Medicine

When I first heard about studies using smartphones to treat anxiety with cognitive therapy I was intrigued, to say the least. However, I had a misconception about what that actually meant. My assumption was that the smartphone app would be automating some basic cognitive therapy, a virtual therapist that could give some reflective feedback and also give basic cognitive tools to deal with anxiety. That sounded like it might be useful, at least for mild cases, and I hoped that the app was designed to refer severe cases to an actual therapist.

I had already been very interested in the concept of online, virtual, or computer-based therapy. It seems like this is coming, but of course it needs to be researched to see how it works and for which patients.

But that is not what the smartphone app is at all. Rather it has to do with a treatment technique called cognitive bias modification (CBM). This therapy is based on research that finds that those with social anxiety have a cognitive bias which makes them attend more than others to signs of threat or to negative emotions. Further, they have a cognitive bias to interpret ambiguous social cues as hostile or negative. This raises a cause and effect question – are they anxious because they have these cognitive biases, or does the anxiety make them attend to negative emotions and interpret emotions negatively. Perhaps it is both, in a reinforcing feedback loop.

There is some evidence from prospective studies that cognitive biases predict future anxiety, suggesting (but not proving) a cause and effect. Another way to address this question, and perhaps to develop a treatment for social anxiety, is to target these cognitive biases directly, rather than addressing possible underlying causes of the biases. That is where the smartphone app comes in. There are two computer-based treatments designed to directly treat these cognitive biases: CBM-Attentional and CBM-Interpretive (CBM-A and CBM-I respectively).

For CBM-A subjects are made to look at a computer screen (or now a smartphone screen) with two faces displayed, one neutral and one disgusted or angry. They are told to note and remember the letters that appear on the screen. A letter than appears where the neutral face was located, drawing their attention toward the neutral face and away from the face displaying a negative emotion. This is supposed to train their brain away from attending to negative emotions – modifying their cognitive bias for attention.

For CBM-I subjects are asked to interpret word-sentence associations, and are given positive feedback for benign interpretations and negative feedback for negative interpretations. Again this is supposed to modify their bias away from negative interpretations.

As always, we like to evaluate any new treatment paradigm on two basic criteria – is it plausible, and does it work better than placebo. Plausibility is a little challenging to assess. There are certainly no laws of physics, chemistry, or basic biology involved. Plausibility depends on whether or not you think this top-down approach to brain training can have a significant and lasting effect on our thinking and emotions. Personally I am not convinced that this approach has much value. It all seems like the “magic wand” approach to therapy – rather than addressing a complex behavior with an approach that reasonably addresses that complexity, it focuses on one perhaps superficial aspect of something as complex as social anxiety.

I have not been impressed with the whole “brain training” approach to cognitive therapy, such as EMDR (eye movement desensitization and reprocessing). At best it seems like treating the symptom of a disease rather than the disease itself. But I could be wrong. Sometimes the symptoms are the disease. In some chronic pain conditions, for example, the pain is the problem, and treating the symptom of the pain may be a reasonable and effective approach. Perhaps at its core social anxiety is being driven by some flaw or bias in brain function that can be tweaked by simple training.

My personal bias, therefore, is that this kind of approach has low (but not very low) plausibility but I am willing to be convinced by reasonable clinical evidence. So what does the clinical evidence show?

There are many pilot studies of CBM (both CBM-A and CBM-I and a couple with combined treatments). A review published in February 2011 concluded:

Although the potential clinical utility of CBM is quite exciting, the existing data do not address a number of limitations. First, the majority of the evidence of CBM’s effect on cognitive bias and anxiety relies on analogue samples and brief (one session) experiments. The field is in need of RCTs to test treatment protocols in clinical samples. A related issue is that all existing RCTs represent researchers’ initial pilot studies rather than large-scale RCTs. Therefore, they comprise of relatively small samples (subject numbers ranging from 29 to 44). Effect sizes from small studies are unreliable [93]; thus we await the results of larger, definitive trials.

While positive, the evidence is still preliminary and there needs to be more rigorous trial design before we can conclude that there is a real specific effect here. My concern with the research to far is that we are just seeing the non-specific effects of treatment intervention, rather than specific effects of CBM.

In a recent New York Times article on the topic, one specifically discussing the smartphone app for administering CBM, the results of perhaps the largest study to date are discussed. The study is yet to be published, but the researchers reported their results so far as:

Participants who got the treatment improved their scores on a questionnaire measuring anxiety, dropping by an average of 22 points, compared with an 8-point drop among people in a “waiting list” group, who got no computer games to play. However, a placebo group in the study practiced with a two-face video program not intended to shift the eyes from one face or the other, and their anxiety levels as measured on questionnaires also fell by about 22 points, just as they had for those who got the treatment.

The comparison to a waiting group showed a significant difference, but to a more rigorous and blinded control showed no difference at all. While the article indicated that these results were “confusing” I don’t find them confusing at all – they are dead negative. The only comparison that matters is the blinded one to a reasonable placebo treatment.

Further the article refers to a review from the University of Pennsylvania that found evidence of publication bias:

The authors noted that there was evidence of what scientists call a “file drawer” problem — in which studies finding no effect are filed away or ignored, while encouraging ones are published. “I think in this field the standards for publishing positive studies are lower than for negative ones,” Dr. Van der Does said in an e-mail.

To summarize: preliminary evidence is mixed but tending toward the positive, but has acknowledged serious limitations and evidence of publication bias. Preliminary results from a large and well-controlled study are negative.

I agree with various reviewers who conclude that this treatment is interesting and deserves more research. I would like to see some rigorous large studies – the kind that are really definitive. I sense a great deal of excitement among researchers. For example, from a recent pilot study the authors write:

Excitingly, these procedures have been shown to reduce bias in attention to threat (CBM-A), and to promote a positive interpretive bias (CBM-I) in anxious populations; furthermore, these modifications are associated with reductions in anxiety. We believe that these techniques have the potential to create a real clinical impact for people with anxiety.

The excitement may be premature, however. I hope this therapy is found to have potential, because it can result in a cheap and convenient treatment method. All the more reason to move beyond pilot studies are perform some rigorous studies that can really answer the question as to whether or not the specific elements of CBM-I and CBM-A, alone or in combination, can have long lasting benefits for social or other forms of anxiety.

Please note: the following refers to routine physicals and screening tests in healthy, asymptomatic adults. It does not apply to people who have been diagnosed with diseases, who have any kind of symptoms or signs, or who are at particularly high risk of certain specific diseases.

Throughout most of human history, people have consulted doctors (or shamans or other supposed providers of medical care) only when they were sick.  Not too long ago, the “if it ain’t broke don’t fix it” mindset changed. It became customary for everyone to have a yearly checkup with a doctor even if they were feeling perfectly well. The doctor would look in your eyes, ears and mouth, listen to your heart and lungs with a stethoscope and poke and prod other parts of your anatomy. He would do several routine tests, perhaps a blood count, urinalysis, EKG, chest-x-ray and TB tine test. There was even an “executive physical” based on the concept that more is better if you can afford it. Perhaps the need for maintenance of cars had an influence: the annual physical was analogous to the 30,000 mile checkup on your vehicle. The assumption was that this process would find and fix any problems and insure that any disease process would be detected at an early stage where earlier treatment would improve final outcomes. It would keep your body running like a well-tuned engine and possibly save your life.

We have gradually come to realize that the routine physical did little or nothing to improve health outcomes and was largely a waste of time and money. Today the emphasis is on identifying factors that can be altered to improve outcomes. We are even seeing articles in the popular press telling the public that no medical group advises annual checkups for healthy adults. If patients see their doctor only when they have symptoms, the doctor can take advantage of those visits to update vaccinations and any indicated screening tests.

The Physical Exam Itself

The physical exam of a healthy, asymptomatic adult is unlikely to reveal any significant abnormality (1) that would not have been detected eventually when symptoms developed and (2) whose earlier detection and treatment would reduce morbidity and mortality in the long run.

A directed physical exam is sometimes indicated in patients with risk factors for specific conditions. A Pap smear is indicated in most women, but not every year, and the accompanying pelvic exam is likely a waste of time.

For healthy adults between the ages of 18 and 65, The American Academy of Family Physicians (AAFP) recommends only these components of the traditional physical exam:

• For men, a blood pressure measurement.
• For women, a blood pressure measurement and a periodic Pap smear.

They have other recommendations including vaccinations, counseling, and screening tests; but none of those require a physical exam.

Because they are so unproductive, routine physical exams are very boring to most physicians. My least favorite chore as an Air Force physician and flight surgeon was doing the required physicals. The system had some really idiotic requirements: for instance, the flight physical required a measurement of pulse rate after exercise, but there was nothing in the regulations that said what readings were considered abnormal or what actions to take if they were!

I heard about one doctor who had to do a lot of exams of healthy young men at a recruiting center and dreamed up a way to make it more interesting. He challenged himself to identify patients with situs inversus. This is a condition where the internal organs are on the wrong side (i.e. heart on the right, appendix on the left). It’s disqualifying for military service, probably because of the implications for battlefield trauma care. He soon held a record for the most diagnoses of situs inversus and was asked how he did it. He explained that he simply looked for men whose right testicle hung lower than the left and subjected those patients to a more intensive evaluation!

Screening Tests

We are increasingly questioning screening tests that were formerly recommended. The annual chest x-ray, tine test, and urinalysis are long gone. The recommended age limits for mammography have changed. Routine PSA testing is being discouraged. A recent study suggested that a woman whose DEXA scan shows normal bone density or mild osteopenia need not be rescreened for 15 years.

We don’t need to examine all the published literature on screening tests, because the U.S. Preventive Services Task Force (USPSTF) has done all the work for us.  They continually update recommended screening tests for different age and risk groups based on the latest studies. There are other organizations in the US and elsewhere that make similar recommendations but that may differ to some degree in different countries. In general, a specialty organization is likely to recommend more screening in its particular area of interest, based on a different focus in interpreting the same published evidence. The American Academy of Family Physicians, with a broader perspective, generally follows USPSTF recommendations.

The Early Detection Myth

There is a general perception, among the public and among doctors, that there’s no such thing as a bad screening test, that early detection is important, that knowing is always better than not knowing. If something is wrong with you, you need to know because, if you find a problem in time, it can be treated effectively to prevent morbidity and mortality. If you get a checkup and everything looks OK, you can breathe a sigh of relief and relax. Unfortunately this is all wrong.

A recent book explains why: Overdiagnosed: Making People Sick in the Pursuit of Health, by Drs. H. Gilbert Welch, Lisa M. Schwartz, and Steven Woloshin. It’s a comprehensive explanation of how test results make people sick and why visiting a doctor can be hazardous to your health. I reviewed it in an earlier article here on ScienceBasedMedicine.org. Please read that link and then come back.

Welch et al. commented

…some people may feel safer having their potential problems diagnosed and treated. For some, that may make the treatment side effects and hassle factors seem worth it… [but] the sense of being safer is likely an exaggerated view of the reality.

For a healthy, asymptomatic patient, the physical exam with the laying on of hands and stethoscope and other rituals is pretty much meaningless. If nothing is found, it can produce false reassurance. If something is found, it is not likely to prolong the patient’s life and it has a significant likelihood of leading to harm from unnecessary treatment or from a diagnostic cascade of tests, unnecessary surgeries, unnecessary expense, and unnecessary worry.

Re-inventing the Check-up

Doctors are not punished for overdiagnosis, but they are punished for failing to diagnose. We mustn’t let fear of lawyers interfere with our good judgment. The annual physical is obsolete.

On the other hand, there is a good argument for a periodic visit with a healthcare provider without the ritual of the physical exam. It’s helpful to have a systematic way of ensuring that the screening tests recommended by the USPSTF get done. An annual visit would be an opportunity for a preventive medicine interview and advice about a healthy diet, exercise, and other lifestyle factors. While an objective benefit has not been proven by any controlled studies, it can only be helpful for a doctor to get to know his patients before they get sick, for a patient’s history to be documented in a chart, and for patients to develop a relationship with a doctor they can trust. Instead of just rejecting the annual physical, maybe we ought to reinvent it.

Anyway, what’s so special about “annual?” The human body can’t read the calendar. A year is only a convenient way to jog the memory. Who’s to say that 365 days is better than 340 or 390 for any given purpose? In the absence of solid data, a range of suggested intervals might be more appropriate.

Welch et al. point out that health is more than absence of disease; it’s also a state of mind. They recommend health promotion efforts that lead people to feel more resilient, both physically and emotionally. Ironically, pursuing health requires not paying too much attention to it.

I am on vacation this week. So for my blog this morning I am going to do a quickie – here is a photo I was just sent by an SGU listener. They wanted our help in explaining the rather creepy image on the photo. Before I even read the e-mail, however, the sender sent another e-mail saying that they figured out the answer. Take a look and see what you think. I will post the answer in a couple days as an addendum below the fold.

A century and a half ago scientists knew very little about how life works, at least compared to what we know today. They knew little about the organelles that make up each living cells, the biochemical pathways involved in living processes, and knew absolutely nothing about genetics (which didn’t even exist yet as a discipline). It was in this context of relative ignorance that Charles Darwin proposed his particular theory of evolution and presented his argument for common descent and natural selection. The notion of evolution and common descent predates Darwin – scientists before him noticed a pattern in the sequence of fossils appearing in successive geological layers. Life seemed to be changing over geological time, with species in younger layers seeming to be derived from species in older layers.

Darwin added to that that basic observation his extensive personal observations of nature – that there is actually a great deal of variation within species, and that many species on the Galapagos seem to be derived from related species on the mainland, but changed to adapt to various niches on the islands. Still, evolution through natural selection was a remarkable hypothesis, but little more than a hypothesis. It is perhaps a good thing that there was so much left to discover about basic biology when evolution was proposed, for that created the opportunity to test this crazy theory.

Every major biological discovery post Darwin was an opportunity to falsify his theory. It could have turned out that the mechanism of inheritance involved a blending of characteristics from both parents (the prevailing notion of the time). This presented a problem for evolution, for then how do newly developed traits persist and change a species, rather than just being swallowed up and diluted in the large population? Mendel discovered that traits are actually discrete things (genes) that are not diluted. They persist as discrete units, so a new mutation would not simply be diluted, but can persist undiminished and spread throughout a population.

Sticking with genetics, it could have turned out that different species or different groups of species had their own pattern of genetic information, or even genetic code. Instead we discovered that every living thing uses the exact same genetic code (which three DNA base pairs code for which amino acids, etc.). Further, when we map out genetic variation we see a branching pattern of relatedness that roughly follows what we would expect from morphology – what living things look like. This same branching pattern of relatedness holds true no matter what bit of genetic code we look at. The same is true when we look at amino acid sequences in various proteins.

This didn’t have to be the case. If common descent through evolution were not true, and let’s say each species were created “according to its kind” then there is no reason why mammals and reptiles could not have had different genetic codes, or completely different proteins, or a different arangement of genes to achieve certain basic functions of  life.

When we look at living things we also see this same pattern of relatedness. Structures all seem to have a derivation, and related species share certain features in common. Giraffes and humans have the same number of vertebra in their necks. Mammals tend to have five digits on each extremity, and when they have fewer than five we see that lose the extra digits through embryological development. Horses are not coded to have one hoof and that’s it. They are coded to have five digits, but then four wither and don’t develop and one toe becomes the hoof. In some cases a mutation results in horses with a couple of extra toes – a throwback to their evolutionary past and connection to other mammals. Some mammals have more that 5 digits, like the panda. When we look closer, however, we see that the extra sixth digit, which functions as a thumb, is really an expanded wrist bone.

This brings up the issue of embryology and developmental biology. We could have discovered that each species develops from a single fertilized egg through an optimal straight path to its adult form – but we didn’t. We found that creatures take a twisting and turning path to their eventual form. While they do not pass through the adult form of evolutionarily more primitive ancestors, the developmental path they do take does reflect this history.

I haven’t even discussed the fossil record yet. We didn’t have to find the fossils that we did, but they were there to be found. We could have found any pattern of fossils, but what we did find is a pattern of changing species through geological time – confirming those earlier observations. We have never found a fossil that is impossibly out of sequence if evolution were true – no horses in the Cambrian fauna. We also do not see species arising without any possible antecedents – completely new morphologies not derived from earlier ones. We could have, but we didn’t. The branching pattern of relatedness we do see follows a temporal and even geological sequence that is compatible with the idea that all life evolved over time from a common ancestor.

Obviously there are still gaps in our knowledge. Evolutionary theory does not predict that there should be no gaps. Over time, however, the gaps are being filled in. It didn’t have to be that way, but it is. Each time critics of evolution point to a gap in the fossil record, the gap gets filled in. No connection between whales and other mammals? No problem, here is Ambulocetus and other “walking whales” and species between whales and terrestrial mammals. Birds and dinosaurs? Here is a host of feathered dinosaurs and primitive dinosaur-like birds. Humans and apes? There are numerous and growing Australopithecus and Homo species to flesh out the branches in between.

Now critics point to bat evolution – where are the missing bat links? Give it time. There are gaps, there will always be gaps – evolution does not predict no gaps, it predicts that they will be filled in as we find more fossils. The gaps are being filled in – but it didn’t have to be that way.

The theory of evolution through natural selection is an overarching theory of life that ties all the biological sciences together with one theory about how life arose. Of course such a theory makes numerous predictions that span every other aspect of biology. Each such prediction was an opportunity to falsify evolution. Instead, over the last 150 years, everything we discovered in biology is compatible with evolution and much of it profoundly supports evolutionary theory, to the point that “it would be perverse to withhold provisional assent” (to quote Stephen J. Gould). There is no other theory that makes the same predictions, or that can tie everything we have discovered about biology into one cohesive theory.

The result of 150 years of biological science is that evolution (natural selection and particularly common descent) is a proven scientific fact, beyond all reasonable doubt. It didn’t have to be that way, but it is.

One of the hallmarks of science as it has been practiced for the last century or so is that scientists share their discoveries in the peer-reviewed literature, where their fellow scientists can evaluate them, decide if they’re interesting, and then replicate them, usually as a prelude to building upon them. While the system of publication and peer review in science is anything but perfect (and, indeed, we have discussed many of its shortcomings right here on this very blog), I tend to like to view it in much the same way Winston Churchill characterized democracy:

Many forms of Government have been tried and will be tried in this world of sin and woe. No one pretends that democracy is perfect or all-wise. Indeed, it has been said that democracy is the worst form of government except all those other forms that have been tried from time to time.

I would rephrase this as:

Many forms of evaluating science have been tried and will be tried in this world of sin and woe. No one pretends that peer review is perfect or all-wise. Indeed, it has been said (by me) that peer review is the worst form of evaluating science except all those other forms that have been tried from time to time.

As mainstream medicine has become more scientific over the last century in the wake of the Flexner Report, physicians and medical researchers have similarly come to view publication in the peer-reviewed literature to be a very important component of communicating and evaluating medical discoveries. It’s not as though this is even a particularly high bar to pass, either. After all, many are the absolutely execrable papers that I (and my partners in crime here at SBM) have discussed over the last four years, nearly all of which were in peer-reviewed journals, some very prestigious. After all, if papers on “energy chelation” can find their way into decent journals and the likes of Mark and David Geier can publish in the peer-reviewed literature, while someone like Christopher Shaw can get cringe-worthy confusions of correlation with causation published, I don’t take seriously the whines of cranks who claim that they can’t publish in the peer-reviewed literature for one reason or another.

That’s why I view being published in the peer-reviewed literature as a minimum, but by no means sufficient, requirement good science. It’s also why, whenever I see a new claim, my first reaction is to see if (1) the person making the claim has published on it and (2) there are publications in the peer reviewed literature that support the claim. The first criterion helps me judge whether the person is a serious scientist; the second, whether there is any plausibility to his ideas. Sure, it’s not a foolproof scheme, but it is helpful.

I only wish antivaccinationists would do the same. That they don’t explains why they seem to be embracing someone named Dr. Hanan Polansky.

Fear and loathing of DNA among the antivaccine crowd

Back in September, I employed what I like to call science-based ridicule to deconstruct the overwhelmingly silly fear mongering by a group known as SANE Vax over the alleged discovery of HPV DNA in the HPV vaccine. SANE Vax, as you may recall, is a group founded by a woman named Norma Erickson dedicated to spreading misinformation about the HPV vaccine. If you peruse the SANE Vax website, you’ll see that the common antivaccine tropes are all there; they’re just directed mainly at the HPV vaccine. The hysterial fear mongering over the alleged discovery of DNA fragments of HPV in Gardasil was, as I described, massively overblown. The full explanation is in my post from September. The CliffsNotes version follows.

Basically, a pathologist by the name of Dr. Sin Hang Lee, who appears to have drunk at least a little of the antivaccine Kool-Aid, was hired by SANE Vax to test Gardasil for the presence of HPV DNA. Dr. Lee apparently made his name by developing exceedingly sensitive nested PCR assays to detect various DNA sequences. It was impossible to tell if his methods were valid, if Dr. Lee controlled adequately for the potential of false positives (which increase rapidly with the sensitivity of a test), and if his analysis was convincing because in September he had not published his results in the peer-reviewed literature. A quick search of PubMed on Saturday failed to find any publications on the topic since September. In any case, even if Dr. Lee’s analysis was correct and his new, allegedly more sensitive methodology had picked up previously undetected traces of HPV DNA from the plasmids used to make the HPV vaccine, it is still incredibly unlikely that such tiny amounts of DNA could cause problems because, as I explained, it’s incredibly difficult to get naked DNA into cells and making the proteins it normally makes, and, even if Dr. Lee were 100% correct about there being undetected HPV DNA in Gardasil, the quantities involved are many orders of magnitude less than what would be needed to have even a whiff of a wisp of a hope of the DNA getting into cells and making its protein. That’s even assuming it could pass the blood-brain barrier or that the DNA fragments were large enough to contain whole coding regions of genes with a proper promoter in front of them to drive their expression.

In other words, the fear mongering about the potential for minute quantities of HPV DNA being in Gardasil was nonsensical and not based on science.

On some level, I rather suspect that even Dr. Lee, Norma Erickson, and Leslie Carol Botha, host of a radio show known as Holy Hormones and, judging by her prominent association with SANE Vax, apparently also a die-hard antivaccinationist, have some inkling how utterly implausible their fear mongering about HPV DNA fragments in Gardasil was. The reason I suspect this is that they’ve latched on to Dr. Hanan Polansky and his “microcompetition” idea as a means of salvaging their fear of the evil HPV DNA that’s supposedly in Gardasil, waiting to make your little girls sick.

With the Oil of Aphrodite and the Dust of the Grand Wazoo

Dr. Hanan Polansky’s apparent coming to the rescue of SANE Vax began two weeks ago, when his Center for the Biology of Chronic Disease issued a press release:

Dr. Hanan Polansky, Director of the Center for the Biology of Chronic Disease, will discuss his discovery of Microcompetition with Norma Erickson, President of SANE Vax Inc. Dr. Polansky will use Microcompetition to explain the biological mechanism underlying the Gardasil adverse events. Leslie Carol Botha will host the event on the Holy Hormones Radio Show. The show will be broadcast on the community radio station KRFC FM in Fort Collins, CO, Monday, February 6, from 6 to 7pm MST.

Dr. Hanan Polansky is the author of the highly acclaimed “Purple” book, entitled Microcompetition with Foreign DNA and the Origin of Chronic Disease. In his book he explains how foreign DNA fragments can cause many major diseases without damaging (mutating) the human DNA. The book has been read by more than 5,000 scientists around the world, and has been reviewed in more than 20 leading scientific journals.

I’ll get to Dr. Polansky’s radio interview and “purple book” a little later. In the meantime, let’s take a look at Dr. Polansky’s background and what he might mean by “microcompetition.” To do this, it doesn’t help to go to the medical literature. A quick search of PubMed this weekend for works by Dr. Polansky reveals only one publication in Acta Oncologica entitled Gene-Eden, a broad range, natural antiviral supplement, may shrink tumors and strengthen the immune system. Remember what I said about how low a bar it is to get a paper published somewhere in the peer-reviewed literature? Let’s just say that this paper is evidence of that. It’s a case report of the use of a supplement called Gene-Eden published as what appears to be a letter to the editor describing how Gene-Eden plus chemotherapy shrank a pancreatic cancer. (Obviously, it must have been the Gene-Eden that worked.) But what is Gene-Eden? According to the Gene-Eden website, Dr. Polansky’s Gene-Eden-VIR supplement contains “five natural ingredients” (Camellia Sinensis Extract, Quercetin, Licorice Extract, Cinnamomum Extract, and Selenium) identified thusly:

Gene-Eden-VIR the the first product of our Science-Based approach. To identify the Gene-Eden ingredients, the scientists at polyDNA used the scientific method developed by Dr. Hanan Polansky. We scanned the scientific literature, analyzed thousands of papers using our proprietary bioinformatics-based computer program, and identified the most effective and safe natural ingredients. Some of the laboratory and clinical studies, which were published in scientific journals, and show that these natural ingredients have a strong antiviral effect, are described here.

The studies listed are, as you might expect, a bunch of cell culture and animal studies. Amusingly, on the Gene-Eden website there is also a table boasting between 913 and 6,753 publications for each ingredient, depending on the specific ingredient. (Take that, skeptics!) There’s that, and, in addition to Dr. Polansky’s single publication listed in PubMed, lots of press releases, for instance about how Gene-Eden-VIR can treat cervical cancer, prevent swine flu, and treat a whole host of viruses.

And ya might not believe this, little fella, but it’ll cure your asthma, too.

In any case, besides apparently shrinking pancreatic cancer, according to Dr. Polansky his Gene-Eden supplement can also help insomnia (which Polansky attributes to “latent viruses”), chronic fatigue syndrome, and a host of other diseases. In fact, Polansky attributes many diseases to “latent viruses,” reminding me of how many supplement hawkers justify the ingredients in their supplements. They cherry pick the literature to find suggestive preclinical or correlative studies for each ingredient that might indicate usefulness for the purpose claimed, with nary a convincing clinical trial to justify the combination of ingredients used at the dose used, because, well, latent viruses cause every chronic health problem known to humans, apparently.

And the rationale for Gene-Eden is based on something that Dr. Polansky refers to as “microcompetition” or the “starved gene hypothesis.” This brings us to how Polansky’s ideas can serve the agenda of a crank organization like SANE Vax. But what is “microcompetition”?

Microcompetition? More like a microhypothesis!

Now here’s where things start to get all “sciencey.” A trip back to the website of Dr. Polansky’s Center for the Biology of Chronic Disease soon leads one to a link to his free book, Microcompetition with Foreign DNA and the Origin of Chronic Disease. It even has an ISBN and everything! But what about Dr. Polansky’s Center? Its address is listed on the website; so I did a bit of Google Maps fun. Here’s where the institute maps to (click to enlarge):

Even though it’s on a major road, it sure looks like a private residence to me. Shades of Mark and David Geier doing their antivaccine research in the basement of Mark Geier’s house as part of their “Institute for Chronic Illnesses” (which sounds eerily similar to the Center for the Biology of Chronic Disease)!

Still, just because Dr. Polansky isn’t affiliated with a university or research institute doesn’t necessarily mean his ideas aren’t worth considering. After all, Albert Einstein did some of his best work when he was still a patent clerk. True, Polansky’s selling of a dubious supplement and his apparent belief that latent viral infections are the cause of most chronic illnesses suggest he might be a few bases short of a full coding sequence, but let’s see what he says. Back to the press release about his appearance on Holy Hormones:

The FDA and Merck admit that Gardasil contains foreign DNA fragments. However, the FDA asserts that these foreign DNA fragments pose no risk. In contrast, Dr. Hanan Polansky, in his highly acclaimed “Purple” book explains how certain foreign DNA fragments, at high concentrations, cause major diseases, such as, cancer, heart disease, diabetes, autoimmune diseases, and even obesity even when the DNA is broken and not functioning.

Note: “…at high concentrations.” (Emphasis mine.) It’s half tempting to stop right here, point out that, even if there is a tiny amount of HPV DNA left in each Gardasil vaccine vial, it isn’t “at high concentrations” and couldn’t possibly get into any cell in the human body at high enough concentrations to induce microcompetition, thus making Dr. Polansky’s ideas about “microcompetition,” right or wrong, completely irrelevant to SANE Vax’s fear mongering, and leave it at that. However, by agreeing to be interviewed it was Dr. Polansky who voluntarily offered up his idea as tactical air support for the SANE Vax campaign of fear mongering about the HPV vaccine. Besides, you come to SBM for more than that; so more than that I will try to deliver. To do that, let’s head to the source:

Dr. Hanan Polansky discovered that fragments of DNA, called N-boxes, can be very dangerous. When foreign N-boxes enter the body (naturally, or artificially, like through an injection of some treatment), they end up in the nucleus, where they attract scarce genetic resources. It is interesting that many common dormant (latent) viruses have strong N-boxes in their DNA. They include the Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Herpes Simplex virus (HSV), Varicella Zoster virus (VZV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Papillomavirus (HPV), and others. In fact, the CMV virus has the strongest N-box known to science. This N-box is so strong that human genes cannot compete with its power to attract the scarce genetic resources.

Sometimes Dr. Polansky compares these fragments of DNA to magnets. Imagine introducing a powerful magnet into the nucleus. What will be the effect of this powerful magnet on the allocation of genetic resources in the nucleus? The weak human N-boxes have no chance. Poor human genes. Poor host.

In the nucleus, “microcompetition” between the foreign N-boxes and the human N-boxes in the human genes can lead to disease. When the foreign N-boxes belong to a virus, microcompetition between the viral DNA and the human DNA can lead to disease even when the virus is dormant (latent), or the viral DNA is broken into pieces and cannot express proteins. As predicted by Dr. Hanan Polansky, many studies found fragments of DNA that belong to these viruses in tumors, clogged arteries (arterial plaque), arthritic joints, and other diseased tissues.

What might come as a surprise to SBM readers is that this is not an entirely implausible hypothesis, at least for some viral infections. What makes it implausible is how Dr. Polansky links it to latent viral infections. Be that as it may, back in the day, way, way back when I used to do a lot of plasmid transfections, we knew about microcompetition, only we didn’t call it that. Plasmids, for those not familiar with them, are DNA circles in which scientists can place whatever genes they want under the control of whatever promoter (DNA sequences that control how much a gene is transcribed into RNA) they want. “Transfection” is a process by which scientists can introduce this foreign DNA into mammalian cells and thereby drive expression of an exogenous gene. For purposes of this discussion, it’s not really that important how the plasmid DNA gets into the cell, only that it gets into the cell.

In the cell, the transcriptional machinery is made up of a number of proteins, among which is a class of proteins known as transcription factors. Transcription factors bind to specific DNA sequences on promoters and activate the transcription of the gene into messenger RNA, which is then used as a template to make protein. The key concept to understand here is that the supply of transcription factors and their protein co-factors in the cell can be limited, which means that there are only so many binding sites that the cell can accommodate. It is possible to “sop up” all of the cell’s supply of a specific transcription factor (or set of transcription factors) by flooding the cell with short length oligonucleotides that contain the correct sequence of nucleotides to bind to the transcription factor. When this happens, the transcription factor supply is tied up and these transcription factors can’t activate transcription of the cell’s DNA. It’s all a matter of chemical equilibrium; if the amount of exogenous DNA binding sequence introduced into the cell is very large relative to the amount of endogenous DNA binding sequences in the genome and the sum total is much larger than what the cell’s transcriptional machinery can accommodate, the transcription of the cell’s genes controlled by that sequence will plummet. This concept is illustrated in a figure from a paper published 12 years ago (click to enlarge).

Note that in this figure a specific sequence of DNA is acting as a “decoy” to tie up the E2F transcription factor. This oligonucleotide decoy strategy is a strategy that’s been studied for at least a couple of decades for shutting down gene activity, with mixed results. It is, however, not a new idea. Nor is it a new idea that certain viruses can do exactly the same thing by flooding the cell with copies of themselves, including sequences that can “sop up” specific transcription factors. This appears to form the basis of Dr. Polansky’s “microcompetition” idea. Indeed, in his book, Dr. Polansky goes way back to the very beginnings of molecular biology and gene transcription assays and points out well-known observations that I was taught in graduate school 20 years ago showing how investigators using pSV2CAT in 1984 showed that two plasmids could compete with each other for the cell’s transcriptional machinery: “taken together, our data indicate that a limited amount of the cellular factors required for the function of the SV40 72-bp repeats is present in CV-1 cells. Increasing the number of functional SV40 enhancer elements successfully competes for these factors, whereas other elements necessary for stable transcription did not show such an effect” (quoted from Scholer et al, 1984). My PhD thesis advisor did studies of this type studying transcription in muscle in the late 1980s.

Right here I should admit that I didn’t read all—or even most—of Dr. Polansky’s book. It is, after all, 427 pages long, not counting indices and the list of references (the latter of which numbers well over 1,000, demonstrating that the number of references doesn’t necessarily correlate with the quality of the science). Much of it is also painfully tedious reading. I’ll do a lot of things for a blog post, but even I have my limits, and trying to slog through 427+ pages of snore-inducing prose prose about a mildly interesting but outdated idea is beyond my limits. That’s why I found this review of Dr. Polansky’s book rather useful, coupled with some careful “cherry picking” of chapters discussing topics about which I’m knowledgeable. Basically, Dr. Polansky zeros in on a DNA sequence known as an N-box, which is also known as the ETS binding site and has a motif that looks like this: (A/C)GGA(A/T)(G/A). This is the core binding sequence of a transcription factor known as GA-binding protein transcription factor (GABP), which is involved in the regulation of transcription of a lot of important genes that regulate important cellular processes. It turns out that some viruses, including the HPV virus, have N-box sequences. Dr. Polansky claims that these N-box sequences in latent viruses compete for GABP and cause disease.

There are, as you might imagine, a lot of problems with this concept, and that’s even before we get to discussing whether this concept has any relevency whatsoever to HPV and its vaccine. For one thing, dormant viruses are by definition dormant. That means they are not replicating. Remember, the concept of “microcompetition” means that the N-box DNA must be present in high concentrations in order to compete with the N-boxes in the cellular DNA. Yet Dr. Polansky seems to think that this N-box in some viruses has some sort of magical powers to attract all the transcription factors in the cell to them. He uses terms like “magnet” and in his interview with Leslie Carol Botha approves of Norma Erickson’s referring to them as “vampires.” In fact, he more than just approves of the term, he even says, “I love the word ‘vampire’; it adds a lot of flavor to it.” Erickson then carries the analogy one step beyond into the ether when she then refers to the cells as functioning like “zombies.”

He analogizes to sucking the nutrients out of cells (hence the “starved gene hypothesis.” In reality, even if it occurs in reality, microcompetition is nothing more than a chemical equilibrium. For “microcompetition” to be the cause of disease, these latent viruses would have to be churning out N-box sequence at prodigious levels, which latent viruses don’t do because, well, if they were replicating themselves they wouldn’t be latent anymore.

None of this stops Dr. Polansky from saying this about N-box sequences in his interview:

At the end of the five years, we had found something pretty amazing, that many of the major diseases originate from the same source, and the source is basically foreign fragments of DNA and specifically one segment of DNA that’s causing all the trouble. This fragment of DNA is called an N-box, that is basically operating as a magnet and competing with human genes for scarce genetic resources available in the nucleus. Once these foreign DNA fragments are found in the nucleus, then as they arrive in high concentrations [difficult to understand], a disease will start and we see all the symptoms that today are recognized for all these major diseases.

Erickson helpfully chimes in later that this is “starvation at a cellular level,” and Dr. Polansky agrees. If this guy can’t even understand the difference between transcription factors and nutrients, I have a hard time taking him seriously. Even as a metaphor, Polansky’s analogy fails. It gets worse than that, though. Later in the interview, Polansky goes on and on about how regular drugs are “synthesized from scratch” and biologicals (like vaccines) are not, but are rather made using plasmids and recombinant genetic technology. This leads Botha and Erickson to gasp in terror at “genetically modified” treatments. Scary! This is followed by an anti-pharma rant about how much money drug companies make selling…drugs! And they’re shocked—shocked, I say!—that Gardasil, being a vaccine, is classified as a “biological.” Run for the hills!

But how does all of this relate to HPV and Gardasil? I think you know. I’ve already alluded to it, but just for the heck of it, let’s take a look at what Dr. Polansky has to say:

In my book, these DNA fragments are dangerous. They are the cause potentially—it has to be investigated further. But potentially, they can be the source of all the adverse effects, side effects, or diseases that we see with the injection… after the the injection, with the woman being vaccinated.

After Botha expresses her gratitude at having “found” Dr. Polansky (the two deserve each other from where I stand), she rants a bit about how many girls are allegedly sick from Gardasil, regurgitating various antivaccine tropes. The discussion (such as it is) then continues and goes beyond Gardasil, with Dr. Polansky opining:

All the modern vaccines are basically sharing the same process and therefore all of them will have DNA or fragments of DNA that are being injected into the people getting the vaccines. Autism, for instance, was linked recently with the MMR and a lot of debate about it, meaning you can read opinions on this issue. I read somewhere recently that MMR was also discovered to have foreign DNA fragments in it. So that’s the way it’s being done. That’s the manufacturing process and the purification pricess. And the limits of the purification process result in DNA residuals in the vaccines. As I said, the dispute is not whether there are DNA fragments in the vaccine, because nobody will argue that. You go online, you check on Google, and you’ll see that the debate is whether these DNA fragments cause disease. And if you ask the maintream scientist or doctor or pharmaceutical officer whether these DNA fragments cause any harm, they’ll say no. My book argues otherwise. So in a way my book is flying in the face of the entire traditional mainstream biology.

Except that it’s not. As I’ve described before, microcompetition is not a new concept, nor is the concept that viruses can cause chronic diseases. All Dr. Polansky has done with respect to this is to repackage old ideas in a not particularly exciting way. Hilariously, even the die-hard antivaccine Australian Vera Schreiber stated this in the comments of one of the SANE Vax posts about Dr. Polansky. He’s also way behind the times when it comes to genomics and molecular biology in that he doesn’t even consider microRNAs as a mechanism that could explain some of the “anomalous” observations he describes in his book about BRCA1 and breast cancer linked to low BRCA1 in women without BRCA1 mutations.

In fact, as Abbie Smith describes, there are a lot of things that Dr. Polansky apparently doesn’t understand about virology and biology, among other things.

Now I understand where microcompetition came from!

Microcompetition as a concept has a modicum of plausibility in a limited fashion for some aspects of cellular behavior. It has not to my knowledge been directly linked to any specific diseases in the 9 years since Dr. Polansky first wrote his book. Certainly Dr. Polansky hasn’t published anything supporting his idea, nor has anyone else as far as I’ve been able to ascertain in my multiple searches of PubMed. As speculation, Dr. Polansky’s concepts are somewhat interesting, but he takes their potential implications far beyond what the evidence can support. Normally, this wouldn’t necessarily be such a horrible thing if it were done as an intellectual exercise. After all, I didn’t mind, for example, the speculative fiction that was Medical Hypotheses until it started providing a platform for quacks to give their ideas a patina of seeming scientific respectability, as it did for Mark and David Geier and their ideas that led to their use of chemical castration with Lupron as a treatment for autism. Besides, sometimes outlandish ideas actually go somewhere.

I consider it higly unlikely that Dr. Polansky’s idea will.

The reasons are numerous. First, his idea isn’t all that new, as much as he tries to labor to represent it as some radical new breakthrough. Yes, I know he’s managed to impress a few doctors and scientists, but that was eight years ago, back when his idea actually seemed mildly innovative. Science has moved on, particularly virology and genomics, the two most relevant scientific disciplines to Dr. Polansky’s ideas. Second, nine years after he proposed it, it hasn’t really gone anywhere. Neither Dr. Polansky himself nor any other scientist that I’ve been able to locate has published any reports linking the concept of microcompetition definitively to a human disease.

Worse, however, instead of doing research to determine whether his idea has experimental evidence to back it up and, more importantly, whether that experimental evidence can suggest strategies to use the concept of microcompetition to intervene in the pathophysiology of any disease, instead Dr. Polansky has devoted himself to selling a supplement that he made up by cherry picking some natural compounds for which he could find a bit of in vitro and animal data supporting antiviral effect and using them to make a supplement that he sells to treat “chronic viral infection.” There’s no clinically acceptable evidence that his supplement works in humans as advertised or that it impacts microcompetition in any way. Not only that, but he’s been warned by the FDA about at least one of his claims for his supplement.

Worst of all, though, now Dr. Polansky appears to have hitched his horse to the antivaccine movement. I don’t know who contacted whom first, SANE Vax or Dr. Polansky. It might have been either. Perhaps the brain trust at SANE Vax saw Dr. Polansky’s website and thought it a perfect way to slap a veneer of plausibility on their utterly ridiculous fear mongering about minuscule bits of DNA in the HPV vaccine, or maybe Dr. Polansky sought out SANE Vax because of their recent “revelation.” Who knows? Does it really matter? Either way, what we have is a crank organization teaming up with a crank to link their respective crank ideas in the service of spreading fear, uncertainty, and doubt about vaccines. They’re two nasty crank ideas that taste cranky together.

There’s still one final question, though: Where did he get this idea? The answer to that question, my friends, is perhaps the silliest aspect of this entire sordid story. Although Dr. Polansky explains how he came up with his idea in his interview, it’s easier to go to another of Dr. Polansky’s websites for the skinny:

Wouldn’t you wish to have Einstein working on your medical problem? Imagine someone with his ability to choose the right direction to work on, his talent to recognize meaningful findings, his genius to leap from old concepts to new and more promising ideas. Think how much you would accomplish with Einstein on your team.

Einstein and other great scientists had one overwhelming talent, their superb intuition. This talent led them to discover pathways not charted on any map, and ensured that these pathways would become highways traveled by generations of scientists in their expeditions to uncover the secrets of nature.

We believe that the above proposition is not merely wishful thinking. Our sophisticated computer program, called Computer Intuition, was modeled to show the characteristics of genius intuition, and therefore, to turns us into “Einsteins.”

The basic premise of the Computer Intuition program is that every future event is preceded by hints, and that the key to realizing these events is recognizing the future significance of these hints.

In 1996, Dr. Hanan Polansky completed a prototype of a computer program that analyzes scientific text and assigns a rating to all ideas found in the text. The rating can be interpreted as intuitive intensity, (or psychological intensity, hence, psytensity). The higher the intuitive intensity, or psytensity, of an idea, the more it hints on future discoveries or future treatments. Dr. Polansky modeled the program after the intuition of the greatest minds in science such as Einstein, Newton, Edison and Tesla, and called it Computer Intuition.

Yes indeed, you read it right. Dr. Polansky wrote a “computer intuition program” and used it to scan the medical literature. In his interview with SANE Vax, he stated that he had used his computer program to scan 500,000 publications. This microcompetition idea is what he came up with. I kid you not. You’d think such a seemingly awesome algorithm could come up with something better, but apparently you’d be wrong.

As a consolation prize, at least Dr. Polansky should be proud that he made it in the alt-med world. He now has his own entry on Whale.to. Now, that‘s an accomplishment!

Yet another study showing that clear signs of autism are present as early as six months of age has been published. In this study researchers looked a high-risk children (siblings of children with autism) at 6 months with MRI scanning (specifically diffusion tensor imaging) and then evaluated them clinically at 24 months to see which children met criteria for autism spectrum disorder (ASD). Some of the children also had imaging at 12 months. The imaging was used to look at the development of white matter – the tracks in the brain that contain the axons or pathways of communication.

When compared as groups the 28 infants who went on to develop ASD had significantly decreased white matter development in 12 of 15 brain pathways examined in comparison to the 64 infants who did not develop clinical ASD.  These results are very robust, although I should point out that the children were compared as groups, not individuals. The purpose of this study was to see if there were detectable changes in the brains of children with ASD at 6 months, not necessarily to explore its utility as a diagnostic tool that can be applied to an individual.

Still, this study supports other research providing increasing evidence that ASD begins at least as early as 6 months. It is probable that ASD begins earlier than 6 months, actually, because in order for detectable differences to be present in the brain, development must have heading down a different trajectory prior to that. These kinds of studies have not looked at children younger than 6 months, and it would be interesting to see how early such changes can be detected. But even without that data, we can conclude the whatever process results in ASD it is active prior to 6 months so that the effects are detectable at 6 months.

This study also supports other research that indicates that autism is partly a disorder of communication within the brain – different parts of the brain have decreased communications with each other. It’s nice when several independent lines of evidence all converge on one cohesive story. With regard to ASD, we have evidence that clinical signs of ASD are present as early as six month and changes in brain anatomy are also present as early as 6 months. Further, there is growing evidence that ASD is the result of a complex set of genetic variations. Autism, in other words, is a genetic disease – which is compatible with detection early in infancy.

This research has several implications. It broadens our understanding of the pathophysiology of ASD – exactly what is happening and how that does that manifest with the signs of ASD. Further it offers the potential for earlier and more objective diagnosis of ASD. Laboratory support for a clinical diagnosis is always helpful – again, because it allows for multiple independent lines of evidence, and therefore increases confidence. Early diagnosis is also helpful in identifying children who might benefit from special services.

It’ s also possible that research such as this will help us identify specific subtypes of ASD, which may have different causes and different clinical needs. ASD, as the name states, is a spectrum – it’s really a group of similar disorders with similar clinical manifestations. It is likely, however, not one discrete entity. The fact that so many different genetic markers have been identified that are associated with ASD support this view.

And of course I need to point out that research showing that autism begins prior to 6 months of age rules out any environmental exposure after 6 months as a significant cause. The MMR vaccine (the specific vaccine that Andrew Wakefield tried to link to ASD) is typically given at 12 months of age, and so cannot be a significant cause of ASD. As you can see from the immunization schedule, many vaccines are given after 6 months. Some vaccines, however, are given prior to 6 months, so those intent on blaming autism on vaccines can still point to those earlier injections.

There is no evidence to link any vaccine or vaccines in general to the development of ASD or any neurological disorder. Evidence is converging on the conclusion that ASD is a set of genetic disorders. If history is any guide it’s also true that evidence is not likely to sway members of the anti-vaccine community. But more evidence is always nice. There is always uncertainty in science, and the more we can narrow that uncertainty with better evidence, the better we will be able to make the case for the safety of vaccines.

This is yet another response to the recent “Integrative Medicine in America” report published by the Bravewell Collaborative. Drs. Novella and Gorski have already given that report its due, so I won’t repeat the background information. Inevitably, I’ll cover some of the same points, but I’ll also try to emphasize a few that stand out to me. Most of these have been discussed on SBM over the years, but bear repeating from time to time. Let’s begin with:

If it Ducks like a Quack…

Misleading language is the sine qua non of ‘integrative medicine’ (IM) and its various synonyms. The term itself is a euphemism, intended to distract the reader from first noticing the quackery that is its distinguishing characteristic. As previously explained, Bravewell darlings Andrew Weil and Ralph Snyderman, quack pitchmen extraordinaires, recognized nearly 10 years ago that if you really want to sell the product, you should dress it up in ways that appeal to a broad market.

Let’s see how this is done in the latest report. Here is the very first sentence:

The impetus for developing and implementing integrative medicine strategies is rooted in the desire to improve patient care.

Who would disagree with improving patient care? (Try not to notice the begged question). Here’s the next paragraph (emphasis added):

The Bravewell Collaborative, a philanthropic organization that works to improve healthcare, defines integrative medicine as “an approach to care that puts the patient at the center and addresses the full range of physical, emotional, mental, social, spiritual, and environmental influences that affect a person’s health. Employing a personalized strategy that considers the patient’s unique conditions, needs, and circumstances, it uses the most appropriate interventions from an array of scientific disciplines to heal illness and disease and help people regain and maintain optimum health.”

Who would dare to disagree with those points? Other than biting off more than it can chew (see below), the definition applies to modern medicine, which tries to be patient-centered, holistic (in the honest sense of the term), “personalized,” scientific, etc. You have to be pretty savvy to recognize the misleading hype in that paragraph:

• “The Bravewell Collaborative…works to improve healthcare.” That would require that highly implausible medical claims—the only things that distinguish IM from real medicine—actually do what their proponents claim. They don’t, as we at SBM have been explaining for years.
• “…puts the patient at the center.” That implies “patient-centered care,” which requires that practitioners provide honest, comprehensive information about the methods in question. IM practitioners are universally dishonest about such matters. They have to be, because otherwise they’d have to tell patients the truth: that the methods are worthless. In a subsequent post I’ll provide examples pertinent to this report.
• “…an array of scientific disciplines.” This is standard quackspeak for “an array of pseudoscientific disciplines.” Here’s an example from that Mother of All IM centers, Andrew Weil’s Arizona Center for Integrative Medicine:

[Iris Bell, MD, PhD] is a clinical researcher with an emphasis on systems theory as a conceptual framework and the use of psychophysiological methodologies (EEG, cardiovascular) to study the linear and nonlinear effects of homeopathic remedies and low level environmental chemicals.

•  ”…to heal illness and disease.” The standard muddling of everything that might bother anyone, whether medical or not, other than being strapped for cash. This effortlessly leads to offering anything that might make someone feel better, whether medical or not, other than money. See how easy IM is?
• “…maintain optimum health.” Another standard IM gambit: its special and specious claim to preventive medicine.

Making Promises they can’t Keep

A recurrent theme is that IM can do, well, everything. We saw evidence of that above:

…an approach to care that puts the patient at the center and addresses the full range of physical, emotional, mental, social, spiritual, and environmental influences that affect a person’s health.

In the very next paragraph, the Bravewell Report makes it explicit (emphasis added):

…very little information had been collected regarding the actual practice of integrative medicine, which by definition treats the whole person.

It may not immediately occur to many readers, in this Era of Hype, but such a claim is ridiculous. Philosophers Clark Glymour and Douglas Stalker recognized this nearly 30 years ago in their essay about ‘holistic medicine,’ previously discussed on SBM here and here:

Another doctrine said to be holistic is that one’s state of health is affected by everything. Whatever this means, it has nothing to do with any possible practice of medicine, for no one can attend to everything. If physicians cannot distinguish relevant from irrelevant factors, important from unimportant causes, then they can do nothing.

Glymour and Stalker’s next few sentences, by the way, were these:

A variation of this doctrine is not vacuous but merely vapid: ‘Fundamental to holistic medicine is the recognition that each state of health and disease requires a consideration of all contributing factors: psychological, psychosocial, environmental, and spiritual.’ [Pelletier 1979] This is not a new revelation about medicine. Insofar as such multiple factors are known and believed to be important, they are routinely addressed in conventional medicine practice.

It would seem not to be a new revelation about ‘integrative medicine,’ either; just a repackaging of the same old stuff by a different label. Even the authors are the same.

An Established Part of Healthcare?

From the Bravewell report’s conclusion:

The strong affiliations to hospitals, healthcare systems, and medical and nursing schools as well as the centers’ collaborative work with and growing referrals from their own health systems reveal that integrative medicine is now an established part of healthcare in the United States.

Being “an established part of healthcare” is not the same as being accepted as valid in any important medical sense. I suppose one would be technically correct to write, “chiropractic is now an established part of healthcare,” but that would ignore the only interesting question about chiropractic.

There is no question that some of the centers looked at in this report are affiliated with hospitals and healthcare systems. Some that claim to be so affiliated are not, however. The Marino Center for Integrative Health in Cambridge and Wellesley, Massachusetts, is identified in the report as having a “hospital affiliation” with the Newton-Wellesley Hospital, which is where I work. In fact, some but not all of the Marino Center physicians have been granted staff privileges at my hospital—a mistake, in my opinion—but there is no institutional affiliation whatsoever. In two weeks I’ll look at the Marino Center in some detail.

More from the Bravewell conclusions:

…high levels of concordance of interventions for specific conditions suggests that integrative medicine practice is informed by a common knowledge base.

The naive reader might assume that a “common knowledge base” suggests something about medical validity. It does not. It suggests something about faddism.

The data from the survey reveals that integrative medicine centers embrace a group of core values that inform and radiate through their practice and interactions with their patients.

Ah, ‘embrace,’ ‘inform and radiate’: you don’t need a baloney detection kit to notice that such metaphors inform and radiate through quack treatises everywhere.

Ultimately, Bravewell Quacks

Here’s the final paragraph of the conclusion in the Executive Summary:

One of the most striking, though perhaps predictable, conclusions of this study is that integrative medicine is, in fact, integrative. It integrates conventional care with nonconventional or non-Western therapies; ancient healing wisdom with modern science; and the whole person — mind, body, and spirit in the context of community.

Don’t you just love how spin doctors occasionally slip, and admit to what you knew was the case all along? I’ve been referring to what Bravewell calls “nonconventional or non-Western therapies; ancient healing wisdom” by the useful and accurate shorthand, “quackery.” For a somewhat broader treatment, let’s go to Glymour and Stalker:

The therapies described and recommended in a typical book of the genre include biofeedback, hypnosis, psychic healing, chiropractic, tai chi, iridology, homeopathy, acupuncture, clairvoyant diagnosis, human auras, and Rolfing. One of the larger books of this kind was even subsidized by the National Institute of Mental Health.

What ties together the diverse practices…? In part, a banal rhetoric about the physician as consoler;… In part, familiar and rather useless admonitions about not overlooking the abundance of circumstances that may contribute to one condition or another. Such banalities are often true and no doubt sometimes ignored, with disastrous consequences, but they scarcely amount to a distinctive conception of medicine. Holist therapies can be divided into those that are adaptations of traditional medical practices in other societies—Chinese, Navajo, and so forth—and those that were invented, so to speak, the week before last by some relatively successful crank.

Insofar as it extends beyond banality, the holistic medical movement constitutes both a deliberate attempt to substitute a magical for an engineering conception of the physician and an attack on scientific understanding and reasoning. Although the holistic movement does not contain a conception of medicine distinct from those we have discussed, it does contain a reactionary impetus to return the practice of medicine to the practice of magic and to replace logic and method with occultism and obfuscation.

“Welfare for the Rich”

The two philosophers warned of what Bravewell calls “integrative medicine” becoming “an established part of healthcare”:

If holistic-health advocates were content with encouraging sensible preventive medicine or with criticizing the economic organization of American medicine, we might be enthusiastic, but they are not. If the movement were without influence on American life, we would be indifferent, but it is not. Holistic medicine is a pablum of common sense and nonsense offered by cranks and quacks and failed pedants who share an attachment to magic and an animosity toward reason. Too many people seem willing to swallow the rhetoric—even too many medical doctors—and the results will not be benign. At times, physicians may find themselves in sympathy with the holistic movement, because some fragment of the rhetoric rings true, because of certain practices and attitudes they encounter in their daily work with colleagues and patients, or because of dissatisfaction with the economic and social organization of medicine. One hopes they will speak bluntly, but it does no good to join forces with cranks and quacks, magicians and madmen.

Bravewell is what can happen when ditzy rich people who know little about medicine or science get it into their heads that they know something—some crucial secret or secrets, little known to most in medicine except for a few cranks who themselves have found the secret to easy money. That would be maddening enough, although we must expect it as part of living in a free, democratic society. What we shouldn’t have to accept is that those rich people haven’t been using their own money. They’ve been using ours.

 

A brief reference on the web site The Quackometer recently drew my attention to a very short book (really more of a pamphlet, in the historical sense) by Dr. Worthington Hooker, Lessons from the History of Medical Delusions, which I thought might be of interest to readers of this blog. Though published in 1850, the book contains many eloquent observations that are just as relevant to understanding how pseudoscience and quackery persist and even flourish in what we otherwise assume to be an age of scientific medicine. The book is available online as a Google eBook, and relatively cheap printed facsimiles are available as well.

Dr. Hooker was a physician, a professor at Yale, and an outspoken critic of homeopathy in it’s early days. His critique of homeopathy still resonates today, and has long drawn the ire of Hahneman loyalists, such as this one who makes reference to Dr. Hooker’s, “periodical fulminations for the destruction of Homoeopathy that have appeared like locusts or cholera at certain dates.” Though Dr. Hooker wrote an entire book discussing homeopathy, Homeopathy: An Examination of its Doctrines and Evidences, he does spare a few words here for this less-than-venerated practice:

The error I have been illustrating is carried to an extreme by the Homeopathist. He attributes palpable results to doses of medicine which are so small that they cannot produce any perceptible effect except by miracle.

He also includes a lengthy and preposterous example of a homeopathic proving, taken from a homeopathic text of the time, illustrating the absurdity of simply listing every imaginable (and imagined) experience following the taking of a substance and then attributing the entire list to that substance in order to guide the selection and use of homeopathic remedies. However, the focus of this booklet is to illustrate more generally the sorts of errors in thinking that lead even otherwise intelligent and reasonable people to believe such nonsense.

And Hooker makes a specific point of reminding us that belief in medical absurdities is not by any means a characteristic only of the unintelligent, the uneducated or the past.

The history of medical delusions most copiously illustrates the truth, that folly is very far from being confined to fools.

The present generation laugh at the follies of the past but have quite as great follies of their own, an follies too of a similar character, and products of the same fundamental errors.

The majority [of believers in quackery] is made up of those who are more or less intelligent and rational on most subjects, but who…are especially deluded on the subject of medicine…The exposition I make is not a partial one. It is not a one-sided argument-a plea for the doctors against the people. But it is an attempt to show how both doctors and people have ever been liable to error, and how they have been alike in the common elements, if not in the forms and modes and fashions of their delusions.

The medical profession, like the community at large, is made up of fallible men, and the elements of delusion are the same in the one class as in the other [though] the error of the physician would be refined, and would have the pomp and circumstance of erudition.

Error gilded with the pomp and circumstance of erudition….That certainly brings a few names to mind, eh?

Some of the specific examples he uses are fine tidbits of historical minutia. Apparently, one of the founding fathers of chemistry, Boyle”>Robert Boyle, a man who distinguished between alchemy and chemistry in a book called The Sceptical Chymist, also expressed his belief that dysentery could be cured through use of the thighbone of an executed criminal. And according to Hooker, Bacon”>Francis Bacon, that luminary of critical thinking and scientific philosophy, advocated for applying healing salves to the weapon that made a wound rather than the wound itself (though given the loathsome nature of many therapeutic unguents of the time, this may not have been a bad idea since apply them to wounds doesn’t sound wise).

So what are the common “elements of delusion” that Hooker wishes to warn us of? He begins with the post hoc ergo propter hoc fallacy.

The first [element] which I shall notice is the too ready disposition to consider whatever follows as a cause as being the result of that cause.

He then points out the most obvious reason why this sort of reasoning so often misleads us in medicine:

The most important of the confounding causes is “vis medicatrix naturae, or the tendency there is in the system to remove disease and cure itself….there is in the system a tendency to spontaneous restoration in case of injury and disease…This tendency is the chief agency in most cases in curing disease. Sometimes it is the only one; and very often it effects a cure in spite of the mistaken and officious interference of art.

And yet quacks, and even physicians, and the public generally, are very prone to leave this agency out of view, and to attribute cures, as a matter of course, entirely to some favorite remedy which has been used. This disposition is the chief source of medical errors of all classes of men.

Hooker also touches on several other key sources of erroneous conclusions in evaluating medical theories, including confirmation bias, availability bias, anchoring, premature closure, sloppy use of analogous reasoning, passionate commitment to theories without empirical evidence, and medical fads, though all describe in a language rather more poetic than we would ordinarily use today.

He then goes on to talk about the issue of the commercial and political success of medical nonsense, which are certainly still relevant issues often discussed here.

So extensive is the popular delusion in regard to quack medicines, that the nostrum system has become an organized system, with an enormous machinery of certificates and advertisements. It has become a monstrous business interest, and is linked in with a thousand ties with other business interests. So powerful is it in this respect, that it has almost entirely subsidized the press, forcing it to be silent except when it speaks in it’s favor. The same may be substantially said when speaking of the action of legislatures on this subject.

Similarly, Hooker touches on the unfortunate aura of legitimacy that attaches to quack therapies when they are embraced by what he calls “medical men in good standing,” which could certainly be applied to the quackademic medicine phenomenon and the endorsement of medical nonsense by the likes of Dr. Oz and others.

Despite the eloquent expression of many issues associated with medical nonsense that are as relevant today as they were in 1850, not all of Dr. Hooker’s book will resonate with a modern audience. Apart from the florid prose style of the time, and the unabashedly sexist language, he scoffs a bit “the skeptic,” who he describes as sitting in “his ‘doubting castle’ well-fortified against all the shafts of truth.” He also was a fan of bloodletting as a remedy, and sneered at the research of Pierre Charles Alexandre Louis and others who demonstrated its lack of effect. In general, he was no fan of the “numerical” methods which have since developed into epidemiology, and he was overly respectful of the experience and judgment on individual doctors. Citing the same sloppy reasoning as is often used by modern proponents of alternative therapies, he argues that such “numerical observations…can be of no practical use to the physician in deciding in regard to any individual case…”

However, as a whole this little historical gem is strikingly applicable to the issues this blog deals with today. And it ends with a nice description of the gradual and imperfect process of vetting ideas through scientific inquiry, from initial unjustified enthusiasm to a gradual withering of bad ideas and a fitting of good ones into their appropriate but limited places.

While many remedies, once potent to cure in the public estimation, have….been wholly discarded, others, which have more real merit, while they have lost the extravagant reputation of their nascent state, have, under the watchful eye of experience, gradually obtained very nearly their right valuation, and the circumstances which should regulate their use have been ascertained with considerable accuracy. Others, in great numbers, are now going through this searching process; and others still are just now wearing the brilliant honors of an enthusiastic reception.

He also suggests, mistakenly I hope, that direct attacks on medical nonsense rarely have a salutary impact on the popularity of such practices. However, he also describes with some hopefulness the goal of his book, which I think to some extent describes the purpose of this blog as well.

No delusion however fiercely it may have been attacked was ever killed. Each after having withstood all assaults, has laid itself down o die in the most quiet manner, benumbed into the sleep of death by the chill of popular neglect, while the warm breeze of popular favor which it once enjoyed are now bestowed upon some other delusion…

And such exposition as this essay presents, of the common causes of medical delusion, both in the profession and in the community, will, I believe, commend itself to the reason and common sense of such persons, and will therefore have some influence, in connection with other kindred efforts, in deterring them from giving heir patronage to quackery in any form…

As I write this, the American news cycle is firmly focused on the issue of drug harms. It’s in the headlines not because of the thousands of cases of drug toxicity, hospitalizations, and even deaths that are documented each year, but because of the untimely death of singer Whitney Houston. While the cause of Houston’s death has not yet been identified,prescription drugs and alcohol are suspected to have played a role. If that’s the case, she’ll join a long list of celebrities whose deaths have been attributed to the abuse of prescription drugs. Over at Natural News, Mike Adams has already added her name to the list of “celebrities killed by Big Pharma“. He elaborated on drug-related deaths back in 2009 when actor Brittany Murphy died, deeming her death to be due to “Acute Pharmaceutical Toxicity“:

As you already guessed, there’s a fatal flaw in this pharmaceutical approach to sick care: Pharmaceuticals have never been tested in combination with other drugs. So all the so-called “gold standard science” is absolutely worthless at knowing what might happen when half a dozen pharmaceutical drugs are combined in a patient’s body. Brittany Murphy may have been on as many as TEN drugs!

Despite the fact that no combination testing has ever been done on pharmaceuticals, they are regularly prescribed in combination. Obviously, this creates a whole new realm of unknown risk based on the way multiple drugs might chemically interact in the human body.

The more pharmaceuticals you take, the more dangerous they become. While one pharmaceutical chemical may at first seem harmless (even though just one drug can actually kill you), when you start adding a second, third, fourth and fifth prescription on top of that, you’re dealing with Acute Pharmaceutical Toxicity (APT) that’s never even been tested in clinical trials.

Pharmacists are trained to help people avoid the most toxic two-drug combinations, but they rarely have any real knowledge about what happens when you combine three, four, five or more drugs. No one does. The science has simply never been done on that question. It’s no wonder: With all the possible combinations and permutations of pharmaceutical toxicity, it would take literally trillions of clinical trials to test them all.

Adams’ ignorance of medicine is obvious here. Combinations of drugs are studied in clinical trials all the time. You can start with the HIV treatments, move on to cancer drugs, and then chronic illnesses to see studies examining two, three and more in combination. But if a particular combination hasn’t been studied, are we still in the realm of science-based medicine? Alternative health proponents, sensitive to the lack of evidence supporting their preferred treatments, see drug combinations as just one example ofSBM hypocrisy. We’re told that “only 10–35% of medical practice is based on randomized controlled trials” as a justification for unproven or disproven treatment strategies.While this particular statistic has been repeatedly examined and debunked, and the risks of polypharmacy have been discussed at SBM, a science-based approach to combining drugs, even in situations when they haven’t been directly studied in clinical trials, hasn’t gotten as much attention.

It’s important to acknowledge that adverse reactions from prescription drugs are a major cause of harms and death. In 2008 poisonings caused more deaths than car accidents, and many of these poisonings were from prescription, not illegal, drugs. It’s been estimated that adverse reactions may cause 2-6% of hospital admissions, and that proportion may be even higher in specific age groups. Each case of drug-related harm has its own set of contributors, which may include health professional culpability, a lack of proper education, and patient factors (including situations of deliberate abuse). The tragedy is not just their absolute numbers, but the fact that many of these events are both predictable and avoidable — particularly those that result from combining prescription drugs, or mixing prescription drugs and alcohol. As Harriet Hall has noted before, it’s misleading to say that combining drugs can’t be evidence-based. How different drugs interact when combined in the body isn’t a scientific black box: An understanding of drug kinetics and of molecular biology allows us to predict with fair accuracy how drugs will behave when combined. So while we cannot anticipate all idiosyncratic reactions to drugs, there already exists the knowledge and tools to be doing a much better job preventing drug-related harms.

There are two main types of drug interactions:

Pharmodynamic interactions change the effect of a drug, without changing the amount of drug in the body. The celebrity overdose is a common example: combining multiple drugs that can depress and impair the central nervous system can lead to significant sedation and even death. These outcomes are not a surprise — they are a direct extension of their pharmacologic action. We can use pharmacodynamic interactions in more positive ways, too: Different types of antihypertensives work in different ways, so a combination of drugs may be effective in lowering blood pressure when raising the dose of a single drug is ineffective or causes unwanted side effects. But not in all cases. Combining drugs like ACE-inhibitors with potassium-sparing diuretics may lower blood pressure, but both drugs also elevate potassium levels, sometimes to life-threatening levels. Another example of pharmacodynamics is the treatment of pain with a narcotic such as codeine, plus an anti-inflammatory,such as naproxen. Both provide pain relief, albeit by different mechanisms of action.

Pharmacokinetic interactions are the result of one drug affecting another drug’s action by modifying its concentration at the site of action. This can be accomplished in four different ways:

1. A change in drug absorption

Unless it’s injected, a drug needs to be absorbed (usually from our gastrointestinal tract). Modifying the environment (say, reducing stomach acidity with a proton pump inhibitor like Prilosec) can modify how extensively some drugs are absorbed, if that absorption is dependent on an acidic environment. Or we can influence absorption by slowing down or speeding up the motility of your gastrointestinal tract: Change transit time, and you can change the extent of absorption. Or kill off some bacteria in your colon antibiotics, and it may reduce the circulation of drugs that are secreted in the bile and then reabsorbed. It doesn’t have to be the stomach, either. Drugs administered via the skin can have their absorption affected by solvents like DMSO.

Cellular pumps allow drugs and other chemicals to cross otherwise impermeable barriers. P-glycoprotein is a cellular pump located in the intestine, kidney, liver and blood-brain and blood-testes barrier. Loperamide (Imodium) is an anti-diarrheal that is structurally similar to narcotics, but lacks the usual narcotic effects on the brain, because p-glycoprotein blocks it from crossing the blood-brain barrier. When the function of one drug depends p-glycoprotein, and another drug modifies its action, unpredictable effects can results.

2. A change in drug distribution

Drug molecules don’t just float along in the bloodstream — they may hitch a ride on proteins, binding to them and effectively decreasing the amount available for activity at the site of action, or in the liver, when the drugs will be transformed (and eliminated). The impact of one drug on the protein binding of another can modify a drug’s action. If one drug displaces another from its protein binding, this can raise the effective or “free” levels in the blood, potentially causing a toxic effect.

3. A change in drug metabolism

Drug metabolism is the process that convert drugs (and other chemicals) into molecules that can more easily be excreted from the body, usually by way of the kidneys. These transformations are catalyzed by enzymes, and some drugs act to inhibit or induce enzyme action. In particular, a group of enzymes called cytochrome P450, or CYP enzymes, are the main metabolic pathway for many drug products. While there are dozens of different CYP enzymes, only a handful act on drugs. Consequently, if we know a specific drug is metabolized by, inhibits, or induces a particular CYP enzyme, it becomes easier to predict the possible effects on other drugs — without the need for direct evidence to verify the interaction.

Many drugs are well absorbed from the gastrointestinal tract, yet fail to appear in high levels in the blood circulation. It’s the liver at work, causing what’s called the “first pass” effect — metabolizing drugs as they first pass through the liver, before they circulate in the body. Inhibition of certain enzymes, particularly CYP3A4, can dramatically suppress this first pass effect, potentially changing usual doses into overdoses.

4. A change in drug elimination

Drugs can induce elimination of other drugs, reducing peak levels and duration of effect, possibly to an extent that efficacy is compromised. Or they can inhibit elimination, raising peak levels and the duration of effect, possibly to toxic levels.

Drug-Food Interactions

We tend to separate drug-drug interactions from drug-food interactions, but from a biochemical perspective, it doesn’t matter: foods are just combinations of chemicals, some of which may interact with drugs. And the mechanisms for these are the same:

• pharmacodynamic effects: alcohol can increase the sedating effects of narcotics, antihistamines, and sedatives like benzodiazepines
• absorption issues: calcium and iron can reduce drug absorption, while some drugs are absorbed more extensively in the presence of food.
• drug kinetic issues: vitamin-K containing foods can antagonize the effects of warfarin; tyramine-containing foods combined with the (now rarely used) monoamineoxidase (MAO) inhibitors can cause a massive increase in blood pressure and even stroke. Grapefruit juice has been identified as a significant cause of drug interactions, through inhibition of CYP enzymes.

Drug-Herb Interaction

Herbal products can be a nightmare from a drug interaction perspective. In general, herbs raise the level of therapeutic uncertainty and risk, compared to drug-drug interactions. Compared to the relative straightforward data on drugs with known pharmacokinetics and predictable interactions, herbs can contain many different chemicals, of which the “active” ingredient(s) may not even be known. Combine the lack of standardization, and the possibility of poor quality control standards, and you’ll see most pharmacists wince when you ask about drug-herb interactions: the unknowns make combining herbs and drugs potentially risky, especially in situations where the drugs have a narrow “therapeutic index“, or when the stakes are high, such as cancer chemotherapy.

While we don’t have good estimates of their true prevalence, we know that some herbs are demonstrably problematic: St. John’s Wort (Hypericum perforatum) (SJW) can cause significant drug-drug interactions, including HIV drugs and transplant therapies. There are multiple cases of transpanted organ rejection linked to initiation of SJW. Why? SJW is a powerful inducer of CYP3A4 enzyme, which increases the metabolism of immunosuppressants, decreasing their effects.

What’s most frustrating about drug-herb interactions is that the natural products industry seems determined to keep consumers in the dark about the potential harms, as Mother Jones outlined this week, in a column entitled What the Supplement Industry Isn’t Telling You About St. John’s Wort:

The real problem here lies in transparency to consumers—a problem that goes directly back to the supplement’s manufacturers. In a 2008 study published in BMC Complementary and Alternative Medicine that tested 74 different SJW brands, less than a quarter of the product labels identified possible interactions with antidepressants. Even more disturbing was that only 8 percent identified possible interactions with birth control.

Many groups, like the Center for Science in the Public Interest, have tried to push the FDA to standardize SJW labels to properly reflect possible dangers. But since supplement makers are not required by law to warn consumer about health risks associated with their products, it hasn’t been easy. “These companies fight warning labels like the dickens, and whether they intend it or not, that affirms the belief that natural products are unequivocally good for you,” says Stephen Gardner, litigation director at CSPI.

And that’s the issue. It’s not that drugs are inherently harmful, and herbs are wonderful and safe panaceas. Any product, whether it’s a herb or a synthetic drug, has the potential to harm, and to interact negatively. And unless the potential for interactions is well understood, we need to approach the combination of herbs and drugs with caution. Part of the solution is ensuring that health professionals and consumers alike are asking the right questions about their safety and efficacy.

Pharmacogenomics

One of the most interesting areas in drug interactions and drug safety is our evolving knowledge of pharmacogenomics: how genetic factors can influence drug behavior. The vision for pharmacogenomics is to maximize efficacy and to avoid adverse drug reactions. The reality is that we’re not there yet, but the science is progressing. For example, the dosing of warfarin (Coumadin), a drug associated with a significant bleeding risk, can be modified to minimize toxicity based in part on testing for the genes CYP2C9 and VKORC1. While it doesn’t eliminate the dosing uncertainty, and the clinical usefulness of testing remains limited, it’s a promising sign of what may become a more predictable way of selecting and dosing drugs. Over time, our accuracy at drug selection and dosing may become much more personalized than it is today.

Where do we go from here?

Harms associated from combining prescription drugs neither validates alternative medicine, nor invalidates science-based medicine. Celebrity or otherwise, many of the harms attributed to prescription drugs are predictable and avoidable. Every treatment decision boils down to an individual evaluation of risk versus benefit, and we can combine therapies with a great degree of confidence based on our understanding of how they will (or will not) interact. Drug-related injuries and toxicity are a real issues, one that medical systems could be doing a much better job of addressing. But when it comes to understanding how these harms are occurring, and preventing them, it’s not just the drugs we need to look at: we already have the information, technology, and capacity to significantly reduce the occurrence of drug-related harms.

Another study, published recently in PLoS One, fails to show a correlation between mercury and autism. This was a study of mercury excretion in the urine, comparing subjects with autism to their siblings as well as controls with out autism spectrum disorder (ASD), both in mainstream and special schools. They found no significant difference among the groups, even controlling for kidney function (creatinine clearance), age, gender, and amalgam fillings.

To put this study into context – there are those who claim that mercury toxicity is what causes ASD, and in fact ASD is simply misdiagnosed mercury toxicity. There is no question that mercury is indeed a neurotoxin, but toxicity is all about dose, so the question is are children being exposed to mercury in high enough dose to cause toxicity. Further, it is difficult to extrapolate from preclinical studies (in test tubes and petri dishes) to living organisms. We need to further know what happens to the toxin in the body, and how the body handles it.

With regard to the forms of mercury found in some vaccines (although much less than in previous years) and tuna fish, the body seems to rid itself of the mercury sufficiently quickly to prevent build up to toxic levels. Of course, this remains a hot topic because of the persistent claims by the anti-vaccine movement that vaccine cause ASD, and some who cling to the discredited notion that it is mercury in vaccines that is the culprit. There are also the so-called “mercury militia” who blame environmental mercury (from vaccine and elsewhere) on all human illness, not just autism.

As further background, it’s helpful to note the chain of argument that has occurred with respect to the role of mercury in autism. Studies have consistently found no correlation between mercury exposure and the risk of ASD. Proponents of the mercury hypothesis have therefore argued that there is a subpopulation of vulnerable children who metabolize and excrete mercury differently than the general population, and it is within this subpopulation that mercury causes ASD.

Logically this may be true, but the argument is little more than special pleading, although a common one. Scientists are familiar with the usual list of special pleading arguments made to dismiss negative evidence. These include: that the dose studied was too low, the treatment duration was too short, the placebo or comparison treatment was also effective, or the looked-for effect only exists in a subpopulation. Each one of these arguments is logically consistent – if true they would explain the negative results without meaning that the phenomenon is not true. They may even be true in specific cases. What makes them special pleading is when they are invoked ad hoc to explain negative evidence without good justification.

With respect to mercury and autism, when studies failed to show a correlation proponents argued that only a subpopulation are vulnerable to mercury toxicity because (they speculated) they have impaired mercury excretion. That is the context for this study – if this particular instance of special pleading were true, then children with ASD would be more likely to have decreased excretion of mercury in their urine. Alternatively, if they are being exposed to more mercury as the cause they would have increased excretion of mercury in their urine. The study found no difference – no increase or decrease in mercury in the urine of children with ASD vs controls.

The authors are appropriately cuatious in their conclusions. They say simply that their study does not provide support for the mercury hypothesis (not that it proves it wrong), and further they acknowledge that their study is modest in size (56 children with ASD and 197 total controls). A larger follow up study would be more definitive. But when we add this study to the existing body of research showing a lack of correlation between mercury and ASD it does add to our confidence in this lack of correlation.

Still, in my opinion, the most damning evidence for the mercury hypothesis is the fact that after the removal of thimerosal (which is mercury-based) from the routine childhood vaccine schedule in the US in 2001-2002, there was no subsequent drop in the rise in ASD incidence. Proponents predicted (correctly) that there should be if their claim was correct. Autism diagnoses continue to rise – now a full decade after the removal of thimerosal from the routine vaccine schedule. The supply of special pleading, however, is endless.

Earlier today, Steve discussed a new report hot off the presses (metaphorically speaking, given that it’s been published online) from the Bravewell Collaborative. Naturally, given the importance of the issue, I couldn’t resist jumping in myself, but before you read the blather I have to lay down, you really should read what Steve wrote about it. It’s that good. (Also, he’s our fearless leader, and I wouldn’t want him to be…unhappy about my having muscled in on his usual day to post.) Have you read it? Good. Now we can begin…

One of the most common (and potent) strategies used by promoters of “complementary and alternative medicine” (CAM)–or, as its proponents like to call it these days, “integrative medicine” (IM)–to convince the public and physicians either to use it (or at least to remain a shruggie about it) is in essence an argumentum ad populum; i.e., an appeal to popularity. Specifically, CAM/IM apologists like to use the variant of argumentum ad populum known as the “bandwagon effect,” in which they try to persuade patients and physicians that they should get with the CAM/IM program because, in essence, everyone else is doing it and it’s sweeping the nation in much the same way New Coke did in the 1980s. (Admittedly, CAM/IM apologists are, unfortunately, much better at sales than Coca-Cola was.) Not coincidentally, this is one type of method of persuasion much favored by Madison Avenue when selling cars, clothing, music, movies, food, beer, and nearly every other product–like Coca-Cola. I say “not coincidentally” because what CAM proponents are doing, more than anything else, is selling a lifestyle, a brand, a belief system, and, of course, many, many products whose value reminds me, more than anything else, of the aforementioned New Coke. In using this appeal to popularity, CAM/IM proponents try to portray stodgy physicians (you know, like pretty much every one of us at this blog) who insist on plausibility, science, and evidence to support the use of drugs and treatments as hopelessly behind the times, dogmatic, out of touch, and in general no fun to be around at all, particularly at parties.

Arguably no single private organization has been more effective at promoting the infiltration of CAM/IM into medical academia (or, as I like to call it, quackademic medicine) than the Bravewell Collaborative. Co-founded by Christy Mack (yes, that Christy Mack), wife of John J. Mack, the former CEO and Chairman of the Board of Morgan Stanley who now serves as a Senior Advisor, and Penny George, the Bravewell Collaborative was formed when Mack and George hit up a bunch of wealthy, woo-friendly donors to form a charitable organization in 2002 to support the “advancement of integrative medicine.” One result has been the proliferation of quackademic departments in medical centers all across North America like so much kudzu fertilized by Bravewell Collaborative money topped off with a bit from the National Center for Complementary and Alternative Medicine (NCCAM) lovingly applied by true believers choking off science-based medicine. Known as the Consortium of Academic Health Centers for Integrative Medicine, this group of divisions, institutes, and departments of quackademic “integrative medicine” now numbers fifty and includes some of the most famous medical schools in the nation, such as, for example, Duke, Harvard, Stanford (as much as Wally Sampson hates to admit it), Yale (as much as Steve Novella hates to admit it), and my alma mater the University of Michigan (as much as I hate to admit it).

So successful has the Bravewell Collaborative been in inserting pseudoscientific and prescientific “healing” modalities right into the heart of medical academia that it decided to update a project that it called a “nationwide mapping project” whose purpose was: (1) to describe the patient populations and diseases most commonly treated with integrative medicine, (2) to define the core practices and models of integrative care, (3) to determine how integrative care is paid for, and (4) to identify the biggest factors driving successful implementation. Christy Mack wrote in 2010 that she hoped the project would be complete by, well, the end of 2010, but apparently there were some glitches along the way, because the project was just released to the Bravewell website as a report entitled Integrative Medicine in America: How Integrative Medicine Is Being Practiced in Clinical Centers Across the United States (executive summary here). As Steve so aptly put it, it’s a massive case of putting the integrative cart before the the science horse in that it is looking at what Bravewell has wrought in terms of promoting quackademic medicine without paying attention to whether any of this stuff actually works or whether “integrating” this woo into medicine does anything whatsoever to improve the quality of care at the medical centers that have jumped on the “integrative” bandwagon.

Before getting into the meat of the report, it’s worth noting that this is not the first survey of this kind. In fact, Bravewell was beaten to the punch by another major promoter of CAM/IM, the Samueli Institute. Together with the Health Forum, the Samueli Institute published a report five months ago entitled 2010 Complementary and Alternative Medicine Survey of Hospitals, which I reviewed in depth. The difference between the Bravewell report and the Samueli report is that the Samueli report focused way more on motivations (i.e., why hospitals decided to start CAM/IM programs), means (how they started up their CAM/IM programs), and finances (how much of do these programs cost and do they make any money?) than the Bravewell report does. The two reports do, however, show considerable overlap in trying to survey the specific CAM/IM modalities offered by the hospitals surveyed that reported having CAM/IM programs. Also, the Samueli report had more breadth and less depth in that the investigators sent out a surveys to nearly 6,000 hospitals, while Bravewell focused its attention on 29 hospitals, nine of which were Bravewell Consortium members, the rest of which were not. In other words, the differences between the Samueli survey and the Bravewell survey can be summarized as looking at a broad sampling of all hospitals (or at least trying to) and taking a focused look at true believers.

Like the Samueli report, the Bravewell report begins with the same distortions of language to which we’ve become accustomed from CAM/IM apologists:

The Bravewell Collaborative, a philanthropic organization that works to improve healthcare, defines integrative medicine as “an approach to care that puts the patient at the center and addresses the full range of physical, emotional, mental, social, spiritual, and environmental influences that affect a person’s health. Employing a personalized strategy that considers the patient’s unique conditions, needs, and circumstances, it uses the most appropriate interventions from an array of scientific disciplines to heal illness and disease and help people regain and maintain optimum health.”

Over the past two decades, there has been documented growth in the number of clinical centers providing integrative medicine, the number of medical schools teaching integrative strategies, the number of researchers studying integrative interventions, and the number of patients seeking integrative care. But whether integrative medicine was being offered in the same, similar, or disparate ways was unknown. In addition, while previous studies focused on the prevalence and use of complementary or alternative medicine (CAM) by patients1, 2 or by practitioners in hospital settings3 by enumerating the use of single CAM therapies, very little information had been collected regarding the actual practice of integrative medicine, which by definition treats the whole person.

That was from the executive summary, but the same sort of language pervades the introduction to the report proper, in which the authors go on and on about how “all factors that influence health, wellness, and disease are taken into consideration,” “care addresses the whole person, including body, mind, and spirit in the context of community,” and how care is “individualized” (in reality this is fake individualization) Note the canard of “holism,” in which (or so it is claimed) CAM/IM is supposedly capable of taking care of the “whole patient” in a way that scientific medicine is not. This is, of course, utter nonsense built on a false dichotomy that says that a practitioner has to embrace pseudoscience and prescientific beliefs, such as those behind homeopathy, “energy healing,” and the like, in order to take care of the “whole patient.” It’s been a successful ploy in that quite a few physicians have apparently bought into the lie inherent in the very name “integrative medicine.” If they hadn’t, there wouldn’t be so many CAM/IM programs that have sprung up over the last ten years, to be surveyed now.

The report is fairly easy to read, and it tells us all sorts of things, including that the most common model of CAM/IM care is consultative care, with less than half of the centers surveyed offering primary care (thank heaven for small favors). We also learn tidbits about which I care almost nothing at all, such as that 72% of CAM/IM centers surveyed use electronic medical records (yawn) and, oddly enough, 72% also offer self-care and wellness programs for their practitioners and staff (double yawn). One notes that my university offers self-care and wellness programs; so this isn’t particularly impressive to me. But I’ll take science-based care over woo any day, and “wellness” is a term that’s been so thoroughly co-opted by CAM/IM that I can’t help but grimace just a little whenever I read or hear it. Then, of course, a huge number of these programs say they do research, which makes me wonder what has become of the word, or, to repeat yet again one of my favorite bit: Research. You keep using that word. I do not think it means what you think it means. Either way, these little tidbits, while useful, were not particularly novel.

More interesting to me were the specific modalities offered in CAM/IM centers in their order of frequency:

The interventions prescribed most frequently across all conditions, in descending order, are:

• Food/Nutrition
• Supplements
• Yoga
• Meditation
• TCM/Acupuncture
• Massage
• Pharmaceuticals

Notice anything? I do. Look at what the number one most frequently prescribed treatment by these CAM/IM centers. It’s nutrition or food. When I saw that, I had two questions. First, when, exactly, did nutrition or food become somehow “alternative” or “integrative”? Did I miss something somewhere? Nutrition is a science-based field (or should be), and the use of nutrition to prevent and alleviate illness is (or should be) science-based medicine. Yet, here nutrition is magically “rebranded” as somehow being part of CAM or IM! That’s what we here at SBM mean when we describe the “bait and switch” of CAM/IM. Plausible, potentially science-based treatments are reborn as CAM/IM and then used as evidence that CAM works. They’re also the Trojan horse that CAM/IM proponents use to trick the guardians of SBM into bringing into fortress of academia. After these modalities have been accepted as “CAM,” out jumps the real woo, such as “energy healing,” to take over. It’s not so far-fetched, given that my alma mater has a program in Steinerian woo known as anthroposophic medicine. I can’t wait until its botany department starts offering courses in biodynamic farming.

Snark aside, note that, out of the top seven modalities reportedly used, only one of them is truly “alternative,” namely TCM/acupuncture, while one is borderline (supplements). For the rest, the same observation I have about nutrition applies. Massage? Since when is that “alternative,” badly interpreted studies of massage notwithstanding? Pharmaceuticals? You might as well see a real doctor! Yoga? Stripped of its woo, it’s just a form of exercise. Meditation? It’s just a variant of relaxation therapy. Supplements could be woo or non-woo, depending upon how they’re used, but when naturopaths, homeopaths, and chiropractors use them they’re almost always woo. And, of course, traditional Chinese medicine and acupuncture are nearly all woo.

Particularly revealing is a section in which the survey asks for what diseases/conditions does IM produce “success.” That is, of course, a question so incredibly vague that, unless the patient dropped dead immediately upon contact with the therapy recommended, centers could claim some level of “success” with almost anything, and they do. No metrics for what constitutes “success” are described. Instead, the survey just takes the word of center directors for it. Basically, center directors were asked what conditions they considered to be conditions “among their top five most successfully treated conditions.” This generated the following, utterly useless table (click to enlarge):

Cancer was number five, with 52% of institutions claiming it to be in their top five conditions for which they have “success”? What do they mean? Certainly they don’t mean better survival, because I’d sure like to see that data if their claim is that they are successful treating cancer with CAM that way. I do have to admit that I chuckled grimly at this passage:

Cancer Treatment Centers of America (CTCA) at Midwestern Regional Medical Center in Zion, Illinois and The Integrative Medicine Center at MD Anderson Cancer Center in Houston, Texas. These two institutions only treat people with cancer. At CTCA, all treatment teams include a dietician, naturopathic doctor, mind-body therapist, chiropractor, and pain management clinician (including an acupuncturist) as well as a medical oncologist. MD Anderson’s integrative medicine center offers acupuncture, massage therapy, and mind-body-spirit practices such as meditation, guided imagery, yoga, tai chi, and music therapy. Therapies are provided to caregivers as well as patients.

Yes, Bravewell actually lumped together the Cancer Treatment Centers of America and M.D. Anderson Cancer Center. In woo, apparently, they are equals, which is far more an indictment of M.D. Anderson these days than it is praise for CTCA.

Next up, this survey touts the “personalized” care that these CAM/IM centers allegedly offer, with 93% of the centers surveyed claiming to offer “individualized care plans” for their patients. No, I’m not doubting that these centers come up with “personalized” care plans designed for each of their patient based on whatever “integration” of science-based medicine and pseudoscience takes their fancy. After all, when a Tarot card reader gives you a reading it’s personalized, as are psychic readings. What irritates me is that this CAM/IM apologists claim they are so much better at “individualizing” care than SBM, a claim that is pure nonsense. In breast cancer, I make individualized care plans for each of my patients as well. Nearly all of our breast cancer patients have multidisciplinary plans individualized to each of them involving multiple specialties (usually surgery, medical oncology, and radiation oncology, sometimes with genetic counseling as appropriate). In other words, Bravewell’s claim and that of its respondents are meaningless. The only thing that surprised me was that it wasn’t 100% of centers that claimed to offer “individualized care plans.” In fact, I’m downright amazed that two of the 29 didn’t claim to make them. It must have been the evil reductionistic “Western” scientists who forced them into offering “one-size-fits-all” treatments, just like us evil reductionistic “Western” doctors.

Finally, I found it interesting to look at where the rubber hits the road, so to speak, namely the practitioners whose salaries these centers are willing to pay (click to enlarge):

Not surprisingly, nearly all of these centers employ MDs. After all, we can bill and feed the referral machine. They also nearly all employ massage therapists and acupuncturists, both of which are what I like to view as gateway CAM, although massage can be justified easily without an appeal to pseudoscience or mysticism. What surprised me is that only 28% of them employ naturopaths, 21% employ osteopaths (maybe they’re all too busy being real doctors), and only 17% employ Ayurvedic practitioners, the last of which is no different than the number employing homeopaths. What didn’t surprise me is that some of these centers employ reflexologists and Rolfers, although I must admit that I have no idea what an “energy psychologist” is. Nor do I really want to know.

So now that we know the “what,” as in what services are offered, what are the outcomes? As it turns out, that is where this survey is unintentionally revealing. Basically, there are no medical outcomes reported. There are, however, lots of patient satisfaction surveys showing that patients like the woo being offered. Sadly, there is little or no discussion of actual efficacy and safety other than self-reported efficacy with no metrics to let us know whether or not the ideas of the center directors filling out the surveys of what constitutes efficacy had any connection with real measures of efficacy when they listed the conditions for which their centers have the most success.

All of this is very thin gruel upon which to base the conclusions of the report, such as:

The number of centers included in this study who expressed to the authors that their patient numbers were growing and/or their roles in their respective healthcare systems were expanding, suggests an increasing acceptance of integrative medicine by the American public and the medical professions.

Remember, there were only 29 centers surveyed. That’s a mighty big conclusion to rest on such a little study, particularly given that the survey used couldn’t measure acceptance of IM by the public anyway. One wonders why it took Bravewell so long to finish the study. Maybe it was the difficulty in figuring out a spin to put on it, although a blog from at least one institution surveyed in the study had no difficulty doing so.

The authors also conclude that IM really, really needs three things, the first of which is outcomes data. No kidding! On the other hand, as Steve points out, this is still putting the cart before the horse, as outcomes studies are usually indicated only after a treatment has been shown scientifically through a combination of basic science and translational research plus well-designed randomized clinical trials to be efficacious and safe. Until that evidence is there, there really aren’t any good reasons to study outcomes because there aren’t any scientifically valid reasons to be using these therapies to begin with. Oh, wait. The whole point of this survey is for Bravewell to congratulate itself on how much it’s managed to legitimize CAM/IM. Never mind. Be that as it may, if there aren’t any good reasons to be doing outcomes research, then there really aren’t any good reasons to be trying to identify best practices, which is the second recommendation of the report. After all, how does one identify best practices when there is so little scientific evidence to support the practices being examined? But don’t worry! Bravewell will definitely be doing another survey. It says it will. That is, after all, its third recommended next step.

None of this stops the authors from concluding:

One of the most striking, though perhaps predictable, conclusions of this study is that integrative medicine is, in fact, integrative. It integrates conventional care with non- conventional or non-Western therapies; ancient healing wisdom with modern science; and the whole person — mind, body, and spirit in the context of community.

The breathtaking inanity of Bravewell’s conclusion took my breath away, and all your bases are belong to us.

My conclusion is different. I conclude that “integrative medicine” integrates pseudoscience with science, quackery with medicine. Where it fails to do that, it rebrands science-based modalities like nutrition as somehow being “alternative” so that it can be listed as being CAM. On the other hand, one thing the writers of this report tell us in no uncertain terms is that, whatever you do, don’t call “integrative medicine” CAM. Just don’t do it, because Bravewell really, really hates it:

As was well articulated by Benjamin Kligler, MD, and Roberta Lee, MD, in the textbook Integrative Medicine: Principles for Practice, “Integrative medicine is not synonymous with CAM.” This survey has shown that integrative medicine centers embrace a group of core values that inform and radiate through their practice and interactions with their patients. Integrative care is, in practice, patient-centered care and is a fundamentally collaborative enterprise fostering cooperation between patients and practitioners, and among the practitioners themselves.

The problem, once again, is that it is not necessary to “integrate” pseudoscience with science-based medicine in order to practice collaborative patient-centered care. It’s really not, just as it’s not necessary to “integrate” pseudoscience into SBM in order to be “holistic” or to “take care of the whole patient.” Bravewell keeps selling that false dichotomy. I’m not buying, and neither is any member of the SBM team. Unforunately, though, a lot of doctors and medical centers are buying what Bravewell’s selling. They seem to want to view themselves as special flowers, but, no matter how much Bravewell, NCCAM, and other CAM/IM apologists try to convince patients and physicians otherwise, as our very own Harriet Hall has so frequently and eloquently said about naturopaths and CAM/IM practitioners, “What they do that is good is not special, and what they do that is special is not good.”

One of these days I’m going to have to try to come up with a statement that so succinctly and accurate describes CAM/IM, but I doubt that I will ever succeed.

The Bravewell Collabortive is a private organization whose stated mission is to, “accelerate the adoption of integrative medicine within the health care system.” They are well-funded, and they have successfully used their money to advance their mission. They also now appear to be an effective propaganda machine, producing what they are calling a “landmark report” on the use of integrative medicine in the US. The report is indeed revealing, but perhaps not in the way Bravewell intends.

The report is simply a survey of 29 integrative centers in the US. Before presenting the major findings the report defines “integrative medicine:”

“an approach to care that puts the patient at the center and addresses the full range of physical, emotional, mental, social, spiritual, and environmental influences that affect a person’s health. Employing a personalized strategy that considers the patient’s unique conditions, needs, and circumstances, it uses the most appropriate interventions from an array of scientific disciplines to heal illness and disease and help people regain and maintain optimum health.”

This is the standard marketing propaganda, which we have dissected many times before (so one more time won’t hurt). It is important to note that this is not a legitimate philosophy or approach to medicine, but pure marketing hype with the purpose of rebranding medical pseudoscience and quackery.  There is a growing list of terms used for this rebranding – first “alternative” or “holistic” then “complementary” now “integrative”, “personalized”, and “patient-centered.” It’s the same nonsense, only the labels have evolved (market-tested, if you will).

The report first equates integrative medicine with patient-centered medicine. This is a false dichotomy based upon a straw-man vision of science-based medicine. Medical ethics places the patient at the center of health care and all health care decisions. The physician is ethically obligated to be an advocate of their patient first and foremost.  Further, the modern (meaning in the last half-century) model of medicine is to treat the patient as a partner in their own health care (replacing the older paternalistic model).  This was a process, of course, not a sudden change.

As part of that process, and the cultural evolution of the physician-patient relationship, the term “patient-centered care” was used within the medical literature to describe this change – centering decision-making more on the patient. It was a shaking off of the last vestiges of paternalism in medicine (at least within the standard of practice, if not ideally achieved by all practitioners). The integrative movement then co-opted this term and made it their own, as if they invented it, and then ironically accused mainstream medicine (who invented the idea and the term) of not being patient-centered.  You will see this pattern repeated.

The next bit of propaganda is the description of holistic care (without using the term – I guess it’s not market-testing as well these days). This too is a fiction. In the 1980s I was taught in medical school about the biopsychosocial model of medicine – taking into account not just the biological illness but the social and cultural factors in which it is embedded, and the patient’s psychological response to their illness and the patient-physician relationship. This has been part of my training and practice from my first day in medical school. So I have always found it frustratingly odd that the integrative movement has (successfully, unfortunately) claimed that they invented this notion and that mainstream medicine is not “holistic”. We have argued on SBM (persuasively, I think) that science-based medicine is much more holistic than most “integrative” medical practices. We actually consider the patient’s biology, psychology, and social situation, whereas most alternative treatments are based upon a very narrow philosophy of all disease. They are the antithesis of holistic.

The tricky item of the integrative holistic list is “spiritual.” Mainstream medicine does consider the beliefs of the patient, and often must accommodate them in deciding on appropriate treatments. However – medical ethics dictates that we do not impose any religious belief onto our patients, neither are we judgmental. To our patients we are neutral on matters of faith, but can certainly be supportive of our patient’s use of faith as a support structure for dealing with their illness. In alternative medicine circles, however, “spiritual” can mean “faith healing” or its equivalent – actually treating the patient’s spirit or “energy”. This is not medicine – this is spiritualism and religion.

Next they throw in the “personalized” marketing term. Again, this is not a concept that is new to the integrative medicine movement. Regular science-based medicine is “individualized” (the term for what Bravewell and others now call “personalized”). The reason we take an elaborate history and perform a physical exam, followed by specific laboratory tests, is to individualize the diagnosis and treatment of each patient. There has been, in fact, a continuous evidence-based effort to more and more individualize treatments for patients, according to their age, sex, and genetic background. I often individualize treatment strategies to a patient’s educational level and socioeconomic status. This is just another false-dichotomy, another rebranding of ordinary medicine as a special feature of “integrative” medicine. It is just more marketing fiction and propaganda.

Next we get to the core fiction of integrative medicine, that it “uses the most appropriate interventions from an array of scientific disciplines.” That, of course, is a description of mainstream medicine. We use any intervention that is science-based – that has an appropriate combination of plausibility and direct evidence for safety and efficacy. Integrative medicine, rather, is the mixing of appropriate science-based interventions with treatments that are not science-based, that are highly implausible, or have been shown to not work. Otherwise they would already be part of medicine.

So what is integrative medicine? When you strip away the rebranding and co-opting of features and treatments of mainstream medicine, you are left with the usual list of pseudoscientific practices that have been trying to insert themselves into mainstream medicine for decades through a series of marketing and propaganda strategies. Bravewell has positioned itself at the forefront of that effort.

The body of the report I found to be almost entirely uninteresting and predictable – integrative centers are using integrative medicine and they feel (of course) that it works. Wow. The one bit I did find interesting was the list, in descending order, of the “integrative” methods these centers use:

• Food/Nutrition
• Supplements
• Yoga
• Meditation
• TCM/Acupuncture
• Massage
• Pharmaceutical

First we see another rebranding – calling nutrition integrative or alternative. We have pointed out numerous times on SBM that nutrition is a medical science. It is already part of mainstream medicine, and it is mainstream medical researchers who have figured out everything we currently know about the role of nutrition in health and disease. This is just one more thing that the integrative movement has tried to steal (metaphorically) from mainstream medicine to make part of its brand.

Two items on the list, supplements and TCM/acupuncture, are methods that do not work but have been the most successful in being marketed to the public. A thorough exploration of these modalities is beyond the scope of this article, but you can find numerous articles on SBM demonstrating the lack of an evidence based for the most popular herbal supplements and for acupuncture, for any indication.

Yoga, meditation, and massage are essentially exercise, stress-reduction, and  relaxation – all things commonly used and recommended by science-based practitioners. There is no evidence to support the notion that there is anything special about these particular manifestations of exercise, stress reduction, and relaxation. Most studies of Yoga, for example, have no comparison group to other forms of stretching and exercise. The implication is that there is something special or magical about transcendental meditation, for example, or Tai Chi, or specific forms of massage – again without evidence. There is no evidence that charging patients for a consultation with a specialist in one of these treatments is any more effective than just telling them to get more exercise – do something convenient and enjoyable.

About the only kernel of utility in this approach is that it may foster compliance with lifestyle changes. I say “may” because evidence is lacking for this as well. And again – there are already voices within mainstream medicine teaching a greater emphasis on patient education to foster compliance with lifestyle changes. Doctors are admittedly not very effective in changing patient behaviors, but that is because nothing is. It is very difficult to change behavior, and “integrative” practitioners have not hit upon any magical way to do so. They simply point out how bad mainstream medicine is, without acknowledging the fact that every studied method of changing lifestyle behaviors has a poor success rate. Even those that tout their success are just incrementally better than simply advising patients to quit smoking, exercise more, or lose weight.

What we need is to continue to experiment and research – to use science to figure out how to more effectively improve health behaviors in the public. Of course, if scientific research ever does develop a really effective method the integrative movement (or whatever it’s calling itself at that time) is likely to steal it and pretend that they invented it, then turn around and criticize mainstream doctors for not using it.

At the bottom of the list is pharmaceuticals. This does, perhaps, distinguish the integrative approach from some alternative approaches that are more purist in their pseudoscience. A homeopath, for example, uses only homeopathy. This appears to be a general trend with alternative practice, however. Naturopaths, for example, are fighting in many states and in Canada to get the right to prescribe actual medicine. This way they get to practice real medicine and then charge for a lot of extra stuff that is either worthless or just an expensive version of a simple healthy lifestyle. It’s quite a racket.

At the end of the report, under the category “next steps,” they write:

Providing funding for analysis of these data, which could provide important information about the efficacy of integrative medicine approaches as well as the treatment of chronic health conditions, should be a priority for funding sources and institutions.

Let me translate that for you, in the context of the whole report: Isn’t it wonderful that integrative medicine methods are being used, now let’s go see if they actually work. If there is anything that defines alternative, complementary, integrative medicine it’s putting practice before evidence. In fact, the evidence is irrelevant to practice. Practice is philosophy-based, not science-based. Evidence is an obstacle, used only for marketing purposes, not for determining which treatments are effective. That is why they keep trying to redefine scientific evidence in medicine. They need science to change to accommodate their treatments, not conform treatments to the science.

In my opinion the Bravewell Collaborative is a force for pushing pseudoscience and nonsense into mainstream medicine. This report reflects that reality.

As you cuddle with your mate your brain receives a comforting surge of oxytocin, reinforcing your feelings of attachment. More intimacy gives your pleasure centers a shot of dopamine, strongly reinforcing the behavior. Your brain becomes increasingly bathed in dopamine, serotonin, and other hormones and  neurotransmitters, resulting in a suite of physiological and behavioral responses evolved to maximize the probability of inserting your genes into the next generation.

In the afterglow of your subconsciously Darwinian act, you contemplate what attracted you to your mate in the first place. If you are male then you probably responded positively to a certain waist to hip ratio indicating good birthing potential. Full lips and facial features with a rosy tone to the skin also indicates youth and health – other good predictors of of breeding success.  Females are also attracted to signs of health and vigor, but also dominance and power (however this specifically manifests in your culture).

Evolutionary changes to your brain’s hardwiring and chemistry have spared you the tedious task of performing a biological assessment of potential mates. Rather, you just have an automatic feeling – an attraction – that is largely based upon a cold subconscious calculus of breeding and life success. You find yourself thinking obsessively about a good mating prospect. You may feel giddy just by being in their presence. The mere sight of them gives you a pleasurable spike of dopamine.

This crazy chemical in love phase will last about 9 months (for most people – the occasional “swan” may last much longer), long enough for longer term attachment mechanisms to take effect. This is also long enough for there to be a high probability of bringing children into the mix, forming other (perhaps even more powerful) chemical attachments.

A host of biological and neurochemical changes have occurred in human evolutionary history to make us a pair-bonding species (mostly). Females no longer advertise their fertility with visible estrus, for example. Males invest heavily in their children, and have formed strong feelings of jealousy to help ensure that their mate’s children are indeed their own as well. Females trade faithfulness and perpetual receptiveness for a promise of male protection and providing for them and their children, and seem to wield a variety of psychological talents for manipulating their stronger partners into staying invested themselves.

At least, this all is the current neurbiological and evolutionary psychology explanation for romantic love. Much of it is based on at least reasonable evidence. The role of dopamine and oxytocin are fairly well described in animals, but human studies are still preliminary and it is not yet definitively proven that the animal data can be extrapolated to humans. The evolutionary psych explanations are reasonable but hard to prove, and likely filtered through cultural norms.

There is also a great deal of natural variability in human behavior related to romance and sex. The most obvious variable is gender attraction, but there are also variations in what people find attractive, as well as interest in sex. Some people have “fetishes” – specific things or situations that trigger an erotic response. It’s not clear why this happens – a quirk of brain development or just life experience.

The scientific view of love and romance can seem anything but romantic, and we can’t even let you have the scientific explanation without pointing out our current uncertainty and the need for more research. The fact is – love and romance are biological/neurological phenomena. They are being studied and we are slowly building a reductionist picture of exactly how and why we feel and act the way we do.

This view, however, is not incompatible with romance. It is a rationalist romantic view. Understanding biology is not inconsistent with embracing and even reveling in the human condition. Feelings of love and attraction are not diminished at all by an understanding of the possible evolutionary advantages of those feelings, or the underlying brain chemistry, any more then they are enhanced by ascribing those feeling to fate or magic.

Understanding the biology of love, rather, can be empowering.  Sometimes we make decisions that are not in our best interest because we are in the grip of neurotransmitters and evolutionary signals of which we are not consciously aware. Thinking that those feelings are due to some magical design of the universe or something akin to fate, or to forces outside of your control, are convenient justifications for giving in to feelings that may be leading you to bad decisions. It’s helpful to understand that evolution does not need you to be happy, just prolific. You, however, may prefer to be happy, and therefore may wish to make more reasoned decisions. It’s also helpful to understand the power of neurochemistry, and therefore perhaps it’s not a good idea to make rash decisions when you are in the grip of “romantic psychosis.”

A scientific understanding of our own brains does not lessen the feelings of love and attraction, but may help us to enjoy and embrace those feelings without being ruled by them.

Happy Valentines Day.

Remember the movie “Attack of the Killer Tomatoes”?  That was fiction, but some alarmists would have us believe that the tomatoes and potatoes on our plates are really out to get us.

I recently got an e-mail inquiry from an MD who said he had read that solanine in tomatoes, potatoes, and eggplants could be responsible for essential hypertension and a number of GI complaints, as well as symptoms of rheumatoid arthritis, apparently through their inhibition of acetylcholinesterase. He had looked for supporting scientific studies and hadn’t found any. He wondered if I had seen any such studies. I looked too. I couldn’t find any either.

History

Tomatoes originated in the New World. They suffered from guilt by association because they were related to the deadly nightshade. Early on, they were used for witchcraft and as an aphrodisiac (“love apples”). They were slow to gain acceptance in Europe and the US, not coming into common use until the early 1800s. Thank goodness they finally did: without them, Italian food just wouldn’t be the same. Potatoes, another import from the New World, were also suspect: they were even accused of causing leprosy. Tomatoes are technically a fruit, although they are generally classified as a vegetable. Remember the attempt to count ketchup as a serving of vegetables in school lunches?

Solanine Poisoning Is Real

Solanine is indeed a poison in large doses, causing everything from gastrointestinal symptoms to hallucinations, paralysis and death. Large amounts are toxic, but the amounts usually found in food are innocuous. It is poorly absorbed and rapidly excreted. It is estimated that it would take 2–5mg per kilogram of body weight to produce toxic symptoms. A large potato weighs about 300g and has a solanine content of less than 0.2mg/gm That works out to around 0.03mg per kilogram for an adult, a hundredth of the toxic dose; I figure a murderous wife would have to feed something like 67 large potatoes to her husband in a single meal to poison him. Unless he’s a phenomenally big eater, arsenic would be a better bet. Potatoes that are diseased with blight or that have sprouted have a larger than usual amount of solanine. They will have a bitter taste and often a green discoloration; such potatoes should be avoided. Even integrative health guru Andrew Weil is not afraid of solanine, pointing out that there hasn’t been a single case of solanine poisoning in the US from eating potatoes in the last 50 years.

Solanine Toxicity Syndrome Isn’t

I found information about “Solanine Toxicity Syndrome” on the website of a chiropractor who uses bogus muscle testing (AK) to diagnose it. He finds that almost all arthritic patients test positive. He claims that in sensitive patients, solanine can:

• act as an endocrine disruptor especially to the thyroid
• cause chronic joint pain, arthritis (all forms), joint inflammation- this is due to solanines ability to remove calcium from the bones and deposit it in any weak or genetically predisposed area of the body
• for the same reason it can be a major contributor to osteoporosis (since it removes calcium from the bones) and arteriosclerosis (it can deposit the calcium in the blood vessels)
• “leaky gut” as well as IBS
• appendicitis
• birth defects including spina bifida
• depression (correcting it in one patient stopped their strong suicidal tendencies)
• migraines
• greatly interfere with calcium and vitamin D absorption, despite supplementation

Scientific Evidence

This will be a very short section. He doesn’t provide references. I looked for credible published evidence to support these claims. I couldn’t find a thing.

Testimonial “Evidence”

He describes his moment of epiphany. While he was treating one of his chiropractic patients, he happened to mention that he had been having pain, stiffness, and swelling in his hands, especially in the mornings (symptoms suggestive of rheumatoid arthritis). The patient asked him if he had eaten eggplant parmesan last night. He had! There you go! That must mean that dietary solanine is hazardous to your health, right?  For someone who believes in AK, that was easy enough to believe. Practice makes perfect: the White Queen in Through the Looking Glass practiced believing as many as six impossible things before breakfast. Believers don’t need no stinkin’ science.

There are a number of testimonials in various places on the Internet from individuals who claim to be unusually “sensitive” to solanine, but no controlled studies to support such claims.

Should We Avoid All These Foods?

Solanine-containing foods from the nightshade family include:

• potatoes
• tomatoes
• paprika
• eggplant
• peppers

Foods that are not part of the nightshade family but that also contain solanine include:

• Blueberries
• Apples
• Cherries
• Sugar beets
• Huckleberries
• Okra
• Artichokes

All these foods can be part of a healthy diet. Their solanine content is not a concern. It’s hard enough to get people to eat their vegetables without this kind of irresponsible fear-mongering.

Bottom line: Avoid green potatoes; otherwise, no worries!

Online surveys are worthless. That is, they are worthless as a source of information about popular belief and opinions. Yet many people still find them compelling, and so they can be useful as a way of driving traffic to your website. I guess that’s why they persist.

A recent poll about teaching complementary and alternative medicine (CAM) in Australian universities has become a matter of unnecessary controversy. Asher Moses wrote an article complaining about the fact that the survey seems to have been “gamed”, in an article: Vote on alternative medicine falls victim to dark arts of the internet. In the article he seems to miss the two real points about the poll – surveys are not reliable, and it’s fallacious to use them as an argument from popularity anyway.  He writes:

Voting progressed steadily at first but on Tuesday votes began rising from about 125,000 to more than 877,000 by the time voting closed on Thursday. The end result was 70 per cent no, 30 per cent yes.  The number of votes in the poll was about eight times more than the number of online readers of the story, a clear indicator that the poll had been gamed.

Moses talks in the article about how easy it is to “game” an online survey, but that is not the real issue. Most surveys are probably not hacked, as indicated above it is easy to detect such manipulation. Rather, there is a problem inherent with polls and surveys.  The only reference to this issue in the article is acknowledgement that the survey was not “scientific” – but what does that mean, exactly?

A scientific survey is a method for estimating the percentage of the general population (or some identified subpopulation) that has one or more characteristics. It does not have to be an opinion, it can be something physical like: what percentage of the population has blue eyes. This is a deceptively difficult task to undertake.

First you would have to clearly define “blue eyes”. Blue can blend into green or even hazel, without a clear demarcation. Should the survey contain a box for “ambiguous”? Do you allow for people to decide for themselves and self-report whether or not they have blue eyes, or do you require a picture, or perhaps an in-person exam under controlled lighting conditions with multiple examiners having to agree on the eye color? Perhaps some people define themselves as blue-eyed because they think it’s more attractive. The point is – no matter how simple you think the question is, there are layers of complexity that will affect the outcome.

The next big problem is how you are going to select the targets of your survey in order to ensure that it is representative of the target population. Are you gong to stratify by race? Otherwise the racial mix of whatever community you look in will have a large impact on the outcome. If you are going to sample widely from many communities, then how are those people going to be selected? Will it be adequately random and sequential? You have to avoid anything that can potentially bias the results by preferentially selecting blue or not-blue eye color.

For surveys about opinions and beliefs there are more layers of complexity. Self selection, obviously, is a huge biasing factor. Any survey that allows people to choose whether or not to respond to the survey is “unscientific” and essentially worthless. Online polls are even worse because people not only can choose whether or not to respond (for example by agreeing to take part in a phone survey or by taking the time to mail back a survey), but they can also choose to seek out the survey, or can be directed there by groups with an interest in one outcome.  For example, about the CAM survey Moses reports:

In the email sent by the Complementary Healthcare Council of Australia to members of its mailing list urging them to vote, the organisation’s consumer affairs director, Justin Howden, noted that the ”no” vote was streets ahead and said: ”We need to fight fire with fire.”

Urging members of one group to vote is breaking the poll. P Z Myers likes to point out this fact by “Pharyngulating” a poll – directing his readers to go to the poll and vote, massively biasing the outcome. He is clear that the point of this is not to engineer one outcome, but to demonstrate how worthless online polls are because they are so easy to bias. What you are really measuring is not public opinion but how effectively one side or the other can mobilize its online community.

A scientific survey is one in which efforts are made to contact random and representative people in a systematic way that avoids any bias. Subjects are chosen – they don’t choose themselves. Response rate is still a huge issue, because people can refuse to participate in the survey. Always look at the response rate of a survey and consider that an error bar. If only 10% of potential responders agreed to take the survey, ignore the results. As above, you can frame the issue as – what are you really measuring? Are you measuring passion for the issue? Comfortableness with the question? The anger that the issue provokes?  Willingness to be honest about the question?

The difficulty of all of these issues is made clear by political polling. Anyone who follows the news in an election year will notice that polls can be very inaccurate. Such polls are simple in the respect that they have a finite number of choices – which candidate are you voting for? This is a clearly defined question. And yet, results often do not predict voting outcomes, for all the reasons I stated above.

Opinion polls suffer from a further layer of complexity that can significantly change the outcome – how questions are framed. Are you asking responders if they agree with a position or disagree with its opposite? This can significantly affect the outcome. Are you making any assumptions about the context of the question? You can also bias survey results by assuming or even presenting facts that might make responders feel stupid, immoral, or just out of the mainstream for answering one way.

For example, surveys about belief in evolution are notoriously easy to bias depending on how the question is framed. If responders are made to feel that by stating they accept evolution they are rejecting God or religion, they are much less likely to do so.

In this CAM survey the question was: “‘Should universities teach alternative medicine?” This sounds simple, but those taking the survey may make many assumptions. What exactly is meant by “alternative medicine?” And teach it how? – Teach about alternative medicine, or promote alternative medicine as legitimate? The survey, of course, was attached to an article, so the content of the article can provide context and hugely bias the survey.

Conclusion

Scientific surveys are very tricky and their results should be viewed with extreme caution and a savvy eye. Surveys that are not scientific are worthless as a source of information. They persist because they are a gimmick for driving traffic to an article or website. Worse – they can be easily biased and then used inappropriately as if they actually represent public opinion. The online skeptical community has actually been effective in “breaking” such polls, not to use the results but to keep them from being used.

Legitimate surveys can be useful measures of public opinion, but in this and many similar cases proponents try to use them in order to make an argument from popularity. Moses throughout his article assumes that the popularity of CAM is an important issue. However, it is entirely irrelevant to the specific issue at hand – how should universities approach the topic of so-called CAM?

I have written several articles about this topic in which I make the point that universities should be thought leaders, helping to define and defend rigorous standards of intellectualism and scholarship. They should not be taking opinion polls and then following the current intellectual fad. Even if the vast majority of the public wanted CAM it would be appropriate for a university or medical school to take the unpopular position that CAM is a false category built largely on bad science, distorting the evidence, and even trying deliberately to water down the standards of science and evidence in medicine.

Thought leaders sometimes have to take unpopular positions. In fact, the issue about teaching CAM in universities is about defending science standards in the face of popular nonsense. It’s an oxymoron to argue that universities should or should not do so because of popular opinion.

If there’s one form of so-called “complementary and alternative medicine” (CAM) that I find more tolerable than most, it’s massage therapy. The reason, of course, is that, whatever else anyone claims about massage, there’s no doubt that it feels good. Indeed, I’ve sort of come around to Kimball Atwood’s way of thinking. Back when he and I were on a panel together at TAM9, Kimball said something somewhat surprising, namely that he’s not sure we even need to test massage in randomized clinical trials because we all know that it feels good and if it feels good it can certainly be helpful at the very least to improve patients’ quality of life. Unfortunately, there’s a lot of woo in massage these days, and massage therapists who buy into the woo aren’t satisfied with simply using the rationale that massage feels good to recommend it to patients. They just can’t resist going beyond that to infuse massage therapy with every bit as much woo as any chiropractor or acupuncturist infuses into his respective specialty. For instance, some of the claims for massage include:

• Decreases muscle pain & tension.
• Rejuvenates the body and mind and lifts the spirit.
• Relieves anxiety, stress and tension.
• Relaxes muscles.
• Alleviates headaches.
• Hastens healing.
• Increases ranges of motion.
• Facilitates removal of waste and inflammation by-products.
• Stimulates the immune system.
• Eases symptoms related to fibromyalgia.
• Promotes relaxation and comfort.
• Reduces nausea in pregnant women.
• Accelerates weight gain in premature infants.
• Helps premature infants become more active and aware.
• Increases energy and alertness.
• Enhances morale and attitude.

Of course, there’s little doubt that a good massage probably can relax muscles, promote relaxation and comfort (which seems like the same thing to me), and enhance morale and attitude. I’d even be willing to concede that massage, properly administered, can probably also alleviate headaches (tension headaches, anyway) and increase range of motion in joints. But facilitate the removal of waste and inflammation byproducts? Stimulate the immune system (the all-purpose meaningless claim)? Hasten healing? Not so much.

All too often massage therapists ruin a perfectly good massage by imposing pseudoscientific and quack claims on it, such as claims that they are stimulating acupressure points or their adoption of the language of “energy healing.” So it was with a bit of trepidation (but also more than a bit of interest) that I took a look at some links that readers sent me about a week ago (too late, alas, for me to write about this last Monday). These links were to news stories with titles like Scientists Uncover Why Massage Heals Sore Muscles and Massage Reduces Inflammation And Promotes Growth Of New Mitochondria Following Strenuous Exercise, Study Finds. My first impression, actually, was that this was somewhat counterintuitive in that one might predict that deep kneading of muscles might actually cause a bit of inflammation and that it’s the counterirritation effect that leads to the perceived reduction in the amount of pain. Yet, according to the press release issued by McMasters University, whose contents were mirrored in many news stories, a study claiming state-of-the-art methods is concluding that massage is reducing inflammation:

Most athletes can testify to the pain-relieving, recovery-promoting effects of massage. Now there’s a scientific basis that supports booking a session with a massage therapist: On the cellular level massage reduces inflammation and promotes the growth of new mitochondria in skeletal muscle. The research, involving scientists from the Buck Institute for Research on Aging and McMaster University in Hamilton Ontario appears in the February 1st online edition of Science Translational Medicine.

The study involved the genetic analysis of muscle biopsies taken from the quadriceps of eleven young males after they had exercised to exhaustion on a stationary bicycle. One of their legs was randomly chosen to be massaged. Biopsies were taken from both legs prior to the exercise, immediately after 10 minutes of massage treatment and after a 2.5 hour period of recovery.

My first thought upon reading this press release was that this was rather interesting and I wanted to find out more. My second thought, which turned out to be correct, was that the investigators were totally overselling their preliminary results.

Unfortunately, my third thought was: Muscle biopsies? Really? Although it is possible to do a needle biopsy of the muscle, most of the time muscle biopsies are surgical procedures, and, although the description of how the muscle biopsies were done is maddeningly vague in this paper, they do not appear to have been needle biopsies, which could not have provided enough tissue to do all the tests the investigators ran. In any case, I’ve done muscle biopsies before. They involve making an incision, carrying it down to the fascia overlying the muscle, cutting into the fascia, and then taking a piece of muscle. Sure, muscle biopsies can be done under local anaesthesia, and they’re not big procedures, but they are surgical procedures, in this case, being done for no therapeutic intent on healthy volunteers. One wonders how the investigators got this study past the Institutional Review Board (IRB), because I know for sure that the IRBs at the two institutions where I’ve been on the faculty would probably have—shall we say?—challenged the investigators on their experimental design. Yet approved this study was by the McMaster University Research Ethics Board. Leaving aside the problems I have from an ethics standpoint of doing not one, not two, but five (!) unnecessary muscle biopsies on research subjects, the next question I have is whether this study actually shows what the investigators claim it shows. To do that, I went straight to the source, namely the study in Science Translational Research by Crane et al. entitled Massage Therapy Attenuates Inflammatory Signaling After Exercise-Induced Muscle Damage. Here’s one of the investigators discussing the study:

Buck Institute Faculty Simon Melov, PhD, Discusses Recent Study on Molecular Benefits of Massage Therapy Following Exercise from Buck Institute on Vimeo.

When I first heard of this study, I couldn’t make up my mind whether it was good science, a fishing expedition that got lucky, or woo-omics. Then I got around to looking up the study, and I wondered if I was the only one disturbed by its design. Its big problem is that the investigators didn’t strike me as having a strong enough preclinical data base to justify doing a clinical trial in which medically unnecessary invasive procedures were carried out on healthy people and then whole genome mRNA expression profiling carried out. From my perspective, before doing five muscle biopsies on research subjects, there should be evidence from other less invasive (or preferably noninvasive) methods compelling enough to justify such an expensive study using invasive testing methods on humans. Yet, here is the authors’ justification:

Massage therapy is a well-known form of alternative medicine that consists of physical manipulation of muscle and connective tissue at a site of injury, inflexibility, or soreness to reduce pain and promote recovery (1, 2). Massage has been hypothesized to moderate inflammation, improve blood flow, and reduce tissue stiffness, resulting in a diminished sensation of pain. The potential benefits of massage could be useful to a broad spectrum of individuals including the elderly, those suffering from musculoskeletal injuries, and patients with chronic inflammatory conditions. About 18 million individuals undergo massage therapy annually in the United States, making it the fifth most widely used form of CAM (1). The functional benefits of massage remain contentious in humans (2–4), and experiments using massage therapy in animals may not properly mimic the human responses, limiting their usefulness. Despite several reports that long-term massage therapy reduces chronic pain and improves range of motion in clinical trials (5–7), the biological effects of massage on skeletal muscle tissue remain unclear.

After going on about various aspects of inflammation, which is what happens to muscle when it’s overworked because there are small tears in the myofibrillar structure of the muscle. So, basically, the authors’ hypothesis seems to be that massage somehow mediates inflammation and their rationale for choosing the study design they chose was that animal models may not mimic human responses, an assertion that, I note, the authors make without citing references to back it up. Is that enough to justify a clinical trial with this many muscle biopsies? I say no, but obviously the McMaster University Research Ethics Board did not agree. I also did not at all like how the authors bought into the language of “complementary and alternative medicine” (CAM), referring to massage therapy as “alternative medicine.” It is not, or, at least, it should not be considered so. The extent that massage is “alternative” depends directly on the amount of woo overlaid on it. It is, after all, physiologically plausible that manipulating muscles can do something to inhibit or release cytokines or other factors that might either increase or decrease inflammation. Of course, this plausibility should have been explored in an appropriate animal model before moving straight to human studies.

Preliminary results overblown

There is little doubt that this particular study is the most “high tech” study ever done on massage therapy in that some fairly heavy duty genomic techniques were brought to bear on the question of what gene changes occur (1) after heavy exercise and (2) in response to massage therapy. It’s a small study (only 11 subjects), which means that there’s the potential for a lot of noise, which further means that the results had better be striking (i.e., at least a two-fold or better change in gene expression) to be suggestive or convincing, and that replication is needed. The former definitely didn’t apply, and the latter is awaited, although I don’t think that I’d want to repeat a study that involves five muscle biopsies per subject.

Let’s take a look at the trial design itself, as shown in Figure 1 (click for full size):

As you can see, there are two visits and a total of five biopsies performed on each subject, one baseline and then two performed on each leg, before and after massage of one leg and before and after no massage on the opposite leg. Total RNA was isolated from these muscle biopsy samples, which were also subjected to additional testing, which will be discussed later. First, since it was the aspect of this study that caught my attention (and that of other scientists), I’m going to look at the results of the whole genome expression profiling. For those of you not familiar with this technique, it basically involves simultaneously measuring the levels of messenger RNAs (mRNAs) for every known gene in the genome. This is done by hybridizing the total mRNA isolated with probes designed to bind to each mRNA coded by the genome. These probes are housed on a chip, and the binding (or lack of binding) can be read by the machine. It’s all very complicated, with several probes designed for normalization, but when it’s done the results of each chip can be compared to other chips, and the results are usually reported as log2 results (i.e. “1″ means a two-fold difference between control and experimental; “2″ a four-fold difference, etc., with negative numbers meaning a decrease by the same factor). Ten years ago these cDNA microarrays, as they’re called, were state of the art. They aren’t now. Next generation sequencing (NGS) techniques, such as RNAseq, are, but that doesn’t mean cDNA microarrays aren’t still useful. NGS probably would have been overkill for this study—or at least prohibitively expensive.

One thing that I immediately noticed about this study is that it didn’t exactly use what is state-of-the-art analysis techniques on the data that were generated. Basically, they analyzed their data pretty much the same way I analyzed microarray data back in 2005, which was to look at single genes that had the most profound increase or decrease in expression compared to control. In this case, each subject served as his own control because these were muscle biopsies done before and after massage therapy or control intervention (i.e., no intervention). These days, more sophisticated analyses, known as network analyses, are usually done. These involve looking for groups of genes that are turned on and off in synchrony that indicate broader pathways that are being turned on and off. Single genes don’t actually mean all that much. It’s the groups of genes going up and down together as part of a pathway that truly indicate specific pathways being turned on and off. To get an idea of what these sorts of analyses look like, check out Figure 5 in this paper. Instead, what we get is a circa 2005 gene list not unlike the ones I produced (click for full size):

The first thing I noticed about this list is that it’s a short list, particularly compared to the number of genes that changed in response to exercise:

Independent of the massage treatment, the control leg muscle exhibited a change in 943 probes (representing 592 genes) at 0 hours after massage (30 min after exercise) and 2307 probes (representing 1309 genes) at 2.5 hours after massage (3 hours after exercise), significant changes that were induced by exercise alone (tables S1 and S2).

In other words, these five genes were a tiny subset of the genes altered by exercise to exhaustion. Less impressive is that none of them were particularly strongly turned on or turned off. The gene most turned on only reached a level 1.68 times control at time zero after massage and was not detectably different from control by 2.5 hours. The gene most turned off only decreased to 0.73 times control, a 27% decrease. Not impressive, at least not to me. This was particularly true after I perused the supplemental data list, in which I found a whole bunch of genes whose expression appeared to change more than this, due to exercise. Unfortunately, the authors didn’t include the table I really wanted to see, namely the table doing the head-to-head comparison of massage versus no massage.

Now, let’s see what the authors said about the identity of the genes whose mRNA levels changed:

One of the five genes whose expression was altered by massage immediately after the treatment was functionally related to actin dynamics (filamin B, b) (Table 1). One of the four genes induced by massage after recovery from treatment (2.5 hours) was related to NFκB nuclear trafficking (nucleoporin 88) (Table 1). Overall, this profile suggested that massage altered processes related to the cytoskeleton the former process being activated early after massage and the latter induced later in recovery.

I found this very questionable based on my own experience analyzing a cDNA microarray. The reason is that what I found my gene of interest to do was to decrease nuclear factor-κB (NF-κB) signaling. I’ve also done studies looking at the nuclear localization of NF-κB using confocal microscopy and NF-κB. When NF-κB is activated or turned off in my experience the changes seen in whole-genome expression profiling assays are not subtle and do not involve just a single gene, like nucleoporin, whose messenger RNA was elevated (but, it should be noted, whose protein was never verified to be also elevated after massage). NF-κB changes the activity of dozens of genes in a pattern that’s so obvious that when I showed my initial microarray results to an NF-κB expert several years ago, he immediately recognized that pattern by “eyeballing it” (and now I can recognize that pattern too). The changes were also much more dramatic. Indeed, I was looking at fold-changes that ranged from two-fold to over a hundred-fold. While it is true that I was studying cultured cells, which are an inherently less noisy system than tissue biopsies, I would have still expected to see a lot more genes altered if massage were truly impacting inflammation in general and the NF-κB signaling pathway in particular.

So how did Crane et al. come to the conclusion that NF-κB was being affected? Basically, they observed that nucleoporin 88 was expressed at an increased level on the cDNA microarray. If that were truly related to NF-κB signaling in stressed muscle, we would expect that massage would increase, not decrease, NF-κB signaling because nucleoporin facilitates the entry of the NF-κB into the nucleus. Increased expression of nucleoporin 88 is associated with increased NF-κB activity, and depleting nucleoporin 88 results in decreased NF-κB signaling. Now, to be fair, the authors did follow up by measuring NF-κB level in the nucleus and found that nuclear NF-κB levels did appear to decrease at T=0 after massage but that by 2.5 hours there was no significant difference. This actually doesn’t really correlate with the changes in nucleoporin, which didn’t increase until 2.5 hours. To try to bolster their case, Crane et al. also looked at heat shock proteins and saw a decrease at 2.5 hours. They also looked at another inflammatory cytokine and noted a truly unimpressive decrease that was statistically significant at 2.5 hours. Finally, they saw an even less impressive decrease in tumor necrosis factor (another inflammatory cytokine) at 0 hrs that was statistically significant but was not significant at 2.5 hr. In other words, the data are not entirely consistent, nor is the magnitude of the decrease in inflammatory factors impressive or persistent. The authors might be correct in their interpretation, but what I see more than anything else is probably either noise or a mild effect that is probably not clinically significant.

Interestingly, contrary to many of the other claims made by massage therapists, anabolic signaling and muscle metabolites, such as lactate, macroglycogen, proglycogen, and total glycogen were unaffected by massage. So much for the idea of “washing out toxins” that we sometimes hear.

O Mitochondria, Mitochondria, wherefore art thou, mitochondria?

Finally, the authors looked at another signaling molecule, nuclear peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α), because they found evidence that upstream signaling pathways that activates PGC-1α were turned on by massage (hmmm, I have to be more careful about how I phrase things). Sure enough PGC-1α levels were slightly increased (by maybe about 20% to my eyeballing the graphs) at 2.5 hours after massage. However, contrary to the way some news outlets reported this story, the number of mitochondria did not increase. Worse, this is a misstatement promoted by Dr. Melov himself:

Buck Institute faculty Simon Melov, PhD, was responsible for the genetic analysis of the tissue samples. “Our research showed that massage dampened the expression of inflammatory cytokines in the muscle cells and promoted biogenesis of mitochondria, which are the energy-producing units in the cells,” said Melov. He added that the pain reduction associated with massage may involve the same mechanism as those targeted by conventional anti-inflammatory drugs. “There’s general agreement that massage feels good, now we have a scientific basis for the experience,” said Melov.

Uh, not quite. This paper doesn’t show that massage promotes biogenesis of mitochondria, only that massage might—I repeat, might—increase the level of one molecule that promotes the development of mitochondria by 20% at most. In fact, our very own Paul Ingraham put it very well when he wrote:

What the authors actually reported is: “potentiated mitochondrial biogenesis signaling” and “promotes mitchondrial biogenesis.” In other words, they didn’t find more mitochondria … they found a mitochondrial growth signal. It’s the difference between finding bigger plants or just some bags of fertilizer.

Whether or not mitochondrial growth actually happens probably depends on many biological inputs, like everything else that our cells do. Inferring from one signal in a small sample that “massage increases mitochondria” is really just an enormous leap. Fortunately, the authors themselves didn’t make that leap — but lots of other people are making it.

Except that at least one of the investigators certainly is implying it very strongly—so much so that it’s a claim appearing in mainstream news articles about the study as though it were fact. As Paul also points out, the very design of this study indicates a lack of clinical insight into how massage therapy is usually used in the real world. What Crane et al. were studying was acute muscle injury in response to exercise to the point of exhaustion. Massage is not often used for that, and, in fact, as he summarizes, we already know that massage has only at best modest effects on exercise recovery; i.e., there isn’t much of a clinical benefit to explain. Rather, massage tends to be used used for chronic soreness. In fact, it might well be that a vigorous massage after a workout to the point where one’s muscles are so exhausted that one can’t even pedal a bicycle anymore would actually be painful.

When interesting results are oversold

My quibbles about the ethics of this study aside (well, they’re more than quibbles), scientifically this is not a bad study. However, as is so often the case in CAM studies, it is in the interpretation of the results that the authors go astray. They try to make something out of a mere five genes compared to hundreds that are changed by exercise when there doesn’t appear to be much to see. (In fact, my guess is that if they did a network analysis, the effect they observed would probably disappear into statistical insignificance.) They infer the wrong conclusion from the observation that nucleoporin 88 messenger RNA is elevated in muscle after massage. The correct inference would be to predict that NF-κB signaling should be elevated after massage, because nucleoporin 88 is involved in bringing NF-κB protein complex into the nucleus, where it does its stuff and turns on all the genes it turns on, which is why shutting down nucleoporin 88 inhibits NF-κB signaling. Yet they found that NF-κB signaling wasn’t increased but was rather decreased. Moreover, if the alterations in NF-κB signaling were significant, then there should have been a whole lot more than just a rather unremarkable change in the level of nucleoporin 88 messenger RNA. There should have been dozens of NF-κB target genes changing their levels in tandem because of NF-κB activation. There weren’t. Thus, the proper conclusion of this study is that there was little or no significant effect in inflammation-related gene expression from massage. That would have been perfectly fine as a conclusion. After all, negative studies happen and should be published.

Yet that’s not what was concluded. They did not report what was in essence a negative study.

Instead, the authors concluded that they had found that massage was anti-inflammatory, and that that’s how it “works.” They concluded that it “promoted mitochondrial biogenesis” without showing any evidence for anything other than the thinnest of thin evidence, a small increase in one signaling protein that promotes mitochondrial formation. And the news media ate it up.

None of this is to say that massage is useless or that it might not have therapeutic benefit in some circumstances. What this is to say is that this study, contrary to how it’s being portrayed, is not slam-dunk evidence that massage is some sort of “non-drug” treatment for inflammation that can replace non steroidal anti-inflammatory drugs. Unfortunately, whether because the authors were naive or desperate to salvage something from a study that didn’t show very much, that’s not how it was sold. The media might be guilty of overselling this study, but at least one of the authors was either complicit or didn’t realize how his words would be represented. Now this study is out there; look for massage therapists who are into woo to be pointing to this study for years to come as “proof” that massage is anti-inflammatory and “regenerates mitochondria.”

I have been casually tracking stem cell research over the years, especially for neurological indications, primarily to have a feel for where we are in the course of research. It takes years to develop a new therapy, and stem cell therapy is a tricky new technology. Right now we are in the post-hype era – the peak of media hype seems to have passed (probably just a short-attention-span effect) while the hard research continues to grind along. We are also in the snake-oil phase where heartless con-artists are capitalizing on the premature hype to sell fake stem cell treatments to desperate patients.

Meanwhile I want to know how the real research is progressing. It seems we are mostly in the animal trial phase and at the cusp of human trials for the most plausible applications. We may see human applications within 5 years for some applications. Heart failure and macular degeneration, for example, seem to be closest.

Some neurological applications are likely to also be among the early applications. Those applications which are likely to cross the finish line of routine clinical use are those in which we simply need to squirt stem cells into some tissue or body cavity and then the stem cells will function as raw material for regeneration or healing. Heart cells work well because they normally will start beating in time along with their fellow heart cells.

Brain applications are plausible because the brain has native stem cells waiting to be recruited in order to make new pathways, either when learning something fairly new or in response to injury. In other words, there is already a mechanism for recruiting stem cells into the recovery process. Adding more stem cells to the mix might therefore be an easy way add raw material and increase the self-healing process.

That is exactly what a new study is looking at. Researchers Martin Meuller et. al. were interested in studying infantile encephalopathy, brain damage in premature infants that results from lack of oxygen (hypoxia) and inflammation. They created a rat model of this damage by infecting young rats’ brains with E. coli (for the inflammation) and tying off one carotid artery to create lack of blood flow. In one group of rats they then  injected placentaderived mesenchymal stem cells (MSC) into one lateral ventricle (a fluid-filled cavity in the brain), and in a second treatment group they also have a hormone called erythropoietin which stimulates blood stem cells. The study is described as “sham controlled”, but only the abstract is currently available and so I do not have more details on the methodology.

The results were encouraging. They found that 22/23 rats survived the procedure (that’s a good start) and that the MSC survived and started to migrate into the brain tissue. There was also some indication of a therapeutic effect – those rats who received the stem cells improved more after the induced injury.

This is still preliminary animal data and a long way away from human trials or routine clinical use. This can probably best be described as a proof of concept trial – we can inject these kinds of stem cells into brains, they will survive, they appear to get into the brain where they are recruited to help recovery, there does not appear to be any major unanticipated complication, and erythropoietin seems to help. We need to learn as much as we can about this procedure from animal studies before it would be ethical to try it out in humans, and the first human subjects are definitely going to be “guinea pigs”. But this is an encouraging step.

The target population, premature infants, also is a highly plausible one, in that young brains are still in the process of developing and have tremendous potential to repair or compensate for damage. Infants with this kind of brain injury, however, tend (25-50%) to have motor, cognitive, and social deficits. Reducing these deficits would have a huge impact on their quality of life in addition to reducing their lifetime healthcare costs. The potential for benefit is therefore very high in this group.

The pace of this kind of research can seem agonizingly slow. Most published studies are baby steps, inching us a bit closer to the ultimate goal of a new and powerful therapy. The research is grinding forward, however, and results continue to be mostly encouraging. I do hope that within my career I will be routinely ordering stem cell infusions for patients with strokes, dementia, Parkinson’s disease, ALS, and a long list of other neurological diseases that we can currently manage but not cure. We just can’t predict the future course of research, however. We can extrapolate current trends, but the unknown elements of research often seem to change the game on us unexpectedly (sometimes for better, often for worse). After the fact progress always seems inevitable. There is a sense of inevitability with stem cell treatments – I hope it is warranted. The hard part is being patient, waiting, and watching.

I start these entries about a week before their due date, and when I saw Dr Hall’s Applied Kinesiology (AK) post from Tuesday, I thought the heck, there goes my post for Friday.  After reading Harriet’s post, I think mine will be both complementary and alternative, and perhaps even integrative, to her entry.  I do have one quibble with her post. She said

“we skeptics don’t dismiss AK just because it sounds silly.”

AK doesn’t just sound silly, it is silly.  I have found over the years writing for SBM that I have developed an increasing bias around the concept of prior probability.  As best I can tell there is a well described reality, and that reality constrains what is not only probable, but what is possible.  Within the limitations of our current understanding of reality, some processes are impossible, i.e. have zero prior probability. AK’s prior probability is exactly zero.   I sometimes think the blog should be called Reality Based Medicine.  Science gives us understanding of reality and AK, like many a SCAM (Supplements, Complementary and Alternative Medicine) discussed in this blog, parted company with reality from the beginning.

This blog has two often overlapping purposes.  Blogs offer timely commentary on contemporary issues, and this blog certainly fills that role.  More than other blogs, SBM also has the opportunity to be a reference source on various SCAM’s .  I have had the recent opportunity to reread the entire oeuvre of SBM, and it is impressive in the breadth and depth of topics covered in its three plus years.  It is not yet encyclopedic and there are many topics not yet reviewed in the blog, such as Applied Kinesiology.  So many many SCAM’s, so little time.

I tend to read about medicine and it’s alternative goatee wearing evil twin  in a nonlinear way.  I have 30 plus years reading about medicine and quackery, so day to day I add to my understanding incrementally, adding a brick here and a daub of mortar there to the edifice of my knowledge.  Such a Victorian metaphor.  Sometimes I need to go back and review a topic from scratch, as if I have no prior knowledge.  I have places to start when I need to review a topic from the beginning.  For infectious diseases I start with The Principals and Practice of Infectious Diseases, the ‘bible’ of my field. For SCAM’s I start with Google, and the Wikipedia entry usually pops up at the top of the list.

AK is like many other SCAM’s having its origin in the epiphany of one practitioner, in this case a chiropractor, George J. Goodheart, who, as Wikipedia mentions, ‘invented’ the process.  Invent.  When I hear the word invent, I think of Edison or Macaroni  Marconi. Damn auto correct.  I do not think of invent when applied to works of fiction, although I suppose Tolkien did invent his characters and world.  Still, invent somehow doesn’t fit, and later the Wikipedia says he originated AK in 1964, which is more in keeping with its fictional characteristics. ‘Made up’ would fit the situation best.

Evidently Goodheart was having difficulty diagnosing and treating problems in his patients who were not responding to the chiropractic conceptual framework. What a surprise: processes that were neither understood nor treatable by standard chiropractic.  That would appear to account for hmmm, let me see, everything.  No wonder he was at an impasse with his patients.  Undeterred and guided by the Triangle of Health, the Chiropractic concept of structural balance,  and a ring of power, by long trial and error he cobbled together AK. Unfortunately for AK, Goodheart was not guided by anatomy and physiology, reality not being a strong point in his understanding of disease.

AK has the following underlying principals:

1) Specific health problems will cause specific muscles to test weak.
2) Testing for muscle weakness can be used to indicate a treatment.
3) Treatments that increase muscle strength demonstrate efficacy of the treatment.

I think I have discovered the cause of obesity: the last century has seen a marked increase in the number of pathways by which SCAM modalities function: all the meridians of the various forms of acupuncture, the connections of reflexology, of iridology, and now of AK, and more are crammed into one small volume of flesh and blood.  Since a major aspect of SCAM the faux understanding that wishing it so makes it so, they are responsible for the proliferation of formerly imaginary pathways in the human body and they only way for all these pathways to fit is for the people to get larger.  The way I lost weight was to quit believing in acupuncture, and when the meridians faded I lost 45 lbs.  Pretty nifty.

The basic concept is that an illness in say, the lung, manifests by making a specific muscle or muscle group weak, and by improving the underlying problem the muscles strengthen.  I still think craniosacral therapy is goofier, but AK is giving it a run for the money.

An example from the first web page I found searching for asthma and AK

Reflex areas that stimulate either the deltoid or the lungs stimulate both. If an individual has a lung infection or an abnormal function in one or both lungs, he or she will probably exhibit weakness of one or both deltoid muscles. Not only would there be a lung infection, but because of deltoid weakness a problem may develop in the shoulder. Under normal circumstances, once the lung infection clears, or if the body adapts to the infection, the deltoid muscle will return to its normal state. On the other hand, if a chronic, low-grade infection lingers, the patient can be left with a weakened deltoid muscle. The applied kinesiologist evaluating the patient will need to stimulate the nerve and blood supply, as well as lymphatic drainage and acupuncture energy to the lungs in order for them to clear. Once the lung problem is resolved, deltoid muscle function can return to normal.

As I said, AK doesn’t sound silly.  It is silly. Multiple videos are available on the interwebs with a quick Google search to get a good idea of the silliness.

While, like all SCAM’s, there is not process to which AK is not applicable, it appears to be most often used diagnose and treat to allergies and food intolerance. The verbs and nouns in the preceding sentence need quotes, as the words diagnose, treat, allergy and food intolerance,  have no resemblance to how the words are used in real medicine. As is often the case in SCAM’s, words are used as if they have one meaning when in fact they have another.  It is like pointing at a chair and using the word dog.  It is the SCAM aphasia.  I wonder where the lesion would be on MRI.

The allegedly  toxic/allergic substance is held in one hand, often in a vial,  and the muscles on the other arm are tested for weakness.  If you cannot resist the force Anakin, then you are allergic/intolerant to the substance. The AK practitioner then does some adjustments or acupuncture or beams a laser on you, then retests and, if the intervention was successful, the weakness is gone. Success.

I think of allergies as an interaction of an antigen (in my world it is often an antibiotic) with antibodies, with a subsequent cascade of physiologic events leading variably to rashes, hives, interstitial nephritis and other adverse physiologic consequences.  Muscle weakness is not involved.  But that is the reductionist in me, trying to understand a process from the level of the antigen/antibody to the effects on the whole human with the allergic reaction.

I live in a word where, although we use short cuts on occasion, language is meant to be precise to describe a situation.  Precision of language represents precision of thought.  It is important to be precise in medicine.  Is it a  Staph infection?  A Staph aureus infection? A methicillin resistant Staph infection?  What is done diagnostically and therapeutically depends on how exactly the problem is described. Reading the kinesiology ‘literature’ indicates that allergy has a far broader, aphasic, use.

…allergies are viewed from a holistic perspective based on Oriental Medical principles and defined in terms of the effect an allergic substance has on the energy flow in the body.

An allergy is a condition of unusual sensitivity of a person to one or more substances which may be harmless to the majority of other individuals. In the allergic person, the allergic substance (known as an allergen) is viewed by the brain as a threat to the body’s well-being. When contact is made with an allergen, it causes blockages in the energy pathways called meridians, disrupting the normal flow of energy through the body’s electrical circuits. This energy blockage causes interference in communication between the brain and body via the nervous system which begins a chain of events that can develop into an allergic response.”

So all diseases are due in part or in their entirety to an allergy.

What do cellulitis, sprue, and cataracts have in common?  Vitamin C allergy. And a vitamin T allergy leads to “low immunity”.  I am not entirely sure what vitamin T is, evidently it is found in sesame seeds, and I pity the  fool who is deficient in vitamin T. So my allergy, and AK allergy are not the same thing. My use of the term allergy is relatively narrow. For the AK practitioner, it may describe everything and anything.

The weird thing, as if the whole process is not weird,  is that the tested foods or chemicals are often in vials. How the allergen, or its essence,  gets out of the vial into the human, sets up a cascade of effects that lead to muscle weakness is not explained.  Glass and plastic are far more porous than I ever suspected.

Oh wait.  It is quantum. I just started laughing as the speaker wrote quantum physics  in the board as he started the talk. I couldn’t get Dr. Science out of my head.  He Knows More Than You Do! The subsequent talk has nothing to do with the quantum physics I learned back in the day for my undergraduate degree. Oh. Sorry. I was wrong. The speaker doesn’t really explain how quantum physics is connected to AK.  Bummer.

And why, as an aside, is he wearing scrubs?  In the hospital we wear scrubs in part to avoid dragging  environmental material into clean areas of the hospital, and in part to avoid  getting blood and other body fluids on street clothes.  Just what kind of AK is he doing that needs scrubs?  Or perhaps it is an Ozian conceit.  I see someone is scrubs outside the hospital, I think doofus.

But others are clearer in the explanation.  I am using clearer and explanation in the SCAM aphasic manner,  just to see what it is like.

This brings us to our theoretical understanding of kinesiology: When you test the viability of a given statement, you are determining whether or not the wave function will collapse.[8] Only something that is true has existence in reality.

Conclusion: AK has no existence in reality.  But I knew that without a wave function collapsing.

Put simply, truth collapses the wave function. If you test a particular statement like “Today is Monday” and your arm (i.e. muscles) stays strong, a wave function collapsed, signifying that it is indeed Monday. Conversely, if you test weak (i.e. your arm drops to your side), there is no collapse of the wave function denoting that your statement was untruthful. Although it may seem counterintuitive, when your arm stays strong while testing a statement with kinesiology, a wave function collapses, but if your arms collapses (i.e. goes weak), there is no affect in reality.

That is more  a Korsakoff’s syndrome than an aphasia, don’t you think?  Neurology is not my strong point.

I see little  difference between AK muscle testing and Power Band muscle testing, just variations on a theme.  Richard Saunders  has nice demonstrations of the amazing quantum physics ability of people to fool themselves and others with muscle testing.

I am old enough to remember when there was not the huge number of clinical trials to help guide clinical decisions. We had a saying when I was a resident:  One patient was “in my experience, 2 patients were “in a series of cases” and three were “in case after case.” But still anecdotes, and still worthless.

The International College of Applied Kinesiology has all the collected papers available online, almost all some version of the saying mentioned above.  While a wide variety of anecdotal cases are presented, my favorite was ROCK MUSIC  AN ENVIRONMENTAL STRESSOR, where they concluded

In this selected group of patients, physical tests of muscle weakness and neurological disorganization appeared after exposure to rock-n-roll music.

It is remarkable the time and energy expended on publishing the fiction of AK, although World of Warcraft has a similar draw I suppose.

Still, there is no tooth fairy science that should go unstudied, no matter how ludicrous.  Much to my surprise there are no Cochrane reviews on the topic.  If homeopathy, why not AK?

There was a review in 2007, Chiropr Osteopat. 2007 Mar 6;15:4. Cuthbert SC, Goodheart GJ Jr. On the reliability and validity of manual muscle testing: a literature review  which concluded that AK was of benefit:

More than 100 studies related to MMT and the applied kinesiology chiropractic technique (AK) that employs MMT in its methodology were reviewed, including studies on the clinical efficacy of MMT in the diagnosis of patients with symptomatology. With regard to analysis there is evidence for good reliability and validity in the use of MMT for patients with neuromusculoskeletal dysfunction. The observational cohort studies demonstrated good external and internal validity, and the 12 randomized controlled trials (RCTs) that were reviewed show that MMT findings were not dependent upon examiner bias.

Conclusion
The MMT employed by chiropractors, physical therapists, and neurologists was shown to be a clinically useful tool, but its ultimate scientific validation and application requires testing that employs sophisticated research models in the areas of neurophysiology, biomechanics, RCTs, and statistical analysis.

The best they could conclude was that AK muscle testing was valid, not that it lead to effective interventions, noting

One shortcoming is the lack of RCTs to substantiate (or refute) the clinical utility (efficacy, effectiveness) of chiropractic interventions based on MMT findings.

This lead to a response by other chiropractors, who did a complete evaluation of  Cuthbert and Goodheart, pointing out the numerous methodologic problems and concluded

Cuthbert and Goodheart conducted a review with important methodological deficiencies. When manual muscle testing as used in Applied Kinesiology is disentangled from standard orthopedic/neurological muscle testing, the few studies evaluating specific AK procedures either refute or cannot support the validity of AK procedures as diagnostic tests. In particular, the use of MMT for the diagnosis of organic disease or putative pre/subclinical conditions is insupportable.

It is an interesting to read the articles sequentially and it underscores the difficultly in conducting a review of any literature and the issues with meta-analyses.

There are other meta-analysis that conclude

There is insufficient evidence for diagnostic accuracy within kinesiology, the validity of muscle response and the effectiveness of kinesiology for any condition. The standards of reporting were low. We recommend a pragmatic study of the effectiveness of kinesiology as the most appropriate initial step to determine whether kinesiology has any clinical value.

The pragmatic study being a study where you do not worry about potential bias and ignore issues like blinding and placebo controls.

and

Several recent studies have refuted the use of applied kinesiology and provocation-neutralization in diagnosis. The placebo effect must not be overlooked as a potentially important factor in some approaches.

SUMMARY:
There have been no studies supporting the use of these techniques, and several have refuted their utility. A beneficial placebo effect may be responsible for the perceived clinical effectiveness in many cases of food intolerance.

Given the prior probability of zero that AK would be useful diagnostically or that therapies based on AK would have efficacy, I would be surprised if there were good clinical trials that demonstrated efficacy.  It is all placebo effect, and those who read the blog know my equation: CAM = placebo. Placebo = nothing.  Therefore CAM = nothing.  In the case of AK, it is less a placebo effect and more of a minor variant of the Stockholm syndrome.   It would be an interesting topic to explore: compare and contrast the placebo effect, response to CAM treatments and the Stockholm syndrome.   They probably have the same underlying psychological etiology.

I have never been fond of the meta-analysis, since they operate in part on the GIGO principle,  Garbage In, Garbage Out.  Given the issues with reading the medical literature second hand, I always prefer to read and evaluate the primary literature myself.

First up was going though the references of  Cuthbert and Goodheart.  It was the Oakland of medical literature: No there there.  There are few  controlled studies looking at the diagnostic and therapeutic utility on defined populations.   There are almost no even mediocre evaluations to asses any aspect of AK, and those that have been published suggest that AK is a little bit less than worthless. I will give the caveat that much of the literature quoted by Cuthbert and Goodheart  is not accessible, published  in journals too obscure to be available on Pubmed or my medical library. Little was added after searching the PubMeds, finding mostly case reports and pilot studies.

One reasonable study Double-blind study on materials testing with applied kinesiology, found AK was no more reliable than chance for  for determining intolerance to dental material.   They evaluated “ two dentists qualified in AK”; there are two dentists I would not want mucking about in my mouth.

No surprise that if the AK practitioner and patient are blinded,

“… results suggest that the use of Health Kinesiology as a diagnostic tool is not more useful than random guessing”

and

“applied kinesiology to evaluate nutrient status is no more useful than random guessing.”

I can see why the first hit on my Pubmed search was an AK practitioner complaining about EBM. Reality doesn’t support their practice.

At least I came across Kinetics of hula hooping: an inverse dynamics analysis,  so the time spent was not a complete waste, in the case of hula hooping, waist.  At least hula hooping is a form applied kinesiology that exists in reality.

Postscript

If you want to hear more of me rant, and really, who doesn’t, try skeptikerpodden  where I was recently interviewed.  The English, or at least the American,  begins 33 minutes into the program. And they used my fat picture on the web site, before I lost all my meridians.

The title is an oblique reference to the AK-47.  I recently read The Gun by CJ Chivers, the history the the AK-47.  Excellent.

The quoted language above is part of the headline of this story in today’s The Scientist:

Citing the rising tide of Americans with Alzheimer’s—projections suggest 10 million people will be afflicted by 2050—the Obama administration and top National Institutes of Health officials are taking action. On February 7, they announced that they will add an additional $80 million to the 2013 NIH budget for the Alzheimer’s research program.

The problem is that there ain’t no such thing as a free lunch:

However, Richard Hodes, director of the NIH’s National Institute on Aging, told Nature that the 2013 dollars still have to be approved by Congress in the next budget and, if not, existing programs may need to be cut. And this year’s $50 million is likely to bump other projects, perhaps at NIH’s National Human Genome Research Institute. “If there’s a finite budget anywhere, once there’s more of something, there is less of something else,” he said.

Often such budget compromises are difficult, because there is no ready way to choose between two or more competing recipients of taxpayers’ money, each of which might be comparably worthy. Thus it is with a great sense of relief that in this case, we in the biomedical community can assure President Obama that no such dilemma exists. This is one of those occasional decisions that requires no hair-pulling whatsoever. The obvious solution is to defund the National Center for Complementary and Alternative Medicine (NCCAM), which, at about $130 million/yr, would solve the problem of funding Alzheimer’s research and take the heat off other worthy programs such as those mentioned by Richard Hodes.

Defunding the NCCAM would serve yet another worthy purpose: to end the period of nearly two decades during which the National Institutes of Health (NIH) has been bullied into acting as though pseudoscientific health claims ought to be taken seriously, thus embarrassing itself and medicine, endangering human subjects for no justifiable purpose, contributing to erroneous content in medical school courses, bankrolling ‘integrative medicine’ centers when there is no evidence that these are useful, and adding to the widespread scientific illiteracy of the American public. Here is a smattering of more articles making those points over the years, only some of which have been written by the authors here at Science-Based Medicine:

• The politics of alternative medicine —Science 1994
• Lobbying Blitz Attacks Alternative Medicine —Science 11 July 1997: 277 (5323), 169. [DOI:10.1126/science.277.5323.169e]
• Let’s Abolish the Office of Alternative Medicine at the National Institutes of Health —North Carolina Journal of Medicine 1998.
• Why the National Center for Complementary and Alternative Medicine (NCCAM) Should Be Defunded —Quackwatch 2002
• The Ongoing Problem with the National Center for Complementary and Alternative Medicine —Skeptical Inquirer 2003.
• Science and government. Review for NCCAM is overdue. —Science 2006
• The National Center for Complementary and Alternative Medicine (NCCAM): Your tax dollars hard at work —Science-Based Medicine 2008
• Let President-Elect Obama know that NCCAM should be defunded! —Science-Based Medicine 2009
• President Obama – Defund the NCCAM —Science-Based Medicine 2009
• Yes We Can! We Can Abolish the NCCAM! —Science-Based Medicine 2009
• Save NIH $$$: eliminate “alternative” medicine —Genomics, Evolution, and Pseudoscience  2010
• Update on Josephine Briggs and the NCCAM —Science-Based Medicine 2011
• Measuring Mythology: Startling Concepts in NCCAM Grants —Skeptical Inquirer 2012 Preview available here.

It is clear that things have not improved much, in spite of the two most recent NCCAM Directors, Stephen Straus and Josephine Briggs, having previously been, at least on paper, legitimate scientists. The explanation for that paradox is two-fold: the very language that spawned the NCCAM makes it impossible for more than a smattering of useful, legitimate science to be done; the two Directors have been company (wo)men first, scientists second.

Regarding the NCCAM mandate, consider these passages in the law that established the Center (emphasis added):

(a) In General.–The general purposes of the National Center for Complementary and Alternative Medicine…are the conduct and support of basic and applied research…and other programs with respect to identifying, investigating, and validating complementary and alternative treatment, diagnostic and prevention modalities, disciplines and systems…
(b) Advisory Council.–The Secretary shall establish an advisory council for the Center in accordance with section 406, except that at least half of the members of the advisory council who are not ex officio members shall include practitioners licensed in one or more of the major systems with which the Center is concerned, and at least 3 individuals representing the interests of individual consumers of complementary and alternative medicine.
(c) Complement to Conventional Medicine.–In carrying out subsection (a), the Director of the Center shall, as appropriate, study the integration of alternative treatment, diagnostic and prevention systems, modalities, and disciplines with the practice of conventional medicine as a complement to such medicine and into health care delivery systems in the United States.
(d) Appropriate Scientific Expertise and Coordination With Institutes and Federal Agencies.–The Director of the Center, after consultation with the advisory council for the Center and the division of research grants, shall ensure that scientists with appropriate expertise in research on complementary and alternative medicine are incorporated into the review, oversight, and management processes of all research projects and other activities funded by the Center...
(e) Evaluation of Various Disciplines and Systems.–In carrying out subsection (a), the Director of the Center shall identify and evaluate alternative and complementary medical treatment, diagnostic and prevention modalities in each of the disciplines and systems with which the Center is concerned, including each discipline and system in which accreditation, national certification, or a State license is available.
(f) Ensuring High Quality, Rigorous Scientific Review.–In order to ensure high quality, rigorous scientific review of complementary and alternative, diagnostic and prevention modalities, disciplines and systems, the Director of the Center shall conduct or support the following activities:
(1) Outcomes research and investigations.
(2) Epidemiological studies.
(3) Health services research.
(4) Basic science research.
(5) Clinical trials.
(6) Other appropriate research and investigational
activities.

That language is anti-scientific for many reasons. I’ll explain a few; feel free to look here for more discussion. Paragraph (a) guarantees a cherry-picking approach to the topic: start with a treatment claim that has no scientific basis, assume that it works for something, then try to find a ‘something’ that seems to ‘validate’ it. This is the opposite of the way clinical research, including that done by most NIH-sponsored trials, proceeds. Paragraph (b) is self-explanatory: if the ‘major systems’ have no scientific validity—and no system other than modern, science-based medicine does—the NCCAM Advisory Council will certainly not be expected to acknowledge that fact, and it hasn’t. Paragraph (c) begs the question and betrays the real agenda of the NCCAM’s creators.

Paragraph (d) presumes that there are scientists “with appropriate expertise in research on complementary and alternative medicine.” There actually are a few such people, such as Edzard Ernst, but the NCCAM has not “incorporated” them. Rather, it has incorporated pretenders to science such as those quoted in this recent post. Paragraph (e) guarantees that the NCCAM will cotton to quacks who, regrettably, have been licensed to practice in one or more states. Paragraph (f) predicts that various implausible ministrations will inevitably be found to “work,” relying as it does on “outcome studies”—a form of Cinderella Medicine—as the first choice in testing.

Regarding my second assertion, that Directors Straus and Briggs forsook their scientific (and ethical) roots in favor of a perceived mandate to go along with the company gag, I can offer numerous pieces of evidence in addition to those already linked above: here, here, here (my response to that is here), here (Dr. Briggs’s contribution to this), and here (circling the wagons in response to this), for example.

Which makes me wonder: if Dr. Briggs were really honest with herself, would she think that taxpayers’ money is better spent on the NCCAM than it would be on Alzheimer’s research? A cheap shot, you say? I don’t think so: once there’s more of something, there is less of something else.

A final note to the president: as easy as this decision is, there’s yet another easy one. You can double your (our) money by defunding the rest of NIH ‘CAM’ research! You’ll find most of that at the National Cancer Institute (NCI).

This story is a classic of cryptozoology. A paranormal researcher claims to have come into possession of a video of an alleged living woolly mammoth. Immediately, skeptical red flags should be flying, but let’s take a deep breath and look more closely at the story.

First, it is always good to go into any exploration or investigation with an open but informed mind. Too often people equate “open mind” with a mind empty of all relevant information. Before scientists embark on a new line of research they typically will first see everything that has already been researched on the topic, to see if the idea has already been answered, or if it is even plausible.

In this case we may or may not be able to come up with a definitive answer, but we can start by considering the plausibility of the claim (what some might call “armchair skepticism”, but should not be denigrated). Mammoths largely died out about 10,000 years ago. Recent fossil evidence suggests that a population of dwarf woolly mammoths survived on Wrangel island, off the coast of Siberia, up until as recently at 4,000 years ago. It is not entirely implausible that a small population of even large mammals could survive in the remote wilderness without being detected.

The probability is fairly small, however. Even dwarf mammoths are large creatures. A sustainable breeding population would require at least 2000 individuals, and large animals would have to range fairly widely to find food. There would also be 4,000 years of frozen or fossilized mammoths to find, if they were alive for this entire time. So while the probability is not zero, it is small. In skeptical terms, this means that we can be convinced that living woolly mammoths are lurking in the Siberian wilderness, but we would need convincing evidence.

That last bit is what we never seem to get. The world of cryptozoology deals largely with those creatures that are unknown to science – which means we have no specimens, either living or dead. There are no articulated skeletons, or even just skulls, in museums. Sometimes cryptozoology deals with creatures that are known to have lived once but are believed (with good reason) to be extinct.

What really keeps cryptozoology on the fringe, however, are their methods. Proponents of bigfoot or Nessie offer consistently ambiguous evidence. Often we get nothing more than anecdotes – some guy’s second or third hand testimony about what they saw.  The typical photo or video is usually just at the edge of detection, so that we can see a provocative suggestion of the alleged creature, but not enough details to make a positive ID. Is that bigfoot or a person in a costume? Pictures and videos seem almost designed to no offer a definitive answer. Sometimes the image is just visual noise, which some humorously call “blobsquatch” (at least in reference to bigfoot). Such images are not evidence – they are little more than pareidolia and wishful thinking.

Now let’s take a look at these current images: video of a large furry mammal slowly strolling across a windy river (I guess it could be a lake). We have no reference for objective scale, so there is a wide range of sizes it could be. The image if out of focus, too distant to make out detail, and the environment appears misty. In other words – it’s perfect for a horror movie when you don’t want the audience to get a clear look at the monster. You want the audience to fill in the details with their imagination, and so does the promoter of this film. When it is suggested to you that the video is of a mammoth, hen that is how your brain constructs the image.

I showed the video to my 12 year-old daughter, without any explanation, and just asked her what she was looking at. Without hesitation or doubt she said it was a bear. That, in my opinion, is the likely answer. The animal can be within the size range of a large bear. Bears are known to walk across lakes and rivers hunting for fish. What might be interpreted as a trunk can easily be a fish in the bear’s mouth. If you look at the video thinking that it is a video of a bear with a fish in its mouth, then that is what you see.

There is nothing in the video to make one suspect that it is a woolly mammoth, or that can rule out a bear eating a fish. Between the two possibilities, Occam’s razor strongly favors the bear – because then we don’t have to introduce the new element of a surviving population of mammoths.