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Yes, drug companies do pay attention to herbal medicine

I’m only a monthly contributor here but between being a SBM reader and having my own blogs, I often grow weary of the blind criticism that researchers and drug companies couldn’t care less about traditional folk medicines as drug products. My laboratory spends every single day working on natural product extracts in the search for compounds that may have selective effectiveness against cancer. So, this is a bit of a sore spot for me.

Two papers this week from Cancer Prevention Research on the potential anticancer effects of a diabetes drug (Nathan Seppa story here) remind me to tell the story of a Middle Ages European herbal medicine used to treat polyuria that gave rise to one of the most widely prescribed drugs in the world, metformin (Glucophage in the US). Metformin, known chemically as a biguanide, dimethylguanide to be precise, traces its roots to the plant Galega officinalis. Known as goat’s rue, French lilac, or professor weed, this plant was shown to be a rich source of guanidine and a less toxic compound later called galegin or galegine (isoamyline guanidine).

Although used as an herbal medicine in Europe for centuries, especially in France, this classic 1918 paper (free PDF) in the Journal of Biological Chemistry was perhaps the first widely-recognized report of the hypoglycemic effect of guanidine. The study was conducted in rabbits by CK Watanabe at Yale University. (P.S. Thank you, JBC, for making your archives freely available – the JBC was founded in 1909 by my blog nymsake, pharmacologist John Jacob Abel.)

While guanidine was to toxic for use in humans, pre-World War II researchers in Germany began synthesizing analogs called synthelins, biguanides with long carbon chains between the guanide moieties. A Parisian physician and clinical pharmacologist, Jean Sterne, probably played the most pivotal role in getting this class of compounds into clinical use. In the 1950s he held both academic and pharmaceutical industry positions, the latter at Aron Laboratories.

While there, Sterne’s group investigated a series of biguanidines that included metformin, a deceptively simple molecule. and they published a crucial paper in 1957 where he coined the name Glucophage for metformin, “glucose eater.” The paper was written in French and appeared in the less-widely read Maroc Medical journal. A paper that appeared later that year in Proceedings of the Society for Experimental Biology and Medicine on a related compound, phenformin, is more widely cited – the authors were then at the US Vitamin Corporation.

A long series of clinical studies with the biguanides ensued over decades but it was the acquisition of Aron Laboratories by Lipha Pharmaceuticals in 1995 that led metformin to come to the US market. It’s a fascinating story that gave rise to a multi-billion dollar market of Glucophage and related dosage forms. And that’s without even getting into studies this week on the potential anticancer effects of metformin – that story is for another day.

There are two superb papers you must read if you want more details on the history of metformin. An unparalleled, short, and free-access history of metformin written by Clifford Bailey and Caroline Day at the Aston University diabetes research group in Birmingham, UK, can be found here (PDF). Much of the historical information I’ve provided here comes from that paper. Second, to accompany the two papers in this month’s issue of Cancer Prevention Research Michael Pollack at McGill University in Montreal wrote an excellent overview of metformin and the critical gaps in our knowledge to investigate and potentially implement the use of the compound in cancer prevention and, possibly, treatment.

Posted in: Herbs & Supplements, History, Pharmaceuticals

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13 thoughts on “Yes, drug companies do pay attention to herbal medicine

  1. windriven says:

    An even more ubiquitous drug – this one tracing its ‘roots’ to willow bark – is acetylsalicylic acid. Aspirin.

  2. Drugs from Plants – Ethnobotany and Chemistry.

    Perhaps people will find the link regarding Drugs from Medicinal Plants interesting. I can’t vouch for the source, though.

    http://chemistry.about.com/library/weekly/aa061403a.htm

  3. Joe says:

    @windriven on 03 Sep 2010 at 8:09 am wrote “An even more ubiquitous drug – this one tracing its ‘roots’ to willow bark – is acetylsalicylic acid. Aspirin.”

    Actually, no, aspirin traces its roots to meadowsweet. I have been meaning to offer an article to SBM on that confusion.

    Thanks, David, for an interesting article.

    MinMich, thanks for that link- I will look at it now.

  4. DonSelgin says:

    How about Taxol, from the Pacific Yew tree?

  5. SomePapa says:

    DonSelgin: I’m not a big fan of youtube videos, but this one does a fair job of explaining, very much in layman’s terms, the process discussed in this piece. It uses Taxol as an example, and is likely to answer your questions in that regard, at least in a simplified manner.

    http://www.youtube.com/user/C0nc0rdance#p/u/17/r3yzXXPeLo0

  6. Zetetic says:

    “It’s a fascinating story that gave rise to a multi-billion dollar market of Glucophage and related dosage forms.”

    Great article but let’s not remind the detractors about those money hungry BIG PHARMA companies!

  7. I’m so glad to see that people also remember the story of Taxol. As I wrote in my introductory post here at SBM almost two years ago, I had the honor to work with the late Monroe Wall and the still-spry Mansukh Wani who are credited as the co-discoverers of Taxol, then “little-t” taxol.

    In fact, my follow-up post discussed a classroom assignment I had with our toxicology graduate students at North Carolina Central University using taxol as an example of the drawbacks faced by using herbal medicines (“Why we don’t prescribe bark for cancer”).

    One of the nice things about blogging is being able to go back to these vignettes.

  8. Galadriel says:

    Digitalis (foxglove).

  9. NicholasTurnbull says:

    I believe we have a three-pronged devil’s pitch fork when it comes to dealing with herbal therapies:

    The first is that the results of negative trials investigating the effectiveness of many traditional herbal treatments leave proponents of herbal medicines with the impression that there is some calculated effort to discredit all such treatments in all branches of medicine, which is very far from the case. It could even be argued that some of these proponents expressly look for these negative studies so that they can firstly claim the study is biased; secondarily claim the results are wrong; and thirdly claim these studies evidence of some concerted conspiracy by Big Pharma. They do these three things to avoid the inescapable conclusion that they themselves may be wrong. Yet when the trials roll out that demonstrate some positive effect, no matter how small, they are the first to celebrate the fact and somehow the conspiracy theory falls by the wayside even when non-CAM organisations run the studies.

    The second is that it is entirely possible some herbal compounds prescribed by herbal practitioners may contain the drugs of the future, but since herbal medicine practitioners have prescribed them for such broad-spectrum diagnoses that are too imprecise to be scientific, it isn’t possible to inspect their data for leads directly; and therefore we simply may not have found the *actual* application for them yet.

    We are not, in science-based medicine, ashamed that the roots of many key drugs were in botanical sources, but in order to find a genuine causality between treatment and “cure”, realistic diagnosis is necessary to examine effectiveness. Since we cannot surely pick out every plant in the entire flora of Earth and test against every possible disease that affects its fauna, we are simply waiting for the chance discovery to occur or molecular targets being identified that are similar to known herbal compounds.

    The third is that chemically-synthesised forms of the herbal compounds are obviously engineered for a very specific pharmacological and pharmacokinetic effect, unlike the raw forms of the herbal compounds that quite frequently contain unwanted chemical components that can have serious side effects. I recall a patient of my acquaintance, under treatment for cervical cancer, who suddenly and inexplicably developed gastrointestinal symptoms analogous to irritable bowel syndrome. Whilst quite frequently gastrointestinal symptoms can be observed from chemotherapeutic agents the onset was well after the patient’s chemotherapy regimen had begun, and the patient at least subjectively had not experienced the symptomatology before.

    On investigation, it turned out she was taking heavy doses of milk thistle as prescribed by a traditional Chinese medicine practitioner, and on advising her to discontinue the compound the symptoms greatly alleviated. So indeed, we must be on the lookout for therapeutic agents lying undiscovered in herbal treatments, but prefer synthesis of compounds over use of raw extracts; and exhort prescription only at best on the basis of efficacy and safety.

  10. Lancelot Gobbo says:

    Colchicine from colchicum, the autumn crocus, and vincristine and vinblastine from the Madagascar periwinkle. I don’t suppose I need to add diacetyl morphine from papaver somniferum to the list, hmm?

  11. MKirschMD says:

    Should we even use the term ‘herbal medicine’ until we have evidence of efficacy? I readily admit that many ‘medicines’ that western trained physicians like me use are of marginal benefit. Nevertheless, all treatments should be tested by the scientific method to determine if they can perform. I realize that ‘herbal medicine’ is chic, but, until proven otherwise, they are still herbs.

  12. NicholasTurnbull says:

    @MKirschMD

    Of course. You are quite right indeed, though of course unproven drugs in evidence-based medicine are still generally termed “medicine”. My, it would be positively a utopia if general discussions of drug research in the media if “potential medicines” were announced rather than “new drugs which may…”. Though, I have to say, the most egregious by far is the term of “healer” and in discussion with cancer patients, nothing jars quite so badly as to hear them repeat the word once per sentence when no apparent significant placebo is being derived and the only “healing” being obtained is of an excess bulge in their wallet.

  13. Ian says:

    @MKirschMD isn’t calling them simply “herbs” downplaying the potential risks? They can and do have active ingredients.

    Herbs are just something I use to make food taste better.

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