Phytomedicinal forest harvest

Phytomedicinal forest harvest

in the United States.

James A. Duke

Botanical Consultant,
Herbal Vineyard, Inc
8210 Murphy Rd; Fulton MD 20759; USA
Fax: + + 1 301498 5738 Email: jimdukeCcpcug.org

Abstract*

The Appalachian deciduous forests have been and continue to be a major source of some minor and major phytomedicinals in the southeastern United States. Fortunately, many important medicinal species are rather weedy and not at all endangered. Indeed massive biological control programs have contained e.g. Hypericum perforatum in the western US. Some American species may have been diminished by medicinal plant collecting, e.g. species in the genera Aristolochia, Cypripedium, Echinacea, Hydrastis, Panax and the like, and several species from the Orchidaceae family. Uses and abundance of some of the native US forest medicinal plant species and weedy invaders are discussed. As with legitimate medicines, herbal medicines are sometimes overplayed (Herbal hype) or intentionally misrepresented (Herbal hoax), with serious implications on their resource availability. Many of the phytomedicinal compounds are widely distributed, either taxonomically or geographically. Biologically active alkaloid's, like: berberine, sanguinarine, arbutin and

pulegone are widely occurring in the plant kingdom. Substitution or even competition among some medicinal plants from different parts of the world might have serious impacts on the present and future resource status of these species as is demonstrated for the case of Chinese-, American-, and Siberian ginseng.

Introduction: resource availability

Fortunately, many important medicinal species are rather weedy and not at all endangered. Indeed massive biological control programs have targeted and, to a degree, reduced infestations of Hypericum perforatum, under the name "klamath weed", in the western US. In 1997, under the name "Saint John's-wort, this species became the top selling herbal medicine for its antidepressant activity. Several species of Hypericum contain the antiretroviral compound hypericin. Pokeweed, Phytolacca americana, is the only source of the antiviral Pokeweed Antiviral Mitogen, which can be delivered to target sites on monoclonal antibodies. For its new Designer Food cancer-preventive program, the late Herb Pierson was looking at a pair of weeds, the garlic-mustard (Alliaria petiolata [M. Bieb.] Cavara & Grande), which may combine the activities and phytochemicals of the garlic and mustard families, e.g., respectively allincin and sulforaphane, and the burdock (Arctium spp. ), an ingredient in two noteworthy "anticancer formulae", the Hoxsey

Formula and the Essiac Formula. Burdock is well endowed with medicinal lignans that might help in Hodgkin's disease. All four of these weeds occur on my 6 acre farmette 20 miles southwest of Baltimore. The Designer Food Programme was also looking closely at licorice, Glycyrrhiza glabra, which is a serious weed, e.g. in Turkish wheat fields. Parallel biological activities will probably be demonstrated by America's Glycyrrhiza lepidota, not yet really a weed.

It is hard for me to call the mayapple (Podophyllum peltatum) a weed, but it is certainly a common woodland "wild flower". Podophyllotoxin was one "Drug of Choice" for brain tumors and Hodgkin's disease. Recently we have witnessed the advent of the semisynthetic etoposide (a modification of the molecule of podophyllotoxin). In 1984 and 1986 it was approved for cancer of the testicles and small cell lung cancer, respectively.

Long before we knew about etoposide andlor vepeside, there was an American market for one hundred tons of mayapple rhizome, mostly for use as a cathartic. It was even a component of the famous Carter's Little Liver Pills. For years, the resin podophyllin from the rhizome was the drug of choice for venereal warts (condyloma acuminatum). Yet at a Symposium on Plant Life in South Asia, 1 heard Tony Nasir complain that Podophyllum hexandxum had all but been eliminated from Pakistan forests by an occidental drug company developing etoposide. Fortunately, it has been brought under cultivation in the hill country of Pakistan. Like our species, it is a bit recalcitrant from seed, but rhizome transplants are easy. If for some reason, Asian trade in Podophyllum hexandrum were discontinued, much greater collection pressure on our American species can be predicted.

According to Principe (1989), etoposide already has annual sales of ca $15 million in the late 1980s but by now, sales are estimated to have topped $400 million a year. Thus economically,Podophyllum has challenged and exceeded the Madagascar periwinkle, Catharanthus roseus, the number 1 antileukemic plant. Products derived from the periwinkle had a wholesale value of $35 million in 1977 which Principe (1989) suggests would have translated to a retail value of $140 million.

The Appalachian deciduous forests have been and continues to be a major source of some minor and major phytomedicinals in the southeastern United States. Established adventives and Native American medicinal species still harvested today include: Achillea millefolium (yarrow), Acorus calamus (sweetflag), Arctium spp (burdock), Asarum canadense (wild ginger),Dioscorea spp. (wild yam), Echinacea spp. (coneflower), Hamamelis virginiana (witch hazel), Hydrastis canadensis (goldenseal), Hypericum spp.

(St John's-wort), Lobelia inflata (Indian tobacco), Lycopodium spp. (club moss), Oenothera biennis (evening primrose), Panax quinquefolius (ginseng), Passiflora incarnate (passion fruit), Phytolacca americana (pokeweed), Pinus strobus (white pine), Plantago major (plantain), Podophyllum peltatum (mayapple), Prunella vulgaris (heal-all), Prunus serotina(black cherry), Rumex crispus (yellow dock), Salix spp. (willow), Sanguinaria canadensis (bloodroot), Sassafras albidum (sassafras), Smilax spp. (sarsaparilla), and Veratrum viride(hellebore).

Markets have existed for others now or in the past decade, e.g. species of Adiantum Agrimonia, Alnus, Aplectrum, Aralia, Arctostaphylos, Aristolochia, Apocynum, Artemisia, Berberis, Cassia, Caulophyllum, Chimaphila, Cimicifuga, Collinsonia, Qpripedium, Dryopteris, Equisetum, Euonymus, Eupatorium, Filipendula, Frangula, Gaultheria,

Geranium, Glechoma, Hedeoma, Humulus, Hydrangea, Juglans, Juniperus, Lactuca, Medicago, Melilotus, Mentha, Mitchella, Myrica, Nepeta, Polygala, Polygonatum, Polygonum, Quercus, Rhus, Sambucus, Scutellaria, Senecio, Solidago, Spigelia, Stellaria, Tanacetum, Taraxacum, Tephrosia, Teucrium, Tipularia, Trifolium, Trilisa, Ulmus, Verbascum, Verbena, Veronicastrum and Zanthoxylum.

However, some American species may have been diminished by medicinal plant collecting, e.g. species in the genera Aristolochia, Cypripedium, Echinacea, Hydrastis, Panax and the like. Sanguinaria could be, unless the Food and Drug Administration lands on a toothpaste manufacturer, reportedly using sanguinarine in its antiplaque toothpaste. American medicinal usage may have contributed to the decimation of Cephaelis ("ipecac") in Latin America, Rauvoffia serpentina ("Indian snakeroot") in India, Podophyllum hexandrum (" Himalayan mayaple") in India and Pakistan, Tabebuia spp ("pan d'arco") and Uncaria tomentosa ("cat's claw") in South America. After a cancer scare re Rauvolfia, more than a decade ago, it looked as though there might be pressure on America's Veratrum viride as an alternative source of tranquilizers. (There are four Veratrum's proposed for listing as endangered of threatened, DOI, 1985). The crunch on Veratrum never came, as the cancer alarm re Rauvoffia was later rescinded. Alternative sources of reserpine exist in other species of Rauvolfia in Africa and Latin America. India has proposed CITES protection for both Rauvoffia serpentine and Podophyllum hexandrum (Marshall, 1989).

America's long courtship with sedatives and tranquilizers may have decimated ladyslipper populations here and there. Once known in Europe as American valerian, the ladyslipper has a long history as an antispasmodic, sedative and tranquilizer. The herb industry is attempting to help preserve ladyslippers. Many of the bigger dealers have publicly announced that they no longer deal in ladyslippers (McCaleb, 1990). North Carolina herbalists are attempting to propagate ladyslippers in tissue culture in hopes of mastering their cultivation, much as they have mastered ginseng cultivation.

Ladyslipper is not the only orchid endangered by medicinal collectors. One Baltimore herbalist told me he could get $18 for the paired tubers of Aplectrum or Tipularia. Like the middle eastern "salep", paired tubers of these species suggest the testicles and hence, following the "Doctrine of Signatures", they are promoted as "aphrodisiac". Indeed the family Orchidaceae may owe its name to the testicle-like tubers.

Availability of similar active plant components amoung different species

In a languishing unpublished draft 1 have, called "Gaia's Galenicals", 1 note that many of the phytomedicinal compounds, e.g. allicin, aloe-emodin, anabasine, arbutin, atropine, berberine, caffeine, capsaicin, chrysarobin, colchicine, dopa, emetine, ephedrine, eugenol, gossypol, harmaline, hypericin, lobeline, menthol, nicotine, podophyllotoxin, querectin, quercitrin, quinine, reserpine, rutin, salicylic acid, sanguinarine, scopolamine, sitosterol, theophylline, trigonelline, xanthotoxin, and yohimbine, are widely distributed, either taxonomically or geographically. On the other hand, some of our abused phytomedicinals have a relatively narrow taxonomic base, cocaine limited to the genus Erythroxylum, codeine, morphine and thebaine limited largely to the genus Papaver, and THC (tetrahydrocannabinol) to Cannabis. It is a sad commentary that the US spends $150 billion on illicit drugs while the world spends $150 billion on legitimate prescription drugs.

Figure 1: Goldenseal (Hydrastis canadensis)

The first major big-buck event that involved a forest medicinal was with the wild yam, Dioscorea villosa, well endowed with disogenin. Wisely, chemist Dr. Russell Marker, back in the forties, realized that all the major expensive hormones could be synthesized from the readily available starter material diosgenin. 1 have two sources of disogenin, the phytochemical to which the steroid and contraceptive industries owe their meteoric ascent in the 1940s and 1950s, Dioscorea villosa and Smilax spp., growing native in my east temperate forest area. In our folklore, there has evolved a belief that the wild yam is more useful for females, the sarsaparilla more useful for males. In Moerman's (1986) excellent and authoritative book, Medicinal Plants of Native America, only one use is cited for Dioscorea villosa, for the relief of pain during childbirth. The macho "Carrion Flower" is used for afterbirth, backache, body odor, boils, constipation, cramps, dysmenorrhea, gastrosis, hoarseness, nephrosis, pain, and pulmonosis. Not only do the yams contain sapogenins, they contain some 100-1,000 ppins sterols, mostly beta-sitosterol (Spiller, 1996). Sixty milligrams a day of sitosterol is reportedly efficacious in the old man's prostate ailment, benign prostatic hyperplasia or hypertrophy (BPH). The literature, erroneously, attributes progesterone (and more recently DHEA) to Dioscorea and testosterone to Smilax. In building my Father Natures Farmacy database (Duke, 1992a,b), 1 find no legitimate reports of those hormones in these plants. Plant extracts may have occasionally been spiked with many different hormones, and there is no doubt that many so-called wild am creams are spiked with progesterone and some are spiked with DHEA.

Over the years, the starter material of choice became soybean, as first the North American yam and then the Mexican yam priced themsevIes out of business. Still today there is brisk trade in the forest species, Dioscorea villosa, for natural wild yam creams, being widely promoted for hormonal balancing problems. Soon, it may become as endangered here as the AsianDioscorea's, overharvested, e.g., in India

Herbal hype and herbal hoax: the case of goldenseal, bloodroot, coneflower and pennyroyal

As with legitimate medicines, herbal medicines are sometimes overplayed (Herbal hype) or intentionally misrepresented (Herbal hoax). Like ginseng, goldenseal (Hydrastis canadensis.) has locally been over collected. Current pressures on goldenseal may partially result from an Herbal hoax, the widely spread untruth that goldenseal could help mask illicit drugs in urinalysis. More pressure may have been generated by testimonials of women who experienced remissions of uterine cancers while or after taking goldenseal.

Granted, goldenseal does contain the biologically active alkaloid, berberine, which has several legitimate uses, and which has proven antitumor activity, in vitro at least. But berberine is widely occurring in the plant kingdom, including some much more common weeds, and some even rarer than the goldenseal. Berberine has been reported, e.g, in Alstonia, Andira, Anomospermum, Aquilegia, Archangelica, Argemone, Berberis, Bocconia, Caltha, Chelidonium, Coelocline, Coptis, Corydalis, Coscinium, Dicentra, Dicranostignia, Enantia, Eschscholzia, Evodia, Fagara, Glaucium, Hunnemannia, Macleaya, Jeffersonia, Leontice, Mahonia, Nandina, Nectandra, Orixa, Papaver, Phellodendron, Platystemon, Podophyllum, Sanguinaria, Thalictrum, Tinospora, Toddalia,

Vepris, Xanthorrhiza, Xylopia, and Zanthoxylum, to mention a few genera. Berberine, still found in certain patent medicines and prescription drugs, has the following activities listed in the FNF (Father Nature's Farmacy) data base: amebicide, analgesic, anticonvulsant, antidiarrheal, antitumor, antiulcer, astringent, bactericide, candidicide, cardiodepressant, carminative, choleretic, collyrium, febrifuge, fungicide, hemostat, hypotensive, irmmunostimulant, myocardiodepressant, protisticide, RNA-depressant, sedative, stomachic, trypanocide, uterotonic and viricide. If berberine is what we are after, there are weeds, like barberries and prickly poppies, or cultivars like the celandine, California, or plume poppies, we could attack rather than goldenseal. Growing several of these species at my Herbal Village, I am trying to catalyze clinical studies of the barberry, a notorious weed here in the US, as an herbal alternative to the endangered goldenseal. It would be a doubled barrelled approach, decimating a weed while taking the pressure off an endangered species.

Sanguinarine, another rather widely distributed alkaloid, occurs in, e.g., Argemone, Bocconia, Chelidonium, Corydalis, Dicentra, Dicranostigma, Eschscholzia, Fumaria, Glaucium, Hunnemannia, Hypecoum, Macleaya, Meconopsis, Papaver, Platystemon, Robinia (?), Romneya (?), Sanguinaria, Sapindus (?), Scabiosa (?), and Stylophorum. The bloodroot,Sanguinaria canadensis, even made TV last year in commercials for an antiplaque toothpaste. This pleased some ethnobotanists while alarming some conservationists and consumers. Consumers were alarmed that the sanguinarine might poison us, even though Amerindians had used the bloodroot orally as an antiseptic.

Conservationists were alarmed that the demand for sanguinarine might endanger the woodland bloodroot. Sanguinarine is not a non-toxic alkaloid. Still it was being put in toothpaste to control plaque. The TV ads showed handsome toothsome ladies with bright smiles and holding the Sanguinaria root. Those smiles have disappeared from my TV screen. I'm told the FDA has challenged the manufacturers to prove that sanguinarine is both safe and efficacious for the prevention of plaque. Should there be a demand for sanguinarine, it might better be supplied by some of our cultivars than by the diminutive bloodroot. In some tropical "Extractive Reserves" there are species of Bocconia which behave like weed trees. These might prove more reliable renewable sources of sanguinarine, taking the pressure off our delightful bloodroot.

German immunological research may increase pressure on our Echinacea's, some of which are common, others of which are under review for listing, e.g., Echinacea laevigata orEchinacea tennesseensis (DOI, 1985). The German research puts the coneflower in the lead among American immunomodulatory herbs, ranking up there with Chinese Astragalus membranaceus, on sale in New York as "huang qui" as an immune booster. Incidentally, there were nearly two pages of Astragali proposed for listing (DOI, 1985). Kindscher (1989)reports recent pharmacological studies showing that a daily dose of 10 mg/kg of coneflower polysaccharide is effective as an immunostimulant. But higher dosages result in "markedly decreased pharmacological activity". As early as 1902, long before the interest in immunomodulators, Kansas yielded up 200,000 pounds of the "Kansas Snakeroot worth over $100,000. Concern over their status led Missouri in 1987 to outlaw the harvest of E. pallida, E. purpurea and E. paradoxa on state parkland, highways, state forest lands, and wildlife areas. The "Missouri SnakerooC, Parthenium integrifolium, was used as a weedy adulterant of the Kansas snakeroot, even in the German studies showing the immunostimulant activity (Foster,1989). But this turns out to be more good news for Parthenium than bad news for Echinacca. Both have immunostimulant activity. In my data base (Duke 1992a,b), now available online at: http://www.ars-grin.govl~ngrlsb/ flowers of Echinacea are the best apparent source of cichoric acid, an integrase inhibitor that may be exploited for the treatment of AIDS. That news may put increasing pressure on Echinacea.

Some people are concerned that there might be endangerment of the trailing arbutus (Epigaea repens), which often shares its habitat with the pink ladyslipper, pipsissewa and wintergreen. All these ericads contain arbutin (Foster and Duke, 1990), which the Merck Index describes as a diuretic urinary antiseptic. This might explain their long folk use for urogenital ailments, especially cystitis. The Merck Index (8th ed) adds: "Gallotannin (also in ericads) prevents enzymes such as B-glucosidase from splitting arbutin which explains why crude plant extracts are more effective medicinally than pure arbutin. In my neighborhood (Howard Co, Md), the trailing arbutus is common while Chimaphila umbellate and Gaultheria procumbens are uncommon. None of these transplant well, and their medicinal use may be on the decline. 1 suspect that wild flower diggers may "endanger" these more than herbalists. At one time, the methyl-salicylate industry put pressure on wintergreen, but the cherry birch proved a much better source of methylsalicylate, now largely if not wholly synthetic. One Canadian boy died last year after ingesting wintergreen oil (NMH Herb Market Review, p. 13. Spring 1990). 1 suspect a teaspoon of almost any pure essential oil could be lethal.

Another aromatic medicinal is the American pennyroyal, Redeoma pulegioides. By no means endangered itself, it does have quite a medicinal folklore, and more importantly, its active ingredient, pulegone, is being studied as an insect repellent. If pulegone repels ants, birds, caterpillars, fleas, and ticks as some claim, you can anticipate increased interest in species that contain it. Assuming that Hedeoma todsenii, known only from two populations in New Mexico, and Dicerandra immaculate, endangered central Florida scrub species, both contain pulegone, we have two Center for Plant Conservation (CPC) Priority "All endangered species" in two genera of the Lamiaceae. Four Dicerandra's and 9 Hedeoma's are proposed for listing (DOI, 1985). Not to worry? Yes! Worry about these species! They might have isomers or compounds somewhat different to pulegone with greater biological activities.

Working with Dicerandra frutescens, Thomas Eisner (Eisner et al, 1990) found just such a compound, (+)-trans-pulegol, "a new natural product ... which stands out as the major defensive compound of this mint , along with 1,8-cineole, isomenthol, isomenthone, 3,8-menthadiene, 2,4(8)menthadiene, menth-3-en-8-ol, neomenthol, alpha-pinene, betapinene, pulegone and sabinene. Endangered species can contain new natural products, useful to man, or they many contain genes with which to improve the agronomic potential of less endangered species! But don't worry about the pulegone itself! Father Nature has been kind and spread the pulegone around. Pulegone is reported, e.g., in Barosma, Capsicum, Dicerandra, Hedeoma, Lycopus, Mentha, Monarda, Nepeta, Pycnanthemum, Satureja, Schizonepeta, and Teucrium. 1 have a Pycnanthemum which smells strongly of pulegone, which grows to nearly 2 m tall, spreads rapidly and produces hundreds of seed. I'll bet it will produce 100 times as much pulegone per hectare as Hedeoma pulegioides produces. Although pulegone has anticholinesterase activity that might prove useful in Alzheirmer's disease, like the anticholinesterase activity of Cognex (Tacrine), pulegone has also been shown to have hepatocarcinogenic and hepatotoxic activities. It is absorbed through the skin, so even its insect-repelling qualities may have negative health consequences.

  

Figure 2  : Ginseng (Panax qiuinquefolius)

Father Nature was not so generous with taxol. It occurs, e.g., in the bark of the western yew, Taxus brevifolia, a slow growing forest tree that may be 24 m tall. Even there, taxol occurs in very small quantities (100 ppm). Trees can provide 5-20 pounds of bark. Alice Christen of the USDA once told me that it would take 2,000-4,000 trees to provide one kilogram of taxol (enough for clinical trials on 500-1000 people). The western yew is a giant, compared to our eastern yew, Taxus canadensis. One eastern yew 1 collected in the North Woods of Maine had - 500 ppm in the renewable needles. The most endangered perhaps is Taxus floridana, almost extinct in the wild in Florida. Taxol also occurs at levels of 20-700 ppra in the needles and 10-90 ppm in stems of Taxus baccata, T. brevifolia, T. canadensis, T. cuspidata, and T. media. (Gordon Cragg, NCI, pers. comm., Apr 10, 1990). Although taxol has been produced in tissue culture, and a fungus can produce it, and although it has been synthesized, 1 predict that in the year 2000, when sales will approximate a billion US dollars a year, that taxol will still be largely produced by extraction from yews, cultivated or wild. Taxol shows great promise in ovarian cancer. Oncologists working with taxol regard it as one of the best new anticancer agents around. It is the only plant product known to promote the assembly of microtubules and inhibit the tubulin disassembly process.

Growing in the forest with my volunteer Taxus seedlings is an even more "primitive" plant, the shining clubmoss, Lycopodium lucidulum. This may well be our occidental analog of oriental Huperzia serrata, source of the anticholinesterase alkaloids, huperzine A and B. Based on the morphological similarities of the two species, 1 predicted we would find anticholinesterase activity, if not huperzine, in our American species. Dr. Alan Kozikowski, then Professor of Chemistry at the U. Pittsburg, and now with the Mayo Clinic in Florida, analyzed my material of L. lucidulum, and concluded that there was no huperzine therein, although there was a chromatographic peak at the same place as the huperzine peak in H. serrata. Kozikowski also advised me that selagine from Lycopodium selago is identical with huperzine. Thus, we do have huperzine in America, in L. selago, common in North America, but perhaps not so easily transplantable. 1 now have three species of Lycopodium transplanted into my forest, and know where to find material of 5-6 other species nearby, if there are chemists wishing to compare their anticholinesterase activity with that of sav'ry, sage, rosemary and thyme, also apparently promising in Alzheimer's. Huperzine is supposed, by optimists I think, to have three times the anticholinesterase activity of phytostigmine (the important alkaloid physostigmine is derived from Africa's Physostigma, of which we have none in the US). Even the condom industry puts a little pressure on other species of Lycopodium. Balick & Beitel (1989) note that ,lone major brand of non-lubricated condoms was coated with spores of the staghorn clubmoss, Lycopodium clavatum, spores 'of known hazardous nature'. Used previously in the manufacture of diverse products including hair powder, suppositories, and surgical gloves, these spores have caused allergic reactions ranging from hay fever to more serious giant cell granulomas. This foreign body response can stimulate neoplastic disease, tuberculosis, or syphilis". That kind of press may reduce the pressure, for Lycopodium spores at least. 1 am actively seeking spores of Lycopodium selago, trying to get the species into tissue culture.

Substitution among medicinal plants: the case of ginseng

Substitution of one medicinal plant with another, or competition among different plants for the same medicinal use, often occurs. An interesting example is ginseng. Conservationists tell me that ginseng, our number 1 crude medicinal export at ca $50 million a year, is being eradicated by collection from the wild. West Virginians and western Marylanders tell me that's not the case, that there is plenty of ginseng, that the armchair botanists don't get far enough off the roads. Certainly the Chinese, importers of most of our ginseng exports, have all but Wiped out their own ginseng in the wild. They are vigorously cultivating both Panax ginseng and Panax quinquefolius, to such a degree that someday they may endanger our ginseng trade, thereby ironically taking some of the pressure off our ginseng. But not completely. Chinese buyers still pay much less for cultivated ginseng, than for the wild, which they believe has more activity. Cultivated ginseng is usually priced '75 to 80 percent below" the wild. Thus, demand for wild American ginseng will probably continue to put stress on natural populations in North America (Singer, 1990). The Chinese have sometimes sold Elcutherococcus senticosus as a poor man's substitute for ginseng and Russian exporters are promoting the species as an adaptogen and immunostimulant. This so-called Siberian ginseng is a spiny, rhizomatous weedy understory shrub that grows in the forest of Siberia and northern China. A few enthusiasts in America have introduced the species. Without its native enemies, it may someday take off to compete with the honeysuckle and multiflora rose, invading some of the little remaining ginseng habitat. While this Siberian ginseng may take a little pressure off the American ginseng today, it may become its deadly enemy in the 21st century.

It seems appropriate to close this discussion with ginseng, America's most famous "medicinal herbal export". Many males consume ginseng in the questionable belief that it is an aphrodisiac. They even cite the population statistics of China to support their contention. Some might even suggest: "The more ginseng, the more babies". That is lamentable. I feel that population pressure is what endangers species the most. As we try to feed more and more people, forests are felled and converted to agroecosystems, further endangering the forest species thru habitat reduction. The better the medicinal plant, the more it threatens its own existence, first by the people who use it and live longer, and second by the collectors who provide the raw materials. I wish to paraphrase what centenarian Dr. R. R. Stewart said at the Plant Life Symposium in his honor at Karachi: 1f you want to conserve plants, you must practice family planning. If you insist on having children, you must teach them. It's much more difficult to teach children than to have them". I'm afraid the bottom line reads, the more people we have, the fewer medicinal plants we'll have to maintain their health. Maybe Gaia will get even with us.

In my backyard in Maryland's eastern deciduous forest, there are four species, three native and frost tolerant, one exotic and frost-sensitive species, that could be or are used as starter materials for four billion dollar drugs. They are Dioscorea villosa for steroids, long a billion dollar a year industry, Podophyllum peltatum, possible starter for etoposide, 1996 sales ca 400 million, Taxus species, all of which contain taxol in their needles, taxol's sales in 1996 ca 600 million, and Catharanthus roseus, for nearly 4 decades source of vincristine and vinblastine, average sales often exceeding 100 million per year. We find starter materials for four different billion dollar drugs in my small piece of the relatively depauperate eastern deciduous forest. How many billion dollar drugs are still waiting for us in the e.g. "ACEER foresC (Amazonian Center for Environmental Education and Research, off the Nape, Ricer in Amazonian Peru, with 300 woody species per hectare).How many of these do we lose before they are even named if we allow such forests to disappear? How many have potential drugs for today's killer diseases, developing resistance to our last-defense antibiotics like vancomycin? How many have potential for other diseases, even some diseases unknown today, of the future?
"Axeman leave that tree alone; the life you spare may be your own!"

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* This chapter is based on an earlier and unpublished draft by Dr. J. Duke, which has been made available in collaboration with Judi DuCellier, Andrea Ottesen, Peggy Duke, and Ed Claflin, of Rodale Press, who allowed to reuse some of the illustrations made by Peggy Duke from 'The Green Pharmacy" (Rodale Press, 1997).

http://www.fao.org/docrep/w7261e/W7261e17.HTM