 2009, researchers in Nevada and Maryland said they had linked chronic fatigue to the so-called XMRV virus, which causes illness in mice. The announcement made headlines and fueled hopes that a cause had finally been found for chronic fatigue syndrome, an illness that affects about 1 million Americans.
But two new studies suggest the purported link between the XMRV virus and chronic fatigue syndrome may have been simply the result of laboratory contamination. On Tuesday, the journal “Science” took the unusual step of declaring the XMRV link “seriously in question.”
In a separate study, yet another team of researchers tested blood from the same chronic fatigue patients used to make that first 2009 link with XMRV. This new testing, which avoided using lab products derived from mice, found no evidence XMRV, further supporting the lab-contamination explanation. In any case, substances in human blood are able to kill the mouse-related virus, said lead researcher Dr. Jay Levy of the University of California, San Francisco.
The National Institutes of Health has begun other studies to settle the issue, but Dr. Levy said it's time to give it a rest and focus on other causes. “Let's use the money to find the real culprit,” he said.
Researchers at Nevada's Whittemore Peterson Institute, who first reported a possible XMRV link, didn't immediately comment Tuesday.
Chronic fatigue syndrome is characterized by overwhelming fatigue for at least six months despite ample rest. The condition also causes weakness, muscle pain, impaired memory and/or mental concentration, and insomnia. Chronic fatigue syndrome can't be diagnosed with a simple test, so scientists diagnose by excluding other disease-causing factors. Women between the ages of 40 and 50 years old are most frequently diagnosed with the disease.
The CDC has more on chronic fatigue syndrome.