Tuesday, July 20, 2010

A COMMOTION
IN THE BLOOD

Timeline & Bloodline

1934:  The first known cluster outbreak of ME/CFS in the United States occurs in Los Angeles, California.

1936:  An outbreak takes place in a convent in Fond-du-Lac, Wisconsin.

1937-1939:  Several outbreaks are reported in Switzerland.

1948:  An outbreak takes place in Akureyri, Iceland. 

1950-1959:  Outbreaks are recorded in: Adelaide, South Australia; Durban, South Africa; the Royal Free Hospital in London, England; Berlin, West Germany; Punta Gorda and Tallahassee, Florida; Bethesda, Maryland; Seward, Alaska; Louisville, Kentucky, Copenhagen, Denmark; Segwema, Sierra Leone; Gilfach Goch, Wales; Athens, Greece; Patreksfordur and Thorshofn, Iceland. Hospital workers are usually the hardest hit, accounting for approximately 40 percent of cases, with nurses being the subset most afflicted.  Except for the outbreak in the British Army military barracks in Berlin where all the cases are in men, the majority of casualties are women.  Most outbreaks occur in the spring, summer or fall.

1960-1980:  More outbreaks are recorded in the U.S. (California, New York, Lackland Air Force Base and Dallas-Fort Worth, Texas), as well as in Scotland, England, Ireland, and Lebanon.


1970:  In the British Medical Journal, psychiatrists Colin McEvedy and A.W. Beard categorize ME/CFS outbreaks as mass hysteria. Many patients and physicians write letters refuting the authors' hypothesis.
 
1982-1984:  West Otago, Dunedin and Hamilton, New Zealand, report cluster outbreaks.

1984-1989:  Cluster outbreaks are reported in Incline Village, Nevada; Truckee, Roseville, Placerville and Sonora, California; Lyndonville, New York; Chapel Hill, North Carolina, and other areas in the U.S.  Outbreaks are also recorded in Canada, England and Wales.  Hospital workers and schools are the hardest hit.  Most cases then and now, however, are sporadic.  In Incline Village on beautiful Lake Tahoe, Dr. Paul Cheney and Dr. Dan Peterson dial up the Centers for Disease Control (CDC) for help.  As chronicled by Hillary Johnson in her book Osler's Web, epidemiologists Jon Kaplan and Gary Holmes arrive at the tony resort town, see about 10 ME/CFS patients, then go gambling and skiing.


1986: As reported by Hillary Johnson, Dr. Stephen Straus, then head of CFS research at the NIH, theorizes to fellow physicians about CFS:  "Maybe these are the individuals who... don't want to drive their BMW unless they feel up to it, and they need our help to get behind the wheel."

1987:  California resident Joan Irvine comes down with Chronic Fatigue Syndrome the day after a blood transfusion during surgery to repair a shattered hip and thigh in 1987.  Seeking answers, she writes in 1992 to Dr. William Reeves, who is heading up research into CFS at the CDC, as well as Dr. George Rutherford, then chief of the infectious disease branch of the California Department of Health.  Both men advise her against donating blood.  Their letters and Irvine’s chronology of events can be read here: http://www.cfs-news.org/joan.htm. Irvine’s ME/CFS case is virulent, and she commits suicide in 1996.  Many other patients have reported being diagnosed with ME/CFS after blood transfusions.

1987:  New Zealand family physician J.C. Murdoch writes a letter to The Journal of the Royal Academy of General Practitioners (now known as The British Journal of General Practice) making a case that ME/CFS is not “hysteria” as some other physicians have concluded but is, he believes, a physiological disease with decreased cell-mediated immunity.  He concludes the letter:  “…. the syndrome is an acquired immune deficiency syndrome and we are presently searching for evidence of retrovirus infection in our patients.”  It is the first known mention of the word “retrovirus” to categorize ME/CFS.

1991:  A young researcher at the University of Pennsylvania’s Wistar Institute named Dr. Elaine DeFreitas discovers evidence of a retrovirus in the blood of ME/CFS patients.  The CDC, however, fails to find DeFreitas’s retrovirus in patients and controls (without using DeFreitas’s protocol).  Tangling with the U.S. government proves costly to the researcher’s career, which scares off likeminded ME/CFS scientists for nearly 20 years.

1994: Dr. Stephen Straus, then head of CFS research at the NIH, launches a CFS workshop with a slide of a Victorian woodcut of a woman recumbent on a couch with her hand clasping her forehead, as chronicled by Hillary Johnson in Osler's Web. 
  
1996:  In 1996, Primetime Live television correspondent Dr. Nancy Snyderman interviews Dr. Philip Lee, then Assistant Secretary of Health.  The exchange, emphasis added:

NS:  Do you believe in clusters [of CFS]?

PL: Do we have clusters of cases?  Oh yes, I do.

NS: Dr. Reeves [then head of CFS research at the CDC] told the producer for this piece that in fact the Lake Tahoe "cluster"didn't exist and the people living there are hysterical.

PL: Well again, that's his view.

NS: But he's a scientist at the CDC; he's responsible for investigating these kinds of things.

PL: The CDC did investigate that. They reached certain conclusions, which many people disagree with.

NS: Do you believe it's a virus?

PL: I really don't know, I mean….

NS: If you had to take….

PL: Well I would guess….

NS: An academic hunch….

PL: Well I would say it would be a retrovirus or a virus, I would think so. 

NS: Lee says the government is making progress.  But Hillary Johnson, whose book [Osler’s Web, the exploration of the ME/CFS epidemic and the government’s apparent disinterest in dealing with it] is being released today, remains unconvinced:

HJ: I think it's one of the most incredible medical stories of our century and it's going to be very, very hard for the government to change its position on this disease. I mean to have to sort of call up the American public and say, hey, you know that disease that we've been calling chronic fatigue syndrome for the last ten years, well guess what, it's really something far more serious and it's transmissible and we made a mistake in [Lake] Tahoe and we've been making a mistake ever since.

Primetime from Barborka on Vimeo.
 
1999:  Dr. Kenny de Meirleir of Brussels, Belgium, finds that 4.5 percent of 752 ME/CFS patients develop their disease a few days to a week after a blood transfusion, pointing to a possible transmissible cause in this group of patients. De Meirleir notes that another eight patients became ill two months after transfusion; those cases de Meirleir does not include, as the connection isn’t entirely clear.  De Meirleir advises CFS patients against blood donation.


2006:  A group of American researchers at the Cleveland Clinic discovers a new human retrovirus in men with a virulent form of prostate cancer.  They christen the retrovirus XMRV, which stands for xenotropic murine leukemia virus-related virus.  There are only two other known human retroviruses:  HIV and HTLV.  XMRV is closely related to a mouse retrovirus.  The last retrovirus to jump species was HIV—from monkeys to humans. 

2008:  German researchers fail to find XMRV in prostate-cancer patients.

October 2009:  Led by principal investigator Dr. Judy Mikovits, a group of American researchers from the Whittemore-Peterson Institute, the National Cancer Institute and the Cleveland Clinic publishes a study in October in Science that identifies:
  • The retrovirus XMRV in 67 percent of 101 patients.
  • The study also finds XMRV in 3.7 percent of apparently healthy controls, which would translate to 10 million  Americans.  In contrast, 1 million Americans live with HIV/AIDS.

More sophisticated testing later shows that 98 percent of ME/CFS patients are infected.  It’s not known if the retrovirus discovered by Wistar’s DeFreitas and XMRV are the same retrovirus.  Twenty years ago, it was not possible to sequence the entire retrovirus, as it is today.

October 2009:  Another set of German researchers fails to find XMRV in prostate-cancer patients.

2009:  The U.S. government stops short of blood-donation prohibition for people with ME/CFS, but the National Cancer Institute advises ME/CFS patients against blood donation in 2009 due to concerns about XMRV.  “Given that the virus has been detected in white blood cells, blood-borne transmission is a possibility,” the NCI states.  “More research is needed before guidelines can be established, but it might be prudent for potentially infected individuals to refrain from donating blood.”

December 2009:  The Japanese Red Cross issues a disturbing report that XMRV has been detected in nearly 2 percent of Japan’s blood supply. 

January 2010: British psychiatrist Simon Wessely and two of his colleagues in the psychiatry department at King’s College London, along with retrovirologist Dr. Myra McClure and other virologists at Imperial College London, conduct the first British XMRV study.  Published in January, the study doesn’t find XMRV in any patients.  Wessely’s psychiatry unit supplies the blood samples.  Critics question the patient group for two reasons:  First, the psychiatrist bills CFS as a biosocial disorder, in which a person’s negative “illness beliefs” cause physical symptoms.  And second, his studies often lump CFS in with “chronic fatigue,” “fatigue" and, most recently,  “burnout,” which are entirely different entities.  The British study doesn’t include controls because, explains McClure to CFS Central, “If we had found one positive, we would have had to go for controls.  It was because we didn’t find any that there was no need.”  To which Dr. Judy Mikovits, principal investigator of the Science study, responds:  “That is unscientific and not worthy of comment.”

February 2010: A second British CFS study published in Retrovirology in February doesn’t find any firm evidence of XMRV.  Like the first British study, the second is not a replication of the Science study.

February 2010:  A week after the second British study comes out, researchers at Emory University’s primate lab inject XMRV into macaques and report that even when the virus is undetectable in the blood, it thrives in the reproductive organs as well as the spleen, gut, bladder, lung, liver and lymph nodes.  It’s possible the British studies couldn’t find XMRV in the blood because it’s not where the retrovirus likes to hang out.

February 2010: A February 25 editorial in the British Medical Journal by Drs. Simon Wessely and Myra McClure categorize the research community as “underwhelmed” by the XMRV link to CFS. 

February 2010.  A small Dutch study doesn’t find XMRV in any of its 32 patient blood samples frozen in 1991 and 1992.  Two of the study’s scientists are psychiatric CFS proponents and have co-authored more than 50 papers on the disease, including the 2008 “Guided self-instructions for people with Chronic Fatigue Syndrome,” which combined cognitive therapy with “email contact.”

April 2010:  Dr. Judy Mikovits of the Whittemore Peterson Institute whose October 2009 study found XMRV in CFS patients states that XMRV has probably entered the U.S. blood supply system, but she's unsure whether the retrovirus would be susceptible to the same heat treatments that successfully kill off the HIV virus in blood products.

Spring 2010:  Concerned that the retrovirus may contaminate the blood supply, health officials in Canada, New Zealand and Australia announce new policies in the spring that ban patients with a current or past CFS diagnosis from giving blood. 

June 2010:  German researchers examine respiratory secretions and find XMRV in 2 to 3 percent of 168 healthy controls and 10 percent of 161 immunocompromised patients.


June 2010:  The Food and Drug Administration and the National Institutes of Health conduct an XMRV study that reportedly finds XMRV in 80 percent of patients with ME/CFS—up from the 67 percent found in the October 2009 Science study.  In addition the FDA/NIH study reportedly finds 3 to 7 percent of apparently healthy controls are XMRV positive as well, raising concerns about the safety of the blood supply.  

CFS Central sources say that the paper had been accepted and in galleys at Proceedings of the National Academy of Sciences, when NIH higher-ups alerted to the paper by the CDC suddenly put the paper on hold. The CDC, meanwhile, has conducted its own XMRV study without finding the retrovirus. The Wall Street Journal reports that the papers will be held up until either a consensus can be reached among the three agencies or until it can be determined why one federal agency can’t find the retrovirus when two others can.  The CDC’s study, however, is published the following month, while the FDA/NIH paper is still on hold.

June 2010:  On June 18, the American Association of Blood Banks (AABB) recommends actively discouraging potential donors who’ve been diagnosed by a physician as having CFS from donating blood or blood components.  One million people have CFS in the U.S. and 17 million worldwide.

July 2010:  On July 1, the CDC releases its XMRV study, which doesn’t find the retrovirus in any of its patients or controls.  One of the authors is Dr. William Reeves, who told the New York Times in October 2009 after the Science paper was published:  “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.”  During his two-decade tenure as the chief of CFS research until he was transferred in February, Reeves focused on psychiatric research into CFS, including his 2006 paper on CFS coping styles, which found patients guilty of “maladaptive coping” and “escape-avoiding behavior.”

CFS Central conducts an interview with two CDC scientists about the paper, asking them if they tested the confirmed positive samples Dr. Judy Mikovits and other labs sent to the CDC, and if so what were the results?  The XMRV principal investigator Bill Switzer MPH sidesteps the question with this reply:  “As reported in Retrovirology, this study used and tested samples that were collected in CDC-sponsored studies of CFS, as well a set of healthy blood donors.  Continued efforts are underway to learn more about XMRV, including work with other HHS [Health and Human Services] agencies and non-governmental organizations to standardize testing methods across all XMRV studies.”

Ongoing:  A United States federal consortium is now working to determine the prevalence of XMRV in the blood supply and the reliability of different detection methods.  Currently there are 12 tests used to prevent infectious pathogens from entering the U.S. blood supply, including screens for HIV I and II, hepatitis B and C, syphilis, and the parasitic disease Chagas.  Blood banks have screened for HIV since 1992.  There are 1 million people living with HIV/AIDS in the U.S.  There are 1 million people living with ME/CFS in the U.S.  If the FDA/NIH study numbers hold, up to 7 percent of U.S. residents are positive for XMRV but as of yet have no symptoms.  That translates to 20 million people.  If 20 million Americans are infected with XMRV and don’t know it, and XMRV proves to be the cause or major player in ME/CFS or prostate cancer, how safe, then, is the blood supply? 


This article, “A Commotion in the Blood,” is 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.

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20 comments:

  1. SomefundingpleaseJuly 20, 2010 at 3:51 PM

    The June 2010 immunocompromised patients received organ or bone marrow transplants. It is not known if they caught XMRV through the transplant and transfusions or lowered immune function.

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  2. Thinking about a good name for the scandal, but how do you summarize all of this madness in the two syllables before -gate? Tahoegate? Reevesgate? Freitasgate? This story makes me ANGRY! And no matter what they think at CDC, the longer they sit on the story, the angrier patients will get. They won't get away with a hush-up, not anymore. This is 2010. They better come up with one hell of an apology letter and one hell of a recovery plan.

    Seeing the footage from Primetime (solid journalism) is surreal. Realising that all this knowledge was already out there in 1996, fourteen years ago. I fell ill in 1999. If they had done the right thing in 1996, or even before that, all of my useless suffering could have probably been prevented. Thanks a lot folks! All this arrogance and lazyness from macho so called scientists, it's sickening.

    But let's not shoot the messenger. This messenger deserves a big kiss. Great article Mindy!

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  3. Thank you for another great article, Mindy. Even though I have been sick with ME/CFS since 1986 and lived through most of this, I still learned new facts here. When you set out the history so clearly, it clarifies the chronology of this illness, and it is looking like a smoking gun at the hands of the CDC. They owe us all a huge apology, and, I think, an explanation detailing what they did, which individual in their employ did it, and what their reasons were.

    Patricia Carter
    www.mecfsforums.com

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  4. Great job on the timeline of CFIDS events. I fully expect that when it ALL comes out what the CDC and NIH have allowed to occur to the nation's blood supply for 30 years and the continued cover-up of CFIDS/XMRV, there is going to be a mob riot at the CDC - by the American public - not the CFIDS sick. Wait for it!

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  5. Great timeline, Mindy; thanks! I think it would make a good mini-series.

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  6. Thanks Mindy! A message for folks to visit CFS CENTRAL and read your blogs - and be EDUCATED!...is the first thing that people see when they go to my FB page! You are making it easy for me to tell the facts to all that will listen. Ill for 58 years/dx'd ME/CFS 1998/surviving on 3200mg daily Acyclovir (4 years and counting!)

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  7. Great coverage, Mindy. Thank you, thank you, thank you!

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  8. Outbreaks of CFS don't make sense to what I understand about the disease. Whatever causes one to come down with CFS does not appear to be very infectious, and there seems to be a large genetic component to who gets sick. So how would cluster outbreaks occur? Did a whole bunch of genetically susceptible people all happen to be together at the same time? Doesn't make sense in my view.

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  9. Mindy - it would be very interesting to hear your thoughts on the near complete absence of journalists covering this story? Do you think the media are just waiting for confirmation from FDA/NIH? The story is significant - from many directions- blood supply, deeply ingrained and universal denial of a debilitating disease with 17 million sufferers worldwide etc...

    Where are the press ???

    And how do we bring people to justice – people like Reeves, Strauss and Wessley. These scientists have been exposed to overwhelming evidence of biological abnormalities within people with ME/CFS for decades - and yet - used their positions to perpetuate a psychologically based theory of illness (and to publicly deny the growing scientific evidence that ran contrary to their views). In fact thousands of people with ME/CFS, have been urging governments for years, to have these people removed from post.

    Governments appeared determined to keep these people in leadership roles– because Reeves and co kept providing the advice that governments were so keen to hear – that ME/CFS is psychological illness. This cycle has had truly devastating consequences – of epic proportions – the truth must come out.

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  10. Makes me cry to read this tragedy. But when we got to the mention of Judy Mikovits, I wanted to cheer! She and the Whittemores are our heros. And Hillary Johnson! And now Mindy!

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  11. Anonymous said...
    Mindy - it would be very interesting to
    hear your thoughts on the near complete
    absence of journalists covering this
    story? Do you think the media are just
    waiting for confirmation from FDA/NIH?

    I pitched "Blood Feud" Part 1 and 2 (the first two articles that I posted) to circa 30 print and online venues. No one was interested. That's why I started this blog. I believe that when it comes to ME/CFS, the attitude from many is ME/CFS, er, fatigue.

    Since the 1984 outbreak in Incline Village, Nevada, when the CDC was called in, it's been a quarter-century roller-coaster ride, and the world, in my view, is sick of it. The problematic name adds to the ennui. Who can get excited about a disease that doesn't sound like a disease?

    That said, when the FDA/NIH paper comes out, I believe there will be renewed interest in ME/CFS, as well as concern about the blood supply.

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  12. Mindy - thank you so much for your continuing excellent work on this!

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  13. Of course governments aren't interested in admitting to anything in relation to ME/CFS. Why would they be? Any admission would open the gates to the possibility of litigation, and then where would they be????

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  14. Let's stop calling CFS CFS. Let's call it ME in the patient community until a clear relationship between XMRV and the disease is established. After that we call it what WPI offers up.

    I'd like to see all things CFS transform, or go by the wayside. The term had been in a thorn in my side from the beginning. I am so stigmatized by the lable. I don't even tell people what I am diagnosed with to avoid blank looks and misperception. I tell everyone I have a seizure disorder, since I experienced seizures in my acute phase.

    By the way, I am angry too over the mishandling of ME. Really really angry.

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  15. Mindy I am wondering why you don't mention Myalgic Encephalomyelitis in this piece when it is the disease in question and so many people need to know the disease was established medically and scientifically before CFS was introduced.

    1934: The first outbreak was called 'Disease resembling poliomyelitis' and later it was called Atypical Poliomyelitis.

    1955: The Wallis description of Myalgic Encephalomyelitis was published in a doctoral thesis.

    1959: Sir Donald Acheson named the disease Myalgic Encephalomyelitis in an editorial in The Lancet.

    1969: ME was accepted as a neurological disease by the WHO.
    (This is very important information, and probably the reason for what happened in 1970.)

    1978: The Royal Society of Medicine held a symposium on ME at which ME was accepted as a distinct entity. 20 papers were submitted. The symposium proceedings were published in The Postgraduate Medical Journal in November that same year.

    1981: Melvin Ramsay published the first definition of ME. This is very important as things were about to change in the US which had been calling the disease Epidemic Neuromyasthenia.

    1987: J.C. Murdoch in his letter to the journal was explaining ME not ME/CFS - that ME was like AIDS and they were searching for a retrovirus. People need to know exactly how much was known about ME before 1988 and the CDC inventing CFS.

    1988: Outbreaks of ME were ignored and CFS was created by the CDC with a definition describing unexplained fatigue, not ME.

    I think these facts are some of the most important in the history of ME and I don't understand why you left them out?

    Thank you for you otherwise great posts, you are a champion!

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  16. Hi Anonymous,
    Thank you for your additions. Why I didn't mention the ones you did was this: Writing a blog isn't like writing an article for a magazine where you have the luxury of time. I researched and wrote 2,500 words and provided numerous links for this post in a few days. There's no way I could record every fact in the long history of this disease in that amount of time. I do appreciate your filling in what I missed.

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  17. Hi Mindy
    I appreciate that you don't have the luxury of time to keep up with the extraordinry developments that have shaken our world, I was just concerned that the most important historical facts were missing, how ME was an medically established disease well before the CDC decided to call it CFS and lie that it was medically unexplained.

    We are still haunted by that coverup with what is going on with the holding of the FDA/NIH confirmation paper so that the XMRV working group doesn't have to deal with replication of WPI's finding of XMRV in ME/CFS. I am off to read your new post on that now. Keep up the great work!

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  18. The timeline event I am waiting for is when they find an XMRV reservoir in ME/CFS patients. That would make it easier to measure XMRV. It may also be a marker for assessing treatment efficacy in trials.

    In a way, that respiratory study you mentioned is kind of a reservoir measurement. The country's researchers couldn't find it in blood but found it in respiratory secretions.

    Thanks for the timeline. It's exciting to see where we fit in history. Maybe we will be making history in the not too distant future, too.

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  19. Oops, I guess the German researchers were looking in prostate and didn't find XMRV. This is one very difficult virus to find.

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  20. The Sharma paper focuses on the dissemination of XMRV in the macaques ( http://www.retroconference.org/2010/Abstracts/39855.htm ) whereas the Hackett paper referenced in your article focuses on the host response.

    In Sharma's oral presentation, she goes into detail on where and when the virus infects the various organs. This includes finding it in the brainstem of the lone female macaque.

    There were some very difficult to explain differences in their response to XMRV including different waning levels in the plasma. I wish I had data to see if these macaques were siblings and how similar their environments were. Also, in the end, they "vaccinated" a couple of the macaques with protein to see if they could raise their titres to return it to a detectable limit. Next time, I hope they might try injecting LNCaP to raise XMRV titers.

    I think Goff said that after a year, he thought all the macaques seemed normal, even though they were positively infected.

    Thanks for the timeline and the paper references. It's keeping me busy reading.

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