In response to the media attention, several groups and individuals came forward to publicly hypothesize about what might be causing this rash of symptoms. Antivaccinationists suspected that it was a vaccine—or environmental toxin, at least—that had caused the illness. Chiropractor Russell Caram speculated that

The other possibility here are HPV vaccines, Gardasil and Cervarix. The timing becomes more easily ex­plained—as most children “get their shots” (and boosters, such as DTaP and the flu shot) before enrolling in school in the fall. It also satisfies the girls-only attack (even though they’re trying to convince boys to get the Gardasil shot also), as well as the age group. (Caram 2012)

Caram’s hypothesis suffers from more than the fact that it is pure speculation. Half of the children affected by the illness did not even receive the Gardasil or Cervarix vaccines, nor is there any evidence to suggest that either vaccine can cause such neurological symptoms in the first place. (Similarly, no evidence supports the claim that Tourette syndrome can be caused by vaccines or toxins.) When Caram wrote the article, only girls showed signs of the illness, but later one boy also developed symptoms, which further suggests that the HPV vaccines are not to blame.

Those who have made it their mission to expose the risks of environmental toxins see in this case a possible environmental toxin. Apparently, some of the parents of the affected children called upon famous activist Erin Broc­ko­vich, who sent her team to investigate. She has speculated about “. . . whether students have been ex­posed to contaminants from the train derailment that occurred within a few miles of the school in December 1970. That derailment spilled cyanide crystals and leaked carbon tetrachloride” (Ciavarri 2012).

Of course, an environmental toxin such as carbon tetrachloride would not explain the timeline of the illness or its predilection for girls. Why would a forty-year-old spill suddenly have an adverse effect on people living in the general area? The results of a search for environmental toxins in the area have already turned up negative, and the students themselves have tested negative for toxic exposure. However, this poses the problem of proving a negative. Brockovich claims that the search has not been thorough enough, but such a claim can be made arbitrarily without limit. You can keep searching for toxins with lower and lower thresholds until you find something. Toxins are ubiquitous in the environment in background concentrations generally too low to worry about, but if you look hard enough you can find something—especially if it’s something you want to find.

Rosario Trifiletti, MD, PhD, is an expert in a rare condition known as PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection), and she has come forward to claim that this is what these children have (Swedo et al. 2012). I cannot get into a thorough evaluation of this complex condition, but suffice to say that Trifiletti, who claims to be personally treating some of its patients, is a major promoter of this diagnosis. There is a tendency to see what we know, and experts in a narrow illness often see their pet disease everywhere. The National Institute of Mental Health’s (NIMH) definition of PANDAS does not seem to fit this case well. Age of onset for PANDAS is supposed to be between three and puberty, but the Le Roy children are between the ages of twelve and eighteen. There is no indication that PANDAS is a selective illness, affecting girls more than boys. Furthermore, PANDAS is a clinical diagnosis without laboratory confirmation; part of that clinical diagnosis is that symptoms are triggered by a streptococcal infection (such as strep throat), which does not appear to be the case here. PANDAS also involves more than tics—it can include mood changes and obsessive compulsive symptoms, too. Altogether, based on publicly available information, PANDAS does not seem a great fit for answering the question of this “mystery illness.”

The “mystery illness” has become a Rorschach test of sorts: people see in the illness a diagnosis that fits their worldview or pet cause. But now that the dust has settled somewhat on this outbreak, what can we reliably say about it? To review the facts of the case, eventually fifteen children were af­fected with involuntary tics, which are sudden “jerk-like” motor movements, between October 2011 and January 2012. All fifteen of the children attend the same junior-senior high school and range in age from twelve to eighteen; all but one of them is female. All of the children have been examined by pediatric neurologists—twelve of the fifteen at the Dent Neurological Institute by the same two neurologists, includ­ing Laszlo Mechtler, MD.

Mechtler—and, in fact, all of the pediatric neurologists who have examined any of the children—has come to the diagnosis of conversion disorder and mass psychogenic illness. A conversion disorder occurs when psychological stress manifests as physical symptoms. We take this for granted to some degree; when people feel anxious they may get sweaty, nauseated, or short of breath and have palpitations. People who experience panic attacks can have these symptoms along with difficulty swallowing and episodes that may resemble certain types of seizures with feelings of being separate from reality or from themselves. These are physical symptoms resulting from purely emotional stress. But in some cases, psychological stress can also lead to neurological symptoms—pretty much any neurological symptoms, such as weakness, difficulty speaking, loss of vision, and involuntary movements.

It is important to note that this is a known and well-established syndrome (Stone et al. 2011). Neurologists see patients with conversion disorder frequently, and many cases positively demonstrate that the neurological symptoms are not due to any damage or lesion in the nervous system but rather to psychological stress. For example, it can be demonstrated in someone with psychogenic blindness that their visual system actually works. Similarly, many patients with psychogenic seizures display features that are neuro-anatomically incompatible with actual seizures.

It is always challenging to deal with conversion disorder. We medical professionals try very hard to accurately and constructively convey to patients and their families what is happening, but unfortunately our culture attaches an undeserved stigma to psychological ailments, and many patients resist such a diagnosis. We tend to focus on the positive—psychogenic symptoms can completely cure themselves (and usually do with encouragement and reassurance to the patient) because there is no irreversible damage to the nervous system.

The diagnosis of psychogenic illness, however, is also partly a diagnosis of exclusion. It is often the case that a physical ailment underlies the psycho­genic symptoms and has, in fact, triggered them. The diagnosis, therefore, is usually made only after a thorough workup to rule out other causes.

In the case of the children in Le Roy, doctors report that they have thoroughly evaluated the children—in­cluding screening them for any toxins, infections, or signs of a physical illness—with completely negative results. The school has been examined also, and no environmental toxins or chemicals have been discovered.

Here we are probably dealing with not only a psychogenic illness but also a case of mass psychogenic illness, which is also a known phenomenon that can even be induced experimentally (Broderick et al. 2011). In cases of mass psychogenic illness, the appearance of symptoms in other people, which causes anxiety about a contagious illness or a toxic exposure, can be the stressful trigger. In susceptible individuals this can induce a psychogenic illness that mimics the symptoms of those already affected. Media coverage only enhances this phenomenon; in fact, some speculate that social media increased the spread of the Le Roy children’s illness.

The Le Roy case has all the hallmarks of a mass psychogenic illness. Most of the symptomatic individuals are women who are part of the same small, close-knit community and have social contact with each other. The diagnosis is therefore not based en­tirely on the exclusion of other causes; the case also has a natural history and epidemiological features that fit a mass psychogenic illness. Al­though the available details of this case point to a mass psychogenic illness as the culprit, there may be one or two index cases of true Tourette syndrome that triggered the outbreak. It is an important lesson, as most people underestimate the ability of our brains to generate physical symptoms.

On the one hand, there are the neurological experts who have presented what seems to be a sound diagnosis. On the other, there is a circling of those who want to promote their causes or ideology. In the middle of all this are the students and their families who have to deal with a delicate neurological ailment before the public eye. We can certainly hope that science and reason win out, but often the most alluring and media-friendly answers come from the cranks who would manipulate the diagnoses of experts to weave a sinister tale.

References

Almasy, S., and J. Spellman. 2012. N.Y. town still baffled by teens’ mysterious tics. CNN (Febru­ary 4). Available at www.cnn.com/2012/02/03/us/new-york-students-illness/index.html.

Broderick, J.E., E. Kaplan-Liss, and E. Bass. 2011. Experimental induction of psycho­genic illness in the context of a medical event and media exposure. American Journal of Disaster Medicine 6(3) (May/June): 163–72.

Caram, R. 2012. Le Roy, N.Y. mystery continues and frustrates. . . . Available at http://drcaram.com/the-LeRoy-n-y-mystery-continues-and-frustrates/.

Ciavarri, A. 2012. Erin Brockovich’s team in town, Le Roy reluctant to allow access. WHEC.com (January 28, updated January 29). Available online at www.whec.com/news/stories/s2473055.shtml.

Stone, J., W.C. Lafrance Jr., R. Brown, et al. 2011. Conversion disorder: Current problems and potential solutions for DSM-5. Journal of Psychosomatic Research 71(6): 369–76.

Swedo, S.E., J.F. Leckman, N.R. Rose. 2012. From research subgroup to clinical syndrome: Modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuro­psychiatric Syndrome). Pediatrics and Therapeutics 2(2).

It is a sign of our times that we have to defend having standards of good science in the practice of medicine and the teaching of a science-based curriculum in universities. High standards of science in medicine are necessary in order to ensure, as best as we can, that treatments and interventions are safe, effective, and ethical. It is extremely complicated and tricky to determine safety and efficacy. Humans suffer from numerous mechanisms of self-deception, cognitive flaws and biases, poor grasp of statistics, and perceptual failings that are likely to lead us astray. In fact our biases tend to systematically lead us to false conclusions that we wish to be true, rather than to the truth.

These flaws, biases, and cognitive errors make it difficult to come to reliable conclusions in any area of exploration, but perhaps particularly so in the applied science of medicine. This field is further plagued by placebo effects, which represent the above effects in addition to a complex emotional and physical response to the nonspecific aspects of getting attention from an attentive practitioner.

Science is the only system that we have developed that systematically controls for all of these biases and flaws to see through to reliable information. Science endeavors to be transparent, thorough, and rigorous. The application of scientific principles has demonstrably transformed medicine (and human knowledge in general) for the better. As a society we should not lightly abandon the principles of science or try to change them to meet the needs of the current fads.

Universities in particular are supposed to be the exemplars of scholarship and intellectual legitimacy. People believe universities are intellectual leaders, not followers, and they are correct (or at least, they should be). Teach­ing a topic in a university is absolutely an endorsement of the legitimacy of that topic. We can distinguish between teaching about something and teaching the thing itself. It is okay to teach about so-called complementary and alternative medicine (CAM) as a sociological phenomenon or even as an example of pseudoscience. Practi­tioners also need to learn about any method their patients may be using or about which they are curious. Credu­lously teaching CAM, however, is an endorsement, the granting of the imprimatur of the university.

It is tempting to cater to prevailing fads, to acquiesce to the vocal advocates and give them what they want, especially when there isn’t much protest. That is exactly what intellectual integrity is about, however—doing the right thing because it is right, not because it is popular or expedient.

I will acknowledge perhaps the only legitimate argument on the other side: that of academic freedom and diversity of opinion. I agree with the principle that a university should also be a place for the free exchange of ideas and should not easily impose censorship. Proponents of nonsense, however, have taken this principle too far. Academic freedom needs to be tempered with quality control. Professors should not be allowed to teach absolutely anything they want without limit. The university has a duty to ensure that the minimal standards of academic legitimacy are met.

This duty includes ensuring that science is taught in science classes. This debate has come up with reference to teaching creationism as science as a matter of academic freedom. Such freedom does not extend to the point of teaching demonstrable pseudoscience as if it were a legitimate science. The exact same thing can be said about teaching homeopathy, for example, as if it were legitimate science-based medicine.

The argument above should not be difficult to make and should resonate with academics. It has worked well in the United Kingdom, spearheaded mostly by David Colquhoun, who has used freedom of information requests to obtain the CAM curricula at universities teaching CAM, and then simply sent them to the dean and/or board of trustees of the university. This one act has led to the removal of CAM courses from universities in the United King­dom. Simply shining a light on what was happening was enough.

In the United States we are having a harder time, although we have had some successes also. The American Medical Student Association (AMSA) has been infiltrated by CAM proponents who have managed to get requirements for CAM to be taught in American medical schools. Of course, we can still teach about CAM (which I actually advocate) rather than promote pseudoscience—something that is not a subtle distinction but is often difficult for some to make.

Australia is perhaps having the most difficult time with this issue, leading to the formation of the Friends of Science in Medicine. Their request is simple: no pseudoscience in universities. They have helped bring the debate to the forefront. CAM’s greatest ally in infiltrating universities is stealth. I have seen this infiltration occur deliberately under the radar with the stated goal of avoiding too much attention, which might draw criticism. This violates the principle of transparency, and it illustrates why focusing attention on this trend is so useful.

Of course, CAM proponents are not going to just lie down and go away. There have been many responses to the criticism of teaching CAM in medical schools, none of which is valid. In Australia, the most frequently quoted defender of teaching on nonsense in universities is Iain Graham, professor at Southern Cross University’s School of Health. He is quoted in several articles, but this quote responding to criticism from John Dwyer, emeritus professor of medicine at the University of New South Wales, is representative:

Professor Dwyer’s sweeping discussion about the issue are to do with quackery really, and the rooting out of poor practise. But if we look historically at the evolution of health care and the health professions, there are many similarities with where things started.

He mentioned homeopathy for ex­ample, well homeopathy is as old as Greek Hypocrates in terms of practising medicine. (Australian Broad­casting Company 2011)

Here we have a blatant misstatement of fact combined with a logical fallacy. Graham probably (if I am being generous) did not mean to state that homeopathy can be traced back to ancient Greece, just that some CAM therapies can. Homeopathy was in­vented by Samuel Hahnemann about 200 years ago (Novella 2009).

But I wonder what CAM modalities he had in mind. Chiropractic? About 100 years ago. Therapeutic touch? A few decades ago. Acupunc­ture is a complex question, but what passes for acupuncture today is less than 100 years old. Perhaps he was thinking about bloodletting or trepanation.

However, it is true that some basic concepts, like the notion of “life energy,” can trace their roots to ancient Greece and other ancient cultures. However, such notions are pre-scientific nonsense. Scientists abandoned the notion of life energy over a century ago because there was no evidence that such a force exists (and there still isn’t). After figuring out all the basic processes of life, there was essentially nothing left for the alleged life force to do.

For some reason, however, Graham believes that antiquity in science is a virtue—the “argument from antiquity” logical fallacy. The unstated assumption is that if an idea has survived for hundreds or thousands of years it must be legitimate. This is demonstrably false. Galenic medicine (bloodletting, purging, etc., based on the notion of the four humors) survived for thousands of years, and yet it was based on complete and utter primitive nonsense. In fact its tendrils still exist. There is still bloodletting, cupping (which is just another form of bloodletting), and similar practices going on in the world. It was replaced in the West because of the advent of science in medicine—a trend that Graham apparently wants to reverse.

Graham’s second swing and a miss: “Eighty per cent of Australians seek alternative therapies,” Graham is quoted as saying by Australian newspaper the Northern Star. “Obviously orthodox medicine is not working for everyone” (www.northernstar.com.au/story/2011/12/12/alternative-therapy-course-not-magic/). I highly doubt that the 80 percent figure is correct. Most such figures are highly inflated by including all sorts of practices in the CAM category, such as exercising and eating organic food—and sometimes prayer is included. U.S. surveys show the percentage of CAM use is around 33 percent (NIH 2008), but this is mostly things like massage and chiropractic manipulations. Home­o­­pathy use is around 3–4 percent, and acu­punc­ture 6–7 percent. In fact, only manipulation and massage were in the double digits.

This is all marketing deception. Create a false category (CAM), pad it out with commonly used methods, and then claim that the extreme fringes are therefore getting more popular. I don’t know how Graham got to 80 percent (I doubt such methods are that much more popular in Australia than in the United States) but it is close to one survey from 2007 that found that 69 percent of Australians used one of the seventeen most popular forms of CAM in the last year (Xue et al. 2007). However, that study included in its list martial arts, yoga, massage, meditation, and taking multivitamins. I am not sure what taking multi­vitamins says about the popularity of homeopathy, but apparently Graham thinks it is significant.

In any case, I will grant that CAM as a marketing concept has been somewhat successful—and even that it has gained popularity recently (although not as much as advocates would have you think). That is entirely irrelevant, however, to the question of whether or not any particular CAM modality is science-based and appropriate for a university curriculum (which is the question at hand).

Universities are supposed to be thought leaders with intellectual standards that rise above the mere notion of popularity. They are supposed to uphold academic standards of scholarship, especially in scientific disciplines with high standards in science. It is therefore very odd and disturbing to defend a university policy based upon popularity. Should we allow surveys of public opinion to determine whether or not we teach creationism or astrology in our universities?

It is good to see some organized backlash against the infiltration of pseudoscience and nonsense into the very institutions that should be teaching against such things. It is good to see more and more articles written about this topic—we want attention for the issue. We want a discussion of the merits of our position verses the pro-CAM position. Let’s have a very public debate about the facts, about what is science, and how we as a society should determine what medical interventions are worth our public support.

We will confidently stand by our position. CAM proponents, like crea­tionists, have nothing but weak and fallacious—and long discredited—arguments on their side.

References

Australian Broadcasting Company. 2011. Uni criticised for teaching alternative therapies (De­cem­ber 9). Available online at www.abc.net.au/local/stories/2011/12/09/3387574.htm.

NIH. 2008. 2007 National Health Interview Survey (NHIS) Adult Alternative Medicine Public Use File (althealt) IDN Variables Wednesday, June 4, 2008. Available online at ftp://ftp.cdc.gov/pub/health_statistics/NCHS/dataset_documentation/NHIS/2007/althealt_freq.pdf.

Novella, S. 2009. Homeopathy awareness week (blog entry). NeuroLogica (June 15). Avail­able online at http://theness.com/neurologicablog/index.php/homeopathy-awareness-week/.

Xue, C.C., A.L. Zhang, V. Lin, et al. 2007. Com­plementary and alternative medicine use in Australia: A national population-based survey. Journal of Alternative and Comple­mentary Medicine 13(6) (July/August): 643–50.

However, to patients suffering from an incurable disease a new idea represents one thing: hope. Science, by contrast, cares only about what works and is dispassionate, which is easily portrayed as heartlessness. Hopeful nonsense thus has a public relations advantage over pitiless science every time.

We are seeing this effect now with a new idea in the science of multiple sclerosis (MS). A lone Italian vascular surgeon, Paolo Zamboni, proposed that MS is not caused by an autoimmune process (the immune system attacking the nervous system) but rather by blockages in the veins that drain blood from the brain. He published his initial study that found a “dramatic” association between MS and these venous blockages (Zamboni et al. 2009). He called the condition chronic cerebrospinal venous insufficiency (CCSVI).

The paper set off a bitter controversy. Zamboni is suggesting that decades of MS research have been on the wrong track and that he has found the true cause—and potential cure—of MS with a simple diagnostic procedure. The press loved it—a lone maverick challenging the status quo with a bold new idea. Many patients with progressive and difficult-to-treat MS also loved it, for it provided hope of an effective treatment. (As an aside, there are several effective treatments for MS but not all types of MS or all patients respond.) When the neurological community treated Zamboni’s claims with (perfectly reasonable) skepticism, some patients began to weave conspiracy theories to explain the resistance. They wanted the new treatment, and they didn’t want stuffy neurologists getting in the way because their turf was being threatened by a surgeon (at least that is the narrative they told each other.) But science is pitiless and doesn’t care for narrative, turf, or good headlines.

Despite the low plausibility and the fact that Zamboni’s claims ran counter to the carefully accumulated MS research to date, many centers set about to replicate his findings. Replication is a key process in science. If a phenomenon is real, then it will be real in any lab. Zamboni’s findings were dramatic, so they should be easy to replicate.

Two years later we have several good replications. One study did produce similar findings to Zamboni, although the association was not as strong (Al-Omari and Rousan 2010). The next three, however, were all dead negative (Sundström et al. 2010; Doepp et al. 2010; Krogias et al. 2010). Skepticism mounted. Another study this year comparing MS patients to normal controls concluded, “This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS” (Mayer et al. 2011).

The largest replication to date (Zivadinov et al. 2011) found a small association between venous blockage and MS and concluded, “Our findings are consistent with an increased prevalence of CCSVI in MS but with modest sensitivity/specificity. Our findings point against CCSVI having a primary causative role in the development of MS.”

These findings are interesting. They do not entirely rule out a correlation between CCSVI and MS. However, the results are very ambiguous. There is a statistical correlation between MS and CCSVI, but there is also a correlation with other neurological diseases—with very different histories and probable causes from those of MS. CCSVI was also found in a quarter of healthy controls. So CCSVI is not specific to MS, and almost half of MS patients do not meet criteria for CCSVI.

To summarize all of the existing research on CCSVI and MS: The results are mixed with variable methodology used but are generally negative. No one has found the dramatic results first published by Zamboni. After a couple years of research, his implausible idea is not looking very good. At best we can say that there may be a small and inconsistent correlation between venous blockages and MS. If the correlation is true, it is also possible that these blockages are a result of MS, perhaps caused by inflammation, and are not necessarily a cause of MS.

Despite these largely negative findings, there are still many MS patients clamoring for treatment. The treatment of CCSVI is called the liberation procedure (essentially opening up the blocked veins, a procedure not without risk). Clinics are opening up offering the treatment to desperate patients—putting treatment ahead of the evidence or even using a treatment in the face of negative evidence, which is always a bad idea.

There are also calls, especially in Canada, for clinical trials of the liberation procedure. Such trials are not justified by the science that has been done so far, but because clinics are already offering the liberation procedure, this may force the hands of MS researchers. Before subjecting people to experimental medical interventions, ethics demands that we do sufficient basic science research to demonstrate that there is at least a reasonable chance of benefit. We have not crossed that line with CCSVI and the liberation procedure. Advocates of the procedure, however, are likely to succeed in making an end run around the usual safeguards of ethical medical research.

Those promoting CCSVI and the liberation procedure are likely to be portrayed by some in the media and by hopeful patients as brave mavericks. That is the hopeful, romantic, and sensational view. I suspect, however, that in the end the science will tell a different story.

References

Al-Omari, M.H., and L.A. Rousan. 2010. Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. International Journal of Angiology 29(2): 115–20.

Doepp, F., F. Paul, J.M. Valdueza, et al. 2010. No cerebrocervical venous congestion in patients with multiple sclerosis. Annals of Neurology 68 (2): 173–83.

Krogias, C., A. Schröder, H. Wiendl, et al. 2010. Chronic cerebrospinal venous insufficiency and multiple sclerosis. Critical analysis and first observation in an unselected cohort of MS patients. Der Nervenarzt 81(6): 740–46, DOI: 10.1007/s00115-010-2972-1.

Mayer, C.A., W. Pfeilschifter, M.W. Lorenz, et al. 2011. The perfect crime? CCSVI not leaving a trace in MS. Journal of Neurology, Neurosurgery and Psychiatry 82(4): 436–40.

Sundström, P., A. Wåhlin, K. Ambarki, et al. 2010. Venous and cerebrospinal fluid flow in multiple sclerosis—a case-control study. Annals of Neurology 68(2): 255–9.

Zamboni, P., R. Galeotti, E. Menegatti, et al. 2009. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 80(4): 392–9.

Zivadinov, R., K. Marr, G. Cutter, et al. 2011. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 77(July): 138–44.

Take antioxidants (or rather, don’t take them): if you believe the hype, then you want them in your food; you want to take them as pills; and you want the maximum most powerful antioxidants that can be found in nature (especially from some obscure tropical fruit). Unfortunately, the evidence does not support the claim that there are any health benefits to taking antioxidants.

The theory behind antioxidant claims sounds very compelling. Oxidants are chemicals (free radicals, also called reactive oxygen species or ROS) that are the products of metabolism; they are highly reactive and can cause damage to proteins and cells. This damage is a major contributor to aging and disease. Antioxidants neutralize these free radicals and prevent damage.

Unfortunately, medical science is rarely so clean and simple. This nice story is true, as far as it goes (the best lies always contain a kernel of truth). Twenty years ago this was the state of our knowledge of ROS and antioxidants, and there was legitimate hope that antioxidants would be a useful therapeutic tool. However, as research continued we learned that the picture is more complex: The body has evolved a natural defense against the onslaught of ROS. These compounds are called free radical scavengers or antioxidants (such as the protein superoxide dismutase and some vitamins like C and E) and their job is to gobble up ROS before they can damage cells.

In addition, some ROS actually serve a purpose in the body, for example as signals to cells or as neurotransmitters (nitric oxide). In fact, the body has evolved a balanced and complex system to maintain homeostasis between ROS and antioxidants. Influencing that system by taking large amounts of exogenous antioxidants may not be such a good idea. In other words, if a balance between ROS and antioxidants has evolved, there is no reason to believe that there are any benefits to tipping the scales in one direction—toward antioxidants. In fact, doing so may cause harm.

What does the actual clinical evidence show? Well, to find out we have to go claim by claim.

The best current evidence shows that antioxidant vitamins are of no use in improving cognitive function or in preventing dementia (Gray et al. 2008). If we look at other specific neurodegenerative diseases, the picture is a bit more complex. Some studies show that vitamin E (but not C) may slightly reduce the risk of motor neuron disease, but only in women (Wang et al. 2011). Overall, the evidence is ambiguous and does not support a benefit for treatment.

In Parkinson’s disease (PD) the picture is more complex. There is some evidence that eating foods rich in vitamin E may help prevent PD, but taking vitamin E supplements does not. So perhaps it is something other than the vitamin E in these foods that is of benefit, or perhaps eating healthy foods in general is simply a marker for some other variable that protects against PD. Other studies show a benefit from taking the vitamin supplements but not changing diet (Miyake et al. 2011). In other words, the evidence is ambiguous.

It is reasonable to conduct further research into antioxidants and degenerative diseases. Current evidence is mixed, without any clear benefit, but there is enough positive preliminary evidence to continue to study the potential of antioxidants in preventing degenerative diseases.

The evidence for taking antioxidant supplements in the general population is also less than definitive. In addition, it actually suggests the potential for harm. A comprehensive review published in 2008 concluded: “We found no evidence to support antioxidant supplements for primary or secondary prevention. Vitamin A, beta-carotene, and vitamin E may increase mortality” (Bjelakovic et al. 2008).

That’s right—there might be an increased risk of death from taking vitamins A and E. The data is far from definitive, but it shows that we cannot assume that supplements, even vitamins, are harmless. It also shows that we need to be humble with our simplistic theories of biology. Until the research has had time to fully explore a biological question, we should not be confident in our extrapolations to clinical effect. Therefore, even when the theory sounds good, we always need to do clinical studies to see what the net effects are in humans.

When it comes to antioxidants, there is still the potential that they may be useful in specific situations. At present, however, there is no evidence to support going out of your way to eat lots of antioxidants in food or to take antioxidant supplements. In fact, doing so may be harmful. This evidence is at odds with the overwhelming marketing hype that has successfully created an irrational demand for a dubious product.

References

Bjelakovic, G., D. Nikolova, L.L. Gluud, et al. 2008. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews 2008, Issue 2. Article No.: CD007176.

Gray, S.L., M.L. Anderson, P.K. Crane, et al. 2008. Antioxidant vitamin supplement use and risk of dementia or Alzheimer’s disease in older adults. Journal of the American Geriatrics Society 56(2) (February): 291–295, doi: 10.1111/j.1532-5415.2007.01531.x.

Miyake, Y., W. Fukushima, K. Tanaka, et al. 2011. Parkinson’s disease study group. Dietary intake of antioxidant vitamins and risk of Parkinson’s disease: A case-control study in Japan. European Journal of Neurology 18(1) (January): 106–13, doi: 10.1111/j.1468-1331.2010.03088.x.

Wang, H., É.J. O’Reilly, M.G. Weisskopf, et al. 2011.Vitamin E intake and risk of amyotrophic lateral sclerosis: A pooled analysis of data from 5 prospective cohort studies. American Journal of Epidemiology 173(6) (March): 595–602.

Actually, stem cell therapies have been around for years, but only for very limited applications such as treating certain blood cancers. The debate surrounding the ethics of using embryonic stem cells, however, has highlighted the great potential of therapies based on stem cells.

Stem cells are undifferentiated cells that have the potential to turn into specific cell types. Embryonic stem cells are the most potent because they can theoretically turn into any cell type in the body. The hope of research into stem cells is that we can learn how to control the process of differentiation so that stem cells can be used therapeutically.

Potential applications that are already being researched include injection of stem cells into failing hearts—cells that will then turn into heart muscle cells and start beating along with the rest, strengthening the heart. While still experimental, this is likely to be an early application of this kind of use of stem cells. Similar experiments are underway using stem cells to repair damaged brains or spinal cords.

Stem cells might also be used not as replacement cells but as support cells. Genetically engineered stem cells can essentially become drug delivery systems or support cells that allow diseased cells to survive longer and function better.

But many hurdles remain, the biggest of which is keeping stem cells from becoming cancer cells. There is a reason our bodies are not already infused with stem cells that have unlimited regenerative ability (our bodies do have natural stem cells, but they are in specific numbers and locations). Stem cells share some characteristics with cancer cells, and injected stem cells are as likely to become cancers as replacements for diseased or injured cells.

Getting stem cells to do what we want them to, and getting them to survive long enough to do it, is also no trivial matter. Stem cells have tremendous potential, and they will likely be playing an increasing role in medical therapies over the next twenty years. But reality has yet to catch up with the hype.

The situation is ripe for exploitation. Stem cell clinics have been set up, mostly in poorly regulated countries such as China, India, and several countries in South America. They exist to lure in wealthy (by international standards) Westerners desperate for a cure (such as the parents of young blind children). Fees range from the tens of thousands to even hundreds of thousands of dollars, including the costs of travel. Most victims are not wealthy people who simply write a check but instead members of middle-class families who need to raise money for the treatments.

Once they have invested so much time, effort, and emotion and so many resources in the stem cell treatment—which often includes taking money from family, friends, and coworkers—these families have a huge investment in believing the treatment has worked, even when all objective evidence says otherwise. Often there is a temporary placebo effect from getting the treatment—or perhaps a temporary effect from the anesthesia or other aspects of the treatment—but no real improvement. But any fluctuation in symptoms is often interpreted as a sign the treatment has worked, which sometimes motivates the patients and their families to raise more money for more stem cell treatments.

The clinics themselves are not producing useful scientific data but are instead simply publicizing anecdotes of their success. There is often little transparency in what they are doing and no way of knowing what they are even injecting into their patients.

What little objective investigation we have into these stem cell clinic treatments reveals that patients are either unchanged or even harmed by the therapies. Ophthalmologist Shakesh Kaushal, of the University of Massachusetts, examined eight children treated with stem cells for blindness. “There didn’t seem to be any ostensible benefit from the stem-cell infusion,” he is quoted as saying in an NPR report, “in all of them, as far as we could tell” (Knox 2010).

Dobkin et al. (2006) reviewed the cases of seven patients who received stem cell injections for spinal cord injury. They conclude, “No clinically useful sensorimotor, disability, or autonomic improvements were found.” In other words, there was no benefit. There were, however, complications, including meningitis in five of the seven patients.

The media, for their part, mostly promote these fraudulent stem cell clinics. They often report stories of “miracle cures” in gushing terms, without the slightest amount of skepticism. These reports are little more than free advertisements for these clinics, driving more desperate patients through their doors.

Hope is a very positive emotion; it can keep us going in hard times, and it motivates all the hard work and investment it takes to develop high-tech treatments such as stem cell therapy. But there is a dark side to hope: false hope, promoted by premature uncritical hype. Unjustified hype also undermines legitimate therapies and scientific research as the public becomes disillusioned. While it is legitimate to discuss the great potential of stem cell therapies, such discussions must include the proper context. Stem cell therapies remain largely experimental, and there is no telling when or even if they will pan out.

The media need to take greater responsibility in relating these stories to the public. Medical professionals need to pay attention to what is happening, and they also need to get involved in properly informing the public. Governments need to pay close attention to how such clinics are regulated. And the public needs to approach claims of stem cell “miracles” with extreme skepticism and get advice from professionals before investing emotion and large amounts of resources into what is likely to be all hype and no hope.

References

Dobkin B.H., A. Curt, J. Guest. 2006. Cellular transplants in China: Observational study from the largest human experiment in chronic spinal cord injury. Neurorehabilitation and Neural Repair 20(1) (March): 5–13.

Knox, Richard. 2010. Offshore stem cell clinics sell hope, not science. NPR.org (July 26). Available online at www.npr.org/templates/story/story.php?storyId=128696529

Acupuncture is often referred to as an ancient Chinese practice, but in actuality it’s neither very ancient nor exclusively Chinese. The modern practice of acupuncture is only decades—not centuries or millennia, as is often claimed—old (Ramey 2010). It has antecedents in ancient times, but the practice of needling in Asia was not much different from the practice of bloodletting in the West (Novella 2010).

The National Center for Complementary and Alternative Medicine (NCCAM) has this to say about the definition of acupuncture:

The term “acupuncture” describes a family of procedures involving the stimulation of anatomical points on the body using a variety of techniques. The acupuncture technique that has been most often studied scientifically involves penetrating the skin with thin, solid, metallic needles that are manipulated by the hands or by electrical stimulation. (NCCAM 2011)

It appears the definition of acupuncture is not tied to any alleged mechanism of action. Some definitions mention Traditional Chinese Medicine (TCM) and either directly state or imply that acupuncture works by influencing the flow and balance of chi, or life energy. Such notions are little more than prescientific superstition, so modern proponents are often vague on mechanism or refer to highly speculative and unproven physiological mechanisms. Regardless of any potential mechanism, there are two features that seem to define acupuncture: the existence of specific acupuncture points at various locations on the body and the stimulation of these points by “a variety of techniques,” most commonly inserting thin needles through the skin.

So-called electroacupuncture is very problematic in terms of scientific specificity, because electrical stimulation through the skin has known physiological effects independent of the existence of acupuncture points. Scientific experiments are designed to control for as many variables as possible; only by isolating variables can we say which variable is having which effect. Electroacupuncture mixes variables, making it impossible to separate out the ones specific to acupuncture from the effects of electrical stimulation itself.

Needle insertion also has nonspecific physiological effects independent of any notion of acupuncture, but these are likely minimal, transient, and local. So for the purpose of experimentation, it is reasonable to define acupuncture as the insertion of thin needles into acupuncture points.

Clinical studies into the effectiveness of acupuncture have evolved over recent years, and there have actually been quite a few well-designed studies that adequately isolate these two variables (acupuncture points and needle insertion). For example, many studies compare verum acupuncture (true acupuncture in which needles are inserted into the alleged proper acupuncture points for the condition being treated) to sham acupuncture (in which needles are inserted into the “wrong” locations). These studies overwhelmingly show that needle location does not matter—verum acupuncture is no more effective than sham acupuncture (Moffet 2009; Ernst 2009).

Some trials also control for the variable of needle insertion, using placebo or simulated acupuncture in which opaque sheaths are used and a dull needle is pressed against the skin when the plunger is depressed, but there is no skin penetration. Alternatively, toothpicks have been used to simulate the sensation of acupuncture without going through the skin. Again, when this variable is isolated, it turns out that simulated acupuncture works as well as verum acupuncture. This is true of the largest and best trials of acupuncture for the most common uses, such as reducing back pain (Haake et al. 2007) and treating nausea (Enblom et al. 2011).

Therefore, if we define acupuncture as using needle insertion to stimulate acupuncture points, and the best scientific evidence shows that acupuncture points do not exist (it doesn’t matter where you stick the needles) and needle insertion has no effect (it doesn’t matter whether or not you stick the needles), then does acupuncture work? I think the only reasonable answer is no; there is no reality to acupuncture or the concepts upon which it is based.

If anything can be said to have a measurable effect in acupuncture trials it is the therapeutic ritual that surrounds acupuncture (but not the acupuncture itself). Even these effects are modest and nonspecific—they result from a subjective sense of well-being gained from the kind attention and relaxation that attends the acupuncture ritual.

We have known for decades that a good bedside manner, with some relaxation and encouragement, makes people feel better. This may create the illusion that whatever specific intervention accompanies these nonspecific effects is itself having some effect. That is the very point of scientific experiments: to isolate these variables. And when that is properly done, it becomes increasingly clear that acupuncture (the sticking of needles into alleged acupuncture points) does not work.

References

Enblom A., M. Lekander, M. Hammar, et al. 2011. Getting the grip on nonspecific treatment effects: Emesis in patients randomized to acupuncture or sham compared to patients receiving standard care. PLoS ONE 6(3): e14766. doi:10.1371/journal.pone.0014766.

Ernst, E. 2009. Acupuncture: What does the most reliable evidence tell us? Journal of Pain and Symptom Management. 37(4) (April): 709–14.

Haake, M., H.H. Müller, C. Schade-Brittinger, et al. 2007. German acupuncture trials (GERAC) for chronic low back pain: Randomized, multicenter, blinded, parallel-group trial with 3 groups. Archives of Internal Medicine. 167(17): 1892–98.

Moffet, H.H. 2009. Sham acupuncture may be as efficacious as true acupuncture: A systematic review of clinical trials. Journal of Alternative Complementary Medicine. 15(3) (March):213–16.

National Center for Complementary and Alternative Medicine (NCCAM). 2011. Acupuncture: An Introduction. Available online at http://nccam.nih.gov/health/acupuncture/introduction.htm.

Novella, S. 2010. Modern bloodletting (blog post). Neurologica (July 6). Available online at http://theness.com/neurologicablog/?p=2099.

Ramey, D. 2010. Acupuncture and history: The “ancient” therapy that’s been around for several decades (blog post). Science-Based Medicine (October 18). Available online at www.sciencebasedmedicine.org/?p=7660.

A Brief History of Homeopathy

Homeopathy was invented (it is not accurate to say it was discovered, which would imply it has some basis in reality) by Samuel Hahnemann in the late eighteenth century. Hahnemann developed his principles of homeopathy from anecdote and superstition without any chain of scientific research, evidence, or reasoning. It is therefore no surprise that more than two hundred years later, scientific progress has failed to validate any of Hahnemann’s ideas (House of Commons 2010).

Scientific knowledge builds on itself, and when someone discovers a fundamental property of nature, it leads to further discoveries and a deepened understanding. Homeopathy led to nothing. Hahnemann’s “law of similars” is the notion that “like cures like”—that a small dose of a substance will cure whatever symptoms it would cause in a high dose. This, however, is not based upon anything in biology or chemistry. It is often falsely compared to the body’s response to vaccines, but this is not an apt analogy.

Hahnemann’s “law of infinitessimals,” the notion that a substance becomes more potent when diluted, violates the law of mass action and everything we know about chemistry. Also, many homeopathic remedies are diluted past the point where even a single molecule of the original substance is likely to be left behind. Hahnemann believed that the water retained the magical “essence” of the substance, which makes homeopathy a vitalistic belief system.

Hahnemann’s ideas are sufficiently silly that even at the time, early in the history of science, they were ridiculed and dismissed. Homeopathy remains utterly nonsensical, but it is now much more sophisticated nonsense.

A recent fascination with unscientific health modalities has caused a resurgence of interest in homeopathy, leading to many clinical trials of the effectiveness of homeopathic products for specific ailments. After hundreds of clinical studies of homeopathy, systematic reviews reveal that homeopathic remedies are indistinguishable from placebos (another way of saying that they do not work) (Ernst 2010).

This is not even a scientific controversy—the evidence that homeopathy cannot work and does not work is overwhelming. Only ideology, wishful thinking, and scientific illiteracy keep it alive.

Water Memory

Modern defenders have desperately tried to justify homeopathy with scientific-sounding explanations, but they have failed miserably. One such attempt is the notion that water is capable of having memory—that it can physically remember the chemical properties of substances that have been diluted in it.

The notion of water memory was first raised by French homeopath Jacques Benveniste in 1988. He was not studying the water structure itself, just trying to demonstrate that water can retain the memory of antibodies or other substances diluted in it. His research, however, has been completely discredited due to the many flaws in Benveniste’s methods, his lab’s cherry-picking of data, his improper statistics, and his recounting data points that did not fit their desired results (Scrimgeour 2007).

Materials scientist Rustum Roy, who was enamored with spiritual healing, built upon Benveniste’s discredited research, claiming that water molecules are like bricks—they can be used to build structures that contain greater complexity and information than the bricks themselves. Specifically, water molecules can encode in their structure the chemical properties of what was diluted in them.

However, the evidence does not support this claim. What has been demonstrated is that water molecules form transient bonds with other water molecules, creating a larger ultrastructure—but these water structures are extremely short-lived. They are not permanent. In fact, research shows that water molecules very efficiently distribute energy from these bonds, making them extremely ephemeral. One such research paper concludes: “Our results highlight the efficiency of energy redistribution within the hydrogen-bonded network, and that liquid water essentially loses the memory of persistent correlations in its structure within 50 fs” (Cowan 2005). That’s fifty femtoseconds, or fifty quadrillionths (10^-15) of a second. Contrary to Roy’s claims, water does not hold memory. In fact it is characterized by being extremely efficient at not holding memory. Scientists can argue about whether or not water can display ultrastructure lingering for longer than femtoseconds under certain conditions—but they are arguing over incredibly small fractions of a second.

Recently Nobel Laureate Luc Montagnier has given a boost to the “water memory” hopes of homeopaths by publishing a series of experiments in which he claims that DNA highly diluted in water is able to generate radio signals (Montagnier 2009). There are numerous problems with these studies, however. Prime among them is that Montagnier’s study design is laughably sloppy (see Myers 2011). Montagnier used a crude signal detection device hooked up to a computer and generated worthless noise-ridden results. His studies proved nothing (and, not surprisingly, have not been replicated), but that has not stopped homeopaths from seizing upon his work to claim vindication.

So we are still left with no plausibility and no evidence that water can form ultrastructures for a biologically meaningful amount of time. It is amazing that Roy, Montagnier, and others so enthusiastically extrapolated from the claim that water can hold structures slightly longer than previously believed (itself probably bogus) to the notion that this can explain the biological effectiveness of homeopathy. Let’s take a close look at the nontrivial steps they glossed over.

If this kind of water “memory” is an explanation for homeopathy, then these structures would have to survive not only in a sample of water but through the physical mixing of that water with other water. In fact, they would have to transfer their structure, like a template, to surrounding water molecules. This would need to be reliably repeatable over many dilutions. Then these structures would have to survive transfer to a sugar pill (often homeopathic remedies are prepared by a drop of the water being placed onto a sugar pill).

These water structures would then have to be transferred to the sugar molecules because before long the water will evaporate. This pill will then sit on a shelf for days, months, or years before it is finally consumed by a gullible patient. The sugar pill will be broken down in the homeopathy proponent’s stomach, and the sugar molecules will then be digested, absorbed into the blood stream, and distributed through the blood to the tissues of the body.

Presumably, whatever molecules are retaining this alleged ultrastructure are sticking together throughout all of these processes and finding their way to the target organ in which they are able to have their chemical/biological effect.

Absurd does not even begin to cover the leaps of logic that are being committed here. In short, invoking water memory as an explanation for homeopathic effects just adds more layers of magical thinking to the notion of homeopathy; it wouldn’t offer a plausible explanation even if the theory of water memory was true, which it isn’t.

Some chemical bonds are strong enough to survive this process intact and make it through the body to the target tissue where they can bind to receptors or undergo their chemical reactions. Even most chemicals, however, cannot make it through this biological gauntlet with their chemical activity intact—which is why the bioavailability of many potential drugs is too low for them to be useful as oral agents. The chemicals are simply broken down by the digestive process. In other words, the ephemeral bonds of this alleged water memory—if this fiction of water memory even existed—would have a bioavailability of zero.

Conclusion

The notion that water has memory is nothing more than a restating of Hahnemann’s superstitious notion that substances can transfer their “vital essence” to other substances. Water memory is another fiction of homeopathy; it is not based upon any science and is implausible in the extreme.

References

Cowan M.L., B.D. Bruner, N. Huse, et al. 2005. Ultrafast memory loss and energy redistribution in the hydrogen bond network of liquid H2O. Nature 434 (March 10):199–202. doi:10.1038/nature03383.

Ernst, E. 2010. Homeopathy: What does the “best” evidence tell us? The Medical Journal of Australia 192(8) (April 19): 458–60.

House of Commons, Science, and Technology Committee. Evidence check 2: Homeopathy. Available online at www.publications.parliament.uk/pa/cm200910/cmselect/cmsctech/45/45.pdf.

Myers, P.Z. 2011. It almost makes me disbelieve that HIV causes AIDS. Pharyngula (January 24). Available online at http://scienceblogs.com/pharyngula/2011/01/it_almost_makes_me_disbelieve.php.

Montagnier L., J. Aissa, S. Ferris, et al. 2009. Electromagnetic signals are produced by aqueous nanostructures derived from bacterial DNA sequences. Interdisciplinary Sciences: Computational Life Sciences 1(2): 81–90.

Scrimgeour, H.J. 2007. Water memory tests all wet: A reassessment of the Benveniste experiments by a DVM. Association for Science and Reason (August 8). Available online at www.scienceandreason.ca/pseudoscience/alternativemedicine/water-memory-tests-all-wet/.

Magnetic charms, bracelets, insoles, and braces remain popular and are sold with claims that they improve athletic performance, relieve arthritis pain, increase energy, and pretty much treat whatever symptoms you might have. These products may seem modern and high-tech, but similar devices and claims have been around for centuries.

The notion that magnets can be used for healing has existed since humans discovered them. Several ancient cultures, such as those of Egypt, Greece, and China, discovered natural magnetic rocks, or lodestones. People had a hard time explaining the unusual properties of these rocks given the scientific knowledge of the time, so they came up with fanciful explanations like “minerals have souls too.” This was compatible with the general belief that everything has an “essence.”

It was also observed that this magnetic property can be transferred. Socrates wrote: “That stone not only attracts iron rings, but imparts to them a similar power of attracting other rings; and sometimes you may see many pieces of iron and rings suspended from one another to form quite a long chain; and all of them derive their power of suspension from the original stone” (quoted in Keithley 1999).

It then seemed natural that because living things have an energy and essence, and certain rocks contain an energy and essence, that such rocks could be used to heal illness-to transfer their energy to a living being. Even today, this idea has an emotional and even rational appeal. Who wouldn't want to be healed by the equivalent of McCoy's medical scanner, which non-invasively uses invisible and painless energy fields to return our tissues to health at the cellular level. When we fantasize about future medicine, that is what we imagine. It is no surprise, then, that through the centuries magnetic healing has been very popular-and its popularity has only increased with advancing scientific understanding of magnetism and the eventual discovery of electromagnetism.

The relationship between medical academia and popular marketing hasn't changed in hundreds of years either. In 1600, William Gilbert wrote De Magnete, in which he described detailed experiments with magnets and electricity and systematically disproved hundreds of popular health claims for such treatments. This established debunking of magnetic therapy continued into the seventeenth century with Thomas Browne (Macklis 1993). Considering how primitive scientific methods and medical knowledge were at this time, the claims of magnetic healers must have been especially fantastical and their treatments remarkably worthless.

But “The Man” was not able to keep magnetic healing down. In the eighteenth and nineteenth centuries, Franz Mesmer dramatically increased the popularity of magnetic healing with his “animal magnetism” theory. Mesmer thought that animal magnetism was a unique force of nature that flowed like a fluid through living things. He also thought he could manipulate it through a combination of hypnotism and laying-on of hands. After a high-profile debunking by a commission led by Benjamin Franklin, however, Mesmer's fame faded, and he died poor and forgotten. But his legacy survived-magnetic healing remains very popular to this day.

Today the relationship among magnets, popular health claims, and the medical/scientific community remains the same. The public is fascinated by the notion of healing with electricity, electromagnetic fields, and magnetic energy. The fact that many medical interventions are legitimately based upon electromagnetism increases this interest. People understand that we use magnetic resonance imaging (MRI) to peer into the body. Recent studies indicate the potential for transcranial magnetic stimulation as an effective treatment for migraines (Lipton and Pearlman 2010). We routinely measure electrical (and now even magnetic) brain waves to assess brain function.

Electromagnetism is the real energy of life, and therefore it is very plausible that all sorts of magnetic and electrical interventions will be useful for diagnostic and therapeutic purposes. But this potential also opens up a market for countless quack magnetic devices that exploit this appeal. You can buy what are essentially refrigerator magnets to strap to your elbow or knee or put in your shoe or under your pillow. These static magnetic fields have no demonstrable effect on blood flow or living tissue, and their fields are so shallow that they barely extend beyond the cloth in which they are encased, let alone to any significant tissue depth. The scientific evidence for their efficacy is negative (Pittler et al. 2007). Even more absurd are magnetic bracelets that are supposed to have a remote healing effect on the body. Their plausibility plummets even further.

It is eternally frustrating that scientific evidence and academic acceptance of medical claims seem to have no bearing on the marketing and popular appeal of those claims. This disconnect appears to be especially true of claims for magnetic devices and treatments-and it has survived for centuries.

References

Keithley, Joseph F. 1999. Measurements from the beginning through the Middle Ages. In The Story of Electrical and Magnetic Measurements: From 500 B.C. to the 1940s. New York: IEEE Press. Available online at http://media.wiley.com/product_data/excerpt/30/07803119/0780311930-2.pdf.

Lipton, Richard B., and Starr H. Pearlman. 2010. Transcranial magnetic simulation in the treatment of migraine. Neurotherapeutics 7(2) (April): 204–12.

Macklis, Roger M. 1993. Magnetic healing, quackery, and the debate about the health effects of electromagnetic fields. Annals of Internal Medicine 118(5) (March): 376–83.

Pittler, Max H., Elizabeth M. Brown, and Edzard Ernst. 2007. Static magnets for reducing pain: Systematic review and meta-analysis of randomized trials. Canadian Medical Association Journal 177(7) (September): 736–42.

A recent study looking into the effects of acupuncture on relieving back pain was widely reported in the media as finding that "acupuncture works, even fake acupuncture." Behind the headlines, the authors were more circumspect in the paper itself, concluding:

Although acupuncture was found effective for chronic low back pain, tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits. These findings raise questions about acupunctures purported mechanisms of action. It remains unclear whether acupuncture or our simulated method of acupuncture provide physiologically important stimulation or represent placebo or nonspecific effects. (Cherkin et al. 2009)

The authors compared acupuncture to placebo acupuncture (creating the sensation of acupuncture with toothpicks that do not penetrate the skin) and found no difference. When a drug is compared with a placebo and there is no difference in the response, the standard conclusion is that the drug has no effect--it does not work. But that logic is being turned on its head by what is being called "placebo medicine," in which the placebo effect is seen as a real, valuable, and desired outcome of patient treatment (Novella 2009).

Placebo effects (plural), however, are varied and complex. For the most part they are not a biological response to the expectation of benefit, which is what most people assume. Understanding placebo effects is critical to making sense of medical research and ever-expanding health claims within an increasingly unregulated market.

Operational Definition of Placebo

In the context of research, the "placebo effect" has a very specific operational definition: it is the treatment effect measured in the placebo arm of a clinical trial, which includes those subjects who have received a fake or inert treatment. If a trial is rigorously designed, placebo effects should include everything other than a physiological response to a biologically active treatment. Therefore, we can subtract placebo-effect findings from the treatment group, who will display treatment effects plus placebo effects, and we are left with a measurement of the treatment effect alone.

This simple but effective logic is the cornerstone of medical research. It is necessary because there are a variety of effects that can create the false impression that a treatment is working even when it isn't. It is a mistake to assume that the only relevant false impression is a "mind over matter" effect resulting from belief in the treatment. This is not the case.

Placebo Effects

Placebo effects fall into several categories: illusions of observation, bias, nonspecific effects, and physiological effects. Much of what is measured as a placebo effect is, in fact, simply an illusion of the process of observation. These illusory effects include regression to the mean, which is a statistical phenomenon that includes extreme symptoms becoming less extreme as a matter of course. For any variable symptom, periods of time when symptoms are at their worst are likely, by chance alone, to be followed by a return to more average symptoms.

Other artifacts include the biases of the researchers and the subjects. Researchers want their interventions to work and may therefore bias their assessments to be more positive. Subjects want to receive an effective treatment and to meet the expectations of the researcher. They want to justify their risk, expense (even if its just time), and their decision to receive a treatment or enter a trial. Conditioning, in which one associates a treatment ritual with feeling better, is another related placebo effect.

There are also a number of nonspecific effects, such as the well-documented observer effect (also called the Hawthorne effect), in which the very fact of being observed in a clinical trial results in a change in behavior and reporting (McCarney et al. 2007). People are more likely to be compliant with treatment, take better care of themselves, and get regular medical attention as part of a trial. Related to this is the cheerleader effect: for any functional assessment, people will tend to try harder if they are being encouraged, if they feel they should be doing better, or if they have hope that the treatment is working.

And finally there are real physiological effects resulting from the ritual of treatment. For example, treatment may involve relaxation or simply taking a break from your otherwise hectic daily routine. Believing one is being treated may reduce anxiety about the illness or symptoms, which in turn may reduce sympathetic activity, reduce blood pressure and strain on the heart, and reduce the levels of stress hormones. Hands-on treatments have the benefit of human contact, which improves mood and provides an overall feeling of well-being.

The perception of pain in particular is subject to these nonspecific effects, such as when an improved mood reduces the perception of pain. In addition, conditioning, expectation, and nonspecific benefits may actually cause the release of natural endorphins that reduce pain transmission (Benedetti 2007) or the release of dopamine in the reward centers of the brain (de la Fuente-Fernández and Stoessl 2004).

Breaking It Down

Given this more thorough understanding of placebo effects, it is not reasonable to assume that the measured placebo effect in a clinical trial is mostly or entirely a real "mind over matter" health benefit. Instead, the placebo effect may consist mostly or entirely of illusion and bias. One might ask, "Which kinds of effects are contributing to the measured placebo effect of specific treatments?" The answer is that it depends on what is being treated.

For example, a study of placebo effects in the treatment of irritable bowel syndrome (Kaptchuk et al. 2008) found a substantial placebo effect in place with the use of placebo acupuncture. The same study also found that the enhanced placebo group--members of which received placebo acupuncture with enhanced interaction between the therapist and the subject--reported added "warmth, attention, and confidence." After three weeks, the waiting-list group (those who received no treatment--not even placebo) had about a thirty-point drop on the symptom severity scale, with almost 30 percent of patients reporting adequate relief; the treatment group (those who received placebo acupuncture) had a forty-two-point drop, with 44 percent of patients reporting relief; the augmented group (those who received placebo acupuncture plus enhanced interaction with the therapist) reported a drop of over eighty points, with over 60 percent of patients reporting relief.

It's very interesting that the group that received no intervention, not even a placebo, still had a 30 percent response. This response is likely entirely due to observational artifacts (Hawthorne effect, etc.). The placebo intervention also led to an improved response--in this case, expectation and conditioning might be having an effect. The enhanced intervention group showed the strongest effect, likely representing an increase in the nonspecific benefits of a positive therapeutic relationship.

Hróbjartsson and Gøtzsche have been studying placebo effects for years. They recently reviewed clinical studies that contain a no-treatment arm as a way of measuring placebo effects. They conclude:

We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed. (Hróbjartsson and Gøtzsche 2010)

Let's break this down a bit. First, Hróbjartsson and Gøtzsche found that when you look at any objective or clinically important outcome--the kinds of things that would indicate a real biological effect--there is no discernible placebo effect. That is, there is no "mind over matter" self-healing that can be attributed to the placebo effect.

What the authors found is also most compatible with the hypothesis that placebo effects, as measured in clinical trials, are mostly due to bias. Specifically, significant placebo effects were found only for subjectively reported symptoms. Further, the size of this effect varied widely among trials.

Conclusion

Increasingly, placebo effects are being used to justify the use of ineffective and even inert treatments, with the assumption that "the" placebo effect is a true healing effect. What the research indicates, however, is that there are many placebo effects, and they are mostly bias and illusion--not real effects. There are also nonspecific effects that are likely valuable, but these effects can mostly be categorized as stress reduction and improvement in mood through attention and encouragement. It should be remembered that any placebo effect worth having will also accompany a legitimate treatment that actually works. On close inspection, placebo effects are not a justification for substituting hocus-pocus for real medicine.

References

Benedetti, F. 2007. Placebo and endogenous mechanisms of analgesia. Handbook of Experimental Pharmacology 177: 393-413.

Cherkin, D.C., K.J. Sherman, A.L. Avins, J.H. Erro, L. Ichikawa, W.E. Barlow, K. Delaney, et al. 2009. A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain. Archives of Internal Medicine 169(9): 858-66.

De la Fuente-Fernández, R., and A.J. Stoessl. 2004. The biochemical bases of the placebo effect. Science and Engineering Ethics 10(1): 143-50.

Hróbjartsson, A., and P.C. Gøtzsche. 2010. Placebo interventions for all clinical conditions. Cochrane Database Systematic Review (1): CD003974.

Kaptchuk, T.J., J.M. Kelley, L.A. Conboy, R.B. Davis, C.E. Kerr, E.E. Jacobson, I. Kirsch, et al. 2008. Components of placebo effect: Randomised controlled trial in patients with irritable bowel syndrome. British Medical Journal 336(7651): 999-1003.

McCarney, R., J. Warner, S. Iliffe, R. van Haselen, M. Griffin, and P. Fisher. 2007. The Hawthorne Effect: A randomised, controlled trial. BioMed Central Medical Research Methodology 7: 30.

Novella, S.P. 2009. The rise of placebo medicine. Available online at www.sciencebasedmedicine.org/?p=672.

Wakefield’s paper has already been thoroughly discredited, and subsequent studies have shown convincingly that there is a lack of association between MMR or vaccines in general and autism. For example, one of the key components of Wakefield’s theory is that autism is linked to gastrointestinal disorders in some children, potentially allowing the measles virus from the vaccine to enter the bloodstream and wreak havoc. A replication of Wakefield’s experiment by Mady Hornig was published last September in PLoS ONE (Hornig 2008). Hornig found no correlation between MMR and autism and also did not find the measles virus in the guts of children with autism and GI complaints, directly contradicting Wakefield.

Far larger than the scientific controversy stirred up by Wakefield, which has largely been settled, is the storm of ethical concerns regarding his scientific behavior. In 2004, ten of Wakefield’s co-authors withdrew their names from the original publication, and The Lancet’s editors published a retraction, citing undisclosed conflicts of interest by Wakefield (Lancet 2004). Specifically, Wakefield did not disclose a large consulting fee he received from attorneys representing clients suing over claims that their children’s autism was caused by MMR. In fact, eleven of the twelve children in Wakefield’s study were part of the litigation. Further, nine months prior to publishing the study, Wakefield applied for a patent for a new MMR vaccine that he claimed was safer. He therefore stood to make phenomenal profits from scares over the current vaccine’s safety (Deer 2008).

Investigative journalist Brian Deer has been putting the pieces of the Wakefield puzzle together for several years now. His investigations recently uncovered evidence that Wakefield may also have faked his original data. He writes: “Our investigation, confirmed by evidence presented to the General Medical Council (GMC), reveals that: In most of the twelve cases, the children’s ailments as described in The Lancet were different from their hospital and GP records. Although the research paper claimed that problems came on within days of the jab, in only one case did medical records suggest this was true, and in many of the cases medical concerns had been raised before the children were vaccinated. Hospital pathologists, looking for inflammatory bowel disease, reported in the majority of cases that the gut was normal. This was then reviewed and The Lancet paper showed them as abnormal” (Deer 2009).

Andrew Wakefield remains under investigation by the U.K.’s General Medical Council for ethics violations. He remains unrepentant about his claims and has since moved to America, where he runs the Thoughtful House autism center in Austin, Texas.

References

• Deer, B. 2009. MMR doctor Andrew Wakefield fixed data on autism. Times Online, February 8. Available online.
• —.2008. The Wakefield Factor. Available online at http://briandeer.com/wakefield-deer.htm.
• Hornig, M, T. Briese, T. Buie, M.L. Bauman, G. Lauwers, U. Siemetzki, K. Hummel, P.A. Rota, W.J. Bellini, J.J. O’Leary, O. Sheils, E. Alden, L. Pickering, W.I. Lipkin. 2008. Lack of association between measles virus vaccine and autism with enteropathy: A case-control study. PLoS ONE, September. Available online.
• Editors. 2004. A statement by the editors of The Lancet. The Lancet 363 (9411).
• Wakefield, A.J., S.H. Murch, A. Anthony, J. Linnell, D.M. Casson, M. Malik, M. Berelowitz, A.P. Dhillon, M.A. Thomson, P. Harvey, A. Valentine, S.E. Davies, and J.A. Walker-Smith. 1998. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet 351 (9103):637–41.