Letter in Response to WSJ Article

Last night the Wall Street Journal published Amy Marcus's article "Chronic-Fatigue Paper Called Into Question."  Here is my response:

As a science reporter and blogger, what I find most perplexing about the Science editors asking Dr. Mikovits to withdraw her study is that the jury is clearly still out. While some laboratories haven’t found XMRV in CFS patients, others have. The ones that haven’t found XMRV failed to replicate the methods and patient cohort of the original Science study, making their findings questionable. The laboratories that have found the retrovirus include a study by National Institutes of Health Lasker Award winner Dr. Harvey Alter and the FDA’s Dr. Shyh-Ching Lo. Their study found variants of XMRV in 86 percent of patients and 7 percent of apparently healthy controls. All the controls were blood donors, signaling a contamination of the blood supply.

In addition, the original Science study was coauthored by the Cleveland Clinic and the National Cancer Institute, both of which also found the retrovirus in CFS patients. Moreover, other laboratories have found the retrovirus in CFS patients but have not yet published their findings. And, finally, respected laboratories have found the retrovirus in prostate cancer patients as well, making the contamination theory less than likely.

Given that others have replicated Mikovits’ findings, given the high stakes in a population that has no treatment after 30 years of government neglect, given that many CFS patients have died from the disease and many others experience a living death, I find it problematic that Science has asked Dr. Mikovits to withdraw the paper.

Some see this move as the first step to shutting down current NIH-sponsored XMRV CFS studies, as the government did 20 years ago, when the first evidence of a retrovirus in CFS patients surfaced at the Wistar Institute at the University of Pennsylvania. Back then, the Centers for Disease Control refused to replicate the methods of Wistar’s Dr. Elaine DeFreitas. When the CDC couldn’t replicate her findings, the research died. Twenty years later, it’s deja vu all over again.

Science seems to be hell bent on consensus, but as Harvard-educated physician and medical thriller writer Dr. Michael Crichton once pronounced: “Let’s be clear: The work of science has nothing whatever to do with consensus. Consensus is the business of politics. Science, on the contrary, requires only one investigator who happens to be right....”

Whether Dr. Mikovits is right is anyone’s guess. But asking her to withdraw her paper before the truth is known is the antithesis of science.

Round 3 for WPI and Chase; Healkick's New Features

From ME/CFS patient Justin Reilly:

There is a silver lining in winning less than $100K in that we are eligible for the $200K discretionary spending prize. (There is also an additional $300K in discretionary spending for which I believe all the charities in round 2 are eligible).

I sent the following letter in case anyone wants any ideas. Thanks to Ann from whom I borrowed some wonderful phrasing!

Dear Chase Community Giving,

I am a Chase customer. I support Whittemore Peterson Institute in the CCG contest. I am writing you to let you know how great WPI is and urge you to award them some of the discretionary contest funds.

I have had ME/CFIDS for ___ years. 17 million people worldwide have this devastating neuroimmune disease, with virtually no viable treatment options and little bona fide research.

That is, until the Whittemore Peterson Institute recently came along. One family, fighting for their daughter's life, footed the bill and opened a state of the art Institute to research neuroimmune disease. As the New York Times noted, comparing WPI to Michael J. Fox's Foundation and others, "Harvey and Annette Whittemore were not the first to start a research foundation out of desperation to find answers for an incurable disease... But few if any of the private groups have produced notable results as quickly as the Whittemore Peterson Institute has."

Unfortunately, the Whittemore family can no longer cover all of the Institute's costs alone. WPI needs help raising money that will all go toward desperately needed research for a cure. This is where you can help. Please award this most deserving of charities as much of your discretionary funding as possible!

Thank you for your consideration.

Sincerely,

http://apps.facebook.com/chasecommunitygiving/rules

(Charities awarded a Round 2 grant of $100,000 or more in the current program are not eligible to receive the $200,000 Advisory Board grant)

 ***

Healkick, the forum for ME/CFS patients under 40, has added new features:

• IM Chat (private and public). "Many patients have said it’s the first time they’ve actually talked to another patient," says Cari Lea, who co-founded Healkick with Joey Tuan. 

• Language friendly. You can choose the language of your choice to read posts. No more struggling to read the forum in English.

• Patient Map.  "Every member that joins the site enters where they live," explains Cari Lea.  "It all gets put on our Patient Map. So patients can see who lives near them, and find patients they can meet up with or at least find some local support--something that is very hard for most of us to find."

Facebook and the Government

A former high-ranking government worker has told CFS Central that in his experience what gets the government’s attention is, yes, Facebook. In his view, the government has learned to ignore phone calls, faxes and emails. But Facebook campaigns, he said, “panic” them because they’re viral, embarrassing, and leave an indelible footprint.  Ideally, a campaign could be started directly on the government's own Facebook pages.

MONEY AND JUSTICE

Ailing biologist Dr. Alfred Kinsey pleaded to A & P supermarket heir George Huntington Hartford II in the 1950s for a research grant to cover his groundbreaking research into human sexuality. “We need money,” Kinsey told Hartford in the film Kinsey.  “We need someone to give us money.  You have no idea what I’ve had to endure just to obtain the same rights other scientists take for granted.  My funding has been slashed, my name has been dragged through the mud in every newspaper and magazine across this country…. We’re broke.  I’m not sure how much time I have left.  Help me.  I have to get it all on the record.”

Hartford refused to give Kinsey the grant:  He found the subject matter too scandalous and controversial.

Sound familiar?

If enough ME/CFS patients vote in round two of the Chase Community Giving contest, they can help ensure that WPI gets the money it needs for ME/CFS research.  

1. Go to facebook: http://www.facebook.com
2. Copy and paste this URL: http://www.facebook.com/ChaseCommunityGiving?ref=ts
3. Click the "like" button (to the right of "Chase Community Giving" at the top. If you’ve  already "liked" Chase Community Giving, you won’t see the “like” button, and you can skip to the next step.
4. Copy and paste this URL: http://tinyurl.com/wpiround2  Click the big green "Vote & Share" button to cast your vote.

ZOMBIE APOCALYPSE NOW

  Sounds Like ME/CFS to Me

 

One of the CDC's polite press guys, David Daigle, whom I've had the pleasure of speaking with on several occasions, posted this how-to manual to prepare for the Zombie Apocalypse, on the CDC's Public Health Matters Blog.  Curiously, what causes folks to transmogrify into zombies appears to be, according to Daigle, an infectious agent passed in a bite or bodily fluids that causes a neurodegenerative syndrome.  Does David Daigle know something we don't know?  Not to mention that patients describe both being a zombie and ME/CFS as "a living death," "death warmed up" and "I feel like such a zombie!" 

Below, in purple, is an excerpt from Daigle's post, which drew a whopping 23,000 readers to the lonely CDC blog--a record--causing the site to crash. 

Preparedness 101: Zombie Apocalypse

There are all kinds of emergencies out there that we can prepare for. Take a zombie apocalypse for example. That’s right, I said z-o-m-b-i-e a-p-o-c-a-l-y-p-s-e. You may laugh now, but when it happens you’ll be happy you read this, and hey, maybe you’ll even learn a thing or two about how to prepare for a real emergency.

A Brief History of Zombies

We’ve all seen at least one movie about flesh-eating zombies taking over (my personal favorite is Resident Evil), but where do zombies come from and why do they love eating brains so much? The word zombie comes from Haitian and New Orleans voodoo origins. Although its meaning has changed slightly over the years, it refers to a human corpse mysteriously reanimated to serve the undead. Through ancient voodoo and folk-lore traditions, shows like the Walking Dead were born.

A couple dressed as zombies - Danny Zucco and Sandy Olsson from the movie Grease walking in the annual Toronto Zombie Walk.

In movies, shows, and literature, zombies are often depicted as being created by an infectious virus, which is passed on via bites and contact with bodily fluids. Harvard psychiatrist Steven Schoolman wrote a (fictional) medical paper on the zombies presented in Night of the Living Dead and refers to the condition as Ataxic Neurodegenerative Satiety Deficiency Syndrome caused by an infectious agent. The Zombie Survival Guide identifies the cause of zombies as a virus called solanum. Other zombie origins shown in films include radiation from a destroyed NASA Venus probe (as in Night of the Living Dead), as well as mutations of existing conditions such as prions, mad-cow disease, measles and rabies.

The rise of zombies in pop culture has given credence to the idea that a zombie apocalypse could happen. In such a scenario zombies would take over entire countries, roaming city streets eating anything living that got in their way. The proliferation of this idea has led many people to wonder “How do I prepare for a zombie apocalypse?”

Well, we’re here to answer that question for you, and hopefully share a few tips about preparing for real emergencies too!

Disaster or Blackout Emergency Supplies

Some of the supplies for your emergency kit

Better Safe than Sorry

So what do you need to do before zombies…or hurricanes or pandemics for example, actually happen? First of all, you should have an emergency kit in your house. This includes things like water, food, and other supplies to get you through the first couple of days before you can locate a zombie-free refugee camp (or in the event of a natural disaster, it will buy you some time until you are able to make your way to an evacuation shelter or utility lines are restored). Below are a few items you should include in your kit, for a full list visit the CDC Emergency page.

• Water (1 gallon per person per day)
• Food (stock up on non-perishable items that you eat regularly)
• Medications (this includes prescription and non-prescription meds)
• Tools and Supplies (utility knife, duct tape, battery powered radio, etc.)
• Sanitation and Hygiene (household bleach, soap, towels, etc.)
• Clothing and Bedding (a change of clothes for each family member and blankets)
• Important documents (copies of your driver’s license, passport, and birth certificate to name a few)
• First Aid supplies (although you’re a goner if a zombie bites you, you can use these supplies to treat basic cuts and lacerations that you might get during a tornado or hurricane)

SHOAH TESTIMONY

A Few of the Speakers at this Week's Chronic Fatigue Syndrome Advisory Committee Meeting at the Department of Health and Human Services in Washington, D.C.

Dr. Mary Schweitzer delineates what's problematic about the CDC when it comes to ME/CFS:



Dr. Joan Grobstein, a neonatologist, discusses transmission and treatment of ME/CFS and what the government needs to do in the next six months to end the inertia:

Lori Chapo-Kroger, the founder of CFS Solutions of West Michigan, talks about the death of three friends from ME/CFS:



Attorney Charlotte von Salis speaks on disability benefits, the problematic definition, and why many patients want to dissociate from the CFIDS Association:



Respiratory therapist Meghan Shannon, who's had ME/CFS for 35 years, gives her moving testimony and explains what's wrong with the CDC website:



Demonstration by playwright Rivka Solomon, who is joined by other patients, outside HHS:



Too ill to testify in person, 22-year-old patient Ben Di Pasquale was filmed by a local TV station.

JUDY MIKOVITS' NEW STUDY

Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome Reveals a Distinct Inflammatory Signature 

Published IN VIVO

VINCENT C. LOMBARDI, KATHRYN S. HAGEN, KENNETH W. HUNTER, JOHN W. DIAMOND, JULIE SMITH-GAGEN, WEI YANG and JUDY A. MIKOVITS

Abstract. Background: The recent identification of xenotropic

murine leukemia virus-related virus (XMRV) in the blood of

patients with chronic fatigue syndrome (CFS) establishes that a

retrovirus may play a role in the pathology in this disease.

Knowledge of the immune response might lead to a better

understanding of the role XMRV plays in this syndrome. Our

objective was to investigate the cytokine and chemokine

response in XMRV-associated CFS. Materials and Methods:

Using Luminex multi-analyte profiling technology, we

measured cytokine and chemokine values in the plasma of

XMRV-infected CFS patients and compared these data to those

of healthy controls. Analysis was performed using the Gene

Expression Pattern Analysis Suite and the Random Forest tree

classification algorithm. Results: This study identifies a

signature of 10 cytokines and chemokines which correctly

identifies XMRV/CFS patients with 93% specificity and 96%

sensitivity. Conclusion: These data show, for the first time, an

immunological pattern associated with XMRV/CFS.

HAVE YOU NO SENSE OF DECENCY?

Here is my testimony at the Chronic Fatigue Syndrome Advisory Committee meeting on Wednesday at Health and Human Services in Washington, D.C.  Below the written testimony is the video clip.

My name is Mindy Kitei.  I’m a science reporter who’s covered ME/CFS for twenty years.  Last June, I began my blog, CFS Central, in honor of my friend Nancy Kaiser.

I met Nancy in 1994, while working on an investigative piece for Philadelphia magazine called “The AIDS Drug No One Can Have” about the experimental HIV and ME drug, Ampligen.

Nancy had a severe case of ME. She had multiple seizures every day. When she tried to sit or stand, her blood pressure plummeted; she often crawled instead. She tried many experimental treatments to get well.

Nancy died on June 15, 2008.  I naively thought she’d never succumb to the illness, as if by sheer will she’d keep herself alive.

Three other ME patients whom I interviewed in 1994 have also died of the disease.

Despite its gravity, despite ample evidence that ME is an infectious disease, the government treats it like a joke. The CDC and parts of the NIH have been playing a shell game:  studying patients with simple fatigue or chronic fatigue or depression—but labeling them CFS patients. 

Even when the CDC conducted its XMRV study, it studied the wrong cohort and refused to do an actual replication of the Science study.  It’s just a different kind of shell game from the bogus psychological CFS studies that are the agency’s trademark.

To the CDC and NIH scientists who’ve been doing this ludicrous research for three decades and sweeping a worldwide human catastrophe of 17 million people under the carpet, I say to you:  Have you no sense of decency at long last?

ME patients are suffering from a serious infection— most likely a retrovirus—but are told by charlatans to exercise and have a positive attitude. 

Researchers in government and at universities, as well as the CFIDS Association, admonish desperate patients that taking anti-retroviral drugs is medically indefensible.  When the healthy reprove the sick that they’re impatient and reckless and foolish and need to wait for treatment, I say there is no treatment, and where are the drug trials?  Thirty years and not one approved drug and none in the offing.

ME patients should have the same freedom to try medications that AIDS patients had in the early days.  The AIDS patients became their own advocates because there was no one advocating for them.  The same holds true for ME patients now. Patients are gravely ill, and they have the right to treatment.  To say that they don’t—that’s what is medically indefensible.

The U.S. government conducted the Tuskegee Syphilis Experiment from 1932 to 1972.  The study tracked the progression of untreated syphilis among poor African American men but didn’t tell them they had syphilis. The men got sicker and many died.

In 1997, President Clinton apologized to the remaining Tuskegee men.  Clinton said:  “What was done cannot be undone. But we can end the silence. We can look at you in the eye and finally say on behalf of the American people, what the United States government did was shameful, and I am sorry.”

The United States government has watched ME patients suffer and die for 30 years, and has done nothing, and that is shameful.

In less than a year, more than 125 thousand patients from 108 countries and territories have found my blog, CFS Central.  Patients write to me asking for help every day.  Toward that end, I request a meeting with Kathleen Sebelius, Howard Koh, Francis Collins, Tony Fauci and Thomas Frieden to discuss how to turn this situation around, by funding good studies and finding effective medications.

About funding ME, Dr. Dennis Mangan said during this meeting:  “We’ll use one dollar and try to make two.”   I’m sure Dr. Mangan means well, but it isn’t enough.  As AIDS activist Larry Kramer said years ago about HIV patients:  “We are not crumbs.” After thirty years of neglect, ME needs research parity with HIV. We also need a czar who will oversee ME and report directly to President Obama. 

Finally, we need to enact the ME/CFS Care Act.  Much like the Ryan White Care Act for HIV patients, the ME/CFS Care Act will provide health coverage to needy patients.

In closing, I ask you, Dr. Wanda Jones, to ensure that this meeting occurs.  Dr. Jones, will you help me? 

BLOGGER LOST ALL THE COMMENTS ON THE POST.  SHOULD ANY OF YOU WANT TO COMMENT AGAIN, I WILL OF COURSE POST THEM AGAIN.

BLOOD VERSUS TISSUE

4generations commented on yesterday’s post on Dr. Ila Singh's XMRV-negative ME/CFS study: 

Singh's primate study found that XMRV left the blood of the infected primates after a few weeks (6, I believe). Isn't that finding plus the finding of XMRV in prostate cancer patient tissue good enough evidence to justify a study looking for XMRV/MLV in the tissues of patients with ME/CFS?

4generations, the primate study at Emory University wasn’t Singh’s. But your point is well taken, as XMRV quickly left the blood and settled in the tissues in the macaques. In addition, in the CDC’s new XMRV study on prostate cancer this week, the three patients who tested PCR positive to XMRV in tissue had no virus in plasma by PCR or Western blot.  

If that can occur in prostate cancer, perhaps that can occur in ME/CFS as well.  Moreover, as some readers have pointed out, Dr. Kenny de Meirleir in Belgium is taking tissue samples in the gut of ME/CFS patients and finding them positive for XMRV.

DR. ILA SINGH:

She believes XMRV isn't in ME/CFS patients but that there's evidence for the retrovirus in prostate cancer

CFS Central emailed University of Utah's Dr. Ila Singh about her new XMRV study, which found no evidence of XMRV in ME/CFS patients. In 2009, Singh found evidence of the retrovirus in prostate-cancer tissue.

CFS Central:  Will you revisit your prostate-cancer XMRV findings in light of this XMRV negative CFS study?  From what you’ve learned in this latest CFS study, do you now believe that the XMRV that you found in prostate cancer is a human infection or just contamination?

Dr. Ila Singh: Prostate cancer and chronic fatigue syndrome are completely different illnesses.  I recognize that recent studies have cast doubts on the prostate cancer association as well, but there is still considerable data supporting the link to prostate cancer that cannot be easily explained by contamination. We will present some of this work at the Cold Spring Harbor meeting later this month.  But clearly more work needs to be done before that question can be settled. 

CFS Central:  Do you believe scientists should be looking for XMRV in CFS patients’ tissues instead of blood?
 

Singh: The original study by Mikovits' group reported finding XMRV only from blood.  They did not examine other tissues.  So blood is where the focus should be. Now if one found it in blood, then of course you'd be interested in finding out where else the virus is.  And then it would be interesting to look at tissues.  But looking at tissues is not trivial and not something to be attempted without good evidence of the virus being present in the body first. 

CFS Central: Did you test the new assays/methods used in the new study against any XMRV positive samples from your prostate-cancer study?

Singh: Our prostate cancer study was entirely on prostate tissues. These were archived in tissue banks in a de-identified manner, so there was no way to go back to those patients and obtain blood samples.  So, we could not test some of the new tests we developed on our material from prostate cancer patients. 

CFS Central:  In your new study it says that “2 positive controls were also included” (line 349 of your study). Were the two positive controls clones or clinical samples from prostate-cancer studies or from Mikovits’s positive CFS patients? 

Singh:  The samples from Mikovits' patients were all tested in a completely blinded fashion.  We did not know which of them were positive, so could not use them as positive controls.  But more accurately, there are no real patient 'positive controls' for XMRV.  In order to use patient samples as controls, you'd have to first be absolutely certain that these patients have XMRV.  How could you do that right now?  So we used what you call a 'clone' for our PCR studies.  But remember, this clone was isolated from a patient (a prostate cancer patient).  And this is over 99% identical to the isolates from CFS patients described in Lombardi et al.  For the viral culture studies, we used very small amounts of titrated virus that was grown in the lab as positive controls. And all of these positive controls were always positive. 

CFS Central:  You grew XMRV in the prostate-cancer cell line LNCaP and the breast-cancer cell line MCF-7 in your study “Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.”  It’s unclear to me why the new study didn’t culture XMRV from those two positives. 

Singh:  Yes, we did.  And these grew just fine.  Apologies for not being clearer in the paper.  None of the patient samples tested positive, but the positive controls were always positive. 

CFS Central:  Some patients on the forums find this sentence from the new study problematic:  “We are forced to conclude that prescribing antiretroviral agents to CFS patients is insufficiently justified and potentially dangerous.”  The Science and the Alter/Lo studies have reported XMRV and related MLVs in CFS patients.  CFS patients are very ill, many for decades, and there are no approved treatments. They believe the decision to try antiretroviral drugs should be between a patient and his or her doctor. Why did you feel the need to put that statement in the study and press release? 

Singh:  The patient and their doctor did not make the decision to try antiretroviral drugs in a vacuum.  It was based on reports of finding XMRV in CFS patients.  We are now convinced that there is no XMRV in CFS patients--so the reason for starting those drugs does not exist.  And there is no good evidence for continuing to use drugs that could lead to serious side effects of liver or bone-marrow failure.

****

I wrote to Singh to ask her to clarify two of her answers:
 

CFS Central:  In your prostate-cancer study, “XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors,” you found 4 percent of healthy controls with evidence of XMRV.  If you’re finding a background rate in controls in your prostate-cancer studies, why do you think you didn’t find a background rate in CFS patients and controls?  

Singh:  Not entirely sure, but there were different assays (e.g. immunohistochemistry) and different sample types (blood vs prostate tissue).

CFS Central: To clarify one of my previous questions, beginning on line 347 of your new study, it states: “We inoculated LNCaP cells with 100 [microliters] of plasma from 31 patients and 34 healthy volunteers, and passaged the cells weekly for 6 weeks. 13 negative controls and 2 positive controls were also included. Only one culture was handled at a time to prevent any cross-contamination. After weeks 2, 4 and 6, cultures were lysed and analyzed by Western blots (Fig. 4) and by qPCR for XMRV. No XMRV protein or DNA was detected in any of the cultures. [emphasis added]  

My question is this: Is the bolded sentence correct, or did the 2 positive controls grow in these cultures and/or did the positive samples continue to test positive in culture?  If the positive controls didn’t grow or if the positives controls didn’t test positive in culture, why didn’t they?  You grew XMRV in the prostate-cancer cell line LNCaP and the breast-cancer cell line MCF-7 in your study “Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.”

Singh:  That was our poor wording in the paper (the words in bold).  All positive controls grew XMRV--as one would expect.  None of the samples from the healthy controls or CFS patients grew any virus in culture.  And of course the negative controls did not grow any XMRV.