By David Tuller, DrPH

First, since I’m in London at the moment, I need to say that it feels weird and even wrong to be posting about PACE-related issues right after Saturday night’s terrible events. But in our f**ked-up world, life goes on for everyone else, including ME/CFS patients, and my job is to report this stuff, and so that’s what I’m going to do.

On Thursday, wearing a beautiful and beautifully ironed shirt, I gave a talk at the dinner before this year’s annual Invest in ME conference, at a hotel right next to the Tower of London. About 100 or so scientists, advocates, patients, caregivers, and others attended the event and had little choice but to listen to my presentation: “The PACE Trial: ‘Thing of Beauty’ or Pile of Trash?” It was Sir Simon Wessely who coined the “thing of beauty” line. I guess he thinks PACE is the Mona Lisa of clinical trials. Of course, “pile of trash” was my own counter-formulation. I assume no one wonders what side of that equation I’m on.

In addition to outlining the unacceptable flaws of the trial, I discussed whether the ethical and methodological lapses could be defined as “research misconduct.” And then, as foretold in the title slapped onto my presentation by Invest in ME (“Tear It Up!”), I engaged in a bit of performance art. I tore up not just one but three papers. First was the 2011 Lancet paper. Next, the 2013 Psychological Medicine “recovery” paper.  Finally, by special request from interested parties, I ripped up an Esther Crawley paper—specifically, her 2016 prevalence study in Pediatrics, which featured her inflated claim that almost two percent of kids in the U.K. suffer from chronic fatigue syndrome when all she documented was that they suffered from chronic fatigue.

(The front desk at the hotel had printed out the three papers on single-sided sheets rather than on both sides. So these were three thick stacks. I have to confess that I slightly pre-tore all three, so I wouldn’t be struggling on the podium to initiate the rip.)

After I finished, with shredded scraps of bad studies scattered on the floor around me, it was time for a few questions. A U.K. doctor stood up and asked me what I thought about some apparently authoritative hearsay: Dr. Crawley’s reported intention to have Bristol University slap me with a cease-and-desist letter (see correction below) to stop “harassing” her. After my initial surprise, I laughed. What a boon to my crowdfunding campaign that would be! Let’s be clear: Dr. Crawley publicly accused me of libel several weeks ago and has since refused to provide either an explanation of her charge or an apology. But, if this hearsay is true, she apparently thinks I’m the one doing the harassing.

Now it’s certainly true that I have e-mailed Dr. Crawley multiple times. I have sent my purportedly  libelous blog posts in which I have outlined what I view as egregious flaws in her research. I have also sent her the various posts I wrote about her accusation of libel, which she made during a recent talk to the British Renal Society. I have assured her in each of my recent e-mails that I would be happy to post a statement of any length from her on Virology Blog, so she can explain why she considers my work libelous. It didn’t occur to me that making such an offer or being persistent in seeking details about her defamatory accusation could be construed as “harassment.” (That being said, I’m perfectly happy to refrain from sending her any more of my blog posts, if she’d prefer. However, that means I will not be able to fulfill my journalistic responsibility to seek comment from her on anything I write involving her actions or her research.)

In fact, as I’ve noted before, Dr. Crawley appears to be unable to distinguish between criticism she dislikes and serious misconduct, like libel and harassment. I’ve written very negative things about her work, and that makes her mad. I get that. But I have based all my statements on documented facts. Any attempt to pull a stunt like sending me a “cease-and-desist” letter (see correction below) in an effort to suppress my accurate reporting and opinionated commentary would further damage her reputation and trigger an uproar from patients. If she is actually considering this, I hope those close to her—Stephen Holgate? Sonya Chowdbury?—have the wherewithal to tell her that such a move would not only be stupid but futile.

Dr. Crawley doesn’t scare me. I know a lot of lawyers, and I have the science on my side; she has her “dysfunctional cognitions” about the effectiveness of CBT and GET, along with her belief that PACE was a “great, great” trial, as she said months ago in a radio interview. But as the open letters to The Lancet and Psychological Medicine have demonstrated, dozens of top scientists and academics from around the world share my poor assessment of PACE and recognize that the reported results cannot be taken seriously.

I don’t know if the hearsay about Dr. Crawley’s intentions is correct. But if it is, and she chooses to pursue this ill-advised strategy, she will have a fight on her hands, and she will lose.


*Correction: In two places, I referred to a “cease-and-desist order.” I have changed “order” to “letter.” My guess is I would first get a letter from Bristol University demanding that I “cease and desist” whatever it is they want me to stop doing. If I refused, they could presumably seek a “cease-and-desist order” from a judge or court or other relevant authority to force me to stop whatever it is they want me to stop doing.


From ASM Microbe 2017 at New Orleans, Vincent and Rich meet up with Kate Rubins to talk about becoming an astronaut, space travel, and doing science in space.

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From ASM Microbe 2017 in New Orleans, I speak with Islam Hussein about his science career, how he became interested in science communication, and his video blog in Arabic, Virolvlog.

At ASM Microbe 2017 in New Orleans, I spoke with Medical Laboratory Scientist Caitlin Cahak about her agar art.

Virolvlog meets TWiV

Islam Hussein of Virolvlog interviews me about my career in virology and my interests in communicating science, at ASM’s Microbe 2017 in New Orleans.

If you appreciate the articles written here by David Tuller on ME/CFS, please consider supporting him financially at Crowdrise.

David is an investigative reporter with a doctorate in public health from the University of California, Berkeley. Since the fall of 2015, David has waged a determined effort to expose the methodological and ethical problems with the PACE trial for ME/CFS. He started this effort because he came to understand that the PACE treatments, graded exercise therapy and cognitive behavior therapy, were not just useless but could actually cause serious harm. Although patients had spent years documenting the trial’s unacceptable flaws, the larger scientific world had dismissed and ridiculed their legitimate concerns. Up until this point, David was able to pursue his investigation as a public service project because of his academic job at Berkeley. But now he needs your help, and your tax-deductible contributions, to continue the effort and try to bring it to its desired conclusion — correction of the scientific record.

Debunking PACE

In October 2015, Virology Blog posted David’s 15,000-word investigation of the PACE trial, the largest-ever study of treatments for the ME/CFS. The findings were published in prestigious journals like The Lancet, Psychological Medicine, PLoS One and others. His investigation and multiple follow-ups revealed how the PACE researchers violated major scientific and ethical principles. Because of these multiple flaws, the trial’s reported findings—that graded exercise therapy and cognitive behavior therapy are effective and can lead to recovery—cannot be taken seriously.

David’s continuing investigation has had a major impact in the debate around PACE and the CBT/GET ideological movement. Here is some of what has happened:

*His work has received coverage in many mainstream and other publications, including The Guardian, Slate, Science, The Wall Street Journal, StatNews, and NPR.  In March, The New York Times published an opinion piece about the issue that he co-wrote with Julie Rehmeyer. (Please also support Julie’s terrific new book, Through the Shadowlands, about her own struggle with ME/CFS.)

*Based on his investigation, Virology Blog published open letters to The Lancet and Psychological Medicine, demanding that journal editors address the serious problems of the published papers. Dozens of scientists and other experts signed these open letters, which received widespread attention..

*Last summer, a British court cited the open letter to The Lancet as evidence that an “impressive roster” of experts, not just irrational patients, had serious concerns about the PACE trial. The court ordered the release of the raw trial data, which has proven what patients have known all along and what David documented on Virology Blog–that the published findings are misleading and unreliable.

*In the U.S., advocates have used David’s work to pressure federal agencies to review their recommendations for GET and CBT. Based on their appeal, the Agency for Healthcare Quality and Research reassessed the literature and significantly downgraded the evidence for CBT and GET.

*David’s efforts seem to have rattled the PACE investigators and their colleagues. At least, they have slipped up when they try to defend themselves and their methodological decisions. Most recently, Dr. Esther Crawley accused David in a public lecture of writing “libelous blogs.” With this false accusation, she not only created a public relations nightmare for herself and her associates but has provided David with a wealth of blogging material.

David has pursued this investigation because of his deep concern for patients and his dismay at the poor quality of the study. He has been able to devote a lot of time to this rewarding project because of the security of his half-time academic position at Berkeley. Unfortunately, his current Berkekely position is ending on June 30th, after nine years. The University of California is in poor financial shape, and grant money is scarce this year.

Current Ask

That’s why David is seeking your tax-deductible contributions for another year of investigating and blogging about the PACE trial and ME/CFS on Virology Blog. He will also continue to write articles for other publications, when possible. There is much, much more investigating, blogging and hammering away to do–about conflicts of interest, about the FINE “sister” trial, about Cochrane’s misleading systemtatic reviews, the false PLoS One claim that the treatments are “cost-effective,” etc, etc.

David wants to be clear that he will continue this effort no matter what he receives through this five-week crowdfunding campaign, which ends June 30th. The question is how much time he will be able to devote to it.

Where the Money Goes

The money raised will be sent to the Center for Scientific Integrity, a non-profit which publishes the terrific site Retraction Watch and has agreed to serve as fiscal sponsor for this campaign. (That agreement does not mean the Center for Scientific Integrity necessarily endorses or agrees with any output of this project, which is editorially independent.) The Center will transfer 100% of the net funds — after credit card fees and Crowdrise fees — to the School of Public Health at UC Berkeley, which will create a position focused on investigating the PACE trial and others issues related to ME/CFS.


David’s goal is ambitious: $60,000, the approximate value of his current half-time salary/benefits package at Berkeley. That will allow him to continue to spend the same amount of time he has been spending on investigating, writing, helping organize open letters, and other activities related to PACE and ME/CFS.

David understands that many patients have few resources to spare. But any donation, no matter how small, will help bolster what has turned into an epic struggle to correct the scientific record. (Crowdrise charges a modest fee and provides donors with the option of having that fee added to the donation or taken from the donation.)

If anyone would prefer to support his efforts by donating off-line directly to the School of Public Health at UC Berkeley, please e-mail David for further information:

David Tuller returns to discuss the continuing saga of the UK’s PACE trial for chronic fatigue syndrome, including the accusation that he is engaging in libelous blogging.

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The TWiVsters reveal the puppet master: an RNA virus injected with wasp eggs that paralyzes the ladybug so that she protects the cocoon until the adult emerges.

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Coccinella septempunctata with Dinocampus coccinellae cocoonHost behavior alteration by viruses is known to assist the development of another organism. An example is a parasitoid wasp that injects viruses along with eggs into a caterpillar. The viral genomes encode proteins that subvert the caterpillar immune response, allowing the wasp larva to develop. A similar strategy may enable safe development of a wasp by a ladybeetle.

The parasitoid wasp D. coccinellae lays its eggs inside a ladybeetle. After 20 days of larval development, a prepupa emerges from the ladybeetle and fabricates a cocoon between the beetle’s legs. At the same time, the ladybeetle becomes paralyzed. It remains on top of the cocoon (pictured; image credit), protecting it until an adult wasp emerges. Remarkably, some ladybeetles then resume their normal lives!

Given what we know about how parasitoid viruses can alter the manipulation of their hosts, it was only logical to search for a virus that paralyzes the ladybeetle. Sequencing of RNA from the heads of parasitized ladybeetles revealed the presence of an RNA virus which the authors call D. coccinellae paralysis virus, DcPV. The virus is a new member of a Iflaviruses, a family of picornavirus-like, (+) strand RNA viruses that infect insects. DcPV was found in wasps in Poland, Japan, and The Netherlands, confirming its cosmopolitain nature.

Viral particles were observed in cells lining the wasp oviducts, but not in the lumen. Viral genomes were undetectable in wasp eggs, became more abundant during hatching, and ceased to replicate in adult wasps. The levels of virus in the ladybeetle abdomen and head increase with time to egress, suggesting that it was transmitted from the wasp larvae to the host. In ladybeetles where the wasp egg did not develop, viral replication does not occur.

DcPV appears to be neurotropic. Before larval egression, no changes were observed in the nervous system of the ladybeetle, but glial cells were full of virus particles. After egression, vaculoles developed in glial cells and neurons degenerated. This damage was less severe in beetles that survived and recovered from paralysis. An expansion of glial cells in these hosts might explain how normal brain functions were restored.

Insects respond to infection with an RNA-based antiviral response. Components of the RNA based immune system were down-regulated during larval development, possibly by viral proteins, allowing virus to invade the nervous system. Resumption of the antiviral reponse might enable recovery of the ladybeetle after emergence of the wasp.

It appears that DcPV is a wasp symbiont that manipulates the behavior of the ladybeetle host to ensure development of wasp offspring. This hypothesis can be tested by removing DcPV from infected wasps, or by adding DCpV to uninfected hosts, and determining the effect on larval development.

We now realize that animals are actually holobionts: an aggregate of eukaryotes, bacteria, and viruses. Therefore host-parasite interactions are really holobiont-holobiont interactions.

By David Tuller, DrPH

I have spent two weeks hammering the CFS/ME Research Collaborative about “Renal-gate”—that is, vice-chair Esther Crawley’s recent lecture at a conference of kidney disease experts, in which she falsely accused me of writing “libellous blogs.” The CMRC’s chair, Stephen Holgate, recently assured me that Dr. Crawley had the “full support” of the executive board—a statement I dutifully conveyed to Virology Blog readers.

To be clear, I don’t know what Dr. Crawley actually said in the lecture, or if she mentioned my name. The slide live-tweeted from her talk, which featured the phrase “libelous blogs” near a screen-shot of one of my Virology Blog posts, speaks for itself. (Esther, if I’ve misunderstood and you meant to highlight my post instead as an example of an accurate, non-libelous blog, let me know ASAP.)

Despite the claim that Dr. Crawley enjoyed “full support” from the board, one of the CMRC’s charity members, ME Research UK, announced a few days later that it was withdrawing from the collaborative, “with immediate effect.” ME Research UK’s announcement did not mention Dr. Crawley, but the meaning was clear given the timing and abruptness of the move. So it appeared that the “full support” of the board for Dr. Crawley was likely less than “full” even as Dr. Holgate made the claim.

I am now trying to ascertain what prompted Dr. Holgate to issue such a statement. I had assumed he canvassed every single member of the executive board to gauge whether there was in fact “full support” for Dr. Crawley. Perhaps he did—and perhaps ME Research UK affirmed support for Dr. Crawley yet decided to leave days later for unrelated reasons. But that just seems unlikely.

On the Phoenix Rising forum, Renal-gate has generated a huge amount of interest. The Renal-gate thread has received more than 31,000 views. One commenter suggested that Dr. Holgate was urged to make the statement by the Science Media Centre’s Edward Sykes, an observer on the CMRC executive board. I have no idea if this is true. I have written to both Dr. Holgate and Dr. Sykes to find out how this statement of “full support” arose. I have asked if in fact every member of the CMRC board was canvassed before Dr, Holgate spoke on their behalf. I don’t expect a response, but will provide an update if I hear from Dr. Holgate or Dr. Sykes or anyone who can shed light on what happened.


In other news, Action for ME also issued a statement last week. The statement came out of a board meeting that took place in April—that is, before these most recent events. So no one should expect it to have addressed the public relations nightmare that Dr. Crawley has since presented to all those within her circle, including Action for ME.

(I want to stress that conscientious organizations really do need to take time in responding to challenges. It is much easier for me to immediately blog and shoot darts than it is for those who run big groups to consult each other and address difficult issues in a responsible way.)

On the positive side, the Action for ME statement noted the ongoing controversy surrounding the PACE methodology and trial conduct, and stressed that the questions and concerns need to be addressed “as a matter of urgency.” The statement highlighted the recent reanalysis of the reported recovery findings from the 2013 Psychological Medicine paper, quoting the new study’s conclusion that “the claim that patients can recover as a result of CBT and GET is not justified by the data.”

The statement also urged NICE, which is re-visiting the issue of clinical guidelines for ME/CFS, to “take full account of emerging biomedical research, the views and experiences of people with ME, and clearly reflect nuances around findings and re-analysis related to the PACE trial.” And it included a strong endorsement of the need for sharing of research data. These are important messages that deserve to be widely disseminated.

But the statement falls short in rejecting the call to sign onto an open letter to Psychological Medicine, which was posted on Virology Blog in March. The open letter requested retraction of the reported recovery findings and was signed by more than 140 scientists, academics and other experts, as well as ME/CFS organizations. The open letter’s retraction request was based on the reanalysis of the recovery data, which documented how the PACE investigators weakened their recovery criteria in ways that jacked up their reported results. Although Action for ME was not informed of the open letter before it was originally posted, it was asked to add its name afterward. The organization declined.

In last week’s statement, Action for ME explained that decision by noting that Psychological Medicine had already refused the retraction request. “Therefore signing now will have no impact,” the statement noted. This is fallacious reasoning. I doubt many of us who signed the open letter believed it would magically result in retraction—certainly I had no such delusion. The decision-makers at journals like Psychological Medicine and The Lancet have long shown themselves to be impervious to arguments based on logic, common sense and scientific integrity.

From my perspective, the function of the open letter was to demonstrate to the journal editors, the PACE authors and the UK medical establishment that the larger scientific world rejects the kind of upside-down evidence cited by members of the CBT/GET ideological brigade. Action for ME’s argument that it “will have no impact” at this point to support the call for retraction is just silly. The opposite is true. An endorsement of the open letter by Action for ME would be viewed as a turning point in the debate, and I assume the organization’s trustees understand that.

I hope Action for ME will rethink this decision. I also believe the organization, given its close association with Dr. Crawley and her work, should specifically address the concerns raised by her lecture, although that seems unlikely to happen. In fact, having been pressed by patients to take a stand on the issue, the organization has already stated the following: “Action for M.E. had no input into this presentation and none of our team were present at the talk, so we cannot comment on its content.”

Unfortunately for those who have allied themselves with Dr. Crawley, however, she has been caught leveraging her prestige and her public platform at a professional gathering to portray those seeking the truth about questionable research as “vexatious” and “anti-science.” She has been caught slandering me personally, along with my friend and colleague, Dr. Racaniello. I doubt she expected her slides to go viral. But they did.

Dr. Crawley has created a real mess for herself and for everyone around her, and she refuses to clean it up. Someone really needs to stage an intervention.