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I’ve subscribed to Nature for many years now, even though I don’t always read it. Nature is one of the oldest and most respected scientific journals around. It’s been around since 1869 and is said to be the world’s most cited journal. What makes Nature unusual these days is that it’s one of the last of the remaining general science journals and one of the two that still publish original peer-reviewed research in a wide variety of scientific fields. Astronomy, physics, chemistry, medicine, biology, Nature publishes it all. The only other journal of its type that I can think of is Science, which also has a similar high impact factor. In any case, getting published in Nature is a big deal, one that can make a career. Believe it or not, I actually have a Nature publication. True, it’s from the 1990s, and, true, I’m only the fourth author, but it is a Nature publication. Ever since then, I keep telling myself that, one of these days, I’ll manage to find a way to be published again in Nature, although I realize that it’s looking increasingly unlikely that that will happen. Such is the power and cachet of Nature. It’s a name that has provided prestige to some of its spinoff journals, such as Nature Medicine, although of late Nature appears to have diluted the brand name beyond belief.

Nature sells out

All of the above is why I’m very, very disappointed in Nature for having dropped a huge lump of coal into the stockings of supporters of science-based medicine a mere three days before Christmas. Maybe its editors thought that it wouldn’t be noticed right before the holiday season. I don’t know. I do know that I noticed. Basically, Nature sold out to a Japanese pharmaceutical company, which, along with a research institute, bought a supplement in Nature that is in essence an advertorial for its point of view. Don’t believe me? Check out this acknowledgment of the sponsors published in the advertorial:

We are grateful for the support of our sponsors, Saishunkan Pharmaceutical Co., ltd. and the Kitasato University Oriental Medicine Research Center. As always, Nature carries sole responsibility for all editorial content.

Yes, you read it right. Nature sold out to a Japanese supplement manufacturer and a quackademic medical center. But what did Saishunkan Pharmaceutical Company and the Kitasato University Oriental Medicine Research Center get in return for their money? Believe it or not, they got a whole supplement entitled Traditional Asian Medicine. This supplement is basically, with a minimal degree of skepticism, an attempt to convince Nature‘s readers that traditional Chinese medicine (TCM) is science-based and, even more than that, represents the cutting edge of medical science based on systems biology. Basically, it’s a mixture of The Good, The Bad, and The Ugly, with the vast majority falling credulously into the latter two categories by a wide margin.

Let’s start by taking a look at the main sponsor of the supplement, Saishunkan Pharmaceutical Co., Ltd., which is described thusly:

Saishunkan is a herbal medicine manufacturer which aims to help people make the most of their natural powers of healing and self-recovery. Based on the idea from herbal medicine that humans are part of the nature, our dream and joy is to ease the worries and concerns of aging, which comes to everyone. We maximize our capabilities to support lively and happy aging by using the power of nature to enhance human revitalization.

Our business started with a herbal formula “Tsusanto” for easing pains of neuralgia and rheumatism. In 1974, “Domohorn Wrinkle”, a family of basic skincare products intended for mature skin came to being from the same principles of herbal medicine.

Interestingly, Tsusanto is mentioned in a report on Pharmaceuticals and Medical Devices Safety Information and described as “ Ephedra Herb/Glycyrrhiza/Apricot Kernel/Stephania Tetrandra/Coix Seed Ephedra Herb/Apricot Kernel/Coix Seed/Glycyrrhiza/Sinomenium Stem/ Animal Bile. Meanwhile, Domohorn Wrinkle is described as containing a selection of about 150 “natural” ingredients. The company itself wants to argue that this is scientific, and, as evidence to support its products, it includes a message published in the supplement. The two-page message is basically a lot of self-serving company propaganda with a couple of Western blots and graphs, the better to make it more science-y. Apparently one of its concoctions increases levels of certain heat shock proteins, and this is trumpeted as evidence that they work. I’m not impressed.

Meanwhile the Kitasato University Oriental Medicine Research Center is described thusly:

The Oriental Medicine Research Center provides two types of clinical activities: medical treatment based on Kampo medicine theory, primarily using decoctions, and acupuncture that follows our country’s traditional techniques. To prepare Kampo medicines, we have set up an exclusive pharmacy that is in charge of dispensing and formulating these medications, focusing on crude drugs. Patients come from all over the country in search of treatments based on Oriental medicine, both Kampo medicine and acupuncture/ moxibustion.

Kampo medicine, for those of you not familiar with it, is simply the Japanese study and adaptation of traditional Chinese medicine (TCM). As practiced today, it does seem somewhat different in that the Japanese government regulates Kampo medications as pharmaceutical products, rather than supplements. It is, however, the same TCM woo, just transplanted to Japan.

The selling of TCM as being “personalized” medicine

The overall approach of the articles in this supplement appear to follow roughly the form and arguments of the very first article by Michelle Grayson, Traditional Asian Medicine. So let’s start there. It’s all on display there, claims that TCM is being “integrated” into “Western” medicine, and, most annoying of all to me, the claim that TCM is so “personalized” that randomized clinical trials are very difficult, if not impossible, to do:

Yet a bit of probing revealed what a complex story this is. Not only are big efforts underway to modernize traditional medicine in China and Japan, but Western medicine is adopting some aspects of the Eastern point of view too. In particular, modern medical practitioners are coming around to the idea that certain illnesses cannot be reduced to one isolatable, treatable cause. Rather, a fall from good health often involves many small, subtle effects that create a system-wide imbalance.

But do traditional medicines actually work? Their personalized nature makes randomized controlled trials — the gold standard for testing drugs — extremely difficult. Rarely are two formulations identical. However, as modern medicine becomes more personalized, using biological and genetic markers, it is inadvertently developing the tools to better test traditional medicines.

The other theme that runs through these articles, besides the implication that TCM is just too personalized to be studied easily using randomized clinical trials is the very conscious effort to link this “personalization” with the new era of genomic medicine, whose fruits (if we ever realize them) will one day be considered truly personalized medicine based on a patient’s genomic profile. Honestly, it should be profoundly embarrassing to Nature that one of its own actually wrote this twaddle. Actually, Nature should be profoundly embarrassed at publishing so much twaddle in this supplement. I could, if I so desired, spend several days, one post per day, deconstructing these articles. I’m not sure if I’m really up for the task right now, given the proximity of the holidays, although I might very well change my mind. I’m also likely to have more to say about this supplement issue on my other blog next week.

In the meantime, the next installment in the series is Convergence: Where West meets East starts with a passage that any supporter of SBM will find incredibly irritating. See how many fallacies you can count in just this short snippet of text:

For around 200 years, two very different systems of medicine have been used in Asia to cure diseases and keep people healthy. The local Asian one is based on traditional Chinese medicine (TCM) — herbal mixtures developed though observation and experience accumulated over thousands of years, but with unknown mechanisms of action. On the other hand, modern medicine, imported from the West, consists of chemically purified compounds that have been discovered through scientific investigation and tested in controlled clinical trials.

Yes, there it is, the the false dichotomy of “East” versus “West,” which portrays the “East” as being more spiritual and the “West” as being unfeeling, scientific, and out of touch with nature. Notice the reference to “chemically purified compounds” compared to the “natural” compounds of TCM. Notice the argument from antiquity, which implies that because TCM is ancient (“Observation and experience accumulated over thousands of years”) contrasted with science. Just this brief paragraph is a veritable plethora of woo-speak! It doesn’t get any better from there.

There’s a long section on TCM diagnosis, which in reality is based on a prescientific understanding of disease and how the human body functions. In essence, they boil down to imbalances in the five “elements,” which are basically the Chinese version of the four humors plus one. Remember that a major component of TCM diagnosis is something called “tongue diagnosis,” which the article even dutifully reproduces, complete with woo diagnoses like Yin Deficiency and Yang Deficiency, not to mention Qi Stagnation. This system is described, in all seriousness by the author, as producing diagnoses that are a “finer level of classification than disease groupings in modern medicine.” I kid you not. In support of this, a study published in the American Journal of Chinese Medicine is cited in which the authors used TCM diagnoses to classify rheumatoid arthritis patients. The study concluded that patients with cold-pattern symptoms (diagnosed by TCM, of course) responded better to real medicine, while patients with qi deficiency responded better to TCM. In any case, this entire article is very much woo-omics, like the Ayurogenomics that I discussed a while back; i.e, a total abuse of genomics and systems biology. They even use and abuse poor Leroy Hood, one of the originators of systems biology. Unfortunately, this abuse appears to be not without basis, as Hood has been known to drop some rather silly statements about how “traditional medicine” is a lot like “multitargeted” therapy, something I hadn’t known until after I did a bit of Googling after having read this supplement.

The rest of the supplement is chock full of similar atrocities against skepticism and science. For example, there’s an article by Felix Chueng entitled TCM: Made in China, which is basically one long appeal to popularity, listing how many people use TCM, how many companies manufacture it, and how this number is growing, as though this were evidence that TCM must be scientifically valid. Chueng even appeals to the one example of how a blind squirrel can find an acorn every so often, namely the example of the antimalaria drug artemisinin, which was isolated from an herb described in TCM. Another article by Chueng extolls the glories of how TCM is practiced in the clinic. It’s nothing more than one long anecdote, in which the author, suffering from a “persistent back problem” that also causes leg pain (which sounds a lot like sciatica) goes to a TCM clinic. There, he’s diagnosed with xinhuo (“heart fire) and then treated with acupuncture, moxibustion, and cupping. He was even treated with–believe it or not–bloodletting to clear the “heart fire.” He concludes:

I walked happily away with my leg feeling much better. As I left the hospital, I saw the women still doing their baduanjin. I began to wonder if maybe I should start practicing baduanjin too.

Baduanjin is a form of Tai Chi.

As I read this account, I wondered: This guy is editor of Nature China in Hong Kong. I couldn’t help but also wonder if Chueng had ever heard of placebo effects, because he was describing a lovely example of them in his anecdote.

A blind squirrel finds an acorn occasionally, or: The use and abuse of systems biology

Much of this supplement has to do with a tactic that I’m seeing more and more from promoters of TCM, Ayurveda, and the like, namely that the principles of TCM are a lot like the new, more “holistic” principles of systems biology and that TCM herbal preparations are really rationally designed mixtures of active compounds designed to “hit multiple biological targets,” an example of which can be found in this bit of pure propaganda for TCM found in an article by Zhiguo Xu entitled Modernization: One step at a time. Once again, the example of artemisinin is trotted out as an example to imply that all TCM must have something to it. Of course, what’s interesting is that the description of artemisinin provided in this article is nothing more than good, old-fashioned pharmacognosy; i.e., natural products pharmacology. In fact, that, and the other example culled from TCM, arsenic trioxide, are used to imply that the view of TCM that purified compounds aren’t the best way to treat disease, that there is synergy between different compounds in herbs:

For decades, European and US regulatory agencies held the view that a drug must be either a highly purified or synthetic agent. Traditional medicines could not qualify under this definition because a TCM preparation is a concoction rather than a single compound, and the chemical structures of the active ingredients are undefined. Consequently, when it came to assessing a traditional medicine for efficacy, most effort went into identifying the principal agent within a herb or mixture of herbs and purifying it as a single chemical compound. However, “academic scientists and the pharmaceutical industry have not been very successful at isolating the active substances in TCM preparations”, says Bai Lu.

Others share Lu’s dour outlook. “Few active ingredients are extracted from TCM herbs by modern scientific approaches,” says Yi Rao, dean of life sciences at Peking University in Beijing. “Those extracted effectively have not been demonstrated to be clinically successful.” Indeed, he says, “artemisinin and arsenic trioxide are perhaps the only two examples”.

The author seems not to realize that these two examples of medications isolated from TCM treatments, far from indicating the importance of having multiple ingredients, actually demonstrate the importance of isolating the active compound and purifying it. Yet the entire focus of this particular article is to claim that there is “synergy” between ingredients of herbs and how to capture it. The problem is, there usually isn’t. Herbs can be drugs, but they are impure drugs. Perhaps the reason that so few active substances have been isolated from TCM herbs is because there just aren’t that many.

Even more amusingly, another example is described, something called the Herbalome project. This is nothing more than high throughput screening of herbs from TCM for active ingredients using liquid chromatography and other methods of separation. Analyzing 500 samples a day, the project has thus far identified the active ingredient from only one herb. Inadvertently, the Herbalome project appears to be demonstrating that there probably isn’t much that’s useful in the herbal medicine of TCM that hasn’t already been identified. Of course, that leads to this excuse:

For example, Liang acknowledges that one of the major tools used by his team as part of the Herbalome — high-throughput screening — is not ideally suited to the task. That’s because TCM concoctions are mixtures of multiple active compounds, and a typical Chinese medicine is intended to hit multiple biological targets.

Notice the rebranding. The originators of TCM had no idea what a “biological target” was. They were trying to “rebalance the elements” or “correct the flow of qi.” They weren’t trying to “hit multiple biological targets,” and they used herbs because that was all they had. Substances found in TCM that actually had some activity against real diseases (substances such as artemisinin and arsenic trioxide) were discovered by accident, not because the principles of TCM facilitated their identification. In any case, what the Herbalome project is doing is nothing different than high throughput screening of natural products that just happened to be used in TCM.

The previous article, at least, had a germ of truth to it in that there might occasionally be active compounds in various TCM medications. However, the next article takes this to the “next level” of woo by claiming that TCM is finally being appreciated because it’s being vindicated by new findings in systems biology and genomic medicine. It’s a horrible, horrible article by Jan van der Greef, principal scientist at the Netherlands Organization for Applied Scientific Research (TNO), professor of Analytical Biosciences at Leiden University and chairman of the Sino-Dutch Centre for Preventive and Personalized Medicine, entitled All Systems Go. Practically every paragraph had seriously cringe-worthy sentences in it (to supporters of SBM like me, anyway), passages like this:

The concepts and practices of systems biology align very closely with those of traditional Asian medicine. Consider the very idea of ‘health’. The current World Health Organization definition of the term is based on a 1948 consensus: “A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” However, an emerging concept of health in the scientific literature describes an ability to adapt and self-manage in the face of social, physical and emotional challenges1. This perspective has, of course, long been central to the concept of health in traditional Chinese medicine (TCM), which further includes spiritual fulfilment and a sense of individual well-being.

And:

But there is a growing realization in the West that single biomarkers are not enough. A better approach is to look at patterns of biomarker responses to a challenge. These data will provide insight into the resilience of allostatic mechanisms, and hence into a person’s health, an approach not unlike the tenets of TCM.

Get it? Understand? According to van der Greef, TCM was ahead of its time, and “Western” science is only now catching up! This assertion is, of course, a pair of fetid dingo’s kidneys. What’s really going on is that woo-friendly “Western” scientists like van der Greef are retrofitting new scientific findings into the framework of TCM and declaring that they fit. In reality, what quackademics are doing is taking parts of TCM that sound vaguely as though they fit in with the latest scientific findings in systems biology and grafting them on to create a Frankenstein monster made up of parts of systems biology with a parts from TCM stitched together. Add to that the typical alt-med excuse that “your science can’t study my woo” because it’s “personalized” and randomized clinical trials can’t handle that, and you have the recipe for the infiltration of quackademic medicine into academia.

In all fairness, I will concede that the Nature supplement isn’t entirely bad. For instance, there is a reasonably good article on biodiversity and how TCM threatens it by using body parts of animals belonging to endangered species, a practice that generates a lucrative trade in endangered species. Unfortunately, the article fails to describe just how cruel some of the techniques used to obtain these body parts and fluids can be and just how much they endanger species like tigers. There is, however, a nice debunking of the idea that rhino horn has been used for thousands of years to treat cancer. (It turns out that it was made up less than 100 years ago.) There’s also an article on the dangers of herbal medicine, which can cause side effects, sometimes severe. However, overall the articles in this supplement leave this reader with the inescapable impression of boosterism. This is, of course, not surprising, given that this supplement should be viewed, more than anything else, as an advertising supplement, bought and paid for by its sponsors.

A thought comparison

As I read this supplement, I couldn’t help but think of what the reaction would be from CAM practitioners to a supplement bought and paid for by a pharmaceutical company. (Actually, this supplement was bought and paid for by a pharmaceutical company; it’s just that it was bout and paid for by a pharmaceutical company that makes TCM remedies.) The reaction would be unrelentingly hostile, and rightly so. In fact, I highly doubt that Nature would agree to publish a supplement funded by, for example, Merck, Pfizer, or Sanofi-Aventis extolling the virtues of their products. I doubt even more highly that it would hire out its own editors to write articles for such a supplement. Yet that’s exactly what Nature has done in this case for TCM.

I’m left with the conclusion that, to their eternal shame, by publishing this issue, the editors of Nature have become willing shills for the TCM industry. Nature has sold out, and its editors and publisher should be called out for it.

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Posted by David Gorski

Dr. Gorski's full information can be found here, along with information for patients. David H. Gorski, MD, PhD, FACS is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute specializing in breast cancer surgery, where he also serves as the American College of Surgeons Committee on Cancer Liaison Physician as well as an Associate Professor of Surgery and member of the faculty of the Graduate Program in Cancer Biology at Wayne State University. If you are a potential patient and found this page through a Google search, please check out Dr. Gorski's biographical information, disclaimers regarding his writings, and notice to patients here.