Let me begin with a story. An assistant professor submits a reasonable application to NCCAM to investigate the potential metabolic and pharmacodynamic interactions of St. Johns wort with conventional chemotherapy. This was the year or year-and-a-half before SJW was known to have significant CYP3A4 inductive activity due primarily to its component, hyperforin. Said investigator used this preliminary data, not explicitly required for theNIH funding mechanism (called an R21), to question whether St. John’s wort used by depressed cancer patients might interfere with chemotherapy. The original proposal earned a priority score of 228 (as with golf, the lower the better: the best is 100, the worst is 500.)

The major reviewer critique was that the assistant professor, Your Humble Pharmacologist, lacked, at the time, significant natural products chemistry expertise. YHP was then doing his sabbatical in the NC Research Triangle area and wisely sought the support and expertise of the now-late Dr. Monroe Wall and surviving Dr. Manuskh Wani. These gentlemen discovered and solved the structures of taxol from Taxus brevifolia and camptothecin from Camptotheca acuminata. Taxol itself became a blockbuster drug for Bristol-Myers Squibb while camptothecin required water-soluble modifications to foster topotecan (Hycamptin) and irinotecan (Camptosar) that collectively saved or prolonged the lives of thousands of men and women subjected to breast, ovarian, lung, and gastrointestinal tumors. In 2003, they received the designation of an American Chemical Society National Historic Chemical Landmark for their three decades of work in this area. (Sadly, they received none of the profits from these drugs as their discoveries pre-dated the Bayh-Dole Act that allowed NIH funded researchers to share in the revenues of intellectual property emerging from their work.).

Being a savvy young investigator, I sought and enlisted the assistance and support of Dr. Wall and colleagues to provide my team with world-class, natural products expertise. Stunningly, the subsequent application was awared a score of 345 (*much worse than the original) with the criticism from reviewers that all Dr. Wall did was to lend a drug development aspect to an otherwise “herbal” applicaton.

To this day, I cannot fathom who better I could have sought for natural products expertise on this grant application.

Since then, three of my colleagues and I have submitted 13 applications to NCCAM, including an application for a comprehensive Botanical Research Center grant. All 13 received unfundable scores. Among these was a 279-page application for a NCCAM Botanical Research Center – reviewed but not discussed by the evaluation panel.

Nonetheless, I have taken the approach that if NCCAM were to continue its existence, I would try to be part of the solution.  I have accepted several invitations to review research and training grants for NCCAM and I am pleased to say that one or two projects that I ranked highly ended up being very productive, specifically in the area of natural products and traditional herbal medicines.  I also have some friends and valued colleagues who contribute to the scientific integrity of NCCAM. However, my collective experiences lead me to believe that they are voices quenched by the vast wilderness of the promotion and advocacy of “integrative medicine” and CAM.

Chris Mooney recently asked the question as to why sci/med bloggers are up in arms about Sen Tom Harkin’s recent complaints about the National Center for Complementary and Alternative Medicine (NCCAM), the arm of NIH charged with funding studies to investigate the mechanisms and efficacy of modalities not currently considered mainstream medicine. I left a comment for Chris that ended up being a blog post so I’ll share it with readers here and expound a bit for good measure.The problem is that Harkin has stated that the establishment is discriminating against alternative medicine and that it seems to him that NCCAM has been doing too much to disprove the efficacy of alternative therapies. [see excellent post by Dr David Gorski and others here at Science-Based Medicine].The story of Harkin’s amazing statements were first popularized last week by Majikthise journalist, Lindsay Beyerstein, daughter of the famous Simon Fraser Univ Prof Barry L Beyerstein whose article, Why Bogus Therapies Often Seem to Work, I have used often in my lectures. Lindsay notes:

Harkin used his clout on the Appropriations Committee in 1992 to create the National Office of Alternative Medicine. In 1998 he co-sponsored legislation with Republican Bill Frist to upgrade the national office to a national center.

Over a decade later, Harkin’s disappointed that the NCCAM’s research is failing to confirm his biases.

Harkin doesn’t seem to realize that by publicly pressuring an ostensibly independent research center to produce positive results, he’s undermining the credibility of the center he worked so hard to create. If even if NCCAM does come up with positive results, Harkin’s giving the scientific community an excuse to discount that research as tainted.

In reality, many things have been tested, especially herbal remedies in my field, but the majority of the results have been negative. To the contrary of Harkin’s view of NCCAM and the researchers they supported, I would submit that the PIs of these grants were primarily advocates of alternative therapies who were sorely disappointed their ideas didn’t flesh out.

Harkin seems to be espousing an advocacy role rather than a scientific role. Moreover, the foursome that he brought to testify to the Senate primarily spoke of preventive medicine approaches that are not considered “alternative” but are rather being co-opted by so-called “integrative medicine” as their own since the more unscientific modalities have not proven effective. Saying that nutrition and cardiovascular preventive approaches are CAM or integrative medicine is utterly ridiculous.

Hence, I submit that integrative medicine is not “transformational.” Instead, it is the thinly veiled adoption of real medicine that works to provide an air of legitimacy around the highly-questionable approaches often offered, packaging it into a new-agey vibe where “patients” can go to spa-like clinics on academic medical center campuses, and have the luxury of paying out-of-pocket for “services.”

Yes, the key to the integrative business model is avoiding that nasty insurance business and capturing those willing and able to pay. I am waiting for a medical economics study to confirm my informal observations but integrative medicine, IMHO, is medicine for the rich and famous.

Believe me, as a natural products pharmacologist I would love to see some of these remedies have therapeutic efficacy. They may ultimately do so if proper basic science is done first that informs the dosing schedules used for clinical trials. However, NCCAM was under political pressure to show some benefit of anything and therefore supported expensive clinical trials in premature, Hail Mary attempts to get quick and early payoffs.

Instead, NCCAM is left with a trash heap of negative data (ginkgo, glucosamine/chondroitin, echinacea, St. John’s wort, shark cartilage) – not because the approaches are being discriminated again but rather because the science did not support their efficacy.

Hence, I argue that NCCAM is a victim of itself and its own establishment as an advocacy arm, not a scientific arm, of NIH.



Posted by David J Kroll