Oct 13 2015

The Nobel and Chinese Medicine

The 2015 Nobel Prize for Physiology or Medicine went to three scientists who discovered treatments for parasites. Tu Youyou shared half the prize for her discovery of artemisinin, an effective drug against malaria.

Youyou is a Chinese researcher and, as has been widely reported, she relied on traditional Chinese texts to search for candidate herbs to test for activity against malaria. This has sparked a public debate about what lessons we can derive from this fact. Promoters of traditional Chinese medicine (TCM) argue that is shows the value of TCM. Amazingly (revealing their intellectual dishonesty) Naturopaths crowed that this was a vindication of naturopathic medicine.

Scott Gavura over at Science-Based Medicine gives a great analysis of what Youyou’s work really means. Meanwhile the New York Times struggles to give a “false balance” approach to the issue. There are a few interesting points worth highlighting.

The story itself is uncontroversial. Youyou set out specifically to find a drug that would be effective against malaria, which remains a serious medical problem for much of the world. Existing drugs, quinine and chloroquine, were developing resistance, and a replacement was needed. Her starting point was TCM texts, looking for any natural product that was used to treat fever. She came up with 2000 candidates.

After narrowing down the list, she finally settled on Artemisia annua as a promising candidate. Tea made from the plant was used to treat fever. Initial attempts at extracting an active ingredient, however, failed. She now recounts that she went back to TCM texts, one of which indicated that the tea was steeped in cold water. This led to the hypothesis that perhaps boiling was inactivating the active ingredient. She then tried ether extraction, which worked. The resulting chemical showed activity in mice with malaria.

The story is not over, however. The drug, which she called artemisinin, had low bioavailability and a short half-life. This means that the drug would essentially not work as a treatment in humans. It would never get to a therapeutic level at tolerable doses. A Swiss pharmaceutical company, Novartis, bought patents on artemether (an artemisinin derivative) and lumefantrine, another drug with activity against malaria. The combination proved clinically effective.

Pharmaceutical chemists are further developing the drug, removing unnecessary components of the chemical structure to maintain efficacy while reducing side effects.

What, then, are the real lessons we can derive from this story?

The first is that traditional Chinese herbalism (part of TCM) generally doesn’t work. That’s right – the opposite of what TCM proponents are claiming. Artemisia annua, as a tea or herb, has too low bioavailability to be an effective treatment for malaria. The TCM herbal treatment does not work. It took modern pharmacology to develop an effective treatment from the plant.

This is not an isolated example, but a problem that plagues all of herbalism. Herbs as treatments are drugs. They are consumed not for their nutritional value but for their pharmacological activity. The plant kingdom is a massive chemical factory, with evolution resulting in many millions of possible chemicals. Plants evolve chemicals to protect themselves from pests, and so many of these chemicals are horrible toxins.

The only difference between a toxin and a drug, however, is dose. A drug is a toxin that has a dose range in which it has one or more effects that can be safely exploited as a medical intervention. Most cultures found the low-hanging fruit in their environment – plants that have obvious and immediate effects, such as pain relief, moving the bowels, sedation, and especially hallucinogenics. They also found poisons that rapidly made people sick or dead.

More subtle effects, however, are very difficult to find with trial and error alone. Without scientific controls, we will tend to come to the conclusion (through subjective validation and confirmation bias) that anything works for anything. This is why TCM has 2000 herbs to treat fever. Most fevers will go away on their own, so anything you take with seem to work.

Using plants directly has other problems. Plants have dozens or even hundreds of chemicals. The concentration of these chemicals will vary by part of the plant, from plant to plant, from season to season, and with the methods of collection and preparation. As this episode demonstrates, boiling herbs to make tea may inactivate a potential active ingredient.

Perhaps the biggest problem, however, is pharmacokinetics. In order for a drug to be useful as a medical treatment it has to have a host of properties at the same time. Lack of any one is a potential deal-killer. First, it has to have one or more active ingredients that have an effect which can be exploited. Those chemicals need to have their useful effect at a dose that does not produce too many unwanted effects.

The active substances need to have adequate bioavailability, meaning that they get absorbed in adequate amounts. This one factor is probably the thing that renders most herbal treatments useless. Part of this is also water or fat solubility. If the substance is not water soluble or fat soluble, there is no way for it to get absorbed, or get into the blood or into the tissue. Once the drugs get into the system they have to get to the target tissue in adequate concentrations and hang out for long enough. If they are rapidly removed by a first pass through the liver, then they will never get to their target. Or they may be removed by the kidneys, or highly protein bound in the blood, or degraded by enzymes.

Then, of course, the herbal drug cannot have any short or long term toxicity. Many drugs fail in their early stages of development because, despite everything else being great, they cause kidney or liver damage. This is true of many herbs, in fact, including those that are used as part of TCM.

When drugs are developed they typically have to be altered in various ways in order to create a derivative that has all the right properties. The probability of a chemical having all the necessary characteristics simultaneously, as it exists in the plant, is vanishingly small. As a result most herbs are dirty drugs that are pharmacologically useless as they exist unaltered in nature. Their common saving grace, however, is that low bioavailability reduces the toxicity of most (not all) herbs that are in use. Trial and error at least weeded out those herbs that are immediately toxic.

The story of artemisinin demonstrates all of this. It took modern pharmacology to develop a useful drug from the TCM herb, out of 2000 candidates. Further, TCM practitioners did not have the knowledge of what they were treating. They treated fever, because they had no germ theory of disease, and did not even recognize the notion of a physiological disease. They did not understand malaria.

All of this makes me think that finding Artemisia in the first place was mostly luck. One in 2000 is not a great hit rate, and is more consistent with mostly luck. Further, as the New York Times reports, in the 40 years since her discovery, Youyou had used the same methods to try to discover other useful drugs, and has discovered – nothing. How many TCM herbal drug candidates did she screen in her career to find artemisinin? If you spent 40 plus years screening tens of thousands of plant chemicals for useful drugs, without any guidance from any traditional herbalism, I wonder on average how many discoveries you would make.

The career of Tu Youyou, if anything, documents the resounding failure of traditional herbalism. It is mostly useless, with a few lucky hits thrown in.

Modern pharmacology, by comparison, is systematic, based on fundamental knowledge of chemistry, pharmacology, physiology, and an understanding of the mechanisms of diseases. When I prescribe a drug I know exactly how many mg of active ingredient the patient is getting, its half-life, how it is eliminated from the body, its tissue penetration, its effects and side effects, its drug-drug interactions, and any potential toxicity. When you prescribe an herb to a patient, you have no idea about any of these things.


The New York Times article indicates that the Tu Youyou Nobel prize award has renewed debate about TCM. That’s good – if we have a real and informed debate. Ironically, while Western CAM practitioners are flirting with TCM and touting its benefits, China is trying to rid itself of this pseudoscience and embrace Western scientific medicine – because it works.

TCM pracitioners are not happy with the Youyou award. As the NYT reports:

“Are we truly respecting this cultural heritage?” Dr. Liu said. “When we think Chinese medicine needs to be modernized and the path it shall go down must be like Tu Youyou’s path, I think it is a disrespect.”

I wouldn’t use the word “disrespect” – that implies that our prescientific past deserves some respect. Liu is correct in that Youyou’s Nobel was a victory for modern science, and shows the inadequacies of TCM. TCM is based on pre-scientific notions, including yin and yang, and the five elements. It is the Eastern equivalent of the four humors, and the medical equivalent of astrology.

I don’t think that pride in Western culture should make us look seriously at Galenic medicine. Likewise, pride in Chinese culture should not be a motivation to cling to harmful prescientific medical traditions.

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