Many other tribal peoples look to the plants and animals of tropical forests for their medicinal needs. Through long experience, they have learned that tropical forests can supply a welter of products, not only drugs and pharmaceuticals, but also stimulants, narcotics, and hallucinogens among diverse other products that make life more livable in remote territories. In northwestern Amazonia, for instance, Professor Richard E. Schultes, Director of the Botanical Museum at Harvard University, has found that forest-dwelling Indians employ at least 1,300 plant species for medicines and related purposes of one sort and another. In Southeast Asia, traditional healers use some 6,500 plants in treatments for malaria, stomach ulcers, syphilis, and assorted other disorders. In the 4,500-square-kilometer island of Siberut, off the west coast of Sumatra in Southeast Asia, medicine men draw on dozens of plant species, many of them found nowhere else, for herbal remedies against a host of illnesses, also for astringents, disinfectant materials, purgatives, emetics, and sedatives.
So promising are many of these ethnobotanical materials when evaluated by scientists, that a good number are being screened and developed in medicinal research laboratories of North America and Europe. Little as we may realize it when we visit our neighborhood pharmacy for a medicinal preparation or a pharmaceutical, there is roughly one chance in four that the product we purchase, whether by prescription or not, owes its origin, in some way or another, to plants and animals of tropical forests. The commercial value of these products worldwide now tops $20 billion per year.
Tropical forests represent nature's main storehouse of raw materials for modern medicine. Plants alone offer a host of analgesics, antibiotics, heart drugs, enzymes, hormones, diuretics, anti-parasite compounds, ulcer treatments, dentifrices, laxatives, dysentery treatments, and anti-coagulants, among many others. The total number of plant-derived products in modern pharmacopoeias amounts to several thousand, including such well-known trade products as emetine, scopolamine, and pilocarpine.
Among the most important materials with which pharmacologists manufacture drugs are alkaloids--complex biocompounds produced by many categories of plants. Of all biomes, tropical forests contain the highest proportion of alkaloid-bearing plants, and the alkaloid yield of these plants is higher than elsewhere. Tropical forests provide a greater abundance not only of alkaloids, but of antibiotic and antibacterial compounds. Plant alkaloids have many medicinal applications, including cocaine, reserpine, quinine, ipecac, ephedrine, caffeine, and nicotine. Moreover, the capacity of plants to produce alkaloids is under strict genetic control, which means that provided we can safeguard sufficient genetic variability in the wild, genetic engineers may soon be able to devise improved varieties of alkaloid-producing plants in order to better serve the needs of modern medicine.
Probably most famous of all alkaloidal drugs are vincristine and vinblastine, developed by Eli Lilly and Company of Indianapolis, after following up clues provided by tribal herbalists and other traditional healers in Madagascar and Jamaica. The Vinca alkaloids derive from a dainty plant of drier tropical forests, the rosy periwinkle, a flower so small that you might overlook it unless you notice its pretty appearance. Thanks to the Vinca alkaloids yielded by this plant, a child suffering from leukemia, who would have faced only one chance in five of remission in 1960, now enjoys four chances in five. The two drugs are also used against Hodgkin's disease and other malignant lymphomas, breast, cervical, and testicular cancers, choricarcinoma and certain tumor-type cancers. Not surprisingly, worldwide sales of these two drugs totaled $90 million per year in the late 1970s, and the commercial turnover continues to expand at a vigorous 15 percent each year.
At least another 1,400 plant species of tropical forests are believed to offer potential against cancer. And while ruminating on these sizable figures, let us bear in mind that scientists have conducted cursory screening of only 1 in 10 of tropical forest plants, and intensive screening of only 1 in 100 plants. In Latin America alone, with its estimated 90,000 species, we have tested no more than 10,000 for their anti-cancer properties; and our experience to date suggests that of the remaining 80,000 at least 8,000, should reveal some form of activity against laboratory cancers, and of these, 3 could eventually rank as "superstar" drugs.
Apart from alkaloids, there are many other complex organic chemicals, sometimes known as secondary plant metabolites, that can serve the cause of modern medicine. Hitherto we have defined, in chemical terms, only about 10,000 of them, even though we can surmise that there could be as many as 400,000 or more on Earth. Of the 10,000, some 4,500 are alkaloids; 1,200 are flavonoids; and 1,100 are terpenes. As with alkaloids, we find that no other biome contains such concentrations of these metabolites as the tropical forest biome.
So much for plant sources of medicinals. How about animal sources? Scientists are finding that many insects, notably butterflies, offer potential for many medicinal products, including anticancer compounds. As we have already seen, tropical forests support between 1.5 and 3.5 million insect species (possibly many times more). So much potential lies ahead of us: if we have so far looked, however superficially, at about 1 plant species in 10, we have hardly glanced at 1 animal species in 1,000. Let us consider the uses of bats, for example. These diminutive creatures use highly sophisticated sonar equipment; they live for an unusually long time; they are resistant to many diseases; they can become torpid at almost any time; and they possess virtually transparent wing membranes. Thus they are much sought for research, having contributed to navigational aids for blind people, to studies of aging processes, to development of vaccines, to testing of drugs, and to studies of creatures in space.
Why, we might ask, do tropical forests appear to contain proportionately more of these biologically active compounds than is the case with other biomes? A leading answer lies with the compressed nature of many assemblies of plants and animals, accommodating a far greater number of species per unit area than we would find elsewhere (with the possible exception of tropical coral reefs). A concentration of species in a limited locality makes for competition, lots of it, as organisms jostle each other for food, light, and living space, generally. They compete constantly, and in every last which way they generate "biological warfare" of the most intense kind we know. In response to this competition, tropical forest species throw up specialist lifestyles, often in the form of unique biocompounds in organisms' tissues, used for defense, attack, whatever purpose that helps the owner to stay alive in circumstances where survival is the principal preoccupation.
Furthermore, many species in tropical forests are either completely immobile, as is the case with trees, shrubs, and the like, or they are only moderately mobile, as is the case with ants, termites, beetles and so forth. While ants and other insects move around busily within their habitats, a habitat may not extend beyond a few square meters. These conservative lifestyles, "tying" the organisms to a single small sector of the forest, mean that the creatures are little inclined or able to quit the scene when a predator or a parasite arrives. Should the most usual form of threat, that is, a bacterium or a virus, happen along, the targeted victim cannot escape by moving on elsewhere. It must stay where it is, risking infection--a threat to which it responds by producing antibacterial and antiviral defenses. In addition, the stationary lifestyle can even mean that an organism becomes overwhelmed, whether suddenly or slowly, by neighboring animals and plants: again, this is a situation that is best resisted through production of defensive organic chemicals that pass a loud-and-clear message to the encroacher, "Keep your distance."
All in all, many tropical forest organisms produce biocompounds that have unusual types of form and function. Such enormous reserves of strange substances occur in tropical forests, that this realm could ultimately prove to be a major source of start-point materials for medicines, drugs, and pharmaceuticals of the future. To help us gain a grasp of this potential, let us look at the forests' capacity to serve our daily health needs.
In practical terms, tropical forest species serve modern medicine in three main ways. First, extracts from organisms can be used directly as drugs; and they can serve in semi-synthesis of drug derivatives and active therapeutic agents. Second, the chemical structures of forest organisms offer templates, or blueprints, to enable researchers to chemically synthesize drug compounds. Third, forest organisms serve as research aids for the development and testing of drugs and pharmaceuticals, also for the needs of biomedical research generally.
1. Direct or Semi-Direct Use of Organisms as Drugs
First off, let us briefly review those biocompound extracts from plants and animals that can be used as drugs with little more ado. A vast number of tropical forests species yield substances that are pharmacologically important in the manufacture of ethical drugs. A survey of U.S. prescriptions in 1973 showed that the plant kingdom was already supplying 76 drug compounds, a total that has grown still higher today. Of these 76, only 7 could be commercially produced through chemical synthesis from start to finish. Most of the drug compounds in question have been successfully synthesized in the laboratory, but it is generally more costly to synthesize them than to extract them directly from wild plants (or occasionally from cultivated, i.e., domesticated, forms of wild plants). While the sales volume of prescription medicines has continued to expand year by year, thus encouraging pharmacologists to cut corners in their manufacturing process whenever possible by synthesizing their materials, they have made no dent at all in the proportion of natural plant products used in modern medicine. In short, we benefit from the plant kingdom more and more as the years go by.
A prime example of this thesis is rauwolfia, a material from the so-called snakeroot plant of monsoon forests in India. Rauwolfia was actually used for more than four thousand years by Hindu seers to treat nervous disorders and mental illnesses, also dysentery, cholera, and fever, before its potential became known to Western-world scientists in the late 1940s--whereupon its alkaloid rescrpine began to form the base of tranquilizer products and of materials for treatment of hypertension, anxiety, and schizophrenia, also for menstrual tension and menopausal disturbances. Before that time, high blood pressure strongly disposed a patient toward stroke, heart failure, or kidney failure. Today, however, this one plant helps many millions of people to lead a reasonably normal and healthy life, partially freed from a set of ailments, that is, hypertension, that constitute the single greatest and fastest-growing source of mortality in advanced societies. As long ago as the early 1960s, this first modern tranquilizer generated sales in the United States alone worth $30 million per year. By the late 1960s, at least four out of five of all hypotensive drugs prescribed in the United States, amounting to almost 6 percent of all community drug prescriptions, contained alkaloidal extracts from rauwolfia species. In recent years, retail sales of reserpine-based products in the United States have exceeded $260 million per year. Although reserpine can be commercially synthesized, the process is a complicated and multi-stage affair, yielding the drug at a price of around $2 per gram, whereas reserpine can be extracted from natural sources at about half that cost.
In addition, the biochemical compounds of many tropical forest organisms serve as building blocks for the manufacture of semi-synthetic drug materials. A case in point is the glycoside saponin from the Dioscorea species of the Mexican yam, which yields steroidal sapogenins--including the well-known product diosgenin, a compound that came into wide use as an anti-inflammatory preparation after World War II, before finding very widespread application in the form of birth-control pills. Of all steroidal drugs on the market today, 95 percent derive from diosgenin as a raw material. These drugs contribute to our everyday welfare in that at least one out of seven prescriptions from community pharmacies contains steroids. Not only are diosgenin-derived steroids used in the manufacture of oral contraceptives, but they serve parallel purposes in sex hormones (progesterone, estrogens, androgens, etc.) and in cortisone and hydrocortisone used against rheumatoid arthritis, rheumatic fever, Addison's disease, several allergies, sciatica, and a number of skin diseases including contact dermatitis.
All in all, at least 125 Dioscorea species have been examined in detail to see if they could be suitable sources of diosgenin. Of these, only 2 have proven to be first-rate sources for commercial needs--both are climbing vines known as the Mexican yam. Until just the last few years, the Mexican yam has yielded virtually the world's entire supply of diosgenin. By the mid 1970s, the world was using up to 180 tons of diosgenin per year; by 1985 the amount could rise to as much as 500 tons; and by 1995, to 3,000 tons, if the contraceptive needs of all women at risk are to be met. In 1980 some 80 million pills were being used each day; if total needs worldwide were to be recognized and supplied, the figure would probably be at least two and a half times as great. At the peak of production of diosgenin from the Mexican yam, at a price of $152.20 per kilogram, the wholesale value per year must have been around $25 million. When we look at further stages in the manufacturing process, we can reckon that chemical composition would have pushed up that figure to $70 million per year, and cross-counter sales for final products could have totaled some $700 million.
In view of this end-product turnover in the commercial marketplace, and in light of the fact that the yam could scarcely be successfully grown outside its native habitats in tropical forests, the Mexican government decided to seize a greater part of the action through jacking up export prices. In other words, the Mexicans decided to "cartelize" their yam product. Regrettably, they misjudged the situation, and the bottom dropped out of the yam market, with the price for diosgenin rapidly falling to $95 per kilogram, as manufacturers looked around for alternative sources, both natural and synthetic. Today the contraceptive industry uses many other plant-derived steroidal compounds, notably from the soybean, the Calabar bean which flourishes in West Africa's forests from Sierra Leone to the Congo People's Republic, and from plants in Himalayan forests and other parts of tropical Asia. Let us note, however, that the demand for contraceptive materials is likely to double between the late 1970s and the mid-1980s, leading to a shortfall of almost half total requirements--a gap that disogenin from the Mexican yam can once again fill.
Many other plant species, around half of them from tropical forests, have been identified as containing antifertility compounds: at least 4,000 such species altogether. Of these 4,000, at least 370 have been shown to offer special promise for safer and more effective contraceptive pills, suitable for both males and females. A leading candidate is the greenheart tree that flourishes in the forests of Guyana, where women of several tribes use the tree's nut as a traditionally reliable contraceptive. Among other promising plants are forest growths in Haiti, Bangladesh, Papua New Guinea, Fiji, Cameroon, Madagascar, Colombia, and Brazil. In addition, more than 600 plant species appear to offer potential as abortifacients, a good number of them from tropical forests. A notable instance is a pretty ornamental plant from the forests of India, Thailand, and Malaysia, widely used locally to induce abortions
2. Chemical Structures as Templates and Blueprints
We have noted that, for all our sophisticated technology, we often cannot manufacture synthesized substitutes for natural materials at competitive costs. In the case of steroids, scientists have tried for twenty-five years to develop synthesising techniques, but we still obtain 95 percent of our startpoint materials for steroids from natural sources.
Even if medicinal technology cannot always stand in for raw extracts from wild species, however, it can benefit from models supplied by biocompounds from plants and animals in tropical forests. Working from these models, pharmacologists determine chemical formulas of natural compounds, and then go on to synthesize mimic compounds in the laboratory. Without model compounds derived from nature, many of our most common synthetic drugs could not have been devised. One century ago, an aspirin-like substance was extracted from the leaves of willow trees; today aspirin is produced artificially, and a lot more cheaply, through replication of the chemical formula that owes its origin to the willow trees' extracts. A notable instance from tropical forests is the ipecac plant of Brazil and Bolivia, yielding the alkaloid emetine, used to treat acute bronchitis, croup, bilharziasis, and guinea worm. In particular, emetine is used against amoebic dysentery: a concentration of 1 part in 100,000 is enough to overcome the amoeba. Emetine is now synthesized commercially, an advance that would not have been practical without the blueprint supplied by the wild plant.
Similarly, the coca bush contains cocaine in its leaves, which, together with other derivatives, serves as a local anesthetic. The chemical structure of cocaine supplies us with chemical information for synthesis of various other local anesthetics, notably procaine and other related drug compounds.
Some observers may suppose that the template insights supplied by biocompounds in tropical forest plants may not persist as a long-term benefit. After all, they say, if pharmacological researchers were to stretch their imaginations a bit, they should surely be able to visualize the chemical structures without waiting for nature to provide the start-off clues. Our experience shows, however, that the scientists' creative capacities fall way short of the challenge. The biochemical makeup of natural drug compounds are simply too esoteric for the most talented white-coated researcher in his laboratory to dream up a fraction of the intricate formulations already designed for us by nature--existing in their most ingenious and sophisticated forms in tropical forests.
3. Organisms as Research Aids
Pharmacological enterprises find much help in their exploitation of plant chemical compounds as aids for research. By way of example, certain plant compounds promote tumors and thus serve to promote understanding of what makes cancer cells work. They also help to alert us to possible sources of tumor-causing agents in our drugs and foods. Salient instances include the betel nut (a masticatory used in Southeast Asia), many tropical cycads, and plants that produce tannins, resins, and rotenone--all being plants that produce potentially oncogenic compounds.
Similarly, neurologists have been assisted by a toxic compound, tetrodotoxin, derived from certain frogs of Central America's forests (also from some tropical coral reef fishes), by virtue of the fact that the compound possesses 160,000 times the potency of cocaine for blocking nervous impulses. As a result, it is much used in studies of nerve impulse transmissions and nervous excitatiom Tetrodotoxin is also employed directly as a drug in Japanese clinics, where it serves as a pain killer, a local anesthetic, and a muscle relaxant, notably for persons suffering from neurogenic leprosy and terminal cancer.
Especially illuminating for psychiatrists are hallucinogenic plants of Latin America, where they play a part in religious rituals by virtue of their psychoactive principles. The same compounds that yield these psychoactive principles can be employed for research into the central nervous system in general, and psychiatric disorders in particular. Of course a number of psychoactive drugs have long been familiar to us, such as analgesics and euphorics (e.g., cocaine and Opium), sedatives and tranquilizers (e.g., reserpine), and hypnotics. But while other psychoactive substances are merely mood modifiers, hallucinogens produce, to cite a leading pharmacognosy expert and ethnobotanist, Professor Richard E. Schultes, "deep changes in the sphere of experience, in perception of reality, space and time, and in consciousness of self." This means that hallucinogens can throw light on research into our perception of the external world, insofar as there seems to be a similarity between psychoactive plant compounds and naturally occurring brain hormones. To date, the principal source of these hallucinogens is Amazonia, but other tropical forest zones may prove promising, as witness the drug hyoscine (scopolamine) from the corkwood tree, a forest plant in eastern Australia, used against several forms of mental illness.
Exotic as they may sound, hallucinogens will almost certainly become more important in the years ahead. Being complex compounds, they serve a variety of purposes, not only in the treatment of mental disorders, but also in experimental psychiatry (and they bring relief to patients with terminal cancer). To date, pharmacologists have tracked down at least 150 plant species with hallucinogenic properties, and several times that number surely await our attention if the scientific researcher can get to the forest habitats before the sawman.
Most important as "research aids" are tropical forest animals, especially primates. The closest relatives of humankind, primates manifest reactions to drugs that all but replicate those of humans. Whatever we may believe about the ethics of using some of the most advanced representatives of the animal kingdom to save us from risks associated with new drugs, we can recall the thalidomide tragedy of the early 1960s as a cautionary tale. Too late we found that we could have alerted ourselves to the disaster if we had undertaken thorough testing with creatures that turned out to display identical birth defects when they were dosed with thalidomide: at least two species of macaque monkeys from the Indian sub-continent could have served as ideal "testing tools" (an abominable but accurate term).
The role of primates in evaluating drugs for pregnant women is plain. Not so apparent but equally important is their capacity for checking on additives in drugs and foods, and for general research in fields such as reproductive physiology and fetal pharmacology, drug metabolism, production of human vaccines, drug abuse, mental health, malnutrition, studies of cancer, the central nervous system, arteriosclerosis, and chronic degenerative diseases of organ systems. Among the most common species in question are the squirrel monkey from forests of tropical Latin America, for research into cardiovascular diseases; the common marmosets from forests of eastern Brazil, for research into cancer and hepatitis; the so-called Celebes macaque, for study of diabetes; and the chimpanzee from tropical Africa, for research into human gonococcal urethritis in particular and psychobiological studies in general.
Along with these three main categories of medicinal applications of tropical forest species, including some major products such as vincristine, reserpine, and emetine, are several other products with pharmacological value. Of obvious importance is curare, derived from a plant of western Amazonia. The compound induces paralysis of skeletal muscles during a number of critical conditions for humans, including abdominal surgery, tetanus convulsions, shock therapy, and spastic cerebral palsy. Without this key compound--originally brought to the notice of modern science through its use by forest-dwelling Indians as an arrow-tip concoction to paralyze prey--today's surgeons would often be severely restricted in their work. A somewhat similar product is picrotoxin, from seeds of the so-called Levant berry plant of forests in Southern and Southeast Asia. The compound helps to relieve schizophrenic convulsions, and is used to restore breathing in persons who have taken an over-dose of barbiturates. The papaya of Central America supplies us with papin, being a proteolytic enzyme that helps with dyspepsia and chronic diarrhea (it also serves to tenderize meat). Various balsams from tropical Latin America are used as antiseptics, as cough preparations, ad as suppositories, also as dental cements. The Calabar bean, from forests of West Africa, already mentioned above as a new source of diosgenin, assists with eye disorders such as glaucoma; it also promotes contraction of the pupil and thus assists ophthalmologists in their work. We have already noted that the corkwood tree of eastern Australian forests alleviates several forms of mental illness; this product, together with atropine from the same plant, relieves goiter, and even helps those people who become sick when they travel in ships or airplanes. Finally, the benzoin tree in Malaysia and Indonesia yields a tincture used as an antiseptic and protective coating; it can also be taken internally for bronchitis.
The interested reader can find many more accounts in the scientific literature. We can see that some sectors of the tropical forest biome rank higher than others as major sources of medicinal products. Let us also note that in India, with its 18,000 flowering plants, a full 2,500 are used for medicine; in the Philippines, with 9,000 flowering species (of which 2 out of 5 are found nowhere else), almost 900 are widely used for health needs; and in Java, with its 4,598 native species, at least 200 are used for medicine. Let us further reflect, then, that even were modern Western-world medicine to eventually find all its drugs and related materials in the synthesizing processes of the laboratory, there would still be a vast need for plant-derived compounds For many years to come, citizens of the Third World are not likely to enjoy the benefits of costly health systems such as are within the reach of Americans and Europeans. So they must depend, as they have for centuries, on the "green medicine" that they devise from their native plants. The most fortunate of these Third Worlders are those living within the tropical forest zone.
On the basis of the figures given above for India, the Philippines, and Java, we can reasonably calculate that a "responsible minimum" figure of 5 percent of all plant species serve the cause of medicine in one way or another. Furthermore, we can presume that at least one-half of these plants occur in lowland primary forests. If we apply these reckonings to Southeast Asia, and to the richest of the region's forests (also those undergoing the most rapid exploitation), we can infer that the Malay Peninsula, Borneo, and New Guinea each probably support some 200 important medicinal species. As we have also noted, it is not unusual for a plant-derived drug to achieve commercial sales worldwide worth many millions of dollars per year, ranging from $30 million to around $250 million. With $50 million as a safe low average, the three sectors of Southeast Asia could well generate plant-derived medicinals worth $10 billion per year.
While this is a very "iffy" speculation, it is advanced solely to cast a little light on a murky issue--and a little light is better than none. There is surely much in the situation that we do not know. Yet even if the figure were too high by a factor of ten, Borneo would still represent a sound bet for humankind's hopes for improved health. What we certainly know is that we already enjoy a sizable number of successful drugs from tropical forests that assist the lifestyles, if not the survival, of many millions of Americans, as of Britishers, Japanese, and Australians--and of Brazilians, Nigerians, and Indonesians. Moreover, we enjoy these naturally occurring medicinals after only the most haphazard examination of just a few species in tropical forests.
So, working with these calculations, crude and approximate as they are, we can hope that better times lie ahead, supposing we can exploit the tremendous pharmacopoeias of tropical forests while they remain in existence. All this is plain to me now as I sit at my Oxford writing desk, conducting my back-of-the-envelope calculations about the potential value of tropical forest drugs.
I did not realize all this in the days when I was running up and down Mount Kenya, otherwise I might have delighted even more in the welcoming embrace of that beautiful forest as I descended off the moorlands. In point of fact, my recent dashes up Mount Kenya, as part of the training of a runner who likes to finish in the leading 5 percent of the giant fields at the New York and Boston Marathons, have not been my fastest efforts on that mountain. My speediest assent was back in the early 1960s, when, as a member of the Kenya Mountain Club rescue team and as a record holder for the up-and-down trip on Kilimanjaro, I used to act as a two-legged medicine mule to rush relief supplies to injured climbers on the topmost cliffs of Mount Kenya. Many of these fallen climbers quickly contracted a disease that is a major threat to injured mountaineers at high altitude--a lung ailment known as pulmonary edema, which causes the lung cavities to fill with fluid, whereupon the sufferer drowns. Little did I know then that the drug I administered, and that appeared to save several climbers' lives, was a heart stimulant known as ouabain, manufactured from the seeds of a strophanthus plant of tropical forests in West Africa. Curious, that a refined product of an obscure plant in the coastal zone of the far side of Africa should serve to keep alive the spark of life in broken humans at lofty altitude in East Africa.
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