I draw on four major sources to support this contention: (1) Products of America's largest pharmaceutical firms listed in the Physicians Desk Reference (PDR 1991), (2) Reanalysis of Farnsworth and Bingel (1977), (3) Canadian OTC Drugs (CPA 1988), and (4) Sittig's Encyclopedia (1988).
American consumers want natural drugs, believing natural drugs are safer than synthetics. The pharmaceutical firms seem to prefer synthetics or semisynthetics, in part due to proprietary economic reasons. The health of the drug company by necessity must concern the drug company before the health of the consumer. As noted in a recent International Trade Commission Study, "Between 1976 and 1990, the cost of developing a pharmaceutical product in the US increased from $54 million to $231 million. Only one out of every 4,000-10,000 compounds discovered can be marketed commercially--after which a company has less than ten years to partially recoup its R&D investment before its patent expires and generic manufacturers enter the market or a me-too drug is created by a competitor" (Chemical Marketing Reporter 1991). Such investments may lead pharmaceutical firms to prefer a proprietary synthetic or semisynthetic to a relatively less proprietary herbal or natural product. American pharmaceutical firms often seek the semisynthetic and avoid the natural compound, when, at least in some cases, the natural compound might be best. The pharmaceutical firm must consider several attributes including, safety, efficacy, reproducibility of results, patentability, and profitability. With at least $7,000 in public relations directed to each physician in this country by the pharmaceutical firms, the physicians may reflect the same priorities as the pharmaceutical firms. Consumers, National Institute of Health, Food and Drug Administration, and the government as a whole should seek the safest, cheapest, most efficacious drugs. Often, these could prove to be standardized herbs or relatively unpatentable natural products, placing the drug companies and the consumers and government's interests in conflict. More than 10% of Americans can't even afford modern medicine and/or insurance. Farnsworth (1990) estimates that about 64% of the world's population or 3.2 billion people use plants as drugs (largely unable to afford modern medicine). If their drugs are worth as much to them economically as modern medicine is to Americans, these plants are worth trillions of dollars.
What can be done to determine which natural alternatives are relatively safe, efficacious, and affordable to the majority of the world's citizenry? There must be some economic incentive for drug firms to investigate natural alternatives. Clearly, it would not make sense for a drug firm to invest $231 million proving that a widely grown ornamental could prevent migraine, when the drug firms are already reaping millions of dollars in the sale of proprietary migraine medications. If, on the other hand, drug companies by mandate, compared new synthetic drugs not only with placebo, but with one of the best herbal alternatives, e.g. feverfew for migraine, those drug companies could be given some marketing exclusivity on natural alternatives that the companies prove efficacious. As a society, we would feel safer in the knowledge that home-grown herbs had been proven efficacious, at least under the experimental conditions.
American consumers are calling for greater use of natural products (certainly they prefer natural antioxidants, cosmetics, dyes, food colors, and pesticides, if not medicines) while the pharmaceutical firms have moved towards the synthetic. It is hard to document the disdain for the natural compound among the druggists. Farnsworth notes, however (1990):
"Of all the pharmaceutical companies I know in the US that are interested in research on plant materials--and that's probably only four--none is interested in discovering active chemical structures which will be patented and marketed as drugs per se. They are looking for lead structures from which they would prepare analogues."
The only pharmaceutical firms that I know in the United States that are interested in natural products are Merck Sharp & Dohme (West Point, Pennsylvania), Eastman Pharmaceuticals (Rochester, New York), SmithKline Beecham (Pittsburg, Pennsylvania), and Glaxo (Research Triangle Park, North Carolina). There are several small start-up companies, getting into this area either from a mass screening viewpoint or from looking to ethnobotany e.g. Shaman Pharmaceuticals (see King 1991), to provide leads. This is a new trend: five years ago, there wasn't a single pharmaceutical company in the United States that had any interest in developing drugs from higher plants." (Farnsworth 1990).
Farther down Sittig's top 100, there are even fewer clearly "green" drugs. There are several estrogenic or androgenic hormones, presumably largely semisynthetic. There are several antibiotics derived from lower plants. Some have salicylic or tartaric acids or maleic-acids, coumarin, ethanol, furfurylamines, triethylamines, guanidine, benzaldehyde, proline, piperidine, heptaldehydes, and some contain semisynthetic opiates. Natural products, if they are used, are often only minor elements in a bigger formula. Stretching to accept guaifenesin (largely guaiacol which could come from a tropical tree), warfarin sodium (based largely on 4-hydroxy-coumarin, which could come from a tropical tree), and "nicotine polacrillex" (presumably based on natural nicotine which could be obtained from tropical trees (Duboisia) or weeds (Nicotiana), only about 5% of the top hundred are based primarily on higher plant phytochemicals. Ten percent are antibiotics derived from lower plants, mostly bacteria by biotechnology. Only by counting all the "iffy" odds and ends can one stretch the percentage to 25% containing at least one compound that could conceivably be derived from a higher plant.
The product monographs appendix of the CPA Book lists hundreds of apparently approved medicines from A&C with Codeine to Zinkosalb, both of which contain salicylic compounds which the American Indians once derived from poplars, willows, and even wintergreens. Such compounds count in the Farnsworth 25%, even though they are now synthetic.
A&C with Codeine illustrates the problems one encounters in trying to make a survey of this type. It contains three major ingredients, the now-synthetic acetylsalicylic acid, the sometimes synthesized caffeine, and the still natural codeine. Thus, it clearly contains one natural ingredient, probably the most expensive ingredient, codeine, still derived from the opium poppy. The caffeine may be synthesized or may be a by-product of decaffeinated coffee. The acetylsalicylic-acid could fall into the category called semisynthetic, if derived by acetylation of natural salicylic acid, but today it is mostly a pure synthetic, involving the utilization of no higher plant phytochemicals.
A and D Ointment is equally problematic. Vitamins A & D, as all vitamins, could come from natural products. But most are not derived from higher plants and all are synthesized (Harold Newmark pers. commun.). A and D Ointment would be scored "non-green," the lanolin of course derived from animals. Vitamins should be scored non-phytochemical ("non-green") unless the monograph specifies that the vitamin is plant derived. Absorbine contains methyl-salicylate and menthol, both natural products, now largely synthesized. Excipients like the glycine and lactose in Acetest are, of course, not scored as major ingredients. Similarly homatropine, while related to atropine, is treated here as a synthetic. How should one score ACI-JEL vaginal buffer which contains some herbal excipients like tragacanth and acacia, and compounds that do occur in plants like acetic and ricinoleic acids which are cheaper as synthetics? Resorcinol is scored synthetic though it too can be derived from umbelliferone. Pseudoephedrine and ephedrine are sometimes synthesized. Although lidocaine is said to have been patterned after gramine, it is not a phytochemical. Aloe in After Burn certainly makes it score "green." Similarly the witch hazel, not the salicylic acid in Aknoderm, makes it score "green." Listerine Antiseptic contains 21.9% alcohol, 0.09% eucalyptol (cineole), 0.06% thymol, and 0.04% menthol (all derivable from plants but probably synthetic).
The score could top 50% "green" if one counts minor ingredients, all vitamins and minerals which occur in higher plants, plus these other even more marginal compounds: acetic-acid, agar and alginates, alcohols, amino acids, all vitamins (even ascorbic acid), benzocaine, benzyl alcohol, benzyl benzoate, citrates, crotamiton, danthron and casanthranol (close to anthraquinoones), dextromorphinan and complex opiates, dextrose and other refined sugars, epinephrine, guaifenesin, homatropine, homosalate, hydrocortisone, hydroquinone, lactulose, lidocaine, paba, phenylephrine, resorcinol, selenium, and other minerals like sulfur, urease, and vanillylamide.
Some argue that we would be better with more natural product medicines and fewer synthetics. If reverting to natural medicines, which also prove safe and efficacious, could also help save the rain forest, there's one more reason to consider natural drugs. The government should consider requiring pharmaceutical firms not only to prove their new drugs safe and efficacious, but compare them not only to placebo, but also to one or more of the better herbal alternatives. If energy costs remain as they are or become less expensive, we should expect even more synthetics to replace naturals, in both Prescription and OTC drugs. If energy costs get more expensive, or if "green" consumers get louder, we may reverse the trend from natural to synthetic in this country.
|Higher plants used||Natural (%)|
|Bristol-Myers||11.2||Mayapple, ephedra, yew||<10|
|Smith Kline Beecham||Pyrethrins||<1|
|American Home Products||7.1||Opium, quinine||30|
|Eli Lilly||5.9||Periwinkle, curare||17|
|Warner Lambert||5.0||Belladonna, ephedra||<5|
|Rhone Poulenc||3.7||Opium, rauwolfia||15|
|Marion Merrell Dow||2.8||Opium, quinine, nicotine||17|
|Johnson & Johnson||Psyllium||10|
|Phytochemical||Percent of total Rxs|
|Steroids (95% from diosgenin)||14.7|
|Country||Number of patents||Percentage|