"Ayurgenomics": The return of woo-omics

Every so often, I come across something in the world of woo that leaves my jaw dangling from its joint in utter astonishment that anyone could think such a thing was a good idea. Sometimes these things are investigations into various paranormal phenomena. Sometimes, it's the latest anti-science denialist screed from a creationist. Other times, it's a contortion of science so egregious that I can't believe anyone would actually do it--or that anyone would actually mistake that woo for good science.

This time around, it's genomics that's being abused.

This is a topic that, although I don't write about it very often, irritates the crap out of me, and that's the abuse of new genomics technologies. I first started noticing it when Dean Ornish reported the results of a rather poorly designed cDNA microarray experiment as evidence that his dietary manipulation changed expression levels of genes related to carcinogenesis. Around the same time, I noticed that the National Center for Complementary and Alternative Medicine (NCCAM) was soliciting applications for applying genomics and other "omics" technologies to existing clinical samples from previous clinical trials of "complementary and alternative medicine" (CAM) therapies. I was so impressed by this Request for Applications (RFA) that I referred to it as "woo-omics." After that, there wasn't much about woo-omics; so I didn't write about it, although I did write a fair amount about the application of genomics technologies to science-based medicine and putting the results of the Human Genome Project and Cancer Genome Atlas into perspective. I found all of this very interesting, but it had nothing to do with alternative medicine or CAM. And it was good.

At least, it was good until this weekend, when I came across a misapplication that led the term "woo-omics" to come back into my brain.

I don't remember how this came to my attention, but it did. It's an article that appeared in ACS Chemical Biology entitled Ayurgenomics: A New Way of Threading Molecular Variability for Stratified Medicine. I kid you not. It's courtesy of Mitali Mukerji at the Institute of Genomics & Integrative Biology (IGIB) in New Delhi, India. Her webpage on the IGIB website even lists her interests as the pplication of polymorphisms in mapping mutations and disease origins in SCAs; Ayur-genomics: exploring the principles of predictive medicine in Ayurveda; and Alu elements in genome organization and function. It all sounds so science-y, and--who knows?--interest numbers one and three sound reasonable enough. But interest number two? Not so much. In fact, it sounds about as far from science as you can get. Think of it this way: It sounds like science; it acts like science; it tries to use the language of science; but it's not science. Get a load of the rationale for the article. After discussing the difficulties in genome-wide association studies in "pinning down human physiology to a few loci," Mukerji writes:

We found this challenge very stimulating, and our understanding of population-wide variability across Indian populations (IGV Consortium)(6) provided a major thrust to further our quest for understanding the variability in healthy individuals. The head start came from the fact that there exists an exquisitely elaborate system of predictive and personalized medicine in India, i.e., Ayurveda, which has been practiced for over 3500 years. The system already has a built-in framework for stratifying healthy individuals who differ in susceptibility to disease and response to drug and environment. In contrast to the empirical approach of contemporary medicine, the Ayurveda therapeutic regimen is tailored to an individual's physiology. Though this system has fueled many drug discovery approaches and some attempts into its integration in pharmacogenetics have been made,(7, 8) a systematic analysis of underlying principles has been lacking. In order to undertake integration of this most ancient system of medicine, which is scripted in Sanskrit, with the language of modern genomics and medicine, we undertook this endeavor with a trans-disciplinary team of researchers. For the first time we could demonstrate molecular evidence for these concepts and build a framework for "Ayurgenomics", which can provide impetus to personalized medicine.(9, 10) We provide a perspective of the concepts and also the further prospects in this field (Figure 1). The original Sanskrit verses with their meanings are available as supplementary online material in our prior publications.

Now, it was news to me that Ayurveda had "fueled many drug discovery approaches"; so I looked up the two articles referenced. Like Mukerji's article, these references looked at the three major constitutions postulated in Ayurveda under the Prakriti classification. One article was in a woo journal of highly dubious value and postulated a "reasonable" correlation between Prakriti classification and certain Prakriti types, while the other article was a commentary suggesting using Prakriti and asserts that the "concept of Prakriti or human constitution plays a central role in understanding health and disease in Ayurveda, which is similar to modern pharmacogenomics." Basically, the whole article argues that, because a few useful compounds from Ayurveda, that Ayurveda could be useful as a basis for drug discovery and the development of "personalized medicine."

Not knowing what the heck Prakriti is, I decided to look it up. Thanks to Wikipedia and other sources, I now know that in Hinduism Prakriti is the "basic nature of intelligence by which the universe exists and functions" and the "primal motive force." In Ayurveda, it's used to refer to a body type in Ayurveda. Here is a test to determine one's Prakriti. Based on the results, one is classified according to three Doshas: Vata, Pitta and Kapha. These three Doshas can be combined into ten ways to produce ten body types. Now, certainly some of these characteristics likely have something to do with health ("overweight, difficult to lose weight," for instance, or "fair skin, sun burns easily," the latter of which could indicate susceptibility to skin cancer). However, just because body types based on a system of classification that is more or less based on an Indian form of vitalism ("primal motive force" or "basic nature of instelligence") might coincidentally have something to do with discoveries found later does not mean that the basis of the system upon which these body types are based has any external scientific validity. One might as well perform omics analyses on people to predict responses to homeopathy. Yet somehow Mukerji thinks that somehow using integrating knowledge of these Doshas into genomics will lead to better control groups and the discovery of biomarkers of disease whose utility will be accentuated by using them in concert with information about Doshas:

An individual's basic constitution, Prakriti, is described to be a consequence of the relative proportion of Vata, Pitta, and Kapha. These proportions of Tridoshas are not only genetically determined (Shukra Shonita) but also influenced by the environment during development, especially maternal diet and lifestyle. Prakriti is fixed at the time of birth and remains invariant throughout the individual's lifespan. Ethnicity (Jatiprasakta), familial characteristics (Kulanupatini), and geo-climatic regions (Deshanupatini) are also implicated in influencing phenotypic variability through their effect on Tridoshas and Prakriti. Thus, most of the factors such as ethnicity, geography, and environment that contribute to interindividual variability at the genetic or epigenetic levels are embedded in Ayurveda's concept of Prakriti. In an individual, the Tridoshas work in conjunction and maintain homeostasis throughout the lifetime of the individual.

Why it is necessary to use a religion-based system in order to ascertain information about a patient's body habitus, familial characteristics, ethnicity, and other traits relevant to disease, I don't know, but apparently Mukerji thinks that we do. None of this prevents Mukerji from proposing this system for "weaving the threads of molecular variability through Ayurgenomics":

This is proposed even though Mukerji basically points out that Prakriti is basically very much like the four humors in "Western" medicine and the five elements in traditional Chinese medicine:

Ayurvedic practitioners deconvolute the "mixture impression" thus obtained to identify proportions of Vata, Pitta, and Kapha in an individual's Prakriti. This "subjective" assessment (which was objectivized to a scoring system through a questionnaire) considers different phenotypic attributes of an individual and links these multiple windows to create intraindividual phenotype-to-phenotype links. A disease according to Ayurveda is a perturbation of Vata, Pitta, and Kapha in an individual from his or her homeostatic state. Ayurvedic treatment aims to bring it back to its native state by appropriate dietary and therapeutic regime.

"Bring it back to its native state"? That sounds a lot to me like "bringing the humors back into balance" or, if you're an aficionado of traditional Chinese medicine, bringing the five elements back into balance. I do like the science-y sounding referencs to "different phenotypic attributes" and somehow creating "intraindividual phenotype-to-phenotype links." It's the sort of meaningless gobbledygook that impresses those who don't know anything about the subject but leads those who do to collapse in fits of hysterical giggling.

Mukerji continues:

Ayurveda describes not only the functional attributes of Vata, Pitta, and Kapha but also their contribution on different scales in seven different constitutions. Therefore, Ayurveda already has a stratified approach as its basic tenet for personalizing therapy. Thus we felt that integration of this stratified approach could complement approaches to development of personalized medicine while gaining insights into systems biology. We realized that before making any attempt toward this endeavor we would have to address an ontological challenge in connecting together the literature from Ayurveda, modern medicine, and molecular biology.

Again, why combining Ayurvedic literature with modern medicine and molecular biology would be a good thing is not explained. To me, that would be a lot like taking the writings of Hippocrates and combining them with the latest cutting edge molecular and systems biology techniques. It would be highly unlikely to be informative or helpful. One might as well take the Edwin Smith papyrus, which described ancient Egyptian medicine, and combine it with the latest omics techniques. The priest-physicians of ancient Egypt would probably have as much or more to say to modern scientists than the writers of the ancient texts of Ayurveda. One wonders why somewhere, somehow, someone doesn't try to resurrect ancient Egyptian medicine.

Not surprisingly, Mukerji cites a lot of her own work in this review article, including an article from 2008 entitled Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda, which Steve Salzberg, a systems biologist and skeptic, looked at in 2008. He was not impressed, and neither was I when I read the paper. Basically, Mukerji and her co-investigators partitioned subjects into the three Doshas based on Ayurvedic principles, but in reality the vast majority of the classification is simply based on body type and body habitus. That's why, when the authors found that genes associated with an elevated risk of cardiovascular disease are more highly expressed in Kapha males, it's not particularly surprising, given that Deepak Chopra and others characterizes Kapha as prone to obesity. In other words, so what if Mukerji found differences in gene expression based on Ayurvedic body types. They're different body types, and we already know that people with different body habitus can be prone to different kinds of diseases. Ayurveda adds nothing new to this knowledge, much less suggests a rationale upon which to base a new "omics" discipline. Taking studies like this and proposing something as ridiculous as "Ayurgenomics" does nothing more than show how far believers in pseudoscience will go to try to conjure up a seemingly scientific justification for their woo. Remember, Doshas resemble, more than anything else, the Indian version of the Four Humors. Do we try to fit humoral theory into a new "omics" discipline? No, we don't, although I fear that some day someone might try.

Unfortunately, as Steve Salzberg points out, NCCAM is funding grants like R21AT001969, which funds the "Ayurvedic Center for Collaborative Research." A quick search for NCCAM grants funding Ayurveda on NIH Reporter reveals several grants in Ayurvedic medicine funded by NCCAM, including Ayurvedic alternatives in autoimmunity and A whole systems approach to the study of Ayurveda for cancer survivorship. One wonders how long it will be before NCCAM starts funding "Ayurgenomics" projects.

I fear it won't be long.

More importantly, I want to know how crap like this finds its way into decent journals like ACS Chemical Biology and PNAS (which one of Mukerji's articles also found its way into). If you want to point to a failure of peer review, there's the place to start.