NCCIH research: Nothing much there behind the curtain

It's an understatement to say that I'm not exactly a fan of the National Center for Complementary and Integrative Health (NCCIH), the institute formerly known as the National Center for Complementary and Alternative Medicine (NCCAM) and, even a year after its name change, probably still better known by its old moniker. Just type "NCCAM" or "NCCIH" into the search box of this blog if you don't believe me. Basically, it's an institution forced upon the National Institutes of Health in the 1990s by Senator Tom Harkin (D-IA), a woo-friendly senator who believed that bee pollen cured his allergies and a man who seven years ago famously chastised NCCAM for not having "validated" enough complementary and alternative medicine (CAM).

While on the surface, it doesn't seem unreasonable to want to study "unconventional" treatments that fall under the rubric of CAM or "integrative medicine," skeptics' criticisms of NCCIH have basically boiled down to these: First, NCCIH has been wasting money on magic, treatments like reiki (faith healing substituting Eastern mysticism for Christian belief), homeopathy (although in fairness I haven't been able to find an NCCIH-funded homeopathy study since 2008), and the like. Second, NCCIH promotes the "integration" of pseudoscience into medicine through its funding of "training programs" in CAM in medical schools, as with Georgetown. Third, it is unnecessary. There is nothing that NCCIH studies that couldn't or wouldn't be studied through grants by other Centers and Institutes at the NIH. As Harriet Hall says about naturopathy, what is good about NCCIH is not unique, and what is unique about NCCIH is not good. It's not as though, if NCCIH ceased to exist, the various areas "rebranded" as "CAM" or "integrative medicine," such as placebo effects, the effect of lifestyle interventions on disease and health, or supplements, to name a few, wouldn't be studied if there were scientific merit. All NCCIH brings to the table is a culture with a willingness to study pseudoscience, complete with quacks such as chiropractors, naturopaths, on its advisory council. Finally, little of value has ever been demonstrated using NCCIH grants or by NCCIH investigators. Studies of supplements have been disappointing at best, and no truly "alternative" treatment has ever been validated by the NCCIH.

Of course, Josephine Briggs, the current director of NCCIH, would apparently beg to differ. The other day, she published a post on the NCCIH blog about what she considers to be notable research from 2015 funded by the center.

Christina Smolke, Ph.D., of Stanford University was featured as one of Nature’s 10 People Who Mattered This Year for her team’s successful engineering of a yeast strain capable of making opioids. This achievement—the most complicated chemical synthesis ever engineered in yeast—was also highlighted as one of the runners-up for “Breakthrough of the Year” in Science.

Ted Kaptchuk’s work on placebo was recently featured in The New Yorker as one of “The Most Notable Medical Findings of 2015.” Ted, a longtime NCCIH grantee, published several articles last year, including about how genes affect the placebo response.

U.S. News and World Report highlighted the work of Dr. Beth Bock at Miriam Hospital in Providence, Rhode Island for her research on yoga as an effective therapy for smoking cessation, particularly for individuals who either cannot use medications, or who choose not to use medications while quitting.

At this, I scratched my head, particularly the first one. Smolke's work, as impressive as it sounds, also doesn't sound as though it has anything to do with "alternative" or "integrative" health. Take a look at Nature's description of her research. About a year ago, there was a race to engineer a strain of yeast that can produce opioids because a more stable production method would be highly useful, given the unpredictable yields of poppy crops. However, no one had been able to identify an enzyme that converts reticuline, a chemical building block of morphine and other narcotics, from one form to another. Smolke used a very clever approach to solving this problem:

Most other labs hunting for the enzyme were working to isolate it from poppies directly. But Smolke and her team at Stanford University, California, took a different approach: they combed through genetic databases, looking for snippets of sequence that looked as if they might be involved in reticuline metabolism. When they found a hit from several different poppy species, they ordered a synthetic version of the gene that had been built letter-by-letter by a machine. They plugged it into yeast and it worked. “I was super excited, really proud and also relieved,” Smolke says. “It was a bit of a Hail Mary.”

The discovery enabled Smolke’s lab to stitch together a pathway of 23 different genes from plants, mammals, bacteria and yeast to produce the world’s first narcotic through synthetic biology (S. Galanie et al. Science 349, 1095–1100; 2015). It was a crowning achievement for a biological wunderkind who started her own lab at the California Institute of Technology in Pasadena at the age of just 28. The opioid-producing yeast cells contain the most complex synthetic-biology pathway developed so far, and mark a turning point for the field by showing how step-by-step engineering can turn microbes into drug factories. “This will significantly impact our future ability to produce many more chemicals through biotechnology,” says Jens Nielsen, a synthetic biologist at the Chalmers University of Technology in Gothenburg, Sweden.

This is truly an impressive achievement, clearly a breakthrough, allowing yeast to turn sugar into thebaine, the precursor of synthetic opioids like hydrocodone and oxycodone, but what does it have to do with "integrative health." Pretty much nothing that I can see. It's standard biotechnology cleverly exploited and pushed beyond its previous limits to do something new. Nature points out that her goal is not just to produce opioids but to design new opioids free of the most troublesome side effects, such as dependency and addiction. This is standard medicinal chemistry, only using a new technology to approach the problem. Science also notes that, as yet, this process is very inefficient and would likely require thousands of liters of culture to produce a single dose. Of course, Smolke is now working on increasing the yeast's output to levels that could be used to manufacture opioids.

I looked up the grant funding Smolke's research, Synthetic Biology Platforms for Natural Products Discovery. This grant was indeed funded by NCCIH and was funded through the NIH Director's Pioneer Award (DP1) mechanism, which is described as a program that "complements NIH’s traditional, investigator-initiated grant programs by supporting individual scientists of exceptional creativity who propose pioneering and possibly transforming approaches to addressing major biomedical or behavioral challenges that have the potential to produce an unusually high impact on a broad area of biomedical or behavioral research." I'd agree that Smolke's work qualifies, but I fail to see anything traditionally considered "integrative" about it. After all, she's trying to develop a technique to manufacture opioids more efficiently and then improve upon them! Most "integrative" techniques try to avoid opioids.

Does anyone think the NIH wouldn't have funded this work if NCCIH didn't exist? I don't, particularly given that this was funded through the Director's Pioneer Award. In fact, given that such special mechanisms usually don't go through specific institutes or centers brings up the question of how, when this grant achieved a fundable score, it got assigned to NCCIH. That might be a more disturbing thing about Smolke's work than anything else, that someone at NIH thought it appropriate to have NCCIH fund this. This is an example of what is good about NCCIH not being unique to NCCIH.

Moving on, I've written about Ted Kaptchuk more times than I can remember. As you might recall, he's the traditional Chinese medicine maven on faculty at Harvard Medical School who's done a lot of research on placebo effects and tried to spin it as evidence that placebo effects can actually have therapeutic effects. Of course, his research hasn't exactly shown that, such as when he showed that a placebo intervention for asthma did indeed make asthmatics feel as good as a real intervention (namely an albuterol inhaler) without having any detectable effect on the pathophysiology of the disease. As I pointed out, that's a very dangerous situation because it could deceive an asthma sufferer into thinking he's doing much better than he is. He could be moments from a respiratory arrest and not realize it. Other times, Kaptchuk tried to show that there can be placebo effects without deception while in actuality showing exactly the opposite. The list of examples goes on.

What I can't figure out is why he's on this list, in particular why Jerome Groopman included him on a list of the most notable medical findings of 2015, as I don't recall any significant findings by Kaptchuk this year. Indeed, a reader showed me Groopman's article a week or two ago, and I briefly considered blogging it. I decided not to because the gruel was so thin:

Ted Kaptchuk is a pioneer in elucidating the placebo effect, acting as a nodal point among researchers ranging from anthropology to genomics. This year, he and his colleagues published a paper that highlights how people may be genetically predisposed to, or resistant to, the placebo effect. The relevant genes govern molecules that shape our moods and goal-driven behaviors. Also this year, Kaptchuk published on the ethics of placebos, which physicians once prescribed routinely for diseases that had no remedy. He and his co-authors emphasize how the placebo effect arises not only from swallowing an inert pill from a bottle but also, as I experienced, from the intimate interaction between the sufferer and the healer. Reading these articles, I couldn’t help but recall a headline that appeared in The Onion, in 2003: “FDA Approves Sale of Prescription Placebo.”

It's interesting that Groopman cites Michael Specter's somewhat misguided article on Ted Kaptchuk and placebo effects. In any case, after this I still couldn't figure out why Groopman would include Kaptchuk as someone with notable scientific achievements in 2015 because, well, I don't really recall there being any. In any case, what article was Groopman referring to when he mentioned an article on the the ethics of using placebos is this New England Journal of Medicine article Placebo Effects in Medicine. It's a Perspective article, which means it's not original research but rather commentary. It's basically the same stuff Kaptchuk has been saying for years, admitting that placebo effects don't have significant effects on disease pathophysiology but insisting that they are not "bogus."

As for the genetics research, all I could find was a review article in which Kaptchuk refers to the "placebome" (because, you know, in this ages of genomes, proteomes, metabolomes, etc., everything has to be an "-ome," even the "woo-ome," as I like to call it). He also published a meta-analysis of placebo responses in genetically determined intellectual disability in PLoS One. Overall, Kaptchuk's output last year hasn't included anything particularly interesting. The "placeboes without deception" study, as poorly interpreted as it does, was at least interesting. Ditto the asthma study. Anything in 2015? Not so much. In any case, Groopman is closer to the truth than he realizes when he compares Kaptchuk's editorial to The Onion. Basically Ted Kaptchuk is an example of what is unique to NCCIH not being good. Instead of objectively studying placebo effects, Kaptchuk has an agenda to promote a message that CAM "works" through placebo effects and that placebo effects have real therapeutic effects.

Finally we come to Beth Bock. This is what the US News & World Report said about her:

Though medications have been effective at helping smokers quit, the majority of smokers don't use them, and more than 40 percent of smokers report failed attempts each year. Researchers at Miriam Hospital in Providence, Rhode Island, are turning to yoga as an alternative therapy for tobacco sensation.

For this research, the NIH awarded the hospital a grant of $593,064.

Basically, it's an R01 grant, Efficacy of yoga as an alternative therapy for smoking cessation. The clinical trial funded by this can be found here. It's still recruiting and apparently hasn't been published. Basically it's an open label study comparing smoking cessation plus yoga consisting of twice weekly, 1-hour yoga classes delivered for 8 weeks combined with once-weekly, 1-hour cognitive-behavioral smoking cessation classes with smoking cessation plus wellness training, consisting of twice-weekly, one-hour Wellness classes given on a variety of health topics twice weekly to match schedule of the yoga classes, plus 1-hour per week of cognitive-behavioral smoking cessation.

What's the rationale for the study? This:

Our research, and the research of other investigators, has demonstrated that traditional (Western) exercise (e.g., brisk walking, bicycling) improves smokers' ability to successfully quit. Exercise may help smokers quit by reducing concerns regarding post-cessation weight gain, and by reducing nicotine withdrawal and enhancing mood. Recent research suggests that yoga is an acceptable and potentially effective alternative therapy for smoking cessation for several reasons: As a form of exercise, yoga shares many of the same properties as traditional (Western) aerobic exercise in that yoga has been shown to improve mood, physical fitness, weight control, self-image and quality of life in healthy and ill populations. Moreover, features of yoga, including a focus on breathing, mental concentration, meditation, stress reduction and enhanced mood are likely to have special relevance for smokers who are trying to quit. Thus, yoga may be particularly attractive as an alternative for individuals who either cannot use medications, or who choose not to use medications while quitting.

I fail to see what's so special here. The investigators state that exercising can help smokers quit. Yoga is a form of exercise. Big deal. Assuming exercise improves smokers' ability to successfully quit, I expect that this study will likely be positive also because it adds a regular exercise program in the form of yoga to cognitive-behavioral therapy for smoking cessation. What would be interesting is what's not being studied: Exercise known to help smokers quit versus yoga. This appears to be yet another example of what is good about NCCIH not being unique. Unfortunately, because pretty much all exercise and lifestyle interventions for health have been "rebranded" as CAM or "integrative," they get lumped in with all the pseudoscience in CAM, such as traditional Chinese medicine, acupuncture, naturopathy, reiki, and the like, and it's frequently the same people studying lifestyle and exercise interventions who also engage in quackademic research into rank pseudoscience. Again, there's no need for an NCCIH to fund this research; it could be perfectly well handled by another center or institute in the NIH.

Presumably, Briggs picked the three best examples of good science she could find from the entire NCCIH portfolio of grants. If that's the case, her list strikes me as pretty pathetic. It includes research that has little or nothing to do with CAM and everything to do with molecular biology, biotechnology, and synthetic biochemistry, research that oversells placebo effects, and a clinical trial that reinvents the wheel by testing yoga as yet another form of exercise to help people quit smoking. More than anything else, this thin research portfolio indicates that NCCIH has no real scientific rationale to continue to exist.


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So two of the three examples Briggs listed are there solely because they were mentioned in the popular press, rather than on the basis of any solid scientific results? And these are supposed to be her best examples? With most government funding agencies, that kind of lack of productivity tends to get your project/mission terminated.

I agree that Smolke's work is significant, but as you say, it seems odd that NCCIH rather than some other NIH program is funding it. This looks like an example of a blind squirrel finding an acorn.

By Eric Lund (not verified) on 07 Jan 2016 #permalink

I see ninjas from Mercola stealing these genetically engineered yeast to sell as "All-natural pain relief Baker's Yeast" on woo web sites.

Next up: yeast engineered to make naloxone.

By Chris Hickie (not verified) on 07 Jan 2016 #permalink

"...traditional (Western) exercise..."


“…traditional (Western) exercise…”


Bronco bustin', calf ropin", headin' 'em off at the pass?

Dogie rollin?

By NumberWang (not verified) on 07 Jan 2016 #permalink

I thought it was *hard( to get grants, and that your study proposal/plan/protocol had to be beyond reproach? Clearly not when your money comes from NCCIH.
If I designed a study that compared two such different things as "yoga" and "wellness classes" in a study about if yoga is as good as aerobic exercise for supporting smoking cessation, my boss would laugh at me.

By JustaTech (not verified) on 07 Jan 2016 #permalink

Dr. Do-little's (back) in the house. Of course. :-)

-Jamie (Ariel) Parsons

(Look up the meaning of the names.)

Dr. Do-little’s (back) in the house

It is tempting to approach NCCIH with a research proposal for talking to the animals.

By herr doktor bimler (not verified) on 07 Jan 2016 #permalink

It looks a lot like Briggs has dredged up references in the popular press to research funded by her agency and is promoting these as notable research. Well, there were notable in that they were noted in the popular press, but other than Smolke's work not that notable as science.

If this is all you have to show for $124 million of funding spent, I would be embarrassed.

By Chris Preston (not verified) on 07 Jan 2016 #permalink

OT but really...

Orac, when I click on some of the 'Insolence returned' I get security warnings about the site -
Danger Danger! blah blah blah.
I thought you should know in case it means anything.

By Denice Walter (not verified) on 07 Jan 2016 #permalink

Denice, for some reason those are the ones where the "http" has been turned into an "https", which is for those with secure certification. Just remove the "s."

@ Chris:

Thanks but now it's not doing it.

By Denice Walter (not verified) on 07 Jan 2016 #permalink

Yeah, it is kind of an inconsistent annoyance.

And I just got it at "The Spudd."

Hi, Orac! Great to see you're still blogging here.
Not sure if you remember me, but I used to blog at the now-defunct Signout, and am trying to get back into my account to manage a few things. Do you know the contact info of the administrator, who might be able to help me regain access?
My email address should show up with this comment, but let me know if not and I can leave it in a second comment.
Thanks in advance, and big regards all around!

Have they lost their minds? As you point out, none of the examples should have qualified for funding under the program. Given those examples, anything goes.

The National Center for Complementary and Integrative Health (NCCIH) is about the most inane title for an institute as I have ever seen, so I suppose I shouldn't be entirely surprised by their confusing behavior. At least the former moniker brandished the word "Medicine", but as you explained in a previous blog, that flew in the face of what the FDA deems to be legal and any treatments funded under the program would therefore become de facto claims in violation of the law, so the name had to be changed to protect the purveyors of so-called alternative and complementary medicines, which are plainly drugs marketed under the guise of dietary supplements. The same goes for anything else used in the treatment or prevention of disease. As a result, clinical trials of dietary supplements will increasingly be conducted elsewhere.

By Lighthorse (not verified) on 07 Jan 2016 #permalink

On the basis of an apparent soft spot for rehab professionals, acquired from his history of treatment for back pain, Groopman includes a paper on genetic predisposition to the placebo effect amongst the most notable medical findings of the year. He doesn't explain what makes the paper medically notable, as he does for his other six most notables.

Instead he links to an interview with the author of the placebo paper - by a very sympathetic placebo-friendly interviewer.
All of which is re-cited by the NIH's institute for placebo medicine: NCCIH. Who just happen to have dished out lots of dosh to the particular placebo researcher in question.

Shame on the lot.

By Leigh Jackson (not verified) on 08 Jan 2016 #permalink

The inclusion of yoga in alternative medicine continues to baffle me; the only reason I can see why yoga would be lumped in with other woo-ly modalities is the insistence of most of its practitioners on needlessly incorporating dollops of Eastern mysticism into the practice, with a view to roping in the gullible.

By Kausik Datta (not verified) on 09 Jan 2016 #permalink

As useless as SETI

@Gary - at least SETI has a chance of paying off....


@Gary – at least SETI has a chance of paying off….

Super off topic, but I heard an interesting thought on SETI a while back. The idea was that an advanced civilization would have encrypt their communications (as we do now) and therefore would be indistinguishable from random noise. For all we SETI has been receiving alien broadcasts this entire time.

By capnkrunch (not verified) on 09 Jan 2016 #permalink

SETI is scientifically plausible, unlike, say, homeopathy.

We might find some sort of life in our solar system, but a program like SETI is the only way we stand a chance of finding intelligent life somewhere other than earth.

PING times will be outrageous.

@Julian Frost: For pete's sake....your #23 needs a "DO NOT DRINK" warning. I laughed until I cried AND inhaled my water.

Thanks for making my lousy snowy Friday better. (hmmmmm...back ache after shoveling the heavy wet snow...acupuncture or reiki?)