Saturday, September 4, 2010


The XMRV conference at the National Institutes of Health (NIH) in Bethesda, Maryland, is days away.

Most of you are familiar with the lineup of speakers by now, including Drs. Judy Mikovits, Shyh-Ching Lo, Frank Ruscetti, Eric Klein, Robert Silverman, John Coffin, Sam Chow, Ila Singh, Kate Bishop, Brigitte Huber and Bill Switzer. 

Getting up to speed on the rules and regs at the NIH, I learned from the agency's website that conference attendees are forbidden to bring explosives, open containers of alcohol and archery equipment.  Supply your own joke here.

I look forward to reporting what I learn.

Monday, August 30, 2010


Susan Douglas, the British producer of the upcoming feature documentary What About ME?, told CFS Central that the filmmakers are seeking one- to two-minute clips from ME/CFS patients—“not prettied up, but as they are.”  Douglas wants to form a video community of patients to garner sources for the film and to get patients communicating with each other.

Annette Whittemore co-founded the Whittemore Peterson Institute and funded research into the retrovirus XMRV to help her daughter Andrea, who has lived with ME/CFS for 20 years.  Douglas’s film chronicles their story.  “It’s the story of what love can do,” explains Douglas, “woven through the world of suffering with ME/CFS.”

XMRV is the spine of the film.  The documentary will also examine the attitudes of governments, the medical profession and sufferers in Great Britain and the U.S.   “As it is a documentary, there will be elements of the story still unknown to us, as they unfold in front of our eyes, but I do promise you a very human drama, that is based on total truth, and an eye opener for the planet,” Douglas says.
Directed by British filmmaker Geoffrey Smith, best known for his award-winning documentary The English Surgeon, the film will be released in 2011.  A DVD is also planned, as are sales to television and cable channels, as well as online virals.  For more information on submitting clips and donating to the film, click here.  To read an earlier CFS Central article on What About ME?, click here.

Friday, August 27, 2010


The Dream Cast

Ixchelkali's comment about awaiting the ME/CFS mini series back on the June 20th post got me thinking:  Who should play the key roles in the ME/CFS saga from the 1984 outbreak in Incline Village, Nevada, to the present?  What's the dream cast?

Sometimes the physical similarities to the actual person drew me to a particular actor.  The energy of other actors dovetailed with that of the real-life people they would portray.  Some of these actors are so versatile—Peter Sarsgaard, Edward Norton, Phillip Seymour Hoffman, Patricia Clarkson, Laura Linney, Sissy Spacek, James Cromwell, I could go on—that they're well suited to more than one role.  Zeligs that they are, Sean Penn, Tom Wilkinson and Chris Cooper could play any of the male roles.

As long as we're dreaming, the mini series would be written by Eric Roth and Michael Mann (The Insider) or Matthew Weiner (Mad Men) or Ted Tally (The Silence of the Lambs), produced by Tom Hanks and directed by any of the following: Ron Howard (Frost/Nixon), Michael Mann (The Insider), Doug Liman (the Bourne films), Luc Besson (La Femme Nikita, The Professional), Martin Scorsese (The Departed; Goodfellas), Florian Henckel von Donnersmarck (The Lives of Others), Jonathan Demme (The Silence of the Lambs), Christopher Nolan (Inception; The Dark Knight), or Roger Spottiswoode (And the Band Played On).

Besides being a science writer, I've served as a TV editor and film critic, so this assignment was especially fun and a break from the usual. After this news-heavy week, a casual Friday seemed long overdue. Please submit your casting suggestions as well.

Dr. Elaine DeFreitas (a former researcher at the Wistar Institute who discovered evidence of a retrovirus in ME/CFS patients in 1991)
Edie Falco
Illeana Douglas
Cher (if she were 20 years younger)

Dr. Paul Cheney (who, along with Dr. Daniel Peterson, reported an outbreak of ME/CFS in Incline Village, NV, to the CDC in 1984)
Edward Norton
Ralph Fiennes 

Dr. Daniel Peterson (co-founder of the Whittemore Peterson Institute and co-author of the Science paper linking XMRV to ME/CFS)
Colin Firth
Peter Krause
Campbell Scott
Peter Sarsgaard
Josh Brolin

Dr. David Bell (ME/CFS physician who reported an ME/CFS outbreak in Lyndonville, NY, to the CDC in 1985)
Philip Seymour Hoffman
Richard Dreyfuss

Dr. Stephen Straus (head of CFS research at the NIH until his death) 

Dr. William Reeves (chief of CFS research at the CDC for 20 years)
Jeremy Irons
Stanley Tucci

Hillary Johnson (author of Osler's Web)

Marc Iverson (founder of the CFIDS Association)
Matt Ross

Kim Kenney McCleary (CEO of the CFIDS Association)

Dr. Anthony Fauci (director of the National Institute of Allergy and Infectious Disease) 

Dr. Nancy Klimas (HIV and ME/CFS physician)
Dr. Anthony Komaroff (Harvard ME/CFS physician and co-author of the FDA/NIH/Harvard MLV paper)

Congressman Jerrold Nadler (who spearheaded the 1996 congressional investigation into the CDC misappropriation of CFS-allocated funds)
James Gandolfini

Dr. Simon Wessely (a well-known British psychiatrist who has long held that ME/CFS is a psychiatric illness)
Ben Kingsley

Dr. William Carter (inventor of the experimental HIV and ME/CFS drug, Ampligen)

Nancy Kaiser (Patient 00, the first person to take Ampligen for ME/CFS)
Judith Ivey

Dr. Kenny de Meirleir (Belgium ME/CFS scientist)

Dr. Lucinda Bateman (ME/CFS physician)
Allison Janney 

Dr. Myra McClure (retrovirologist on the first British XMRV study)
Tilda Swinton

Andrea Whittemore (ME/CFS patient and daughter of Annette Whittemore)
Amanda Seyfried
Keri Russell
Michelle Williams
Evan Rachel Wood
Sarah Polley
Deborah Ann Woll
Dakota Fanning
(the early years)
Sofia Vassilieva (the early years)

Annette Whittemore (co-founder of the Whittemore Peterson Institute and mother of Andrea Whittemore)
Vera Farmiga
Susan Sarandon

Dr. Judy Mikovits (retrovirologist and principal investigator of the first XMRV study in ME/CFS patients)
Frances McDormand

Dr. Leonard Jason (ME/CFS researcher)

Dr. Wanda Jones (deputy assistant secretary for Women's Health in HHS) 
Angela Lansbury (15 years ago)
Betty White (15 years ago)

William Switzer (principal investigator of the CDC XMRV study)
Dr. Eric Klein (Cleveland Clinic urological surgeon and coauthor of the first XMRV study linking XMRV to prostate cancer)
Tom Wilkinson  

Dr. Robert Silverman (Cleveland Clinic researcher and coauthor of the first paper linking XMRV to prostate cancer)

Dr. Ila Singh (XMRV researcher)

Dr. Randy Schekman (editor-in-chief, Proceedings of the National Academy of Sciences)
Ron Rifkin

Dr. Harvey Alter (NIH scientist and coauthor of the FDA/NIH/Harvard MLV study)

Dr. Shyh-Ching Lo (FDA scientist and coauthor of the FDA/NIH/Harvard MLV study)

Monday, August 23, 2010


by Mindy Kitei 

The just-released study detects variants of the retrovirus XMRV in most CFS patients.  In addition, nearly 7 percent of the healthy U.S. controls—all of whom are blood donors—test positive, signaling the contamination of the U.S. blood supply. 

Patients, physicians and virologists have been anxiously awaiting the Proceedings of the National Academy of Sciences (PNAS) paper on Chronic Fatigue Syndrome and the retrovirus XMRV.  The paper, "Detection of MLV-related virus gene sequences in blood of patients with Chronic Fatigue Syndrome and healthy controls," was published today.  In it, the authors state that their conclusions “clearly support” the October 2009 Science study linking the retrovirus XMRV to the neuroimmune disease Chronic Fatigue Syndrome (CFS), which afflicts 17 million people worldwide, 1 million of them in the U.S.  XMRV has also been linked to a virulent form of prostate cancer.

Most surprising is that the PNAS study didn’t find XMRV, which stands for Xenotropic Murine Leukemia Virus-Related Virus, in any patients or controls.  Instead, researchers from the National Institutes of Health (NIH), the FDA, and Harvard Medical School detected novel close cousins to XMRV called MLVs—which stands for Murine Leukemia Viruses—in 86.5 percent of 37 patients and nearly 7 percent of 44 controls.

Seven percent is approximately 20 million people, a robust signal that these retroviruses have entered the blood supply. What makes this most likely a fait accompli is that the healthy controls in this study were all blood donors. Before the discovery of XMRV, there were only two known human retroviruses: HTLV and HIV.

A family of viruses
The NIH’s principal investigator on the study, Dr. Harvey Alter, believes his group and the earlier Science group are looking at the same retrovirus.  “Viruses tend not to be homogeneous,” Alter explained to CFS Central in a telephone interview. “The fact that we didn’t find XMRV doesn’t bother me because we already knew that retroviruses tend to be variable. They mutate a lot, basically. This is true of HIV and HCV [hepatitis C virus]. It’s not one virus. It’s a family of viruses.”

Dr. Judy Mikovits, principal investigator of the 2009 Science study, agrees. “We presented a paper at the Cold Spring Harbor RNA tumor virus meeting in May showing that patients reported in Lombardi [the Science paper] contained both X [XMRV] and P [polytropic MLV] variants as well as at least one other family member,” Mikovits told CFS Central.

The Murine Leukemia Viruses detected in the Alter paper have been studied for more than 40 years and are known to cause leukemias and neurological disease.  As documented in more than 2,500 studies, patients with CFS suffer from neurological symptoms, including seizures, short-term memory problems and abnormal brain scans, as well as cancers, particularly lymphomas. The "Murine" in Murine Leukemia Virus is another word for mouse. The last known retrovirus to jump species was HIV—from monkeys to humans.

Alter said that the paper’s conclusions haven’t changed since June. That’s when his paper was put on hold, along with a CDC XMRV paper that didn’t find the virus in CFS patients. Back then, a spokesperson for the Department of Health and Human Services (HHS) announced that the papers were pulled to reconcile or at least to understand why the CDC didn’t find XMRV, and the FDA and the NIH did. At that time, Alter’s paper not only had already been accepted by PNAS, it was in galleys—the final stage before being printed in the journal.

Scientists disagree all the time, particularly with new discoveries, so holding up the PNAS paper at that phase was surprising and unusual. PNAS Editor-in-Chief Dr. Randy Schekman told CFS Central in July that putting a paper on hold had occurred only one other time that he knew of in his nearly four-year tenure at the journal.

Science or spin
The HHS announcement of pulling both papers morphed into political spin when the CDC study was published in the journal Retrovirology a few days later, on the listless Friday before the July 4th holiday weekend. Meanwhile, the scientists on the FDA/NIH/Harvard study were sent back to the drawing board to do more work on their study.

Their study, said Alter, has only gotten stronger in the interim. “There were no changes in the conclusions, but we added data that made the conclusions stronger,” he explained. “For one thing, we did some further work to feel confidant that there was no contamination…. We had hundreds of negative controls, and every assay had negative controls. And then we used an assay from mouse mitochondrial DNA and found that there was no evidence of mouse contamination. We had variation in the viruses we were finding. If there was a contaminant, you’d find one species, not several.”

The key scientists
Along with Alter and fellow scientists at the NIH, researchers at the Food and Drug Administration led by Dr. Shyh-Ching Lo, and Professor of Medicine at Harvard Dr. Anthony Komaroff, conducted the PNAS study. Alter’s earlier NIH research led to the discovery of hepatitis C. Chief of the NIH’s infectious diseases section and associate director of research in the department of transfusion medicine, Alter developed methods to screen the blood for hepatitis, essentially eradicating the risk of acquiring hepatitis from donor blood.

The highly respected Lo is best known for isolating the pathogen mycoplasma fermentans from HIV patients. And Harvard’s Komaroff, senior physician at Brigham and Women’s Hospital in Boston, has been publishing steadily on a viral connection to CFS since 1987.

The researchers caution, as did the earlier Science researchers, that their study doesn’t prove these retroviruses cause CFS, only that they’re associated with CFS. The next step is to determine if they’re causative for the disease and transmissible by blood. The latter seems likely, based on a recent study by researchers at Emory University’s primate lab.

“I think these retroviruses are likely to be associated with a subset of cases,” wrote Harvard’s Komaroff in an email to CFS Central. “Until larger studies are done, we won’t know how large that subset is…. The two important questions at this stage are: 1) Based on larger studies from a broader geographic area, what fraction of cases are associated with these MLVs; 2) Are these MLVs a cause of CFS, or just ‘innocent bystanders.’ ”

Four MLVs
The FDA/NIH/Harvard researchers detected four MLVs, which they referred to as “CFS Type 1,” “CFS Type 2” and “CFS Type 3.” Type 4 was found only in one control. “Not that we can tell,” Komaroff replied when asked if the different types exhibited different symptoms, “but the total numbers are small: We need much larger studies to answer this important question.”

In addition, the blood from eight of the 25 patients Komaroff supplied from 15 years ago had blood draws again in March 2010.  Seven of the eight remained positive. According to Komaroff, the patient who became negative hadn’t recovered.

However, that doesn’t mean that this retrovirus doesn't cause CFS, and it doesn’t mean that the patient isn’t still infected with the MLV. Since the host’s DNA becomes inextricably intertwined with a retrovirus, infection lasts for life. Besides, as noted in both the Science study and in the PNAS study, finding this retrovirus in the blood is difficult. In fact, Emory University scientists who injected XMRV into macaques this past spring reported that even when the virus was undetectable in the blood, it thrived in the reproductive organs as well as the spleen, gut, bladder, lung, liver and lymph nodes. Explained Alter, “When viruses are in low titer, sometimes you can find them one day and not find them another day.”

Mutating MLVs
Important to note is the retroviruses detected in those seven patients in 2010 had mutated in the 15-year interim. “That’s just what you’d expect from a retrovirus,” said Alter. “That’s more evidence that this is a real agent, not a sequence floating around in the lab.”

What's next
Alter said he’ll look at other cohorts of CFS patients as well as patients with other diseases, including hepatitis C, HIV, fibromyalgia and autoimmune diseases to see if they harbor these MLVs. He’ll also be examining larger populations of blood donors to determine if the MLVs are transmitted by blood.

The 2009 Science XMRV study led to Australia, Canada and New Zealand banning patients with CFS from giving blood. And the Japanese Red Cross issued a disturbing report that XMRV has been detected in nearly 2 percent of Japan’s blood supply. The U.S. government has stopped short of prohibition, but the National Cancer Institute has advised CFS patients against blood donation. Will the U.S. be next?   “Our policy now is that if someone says they have Chronic Fatigue Syndrome, we will not use them as blood donors,” said Alter.

Judy Mikovits believes that the prevalence of MLVs in the healthy population—3.7 percent in her study and 6.8 percent in the FDA/NIH/Harvard study—“represents a serious public health threat that demands research dollars and clinical trials for those who are infected and ill.”

Researchers at several governmental agencies have formed a working group to examine the blood supply for XMRV.  Now that the FDA/NIH/Harvard study has found additional MLVs, that pursuit will be broadened. “The current assays are very difficult,” admitted Alter, one of the researchers looking at the blood supply.  “The viruses are present in very low titers so you need a very sensitive assay.  They will have to be broadened to more than just XMRV."  No easy task.  An antibody test, Alter explained, would be simpler than the current methods of PCR and culture. "It would be more broad, and it wouldn’t require amplification or sequencing. The NCI [National Cancer Institute] has been working on an [antibody] assay, but it’s not so robust yet.”

Bishop paper
Interestingly, a group of British researchers led by retrovirologist Dr. Kate Bishop reported in 2010 that 26 of their group of 170 patients and 395 controls exhibited antibodies to XMRV. The surprise came when the scientists unblinded the study and discovered that 25 of the 26 were controls. “I was quite shocked,” divulged Bishop to CFS Central in June. Bishop understandably expected that most of the 26 would be patients. However, she wasn’t convinced that the antibodies were caused by XMRV. That’s because the antibodies of all but three controls and one patient weren't specific for XMRV and neutralized other viruses as well as XMRV. In hindsight, could those antibodies have been mounted against the MLVs that Alter and Lo found? At this juncture, it’s anyone’s guess.

FDA/NIH versus CDC
In late June, when HHS spokesperson announced the unusual decision to pull the PNAS paper as well as the CDC XMRV paper to reconcile or at least to understand the disparate findings of XMRV studies by the CDC, it became nail-biting time for patients. Several 2010 European studies failed to find any evidence of XMRV in CFS patients, and without confirmatory news many feared the XMRV connection would be severed.

Many patients and researchers have been ruminating whether the FDA/NIH/Harvard paper would ever be published. Indeed, one highly placed CFS Central source believed the study would have been quashed had some of its findings not been leaked in June by Dutch journalists at a blood-borne pathogen conference in Zagreb, Croatia. Ever since, online forums have been rife with uneasy posts from patients speculating whether the findings would be changed to fall in line with the XMRV negative CDC study.

Byzantine history
Given the 26-year Byzantine history of the government response to Chronic Fatigue Syndrome (see sidebar for more, below), including a retroviral link to CFS first detected—and then ignored—nearly 20 years ago, it’s been an understandable concern.

In 1991, a young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas discovered a retrovirus in the blood of CFS patients and, ironically, published her findings in PNAS. (Whether XMRV and DeFreitas’s retrovirus are one and the same is not known with certainty.) When the CDC couldn’t reproduce the results, DeFreitas’s discovery was dismissed.

Tangling with the U.S. government proved costly to the researcher, which scared off likeminded scientists for nearly 20 years, silenced patients and split the research community into two nonintersecting camps: Those who championed a viral cause, and those—including the CDC, several British psychiatrists and Emory University psychologists—who championed a psychogenic cause.

The scales tipped in the viral direction when Dr. Judy Mikovits of the Whittemore-Peterson Institute in Reno, Nevada, led the U.S. group that connected XMRV to CFS in 2009. Longtime CFS viral researchers, physicians and patients were hopeful for the first time in nearly two decades that maybe, just maybe, their time had finally come.

But after the spate of European studies that didn’t find XMRV in 2010, and after the CDC didn’t either, there was an elegiac sense of déjà vu—that what happened with Wistar’s Elaine DeFreitas was about to happen all over again. Blogged one patient: “If anyone can put a positive spin on this then please post now. I sense defeat (in myself). And another 13 yrs (to life) in the wilderness.”

Given today’s findings in the FDA/NIH/Harvard paper and the studies by Alter and other scientists in the works, that scenario no longer seems likely.

This article and sidebar, below, are copyright CFS Central 2010. All Rights Reserved. You may quote up to 150 words from this article as long as you indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is by Mindy Kitei for CFS Central. You may not reprint more than 150 words from this article on blogs, forums, websites or any other online or print venue. Instead, refer readers to this blog to read the article. 
The CFS Political Backstory 
In 1984, Dr. Paul Cheney and Dr. Daniel Peterson dialed up the CDC for help with an outbreak of a flu-like illness that had hit their picturesque town of Incline Village, on beautiful Lake Tahoe, Nevada. When the epidemiologists arrived, they saw about 10 patients, and then went skiing. That outbreak turned out to be one of several outbreaks of Chronic Fatigue Syndrome seen worldwide in the 1980s.

In 1991, a young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas discovered a retrovirus in the blood of CFS patients. Twenty years ago, newspapers and TV news shows latched onto DeFreitas’s finding, spreading the word that the cause of the debilitating disease had, perhaps, been found.

The jubilant atmosphere was short-lived. The CDC failed to find DeFreitas’s retrovirus in patients and controls (without using DeFreitas’s protocol) and British researchers found the retrovirus in all the controls and the patients—again without using her protocol. Given the diametrically opposed findings, DeFreitas reasoned the problem was rooted in the methods. But by that time, retroviral disbelievers outnumbered believers, media interest had flagged and the CDC took the unusual step of publicly chastising DeFreitas, which halted retroviral research into CFS.

In 1996, a congressional investigation proved that CDC scientists siphoned millions of Congress-appropriated CFS dollars to what then-CDC director Jeffrey Koplan told the Washington Post were "more important" maladies, including measles and polio.

The first report of an association of XMRV with human disease came in 2006—from U.S. researchers at the Cleveland Clinic studying a virulent form of prostate cancer, not CFS. But then a German study found no such association, a harbinger of the conflicting findings of the CFS XMRV studies to come.

Dr. William Reeves and the CDC
After Dr. Judy Mikovits's paper linking XMRV to Chronic Fatigue Syndrome was published in Science in October 2009, Dr. William Reeves, the head of CFS research at the CDC for 20 years until February of this year, told the New York Times: “We and others are looking at our own specimens and trying to confirm it. If we validate it, great. My expectation is that we will not.” Reeves also told the Times that the culprits behind CFS were more likely sexual and emotional abuse and an inability to handle stress.

Privately, insiders have told CFS Central that they did not expect the CDC to find the retrovirus because the agency’s CFS definition has been watered down from one neuroimmune disease to five different combinations of depression, insomnia, obesity and “metabolic strain,” as Reeves himself explained in a 2009 paper. In a 2008 CDC paper, “An extended concept of altered self,” Dr. Jim Jones argued that illnesses such as CFS are “illness states” rather than “true diseases.” A CDC paper from 2006 on coping styles found CFS patients guilty of “maladaptive coping” and “escape-avoiding behavior.”

However, studies by Dr. Leonard Jason have shown that using the CDC’s latest definition of the disease, 38 percent of patients have major depression, not CFS, which is a serious neuroimmune disease, as shown in more than 2,500 peer-reviewed studies.

Though Reeves was transferred from CFS research to senior adviser for Mental Health Surveillance in February, he's still authoring studies on CFS. His latest, released in July, is “Personality Features and Personality Disorders in Chronic Fatigue Syndrome.”

For more information on the retroviral link to CFS, see "Blood Feud: Part 1" and "Blood Feud: Part 2" or contact CFS Central at