By Eric Brand

The other day I read an interesting article by Andrew Weil entitled “why plants are (usually) better than drugs.” The article is an interesting read, and it touches upon why most modern pharmaceutical companies focus on synthetic derivatives rather than full-spectrum plant-based drug products. Dr. Weil makes a number of good points in the article, and it ties into a topic that has been on my mind for some time: the strengths and limits of testing and our current state of knowledge regarding the chemistry of Chinese herbal formulas.

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From the sidelines, it is easy to look at Chinese medicine and say: “clearly there are a lot of valuable and clinically effective remedies there, why don’t drug companies simply focus on these plant-based drugs?” Dr. Weil makes the point that most of our readers already know- natural compounds aren’t patentable so their synthetic derivatives offer the most expedient way to recoup the investment costs of bringing a drug to market. But beyond this, there are a number of other factors involved.

Herbs are clearly a powerhouse of potential medical applications. For centuries, herbal medicine and pharmaceutical science were one and the same, and scientific testing gives us fascinating insights into the complexity of herbs. However, while we would all like to have more scientific knowledge about herbs, each question has a price tag. We don’t have all the answers we want because the questions are so numerous and expensive.

Scientific funding generally comes from academia and industry. Each has its limitations but each makes a significant contribution to the state of scientific knowledge. Industry can benefit from natural product research, and this industry research can enhance our understanding of natural products. While it isn’t possible to patent a natural product, it is possible to have a patented process of extraction. Thus, a drug company could manufacture a product derived from a full-spectrum extract of multiple botanicals, patent the process, sell the extract as an FDA approved drug, and make money. No inherent problems there.

However, the devil is in the details. FDA drug laws require batch-to-batch consistency, so the drug company has to design a tested process to ensure consistency across each batch despite natural fluctuations in the raw materials. While complex, this can be done. Yet how do they determine which marker compounds to look for in a multi-herb formula, how does one know which chemical or mix of chemicals is responsible for the activity of the drug?

HPLC (High Performance Liquid Chromatography) is one of the most commonly used testing methods to evaluate the constituents in an herbal product. Let’s use HPLC as an example to ponder the scope of the scientific challenges in evaluating the activity of even a single traditional formula.

Any given herb contains many chemicals, and the most common herbs have well-known active ingredients or chemical families of interest. For example, we can test a product like Huang Qin for its baicalin content, or ginseng for its ginsenoside content. Such a test typically costs about $300 per test. Easy enough, assuming that the active drug of interest is one that is already well-established in the scientific literature.

But how do we discover new chemicals? Let’s say that you cook the Ren Shen and Huang Qin together. Now let’s say we want to test those same two constituents to see how they came out when the herbs were cooked together (baicalin from HQ and ginsenosides from RS). First, we would need to establish an appropriate testing method. Validated methods exist to look at these constituents in single herbs, but a method to assess them in the formula would need to be developed and validated before it could be assumed to be accurate (one could use the standard testing method but its validity wouldn’t be scientifically proven until it was repeatedly shown to work in the formula in question).

So let’s say we devise a method that works repeatedly with a high degree of accuracy. Now we can measure the constituents that we were originally aware of. But let’s say that the chromatograph shows a new peak that we never saw before in the ginseng or the scutellaria when it was extracted on its own. This peak probably represents a new chemical formed in the decoction process that didn’t occur in either of the herbs independently, and we could easily miss it if it showed up at a different wavelength than the chemicals that we were originally looking for. This new compound may well be the active drug in the new formula. But what is it?

Well, when it comes time to answer that question, better keep the wallet handy. Determining the basic chemical identity of that one peak on the chromatograph will cost about $10,000. That is, $10K if it happens to be a chemical that is already known and classified, and available as a pure commercial reference sample.

The HPLC machine can only tell you what you are looking at if you already know what you are looking for- a sample of the pure known compound needs to be put in the machine side-by-side as a reference. If the chemical is novel, determining its identity and chemical structure without any existing comparisons to reference will be VERY expensive. Then to determine if it has pharmacological activity, reach for the wallet again. Think of how much it will cost to synthesize or isolate enough of the stuff to test it in rats, then other animals, cells, and finally live humans. Maybe it is a dead end, but maybe we end up with a new, novel active ingredient with medical value. But is it part of the activity of Xiao Chai Hu Tang? How many other novel chemicals are in that one formula alone? How many more possibilities are there if we add two more herbs? It boggles the mind.

It is clear that herbs are very effective clinically. It is clear that botanicals will continue to have a tremendous impact on medicine, as they always have. But when I actually stop to ponder the scope of the questions involved, it really blows me away. Just determining the chemical structure of all the chemicals in a common formula would be a monumental task, much less determining their activity. Every test costs money, every test answers one more ‘yes or no’ question, and every test raises a hundred new questions. Thankfully, traditional theory and pattern diagnosis gives us a time-tested method that often results in successful clinical results. And the technology has many uses; for example, HPLC machines can be used to capture a digital image that illustrates the flavor of a particular batch of wine with incredible sensitivity and better memory than the human palate. So even if we will never have all the answers, we can have fun asking the questions.