I recently joined the audience at a NCCAM think tank meeting on their development of “Principles Guiding Center of Alternative Medicine Natural Product Discovery Research”. A number of well known and respected Natural Product researchers, industry representatives, government regulators and funding agency representatives were present. The principles discussed were:
1. It is necessary to understand biological effects and mechanisms of action of CAM natural products (NPs) in order to pursue clinical research and development on their potential
2. Powerful “high throughput” tools and technologies (“omics”) are now available and should be actively pursued in helping to fill these important gaps in knowledge of biological effects and mechanisms of action of CAM NPs.
3. It is important to elucidate relationships between CAM NPs and host biology.
4. There remain major needs for development of better tools and methods for plant characterization and natural product analysis.
5. Look to various herbal traditions for promising leads regarding the potential of CAM natural products.
Dr. Chris Austin, Chief of the NIH Chemical Genomics Center, provided insight into genomics tools using molecular libraries as high throughput screens to uncover chemical probes or biological activity. Particularly encouraging were the numbers of molecular screens run simultaneously, their use of concentration curves to provide activity profiles, and the very small amounts of NPs required to run the screens.
During round table discussions, speakers offered several insights: reproducibility or botanical standardization continues to be a challenge; intellectual property claims can prevent development and sharing of data; the peer review process to often dismisses the use of botanical CAM: the therapeutic index for herbals is lower than drugs and thus, is better suited to milder conditions (see St. John’s Wort and depression); the need to measure chemo-prevention of disease. Unlike previous forums, discussion of multi-component effects now appear to be accepted as a major issue when discussing the efficacy of herbal medicine. To my mind, herbalist were sorely lacking from the table. Continued effort to clean up crude fractions goes against the idea that the “activity” is in the extract. When does the scientific community stop trying to turn herbals into drugs?
For the most part, the research community seems unwilling to embrace the importance of traditional knowledge in learning how to use botanical medicine effectively. Part of the issue revolves around how our allopathic medical system defines an etiology vs. traditional medical systems. Language and the underlying ideas of imbalance vs. disease are important to making choices on whether to use an isolated component or a crude extract, and how to decide whether the treatment worked. We do not as yet have measurement tools to fit how traditional knowledge defines the “condition”.
We also need more complex pharmacokinetic models to account for multi-component effects. Pharmacogenetic studies are important in teasing out confounding effects due to either the lack of exposure to or long-term ingestion of plant chemicals and the corresponding alteration in human gene expression. Can statistical tools be developed to include “lifestyle” choices that are often a part of a larger CAM approach among botanical supplement users? And can we find a way to apply the molecular screens developed in Dr. Austins lab as an epidemiological screen in clinical trials? We may find that our appreciation for the crude extract increases when we realize that numerous pathways are being expressed in responde to a plant extract containing multiple classes of phytochemicals? Now go eat some bitters!