Researchers in John Coffin’s Boston lab thought the 2009 study linking Chronic Fatigue Syndrome (CFS) with an unusual virus looked solid. But, when it wasn’t replicated by other scientists, Coffin, a Tufts Medical School virologist and grad student Oya Cingöz went looking for an answer. And, they believe they found one. But, it was not the answer some people with CFS wanted to hear.
In a study published earlier this month, they concluded that the retrovirus virus, known as XMRV, is not linked to the disease. Instead, working with scientists from that National Cancer Institute and UC-Davis, they concluded that it had emerged from a combination of two unrelated viruses in lab mice. The study promises to be the last word on the link between XMRV and CFS. But, it has put Coffin and Cingöz at the center an emotional debate that extends far beyond their Chinatown lab, to the clinic, the web and beyond.
CFS, which is linked to symptoms like ceaseless exhaustion and joint pain, has no known cause and no known cure. Many patients put a huge amount of faith in the original findings and some are rallying around Judy Mikovits, the Nevada scientist who first linked the virus and the disease. In an era where patients do their own research, post their comments on blogs and debate finding via internet forums, that means the Tufts researchers have found their work questioned not by just by scientists, but also by patients on the open web.
Grad student Cingöz said she is sympathetic to people with CFS. And, she and her mentor Coffin both think it is possible the disease is caused by a virus – just not this one.
“In light of the new finding and many other previous findings that failed to find to find a connection between XMRV and CFS, I do believe that the continued research on XMRV for this condition might actually be taking away from the resources that could potentially be used to find the real cause of disease,” she said.
So do the editors of Science. After publishing the Tufts study, journal editors asked for a retraction of the seminal XMRV paper, which also ran in Science. Mokovits has refused.
One issue she raises is that researcher who failed find the virus used different methods that are less effective than hers. In a letter to the journal, Mokivits said that the Tufts/NCI research also failed to explain the presence of XMRV in human test subjects.
She’s not alone in her insistence that XMRV may be the cause of the illness – many patients are standing by her. And, they can now weigh in scientific debates via “”https://dancingwiththesandman.blogspot.com/">online “communities” and social media. Science once debated among experts at academic meetings is now the stuff of Twitter and Facebook. These days, patients are even generating data their own reseach, most famously by the Cambridge company called Patients Like Us.
A March profile of Moskovits in Nature described adoring patients who gave her a standing ovation even though she was two hours late for a talk. But, it also notes that the researcher was “discomforted” by the attention. Coffin has also taken note of patient blogs.
But, not all CFS activists are lining up with Moskivits. A blog post on the “Phoenix Rising,” web site described the release of the recent studies as “MXRV’s worst week.” Some on the site reluctantly admit that new research bodes poorly for the link between this virus and the disease; others say it is too early.
Rivka Solomon says she has been living with CFS for 20 years and has tested positive for the virus. Solomon, who lives in rural Massachusetts, said CFS patients are "hurt and confused’ by the new findings.
“We feel pretty strongly that it is premature to declare the link between CFS and XMRV is dead.”
Like Solomon and others — including several prominant scientists — are holding out for the results of an upcoming comparison of three research teams that promises to settle the debate over research methods.
Back at Tufts, Cingöz said she began looking for the origin of the virus in endogenous murine leukemia viruses that are naturally present in the genomes of mice. She thought she might find viruses that look like XMRV that could be either reservoirs or ancestors of XMRV.
At the same time, collaborators at NCI retraced the cell line looking for MLV viruses, which cannot infect cells from inbred mice but can infect cells from other species, including humans.
“I found this one virus that looks like XMRV in maybe half of its genome, but the rest of its genome was quite different,” she said. “At the same time, our collaborators in at the NCI identified a different MLV, which explained the regions that my virus could not explain. So when you put the two sequences together, they fit perfectly to create a virus that is identical to XMRV.”
The researchers then went back and looked at different passages of the tumor cell line – using a paternity test to be sure they were looking at cells from the same tumor. What they found, Coffin said, was that tumors sample from 1993 did not contain XMR but that sample from 1999 did.
The two mouse retroviruses found by the Tufts and NCI teams must have infected the human prostate cells, where they combined to become XMRV.That data proves that cell were not present in the original tumor but must have passed from the mouse into tumor cells and ultimately into the CFS samples, Coffin said.
“The disease may well be caused by some other virus.” He said. “Whatever virus it is, it is certainly not this virus. This virus somehow accidently found its way into the samples that are being assayed in the lab.”
In a letter to Science, Mikovits said she too is concerned about the inability of her peers to repeat her studies. But, she said that the journal’s publication of an “editorial expression of concern” about her original findings would “be premature and would have a disastrous impact on the future of this field of science.”
She also makes a plea:“Please do not proceed down a path that could be detrimental to the scientific exploration of human retroviruses in infectious disease, cancer, and, therefore, the future health of millions around the world.”
Click here for a “Tufts Today” story on the research.
Click here for a NYTimes story on the research.