By David Tuller, DrPH

In February, 2011, I wrote a bad article about the PACE trial. At that time, I was reporting on the XMRV situation and had never heard about this piece of crap. As happens at news organizations, my editor at The New York Times sent me the Lancet paper and asked me to write it up for publication later that day. I did the best I could. Not knowing any of the background, I took the study at face value and reported the bogus findings—that cognitive behavior therapy and graded exercise therapy appeared to be effective treatments. I did include a few caveats—that the authors had links to disability insurers, that they used a broad definition for the illness, and that patients had reported that exercise made them worse.

I got immediate push-back from patients, which was what persuaded me to examine the concerns they were raising—and that ultimately led to my 15,000-word investigation of this disastrous piece of research. Little did I know at the time that my article had triggered a crisis for someone who would later become a valued friend and colleague—journalist and ME/CFS patient Julie Rehmeyer, who has been instrumental in the ongoing efforts to discredit and debunk the PACE paradigm. As this campaign has progressed since Virology Blog posted my initial investigation in October 2015, we have strategized together and have reviewed and supported each other’s work, culminating in the opinion piece we co-wrote for The New York Times this spring.

Last month, her terrific book—Through the Shadowlands: A Science Writer’s Odyssey into an Illness Science Doesn’t Understand—was finally published. It deserves to be widely read. It is an engrossing and deeply moving account of an intelligent, curious, open-minded person forced to engage with this devastating illness. It is a meditation on the strengths and weaknesses of science and scientific institutions. And it is a cautionary tale about the importance of questioning widely accepted but unfounded assumptions and the flawed scientific findings that result. Finally, it advances the push to get rid of the PACE “treatments” once and for all and to find legitimate answers to this medical mystery. Julie and I recently spoke and e-mailed about her book, her initial encounter with my work, and other issues.

 

Why did you write the book?

The book had to be written. It wasn’t really a choice!

At the time my chronic fatigue syndrome got really bad, I was making my living writing about math research for science magazines. That’s pretty cognitively demanding, so when I was really sick, it was a struggle.

On the other hand, I was of course hugely motivated to figure out what was going on with me health-wise, and I started writing long e-mails to friends just about what was happening and how I was thinking about it. One of my friends wrote back and responded and basically laid it out for me, saying, ‘You have to write a book about this.’ I read his email and immediately thought, ‘That’s my book.’

And this is when you were in the middle of it?

Very much in the middle of it—I was at my sickest, often too weak to turn over in bed. I was too ill to work on it in a concerted way, but that was the point that I knew I’d be writing a book about this and had a fairly clear sense what it would be. It wasn’t a decision — it was more an expectation about what was going to happen.

This was in 2011, right at the time the PACE trial came out. At that time, there was very little good information about ME/CFS. So on a practical level, I felt like the book was needed. But on another level, I had this bigger sense that I was in the middle of this huge experience, and while I didn’t know where it was going to take me, it felt so much bigger than me. A million other Americans were going through something similar, and society had pushed all of us into the shadows—our experience was almost completely invisible. To the extent it was seen at all, it was seen negatively, because there was so much prejudice about chronic fatigue syndrome, and there still is.

So I sort of felt like Jonah in the belly of the whale, in a dark place being carried to who-knows-where. Even then, it had a mythic quality, and as the events I recount in the book unfolded, it became even more mythic.

Is the book just about this illness, or is there a larger issue?  

It’s about a lot more than illness.

Chronic fatigue syndrome has attracted so much prejudice in part, I think, because it’s so scary. The idea of getting sick in such a formless way and becoming so powerless is frightening. We like to imagine that our energy is ours, that it can’t be taken away from us. But of course, that’s not true.

In a more general way, ME/CFS forces you to realize how little control you have really have over your life. Of course, none of us has perfect control over lives—we could get hit by a car any moment. But most people are able to construct lives where they feel enough control in a day-to-day way that they can push the ways they don’t have control out of their minds. That’s not a luxury you have with this illness. You never know from day to day what you’ll be capable of.

So the deepest question the book asks is, how can we live with the immediate knowledge of our own powerlessness? How can we construct meaningful lives in face of that fact?

The book has many other layers as well. On one level, it’s just a really entertaining story, one that, I hope, will suck you in, even if you’re lying on a beach digging your toes into the sand. It’s also a meditation on the nature of science, a mystery, a story of personal transformation, and a love story. I hope that people will pick it up, get sucked in, and emerge at the end with a greater feeling of spaciousness and curiosity and hope in their lives.

So you were first aware of my work when you read the first New York Times article I wrote about the PACE trial, when it was published in early 2011. What happened?

It’s a funny story in retrospect, though it didn’t feel funny at the time. That first story of yours was a fairly straightforward news article about the trial. It expressed some criticism, but not in a prominent way. And I was at my very sickest then, often too ill to turn over in bed. So I was lying in bed one morning reading The New York Times on my cellphone, and I saw the headline, ‘Psychotherapy eases chronic fatigue syndrome.’ I thought, ‘Therapy? They’re saying it’s all in my head?’

The fundamental premise of the trial was an offensive one: It was that patients like me were simply out of shape and obsessed about our symptoms, and all we needed was to stop worrying, build up our exercise and we’d be fine. I had this horrifying image of my editors reading this and thinking, “Ah, so that’s why Julie hasn’t gotten me that story! She’s just screwed up in the head!”

Your story was a shocking awakening for me. Until then, I knew that there was a prejudice about chronic fatigue syndrome, so that came as no surprise. But I’d been able to push it out of my consciousness. My friends certainly never expressed that.  But this was in the New York Times. The study had been published in The Lancet. It really made me feel that science and journalism were not on my side.

It sharpened a feeling I’d been struggling with already, and that I think pretty much all patients deal with: I felt abandoned by the world. And with the PACE trial, it was not only the world at large abandoning me, but the specific communities I had made my life in, science and journalism.

Of course, at the time, I didn’t know what the scientific problems with the trial were—I just knew that it didn’t fit with my experience. And I did hold out the possibility that I had either misinterpreted the trial or misinterpreted my own experience, and they were more compatible than I realized. But bit by bit, I realized the true explanation was that they had distorted their results, and I learned from many of the same sources you drew on for your huge expose.

On the one hand, it was comforting to understand what the heck was going on. On the other hand, it was enraging. It was enraging to see science so abused, but it was also enraging because I couldn’t figure out how to expose the problems myself. I describe the situation this way in the book:

I contemplated pitching a story about the PACE trial myself: “Dear Editor, I want to write a story about the biggest treatment trial in the history of chronic fatigue syndrome, published in the Lancet, led by some of the most reputable psychiatrists in Britain, which has influenced public health recommendations around the world and has received nearly no public criticism by the scientific establishment. But I, Julie Rehmeyer, can tell you it’s a crock of shit. Oh, and by the way, I’m a patient, I’m personally offended by this work, and I might be too sick to finish the story.” Hmm. Not a very compelling pitch.

Nor could I get other journalists interested in writing about the problems with the trial. I wrote a chapter of my book about PACE, but of course that was years after this.

I was working on that chapter when I heard from you about your expose about the trial, and I thought, “Hallelujah!” I was thrilled both because it meant that the PACE trial would be taken down sooner than when my book came out — and also because my book didn’t have to do the very hard work you did, making a scientifically bulletproof argument against it. Instead, I could give a readable, emotionally powerful summation of the “low lights,” as it were. Which is a lot better for my book, because I tried to write it to be a compulsively good read for anyone, even those who aren’t especially interested in science.

So did your experiences with this illness change your relationship to science?

Absolutely. I’d always known, of course, that science can go wrong, but I’d never seen the kind of breakdown that happened with the PACE trial. The problems there were on all levels: with the trial itself, with peer review, with the way it was marketed, with the journalism about it, with the response of the scientific community and the public health agencies, on and on and on. In that case, science — at least as practiced in this case — was not my friend.

But it wasn’t just the PACE trial that affected me. When I first got sick, I expected that science would save me, whatever was wrong with me. But I came to realize that the existing science about the illness was terribly weak, lots of small, unreplicated studies that might or might not mean anything. And the NIH had been spending only around $5 million a year on ME/CFS research for the previous couple of decades — five bucks a patient, since there about a million American ME/CFS patients — that wasn’t likely to change anytime soon. So I was forced to accept that I was on my own.

And my situation got pretty desperate: I had pretty much run out of medical options, I was living by myself but not really able to care for myself, I was running out of money, I had no family to turn to. So I, uh, relaxed my standards as I considered treatments that didn’t have a lot of scientific backing. In particular, I heard from other patients who said they’d improved enormously by taking extreme measures to avoid toxic mold. I thought the idea was almost certainly hooey — as far as I knew, mold might exacerbate allergies or asthma, but it couldn’t paralyze you. But these patients were smart and impressive, and their stories were mind-blowing. One patient wrote about how after two months living in a cargo trailer in the desert, he could run and lift weights again. I read his post over and over again, and cried.

The very short story is that I tried it, and it worked spectacularly well for me.

I was thrilled, but also puzzled. Why did so many scientists say that people like me, who said that mold had neurological effects, were wacko? What did we know scientifically about the health effects of mold? And what could explain my experiences? I found answers to these questions, ones I found pretty compelling, and it increased my sense that our scientific institutions often don’t function well in the face of complex and confusing illnesses.

At the same time, science was an enormous tool for me personally in navigating all of this. I absolutely relied on scientific thinking in evaluating, and sometimes rejecting, my theories. And even with no research budget, as individuals, we can apply science to our lives to great effect.

Here’s one example of that: I wanted to make sure that I was correct in my belief that mold was indeed an enormous factor in my illness, that I wasn’t somehow fooling myself. In particular, I was concerned that I could be experiencing what scientists call a “nocebo effect,” the evil twin of the placebo effect: being convinced that something will hurt you can itself bring on physical symptoms. So I performed a placebo-controlled, double-blind experiment on myself, by sending a half-dozen washcloths to a moldy building and keeping a half-dozen washcloths clean, and then seeing if I could distinguish them. I ended up doing so well enough that I would have had only a two percent chance of doing as well if I were just guessing (that is, I had a p-value of .019).

The PACE trial came out in 2011. Do you think things have changed in the ME/CFS world since then?

Things have changed hugely over the last six years, on a lot of different fronts. Your work has made an enormous difference. I’ve called you a hero and I really think that’s true. Having the flaws of the PACE trial finally brought to light in a really serious way has been transformative, as has your work galvanizing the previously-quiescent research community against it.

Things have changed on other fronts, too: A few other journalists, like Miriam Tucker, have gotten very interested in the illness. And other journalists have gotten interested too — folks who may not know much about it initially but they are taking it seriously and writing good stories.

The scientific world is finally taking the illness seriously, too. The attitude at the NIH has really changed in the last six years. We’ve got a long way to go, but nevertheless it’s a really different world than it was. As much as anything, we’ve got their attention, they’re thinking about it and they care about it. Plus, some really good researchers are now seriously interested in the disease.

And on top of all that, the patient community has become far more organized and active, for example organizing the Millions Missing marches around the world (for the millions of patients missing from their lives and the millions of dollars missing from ME/CFS research budgets).

What about in the UK?

There’s no question that the UK has a lot further to go. And I don’t mean to be at all ignoring them in expressing optimism. We’re not done until things have changed over there too. But as research comes out in the U.S. and elsewhere it changes attitudes more broadly. And also, your work has made taking PACE seriously less tenable. The U.K. is slower to pay attention, but these developments are still having an impact and making their way through.

I also hope that my book will have an impact in the U.K. as well. Rational arguments reach people on one level, and emotionally powerful stories reach them on another. Part of the book’s work in the world is to reach people without any particular interest in ME/CFS, keep them fascinated and invested for 300 pages, and in the process, to shift their attitudes a bit. And hopefully, that will help to make life less miserable and difficult for my patient friends in the rest of the world as well.

 

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.

Goal

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: davetuller@berkeley.edu

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.