Despite the variety of health systems across hundreds of different countries, one feature is near-universal: We all depend on private industry to commercialize and market drug products. And because drugs are such an integral part of our health care system, that industry is generally heavily regulated. Yet despite this regulation, little is publicly known about drug development costs. But aggregate research and development (R&D) data are available, and the pharmaceutical industry spends billions per year.

A huge challenge facing consumers, insurers, and governments worldwide are the acquisition costs of drugs. On this point, the pharmaceutical industry makes a consistent argument: This is a risky business, and it costs a lot to bring a new drug to market. According to PhRMA, the U.S. pharmaceutical industry’s advocacy group, it cost $1.3 billion (in 2005 dollars) to bring a new drug to market. The industry argues that high acquisition costs are necessary to support the multi-year R&D investment, and considerable risks, in to meet the regulatory requirements demanded for new drugs.

But what goes into this $1.3 billion figure? To understand the cost of a new drug, we need to consider both the cost of drugs that were marketed, but also factor in the costs of the failures – those discontinued during development. While most pharmaceutical companies are publicly held, no company produces detailed breakdowns of “per marketed drug” R&D costs, or the specific amounts spent on drugs that were later abandoned. Yet there have been attempts to estimate these values. The most detailed and perhaps controversial paper is a 2003 paper from DiMasi et al, entitled, The Price of Innovation: New Estimates of Drug Development Costs.[PDF] DiMasi’s estimates has been subject to considerable criticism, most recently in a paper by Light and Warburton, entitled Demythologizing the high costs of pharmaceutical research. They claim the median R&D cost is a fraction of DiMasi’s estimate: Just $43.4 million. “Big Pharma lies about R&D to justify illicit profits” shouted Natural News. Who’s right?

Drug Development
Drugs can be developed in different ways, but the usual model used describes a series of phases. The pre-clinical development stage constitutes preliminary studies of chemicals that have been synthesized or isolated, and are then screened. This process can take years: Identifying promising leads, validating them, tweaking with their chemical structures, and conducting endless in vitro studies. Only a fraction of drugs that show promise in pre-clinical studies will every progress to clinical trials. Clinical trials are generally grouped into three stages, each one representing an important milestone in a drug’s development. Phase I studies are small studies in healthy volunteers designed to help understand the basic pharmacology and pharmacokinetics in humans: how a drug is absorbed, distributed, metabolized, and eliminated. It’s in Phase II that the drug is tested in groups with the condition of interest. These trials are larger, and may be randomized, with multiple arms, possibly evaluating different dosing regimens. Endpoints are usually related to basic efficacy and safety parameters. Phase III studies are the largest studies, that may be randomized and double-blind, in order to establish a drug’s efficacy against a given condition. Regulators like the FDA will usually require one or more Phase III trials to support an approval to market a drug. In cases where real outcomes need to be measured (like mortality or morbidity), phase III studies can be massive. (Like this one, with over 18,000 participants!).

While the trial pathway is usually illustrated as a straight-line path, that’s a post hoc view: A tree may be a more appropriate model. Clinical trials may be conducted in different doses, treating different patient groups, using different protocols, in order to understand a drug’s effectiveness.

At any one time, multiple drugs may be in development, so only the most promising products may move forward in the development pathway, as subsequent phases of development mean a significant increase in costs. A drug’s development can be discontinued at any point along the path. Developers may identify toxicity issues, or lack of effectiveness issues. Or clinical practice may change, and all of a sudden, the clinical trials are measuring the wrong endpoints in the wrong patients. Decisions are always made in the face of uncertain evidence about efficacy and toxicity, and for every drug that moves forward that is eventually found to fail, it could be that there is an effective drug that didn’t reveal itself as promising, and went back on the shelf.

The development process is laborious and typically takes several years from discovery to clinical trials. The pharmaceutical industry estimates that it takes 10,000 molecules developed to bring a single drug to market. Without validating that number (a whole other post), it’s fair to say that the number of drugs that make it to market is a tiny fraction of the number of products identified or synthesized that enter initial screening. So there will be a substantial investment into drugs that never make it to market. Without including the cost of abandoned drugs into the costs of drugs that are marketed, we’d be underestimating the investment incurred. So any analysis needs to consider this cost, too.

The DiMasi Paper

The DiMasi paper, from the Tufts Center for the Study of Drug Development is the most widely cited paper on drug development costs. While the methodology they use is described in detail, some  essential information is unfortunately (though perhaps understandably) opaque. The authors used a sample of drug costs drawn from ten companies that volunteered (out of 24 that were asked) that were willing to provide R&D data on a per-chemical basis. Data were collected, and stratified by development phase. Only the costs of self-originated drugs (i.e., they developed the drug themselves) were included. In total, data on 68 products were collected, and the sample consisted of mostly small-molecule drugs, but also included four recombinant proteins, two monoclonal antibodies, and one vaccine. No further information is provided, so there’s no way to know just how representative this sample is.

The methodology for the different calculations is fairly well detailed, but as I noted, the underlying data are not provided. Whether this basket of drugs studied represents a fair measure of the market is impossible to determine. The authors compiled actual costs wherever possible, broken down by development phase. A notable exception is the “preclinical” development period where it’s difficult to draw a direct link between expenditures and a specific drug that ends up being commercialized. For this segment, they inferred, using their own database, costs of $121 million per approved new drug.

To account for the costs of drugs that were abandoned (for any reason) during development, the authors used their own database of investigational drugs to estimate the odds any given new drug would reach a particular development milestone. Setting aside a detailed analysis of the methodology, let’s look at the two biggest cost drivers of the final that have been subject to repeated criticism: Tax issues, and the cost of capital.

Tax Issues
A major criticism of the DiMasi paper has been that the preferential taxation provisions for R&D expenses have not been factored into the analysis. Essentially, if R&D costs are given preferential tax treatment, this should reduce the net cost of R&D to the company. I have no particular insight into this issue other than to flag it as one that has caused controversy. Given preferential treatment of R&D expenses isn’t unique to the pharmaceutical sector, the extent to which this biases the validity of this particular analysis isn’t clear to me.  But I’m a pharmacist, not a tax expert.

The Cost of Capital
Probably the biggest criticism of the DiMasi paper is that the authors factor in what’s called the cost of capital into the development cost. Looking at the calculations, DiMasi estimated the out-of-pocket costs per new drug at $403 million (2000 dollars). But this is then capitalized, based on the opportunity cost of that investment – at 11%, bringing the “total” cost up to $802 million. Adjusting this cost to 2005 dollars, and we’re at the $1.3 billion that PhRMA is calling “the average cost to develop one new drug.”

The cost of capital can be a bit baffling to understand. If I’m going to invest my money in something now, with a possible payoff down the road, I need to factor in the opportunity cost of something else I could have invested in – but decided not to. It is a true cost, because by choosing to invest in one thing, you’re forgoing the investment in another.

DiMasi uses a cost of capital of 11% – that is, they assumed that the drug developers, by moving forward with the development of a drug, where forgoing investments which would be expected to yield 11%. Is 11% valid? From a personal investment perspective, 11% seems rich. But the cost of capital that companies use is dependent on the risk involved. Different industries have different business risks.  The DiMasi paper bases the 11% estimate based (in part) on historic returns in the industry. Given that half of the reported “cost” of a new drug is based on the cost of capital, the value we use use has a massive influence on what the final “cost” of a new drug will be.  But is 11% appropriate? Many argue no – that current returns don’t match past returns, and therefore the CoC should be lower. I took a look at a cost of capital table created by Aswath Damodaran, a Professor of Finance at the Stern School of Business at New York University. He calculates that pharma’s cost of capital is 8.59%. But there is no single “right” answer here. It’s an assumption that goes into our calculation.

Other Reviews
Other authors have made their own attempt at estimating the cost of a new drug. Paul Adams of the Federal Trade Commission, writing in Health Economics estimates that the DiMasi estimate is low, and the 2003 cost is closer to $1 billion per new drug, but noted there is significant variation between products. A 2006 Congressional Budget Office report on drug development [PDF] largely supports the DiMasi estimates. Most recently, Light and Warburton argued that, “based on independent sources and reasonable arguments, R&D costs companies a median of $43.4 million per new drug, just as company supported analysts can conclude they are over 18 times larger, or $802 million.” This figure seems implausibly small, given a single clinical trial can involve hundreds to thousands of patients. (For a more detailed critique of the Light and Warburton paper, I’ll refer the interested reader to Derek Lowe’s excellent In the Pipeline blog (and its comments) where it was dissected in detail here and here.) One of the best ways to contemplate the costs and calculations is to manipulate the numbers yourself: There’s a model developed by venture capitalist Bruce Booth, where you can enter your own estimates and see what cost it spits out. I tried working with the model for a while, and I couldn’t get it anywhere near $43 million – it was always in the hundreds of millions.

Other considerations
One important factor that isn’t considered in any of these analyses (from what I can see) are the costs of new indications for existing chemical entities. Consider the case of cancer drugs, where drugs are often approved for the treatment of metastatic disease, and only after efficacy is demonstrated, is it studied as a potential “adjuvant” treatment for early stages of disease. Additionally, the DiMasi analysis only looked at drugs developed solely in-house. Given the growing role of smaller biotech companies that develop, and then sell, promising drugs to pharmaceutical companies, the impact on costs isn’t clear. In contrast, the cost of the “me-too” drugs that seem to fill the pharmaceutical marketplace aren’t discussed explicitly, either. When your new drug is a variation on a competitor’s (or your own) product, how does this influence overall R&D expense? Again, it’s not clear.

Conclusion
Is the $1.3 billion new drug a myth? New drugs could be hitting, or even exceeding this mark – it depends on what your assumptions are. When we try to summarize all the variables of drug development into a single number, accounting for the hits and the misses, we can end up with a number that sounds impressive. But is it meaningful? Without transparency, only the manufacturer will know what it cost for their own drugs. It’s probably more important to understand the key drivers of R&D costs, noting that there are a huge number of variables that may influence the final cost of bringing a new drug to market.

A recent US News and World Report article on the incorporation of complementary and alternative medicine (CAM) into US medical schools credulously repeats the pro-CAM marketing hype. There is no evidence that the author, Meryl Davids Landau, spoke to a single critic of CAM, or is even aware that such criticism exists. The result looks more like marketing copy than serious journalism.

She begins:

Now that nearly 40 percent of American adults swear by some form of complementary and alternative medicine, or CAM—from nutrition and mental relaxation to acupuncture, magnet therapy, and foreign healing systems like traditional Chinese medicine and Indian ayurveda—a growing number of medical schools, too, are supplementing medication with meditation.

There is much to deconstruct just in this first paragraph. The entire article in an argument from popularity. This is a game the pro-CAM community has been playing for years. People are using CAM because it’s popular; medical schools should teach it because people are using it; the government should research it because of all the interest in it; and CAM should be popular because it’s being researched and taught in medical schools. CAM is like Paris Hilton – famous for being famous.

What’s missing from this circular argument for popularity is evidence that any particular CAM modality actually works, or even has scientific plausibility or the potential to teach us something new about the human body and healing.

The argument is not only fallacious – it’s wrong, or at least highly deceptive. This stems from the core fallacy of CAM, and that’s the very concept of CAM itself. It is a false category, which does not describe any cohesive philosophy or approach to medicine but rather exists solely as a marketing ploy to carve out a double standard – to exempt certain modalities from the rigors of science, evidence, and logic. This false dichotomy results in lumping a wide variety of treatments under one umbrella, and then claiming that the entire category is popular.

When we look a little closer at the numbers we find that the vast majority of so-called CAM use in the US is either massage (16%), chiropractic or osteopathic manipulation (21.9%), and yoga (9.5%). (There is overlap in use so you can’t simply add these percentages, but the vast majority of the mythical “40%” figure comes from these categories.) So some form of exercise, stretching, or muscle manipulation accounts for the vast majority of CAM use. Throw in some other modalities that are not really CAM, like relaxation and nutrition (since when has the science of nutrition been alternative to science) and that accounts for even more.

What’s left for the real hardcore CAM modalities like homeopathy and acupuncture? Not much. These modalities have been languishing in the single digits and not significantly increasing. But by lumping them in which relaxation and massage you can generate the false impression that the whole category is popular. The entire exercise is intellectually sloppy and deceptive – by design. And this deception is being used to convince medical schools that “CAM” deserves access to the limited resources of the school, which is then used to convince patients that it’s legitimate (more circular reasoning).

And we’re just at the first paragraph. She continues:

Interest in teaching alternative approaches “has exploded, especially this last year,” says Laurie Hofmann, executive director of the Institute for Functional Medicine, which is based in Gig Harbor, Wash. The nonprofit institute educates healthcare professionals to look for underlying systemic imbalances as a cause of illness rather than focus on treating symptoms and, when possible, to correct with lifestyle changes and mind-body techniques.

No evidence is offered for this alleged “explosion” in interest. What’s missing from the article is any mention of the Bravewell Collaboration – a funding organization that pays medical schools to open up CAM centers. This is part of a very deliberate “quiet revolution” that Wally Sampson has written extensively about, an attempt to change the practice of medicine by influencing medical education (rather than through compelling evidence).

Landau then repeats, without the slightest hint of journalistic skepticism, the claim that “integrative” medicine looks for underlying causes of illness, while mainstream medicine simply treats the symptoms. This is pure CAM marketing mythology, having no basis in reality. Science-based medicine is built upon a systematic attempt to understand the underlying cause of illness. Of course, when scientific medicine searches for underlying causes this is denigrated by CAM proponents are “reductionist.” When they do it, it’s “holistic.”

The difference between the scientific approach and the typical CAM approach is that science is based in reality. It slowly builds a knowledge base that is internally consistent. Whereas most CAM modalities are philosophy-based – they are based on pre-scientific superstitious notions of health and illness that have not been subjected to any kind of systematic study, or that have been left behind by scientific advance (such as the notion of life energy). These philosophies are often mutually exclusive, which doesn’t seem to bother the “big tent” CAM movement. In the end, the alleged underlying “imbalances” sought for by CAM practitioners are illusory and not based in reality. That doesn’t stop them from being smug in their dismissal of scientific medicine.

What follows is a long list of medical schools integrating nonsense into their curriculum – as if this is a good thing. Landau admits that many medical schools find it difficult to find time in their busy curriculum for CAM teaching. This is because there is a large body of medical knowledge that needs to be crammed into four years of medical school. At Yale where I teach every department is clamoring for one more hour here or there to teach their material. There just isn’t enough time, and we have to be creative in maximizing classroom time for the students. This just highlights the importance of not wasting this limited resource teaching the fads of the day.

This gets to the deeper question that is not even addressed in the article – what is the responsibility of academic medicine in determining the standards that should be followed in medical education? Medical schools are being offered what are essentially bribes, and are being told that CAM is popular as reasons to spend precious time teaching (often really promoting) CAM. This is often accomplished without open debate and discussion, and many faculty members are shocked to find out what is going on in their own institution (quiet revolution indeed). But isn’t it the responsibility of medical schools to maintain high standards of science and academia, to resist the forces of pseudoscience, sectarian beliefs, and popular culture? Perhaps I am being too idealistic.

In the end Landau’s article was devoid of any serious discussion of the actual issues. The result was a propaganda piece (intentional or not) for the sectarian beliefs and economic agenda of CAM, at the expense of academic integrity.

Before we had EBM (evidence-based medicine) we had another kind of EBM: experience-based medicine. Mark Crislip has said that the three most dangerous words in medicine are “In my experience.” I agree wholeheartedly. On the other hand, it would be a mistake to discount experience entirely. Dynamite is dangerous too, but when handled with proper safety precautions it can be very useful in mining, road-building, and other endeavors.

When I was in med school, the professor would say “In my experience, drug A works better than drug B.” and we would take careful notes, follow his lead, and prescribe drug A unquestioningly. That is no longer acceptable. Today we ask for controlled studies that objectively compare drug A to drug B. That doesn’t mean the professor’s observations were entirely useless: experience, like anecdotes, can draw attention to things that are worth evaluating with the scientific method.

We don’t always have the pertinent scientific studies needed to make a clinical decision. When there is no hard evidence, a clinician’s experience may be all we have to go on. Knowing that a patient with disease X got better following treatment Y is a step above having no knowledge at all about X or Y. A small step, but arguably better than no step at all.

Experience is valuable in other ways. First, there’s the “been there, done that” phenomenon. Older doctors have seen more: they may recognize a diagnosis that less experienced doctors simply have never encountered. My dermatology professor in med school told us about a patient who had stumped him: she had an unusual dermatitis of her hands that was worst on her thumb and index finger. His father, also a doctor, asked her if she had geraniums at home. She did. She had been plucking off the dead leaves and was reacting to a chemical in the leaves. The older doctor had seen it before; his son hadn’t.

Then there’s what we loosely call “intuition.” It can be misleading, but it can also be a function of pattern recognition that has not risen to the level of conscious awareness. Experience can help us perceive that “something just isn’t right” about a patient or a working diagnosis. An experienced doctor may get a feeling that a patient might have a certain disease. He couldn’t justify his hunch to another doctor, but he has subconsciously recognized a constellation of findings that were present in other patients he has seen. Of course, he would still need to do appropriate tests to confirm the diagnosis, but he might do more tests and do them sooner than a less experienced doctor. This kind of pattern recognition has been called the “Aunt Tillie” phenomenon: you can spot your Aunt Tillie’s face in a crowd, but you couldn’t tell someone else how to do it. You just know Aunt Tillie when you see her. Computer face recognition is learning how to do this, but it uses measurements, not the gestalt method our brains use.

Then there’s the wisdom that (sometimes) comes with age. I’ve just been reading Marc Agronin’s book How We Age where he shows that old age is not all bad. As we get older, we are not able to accomplish mental tasks as fast, and our short-term memory declines; but there are compensations. We are more able to integrate thinking and feeling, less likely to get carried away by emotions, better able to see both sides of an issue, and better able to cope with ambiguity. We can develop more patience, acceptance, tolerance, and pragmatism in dealing with complex situations. We have a vast store of life experiences to bring to the table, helping us put things into a more realistic perspective. Wisdom is elusive: not every elder develops it. I’m sure you can all think of many counterexamples.

Medicine is an applied science, and the same science can be applied in different ways by different doctors. There are times when two science-based doctors can look at the same body of evidence and still disagree about what it really means or about what to do for a specific patient. There is room for disagreement and for different approaches. Scientific medicine is often criticized for focusing on the disease rather than on the person who has the disease. I have known patients who have turned to alternative providers because of a bad experience with a science-based doctor’s poor communication skills or “bedside manner.” We can aspire to a kinder, gentler, more personal science-based medicine where experience and improving people skills are integrated with science (a kind of “integrative medicine” that actually makes sense.)

It’s not clear whether you are better off with a young doctor or an older one. A young doctor is more likely to be up to date on the latest science; an older doctor might make better patient-centered decisions. A younger doctor might be better at tuning up your bodily vehicle; an older one might be better at helping you decide when to drive it, where to go, and how fast. A young doctor might offer the latest treatment; an older one might question whether it is really preferable to an older treatment for that particular individual, or even question whether any treatment is really necessary at all.

Conclusion:

In summary, while “in my experience” claims can be dangerous, experience does have a role to play in science-based medicine.

Disclaimer:

As an ORF (Old Retired… something) and a Medicare-card-carrying senior citizen, I am biased. I have a vested interest in thinking that I have improved with age and experience. This is an opinion piece and I can’t cite any controlled studies to support my opinions. I’m almost tempted to insert tongue firmly into cheek and say “Trust me; I’m a doctor.”

“Personalized medicine.” You’ve probably heard the term. It’s a bit of a buzzword these days and refers to a vision of future medicine in which therapies are much more tightly tailored to individual patients than they currently are. That’s not to say that as physicians we haven’t practiced personalized medicine before; certainly we have. However it has only been in the last decade or so that our understanding of genomics, systems biology, and cell signaling have evolved to the point where the vision of personalized medicine based on each patient’s genome and biology might be achievable within my lifetime.

I was thinking about personalized medicine recently because of the confluence of several events. First, I remembered a post I wrote late last year about integrating patient values and experience into the decision process regarding treatment plans. Second, a couple of months ago, Skeptical Inquirer published an execrably nihilistic article by Dr. Reynold Spector in Skeptical Inquirer in which he declared personalized medicine to be one of his “seven deadly medical hypotheses,” even though he never actually demonstrated why it is deadly or that it’s even really a hypothesis. Come to think of it, with maybe–and I’m being very generous here–one exception, that pretty much describes all of Dr. Spector’s “seven deadly medical hypotheses”: Each is either not a hypothesis, not deadly, or is neither of the two. Third, this time last week I was attending the American Association for Cancer Research (AACR) meeting in Orlando. I don’t really like Orlando much (if you’re not into Disney and tourist traps, it’s not the greatest town to hang out in for four days), but I do love me some good cancer science. One thing that was immediately apparent to me from the first sessions on Sunday and perusing the educational sessions on Saturday was that currently the primary wave in cancer research is all about harnessing the advances in genomics, proteomics, metabolomics, and systems and computational biology, as well as the technologies such as next generation sequencing (NGS) techniques to understand the biology of each cancer and thereby target therapies more closely to what biological abnormalities drive each cancer. You can get an idea of this from the promotional video the AACR played between its plenary sessions:

Which is actually a fairly good short, optimistic version of my post Why haven’t we cured cancer yet? As I mentioned before, with this year being the 40th anniversary of the National Cancer Act, as December approaches expect a lot of articles and press stories asking that very question, and I’m sure this won’t be the last time I write about this this year.

“Personalized medicine” in CAM

In the meantime, before I discuss a couple of examples of how science-based medicine is moving ever more closely to personalized medicine, I can’t help but note that part of what inspired this bit of my typical blather on this topic was sitting in the audience at AACR hearing about all these tour de force genomic analyses that begin to reveal the individuality and complexity of tumors, and, more importantly, to suggest strategies to target the specific abnormalities that drive the growth and metastasis of each cancer and contrasting in my mind the claims of “personalized” or “individualized” medicine that practitioners of “complementary and alternative medicine” (CAM) and “integrative medicine” (IM) like to make. As I pointed out about a year ago, “individualized” treatment in CAM-world basically means “making it up as you go along.” Consider, for example, homeopathy, which postulates prescientific ideas for the cause of disease, claiming that “like cures like,” and then using unscientific “provings” to determine which remedies can be used to “treat” each condition. Never mind that homeopathy is water (does it really need to be repeated?), consisting of remedies serially diluted and succussed so many times that in many of them it is highly unlikely that there is a single molecule of remedy left in the concoction. Not only that, but one of the most popular homeopathic remedies for flu consists of basically the ground-up liver and heart of a Muscovy duck.

In CAM-world, “personalization” or “individualization” means “making it up as you go along.” A good example of this is a post on that wretched hive of scum and quackery, The Huffington Post, by Dr. Mark Hyman, he of “functional medicine” fame, where, under a section entitled “Treating individuals, not diseases” he writes:

There is no effective known treatment for dementia. But we do know a lot about what affects brain function and brain aging: our nutrition, inflammation, environmental toxins, stress, exercise, and deficiencies of hormones, vitamins, and omega-3 fats.

It is not just one gene, but the interaction between many genes and the environment that puts someone at risk for a chronic disease such as dementia. And we know that many things affect how our genes function — our diet, vitamins and minerals, toxins, allergens, stress, lack of sleep and exercise, and more.

Hyman then goes on to describe an anecdote of a man with developing dementia. Typical of many CAM doctors, Dr. Hyman chased down all sorts of “abnormalities,” prescribed all sorts of supplements to “fix” those abnormalities, and subjected the man to various “detox” regimens, including unspecified “medications that helped him overcome his genetic difficulties by getting rid of toxins.” As Steve Novella pointed out at the time, in reality what Dr. Hyman was doing was a “bait and switch,” in which he extrapolates from preliminary results in real science and uses them to come up with proposed treatments that have not been validated for the purposes that he uses them for. His evidence for success? Not science, not clinical trials, not even preclinical data, that’s for sure. Instead Dr. Hyman presents a couple of anecdotes.

Indeed, much of this sort of “making it up as you go along” is on full display in the anti-vaccine movement. Indeed, the anti-vaccine crank blog Age of Autism has numerous examples of just this sort of “personalization,” including the hijacking of mitochondrial disorders as a predisposing factor for “vaccine injury” causing autism, the serial use of all manner of “biomedical quackery” to “recover” their children, up to and including stem cells, and de facto unethical experimentation on autistic children. Be it chelation therapy, supplements, hyperbaric oxygen, dubious stem cell therapies, and other quackery, the anti-vaccine movement, “biomedical” quacks “individualize” their treatments to each autistic children, using dubious labs like Doctor’s Data to come up with lab abnormalities to “treat.” Of course, there is a fundamental disconnect between the claims of DAN! doctors to “individualize” therapy to each patient with their unwavering belief that vaccines cause autism. No matter how much they try to hide it, vaccines remain The One True Cause of the conditions known as autism and autism spectrum disorders.

There are many, many more examples of this kind of “personalization” of medicine in CAM based on either no science or unjustified extrapolation from existing science, dubious lab tests, practitioner biases, and a veritable panoply of One True Causes of disease. So let’s contrast with evolving personalized medicine in science-based medicine.

Personalized medicine in SBM

Because I’m a cancer researcher and surgeon, I find that currently the most promising examples of how genomics can contribute to personalized medicine come from cancer. This should not be surprising, because cancer is not one disease. It’s hundreds, perhaps thousands, of diseases, and even cancers arising from the same cells in the same organ can have very different biology. Basically, as I put it before, stealing liberally from The Hitchhiker’s Guide to the Galaxy, Cancer is complicated. You just won’t believe how vastly, hugely, mind-bogglingly complicated it is. I mean, you may think it’s complicated to understand basic cell biology, but that’s just peanuts to cancer. This point was driven home in the AACR video above, and I see it driven home with each new study of cancer genomics or heterogeneity that comes out in high impact journals every month.

For example, couple of months ago, I described a tour de force study of changes that occur in the genome of prostate cancer cells compared to normal prostate. The study demonstrated a number of alterations in the genome affecting molecular pathways that drive growth and metastasis and that could potentially be targeted for therapy. Then, not long before going to the AACR meeting, I came across this article in my news feed, Lung Cancer Evolves With Treatment, Study Finds, which refers to this study from Harvard by Sequist et al, Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors. The study itself demonstrates something we’ve known for quite some time, which is that tumor cells evolve under selection by various modalities used to treat them. In this case, the authors studied how non-small cell lung cancer (NSCLC) evolves resistance under treatment with drug therapy targeted to the specific mutation driving their growth. In this case, the gene in which mutations result in its being turned on is the epidermal growth factor receptor (EGFR), and the targeted therapy consists of inhibitors of EGFR such as gefitinib (brand name: Iressa) or erlotinib (brand name: Tarceva). Basically, the investigators subjected tumor tissue from patients who had developed resistance to EGFR tyrosine kinase inhibitors to systematic genetic and histological analysis. What they found represented a confirmation of some known genetic changes that occur to result in resistance but also some unexpected changes, including:

All drug-resistant tumors retained their original activating EGFR mutations, and some acquired known mechanisms of resistance including the EGFR T790M mutation or MET gene amplification. Some resistant cancers showed unexpected genetic changes including EGFR amplification and mutations in the PIK3CA gene, whereas others underwent a pronounced epithelial-to-mesenchymal transition. Surprisingly, five resistant tumors (14%) transformed from NSCLC into small cell lung cancer (SCLC) and were sensitive to standard SCLC treatments. In three patients, serial biopsies revealed that genetic mechanisms of resistance were lost in the absence of the continued selective pressure of EGFR inhibitor treatment, and such cancers were sensitive to a second round of treatment with EGFR inhibitors. Collectively, these results deepen our understanding of resistance to EGFR inhibitors and underscore the importance of repeatedly assessing cancers throughout the course of the disease.

Or, as Dr. Lecia Sequist, lead author of the study, put it:

“It is really remarkable how much we oncologists assume about a tumor based on a single biopsy taken at one time, usually the time of diagnosis,” lead author Dr. Lecia Sequist said in an MGH news release. “Many cancers can evolve in response to exposure to different therapies over time, and we may be blind to the implications of these changes simply because we haven’t been looking for them.”

“Our findings suggest that, when feasible, oncogene-driven cancers should be interrogated with repeat biopsies throughout the course of the disease,” Sequist said. “Doing so could both contribute to greater understanding of acquired resistance and give caregivers better information about whether resumption of targeted therapy or initiation of a standard therapy would be most appropriate for an individual patient.”

Now, that would be personalized medicine, based on science, in marked contrast to what passes for “personalized” medicine in CAM.

Another cancer for which new findings in genomics and systems biology hold great promise is the cancer I spend most of my time treating and researching, breast cancer. Current methods to predict prognosis and guide treatment are crude and include stage as measured by volume of the primary tumor; presence and number of lymph node metastases; presence or absence of distant metastases; tumor grade as measured histologically; expression or lack of expression of important hormone receptors such as estrogen receptor (ER) and progesterone receptor (PR); and amplification of ErbB2 (HER2). Used together, these factors allow, albeit roughly, a degree of prediction of prognosis, as well as of personalization of therapies such as hormonal treatments (tamoxifen or aromatase inhibitors) or agents targeted at HER2 (trastuzumab). Aromatase inhibitors had not yetbecome widely available, and Herceptin (trastuzumab) had been FDA-approved for women with HER2-positive metastatic cancer but not yet for the adjuvant therapy of women with earlier-stage HER2-positive breast cancer. (That did not come until 2006, and then only with chemotherapy.) Then, in 2000, Perou et al published a classic paper in Nature that used then state-of-the-art cDNA microarrays to divide breast cancers into subtypes based on gene expression patterns, which, based on this work and work done since then, currently include normal-like, basal-like, luminal (A and B), and HER2(+)/ER(-), and there is a growing body of literature (for example, this study) that suggests that these different subtypes respond differently to different chemotherapy and targeted agents.

We learned many things from this work, which has accelerated over the last decade. For example, we now know that there are several intrinsic groups of breast cancer based on the patterns of gene expression they exhibit, and these groups subdivide many of the “classic” divisions we have been using for at least two decades, such as ER(+) or ER(-). More importantly, there is one form of breast cancer that expresses none of these markers. Dubbed “triple negative breast cancer” (TNBC), this form of breast cancer is defined as expressing neither ER, PR, nor HER2. TNBC is a close relative of a type of breast cancer categorized a decade ago through gene expression profiling and dubbed “basal-like” (synonymous terms include “basal-type,” “basal-epithelial phenotype,” “basal breast cancer,” and “basaloid breast cancer”). For the most part, currently the same treatments are used for TNBC and basal-like breast cancer because the sine qua non of TNBC is that there are no known molecular targets in this breast cancer subtype, while non-TNBC basal-like breast cancer tends to express HER2 and thus be susceptible to Herceptin. Because TNBCs do not respond to drugs targeting ER or HER2, cytotoxic chemotherapy is currently the only option for adjuvant or neoadjuvant therapy in women with operable TNBC or for systemic treatment for metastatic disease. Paradoxically, TNBCs are more sensitive than ER(+) luminal tumors to standard chemotherapy regimens, but unfortunately this increased chemosensitivity does not translate into prolonged overall or disease-free survival. Consequently, the identification of new molecular targets or oncogene signatures that can be targeted for therapy, either with new agents and/or of new synergistic combinations of old agents, is a critical problem to be overcome for TNBC. Tantalizing hints of how this might be done arose at AACR, for example, this study in which the genomes of 50 breast cancers were sequenced.

Another area in which genomics might assist us as clinicians in breast cancer is through answering a rather vexing question regarding racial disparities in cancer outcome. For example, although the incidence of breast cancer among premenopausal African-American women is lower than among Caucasian women, African-American women are more likely to die from their disease, with a breast cancer-specific mortality of 33 per 100,000 and five year survival of 78% compared to 23.9 per 100,000 and 90%, respectively, for Caucasians. Breast cancer among African-American women tends to be characterized by higher grade, later stage at diagnosis, and worse survival, even after controlling for age and stage. Although it is true that the causes of these observed differences are likely to be multifactorial and include socioeconomic factors, such as differences in access to screening and treatment, there also appear to be biological differences in breast cancer in AA women. Indeed, evidence supporting biological differences as a major part of the explanation for these observed racial disparities was reported from the Carolina Breast Cancer Study. This study reported that that the TNBC/basal-like breast cancer subtype is nearly three times more common among premenopausal African-American women than among Caucasian women In marked contrast, the HER2(+)/ER(-) subtype did not vary appreciably with race or menopausal status, and the less aggressive ER(+) luminal A subtype was less prevalent in premenopausal African-American women. These results suggest that two questions remain open: (1) whether there is a difference in breast cancer biology that drives the tendency of young AA women to develop TNBC at a much higher rate than Caucasian women and (2) whether these biological differences, if they exist, can be exploited therapeutically to develop personalized regimens targeted at patients’ individual tumors. These are the sorts of questions that genomics can potentially answer and personalized medicine be based upon.

Don’t get me wrong. We are not yet near true personalized medicine for breast cancer. Indeed, if you want to get an idea of the challenges that remain, several of the talks I attended are available for free at the AACR website. Talks that are worth watching include:

• Harold Varmus, New Directions in Cancer Research
• Lynda Chin, Translating cancer genomics: From discovery to medicine (unfortunately, nearly none of the slides from this talk have been made available)
• Waun Ki Hong, The landscape of cancer prevention: Personalized approach in lung cancer
• Andrea Califano, A systems biology approach to integrative cancer genomics (Another one without slides.)

There are many others, but unfortunately most of the relevant talks are either not posted yet, require payment, or both. It’s annoying to me, but on the other hand I understand that it costs money to produce these and put them up on the web. Still, the sheer number of talks on The Cancer Genome Atlas, which goes by the annoyingly cutesy acronym TCGA, is telling. Every day, or so it seemed, there were multiple talks on TCGA, reporting findings, telling investigators how to access the data on its website, and discussing the progress. Basically, TCGA is becoming a repository of genome sequences of many cancers, a resource that can be mined. It’s not too hard to envision that one day, when it has many thousands of cancer genomes stored away from before and after treatment, its database might serve as the basis for computer algorithms that compares a patient’s tumor genome to the database and comes up with a list of recommended treatments.

Unfortunately, the move towards personalized medicine not without its share of opportunists and companies selling kits based on genetic tests that either haven’t been validated in clinical trials sufficiently to support their clinical use, for example Anne Wojcicki of 23andMe, whose pitch is has a lot more in common with “health freedom” arguments than it does with actual scientifically validated uses of genomic data, complete with heavy promotion in various social media. It’s a trait shared with enthusiasts of direct-to-consumer genetic testing, whose language really does harken to that of the “health freedom” movement. For example, compare this post with this post by Mike Adams, and the main difference you’ll find in the arguments will be in degree, not kind. It’s “health freedom” all around. Even while promoters, in a fit of cognitive dissonance, simultaneously accuse physicians of paternalism on this issue and admit that the burgeoning personal genomics industry needs to be “purged of scammers and bottom feeders,” it’s an effort designed to create an army of people who “will go nuts” at any attempt by legislators to legislate direct access to personal genomic data or regulatory agencies to control more tightly access to direct-to-consumer genetic testing. As Harriet Hall put it correctly, when it comes to routine genomic testing, we’re not there yet, not the least of which because, as Scott Gavura has pointed out, there are lots of problems with the testing. As I put it, much of the promotion of personal genomic testing is disturbingly similar to the promotion of various autism “biomedical” therapies by DAN! doctors or Dr. Hyman’s panoply of woo to which he subjects his patients in that it is an extrapolation from data that are too preliminary to justify widespread use. That may well change one day, but today is not yet that day, and saying so, to me at least, is akin to pointing out that the “do it yourself” use of unproven cancer therapies like dichloroacetate is usually not a good idea.

We are, however, making progress, and we’re making that progress not based on speculative extrapolation of preliminary science or accepting dubious science as true. I’ll close with an example that is now routinely used in the treatment of ER(+) breast cancer. As I mentioned above, ER(+) breast cancer tends not to be as sensitive to chemotherapy as ER(-) (and in particular, triple negative) breast cancer, even though it has a better prognosis. Over the last decade, a 21-gene assay has been developed for women with ER(+)/HER2(-) cancer that has not yet spread to the axillary lymph nodes called the OncotypeDX® assay. Based on the results of this assay, a recurrence score can be calculated. If it’s high, the tumor is likely to be sensitive to chemotherapy, which will improve the woman’s chances of survival. If it’s low, the tumor is likely to be insensitive to standard chemotherapy, and the recommendation is for the woman not to undergo anything other than anti-estrogen therapy. In this way, thousands of women will be spared chemotherapy that will not help them. Current trials are investigating the utility of this and other genetic prognostic tests in node-positive tumor or, in the case of Oncotype, in determining whether patients with intermediate scores can be spared chemotherapy, and, if so, which ones.

The revolution in genomics has been likened to a flow of water. In the late 1990s, it was a trickle. Five years later, it was a firehose. Today, it’s Niagara Falls, with terrabytes of data being produced every month. The cost of sequencing an entire genome has fallen from $100,000,000 ten years ago to under $30,000 per genome by late 2010, with the era of sub-$1,000 genome sequences in sight. There is definite promise in genomics to result in truly personalized medicine. The key will be to combine it with proteomics, metabolomics, and an understanding of environmental influences. Doing that will not be easy, and, despite the Niagara Falls of data currently deluging us, it will not be fast. Unlike the claims of personalized medicine that arise from CAM and IM, it will take science and clinical trials to tease out the true associations from the noise, to differentiate correlation from causation, to separate and quantify effects of environment from effects of genome, and to figure out the interactions between them all. Oddly enough, that’s why I find last year’s AACR promotional video to be a bit more realistic than this year’s, annoying techno background music aside:

There are successes, challenges and even failures, but always hope. It’s our time, but we have to stick to science-based medicine.

I do a lot of driving as part of my job.  I am the sole Infectious Disease doctor at three hospitals and I can spend an hour or two a day in the car, depending on traffic.  What prevents me from going crazy sitting in traffic is listening to podcasts and audible books.    I especially like reading (and yes, audio books is reading, pedant) multivolume epics.   Currently I am reading Steven King’s Dark Tower series, which occurs in a universe “where the world has moved on.”  In Mid-world there was once a world with science and beauty and art, but something changed, what I do not know yet (I am only on the third volume; no spoilers in the comments), and the world moved on, leaving behind some artifacts of science and technology, but it appears to be an increasingly primitive world.  Being fantasy, there is, unlike the world I live in, magic as well.

I like that phrase: “the world has moved on.” I have an understanding of the world and medicine, based mostly, but not entirely, on science.  My understanding of the natural world is not complete, but mostly consistent and validated by hundreds of years of research.  My undergraduate degree was in physics, and, like all premeds and medical school students, have an extensive education in chemistry, biology, biochemist, physiology, anatomy, biochemistry, etc.  It all ties together nicely, especially in my specialty , where I have the most knowledge.  I consider infections at many levels, from issues of single molecule changes that may confer antibiotic resistance, up through the patient and their family, and sometimes at the level of the entire planet.  Truly wholistic, not the pseudo-wholism of SCAM.

The sciences gives a mostly coherent understanding of the world.  Mostly coherent. It does give an understanding of the possible, the probable, the improbable and the impossible.  Most of the sciences, unlike parts of medical science,  are not concerned with the impossible.  There is not complementary and alternative physics, or chemistry, or biochemistry, or engineering.  These disciplines compare their ideas against reality, and, if the ideas are found wanting, abandoned.   Perpetual motion is not considered seriously by any academic physicist; if perpetual motion were an alternative medicine it would be offered at a Center by a Harvard Professor of Medicine.

Most scientists outside of medicine are aware of how easy it is to fool themselves and, by extension, others. As Richard Feynman said.

“We’ve learned from experience that the truth will come out. Other experimenters will repeat your experiment and find out whether you were wrong or right. Nature’s phenomena will agree or they’ll disagree with your theory. And, although you may gain some temporary fame and excitement, you will not gain a good reputation as a scientist if you haven’t tried to be very careful in this kind of work. And it’s this type of integrity, this kind of care not to fool yourself, that is missing to a large extent in much of the research in cargo cult science.”

My archetype for scientists fooling themselves, and others, is the story of N-rays, which I have discussed before.

For whatever reason, and I do not pretend to understand why, medical people are occasionally unable to incorporate the simple concept that unless they are very careful, they can be fooled.  The result is complementary and alternative medicine.  It is the place that remains after the world has moved on.

That phase constantly popped into my head as I looked at the Huffington Post sections on Intergratve Medicine. The world of medicine, at least, has moved on and left the Huffington Post behind.  So much on the HuffPo Intergrative medicine site is at odds with reality that I will mention only a few of the more egregious examples of medical nonsense.  HuffPo is giving Natural News a run for their money in the production of fantasy. Most striking was the homeopathic (the facts being seriously deluded; isn’t that an underlying principle of homeopathy?) article by Dana Ulman entitled Homeopathy for Radiation Poisoning.  Water for radiation toxicity.  Seriously.  And not even heavy water, which might catch the extra neutron.  And the reasoning for its use is even more goofy, if possible, than that of oh-so-silly-ococcinum.

“Because one of the basic premises of homeopathic medicine is that small doses of a treatment can help to heal those symptoms that large doses are known to cause, Ludlam suggested to Grubbe that radiation may be a treatment for conditions such as tumors because it also causes them. This incident is but one more example from history in which an insight from a homeopathic perspective has provided an important breakthrough in medical treatment.”

I suppose since smoking causes cancer you should treat lung cancer with cigarettes and since alcohol causes cirrhosis you should treat cirrhosis is with vodka and guns cause acute lead poisoning so maybe we should shoot gunshot victims. That I suppose, would be reasonable conclusions from homeopathic theory derived from metaphor and faulty metaphor that.

What nostrums are recommend for radiation therapy? Cadmium iodatum, Ceanothus, and Cadmium sulphuratum, for which there are no Pubmed references to support treating radiation toxicity, even though the author says they are a well-known remedies for that condition. Not well known to medical science I suppose.  Ah the wisdom of homeopathy, where saying it makes it so.

Then the author suggests

“Calendula (marigold) is a well-known herbal and homeopathic medicine. Highly respected research has found excellent results in using Calendula ointment on people who experienced radiotherapy-induced dermatitis.”

Now why is Calendula a homeopathic medicine? I went to the original reference and it appears from the literature to be a worthwhile agent  for the prevention of radiation term burns. But  I am not so sure I would classify Calendula as a homeopathic preparation. According to the producers site it is “Calendula Fresh Plant 4%” and in the original article it is “is fabricated from a plant of the marigold family, Calendula officinalis. The digest is obtained by incubation at 75°C in petroleum jelly to extract the liposoluble components of the plant.”  The authors  do not use the word homeopathic anywhere in the reference.

Real product came containing real parts of the plant at a measurable concentrations, hardly homeopathic in nature.  Calendula ointment has not been subjected to proving, nor has it been potentiated, as if either are helpful.  It is not a homeopathic preparation  just because a preparation made by a producer of homeopathic nostrums, although that appears to be the reason. It is a new definition of a homeopathic preparation: if it is made by a homoepathic producer it is therefore a homeopathic preparation. By this standard, the effluent of the Boiron toilets would also be considered homeopathic preparations.

When it comes to homeopathy, not only has the world moved on,  rational thought and consistency has moved on.

And there is acupuncture. There is a link to an article entitled As Medical Costs Rise More Americans Turn to Acupuncture. This is an article from AOL linked from the Huffington Post (now owned by AOL). If you want to get the heebie-jeebies take a look at the opening picture on that page. The text says “Practitioners must use needles produced and manufactured according to U.S. Food and Drug Administration standards, which require needles to “be sterile, nontoxic, and labeled for single use by qualified practitioners only.” The needles may be sterile, but what good is a sterile needle used by a bare hand?

Look at the accompanying photograph. That middle finger does not inspire confidence. It is no wonder that acupuncture is associated with outbreaks of hepatitis C, hepatitis B, and MRSA infections. Most the pictures of acupuncture on this website  demonstrate that acupuncturists lack understanding of basic technique. It is hard to infect people with an injection.  Heroin users inject themselves with a rich melange of bacteria every day without getting infections.  It is hard to infect patients in the hospital with blood draws and IV’s.  But if an infection can happen, it will happen. And those fingers, just recently in a nose, or picking a tooth, or scratching a butt, will spread an infection with an acupuncturist’s needle to one unlucky patient. Not only has the world moved on for acupuncture, it took with it an appreciation of germ theory.

The Huffington Post  seems to be immune from advances in understanding of all of so-called intergrative medicines, or even basic anatomy and physiology. They  link to a video entitled The Meridian System in Oriental Medicine. They might have linked to the anatomy of Orcs or the physiology of Dementors, for all the application to reality it represents.   The video is gibberish when compared to nature as we understand it. The world has moved on.

When Huffington Post published absolute nonsense, I have to wonder how good their analysis is on issues like politics, war,  the environment and other important areas. I was always taught to judge a man by the company he keeps. I have the same problem with my local newspaper, the Oregonian, which publishes the occasional nonsense piece in the Living section.  They often get things wrong in Infectious Diseases, the one area I have expertise.  If they are wrong in areas I know,  can I trust their writings on other topics?

When I finish the series, I’ll let you know, metaphorically, what the alt med Dark Tower is.

Editors Note: This is a guest contribution from two medical students, one from Chicago and one from Queensland. If you like their work, we’ll consider having them write more for us.

Authors:

Andrey Pavlov Jr.
UQ-Ochsner
University of Queensland School of Medicine

Igor Irvin Bussel
Chicago Medical School
Rosalind Franklin University of Medicine and Science

In hopes of joining the SBM movement as medical students, we wanted to take aim at a topic that has yet been finely dissected a la Novella or logorrheicly dismembered a la Gorski. Having realized that a fellow medical student, Tim Kreider, is already addressing integrative medicine on campus, we decided that we would attempt to find a controversial topic that has yet to be addressed on SBM. A serendipitous question from a friend sent us on a mission to explore the pseudo-scientific underbelly of the web and science-based rationale of the claim that vitamin C can induce abortion.

The World Wide Web is a stranger place than we can ever imagine. Most users are aware that they can’t believe everything they read on the Internet, yet they often feel like Sherlock Holmes when they find an esoteric and isolated clue to their own unique health puzzle. Recently, we were asked if there was a connection between vitamin C, menstruation and abortion. We were caught off guard by the question, finding it such a strange connection to make. The story, it seems, is that our friend had come down with a cold and taken mega doses of vitamin C to stave it off (another false belief, but not the subject here). A couple of days later her menses began and she was surprised since it was 4 days earlier than normal. She of course turned to Dr. Google and was quickly provided with numerous sources indicating that indeed, vitamin C would induce the start of a menstrual cycle and can even act as a “natural” abortefacient and a substitute for the ‘morning after’ pill. Being a bit more keen than your average Dr. Google user, she was surprised and continued searching, trying to find evidence to contradict these claims. Alas, she found nothingexcept more sites parroting and corroborating the claim. Then she realized she knew a couple of medical students and asked us what we thought. Our literature review turned up a slew of websites using the standard repertoire of trite pseudo-scientific tactics. Any attempt to find a credible source, validated claim, or independent consensus proved futile.

At the time of this writing, Google yielded over 400,000 results when searching for “vitamin C abortion” and around 45,000 results when searching “ascorbic acid abortion.” While both search queries resulted in about 38 entries on PubMed, nothing was found using Up-To-Date or Cochrane Collaboration. However, regardless of query terms, we could find no sites that refuted the claim of vitamin C as an abortefacient.
The top returned website references a Russian article written in 1966 by Samborskaia and Ferdman. This site will be the focus of our piece since it appears the most legitimate having a complete “references cited” section. This gives the illusion of credible research and bears thorough debunking. Sadly, the Russian article is the most relevant and “scholarly” article. The author of the site offers this analysis to support her claim:

The article is in Russian, and finding a copy was a problem… as was the language barrier. I had been corresponding with a lady from Slovak Republic (Slovakia) and mentioned the article. She went out looking for it, and was able to find a copy. She was able to translate it for me, and noted that the author did not specify the doses of ascorbic acid administered to the women, and the author also did not say specify how the women received the ascorbic acid; ie, liquid, injection, tablet.

The scientists who conducted the research, Samborskaia and Ferdman, came to the conclusion that high doses of Ascorbic Acid appeared to increase estrogen levels which contributed to the interruption of an otherwise normal pregnancy. 20 women who approached doctors requesting an abortion participated in the study. Research was conducted by ob/gyn L.I. Ivanyuta. The women ranged from 20 to 40 years of age. The article does not say if a positive pregnancy test was obtained from the participating women. We also don’t know how much ascorbic acid the women were given. They did however measure estrogen levels before and after treatment with ascorbic acid, finding that estrogen levels were higher after taking the ascorbic acid. Of the 20 women, 16 began menstrual type bleeding within 1 to 3 days from administration of ascorbic acid.

So the evidence cited here is from an article the author could not find, in a language she could not understand, translated by some unknown woman in Slovakia, with a sample size of 20, no known dosages or methods of administration, and even an admission that there was no documentation that all 20 women were even pregnant. Already riddled with biases, flaws, and fallacies, the author continues:

Also, in my own personal research, I’ve come into contact with numerous women who did confirm their pregnancies with a test, then used ascorbic acid (sometimes in conjunction with other herbs) to terminate those pregnancies successfully… While it can’t be considered scientific data, it is none-the-less proof that these home remedies do work for some women.

That which can’t be considered scientific data can’t be asserted as proof. This is a common failing in pseudo-scientific writings – an appeal to some other form of proof or “other ways of knowing.” The author continues with the empiric discussion:

It is said that on average 1 in every 4 pregnancies end in miscarriage. This would be 25% of all pregnancies. Statistics vary somewhat, and age is a factor, some say as few as 16% up to as much as 30% of all pregnancies end in miscarriage. A government website says 50% of all fertilized eggs die or are lost spontaneously – usually prior to the woman knowing she is pregnant, many of which do not implant in the uterine wall. In known pregnancies, they say that about 10% miscarry naturally and this normally happens between the 7th and 12th week of pregnancy. With this in mind, observations from my own research and data collection, about 45% of women with confirmed pregnancies are successful when using vitamin c (ascorbic acid) with the intention to end a pregnancy at home. This is well above the estimated rate of natural miscarriages (non-induced), so even if some of these women would of miscarried on their own without the steps they took to induce miscarriage at home (10% of known pregnancies miscarrying naturally or 1 in 4 pregnancies (known or unknown) ending naturally) these figures do not account for the increased rate of spontaneous abortion that I’m seeing through the data these women voluntarily provide.

The author cites a wide range of data on spontaneous abortion rates and concludes that “up to 30%” of all pregnancies end in miscarriage, though “a government website says 50% of all fertilized eggs die or are lost spontaneously”. From her own personal anecdotal “data” she finds that “45% of women with confirmed pregnancies are successful when using vitamin C… with the intention to end pregnancy at home.” For her, this is “well above” the estimated rate of “natural miscarriages” and therefore evidence that vitamin C works for this purpose. She further states that if the attempted vitamin C abortion does not work, it is important to go ahead and obtain a clinical abortion since even though the USDA does not list vitamin C as teratogenic, such a mega dose in an embryo has “too many unknowns” and one should not risk “having a messed up kid.” How can we ignore such sage medical advice and dutiful statistical analyses?

At least she can admit that “[n]atural or do-it-yourself does NOT mean it is SAFE [her emphasis].” That is about the only redeeming part to this travesty of medical advice. However, even the author’s own “statistics” indicate that, at best, there is only a very slight increase in the rate of abortion with vitamin C over spontaneous miscarriage. Considering the very small sample size, poor data quality, and complete lack of rigor it is safe to say this is either just completely false or normal noise with no statistical significance at all – not that we could even run a statistical analysis with the “data” we are given. Once again, the common pseudo-science tactic of asserting a statistical conclusion with no actual analysis rears its head.

Although we focus here on only one site devoted to this “naturalistic” nostrum, the remaining sites we found either reference this one, the original Russian article, or simply parrot the same piffle with no references at all. For example, NaturalMiscarriage.org has similar preposterous claims to the efficacy of many herbal abortefacients, including vitamin C, and even claims that in their respondent survey that 171 of 235 women (73%) who tried vitamin C had successful miscarriages. A few lines down we find that 93 of 118 women (79%) who tried “visualization and prayer” had a successful miscarriage. And apparently 38 of 46 women (83%) who tried avocados had a successful miscarriage – so we should clearly suggest avoiding guacamole at your church social if you are pregnant.

This pseudo-scientific claim has already failed from an evidence-based medicine perspective, but how about throwing a little science in the mix and conjecturing a prior probability? From the only article cited as reference to a human population, the mechanism is described as both “elevating estrogen levels to interrupt a normal pregnancy” and the “acid” of ascorbic acid (vitamin C) acting to disrupt the endometrium directly leading to the sloughing of menses. A quick PubMed search reveals four articles relating in at least some way to “vitamin C and abortion” in humans. One is a 2005 Cochrane review that examines multi-vitamin prenatal treatment as a prevention of miscarriage and stillbirth (not specifically vitamin C) and finds no relation between miscarriage and prenatal vitamin consumption. A 2011 update to the review holds the same conclusions. Two have no article or abstract available (one is in Polish from 1987 and the other in the Lancet from 1974). The last one is also a very small study (n=50) and found no causal relationship between vitamin C and spontaneous abortion. Furthermore, any biology undergraduate who passed physiology would know it is the drop in hormonal levels (including estrogen) that triggers the start of menses. Additionally, from a simple physiological point of view, the notion that ingesting a large amount of “acid” can alter the pH balance of the endometrium significantly enough for a physiological response is ludicrous. There is no mechanism by which vitamin C would be preferentially localized to the uterine wall and if the blood pH was changed enough to cause an endometrial sloughing, late menses would be the last of your worries.

In today’s political climate in America, especially in light of the recent vote to remove the federal funding for Planned Parenthood, having access to accurate medical advice based in science is important, regardless of your personal stance on the issue. Notably, based on a 2011 study in the American Journal of Obstetrics and Gynecology, 1.4% of 9,493 women surveyed, reported using vitamin C or herbal products to attempt to end a pregnancy. Though this is not an urgent danger to public health, others on the web have snagged onto this idea and have begun posting this same advice on forums such as eHow and women are actually seeking advice since these authors give the impression of authority on the matter. The startling thing is that there are simply no sources out there that say anything else about vitamin C and abortion – every searched source claimed efficacy of the method. The echo chamber of the Internet repeats the original assertion without any information to the contrary. For a person like our friend, there is little recourse except to assume that there must be some truth to this farcical claim. She had us to ask and it is our hope that this piece will give others a credible source to refute the claim that vitamin C induced abortion is legitimate.

Science is a philosophy, a technology, and an institution. It is a human endeavor- our collective attempt to understand the world around us,  not something that exists solely in the abstract. All of these aspects of science have be progressing over the past decades and centuries, as we refine our concepts of what science is and how it works, as we develop better techniques, and organize and police scientific activities more effectively. The practice of science is not relentlessly progressive, however, and there are many regressive forces causing pockets of backsliding, and even aggressive campaigns against scientific progress.

So-called complementary and alternative medicine (CAM) is one such regressive force. It seeks to undermine the concepts, execution, and institutions of medical science in order to promote sectarian practices and ideological beliefs. Examples of this are legion, exposed within the pages of this blog alone. I would like to add another example to the pile – the recent defense of homeopathy by Dana Ullman in the Huffington Post (names which are already infamous among supporters of SBM).

In a piece titled: Homeopathy for Radiation Poisoning, Ullman demonstrates yet again the pseudoscientific aspects of homeopathy and its proponents. The primary principle that is abused by Ullman this time is the need for scientists to carefully define their terms and concepts. Scientific concepts should be defined as carefully, precisely, and consistently as possible. Squishy concepts are very difficult to deal with in science – but are the bread and butter of pseudoscience.

The fuzzy concept is particularly useful to the pseudoscientist (someone pretending to do real science, but whose activity is devoid of genuine scientific exploration or rigor). Pseudoscientists generally start with a desired answer and then work backwards to their logic and evidence. Whereas genuine science endeavors to follow logic and evidence wherever it leads. Having a poorly defined term or concept allows pseudoscientists to better shoehorn in evidence and logic – to create the appearance of support for their beliefs where none exists.

Ullman’s article is typically full of anecdotes, cherry picked evidence, and tortured logic. There is far too much there to pick apart in detail, so I want to focus on his exploitation of poorly defined concepts. He writes:

Grubbe got the idea of using radiation as a treatment for Lee’s breast cancer from Reuben Ludlam, M.D., a professor at the homeopathic medical school. Ludlam knew that Grubbe had previously experimented with X-ray as a diagnostic procedure so much that he developed blisters and tumors on his hand and neck as a result of overexposure to this new technology.

Because one of the basic premises of homeopathic medicine is that small doses of a treatment can help to heal those symptoms that large doses are known to cause, Ludlam suggested to Grubbe that radiation may be a treatment for conditions such as tumors because it also causes them.

The toxicity and medical uses of radiation have absolutely nothing to do with any concept that can reasonably be considered part of homeopathy. But Ullman exploits superficial similarities to twist it into support for the deliberately squishy concept of homeopathy. Radiation is toxic to cells – high energy particles impart their energy to cell structures, breaking chemical bonds, killing cells outright in some cases or damaging their DNA. Radioactivity has greater toxicity to cells that rapidly reproduce, because they are more sensitive to DNA damage (partly because they have less time to repair DNA damage).

Low levels of radiation exposure carry a low risk because the repair mechanisms of cells can largely handle any damage done, and the number of lost cells is insignificant. It is not clear if low levels of radiation (such as the background radiation in which we all live) conveys zero risk or simply a very low risk – that type of distinction is inherently difficult to make with empirical studies.

But at all levels of exposure the effect of radiation is a toxic one – to do damage to cell structures. In this way radiation is very much like a drug. All drugs cause biological changes to the body. But those used as pharmaceutical agents have a dose range in which their effects can be exploited while the risk of negative effects is minimal. There are threshold at which certain toxic effects  become significant, but at lower doses they are still present, just tolerable or insignificant. Some effects may display a threshold effect because of compensatory mechanisms, or because there are certain levels at which metabolic processes are overwhelmed.

Radiation damages and kills cells. Rapidly dividing cells are more susceptible to damage. There is therefore a dose range in which radioactivity can kill rapidly dividing tumor cells significantly more than surrounding healthy tissue. But in order to exploit this effect techniques must be use to focus the radiation on the tumor while minimizing exposure to surrounding tissue. And a certain level of damage to surrounding tissue is unavoidable. There is even the risk of later damage, and even cancer, from therapeutic radiation exposure. The use of radiation, like the use of drugs, is about risk vs benefit, or beneficial effects vs side effects. Given that the condition being treated is a potentially fatal cancer, a high level of side effects and risk are considered reasonable.

Ullman, however, would have you believe that what I described above is analogous to homeopathy, in which tiny or (more commonly) non-existent doses of a substance that causes certain symptoms in a healthy individual will treat those symptoms in an unhealthy person. This is not analogous to exploiting different levels of toxicity for a therapeutic effect. There is a superficial similarity in that different doses cause different effects – but with drugs and radiation there are specific mechanisms for this dose-response effect. Homeopathy does not display a dose-response effect – even as homeopaths understand it.

Science and evidence dictates that homeopathy shows no effect at all, but even within the belief system of homeopaths there is no consistent dose-response curve for their potions. There is, if anything, a mysterious and inconsistent relationship between dose and effect, without any plausible mechanism at all. This bizarre relationship between dose and effect claimed by homeopaths is such that dilutions where not even a single molecule of original ingredient is likely to remain behind are often claimed by homeopaths to be the most potent.

Further, while there are specific mechanisms for toxicity and therapeutic effects for interventions like radiation and drugs (although certainly we do not fully understand the precise mechanisms of every drug), there is no plausible mechanism behind the claims of homeopathy. The best that they can come up with is false analogies to vaccines, the speculative concept of hormesis, and now the dose-response effect of standard treatments. When pushed they speak vaguely about the “essence” of the drug, and restoring “balance”. But this is no closer to an actual explanation of how homeopathy might work than saying that it is “magic”, “witchcraft”, or “faith healing.”

Conclusion

The exploitation of poorly defined concepts is a hallmark of CAM. We see it in homeopathy, as above, with strained analogies and fallacious logic. We see it with acupuncture, for example, when “placebo acupuncture” (where there is no needle penetration and no acupuncture points) and electroacupuncture (where electrical stimulation is given) are used as support for acupuncture. This leads to the question – what is acupuncture? What is it that is specific an unique to acupuncture?  Nothing, apparently – but this allows for a wide range of non-specific and other effects to be used as support for the vague concept of “acupuncture.”

And we can ask – what is homeopathy? What scientific concept that has been validated by experimentation constitutes the body of knowledge that is homeopathy? The answer is – nothing. There is no law of similars, nor a law of infinitessimals. There is no plausible mechanism to explain homeopathic potions. So instead we are given invalid analogies, innuendo, and a desperate attempt to confuse the public as to what homeopathy actually is.

The word “frequency” ranks right up there with “quantum” and “energy” as a pseudoscientific buzzword. It is increasingly prevalent in product advertisements and in CAM claims about human biofields and energy medicine. It doesn’t mean what they think it means.

I have written about Power Balance products, the wristbands and cards that allegedly improve sports performance through frequencies embedded in a hologram. They amount to nothing but a new version of the old rabbit’s foot carried for superstition and their sales demonstrations fool people with simple musculoskeletal tricks. I addressed their ridiculous claims (including “We are a frequency”). I pointed out that

The definition of frequency is “the number of repetitions of a periodic process in a unit of time.” A frequency can’t exist in isolation. There has to be a periodic process, like a sound wave, a radio wave, a clock pendulum, or a train passing by at the rate of x boxcars per minute. The phrase “33? per minute” is meaningless: you can’t have an rpm without an r. A periodic process can have a frequency, but an armadillo and a tomato can’t. Neither a periodic process nor a person can “be” a frequency.

There are a number of similar embedded frequency products with different names. I got an e-mail from a man who thought he had found the best one yet: Ancestor Bands that promised to put him in contact with his forebears and allow him to benefit from their wisdom.

I thought he was pulling my leg, but he insisted he wasn’t. I asked him to wonder how they might have determined which frequencies the ancestors use. I asked him to question how he would know that any messages he got were really from his ancestors rather than from Pol Pot, from Hitler, from Jeffrey Dahmer, from an ignorant Stone Age caveman, or from some random village idiot. He said I had given him some things to think about, but he was trying to keep an open mind and really wanted to believe they worked. The website says

We are all uniquely connected to our ancestors genetically. The bands you see here will help you tap into the proper frequencies that your Ancestors transmit throughout the Cosmos. They are desperately trying to connect with you and impart their Newfound Universal knowledge of the Universe. The bands are designed to increase your mental power, physical strength, and reverse the effects of aging. Try it today, feel the difference tomorrow.

They start with the idea that all living things are interconnected and produce energy waves that we can tap into, apparently even after they have stopped living! The Ancestor Band uses “energetic therapy and informational balancing” to

directly address the energetic level using light, sound, electricity and magnetism as carriers of client- and condition-specific information… to remove tiredness, weakness, reduce pain, and eliminate stress… a group of spiritual advisors have transformed each piece into a Unique Genetic Communications link to the Past, Present, future, and beyond.

That’s about as silly a piece of gobbledygook as I have ever read. It would be impossible to test their claims because you can’t even figure out what they are claiming. For starters, I can’t begin to guess what “beyond the future” means.

Recently I’ve been getting e-mails advertising Philip Stein watches. They use “natural frequency technology” to embed frequencies in watches. This provides improved sleep. And they even have a published double blind randomized placebo controlled study that proves it. Only it doesn’t. It did not give statistically significant results, but they interpreted it as positive because 96% of subjects reported improvement on at least one variable. That is not a meaningful scientific finding. In fact, it reminds me of a clever ploy that is taught to chiropractors: instead of asking whether the patient’s back pain got better after the last spinal adjustment, they are supposed to ask “What’s better?” until the patient admits that something is better (he slept better last night, or his appetite has improved, or his ingrown toenail hasn’t been hurting as much, or whatever). Then they can say “See, the treatment is helping you.”

The frequencies they are talking about are electromagnetic frequencies, and several of these were somehow embedded in a disc in the watch. It is a metal disk that has been “infused with key frequencies.” One of the key frequencies is 7.83 Hz, the Schumann Resonant Frequency. (Actually, there are several Schumann frequencies, which are observed peaks in the Earth’s electromagnetic spectrum.)  It doesn’t make sense that they could embed electromagnetic frequencies without embedding something that produced those frequencies, with a power source. Or do they mean they are embedding something that will vibrate in resonance with those frequencies? It’s far from clear, and of course they won’t try to explain because of proprietary secrets.

They’re really proud of these watches. They charge anywhere from $1400 to $23,000 for them. Soon the company will launch a new product that, when combined with the frequencies found in Philip Stein watches, delivers even greater benefits in improved sleep. I can’t wait.

I’d love to see these products taken apart by engineers who are competent to analyze what is in them. Even if these products did contain something that generates electromagnetic frequencies or that resonates in response to certain outside frequencies, it would take a big leap of faith to imagine that process would have specific beneficial effects on health. You would first have to accept the concept of a human “bioenergy” field that can’t be measured. Then you would have to accept that the field changes in response to a specific frequency and that those field changes somehow produce a specific physiologic effect. Not only is there no plausible mechanism, but there are no studies showing evidence of benefit. It might work; but in the absence of evidence, believing it does work would require you to have such an open mind that your brain would be in grave danger of falling out.

Perhaps we should monitor the frequency of pseudoscientific claims about frequencies: it might serve to track the degree of idiocy in public misunderstanding of science.

Note: My spell checker didn’t like the word bioenergy any better than I do. (There is a legitimate use for the word, but this is not it.) The spell checker suggested I might want to substitute “beanery” or “baboonery.” I confess to being sorely tempted by the latter.

Another note: my title is a reference to Dr. Oliver Wendell Holmes’ classic 1842 article“Homeopathy and Its Kindred Delusions.”

NOTE: This post was taken down and reposted as a new and different post. For some reason, comments were disabled in the original and I couldn’t figure out how to re-enable them. I suspect a glitch in WordPress. Very annoying. Sorry about that. Comments should be open now.

I’m not infrequently asked why the myth that vaccines cause autism and other anti-vaccine myths are so stubbornly resistant to the science that time and time again fails to support them. Certainly useful celebrity idiots like Jenny McCarthy are one reason. So, too, are anti-vaccine propaganda websites and blogs such as Age of Autism and anti-vaccine organizations like Generation Rescue, the National Vaccine Information Center, and SafeMinds and the organizations that publish them. However, these are clearly not the only reason. Alone, these people and organizations are in general quite rightly viewed as fringe, although they are very popular among the anti-vaccine movement. It is when such groups find a willing conduit for their pseudoscience in the “mainstream media” that they see the opportunity to attain a degree of seeming respectability that they can’t achieve on their own based on science. Worse, when mainstream news organizations or reporters fall for the pseudoscience claiming that vaccines cause autism, they contribute to the persistence of this myth outside the activist core of the anti-vaccine movement in the public at large.

In the past, anti-vaccine activists tried to accomplish this with the help of formerly respectable journalists such as David Kirby and Dan Olmsted, the former of whom wrote Evidence of Harm: Mercury in Vaccines and the Autism Epidemic: A Medical Mystery and the latter of whom wrote and promoted the Age of Autism series when he was an editor at UPI. However, although Kirby was never really that prominent or trusted, Olmsted was an editor of UPI. Now that he’s given up his UPI gig to become full time editor of AoA and to team up with Mark Blaxill to write a book (Age of Autism: Mercury, Medicine and a Manmade Epidemic) that regurgitated all the old misinformation about thimerosal and autism in a way that’s so 2005, Olmsted’s lost all credibility as a serious reporter. That’s a good thing.

The bad thing is that he has a replacement. Or at least so it would appear.

THERE’S A NEW ANTI-VACCINE REPORTER IN TOWN, AND SHE’S PUSHING SOME PSEUDOSCIENCE

Unfortunately, at CBS News, there now appears to be a woman who was willing to take over the role of mainstream media propagandist for the anti-vaccine movement. Her name is Sharyl Attkisson, and, oops, she did it again just this Thursday with an article entitled Vaccines and autism: a new scientific review, in which she pimps a truly horrible “review” of the evidence base regarding whether vaccines cause or predispose to autism. Interestingly, she’s quite late. AoA was promoting this article two months ago. On the other hand, April is Autism Awareness Month, and I can always count on the anti-vaccine movement to lay down some vaccine pseudoscience on or around April 1 every year (I leave it to the reader to judge the appropriateness of that date); so perhaps this latest from Attkisson is the opening salvo for this year’s campaign. Her article opens:

For all those who’ve declared the autism-vaccine debate over – a new scientific review begs to differ. It considers a host of peer-reviewed, published theories that show possible connections between vaccines and autism.

The article in the Journal of Immunotoxicology is entitled “Theoretical aspects of autism: Causes–A review.” The author is Helen Ratajczak, surprisingly herself a former senior scientist at a pharmaceutical firm. Ratajczak did what nobody else apparently has bothered to do: she reviewed the body of published science since autism was first described in 1943. Not just one theory suggested by research such as the role of MMR shots, or the mercury preservative thimerosal; but all of them.

Ratajczak’s article states, in part, that “Documented causes of autism include genetic mutations and/or deletions, viral infections, and encephalitis [brain damage] following vaccination [emphasis added]. Therefore, autism is the result of genetic defects and/or inflammation of the brain.”

Note the classic crank technique of trying to convince the reader that the “debate is not over,” that the hypothesis that vaccines cause autism is, in fact, “pining for the fjords” when in fact, on a strictly scientific basis, the hypothesis is at least as dead as that famous parrot, with Attkisson playing the role of the shopkeeper trying to convince his customer that “‘E’s resting” while raving about the parrot’s “beautiful plumage.”

Attkisson then goes on to write:

Ratajczak also looks at a factor that hasn’t been widely discussed: human DNA contained in vaccines. That’s right, human DNA. Ratajczak reports that about the same time vaccine makers took most thimerosal out of most vaccines (with the exception of flu shots which still widely contain thimerosal), they began making some vaccines using human tissue. Ratajczak says human tissue is currently used in 23 vaccines. She discusses the increase in autism incidences corresponding with the introduction of human DNA to MMR vaccine, and suggests the two could be linked. Ratajczak also says an additional increased spike in autism occurred in 1995 when chicken pox vaccine was grown in human fetal tissue.

Why could human DNA potentially cause brain damage? The way Ratajczak explained it to me: “Because it’s human DNA and recipients are humans, there’s homologous recombinaltion tiniker. That DNA is incorporated into the host DNA. Now it’s changed, altered self and body kills it. Where is this most expressed? The neurons of the brain. Now you have body killing the brain cells and it’s an ongoing inflammation. It doesn’t stop, it continues through the life of that individual.”

Dear readers, I apologize to those of you who don’t like my “tone” (well, no I don’t, at least not in this case), but those two paragraphs almost made me spit the iced tea I was drinking as I composed this all over the keyboard of my precious MacBook Air. The reason is that I have experience with working with DNA, human, mouse, and otherwise, including injecting it into tissues and trying to get it to express the protein for which it encodes. This is not a trivial matter. Think of it this way. If it were, gene therapy would be an almost trivial matter. But it’s not. In general, it’s difficult to induce human cells to take up foreign DNA in tissue. Even with viral vectors, it’s hard to get more than a small percentage of cells not only to take up the DNA but to express detectable levels of protein. Muscle is one tissue that can take up naked plasmid DNA and actually express it. Indeed, this technique has been used to generate cancer vaccines, where plasmid DNA is injected into the muscle in order to cause it to make a certain protein, which then provokes an immune response. But doing this is not easy, and the DNA is not detectably incorporated into the DNA of the muscle cells. Its gene expression is extranuclear (outside the nucleus).

But that’s not all. Even human cells that can take up random bits of extracellular DNA at very low efficiency (like muscle) do not integrate that DNA into their genome. Even if the DNA did reach the nucleus, recombination into the host genome would be both random and rare. Each cell would incorporate different bits of DNA into different locations in its genome. Does Dr. Ratajczak even know basic molecular biology?

But that’s still not all.

Dr. Ratajczak states that the DNA from vaccines is human DNA. Even if that human DNA did undergo homologous recombination, it would still be human DNA making human proteins. Yet Dr. Ratajczak claims that homologous recombination turns that cell into “altered self.” However, the body recognizes a cell as foreign or “altered” through the expression of its cell surface proteins. Consequently, the only likely currently known mechanism by which homologous recombination of human DNA from vaccines might conceivably result in such an autoimmunity phenomenon would be if the DNA from the vaccine somehow resulted in the expression of a foreign or altered protein on the cell surface that the immune system could recognize as foreign. That would mean either integrating into the gene for a cell surface protein or producing a cell surface protein itself. While not impossible, that’s pretty darned unlikely to happen on a scale that would affect more than a single cell, a few at most. To recap: To do what Dr. Ratajczak claims, human DNA from vaccines would have to:

• Find its way to the brain in significant quantities.
• Make it into the neurons in the brain in significant quantities.
• Make it into the nucleus of the neurons in significant quantities.
• Undergo homologous recombination at a detectable level, resulting in either the alteration of a cell surface protein or the expression of a foreign cell surface protein that the immune system can recognize.
• Undergo homologous recombination in many neurons in such a way that results in the neurons having cell surface protein(s) altered sufficiently to be recognized as foreign.

That’s leaving aside the issue of whether autoimmunity in the brain or chronic brain inflammation is even a cause of autism, which is by no means settled by any stretch of the imagination. In fact, quite the opposite. It’s not at all clear whether the markers of inflammation sometimes reported in the brains of autistic children are a cause, a consequence, or merely an epiphenomenon of autism.

In other words, Dr. Ratajczak’s hypothesis is incredibly implausible on the basis of what we know about molecular biology and human biology. It’s not quite homeopathy-level implausible, but nonetheless quite implausible. Even so, I’m willing to have my mind changed for me, but there’s only one thing that can possibly do that: Scientific data. Experiments. Clinical trials. Good ones. So I “went to the source,” so to speak, and actually looked at Dr. Ratajczak’s review article being touted by Attkisson to see what she actually said about homologous recombination of human DNA in vaccines as one cause of autism. Here is the sum total of what she said:

Data from a worldwide composite of studies show that an increase in cumulative incidence began about 1988–1990 (McDonald and Paul, 2010). The new version of the measles, mumps, rubella vaccine (i.e., MMR II) that did not contain Thimerosal was introduced in 1979. By 1983, only the new version was available. Autism in the United States spiked dramatically between 1983 and 1990 from 4–5/10,000 to 1/500. In 1988, two doses of MMR II were recommended to immunize those individuals who did not respond to the first injection. A spike of incidence of autism accompanied the addition of the second dose of MMR II. Also, in 1988, MMR II was used in the United Kingdom, which reported a dramatic increase in prevalence of autism to 1/64 (noted above). Canada, Denmark, and Japan also reported dramatic increases in prevalence of autism. It is important to note that unlike the former MMR, the rubella component of MMR II was propagated in a human cell line derived from embryonic lung tissue (Merck and Co., Inc., 2010). The MMR II vaccine is contaminated with human DNA from the cell line. This human DNA could be the cause of the spikes in incidence. An additional increased spike in incidence of autism occurred in 1995 when the chicken pox vaccine was grown in human fetal tissue (Merck and Co., Inc., 2001; Breuer, 2003). The current incidence of autism in the United States, noted above, is approximately 1/100.

The human DNA from the vaccine can be randomly inserted into the recipient’s genes by homologous recombination, a process that occurs spontaneously only within a species. Hot spots for DNA insertion are found on the X chromosome in eight autism-associated genes involved in nerve cell synapse formation, central nervous system development, and mitochondrial function (Deisher, 2010). This could provide some explanation of why autism is predominantly a disease of boys. Taken together, these data support the hypothesis that residual human DNA in some vaccines might cause autism.

Later, she writes:

Other reports have also used prevalence data that support an association of the MMR vaccine with an increased prevalence of autism. Furthermore, an examination of the continuing increase in prevalence in autism in the context of the dates of spikes in increase in prevalence which point to the MMR II vaccine (which did not contain Thimerosal) suggests that something “new” caused the increase in incidence of autism. Changes in vaccine schedule occurred over the years such as changes in the age at which vaccines were given (Ramsay et al., 1991). These changes could contribute to the increases in incidence of autism. Another change was how some vaccines were propagated. The “new” component could be the human DNA from the preparation of the rubella component of the MMR II vaccine and the chicken pox vaccine. See “Changes in Rates of Autism Incidence” above. The United States Government and Dr. Geberding, Director of Vaccines at Merck & Co., Inc. say that autistic conditions can result from encephalopathy following vaccination (Child Health Safety, 2010).

I’m the sort of guy who’s data-driven. If there were scientific data that convincingly suggested a hypothesis, even one as implausible as the one above, I’d think about it and possibly even conclude that this is an area worthy of investigation. There were no data presented. There weren’t even studies cited that convincingly supported Ratajczak’s assertions. That’s it? I was thinking as I read her article. That’s all she’s got? Seriously? I thought it was a joke; so I read the entire article again. Yes, that is all that she has got: Implying that correlation equals causation, combined with an observation that there are “hot spots” for DNA insertion in the X chromosome in some autism-associated genes. From that, she concludes that the existing data support the hypothesis that human DNA in MMR II could be at least responsible for the “autism epidemic” through homologous recombination in the brain resulting in autoimmunity and chronic inflammation? And she cites the anti-vaccine blog Child Health Safety as one of her references? The date of the CHS entry cited is June 30, 2010. All I could find was this entry, which purports to argue that both Merck’s Director of Vaccines and the U.S. government have admitted that vaccines cause autism all based on the long known science showing that a maternal case of rubella while carrying a fetus can result in autism in the child, something that’s been known for several decades and is in fact one reason why vaccination against rubella is so important. How on earth did this get through peer review. Obviously, the peer reviewers of Dr. Ratajczak’s article were either completely ignorant of the background science (and therefore unqualified) or asleep at the switch.

The rest of Dr. Ratajczak’s article is a greatest hits collection of anti-vaccine hypotheses, speculations, ideas, and brain farts mixed with the occasional–and I do mean occasional–grain of scientifically supportable hypotheses regarding autism. The vast majority of what is discussed, however, is pure vaccine pseudoscience. The scientifically unsupported idea that mercury in vaccines causes autism? It’s there. The work of the tag team of Geier père et fils, the same team who came up with the idea of chemical castration as a treatment of autism that “works” because according to them testosterone binds mercury, making it easier to chelate? Copiously cited. True, Ratajczak doesn’t specifically cite the Geiers’ unethical clinical trial testing Lupron as a treatment for “precocious puberty” and autism, but she does cite the “scientific” basis that the Geiers used to justify that trial, as well as a lot of the Geiers’ usual execrable studies linking mercury in vaccines with autism. Mitochondrial dysfunction, which has been co-opted by the anti-vaccine movement as an “explanation” for how vaccines supposedly cause autism? It’s there too. She even cites David Ayoub, who is known for thinking that black helicopters are watching him. In other words, her review is 95% pseudoscientific garbage, maybe 5% reasonable science. On second thought, I’m clearly being generous.

Remember that Sharyl Attkisson is taking advantage of the start of National Autism Awareness Month to promote this nonsense.

SHARYL ATTKISSON: THE ANTI-VACCINE REPORTER FOR CBS NEWS

This is not the first time that Sharyl Attkisson has demonstrated herself to be biased in favor of the anti-vaccine movement. Indeed, I’ve known about her activities in this regard going back nearly four years. One particularly prominent example that sticks out in my mind is an article she published on the CBS News website back in 2007 entitled Autism: Why the debate rages, in which she made assertions and arguments of these sorts:

• Science has been wrong before. She used Vioxx and Thalidomide as examples. Never mind that Thalidomide was never approved in the U.S. at the time of all the birth defects (it’s approved now to treat multiple myeloma), and in fact was an example of the FDA doing its job. In classic crank fashion, Attkisson used these examples to argue that science must be wrong now about thimerosal in vaccines. She even pulls out the hoary “refrigerator mother” gambit, implying that because there was a time that scientists speculated that cold, uncaring mothers contributed to or triggered autism and were clearly wrong about that, they must be wrong about vaccines now.
• The classic “pharma shill gambit.” Attkisson ranted on about how scientists do research for vaccine companies, linking the pro-vaccine group Every Child By Two to pharmaceutical companies.
• Science doesn’t know everything. Sample quote: “There is no definitive research proving a link between vaccines and autism or ADD, but there is also no definitive research ruling it out.” Well, there is no definitive research ruling out a link between autism and pixies, either.
• Because scientists don’t know what is causing the “autism epidemic,” vaccines are a plausible cause.

Truly, Attkisson’s 2007 article was a crank trifecta plus one!

Then, in 2008, Sharyl Attkisson appeared to have been caught almost red-handed taking a letter of protest from a pro-vaccine group called Voices for Vaccines complaining about her reporting to the anti-vaccine group blog Age of Autism, an incident that led Liz Ditz to ask, “How much of Attkisson’s “investigating” consists of rewriting and rewording statements from principals at the advocacy–even propaganda–organization, Age of Autism?” I don’t know the answer to that question, but I do know that Attkisson’s reporting on vaccines is nearly indistinguishable from the message put forth by anti-vaccine groups like Generation Rescue, SafeMinds, and the NVIC. Attkisson even falls for bad science in other areas, such as breast cancer research. In fact, you could say that her science reporting when it comes to breast cancer causation is of the same quality as her reporting on vaccines and autism, and I don’t mean that as a compliment.

Nor do I mean it as a compliment when I say that, in the wake of Wakefield’s infamous “monkey business study” in 2009, Attkisson inserted her nose farther up Andrew Wakefield’s posterior than even the crew at AoA has yet managed:

After all of Attkisson’s pandering to the anti-vaccine movement and promoting its message, one huge question remains. Why does CBS News tolerate Attkisson’s horrible reporting on vaccines and other scientific issues? I can’t speak about her other reporting, but when it comes to science, Sharyl Attkisson is a crank par excellence. She has an agenda; and she tortures the evidence to make it seem to agree with her biases. All of this wouldn’t matter so much if she weren’t a national correspondent for CBS. Unfortunately, there her crank magnetism allows her to engage in fear mongering on a national level.

I also wonder how long it will be before Attkisson joins Dan Olmsted as a writer for AoA. My only surprise is that, nearly four years since I first noticed her, she hasn’t made that move already. I suppose I can always hope that CBS News wises up to the anti-vaccine propagandist working as one of its correspondents and forces Attkisson finally to make that move.

Steven Salzberg, a friend of this blog and Director of the Center for Bioinformatics and Computational Biology at the University of Maryland, is on the editorial boards of three of the many journals published by BioMed Central (BMC), an important source of open-access, peer-reviewed biomedical reports. He is disturbed by the presence of two other journals under the BMC umbrella: Chinese Medicine and BMC Complementary and Alternative Medicine. A couple of days ago, on his Forbes science blog, Dr. Salzberg explained why. Here are some excerpts:

The Chinese Medicine journal promotes, according to its own mission statement, studies of “acupuncture, Tui-na, Qi-qong, Tai Chi Quan, energy research,” and other nonsense. Tui na, for example, supposedly “affects the flow of energy by holding and pressing the body at acupressure points.”

Right. What is this doing in a scientific journal?… I support BMC…But their corporate leaders seem to care more about expanding their stable than about maintaining the integrity of science. Chinese Medicine simply does not belong in the company of respectable scientific journals.

Forming a scientific journal whose goal is to validate antiquated, unproven superstitions is simply not science, whatever the editors of Chinese Medicine claim.

BMC should be embarrassed to be publishing journals that promote anti-scientific theories and otherwise muddy the literature. By supporting these journals, they undermine the credibility of many excellent BMC journals. They should cut these journals loose.

Matthew Cockerill, a molecular biologist and self-described skeptic who is Managing Director of BMC, responded. Quoting Tim Minchin’s poem Storm (“You know what they call alternative medicine that’s been proved to work?…Medicine”), he wrote:

Well-known examples of “alternative medicines” that have made the transition to “medicine” include aspirin (explicitly cited in ‘Storm’) and artemisinin, a compound identified in a type of traditional Chinese herbal medicine, derivatives of which are now used to treat malaria.

Clearly for this transition to be possible, there must be a way for effective aspects of Complementary/Alternative Medicine (CAM) to prove themselves and to become “Medicine”. Journals focused on evaluating CAM are not the only approach to doing this (such research might also be published in a regular medical journal), but they are one valid approach…

… Regular medical journals may tend to be dismissive of anything with CAM-associations…

In a second comment (which at the time of this writing is unavailable, but Dr. Salzberg sent me a copy) Dr. Cockerill continued:

Steven,

In your post you suggest that journals relating to complementary/alternative medicine (CAM) including Traditional Chinese Medicine have no place in BioMed Central’s portfolio, and your broader implication is that these fields represent nothing but pseudoscience and are unworthy of (or indeed are incompatible with) scientific investigation.

BioMed Central does not share this view. We accept that this is a challenging and controversial area, and that one of the problems to be addressed is that much CAM research is lacking in scientific rigor. However, to dismiss all aspects of CAM out-of-hand and to exclude research on CAM from scientific discourse would only give ammunition to those who try to characterize the scientific process as being close-minded and based on presumptions which are not open to question.

You refer to BMC Complementary and Alternative Medicine as a “pseudoscience journal” which “promote[s] anti-scientific theories”, but this is really not the case.

Dr. Cockerill argued that standards of peer-review and methodological rigor for that journal are not different from those for the rest of the BMC group. He named Edzard Ernst as a member of the editorial board. More:

Moving to the field of Traditional Chinese Medicine – while it is true that there are some aspects of TCM as traditionally practiced that are likely to hold only anthropological/psychological interest from a scientific point of view, it is also clear that there are many active ingredients in traditional Chinese Herbal Medicine (CHM) which are worthy of further investigation in terms of biological mechanism and clinical effectiveness. This is an area that has attracted significant funding from commercial and public sources – see for example this article from Science magazine in 2003. http://www.sciencemag.org/content/299/5604/188.long

Looking at articles published in the journal Chinese Medicine, the evaluation of active components within herbal remedies accounts for a large fraction of research articles published, and this cannot easily be dismissed as either irrelevant or inherently pseudoscientific.

In an earlier email to Steven Salzberg, Dr. Cockerill had written:

The major problem I have with such a blanket dismissal is that it lumps everything together as being equally valueless, whereas the goal of the scientific process is to winnow the wheat (however rare) from the chaff…

If you look at articles published in Chinese Medicine, you will find little if anything on “Energy fields” (not a fruitful area for scientific investigation, I quite agree, and not something which I believe should be in the scope of the journal), but a great deal on biochemical and functional genomic work in relation to traditional herbal medicine, which is quite a different matter.

Bait and Switch: the Yin and the Yang

Sigh. Where to begin? Let’s start by trying a slight revision of Dr. Cockerill’s own words: The major problem I have with such a blanket acceptance is that it lumps everything together as being equally valuable, whereas the goal of the scientific process is to winnow the wheat (however rare) from the chaff…

That’s more like it. I imagine that Dr. Cockerill will find that statement unfair, in that it fails to acknowledge that there may be reports in the two journals that disconfirm hypotheses that are not fruitful for scientific investigation (if you catch my drift). I concede that, but the point here is a different one: Dr. Salzberg objects to including anti-scientific topics in the journals precisely because doing so gives the appearance that real scientists believe that they must be intriguing enough to warrant space in real biomedical journals.

But they are not: it is clear, after a moment’s reflection, that natural products research is the ONLY worthwhile scientific endeavor within the editorial purview of Chinese Medicine, so why pretend that it justifies the rest? Matthew Cockerill may agree that “energy fields” should not be included; nevertheless they are—which was Dr. Salzberg’s point. Tim Minchin, bless his heart, probably doesn’t realize that his statement about “alternative medicine that’s been proved to work” is itself purely hypothetical: there has yet to be an example of such a medicine. Dr. Cockerill ought to know that, as I will explain a bit later in this piece.

An Article Brings Homeopathy to Mind

I have little time to investigate the non-[natural products pharmacology] articles in Chinese Medicine; Dr. Salzberg cited one, which he characterized as “a laughably bad study.” I’ll tell you a bit about another, just published in January:

Misdiagnosis and undiagnosis due to pattern similarity in Chinese medicine: a stochastic simulation study using pattern differentiation algorithm

The article is nearly incoherent. Passages such as this abound:

In Chinese medicine, diagnosis is also important. Practitioners recognise and label nosological conditions based on inspection (Ip, wang), auscultation and olfaction (AO, wen), inquiry (Iq, wen) and palpation (P, qie), also known as the Four Examinations (Sizhen). According to traditional literature, these methods should be applied in order to enhance recovery of the patients. Manifestations (ie signs and symptoms) collected from patients are interpreted using Chinese medicine theories (eg eight principles, five phases, vital substances, six channels, four levels, triple burner and Zangfu), which were developed on the basis of some observations of Nature. Similar to Western medicine, the collected manifestations are interpreted collectively; however, diagnosis is established through a pattern differentiation process whereby a unique, stable manifestation profile is obtained for the identification of a pattern among other diagnostic hypotheses.

The article appears to torture statistics to show that each additional Examination among the Four confers a slightly greater degree of certainty that the examiner will not confuse two different “diagnoses” (in the TCM sense of the term). At least I think that’s the point. But the investigator didn’t determine this by testing actual practitioners, as far as I can tell; he did it using “a stochastic computational simulation based on Monte Carlo method implemented for patient simulation from ZFSP in a dataset.” And a good thing, too, because if there’s anything useful to be gleaned from this paper, it’s found in references 19-24. They show, unsurprisingly, that there isn’t much agreement from one TCM practitioner to the next about either “diagnoses” or treatments.

Hmmm. No surprise when you consider what those diagnoses, i.e., patterns, involve. Here is the pattern of “Deficient Cold of Small Intestine…often discussed as Deficient Spleen Qi,” according to Ted Kaptchuk, an American who seems to have invented the “OMD” degree that won him a professorship at the Harvard Medical School, and who is on the editorial board of Chinese Medicine:

Signs: slight, persistent discomfort in lower abdomen; gurgling noises in abdomen; watery stools.

Tongue: pale material; thin white moss

Pulse: empty

Here is the pattern of “Deficient Cold in Stomach…often called Deficient Spleen Yang”:

Signs: chronic diarrhea; slight persistent pain in epigastrium; discomfort relieved by warmth, eating, and touching; shy; easily influenced by others

Tongue: pale material; most white moss

Pulse: deep or moderate without strength

And so on, for hundreds of patterns. According to Kaptchuk, “pulse examination can be the most important of the Four Examinations and is crucial to pattern discernment in general.” Paul Unschuld, a prolific historian of Chinese medicine, explains how this is done:

The physician has the choice of either feeling the (radial) pulse with three fingers or with one finger. Using three fingers, light pressure with the index finger above the imaginary line level with the styloid process allows him to feel the state of the lung and heart, greater pressure with the middle finger on the imaginary line enables him to feel the state of the spleen, and greater pressure still with the ring finger allows him to feel the liver and kidney. According to a third (and certainly not the last) variant, he can, with one finger, apply a pressure equal to the weight of three beans to feel the lung, a pressure of six beans to feel the heart, a pressure of nine beans to feel the spleen, a pressure of twelve beans to feel the liver, and finally a pressure that brings the fingertip almost to the bone, to feel the kidney.

What does “correct” pattern recognition mean, in the practical sense? Well, it means that the correct therapeutic intervention will occur. Kaptchuk again:

The goal of all treatment methods in Chinese medicine is to rebalance those aspects of the body’s Yin and Yang whose harmonious proportion and movement have become disordered…inappropriate anger such as that characterized by excessive Liver activity must be calmed…insufficient activity, say of the Kidney Yang, must be tonified to avoid lack of sexual energy…If there is not enough Qi in the Lungs, it must be replenished…If the Qi in the Spleen descends, causing chronic diarrhea, it must be lifted; if the Qi of the stomach ascends, it causing nausea, it must be sent down. Stagnant Qi must be moved…Too much Cold in the Kidney must be warmed; extra Fire in the Lungs must be cooled. Whatever is out of balance must be rebalanced. The complementary aspects of Yin and Yang must be harmonious.

Here’s how it’s done:

…the insertion of very fine needles into points along the Meridians can rebalance bodily disharmonies. A related technique [is] moxibustion…The action of the needles or of moxibustion affects the Qi and Blood in the Meridians, thus affecting all the fundamental textures and Organs. The needles can reduce what is excessive, increase what is deficient, warm what is cold, cool what is hot, circulate what is stagnant, move what is congealed, stabilize what is reckless, raise what is falling, and lower what is rising.

OK, enough already. Is it not obvious that this is the classic assortment of metaphors, myths, traditions, and appeals to authority that is common to the medicine of pre-scientific cultures? Were Chinese medicine theories developed on the basis of some observations of Nature? I don’t think so.

The claims regarding pulse examination are quite fanciful, to say the least: that changing the pressure of the examining finger would allow the practitioner to feel the state of the various, named organs is hard to conceive, given what is now known about anatomy and physiology; it’s also clear that pre-modern Chinese physicians would have had no way test this claim. There is a smattering of empirically gathered symptoms and signs that are based on history taking and external examinations, some of which are repeatable and might have eventually become useful, if pre-modern Chinese medicine had pursued anatomy, physiology, and pathology before those fields were developed elsewhere—thus making that aspect of “TCM” moot.

Funny: the “patterns” remind me of another conspicuous pre-scientific “school” of medicine: homeopathy, with its elaborate ‘symptom’-gathering scheme, its voluminous repertories, rubrics, and simillima. And, of course, its lack of agreement from one homeopath to the next regarding the ‘correct’ constellation of ‘symptoms’ and therefore the correct ‘remedy.’

Pharmacognosy is neither “CAM” nor “Chinese Medicine”

Dr. Cockerill’s other points are a mixture of reason and misunderstanding. Legitimate natural products research is not “CAM,” and should neither be billed as such (or as some other misnomer such as “Chinese Medicine”) nor should it be purported to justify “CAM,” which, if anything, hinders such research. Aspirin is not an example of an “alternative medicine that made the transition to medicine” any more than quinine or atropine or digoxin are such examples. Nor is artemisinin. Everyone with a modicum of education knows that many useful drugs have been, and will continue to be, derived from natural sources, exactly as biology would predict. This is completely unsurprising. The term “alternative medicine,” along with its various synonyms, refers to a recent political and quasi-religious movement, not to a longstanding branch of drug development that is scientific and that has not required the help of pseudoscientific zealots to pursue its investigations.

If Chinese Medicine were limited to pharmacognosy and had a more appropriate title—Asian Pharmacognosy, for example, referring to the geographic origin of the products studied, not to some pre-scientific medical ‘system’—I’d have little problem with it, assuming that the natural products reports are as rigorous as Cockerill claims them to be.

“Chinese Medicine” is a misnomer in several ways. First, the medicine overwhelmingly used in China today is modern, scientific medicine. Second, pre-scientific Chinese Medicine was not one or even a few schools of medicine but many disparate schools, occurring at various times over millennia and in various places over a huge geographical region. Some schools were completely unrelated or even contradictory. There was much influence from abroad, including India and Greece. Third, the term “Traditional Chinese Medicine” was coined only about 55 years ago in the PRC, mainly for pitching to (gullible) Westerners. It heralded something that, paradoxically, had never before been true in China: a forced standardization, such as to make ‘Chinese Medicine’ appear to be something that it was not: a conceptual whole.

Last Thoughts

I’m running out of gas, but another straw man used by the “CAM” movement, repeated by Matthew Cockerill, is that “Regular medical journals may tend to be dismissive of anything with CAM-associations.” There was a time in the 1990s when editors of the major journals had to answer this charge on a regular basis, and each time it went something like this:

Dr. Siegel’s charge that medical journals will not publish studies of alternative medicine comes out of thin air. Journals compete avidly to publish important new clinical research, if it is rigorously done. As we indicated in our editorial, the problem with the studies funded by the Office of Alternative Medicine in 1993 was not their size, as suggested by Dr. Cherkin and Ms. Street, but their quality.

In fact, major medical journals have, to their own embarrassment and to the detriment of uninformed readers, bent over backward to accommodate substandard “CAM” treatises.

“CAM” advocacy journals, moreover, have become far more evident in the past few years, thanks in part to political pressure applied by anti-intellectual demagogues such as Dan Burton—even as the only journal committed to an appropriate, skeptical view of “CAM” was excluded from listing by the US National Library of Medicine after similar political pressure.

Perhaps someone else will look at some of the articles in BMC Complementary and Alternative Medicine. I have neither the time nor the inclination, but I would like to reiterate a point that Steven Salzberg and we have all made at one time or another: even the subsequent publication of a reasonable scientific report doesn’t justify creating a journal for the purpose of “helping aspects of CAM prove themselves.” If there’s scientific promise for some new way to solve a problem, and if a legitimate study is done, there are plenty of opportunities to report it in the medical literature.

Could a vitamin with proven benefits in one group cause harm to another? That’s the growing concern with folic acid, the vitamin that dramatically reduces the risk of neural tube birth defects such a spina bifida. Studies designed to explore the possible benefits of folic acid for heart disease, stroke and cancer are giving out some worrying signs: At best, folic acid is ineffective, and at worst it may be increasing the risks of some cancers. So what does this say about routine supplementation for the typical healthy individual, and its overall risk and benefit?

Folate (vitamin B9) is an essential nutrient found green, leafy vegetables, broccoli, peas, corn, oranges, grains, cereals, and meats. Folate has important roles in the synthesis of DNA, and consequently cell division. Significant folate deficiency can lead to macrocytic anemia. Folic acid, a synthetic form of folate, is used in multivitamins supplements because it is better absorbed.

Folic acid’s benefits in pregnancy are well documented. Supplementation before conception, and in the first few weeks of pregnancy, significantly and substantially lower the risk of several different birth defects, including neural tube defects (NTDs). The neural tube is the embryonic precursor to the brain and spinal column. NTDs include very serious defects like spinal bifida and anencephaly, birth without part of the brain.

The stakes are high, and because the neural tube forms so early in pregnancy (day 26 to 28), deficiencies must be corrected before a woman knows she is pregnant. This has led to public health strategies that mandate supplementation in food products: In both the United States and Canada, folic acid has been added to white flour since the late 1990’s, where it finds its way into baked goods like bread. Following food fortification, neural tube defects have subsequently dropped.

In addition to food fortification, women that could become pregnant are generally advised to take a multivitamin containing at least 0.4mg of folic acid daily. Women at high risk of NTDs may be advised to take higher doses. But as higher doses of folic acid can mask the symptoms of Vitamin B12 deficiency, higher doses warrant medical advice and supervision.

Even with fortification, it’s clear there are still opportunities to improve folic acid consumption in pregnancy. A Canadian population study showed that 20% of women of childbearing age failed to have appropriate folic acid levels in their blood. And while virtually no-one was dangerously deficient, over 40% had levels that would be considered high.

Beyond pregnancy

Observational trials have correlated a diet rich in fruits and vegetables with a lower risk of diseases like colorectal cancer. Based on this epidemiologic evidence, several randomized controlled trials were initiated investigating the effect of the B vitamins (including folic acid) on cancer risk. Folic acid held particular promise because of its proven effects preventing neural tube birth defects.

But the effects were not as expected.

The Warning Signals

That folic acid may interfere with cancer has been known since the 1940’s. The chemotherapy drug methotrexate is an antifolate agent that blocks the metabolism of folic acid, developed after it was noted that a diet deficient in folic acid helped patients with leukemia.

Studies of folic acid supplementation are raising flags about the potential risks of therapy, possibly as a result of excessive consumption. One of the most startling was a study that looked at folic acid supplementation in patients with colorectal adenomas, which are cancer precursors. Participants were randomized to folic acid 1mg or placebo for up to six years. While it was hypothesized that folic acid would provide a protective effect, the results were disappointing. Not only did folic acid have no effect on adenoma incidence (even in those with low folate status),  there was a significant increase in the risk of non-colorectal cancers (10.5% vs. 6.3%), due mainly to an excess of prostate cancers.

Futher worrying evidence emerged in 2009, when a Norwegian study of heart failure patients was published. Researchers randomized almost 7000 patients to folic acid and vitamin B12 versus other vitamins or placebo. The vitamins significantly raised the risks of both cancer and all-cause mortality, driven mainly by more cases of lung cancer. On balance, looking at heart disease, folic acid supplementation don’t seem to have any persuasive effects, either. In combination with other B-vitamins to lower homocysteine levels it hasn’t been shown to have meaningful effects on cardiovascular disease prevention, either.

The same worrying cancer signal has appeared with breast cancer in postmenopausal women, even while dietary folate seems to be beneficial. And in studies looking at prostate cancer, when folic acid is combined with other vitamins, the data are unclear.

So could fortification be causing harm? While correlations have been drawn between food fortification and population studies of colorectal cancer, causality hasn’t been established. Screening rates or other factors could be contributing. Still, the idea is troubling, even though the harms (if real) are slight compared to the demonstrable and significant benefits fortification has played  in reducing NTDs.

Conclusion

In women of childbearing age, folic acid supplementation has a demonstrable and meaningful benefit, reducing the incidence of NTDs. Its use in this population is evidence-based and demonstrably effective. And for treatments for conditions like end-stage kidney disease, folic acid may be of benefit. But when we look at the use of folic acid for primary prevention, the data are less clear. In children, men, and women beyond their childbearing years, supplementation in the absence of deficiency has no demonstrated health benefits, and there are worrying signals that it may raise cancer risks, possibly by “feeding” existing cancers.

Is fortification of our food supply harming and hurting? The benefits on NTD incidence have been demonstrated, while the harms haven’t been proven yet. Still, folic acid’s evolving story may become a cautionary tale about the consequences of fortification and supplementation with the hope of improved health outcomes. If we’re not in our childbearing years, we may be better off relying only on food sources for folate. So pass the spinach, and hold the multivitamins with folic acid.

The scientific approach to understanding the world includes the process of carefully separating out variables and effects. Experiments, in fact, are designed specifically to control for variables. This can be especially challenging in medicine, since the body is a complex and variable system and there are always numerous factors at play. We often characterize the many variables that can influence the outcome in a clinical study as “placebo effects” or “non-specific effect” – things other than a specific response to the treatment in question.

A common error to make when interpreting clinical studies is to confuse non-specific effects – those that result from the therapeutic interaction or the process of observation – with a specific effect from the treatment being studied. While this is broadly understood within the scientific medical community, it seems that within certain fields proponents are going out of their way to sell non-specific effects as if they were specific effects of the favored treatment.

This is perhaps most true for acupuncture. As has been discussed numerous times on SBM, the consensus of the best clinical studies on acupuncture show that there is no specific effect of sticking needles into acupuncture points. Choosing random points works just as well, as does poking the skin with toothpicks rather than penetrating the skin with a needle to elicit the alleged “de qi”.

The most parsimonious interpretation of the evidence is that the needles (i.e. acupuncture itself) are superfluous – any perceived benefit comes from the therapeutic interaction. This has been directly studied, and the evidence suggests that the way to maximize the subjective effects from the ritual of acupuncture is to enhance the interaction with the practitioner, and has nothing to do with the acupuncture itself. Acupuncture is a clear example of selling a specific procedure based entirely on non-specific effects from the therapeutic interaction – a good bedside manner and some hopeful encouragement.

This phenomenon is by no means limited to acupuncture. Perhaps another example is Eye Movement Desensitization and Reprocessing (EMDR), a practice that is increasingly popular among psychiatrists.

The concept of EMDR – how it is supposed to work – sounds pseudoscientific to this neurologist. According to the EMDR Institute:

During treatment various procedures and protocols are used to address the entire clinical picture. One of the procedural elements is “dual stimulation” using either bilateral eye movements, tones or taps. During the reprocessing phases the client attends momentarily to past memories, present triggers, or anticipated future experiences while simultaneously focusing on a set of external stimulus. During that time, clients generally experience the emergence of insight, changes in memories, or new associations.

The external stimulus – whether moving the eyes or tapping on the client or playing certain tones – is supposed to help the brain reprocess memories and information, and is alleged to be useful for a wide range of psychiatric symptoms. The proposed mechanism sounds highly dubious. While the brain certainly has plasticity, the ability to change its wiring through use, it is hard to imagine how such a simple procedure could have a significant effect on this plasticity. There are many who suspect that the eye movement component to EMDR therapy may be the equivalent to the needle component of acupuncture.

In psychotherapy there are many sources of non-specific effects that would need to be carefully controlled for before the effects of any specific component can be determined. The interaction with the therapist, the time taken to focus on ones problems and symptoms, and the introduction of a novel element into the therapeutic relationship are all recognized factors. In addition, EMDR (not surprisingly) has evolved into a multifaceted treatment approach, that includes many standard elements of therapy. This always reminds me of the commercials who proudly advertise that their products are “part of this nutritious breakfast.” Yes, but are they an important part – or is the breakfast nutritious without it?

A 2002 review of EMDR in general concluded:

Current component analyses of EMDR have failed to effectively evaluate the relative weighting of its procedures.

And a more recent 2006 review of EMDR compared to cognitive-behavioral therapy for post traumatic stress disorder (PTSD) concluded:

Our results suggest that in the treatment of PTSD, both therapy methods tend to be equally efficacious. We suggest that future research should not restrict its focus to the efficacy, effectiveness and efficiency of these therapy methods but should also attempt to establish which trauma patients are more likely to benefit from one method or the other. What remains unclear is the contribution of the eye movement component in EMDR to treatment outcome.

The last line is most significant – what contribution, if any, does the actual EMDR have? The research has not clearly established that the eye movements are having a specific neurological or psychological effect. Perhaps it’s just all the other components of the therapy that is having the perceived effect. And yet EMDR has been widely accepted as a treatment modality. This acceptance seems premature.

It also seems that this is another failure of the evidence-based medicine (EBM) approach – EMDR  is being hailed as an evidence-based practice. There are indeed studies that show that EMDR therapy works. But a science-based approach would consider more deeply the question of plausibility and mechanism, and from this question whether or not EMDR has indeed been established as having specific efficacy.

Conclusion

EMDR, like acupuncture, is likely nothing more than a ritual that elicits non-specific therapeutic effects.  While there are some who may consider this a justification for both modalities, there is significant risk to this approach. First, the non-specific effects are often used to justify alleged specific mechanisms of action which are likely not true. This sends scientific thought and research off on a wild-goose chase, looking for effects that do not exist. Science is a cumulative process built on consilience – scientific knowledge must all hang together. These false leads are a wrench in the mechanics of science.

Second, the false specificity of these treatments is a massive clinical distraction. Time and effort are wasted clinically in studying, perfecting, and using these methods, rather than focusing on the components of the interaction that actually work.

And in the end these magical elements do not add efficacy. For example, as the review above indicates, EMDR is no more effective than standard cognitive-behavioral therapy.

Rather than getting distracted by alluring rituals and elaborate pseudoscientific explanations for how they work, we should focus on maximizing the non-specific elements of the therapeutic interaction, and adding that to physiological or psychological interventions that have specific efficacy.

Believers in acupuncture claim it is supported by plenty of published scientific evidence. Critics disagree. Thousands of acupuncture studies have been done over the last several decades, with conflicting results. Even systematic reviews have disagreed with each other. The time had come to re-visit the entire body of acupuncture research and try to make sense out of it all. The indefatigable CAM researcher Edzard Ernst stepped up to the plate. He and his colleagues in Korea and Exeter did an exhaustive study that was published in the April 2011 issue of the medical journal Pain:   “Acupuncture: Does it alleviate pain and are there serious risks? A review of reviews.” It is accompanied by an editorial commentary written by yours truly: “Acupuncture’s claims punctured: Not proven effective for pain, not harmless.” (The editorial is reproduced in full below.)

Ernst et al. systematically reviewed all the systematic reviews of acupuncture published in the last 10 years: 57 systematic reviews met the criteria they set for inclusion in their analysis. They found a mix of negative, positive, and inconclusive results. There were only four conditions for which more than one systematic review reached the same conclusions, and only one of the four was positive (neck pain). They explain how inconsistencies, biases, conflicting conclusions, and recent high quality studies throw doubt on even the most positive reviews.

They also demolished the “acupuncture is harmless” myth by reporting 95 published cases of serious adverse effects including infection, pneumothorax, and 5 deaths. Some but not all of these might have been avoided by better training in anatomy and infection control.

Their analysis does not prove that acupuncture doesn’t work (negatives are hard to prove) but it unquestionably sheds serious doubt on the claim that it does work. Overall the evidence is inconsistent, and the results tend to be negative among those studies judged to be of the highest quality. Where the results are positive, the reported benefits can be explained by the surrounding ritual, the beliefs and expectations of patient and practitioner, and other nonspecific effects of treatment. There is no evidence to support the vitalistic concept of qi or the prescientific mythology of acupuncture points and meridians; it doesn’t seem to matter where you put the needles or whether the skin is pierced. More modern science-based explanations like increased endorphin production are not convincing, since placebo pills can produce the same effects.

I was delighted when the editor of Pain asked me to write a commentary to accompany the article. It gave me a soapbox in a major medical journal to say all the things I thought needed to be said about acupuncture.

My commentary was edited, but it was a very different experience from the kind of editing I experienced with O,The Oprah Magazine. It was a pleasant collaborative process aimed only at improving the clarity of the writing and strengthening the impact of what I wanted to say.

The journal thought our articles were important enough to warrant a press release. Both Ernst’s article and my commentary immediately got some attention in the media: Science Daily, Medical News Today, e! Science News, and the American Council on Science and Health all reported on them.

Believers in acupuncture will not be pleased. I expect a hostile response and am wondering if Ernst and I should invest in needle-proof vests.

Here is the entire text of my commentary. Thank you to the publishers of Pain, the IASP and Elsevier, for their permission to reproduce it here.

Acupuncture’s claims punctured: Not proven
effective for pain, not harmless

Commentary from Hall H. Acupuncture’s claims punctured: Not proven effective for pain, not harmless. PAIN 2011 Apr; 152(4): 711-712

© 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. This article has been reproduced on ScienceBasedMedicine.org with permission of the International Association for the Study of Pain® (IASP®). The commentary may not be reproduced for any other purpose without permission. Permission to alter the article is not permitted. Permission to translate the article is not granted.

In this issue of Pain Ernst et al. [1], systematically reviewed a decade’s worth of systematic reviews of acupuncture. They found a mix of negative, positive, and inconclusive results. There were only four conditions for which more than one systematic review reached the same conclusions, and only one of the four was positive (neck pain). They explain how inconsistencies, biases, conflicting conclusions, and recent high quality studies throw doubt on even the most positive reviews. Ernst et al.’s analysis cannot prove that acupuncture does not work (negatives are hard to prove) but their study unquestionably sheds serious doubt on the claim that it does work. Overall the evidence is inconsistent, and among those studies judged to be of the highest quality, the results tend to be negative.

Acupuncture is based on pre-scientific concepts of a vitalistic entity (qi) and of meridians and acupuncture points unknown to anatomists. More scientific explanations have been offered as to how it might work, including a counterirritant effect or the gate control theory of pain. There is evidence that acupuncture can stimulate endogenous endorphin production, but there is evidence that placebo pills can do that as well. Importantly, when a treatment is truly effective, studies tend to produce more convincing results as time passes and the weight of evidence accumulates. When a treatment is extensively studied for decades and the evidence continues to be inconsistent, it becomes more and more likely that the treatment is not truly effective. This appears to be the case for acupuncture. In fact, taken as a whole, the published (and scientifically rigorous) evidence leads to the conclusion that acupuncture is no more effective than placebo.

Acupuncture research is inherently riddled with pitfalls. What constitutes an adequate control? People can usually tell whether or not you are sticking needles in them. Various controls have been devised, such as comparing ‘‘true’’ acupuncture points to ‘‘false’’ ones. The best control so far is an ingenious retractable needle similar to a stage dagger, where the needle just touches the skin and retracts into a sheath. Unfortunately, there is no way to blind the practitioner, so double blind studies are impossible.

The practice of acupuncture is also not sufficiently standardized, which makes it difficult, if not impossible to pin down reliably for objective study: there are various schools of acupuncture with different acupoints, and studies of acupuncture have included ‘‘electroacupuncture’’ (with or without needles), ear acupuncture, cupping, moxibustion, and other loosely related procedures. In their book, The Biology of Acupuncture, Ulett and Han [3] showed that transcutaneous electrical stimulation at a single arbitrary point on the wrist was just as effective as piercing the skin at traditional acupuncture points.

In more than one recent study, researchers have chosen not to use a sham acupuncture control group. Their reasoning? Since sham acupuncture has been shown to work as well as real acupuncture, then sham acupuncture must be an effective treatment too! Imagine applying this reasoning to a drug trial: if the drug and placebo got the same results, would you decide that the drug worked and that the placebo was just as therapeutic as the drug?

It does not make any difference where you put the needles or whether you use needles at all. Touching the skin with toothpicks works just as well. The crucial factor seems to be whether patients believe they are getting true acupuncture. It is becoming increasingly clear that the surrounding ritual, the beliefs of patient and practitioner, and the nonspecific effects of treatment are likely responsible for any reported benefits.

Is there really any need for more studies? Ernst et al. point out that the positive studies conclude that acupuncture relieves pain in some conditions but not in other very similar conditions. What would you think if a new pain pill was shown to relieve musculoskeletal pain in the arms but not in the legs? The most parsimonious explanation is that the positive studies are false positives. In his seminal article on why most published research findings are false, Ioannidis points out that when a popular but ineffective treatment is studied, false positive results are common for multiple reasons, including bias and low prior probability [2]. More studies are not the answer. No matter how many studies showed negative results, they would not persuade true believers to give up their beliefs. There will always be ‘‘one more study’’ to try, but there should be a common-sense point at which researchers can agree to stop and divert research time and funds to areas more likely to produce useful results.

Of course, advocates of acupuncture have argued that it is worthwhile even if it only produces a placebo response; and that it is harmless, so it does not hurt to try it. Ernst et al. however, have shown that acupuncture is not harmless. While many of the reported adverse effects could be avoided by proper training in sterile precautions and anatomy, they correctly point out that even one avoidable adverse event is too many. With any treatment, we have to consider the risk/benefit ratio. If there is no benefit, any risk is too much. And there are other harms that they did not mention: time and money wasted, effective treatment delayed, unscientific thinking encouraged.

Placebos are unethical: our patients trust us not to prescribe them. With the current state of the evidence, I do not think we should be recommending acupuncture to our patients. On the other hand, if patients ask about it and want to try it, we should not try to stop them. We have a responsibility to educate them, but not to make decisions for them. We can tell them that although some patients believe it has helped them, the evidence does not show that it works any better than placebo, and there is a small risk of infection and other complications. With this information, they can then make their own informed decision.

In summary, Ernst et al. have shown that the evidence for efficacy of acupuncture for the treatment of pain is questionable, to say the least, and of particular concern is that its use can be dangerous. If the 57 systematic reviews they surveyed had been for a prescription drug and a similar list of serious adverse effects had been reported for that drug, we would hesitate to prescribe that drug. Is there any reason not to hold acupuncture to the same standards?

Conflict of interest statement

I have no conflicts of interest to report.

References

1. Ernst E, Lee MS, Choi TY. Acupuncture: Does it alleviate pain and are there serious risks? A review of reviews. Pain 2011;152:755–64.
2. Ioannidis JP. Why most published research findings are false: author’s reply to Goodman and Greenland. PLoS Med 2007;4:e215.
3. Ulett GA, Han SP. The biology of acupuncture. St. Louis, USA: Warren H. Green Inc.; 2002. 160p.

EDITOR’S NOTE Today is a big grant deadline for me; at 5 PM EDT, the grant is due. As a consequence of working on my grant application into the wee hours of the morning last night, I didn’t have a chance to write my usual bit of logorrhea of the sort that I’ve laid down each and practically every Monday for the last three-plus years. Fortunately, retired chiropractor turned skeptic of chiropractic Sam Homola was ready to fill in admirably just for this week. Although I might throw up a post later this week, worst case scenario, I’ll be back here, same time, same day, same Bat Channel. In the meantime, take it away, Sam!

As a chiropractor, I am often asked why the image of chiropractic is so bad. “Why is chiropractic so often ignored by the media and ridiculed by physicians?” Journalists and health professionals tend to judge chiropractic by the worst of what they see, and what they see is often bad. This March 15, 2011, post from a chiropractic group asking for money to provide chiropractic services for earthquake and tsunami victims in Japan is a good example of why chiropractic has a bad image:

Please consider donating whatever you can to the SOTO-I/PAAC [Sacro Occipital Teaching Organization International-Pacific Asian Association of Chiropractic] Japan Relief Fund. 100% of your donation will go directly to helping the needy Japanese people through SOT Chiropractic treatments and services.

Please consider this avenue of donation rather than the Red Cross etc. While they are worthy organizations, we have ZERO overhead to administration and the funds will provide CHIROPRACTIC services to the needy. Please recommend this avenue of aid to your patients and friends also. Any and everything will help!

Practitioners of Sacro Occipital Technic (SOT) and SOT Craniopathy claim to restore innate healing capacity by removing neurological interference and improving the flow of cerebrospinal fluid (“craniosacral respiration”). Vertebral subluxations affecting certain organs are found by palpating tendon insertions at the base of the skull. Craniosacral respiration is improved by adjusting the bones of the skull and the sacroiliac joint.

There are dozens of such nonsensical chiropractic treatment methods foisted on the public through “press releases” and junk-science journals. NUCCA (upper cervical technique), which identifies slight misalignment of the atlas as a major cause of human ailments, is a commonly-promoted technique based on chiropractic vertebral subluxation theory.

This press release further illustrates the reason for chiropractic’s bad image:

A revolutionary neuro relief technique is being used by chiropractors across the United States and Canada to treat a wide-array of Symptoms and Chronic Disorders they were never before able to handle. This technique, when applied correctly performs absolute miracles for patients who have been suffering for an extensive period in their lives. Thus patients are happier and chiropractors are increasing their visibility and incomes!

Online PR News – 12-March-2011

An article titled “Second Opinion: Of Chiropractors & Christians,” published in a Baptist news magazine, describes an “inherently unbelievable” chiropractic message:

My back hurt, so I went to a chiropractor. He is helping my back pain. That’s a good thing.

But that is not what this article is about.

My chiropractor is an evangelist for his particular brand of chiropractic. Literally, he and his staff are religious about it. They preach the word. They offer written materials. They make promises of a greater life. I am unmoved. I just want him to make my back feel better.

I have a better understanding now of how nonbelievers may react to Christian witness. My reactions to the “message” I get at my chiropractor’s office could also be the reactions of someone you know to church, Christianity or the gospel message of Christ:

• These folks are extremely nice, and I appreciate that, but that does not mean I am going to believe what they believe or what they tell me to believe.
• They sincerely believe what they say. I do not doubt that. Their sincerity does not persuade me to change my mind.
• They walk the walk. They cleanse their toxins, go to burst training, take supplements and get regular adjustments. As far as I can tell, they are not hypocrites. But I am not moved.
• They go out of their way to educate me. They offer written information. They invite me to seminars, dinners and meetings. I do not have the excuse that “I don’t understand.”
• These folks care about me. I believe that.

So, why am I not fully sold? Why won’t I buy into the full program instead of just “settling” with having them make my back feel better?

• Their message is inherently unbelievable.
• Their message runs counter to what I know and to what I read and hear everywhere else.
• Their message is too demanding of my time, energies and commitments.

Sound familiar? Those are reasons why people routinely reject our Christian witness…

Published: March 11, 2011 (The Baptist Standard)

Sorting out a Few Good Apples

As illustrated by the above clips, it’s not hard to understand why chiropractic has such a bad image. If the chiropractic profession does not take steps to eliminate the nonsense in chiropractic, it may be difficult for ethical, science-based chiropractors to separate themselves from questionable treatment methods that have been traditionally supported by chiropractic subluxation theory. The practice-centered approach of chiropractors who disseminate misinformation, whether they are true believers or not, hurts the public as well as the profession. It is unlikely that unethical chiropractors will voluntarily give-up a faith-based or money-based approach they are using to make a living. Ethical chiropractors, many of whom are well-meaning but misinformed, struggle while pitch masters thrive. Guardians of public health feel compelled to issue warnings about chiropractic. Science-based chiropractors, as individuals, are forced to distance themselves from misguided colleagues and from purveyors of bogus methods based on the tenets of chiropractic. My heart goes out to those well-meaning chiropractors whose education left them totally dependent upon belief-based self-employment. Few of them have the faculties or the means needed to take a different path.

While it would be painful for chiropractors to point out and renounce obviously worthless diagnostic and treatment methods used by some of their colleagues, it might be prudent for chiropractic associations to do so to establish credibility in the eyes of the public. No other health profession has such a negative image. Good chiropractors are mixed in with bad chiropractors, like a crate of partially spoiled fruit that still contains a few good apples but is often discarded.

The chiropractic profession has to face the reality that chiropractic as a method of treating human ailments by adjusting vertebral subluxations is not acceptable in the scientific community and is unrelated to the generic spinal manipulation now being used by physical therapists and science-based chiropractors. A look at chiropractic journals, advertisements, and office procedures, however, reveals that a large number of chiropractors still cling to Palmer’s subluxation theory, some combining science with pseudoscience. I suspect that chiropractic has survived primarily because its use of manipulation in the treatment of back pain has provided a service not readily available in medical care, that is, symptomatic relief for mechanical-type neck and back pain or a good back-cracking back rub for providing pleasure and relieving tension. I believe the chiropractic profession today would be better off if it renounced the subluxation theory that gave it birth and concentrated on caring for back pain. So far, there is no indication that this will happen any time soon. Until the chiropractic profession does discard the vertebral subluxation theory, it will be difficult for the profession to condemn a multitude of popular, wacky chiropractic techniques based on a theory that defines the profession.

Entrenched Subluxation Theory

When the Council on Chiropractic Education (CCE) proposed new accreditation standards for chiropractic colleges, subject to take effect in January of 2012, all reference to “subluxation” was omitted. (“The CCE does not define or support any specific philosophy regarding the principles and practice of chiropractic, nor do the CCE Standards support or accommodate any specific or political position. The Standards do not establish the scope of chiropractic practice. They specify core educational requirements but do not otherwise limit the educational process, program curricular content, or topics of study.”) The American Chiropractic Association (ACA), the largest association in America representing the chiropractic profession, responded, in part, with this comment regarding the subluxation:

The document removes all references to the term “subluxation” – a core element of the practice of chiropractic that has been integral since the profession’s beginnings over 100 years ago. While the term “subluxation” and its role in the practice of chiropractic is sometimes misunderstood or not fully appreciated by all parties involved in medical related research and the delivery of health care, the term is one which is explicitly recognized in federal law (Section 1861(r) of the Social Security Act) and has been widely recognized by the courts, state legislative bodies and licensing authorities. The elimination of any reference to this term in the proposed standards will be viewed by many within the profession as a counter-productive action that will, in the long-term, likely weaken the profession’s collaborative strength and historic identity. We would propose placing “subluxation theory” back into Section 2, H. Educational Program for the Doctor of Chiropractic Degree and Vertebral Subluxation Complex into Section 3 Initial assessment and diagnosis as a required component.

As a chiropractor and a critic of chiropractic, I often found common ground with other health-care professionals by noting the value of generic spinal manipulation while providing guidelines to separate science-based chiropractors from subluxation-based chiropractors. Failure to point out obvious chiropractic nonsense may simply allow a believing public to assume that all chiropractors are the same, most of whom do not deserve to feed off the positive image projected by a few ethical, science-based chiropractors. Subluxation-based chiropractors peddle dubious services without opposition from their colleagues or from their associations, alienating chiropractic from the scientific community.

When I published my book Bonesetting, Chiropractic and Cultism in 1963, I renounced the vertebral subluxation theory and recommended that chiropractic be developed as a back specialty. It has always been my hope that chiropractic would become a form of physical medicine, a sub-specialty of medicine offering physical treatment methods for mechanical-type neck and back problems. If chiropractic aspires to become an independent, primary non-surgical specialty capable of accepting full responsibility for treating neck and back pain and related problems, it would have to have access to certain prescription medications and all available rehabilitative and physical treatment methods as well as access to hospital facilities, requiring changes in state laws and chiropractic college curriculum. As a back-pain specialty or sub-specialty, the chiropractic profession could be sustained by referrals from other health-care professionals.

Back Specialists?

In 2005, the World Federation of Chiropractic defined chiropractors as “…spinal health care experts in the health care system…with emphasis on the relationship between the spine and the nervous system…” This ambiguous definition fails to place proper limitations on the practice of chiropractic, leaving the door open for subluxation-based chiropractors who use spinal adjustments to treat general health problems. Such chiropractors, with only a hammer in their tool box, cannot qualify as a legitimate “back specialist” or “spine specialist.”

According to the Agency for Healthcare Policy and Research, low-back trouble is the second most common reason for office visits to primary care physicians and the most common reason for office visits to orthopedic surgeons, neurosurgeons, and occupational medicine physicians. Back problems are the most common cause of disability among persons under the age of 45 (Acute Low Back Problems in Adults, 1994). Despite the fact that back pain is one of this nation’s most common ailments, the niche for a back-pain specialty remains unfilled. With changes, chiropractic could have filled this niche (specializing like optometry or chiropody), but instead chose to be defined as a form of alternative medicine with a limited treatment method and an unlimited scope of practice .

Most people think of a chiropractor as a “back doctor.” And most people who go to a chiropractor go for treatment of a neck or back problem. It is certainly ironic that many chiropractors consider it demeaning to be called a “back specialist,” preferring to “treat human ailments without use of drugs and surgery.” Unfortunately, most state laws define chiropractic in this way, resulting in scientific and societal suspicion that hinders change and keeps utilization of chiropractic low.

Today, 48 years after publication of my Bonesetting book, I am still of the opinion that the chiropractic profession is not properly defined and limited. Chiropractic associations continue to tolerate implausible theories that provide an umbrella for inappropriate use of spinal manipulation and a variety of proprietary treatment methods applied to the gamut of human ailments. Many subluxation-based chiropractors seek support in the camp of alternative medicine where they are more readily accepted and where quackery is rampant. They are not representative of chiropractors who follow the guidelines of science in limiting their scope of practice. The uncontested proclamations of chiropractors who make vague and all-inclusive claims continue to drag the profession down, as indicated by figures showing that the percentage of the population seeing chiropractors annually decreased from 9.9% in 1997 to 7.4% in 2002 (Altern Ther Health Med. 2005;11:42-49), despite increasing popularity of alternative medicine.

Scientific presentations will not eliminate a belief system such as homeopathy or subluxation-based chiropractic, nor will the actions of a few science-based chiropractors. It seems likely that there will always be subluxation-based chiropractors. Until the majority of chiropractors make a clean break from what has traditionally been known as chiropractic (adjusting the spine to restore and maintain health), changes for the better in the profession as a whole will be problematic. Chiropractic associations will tend to represent the views of the majority, even if these views are scientifically indefensible. And the definition of chiropractic will continue to be based upon consensus rather than upon science.

Since physical therapy as a sub-specialty of medicine is now incorporating use of science-based manipulation in an armamentarium designed for treatment of neck and back pain and other musculoskeletal problems, it might be too late for the chiropractic profession to establish itself as a preferred back-pain specialty or sub-specialty. Forty-six states now allow direct access to the services of a physical therapist without physician referral. According to the American Physical Therapy Association, physical therapy, by the year 2020, will be provided by physical therapists who are doctors of physical therapy and who may be board-certified specialists.

The Majority Rules

Chiropractors who use manipulation appropriately may be in the minority, making it necessary for them to seek refuge and camaraderie in small groups of like-minded chiropractors who voluntarily follow the guidelines of science in offering patient-centered care. It would certainly be nice if these chiropractors could be separated from the herd with a special degree in a separate camp until they become a majority and the national associations are forced to follow suit.

Until then, I hope that good chiropractors will offer their patients (and the public) tips on how to recognize questionable claims so that good judgment can be exercised in selecting a chiropractor. It may be necessary for chiropractors themselves to openly criticize esoteric techniques used to locate and correct the mysterious, asymptomatic, and undetectable chiropractic vertebral subluxations alleged to be a cause of disease. Scientifically indefensible theories and treatment methods must be labeled as such to discourage use by the public as well as by chiropractors. As the undesirable aspects of chiropractic (e.g., “killer subluxations”) become less acceptable in the eyes of the public, fewer chiropractors will tout such nonsense. When science-based chiropractors are in the majority, if that ever happens, chiropractic associations might then define chiropractic properly and make appropriate changes in state laws.

Finding a Good Chiropractor

Here are the guidelines I offer patients who might want chiropractic treatment for back pain:

• While a good chiropractor can do a good job treating back pain, not all chiropractors are the same; some follow the guidelines of science, some do not.
• Look for a chiropractor who limits his/her practice to care of musculoskeletal problems and who uses hands-on generic spinal manipulation in combination with physical therapy modalities. Such a chiropractor can often be found working in a multi-disciplinary back-pain clinic.
• Avoid chiropractors who propose to locate and adjust “vertebral subluxations” as a treatment for disease or to “restore and maintain health.”
• Avoid chiropractors who ask for payment in advance for a long course of treatment. As a general rule, treatment should be discontinued if symptoms worsen after one week or have not improved after two weeks.
• Avoid chiropractors who routinely x-ray new patients or who do full-spine x-rays on every patient. Remember that simple back strain will usually resolve on its own in a few weeks and does not require an x-ray exam.
• Do not accept the services of a chiropractor who refuses to share his/her records with your family physician or a medical specialist. An orthopedist who has exchanged office notes with chiropractors can often offer guidance in selecting a chiropractor.
• Persons who want manipulative therapy for a back problem but are reluctant to see a chiropractor should ask for a referral to a physiatrist, a physical therapist, or an orthopedic manual therapist who has been trained in the use of spinal manipulation.

Everybody’s Doing It

One argument that often comes up when skeptics and proponents of so-called complementary and alternative medicine (CAM) debate is the question of the popularity of various CAM practices. Advocates of CAM often claim these practices are widely used and growing rapidly in popularity. Obviously, CAM proponents have an interest in characterizing their practices as widely accepted and utilized. Even though the popularity of an idea is not a reliable indication of whether or not it is true, most people are inclined to accept that if a lot of people believe in something there must be at least some truth to it. The evidence against this idea is overwhelming, but it is a deeply intuitive, intransigent notion that can only rarely be dislodged.

It might therefore be useful to get some idea of whether or not the claims of great popularity for CAM treatments are true. If they are not, fruitless debates about the probative value of such popularity could potentially be avoided, and it might be possible to diminish the allure associated with the belief that “everybody’s doing it.” 

Surveys of CAM Use

It is difficult to find good quality objective data on the popularity of particular CAM interventions, and many of the surveys that have been done are potentially misleading. For example,. the 2007 CDC National Health Interview Survey (NHIS) is widely cited as showing that about 30% of Americans use CAM therapies. A careful look at the details of this survey, however, shows that many of the supposed CAM therapies are really relaxation or exercise practices, such as massage and yoga, not medical therapies. Chiropractic is the only medical therapy generally classified as alternative that was used by more than 10% of people in the survey. And that was primarily for idiopathic lower back pain, an indication for which it is generally accepted, even by skeptics such as myself, as having some demonstrated benefit, about equal to standard medical interventions. These usage numbers haven’t changed in decades, which belies the notion that CAM is growing in popularity.

Similarly, much was made by the media of a recent CDC survey that supposedly showed widespread use of CAM therapies in hospice care facilities. A close analysis of this survey, also shows that most of the therapies listed are not truly alternative medical interventions and that fewer than half the facilities surveyed offered true CAM therapies, and fewer than 10% of patients in those facilities actually employed the CAM practices offered.

Studies of Acupuncture Use

I thought it might be useful to look at some of the data concerning the popularity acupuncture, since it is probably the most widely used and accepted CAM therapy after chiropractic, and there have been a few interesting studies in this area. There are certainly no comprehensive, high-quality data concerning how many people use acupuncture, for what indications, and with what sort of beliefs in its underlying theory or effectiveness. My purpose is not to make a definitive statement about how popular acupuncture is but simply to take a small step beyond vague impressions and unsupported claims about the popularity of this intervention and look at what research there is and what insight, if any, these numbers might give us. 

The 2007 NHIS data indicated 6.5% of Americans had reported ever using acupuncture. Of these, 22% had seen an acupuncturist in the last 12 months. 25% of those who had tried acupuncture had done so once, and 70% had seen an acupuncturist fewer than 5 times. The vast majority of those who had seen an acupuncturist had done so for some kind of pain, primarily arthritis and other orthopedic pain, headaches, or fibromyalgia. About 40% of the people who reported using acupuncture for a specific condition specifically reported not using conventional therapies for that condition, while 20-40% reported using some kind of conventional medical therapy for the same condition. 

It is often argued that lack of interest in the utilizing acupuncture is driven more by cultural prejudice or belief systems than by concerns about the evidence for its efficacy. There is likely some truth to the fact that people from different cultures prefer familiar styles of medical treatment, though of course this says nothing about what is actually safe or effective. And part of the appeal of acupuncture in the West is likely its exotic, “foreign” associations.

Some surveys of acupuncture use have looked at whether different ethnic groups in the West have differences in their utilization of acupuncture. Interestingly, one study from Canada found that while White and Chinese Canadians differed in their use of some CAM modalities, their overall use of CAM was the same, and their use of acupuncture specifically was about the same: roughly 8%. (Therapies included in definition of CAM in Quan et al 2008: Herbal remedies, massage therapy, chiropractic, acupuncture, amino acids, naturopathy, homeopathy, reiki, ayurvedic medicine, biofeedback, hypnosis.)

In contrast, a survey of Chinese Americans in a mental health services program found about 25% used acupuncture, and that this use was more prevalent among “less acculturated” individuals. This, of course, is a group not at all representative of the general population, so the relevance of this to overall acupuncture use among Chinese Americans and Americans of other ethnicities is not clear. Other studies have shown significant but complex relationships between ethnicity, education, and other variables and the likelihood of acupuncture use.

It seems reasonable that cultural traditions play some role in the acceptance or rejection of acupuncture as a medical therapy, but the current data do not support that cultural affiliation alone is the most important variable, and the reasons people use acupuncture seem quite consistent regardless of ethnicity or nationality. In any case, studies of populations in North America do not show anything approaching a majority of the population regularly using acupuncture as a medical therapy. Numbers vary from less than 10% to as high as 50% in some populations, but most tend to be in the lower end of that range.

Since acupuncture as it is currently understood and practiced in Europe and North America originated in China and has been employed there and in other Asian countries for a lot longer than it has been used in the West (though not nearly as long as is usually claimed), it makes sense that it would be far more widely used in that part of the world if it is truly as popular a therapy as its proponents claim.

One 2007 study in Taiwan found about 11% of beneficiaries of national health insurance had used acupuncture in a given year. Interestingly, while the survey found that overall use of Traditional Chinese Medicine (TCM) therapies was much higher than this (primarily due to use of herbal remedies), the use of TCM was still far behind the use of so-called “Western” medicine. TCM clinic visits accounted for only 9% of outpatient visits reimbursed under the national health insurance. This is similar to another study which found Chinese medicine (of all covered types) accounted for only 5% of the reimbursed care under the national health insurance system. The same study indicated that “Western” medicine was utilized more than Chinese medicine, especially among children, the elderly, and those with severe disease (consistent with the pattern of CAM use in the U.S., which is generally for self-limiting or chronic disease).

Yet another study in Taiwan specifically investigated acupuncture use and found about 6.2% of people covered by national health insurance utilized acupuncture in a given year, and over the seven years surveyed about 25% of covered individuals had received acupuncture treatment. As in the U.S., the vast majority of the acupuncture treatment sought was for musculoskeletal conditions or injuries (88%).

And a recently published series of surveys conducted in Japan found that about 5-7% of respondents used acupuncture in a given year, and that over a lifetime between 20-27% of respondents had at some time tried acupuncture. More than 80% of the use of acupuncture was for musculoskeletal complaints. About half of those who had used acupuncture indicated they would use it again, and about 37% indicated they would not.

The Bottom Line

So what does all of this mean? Well, probably not very much. Of course, differences in healthcare systems, insurance systems, study methods, and many other factors that are difficult to identify and asses, make direct comparisons between the use of specific CAM interventions in different countries very unreliable. I don’t believe the quality of the data generally allow very confident statements about the popularity of acupuncture or other specific CAM methods. However, proponents of acupuncture, and CAM generally often make such statements, trying to convey the impression that their approaches are growing rapidly in popularity and only perverse, closed-minded curmudgeons still resist them. The little evidence we have certainly does not support such claims. 

In the case of acupuncture, for example, the data show relatively low levels of utilization even in those countries generally regarded as having long historical traditions of using acupuncture. Informal investigations (e.g. 1, 2) have suggested that acupuncture and other CAM practices associated with China may not be as popular even in their native land as proponents in North America claim, and the formal studies I have discussed here seem to support that impression.

A large majority of people who seek acupuncture therapy, regardless of ethnicity or nationality, do so for treatment of musculoskeletal conditions and pain. There is good evidence that the therapeutic ritual of acupuncture has some symptomatic benefit for such indications. This is almost certainly a non-specific treatment effect (aka “placebo”). It does not seem to matter where needles are inserted or if they are inserted at all, and acupuncture therapy does not appear to measurably affect the course of any actual disease. (The Skeptic’s Dictionary has a clear and concise review).

The research data on acupuncture utilization suggests that from about 5-25% of people, regardless of nationality or ethnicity, will at some time try acupuncture for, mostly for some kind of musculoskeletal pain. Conventional therapies are often used along with acupuncture, and they are far more popular overall, especially for serious or acute conditions. So the little research there is suggests that acupuncture occupies a niche common to many CAM therapies. It is used at a low level by a small to moderate proportion of the population for conditions that are either mild, self-limiting, or without a definitive conventional treatment, and it is rarely used in lieu of conventional medical care. This is hardly a mounting wave of enthusiasm for acupuncture itself, much less the mystical theories and postmodern cognitive relativism often associated with it. 

So when proponents of acupuncture say it must work because it has been widely used for thousands of years in Asia and is growing rapidly in popularity in the West, rebutting the argumentum ad populum and argumentum ad antiquitatem fallacies may not be the skeptic’s only option. It may be worthwhile, and simpler, just to point out that acupuncture is neither as old nor as popular as is commonly supposed.

References

Chang LC. Huang N. Chou YJ. Lee CH. Kao FY. Huang YT. Utilization patterns of Chinese medicine and Western medicine under the National Health Insurance Program in Taiwan, a population-based study from 1997 to 2003. BMC Health Serv Res. 2008 Aug 9;8:170.

Chen FP. Chen TJ. Kung YY. Chen YC. Chou LF. Chen FJ. Hwang SJ. Use frequency of traditional Chinese medicine in Taiwan. BMC Health Serv Res. 2007 Feb 23;7:26.

Chen FP, Kung YY, Chen TJ, Hwang SJ. Demographics and patterns of acupuncture use in the Chinese population: the Taiwan experience. J Altern Complement Med. 2006 May;12(4):379-87.

Eisenberg DM. Kessler RC. Foster C. Norlock FE. Calkins DR. Delbanco TL. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med. 1993 Jan 28;328(4):246-52.

Ishizaki N. Yano T. Kawakita K. Public status and prevalence of acupuncture in Japan. eCAM 2010;7(4):493-500.

Quan H. Lai D. Johnson D. Verhoef M. Musto R. Complementary and alternative medicine use among Chinese and White Canadians. Can Fam Physician. 2008 Nov;54(11):1563-9.

Upchurch DM. Burke A. Dye C. Chyu L. Kusunoki Y. Greendale GA.A Sociobehavioral Model of Acupuncture Use, Patterns, and Satisfaction Among Women in the US, 2002Womens Health Issues. 2008; 18(1): 62–71. 

Imagine living 20 years spending 24 hours a day in a cage that tightly fits your body, not giving you room to stand up, stretch out, turn around, or move at all.

Imagine that twice a day during these years you would have a metal catheter inserted into a hole which has been cut into your abdomen, allowing the catheter to easily puncture your gall bladder, or maybe a long syringe inserted into your gall bladder, piercing through your skin again and again, by people who are not doctors.

Imagine becoming infected and cancerous because of this twice-daily physical invasion, and becoming neurotic due to your claustrophobic imprisonment.

Imagine having one or both of your hands cut off so someone can sell them for a lot of money.

Imagine you begin to chew at your hands, if you are lucky enough to have one or both left, due to your developing neuroticism, and to distract yourself from the pain you experience twice a day, every day, for your entire life.

This is reality for an estimated minimum of 12,000 bears across Asia.

– Sara Pegarella, JD

Currently, animal activists across China are up in arms because Gui Zhen Tang Pharmaceutical Corporation, a Fujian-based company that sells bear bile for use in Traditional Chinese Medicine (TCM), has tried to increase production through an initial public offering (IPO). The company is being accused of cruelty towards animals in the process of extracting their bile at an industrial scale. Bear bile, or Xiong Dan (??), is an important ingredient in TCM.

The issue is not new: since the early 2000s, animal activists have circulated hundreds of shocking articles, images, and videos that recount unimaginable cruelty towards caged bears in Asia. The practice has even outraged celebrities, such as Jackie Chan, who have pleaded with consumers to stop buying products made from bears and other endangered species. But now it’s all over the news. Gui Zhen Tang’s IPO has met with fierce public opposition, and has once again led environmentalists to appeal against the cruelty of live bear bile extraction.

As this documentary shows, bear bile is sold throughout Asia for a variety of conditions. The Chinese Herbal Medicine: Materia Medica (1986) by Dan Bensky, Andrew Gamble, and Ted Kaptchuk lists bear bile as a remedy for trauma, sprains, fractures, hemorrhoids, conjunctivitis, severe hepatitis, high fever, convulsions, and delirium. The Materia Medica also states that “because of the high price of bear bile (Xiong Dan), often cow bile, Fei Bovus (Niu Dan), is substituted at a higher dose.”¹ There is no mention, however, of the horrific means by which the animal bile is obtained. The guide also lists other animal products (rhinoceros horn, tiger bones, deer musk, and bat and squirrel feces [sic]) used as medicine.

Image 1. The bear bile entry in the 1986 version of Materia Medica by Bensky et al. The entry in the latest edition (3rd ed. 2004) has been moved to “Obsolete Substances.” Image used with the explicit permission of Eastland Press.

The globalization of TCM has lead to a dramatic increase in the demand for bear bile along with other traditional remedies. Bear bile is sold in Asian apothecaries throughout the world in the form of powder, solution or pills. It is likewise the key ingredient in many Asian “patent medicines” used for tapeworm, childhood nutritional impairment, hangovers, colds, and even cancer. Bear bile is even found in Chinese throat lozenges, shampoo, wine, and tea.

Image 2. Raw bear bile in both liquid and powder forms. Photo: Kathleen E. McLaughlin, the Chronicle Foreign Service correspondent in Beijing

Overall, the worldwide trade in bear parts, including bile, is estimated to be a $2 billion industry. Research in August 2007 by the animal rights group Animals Asia shows its staggering profitability: while the wholesale price of bile powder is around US$410 per kg in China, the retail price increases exponentially to 25 to 50 fold in South Korea, and to 80 fold in Japan (US$33,000 per kg)!

While the trade in bear products is prohibited under the Convention on International Trade in Endangered Species (CITES), and the importation and trade of bear bile products to North America is illegal under both US and Canadian law, many products are still openly offered for sale in Chinese stores. Back in 2001, when the World Society for the Protection of Animals conducted a probe of Asian shops in Canada and four US cities — Chicago, New York, Washington, and San Francisco — it found that 91% of the shops surveyed sold some form of bear part, including farmed bile powder, bile medicines, and whole gallbladders, which the merchants claimed originated from wild bears in China. When WildAid, an animal rights group based in San Francisco, sent an undercover investigator into Chinatown in 2004, two shopkeepers readily produced vials in velvet-lined boxes with pictures of a bears on the lid.

Bear bile is obtained through surgically implanting a tube in the animal, in a process called “milking,” that produces an average 15 ml (.5 oz) of bile each time. The Humane Society of the United States reports that the process of milking is so painful for the bears that they moan and often chew their paws during the procedure. In order to make access to the animals easier, the farmers often break the bears’ teeth and pull out their claws, sometimes brutally removing whole digits. If the bears stop producing bile, they are left to die, or are killed for their gallbladder and paws (considered a delicacy in China).

According to Jeanette McDermott, the founder of Ursa Freedom Project, bear farming in Asia increased during the 1980s in response to the dwindling supply of bear parts obtained from bears hunted in the wild. Tragically, the situation grew out of control, and by the early 1990s, there were over 400 bear farms in operation, containing more that 10,000 bears. Plans were in place to increase the number of bears in farms to 40,000 by the year 2000.

Today, China produces 7,000 kilos of bear bile annually, much of which is illegally exported to Japan, Korea, Australia, Canada, and the US. Whole bear gallbladders are also exported: the Humane Society of the United States says smugglers have been caught with gallbladders packed in coffee to conceal their smell, or dipped in chocolate to disguise them as chocolate-covered figs.

Most of the bears used in bile farming are Himalayan black bears (Ursus thibetanus), also known as “Asiatic black bears” or “Moon bears,” due to the cream-colored crescent moon shape on their chests. As their population has decreased by almost 40 percent over the past few decades, they have been listed (since 2000) as among the most critically endangered species on the International Union on Conservation of Nature’s Red List of Threatened Species.

A number of the bears in bile farms are captured illegally in the wild as cubs. Poachers either wait to capture new-born cubs until the mother leaves the den in search of food , or sometimes they simply kill her to get to the babies. Some of the cubs are born in captivity — but in either case, bear cubs rarely survive to adulthood — and those who do often grow into the bars of their cages as their bodies mature.

Image 3. Is this traditional medicine or savagery and barbarism? Photo: Cornelius Maarselar/Animals Asia

Animal activists posing as potential clients report that the caged bears moan, writhe in pain, and clutch their stomachs as the bile drains from their bodies. Sometimes the bears try to pull out the catheters. Those that succeed are immobilized in an iron corset. Under-nourished and highly stressed from horrific pain and unnatural confinement, the bears lie in agony, in their own filth.

According to Jeanette McDermott, bile is not the farmers’ only source of profit from the bears. Some farmers amputate one or two paws from live bears to sell to restaurants. When bears are no longer able to secrete bile, they are left to die from sickness or starvation. Bears might endure this torture for up to 25 years, making their lifetime a reality of suffering and pain in the name of “natural” and “traditional” medicine.

Image 4. This metal clamp is placed around bears who might struggle or move around excessively in order to ensure they remain still through the painful bile extraction. Photo: Animals Asia

There are a number of extremely painful techniques used for milking bear bile. Image 4, above, illustrates the common extraction technique that relies on plastic or metal catheters, and often necessitates a metal jacket in order to restrain the bears (the chilling details can be found at the Animals Asia website). Some farms rely on an ultrasound machine to guide a catheter connected to a medicinal pump. In this method, the bears are sedated — usually with ketamine — restrained with ropes, and have their abdomens jabbed repeatedly with four-inch needles until the gallbladder is located. Animals Asia suspects that this process leads to dangerous leakages of bile into the body, and to a slow and agonizing death from peritonitis.

In recent years, China has introduced a new, “humane,” free-dripping extraction method, which does away with the need for catheters. Free-dripping involves carving a permanent hole, or fistula, into the bear’s abdomen and gall bladder, from which bile drips out freely. The damage caused by the bile’s leaking back into the abdomen, together with infection from the permanently open puncture, is even worse than the catheters method, and results in a high mortality rate. Often, the bears’ livers and gallbladders become severely diseased through this process, and the collected bile is contaminated with pus, blood, urine and feces.

Image 5. Sometimes a hollow steel stick is pushed through the bear’s abdomen, and the bile runs into a basin under the cage. In this case, about half of the bears die from infections or other complications. Photo: Animals Asia

Image 6. Ultrasound bile extraction from a bear in Vietnam. Photo: Asia Wild Life

A healthy bear’s bile is as fluid as water, and ranges in color from bright yellow-orange to green. However, Animals Asia’s vets have described bile leaking from the gallbladders of farmed bears as “black sludge.” Eminent Chinese and Vietnamese pathologists have warned the public not to use bile taken from sick bears.

The active substance in bile (of bear and all other mammals) is ursodeoxycholic acid (UDCA), also known as Ursodiol, which is easily synthesized, and has been available for several decades. It is estimated that 100,000 kilos of synthetic UDCA are already being used each year in China, Japan, and South Korea, and that the total world consumption may double this figure.

Despite the availability and affordability of synthetic UDCA and suitable herbal alternatives, some practitioners obstinately continue to prescribe bear bile, which in turn drives up the market demand, and pressures the Chinese government to continue to allow the practice of bear farming.

The world’s appetite for bear bile and other parts has also led to the hunting and killing of wild bears in the North America. The media reports that the poaching of bear gallbladder for its use in TCM is on the rise in the US. The Los Angles Times, of August 22, 2008, writes that Fish and Game Wardens in California (CA) often report finding dead black bear carcasses that have been skinned and dismembered. The gallbladder is by far the most often stolen part (see the Los Angeles Times of November 29, 2010). The CA animal safety group, BEAR League, reports that since the beginning of 2007, as many as 87 dead bears have been found near state roadsides. On occasion, they report the bears’ heads or paws are cut off, but they also report finding bear carcasses with the gallbladder missing.

Image 7. This California black bear was struck and killed on State Highway 89 near Lake Tahoe in August 2008. State wildlife officials say the gallbladder was removed. Photo: BEAR League

The appalling impact of TCM on endangered species goes well beyond bears though. It affects the world’s most precious and protected animals, such as Bengal tigers, American bears and African rhinos. A worldwide interest in alternative medicine and the ease of international commerce now put dozens of species worldwide at risk. And while most of traditional Chinese medicines rely on herbs, the demand for products made at the expense of threatened animals continues to grow. In reality, many of the current claims associated with the medicinal value of animal products are spurious; but reality hasn’t stopped the rising demand for these illegal substances, and the profits to be made by poachers and smugglers rise.²

While the use of some animal products was perhaps justifiable in the past  — when there were no alternatives available, the extent of demand was limited, and the particular species were plentiful in their natural habitat — it is no longer sustainable, or justifiable, given our modern, globalized, and technically-advanced world. Today, with other approved therapeutic alternatives available, there is little justification for the use of endangered species such as the black bear.³

The belief advanced by the Counterculture of the 1960s and the New Age movement — that “natural” curatives are better than their synthetic equivalents — contributes enormously to TCM’s popularity in North America today. These groups originally objected to the growing over-consumption and over-reliance on synthetically-produced medicines, over natural alternatives. And while these concerns should be considered serious, the apologists of TCM and other types of traditional medicines fail to recognize that at present, their massive demand for “natural” products has made crime against animals commonplace. TCM has behind it a powerful, moneyed group of consumers whose “needs” now drive a whole black market economy — one that supports poachers, bear bile farmers, and all types of heinous torture.

As I wrote his article, I was overwhelmed with rage, and repulsed not only by the horrific images of the animal holocaust in Asia, but also by the enormous hypocrisy of the proponents of TCM, who effectively claim that pus-infested bear bile, and the by-products of animals tortured, disfigured, and dismembered in the name of the“natural” are better, safer, and “gentler” than synthetic pharmaceuticals.

With many thanks to Sara Pegarella, JD, and Kristin Koster, PhD, for their valuable comments.

The above mentioned animal rights advocacy groups (Animals Asia, Asia Wild Life, etc.) were not interviewed for this piece and any information attributable to them was taken from their websites. I encourage you to visit these sites to become more informed and involved.

REFERENCES

1. Bensky D, Gamble A, Kaptchuck T. Chinese Herbal Medicine: Materia Medica. Revised Edition. Eastland Press. 1986. Return to text
2. Ellis R. Tiger Bone & Rhino Horn: The Destruction of Wildlife for Traditional Chinese Medicine. Island Press; 1 edition. 2005. Return to text
3. Still J. Use of animal products in traditional Chinese medicine: environmental impact and health hazards. Complement Ther Med. 2003 Jun;11(2):118-22. Return to text

Mark Tonelli, MD has problems with evidence-based medicine (EBM). He has published a few articles detailing his issues, and he makes some legitimate points. We at science-based medicine (SBM) have a few issues with the execution of EBM as well, so I am sympathetic to constructive criticism.

In an article titled: Integrating evidence into clinical practice: an alternative to evidence-based approaches. The abstract states:

Evidence-based medicine (EBM) has thus far failed to adequately account for the appropriate incorporation of other potential warrants for medical decision making into clinical practice. In particular, EBM has struggled with the value and integration of other kinds of medical knowledge, such as those derived from clinical experience or based on pathophysiologic rationale. The general priority given to empirical evidence derived from clinical research in all EBM approaches is not epistemically tenable. A casuistic alternative to EBM approaches recognizes that five distinct topics, 1) empirical evidence, 2) experiential evidence, 3) pathophysiologic rationale, 4) patient goals and values, and 5) system features are potentially relevant to any clinical decision. No single topic has a general priority over any other and the relative importance of a topic will depend upon the circumstances of the particular case. The skilled clinician must weigh these potentially conflicting evidentiary and non-evidentiary warrants for action, employing both practical and theoretical reasoning, in order to arrive at the best choice for an individual patient.

I certainly agree that clinical evidence (what he he referring to by “empirical” evidence above) is not, and should not be, the sole type of knowledge that is incorporated into clinical decision-making. However, I think this criticism is a bit of a straw man, at least with regard to items 2, 4, and 5. The goals and values of the patient are definitely part of clinical decision-making, even in a rigorously evidence-based practice. We are, after all, treating people, not diseases. When I was in medical school this was called the biopsychosocial model of medicine. Now it is also not uncommon for quality of life measures and overall satisfaction to be incorporated as outcome measures in clinical trials, blurring the lines between empiricism and personal goals and values.

So while I agree that patient values and goals absolutely need to be taken into consideration when practicing medicine, I don’t see this as a new idea or one that is at odds with EBM, nor entirely distinct from empiricism. By including this as he does, however, there is the implication that EBM excludes such considerations, and I do not believe that is fair.

Where we likely mostly agree is on number 3 – pathophysiological rationale. I could expand this to include all of basic science – medical practices should be plausible. I also think he has a legitimate point in that EBM gives too much emphasis to clinical science and shortchanges basic science. But it is interesting to note that the EBM grading system for recommendations do allow for extrapolation (i.e grade B=.consistent level 2 or 3 studies or extrapolations from level 1 studies). Extrapolation involves considering pathophysiology and mechanism of action. While extrapolation (rather than direct evidence) downgrades the recommendation by one category (which is appropriate) it does not exclude it altogether.

Further, I think the real problem with failing to consider pathophysiology is not for support of a plausible treatment, but to be extra cautious about an implausible treatment. When the basic science dictates that a proposed treatment is highly implausible, the bar for clinical evidence should be raised proportionately.  I don’t think this is what Tonelli had in mind, however, as we will see.

Item #2- Experiential evidence, is highly problematic. While experience is great for some things, like recognizing diagnoses, being sensitive to the subtleties of history taking, and interfacing with patients – it is highly misleading when it comes to determining safety and efficacy. The simple fact is that personal experience is too limited, quirky, and uncontrolled, and is overwhelmingly likely to simply confirm our biases than actually lead us in the direction of truth.

In another related article (actually published in 2001, earlier than the 2006 paper above), Tonelli clarifies:

Empirical evidence, when it exists, is viewed as the “best” evidence on which to make a clinical decision, superseding clinical experience and physiologic rationale. But these latter forms of medical knowledge differ in kind, not degree, from empirical evidence and do not belong on a graded hierarchy.

He is partly correct here – these other forms of evidence are not necessarily below, but are tangential to, empirical evidence. But I think Tonelli is missing the context of EBM. EBM is not a method for solely determining clinical practice (clinical decision-making) but for determining safety and efficacy, which is one factor that informs practice. Values, the system, and the human side of medicine also go into clinical practice, but they should not be used to determine efficacy. So it seems his criticism is based upon a straw man constructed of his own confusion.

I might have been inclined to give Tonelli some benefit of the doubt, were it not for this:

The methods for obtaining knowledge in a healing art must be coherent with that art’s underlying understanding and theory of illness. Thus, the method of EBM and the knowledge gained from population-based studies may not be the best way to assess certain CAM practices, which view illness and healing within the context of a particular individual only. In addition, many alternative approaches center on the notion of non-measurable but perceptible aspects of illness and health (e.g., Qi) that preclude study within the current framework of controlled clinical trials. Still, the methods of developing knowledge within CAM currently have limitations and are subject to bias and varied interpretation. CAM must develop and defend a rational and coherent method for assessing causality and efficacy, though not necessarily one based on the results of controlled clinical trials. Orthodox medicine should consider abandoning demands that CAM become evidence-based, at least as “evidence” is currently narrowly defined, but insist instead upon a more complete and coherent description and defense of the alternative epistemic methods and tools of these disciplines.

This casts a new light on all of Tonelli’s other publications. It seems he is making an elaborate argument for the inclusion of other kinds of evidence (other than rigorous, controlled, clinical studies) as support for fanciful but ideologically appealing treatments.

This is a refrain that is becoming common in the CAM community -  that we need to redefine “evidence”, not restrict ourselves to narrow definitions of evidence, and that CAM modalities cannot be properly studied by traditional scientific methods. There is always a flavor that CAM must free itself from the tyranny of scientific evidence.

What is it, exactly, about scientific methods that they feel is incompatible with CAM methods – being thorough, counting all the data, controlling for variables, minimizing the effects of bias, carefully defining terms and outcomes, or being statistically rigorous?  Even individualized treatments can be studied rigorously – so that is an insufficient excuse. In the end, the call to expand the definition of evidence is just a deceptive way of asking for sloppy methods of research, because CAM modalities generally do not hold up under rigorous standards.

We don’t need to redefine or expand the methods of science – we need to return common sense to medicine.

Here’s something for you all to check out. Trine Tsouderos, the journalist from The Chicago Tribune who’s distinguished herself as being one of the few reporters who “gets it” when it comes to quackery and the anti-vaccine movement (just put her name in the search box of this blog for some examples) will be hosting a web chat about vaccines featuring none other than Dr. Paul Offit, one of the gutsiest (if not the gutsiest) defender of vaccine science out there. The chat will occur here at noon CDT today. Questions can be submitted in advance to Tsouderos at ttsouderos@tribune.com.

Head on over, everyone. The anti-vaccine movement is clearly out in force in the comments. Although the usual intrepid defenders of science are there, reinforcements are always welcome.

David Kroll’s recent article on thunder god vine is a great example of what can be learned by using science to study plants identified by herbalists as therapeutic. The herbalists’ arsenal can be a rich source of potential knowledge. But Kroll’s article is also a reminder that blindly trusting herbalists’ recommendations for treatment can be risky.

Herbal medicine has always fascinated me. How did early humans determine which plants worked? They had no record-keeping, no scientific methods, only trial and error and word of mouth. How many intrepid investigators poisoned themselves and died in the quest? Imagine yourself in the jungle: which plants would you be willing to try? How would you decide whether to use the leaf or the root? How would you decide whether to chew the raw leaf or brew an infusion? It is truly remarkable that our forbears were able to identify useful natural medicines and pass the knowledge down to us.

It is equally remarkable that modern humans with all the advantages of science are willing to put useless and potentially dangerous plant products into their bodies based on nothing better than prescientific hearsay.

Ancient Sumerians used willow, a salicylate-rich plant that foreshadowed modern aspirin. Digitalis was used by the ancient Romans long before William Withering wrote about its use for heart failure. South American natives discovered that chinchona bark, a source of quinine, was an effective treatment for malaria. These early herbal remedies pointed the way to modern pharmaceuticals. How many other early remedies fell by the wayside? What else did the Sumerians, the Romans, and the natives use that did more harm than good? If “ancient wisdom” exists, so does “ancient stupidity.”

Plants undeniably produce lots of good stuff. Today researchers are finding useful medicines in plants that have no tradition of use. Taxol, the cancer-fighting product of Pacific yew trees, was discovered by the National Cancer Institute only by screening compounds from thousands of plants.

There is a reason pharmacology abandoned whole plant extracts in favor of isolated active ingredients. The amount of active ingredient in a plant can vary with factors like the variety, the geographic location, the weather, the season, the time of harvest, soil conditions, storage conditions, and the method of preparation. Foxglove contains a mixture of digitalis-type active ingredients but it is difficult to control the dosage. The therapeutic dose of digitalis is very close to the toxic dose. Pharmacologists succeeded in preparing a synthetic version: now the dosage can be controlled, the blood levels can be measured, and an antibody is even available to reverse the drug’s effects if needed.

“Ancient wisdom” argues that if an herbal remedy has been used for centuries, it must be both effective and safe. That’s a fallacy. Bloodletting was used for centuries but it wasn’t effective and it did more harm than good. If a serious side effect occurred in one in a thousand recipients of an herb, or even one in a hundred, no individual herbalist would be likely to detect it. If a patient died, they would be more likely to attribute the cause to other factors than to herbs that they believed were safe. Even with prescription drugs, widespread use regularly uncovers problems that were not detected with pre-marketing studies.

Arguments in favor of herbal remedies include:

• They’re natural. (So what? Strychnine is natural.)
• They’re safer than prescription drugs. (Maybe some are, some aren’t; how would you know?)
• They’re milder than prescription drugs. (That would depend on the dosage of active ingredient.)
• They’re less likely to cause side effects. (When they have been as well studied as prescription drugs, they may turn out to have just as many or more side effects. All effective drugs have side effects, and if an herbal medicine has fewer side effects it might have fewer therapeutic effects too. Formal systems for reporting adverse effects have long been in place for prescription drugs; not so for herbal remedies.)
• They’re different from prescription drugs. (Some are identical to prescription drugs, like red yeast rice which contains the same ingredient as prescription lovastatin; and some herbal products have been found contaminated with prescription drugs.)
• They’re less expensive. (True, but is a cheaper, inferior product a good bargain?)
• They’re easier to obtain. (True, you don’t have to make an appointment with a doctor; but that means you don’t get the benefit of a doctor’s knowledge.)
• The mixture of ingredients in a plant can have synergistic effects. (This is widely claimed but almost never substantiated. The other ingredients are just as likely to counteract the desired effect or to cause unwanted adverse effects.)
• For every disease, God has provided a natural remedy. (Perhaps this is a comforting thought for believers, but it is not based on any evidence and is not convincing to atheists and agnostics. And it doesn’t help us find that natural remedy.)

Even when an herbal remedy works, finding a safe and reliable source is problematic. Horror stories abound:

• Contaminants (such as heavy metals, pesticides, carcinogens, toxic herbs, and insect parts).
• Wild variation in content (from no active ingredient to many times the amount on the label).
• Mislabeled products that contain an entirely different herb.

I won’t list specific examples here; they are easy enough to find. I’ll just say that natural medicines are not regulated the way prescription drugs are, thanks to the infamous Diet Supplement and Health Education Act (DSHEA) of 1994.

When you take an herbal remedy, you are taking

1. An active ingredient that usually has not been adequately tested,
2. Other components that have not even been identified, much less tested,
3. An uncertain amount, and
4. Possible contaminants.

The term “street drugs” comes to mind: you don’t really know what you’re getting.

Here at Science-Based Medicine, we try to be relatively apolitical. We might not always succeed, but in general our main concern is not so much with right-wing or left-wing politics, but rather with how prevailing government policies and regulation impact the delivery of medical care, in particular whether they tend to prevent, do nothing about, or promote the proliferation of non-science-based medical care. Consequently, when Kimball or I call for the disbanding of the National Center for Complementary and Alternative Medicine (NCCAM), it does not matter one whit to us who is President or which party controls Congress. All that matters is that we see NCCAM as a government entity that, through credulously studying many “alternative medicine” modalities, ends up inadvertently promoting them and providing them with the imprimatur of government approval. The same concept applies to state medical licensing boards licensing pseudoscientific modalities, such as naturopathy, acupuncture, and homeopathy. By regulating these “disciplines,” states also provide them with an unmerited mantle of respectability through their imprimatur of regulating them as professions, just like medicine and nursing.

As far as political views, although all of us have them and they occasionally even come to the fore in disagreements (remember when Wally Sampson occasionally clashed with others with differing political viewpoints?), we generally subsume them for purposes of the SBM blog experience into our advocacy for basing medicine on the best science available. Sometimes, however, when a pundit or politician makes claims that are either contrary to or distort science for ideological or political advantage, I feel the need to discuss those claims, sometimes even sarcastically. Such was the case last week, when Ann Coulter wrote a blisteringly ignorant column, entitled A Glowing Report on Radiation. She wrote this article in the wake of the fears arising in Japan and around the world of nuclear catastrophe due to the damage to the Fukushima nuclear power plant caused by the earthquake and tsunami that hit northern Japan on March 11. Coulter was subsequently interviewed by Fox News pundit Bill O’Reilly on The O’Reilly Factor on Thursday evening:

Yes, according to Coulter, radiation is good for you, just like toxic sludge! Even more amazing, in this video Bill O’Reilly actually comes across as the voice of reason, at least in comparison to Ann Coulter. He’s very skeptical of Coulter’s claims and even challenges her by saying, “So by your account we should all be heading towards the nuclear reactor.”

So, fellow SBM aficionados, is Coulter right? Are all those scientists warning about the dangers of even low-level radiation all wrong? Should we start hanging out in radioactive mine shafts, as Coulter mentions in her column (seriously) in order to boost our health and decrease our risk of cancer?

Not so fast, there, Ann. Here’s a hint: If Bill O’Reilly can lecture you on science and look more reasonable than you, you’re off the rails.

Coulter, hormesis, and “Don’t worry, be happy!”

Actually, the scientific assessment of what levels of exposure to ionizing radiation are dangerous is, as you might imagine, a wee bit more complicated than my little sarcastic rejoinder makes it, but you’d never know that from Ann Coulter’s article and her interview with Bill O’Reilly. The reason for my sarcastic characterization of Coulter’s scientific nonsense is because her article uses many of the same tactics as any denialist. Chief among these is that Coulter takes the germ of a scientific controversy and then uses it to try to imply that the scientific consensus is fatally flawed. In this case, the scientific controversy is over how dangerous low level exposure to radiation is used to imply that the radiation from a nuclear disaster is not potentially harmful. All you former residents of Chernobyl, take note! It’s fine to move back to your homes that you were forced to abandon 25 years ago!

Here is what Coulter claims in her article:

With the terrible earthquake and resulting tsunami that have devastated Japan, the only good news is that anyone exposed to excess radiation from the nuclear power plants is now probably much less likely to get cancer.

This only seems counterintuitive because of media hysteria for the past 20 years trying to convince Americans that radiation at any dose is bad. There is, however, burgeoning evidence that excess radiation operates as a sort of cancer vaccine.

As The New York Times science section reported in 2001, an increasing number of scientists believe that at some level — much higher than the minimums set by the U.S. government — radiation is good for you. “They theorize,” the Times said, that “these doses protect against cancer by activating cells’ natural defense mechanisms.”

What Coulter is referring to is the phenomenon of radiation hormesis. This is nothing more than a biphasic dose-response curve to radiation in which the curve initially goes down with increasing dose (less risk of disease with increasing radiation exposure) and then curves upward and at some point crosses a threshold where radiation exposure is no longer beneficial but harmful with further dose increases. Basically, it’s a scientific model wherein low level exposure to radiation is not only not harmful but in fact beneficial. The reason for this effect, if it exists in humans, is hypothesized to be that low level radiation activates DNA damage repair and other protective mechanisms that are not activated in the absence of radiation; moreover, it is further hypothesized that these mechanisms are activated more than they need to be, so that low level radiation is actually protective against radiation-induced diseases such as cancer.

The radiation hormesis model is markedly different from the currently prevailing model that is used for regulatory purposes by most governments, the linear no-threshold (LNT) model, which states that there is no such thing as a “safe” dose of radiation and that radiation dammage accumulates in a linear fashion with dose. For completeness sake, I will note that there is also at least one other model for the biological effects of radiation, specifically a model in which there is a threshold dose under which radiation is not harmful. In practice, distinguishing between a threshold model and a hormesis model can be very difficult.

In order to give you an idea of what hormesis would look like in a radiation dose-response curve, I stole this graph from Wikipedia. Actually, I didn’t steal it; it’s public domain because it’s a product of a U.S. government agency. However, it illustrates the concept of hormesis quite well:

Curve A demonstrates supralinearity, in which toxic effects are actually more intense per unit of radiation at lower doses; there is no evidence that this is indeed the case. Curve B is linear, and Curve C is linear-quadratic, in which low doses of radiation are less harmful per unit of radiation than higher doses. Curve D represents hormesis, where low doses of radiation are actually protective up to a certain threshold, where the curve shifts from a protective effect to a harmful effect with increasing radiation. The main contenders for the model that best describes radiation effects are either curve B, C, or D.

The key aspect of Coulter’s article that makes it so irresponsible is what she leaves out. What she neglects to mention is that, even if hormesis is an accurate model for radiation effects in humans, it only applies for very low dose exposures. (More on how low in the next section.) True, Coulter does at one point concede that it is “hardly a settled scientific fact that excess radiation is a health benefit,” throughout the rest of her article she presents the idea of hormesis as though it were–you guessed it!–a settled scientific fact. Indeed, Coulter’s earlier assertion that “excess radiation acts as sort of a cancer vaccine” is the sheerest exaggeration, even if hormesis is an accurate model of radiation exposure. Aside from this major exaggeration, how do Coulter’s assertions, which appear to be based largely on studies cited in a single NYT article that is nearly a decade old, stack up against science?

Not very well. Surprise! Surprise! As is the case with many denialists, Coulter takes a germ of actual science and then twists and exaggerates it beyond all recognition in order to support a preconceived notion, namely that those pointy-headed (and, of course, liberal) environmentalists are hiding the evidence that radiation at low doses is good for you. To accomplish this, Coulter cherry picks studies, failing to put them into their proper context with existing research, all for the purpose of advancing her ideological viewpoint.

Radiation hormesis: Ann Coulter’s claims versus reality

Before I discuss what the data regarding radiation hormesis actually show, it’s essential to discuss briefly why it is that the LNT model predominates when it comes to policy-making and setting limits on what is considered “safe” radiation exposure. The reason is not that biased scientists are “hiding” the evidence that radiation is good for you. Rather, it boils down to a few reasons. The first is probably that an LNT model is the simplest, most conservative model that can be fit to currently existing evidence. The problem with the LNT model is the same as the problem with the hormesis model. While at higher radiation doses, effects due to radiation are, like effects due to pretty much any other high-level environmental exposure, much more robust and reproducible, at lower radiation doses, the effects are weaker, and the scatter in the data is much greater. In other words, at low doses the signal-to-noise ratio is much lower due to a lot more “noise” and a lot less signal in the data. Moreover, the data are more difficult to collect, and variability from system to system, organism to organism, and cancer to cancer is likely to be much greater.

As imperfect as it is, the LNT model is a reasonable approximation for purposes of policy-making because it is conservative and safe. Admittedly, there are problems applying such a model when the doses get really low, as in lower than the normal background radiation that we all live in, but it’s a useful approximation. When it is very hard to distinguish between an LNT model and a hormesis model at very low radiation exposures, until better data can be gathered that clearly demonstrate the superiority of one model over another, the responsible and safe model to choose is the most conservative one that fits reasonably well. Basing public policy on a model that, if incorrect, has the potential to result in considerable harm in the form of increased radiation-induced disease prevalence is not wise policy at all, at least when the alternate model is not demonstrably wrong.

As far as Coulter’s reliance on an old NYT article, I thought I’d take a look at the article itself. As an aside, I can’t help but note that I really hate it when the online version of an article doesn’t include links to cited articles, and Coulter is no different in this regard. However, I do believe I managed to find this 2001 NYT article anyway from November 27, 2001, entitled For Radiation, How Much Is Too Much? It’s by Gina Kolata and discusses the controversy that had begun to bubble up about what doses of ionizing radiation might be considered safe. If you read it, you’ll see that it’s much more balanced than how it is portrayed by Coulter. For example, here is what Coulter writes about two studies cited by Kolata:

Among the studies mentioned by the Times was one in Canada finding that tuberculosis patients subjected to multiple chest X-rays had much lower rates of breast cancer than the general population.

Here is what Kolata actually wrote about these studies:

Now, some scientists even say low radiation doses may be beneficial. They theorize that these doses protect against cancer by activating cells’ natural defense mechanisms. As evidence, they cite studies, like one in Canada of tuberculosis patients who had multiple chest X-rays and one of nuclear workers in the United States. The tuberculosis patients, some analyses said, had fewer cases of breast cancer than would be expected and the nuclear workers had a lower mortality rate than would be expected.

Dr. Boice said these studies were flawed by statistical pitfalls, and when a committee of the National Council on Radiation Protection and Measurement evaluated this and other studies on beneficial effects, it was not convinced. The group, headed by Dr. Upton of New Jersey, wrote that the data “do not exclude” the hypothesis. But, it added, “the prevailing evidence has generally been interpreted as insufficient to support this view.”

Notice how the finding in “some analyses” that there were fewer cases of breast cancer than might be expected has magically morphed into “tuberculosis patients subjected to multiple chest X-rays had much lower rates of breast cancer than the general population” in Coulter’s words. Also note that this appears to be the NCRPM report that analyzed the data. Unfortunately, it would have cost me $40 to download the PDF; so I didn’t. But what about these studies?

The first study to which Coulter refers appears to be a study from Canada that was reported in the New England Journal of Medicine in 1989. This study examined the mortality from breast cancer in a cohort of 31,710 women who had been treated for tuberculosis at Canadian sanatoriums between 1930 and 1952. A significant proportion (26.4%) of these women had received radiation doses to the breast of 10 cGy or more from repeated fluoroscopic examinations during therapeutic pneumothoraxes. It should be noted that these sorts of doses of radiation are far in excess of anything likely to be received using modern radiological equipment, in particular given that we no longer perform fluoroscopy and therapeutic pneumothorax to treat tuberculosis. Interestingly, this is how the abstract summarizes the results of this study:

Women exposed to ? 10 cGy of radiation had a relative risk of death from breast cancer of 1.36, as compared with those exposed to less than 10 cGy (95 percent confidence interval, 1.11 to 1.67; P = 0.001). The data were most consistent with a linear dose–response relation. The risk was greatest among women who had been exposed to radiation when they were between 10 and 14 years of age; they had a relative risk of 4.5 per gray, and an additive risk of 6.1 per 10⁴ person-years per gray. With increasing age at first exposure, there was substantially less excess risk, and the radiation effect appeared to peak approximately 25 to 34 years after the first exposure. Our additive model for lifetime risk predicts that exposure to 1 cGy at the age of 40 increases the number of deaths from breast cancer by 42 per million women.

Oops! Maybe I found the wrong study! On the other hand, this is a Canadian study that looked at women with tuberculosis who received numerous chest X-rays (fluoroscopy, actually), and I can’t find another one like it. I also couldn’t find other publications with other analyses. The analysis that exists in the published literature, for better or for worse, concludes that the risk of breast cancer is elevated with exposures to radiation greater than 10 cGy. So, what are these other “analyses” that purport to claim that these patients actually had a lower risk of mortality from breast cancer? I smelled a rat.

My first hint came from an article published in the Journal of the Association of American Physicians and Surgeons (JPANDS) by Bernard Cohen entitled The Cancer Risk From Low Level Radiation: A Review of Recent Evidence. I’ve discussed JPANDS and how it plays fast and loose with science for ideological reasons before, in particular its antivaccine views and its publishing studies so bad that laughter is the only appropriate response. In his article, Cohen claims that hormesis “found for breast cancer among Canadian women exposed over longer periods of time to X-ray fluoroscopic examinations for tuberculosis (13); when appropriately evaluated, this evidence shows a decrease in risk with increasing radiation dose at least up to 20 cSv (20 rem).” Unfortunately, no evaluation of this evidence is included; Cohen simply asserts that this is so.

Fortunately, it didn’t take long for me to find other JPANDS articles making the same argument. For example, this one by Joel M. Kauffman. In it, Kaufmann divides up the subjects into several radiation dose ranges, while rejecting data from Nova Scotia because “too few” low radiation points were included. Conveniently he fails to define what “too few” is. However, if one looks at Table I in the NEJM paper, it’s obvious that in the dose range between 10 and 99 cSv, the death rate in Nova Scotia was much higher than the other provinces. One wonders if that had anything to do with leaving out the data, rather than writing the authors for a more detailed breakdown of the data between those dose levels, one does. In any case, what Kaufmann appears to have done is what JPANDS writers frequently do: Cherry pick the data. He took the lower end of the dose ranges, used “eyeball” fitting instead of statistical fitting to models, and left out any hint of a statistical analysis. The authors of the NEJM article went to great lengths to demonstrate that a LNT model was the best fit to their data; Kaufmann expects you to “eyeball” his graph and accept his claim of hormesis. Similarly, Jerry Cuttler and Myron Pollycove, in another JPANDS article, plotted the Canadian data on a semilog scale to make a hormesis effect look far more convincing than the actual data support, all the while simply claiming that a hormesis model fit the data better than an LNT model. Unfortunately, they didn’t “show their work,” so to speak. No discussion of how they modeled the data is included. No wonder the NCRPM found these “other” analyses unconvincing. Also, while it’s not surprising that Coulter would have gotten her data on this from JPANDS, it’s rather disappointing that Kolata didn’t look deeper back in 2001.

The second study cited by Kolata and exaggerated by Coulter was a study of U.S. nuclear industry workers. Regarding this sort of data, the scientists at the Lawrence Berkley National Laboratory have included on their website this analysis:

The results of individual studies have been inconclusive, and to investigate the matter further a combined analysis has been carried out of seven studies–three for sites in the United States (Hanford, Oak Ridge, and Rocky Flats), three for sites in the United Kingdom, and one for Canada. A total of 95,673 workers was included, of whom 60% received effective doses above 10 mSv (1 rem). In the entire population, there were 15,825 deaths, of which 3,976 were from cancer. The comprehensive results for all cancers taken together showed a very slight decrease in cancer rate with increasing dose. However, this result had no statistical significance. Of possible greater statistical significance is a slight increase with radiation dose for some types of leukemia. Overall, the statistical uncertainties were large enough that the analysis did not rule out linearity or any of the other alternative dose-response curves indicated in Figure 15-1–although it does set an upper limit on the possible magnitude of a hypothesized supra-linearity effect.

The study being discussed it this one, which, by the way, concludes:

These estimates, which did not differ significantly across cohorts or between men and women, are the most comprehensive and precise direct estimates of cancer risk associated with low-dose protracted exposures obtained to date. Although they are lower than the linear estimates obtained from studies of atomic bomb survivors, they are compatible with a range of possibilities, from a reduction of risk at low doses, to risks twice those on which current radiation protection recommendations are based. Overall, the results of this study do not suggest that current radiation risk estimates for cancer at low levels of exposure are appreciably in error.

Coulter also makes much of a study of shipyard workers from 1991:

A $10 million Department of Energy study from 1991 examined 10 years of epidemiological research by the Johns Hopkins School of Public Health on 700,000 shipyard workers, some of whom had been exposed to 10 times more radiation than the others from their work on the ships’ nuclear reactors. The workers exposed to excess radiation had a 24 percent lower death rate and a 25 percent lower cancer mortality than the non-irradiated workers.

The reference for this is:

Matanoski, G. M. (1991) Health Effects of Low-Level radiation in Shipyard Workers, Final Report, DOE/EV/10095-T2, National Technical Information Service, Springfield, Virginia, USA.

Unfortunately, I couldn’t get a hold of this report online over the weekend. I did, however, find the more recent reanalysis of the data from 2008 by Matanoski et al published in the Journal of Radiation Research. What Matanoski found wa that most of the differences in mortality and cancer rates found between shipyard workers who serviced nuclear ships and shipyard workers who did not were not significant, although there did appear to be trends towards increased risk of leukemias and other cancers with increasing dose. Overall, as far as saying anything about the association between radiation exposure and cancer, at best this study could be described as inconclusive. Certainly it’s exceedingly thin gruel to make such definitive statements about hormesis. As for the lower all-cause mortality among the nuclear workers, that is almost certainly due to phenomenon known as the “healthy worker effect“; i.e., the selective recruiting of healthier than average persons into the industry who have continued access to better than average health care.

Similarly thin gruel is this claim by Coulter:

In 1983, a series of apartment buildings in Taiwan were accidentally constructed with massive amounts of cobalt 60, a radioactive substance. After 16 years, the buildings’ 10,000 occupants developed only five cases of cancer. The cancer rate for the same age group in the general Taiwanese population over that time period predicted 170 cancers.

The people in those buildings had been exposed to radiation nearly five times the maximum “safe” level according to the U.S. government. But they ended up with a cancer rate 96 percent lower than the general population.

Not exactly. Actually, not at all. It’s not even thin gruel; it’s misrepresentation, either intentional or through Coulter’s laziness in researching the article. Coulter, as usual, is exhibiting willful ignorance by citing old data. In fact, more recent analyses of the Taiwanese population that lived in these buildings do not support her claims at all. The most recent followup study I could find was published in 2006 in the International Journal of Radiation Biology by Hwang et al. The results were:

A total of 7271 people were registered as the exposed population, with 101,560 person-years at risk. The average excess cumulative exposure was approximately 47.8 mSv (range 5 1 – 2,363 mSv). A total of 141 exposed subjects with various cancers were observed, while 95 developed leukemia or solid cancers after more than 2 or 10 years initial residence in contaminated buildings respectively. The SIR were significantly higher for all leukemia except chronic lymphocytic leukemia (n1?46, SIR1?43.6, 95% confidence interval [CI] 1.2–7.4) in men, and marginally significant for thyroid cancers (n1?46, SIR 1?4 2.6, 95% CI 1.0 – 5.7) in women. On the other hand, all cancers combined, all solid cancers combined were shown to exhibit significant exposure-dependent increased risks in individuals with the initial exposure before the age of 30, but not beyond this age.

Hwang et al concluded:

The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers in specific subgroups of this population in Taiwan.

So, basically, Coulter is completely wrong about the Taiwan incident. There is an increased incidence of cancer in young people, at least, who lived in those apartment buildings. Science is hard, isn’t it? Coulter’s also on seriously dubious footing when she cites Professor Bernard L. Cohen, whose various studies of the relationship between radon and lung cancer buck the established consensus that radon is a risk factor for lung cancer. (Yes, this is the very same Bernard Cohen who wrote the JPANDS article I mentioned earlier in this post; to me his having published in JPANDS is to me a huge hit on any credibility he might have had.) It turns out that Cohen probably didn’t control adequately for smoking in his studies because a reanalysis of his reported data demonstrated similar, strongly negative correlations between radon exposure and cancers strongly linked to cigarette smoking and weaker negative correlations between radon and cancers moderately associated with smoking. No such correlation was found for cancers not linked to smoking. These results strongly suggest that Cohen didn’t adequately control for smoking in his analysis. Another criticism points out that Cohen fell prey to the ecological fallacy and suggested that county-level data probably do not represent the best units to detect a correlation between radon and lung cancer.

Coulter’s final claims center on the Chernobyl disaster and victims of the atomic bombings of Hiroshima and Nagasaki. In particular, she claims that only 30 people died in the plant as a direct result of the disaster and further downplays the risk of cancer in the survivors, stating:

Even the thyroid cancers in people who lived near the reactor were attributed to low iodine in the Russian diet — and consequently had no effect on the cancer rate.

As is usually the case for any scientific claims made by Coulter, this is utter rubbish. Unfortunately for Coulter, her timing in publishing her article was exquisitely bad. On the very next day after her article was published, the National Cancer Institute released the most comprehensive study yet of thyroid cancer in Chernobyl survivors. The findings indicated that radioactive iodine (¹³¹I) from the fallout from the reactor was likely responsible for thyroid cancers that are still occurring among people who lived near the reactor and that the risk of this cancer is not declining. In other words, no, Ann, the hugely elevated levels of thyroid cancer among people who live near Chernobyl when the reactor disaster occurred are not due to iodine deficiency in the Russian diet. There is some evidence that iodine deficiency might have increased the risk of ¹³¹I-induced cancers, particularly in the youngest, but that’s not what Coulter said. She implied that iodine deficiency could account for the elevated incidence of thyroid cancer among those affected by the fallout. Much more about the health effects of the Chernobyl disaster can be found here. It should also be noted that most people who lived in the area were not exposed to that much radiation according to the United Nations-sponsored team investigating. Most were exposed to about 9 mSv, about 1/3 the equivalent of a CT scan of the chest, abdomen, and pelvis, once the short-term doses to the thyroid were subtracted

Poor Ann. That’s what you get for not doing a bit more research. Basically, every claim she makes in her article can be shown to be either mistaken, grossly exaggerated, or based on old evidence. She even cites Tom Bethell, author of The Politically Incorrect Guide to Science, as a source. Bethell is an all-purpose right-wing science denialist, who, besides viewing scientists as attention whores who trump up alarmist findings in order to secure more research funding and castigates science for its commitment to “materialism,” also denies evolution and anthropogenic global warming. He even rejects relativity and embraces “AIDS reappraisal,” while extending his view on hormesis to argue that hormesis actually protects us from toxic chemicals in the environment that, according to him, we don’t have to worry about nearly as much as environmentalists say we do. In fact, Coulter includes a paragraph in her article that is so unintentionally hilarious that I can’t help but cite it:

Although it is hardly a settled scientific fact that excess radiation is a health benefit, there’s certainly evidence that it decreases the risk of some cancers — and there are plenty of scientists willing to say so. But Jenny McCarthy’s vaccine theories get more press than Harvard physics professors’ studies on the potential benefits of radiation. (And they say conservatives are anti-science!)

I doubt that Coulter appreciates the irony encompassed by this paragraph, given that this paragraph is further encompassed by an article that uses many of the same deceptive techniques of argumentation that the anti-vaccine movement, as epitomized by Jenny McCarthy, likes to use. She then digs herself in deeper by correctly mentioning that Botox is a poison that is safe to use at high doses (Jenny McCarthy loves Botox, actually) and then pointing out the principle that many poisons are safe and beneficial at low doses but dangerous at high doses. If these arguments didn’t occur within the context of her spewing of misinformation, Coulter might actually be making some sense. Too bad she couldn’t resist adding:

Every day Americans pop multivitamins containing trace amount of zinc, magnesium, selenium, copper, manganese, chromium, molybdenum, nickel, boron — all poisons.

They get flu shots.

Perhaps Coulter has more in common with Jenny McCarthy than she would like to admit. Actually, there’s no “perhaps” about it. Coulter will also say whatever fits her political viewpoint. Last week she was ranting about how radiation is good for you. Back in November, she was complaining that the new Transportation Security Administration scanners do pose a “radiological danger.”

These scanners result in a dose of 0.001 mSv for about 5 seconds of full body exposure, and even frequent fliers would be exposed to much less radiation than Coulter is claiming to be just fine. Indeed, Ann Coulter should be lining up to be scanned. After all, that little radiation is good for you!

Is hormesis a real phenomenon?

Despite my irritation, I was rather grateful for Coulter’s article. It did remind me of a rather fascinating debate in radiobiology over what model best describes the biological effects of radiation. Hormesis might indeed be a real phenomenon in humans, but it’s been very difficult to demonstrate. Even one of the best review articles I’ve found that argues for the existence of hormesis as a phenomenon, an article by Tubiana et al entitled The Linear No-Threshold Relationship Is Inconsistent with Radiation Biologic and Experimental Data doesn’t exactly argue for hormesis. Rather, it argues that the LNT model is inconsistent with the data and needs to be modified to more of a threshold model, in which doses below a certain threshold are probably harmless but above a certain threshold start to increase the risk of disease. Arrayed against these sorts of arguments are scientists like Rudi H. Nussbaum and Wolfgang Köhnlein, who call hormesis and the zero-risk threshold dose “scientifically refuted, but stubborn myths.” They even argue that in some cases the risk of low level radiation exposure might well be underestimated. Not surprisingly, in her article Coulter used nearly every myth that Nussbaum and Köhnlein deconstruct in their paper.

Hormesis is clearly an area of science that is as yet controversial. The reason is because it’s difficult to demonstrate definitively one way or another whether hormesis occurs in humans in response to low dose radiation. As I mentioned above, the signal-to-noise ratio for studies of low dose radiation is very low. Moreover, studies of low dose radiation have been conflicting, although we can say with a fair amount of confidence, based on my review of the literature, that, if hormesis occurs, it probably occurs only below doses of 100 mSv. Remember, 30 mSv is the dose received from a CT scan of the chest, abdomen, and pelvis and can be estimated to increase one’s lifetime risk of a fatal cancer by 1 in 1000 to 1 in 500 in pediatric patients, while most people receive around 3 mSv per year from background radiation. To put this all into context, XKCD has a very useful chart that describes how much radiation we receive from various sources. Another good perspective comes from a recent AP article on the topic, which takes a much more balanced perspective.

The bottom line is that we just don’t know whether hormesis is a real phenomenon for radiation response in humans. Lacking that knowledge, we do know that the LNT model is a reasonable approximation for purposes of regulation because it is simple and defensible. Even so, different professional organization bodies have started to question it. For example, the French Academy of Sciences and National Academy of Medicine published a report in 2005 that stated:

In conclusion, this report raises doubts on the validity of using LNT for evaluating the carcinogenic risk of low doses (< 100 mSv) and even more for very low doses (< 10 mSv). The LNT concept can be a useful pragmatic tool for assessing rules in radioprotection for doses above 10 mSv; however since it is not based on biological concepts of our current knowledge, it should not be used without precaution for assessing by extrapolation the risks associated with low and even more so, with very low doses (< 10 mSv), especially for benefit-risk assessments imposed on radiologists by the European directive 97-43.

The Health Physics Society’s position statement, revised in July 2010, states:

In accordance with current knowledge of radiation health risks, the Health Physics Society recommends against quantitative estimation of health risks below an individual dose of 5 rem in one year or a lifetime dose of 10 rem above that received from natural sources. Doses from natural background radiation in the United States average about 0.3 rem per year. A dose of 5 rem will be accumulated in the first 17 years of life and about 25 rem in a lifetime of 80 years. Estimation of health risk associated with radiation doses that are of similar magnitude as those received from natural sources should be strictly qualitative and encompass a range of hypothetical health outcomes, including the possibility of no adverse health effects at such low levels.

Again, we just don’t know. My guess is that hormesis, if it occurs in humans in response to radiation, is not nearly as potent a phenomenon as its adherents claim. My further guess is that the way hormesis is invoked as a scientific explanation for homeopathy doesn’t help its reputation. Be that as it may, until science settles the question, I do know that, contrary to what Coulter claims in her nonsensical arguments, low dose radiation is not a magical “cancer vaccine.” At the very best, low dose radiation might not hurt you or might have some very slight benefits. At worst, it might actually hurt you more than the current scientific consensus accepts. That’s too wide range of possibilities and too much uncertainty to be laying down a barrage of misinformation as intense as Coulter’s.

ADDENDUM: Here’s an amusing little takedown of Coulter’s nonsense, for your edification. I had a good chuckle at this comment by Gordon Bloyer, who writes:

Schultz telling anyone about science, LOL. Coulter wrote an extensive column using back-up from science. Sgt. Ed should learn to read.

Coulter didn’t give her “theory” she cited science. She is right and O’Reilly just shoots off his mouth before he lets others complete a sentence. In this case he had NO IDEA what Coulter was talking about.

I invite Gordon to read my discussion of hormesis and see that the “back-up from science” that Coulter used is anything but. I do thank Gordon, though, for a moment of hilarity in a painful day of grant writing. Ditto felixw, who comments:

I know that O’Reilly went to Harvard. And Ann Coulter graduated cum laude from Cornell, where she founded The Cornell Review before getting her law degree at the University of Michigan, where she edited the law review. Then she clerked for the United States Court of Appeals for the Eighth Circuit.

Given how much a law school education has to do with science, by this logic, I should be able to confidently and definitively make pronouncements on the law! After all, I graduated from the University of Michigan, too, just like Ann Coulter!