Folklore, Tradition, or Know-How? The ethnopharmacological approach to. drug discovery depends on our ability to value non-Western knowledge of medicinal plants
MEDICINAL PLANT RESEARCH has been and continues to be considered a fruitful approach in the search for new drugs (Svendsen and Scheffer 1982; Samuelson 1989). The scientific basis that accounts for the presence of medically useful compounds in plants is by now well known. Evolution has been selecting plants whose metabolism generates compounds with adaptive value; for instance, a bitter-tasting plant is less likely to be eaten by herbivorous animals (the same with a pepperish one, an allergenic one, a bad-smelling one, and so on). These compounds are, therefore, active on biological systems. The bioactivity of such compounds might eventually have therapeutic value; the chemical compounds will be absorbed by the body and interact with its receptors as any Western drug. There is no magic or folklore; Western-trained pharmacologists have no problem in accepting the fact that some plants that produce certain chemicals are, indeed, medicines.
The bioactive compounds are by-products of the species' primary metabolism; plants are therefore regarded as an invaluable repository of unusual chemical compounds, since these secondary metabolites are like chemical fingerprints of individual species (Eisner 1990). There are several reasons to believe that many drugs are yet to be found within the plant kingdom. A quick look at the pharmaceutical market shows the importance of known medicinal plants: 1 Some 7,000 natural compounds are currently used in modern medicine (Farnsworth and Morris 1976); most of these had been used for centuries by European, Asiatic, and Amerindian healers. 2 Twenty-five percent of US prescription drugs contain one or more plant-derived active ingredients (Farnsworth and Morris 1976). 3 In 1985 the world market value of drugs was estimated at US $90 billion; medicinal plants accounted for $43 billion (Principe 1989). 4 In 1980 the imports of medicinal plants worldwide were estimated at US$551 million (Principe 1989).
With plants making such an impressive contribution to our drug supply, it seems obvious that the search for drugs in plants not yet studied is likely to be a fruitful one. Nevertheless, fewer than 2 percent of higher plants have been thoroughly screened for biological activities. Even focusing only on alkaloids, one of the most important chemical classes of plant-derived medicines, it is estimated that only one to two percent of flowering plants (some 250,000 species) have been screened for the presence of alkaloids (Eisner 1990). Tropical forests, hot spots of biodiversity, have almost twice as many alkaloid-producing species as do temperate areas; moreover, mean alkaloid content is higher in tropical than in temperate species (Oldfield 1981).
APPROACHES TO PLANT-DRUG DISCOVERY
How should we advance in the search for drugs with such a vast number of plants to be studied? One can simply screen everything that can be collected in quantity, the so-called massor blind-screening approach. Obviously, such a strategy requires enormous investments of money and time and a fair amount of luck. A more guided approach is to select for screening species that belong to certain families or genuses that are likely to contain certain classes of compounds (alkaloids, steroids, amino acids, etc.) - that is, the chemotaxonomy-oriented approach. Or one can choose simply to learn from the peoples who already use the flora for medicines, selecting for further study those plants already used as remedies.
This last approach is known as ethnopharmacology; it is defined as "the interdisciplinary scientific exploration of biologically active agents traditionally employed or observed by men" (Holmstedt and Bruhn 1983). It involves the joint efforts of anthropologists, botanists, pharmacologists, and chemists. Detailed ethnographic research is crucial in understanding traditional drug use and medical practices. Traditional medical systems are holistic in nature and often consider illness, healing, and human physiology as a series of interrelationships among nature, supernature, society, and the individual (Fabrega 1975). It is the ethnopharmacologist's task to analyze what we learn from indigenous specialists and correlate those practices with our own biomedical concepts. Only then can we select species to be studied for specific pharmacological activities, an invaluable shortcut for drug discovery.
The knowledge of medicinal plants preserved by indigenous specialists is priceless information. As with genetic diversity, once lost, it cannot be recovered. Without it, we must use random screening, which is like searching for a needle in a haystack. Past experience is the best argument here: 74 percent of chemical compounds used as drugs today have the same or related use in Western medicine as they do in traditional medical systems (Farnsworth 1988). It has been estimated that ethnobotanical information might have increased the yield of active plants by 50 to 100 percent in the National Cancer Institute (NCI) research program in the search for anti-cancer and anti-AIDS drugs. Some of the samples for this program, recently collected in Belize, show that 25 percent of the ethnobotany collection showed preliminary activity, compared to 6 percent of active plants in the random collection (Balick 1990).
The advantages of doing drug development based on ethnopharmacology, therefore, are manifold: 1 plant selection 2 "leads" from traditional use that allow for narrowing the pharmacological study. 3 leads from traditional modes of preparation that provide clues to active chemical compounds 4 lower laboratory investments (once a laboratory is equipped it can analyze several species used traditionally for the same purpose)
Altogether these advantages could shorten the research/productivity cycle - currently estimated at 20 years. Also, if an industry chooses to produce plant extracts (or phytotherapics), it will have lower industrial costs for production. These cuts in R&D are indeed very important: the estimated costs for developing new drugs based on chemical synthesis and/or mass screening range from US $50 million to $200 million.
TRADITION OR KNOW-HOW?
The World Health Organization (WHO) estimated in 1978 that as much as 80 percent of the world's population relies on plant-derived medicines for most health-related products. Traditional remedies, although based on natural products, are not found in "nature" as such; they are products of human knowledge. To transform a plant into a medicine, one has to know the correct species, its location, the proper time of collection (some plants are poisonous in certain seasons), the part to be used, how to prepare it (fresh, dried, cut in small pieces, smashed), the solvent to be used (cold, warm, or boiling water; alcohol, addition of salt, etc.), the way to prepare it (time and conditions to be left on the solvent), and, finally, posology (route of administration, dosage). Needless to say, curers have to diagnose and select the right medicine for the right patients. Why, then, do we easily give credit to pharmacists or physicians for their know-how and only refer to indigenous knowledge as "tradition," "folklore," or just "knowledge"?
The scientific community is giving more recognition to traditional know-how - in other words, the intellectual input of informants - as a crucial part of research. Current strategies in the search for therapeutic drugs include analyzing traditional use in the search for immunomodulators (Labadie et al. 1989), antitumor compounds (Duke 1986), analgesics (Elisabetsky and Castilhos 1990), and bactericides (Caceres et al. 1990). As a matter of fact, most of the pharmacological or chemical studies reported in the several journals in the field start by quoting the traditional use of a given plant species promising enough to stimulate further research. It is therefore reasonable to assume that indigenous knowledge did and will continue to play an important role in medicinal plant research, either in terms of plant selection for laboratory scrutiny and/or as clues regarding the expected pharmacological activity.
Considering the results to date, the most popular strategy evidently still involves the union of laboratory work in developed countries (where most chemical and pharmacological studies are done) with fieldwork in Third World countries, with the assistance of local inhabitants (where traditional use and the plant material itself are collected). To efficiently discover new plant drugs, we need the forests and their inhabitants. In every pill we buy, we are all paying for the prices of drug discovery. Can we count with it? In recent years tropical forests in general, and the Amazon in particular, have become the main focus of conservationists' worries. Amazonia, estimated to contain at least 50 percent of the planet's species, is suffering a faster rate of depletion than any other ecological zone (Myers 1988). Since most of the chemically unknown flora and associated medicinal lore exist in Third World countries, especially those which still possess extensive tropical forests, the rapid loss of biodiversity does indeed become an issue for future medicinal plant research. Looking at the history of South America, marked by the physical and cultural extermination of dozens of Indian nations and the destruction of countless hectares of forests, one wonders how many important leads for drug discovery, too, have been lost. For the ethnopharmacological search for new, plant-derived drugs, cultural diversity is as important as biodiversity.
Why would an informant or an indigenous group resist cooperating in a research effort that could lead to the discovery of a drug, one that in principle could benefit all who need it? Tyler (1986), in discussing the role of plant-derived drugs in the twenty-first century, stresses the diseases for which satisfactory cures remain to be found: viral diseases (herpes, AIDS, certain cancers), "self-inflicted" diseases (drugs dependency, obesity, etc.), diseases of unknown etiology (arthritis, some cancers, muscular dystrophy, Parkinson's), and genetic diseases. Since 1967, the top four categories of drug development efforts in the United States have been analgesics, anti-infectives, cardiovasculars, and psychopharmacologics/neurotropics (Mattison et a. 1988). These categories will be more intensively examined in the coming years in medicinal plant research. Nevertheless, in 1978 the WHO cited malaria, diarrheal diseases, tuberculosis, leprosy, and sexually transmitted diseases as the major health problems in developing countries. Although the modern world gave its diseases to indigenous groups in developing countries, it does not share to the same extent the benefits of modern pharmacopoeia. One can argue that these health problems are the consequence of poverty, poor living conditions, and a lack of resources to acquire the proper medicines. Even so, this discrepancy between research objectives and local needs helps to explain why the results of many research projects will most likely lengthen the list of inaccessible cures. In this context, it is understandable that informants or governments ask themselves why they should preserve the forest or cooperate with yet another research effort that, considering past experience, will not benefit all parties involved.
INTELLECTUAL PROPERTY RIGHTS
Boom (1990) asks, What are the ethics behind utilizing traditional knowledge without adequate compensation to the societies from which it originates? This is not an easy question to answer. To begin with, what constitutes adequate compensation? Certainly a great deal of expertise and funds are used in the research process that eventually transforms a plant into a commercial medicine. The monetary value of technological development as a whole cannot be neglected, yet the actual cost of each step in an R&D program is by no means easy to quantify.
As discussed by Kloppenburg (1987), soil, air, water, and germplasm must be counted as resources of prime importance. The impact of the last glaciation on the Northern Hemisphere concentrated biotic diversity in what is now the Third World. Necessarily, then, the development of the rich but "gene-poor" nations of the North has depended on transfers of plant genetic resources from the poor but "gene-rich" nations of the South. Genetic resources received as free goods (common heritage) from the Third World have been worth untold billions to the advanced industrial nations. In the context of medicinal plants, Oldfield (1981) quotes the US Interagency Task Force on Tropical Forests (1980) in its estimation of an annual US $25 million as the wholesale value of medicinal compounds imported to the United States from tropical forests. The alkaloid Pilocarpine, extracted from several Brazilian Pilocarpus species, might be used as an example of a typical item that contributes to this figure: estimated US sales of Pilocarpine in 1989 were $28 million. The 1989 price for a kilogram of dried Pilocarpus leaves was $0.28, maintaining the trend found in the last decades (808 tons were exported in 1962 for $0.22/kg, and 1,290 tons in 1970 for $0.36/kg [IBGE 1985]). It is clear that the role of raw material supplier is not adequate compensation.
Could or should this picture be modified? Posey (1990), among others, calls for legislation to secure intellectual property rights (IPR) for indigenous people. IPR is a somehow obvious means of compensation, commonly used by modern society. In fact the legal basis for protecting rights on inventions has been in effect in the United States since 1790. The so-called utility patents, in effect since the early 1980s, provide protection to new and useful manufacture or composition of matter. Utility patents can be used to patent chemicals and/or chemical composition of medicinal plants; if traditional healers showed the therapeutic activity of certain plants; if traditional healers showed the therapeutic activity of certain plants, they would be entitled to royalties. Pharmaceutical industries have been successful industries have been successful in patenting compounds extracted from plants; traditional healers and/or users who show Western researchers the value of a given medicinal species could be granted the same benefits. When traditional knowledge is used as the basis for selecting plants for laboratory analysis and for promoting a research strategy, the indigenous group has an implicit and genuine claim for compensation.
We hear over and over that conservation is needed. But what does this really mean? Conservation is the wise use of natural resources, and therefore implies the use of the resources compatible with the degree of preservation needed to insure their renewability (Barlowe 1972). Habitat destruction, the primary cause of natural resource depletion, results when human populations and activities expand (Erlich 1988). It follows that forest peoples must adopt ecologically sound economic activities if any conservation is to be expected. Medicinal plants can be a vital part of environmentally sensitive economic development in Third World countries; the development of plant-based products could be the basis for new economic activities in tropical regions since, besides royalties, planting, processing, and distributing medicinal plants is a nonaggressive activity both to the environments and most cultures in these regions.
An important distinction needs to be made between market value and economic value. Market value is the value that the marketplace attributes to a certain commodity. Economic value represents all social benefits of a particular type of product, including the market value; absence of demand, therefore, does not imply an absence of value (Principe 1989). Norton (1988) argues that medicinal species have important indirect value, since many valuable medicines are synthetic copies of natural compounds. Furthermore, he states that species have amenity value, since "its existence improve[s] our lives in some nonmaterial way" (Norton 1988:201). The economic value of medicinal plants includes social benefits (more effective health coverage, better health, less wage losses, templates for synthetic drugs, new pharmacological tools, conservation of genetic resources as sources of drugs from yet-unknown diseases and/or new compounds for resistant germs and/or for yet untreatable diseases, and environmental benefits (by showing the plants' value we gain a better position from which to defend the forest).
POLICIES FOR PRESERVING THE FORESTS
In reviewing the past three decades of medicinal plant research, Tyler (1988:100) states, "the most productive period of medicinal plant research lies ahead of us." Behind this statement is his consideration that the development of screening methods (bioassays) and analytical methods available today are the means to solve what he considers to have been the main problems encountered so far. It would be rather unfortunate if, at the same time we seem to have overcome major technological obstacles, we also lose the cooperation of those who can point out promising species for screening, leaving us with no option except random screening.
Indigenous people enrolled in extractivism do indeed want to live with and preserve the forests. To make it happen, we must create the legal basis to ensure intellectual property rights at the local and national levels. Such policies could: 1 serve to promote the conservation of native flora and its culturally based lore. 2 help to prevent the clearing of new land (given that agriculture would be more successful with native species of commercial value). 3 give value to traditional knowledge by regarding it as true expertise. 4 reinstate the social role of indigenous cultures. 5 help to instate the self-sufficiency of native communities by developing renewable plant-based products. 6 provide specific solutions for local health problems by orienting drug discovery to specific needs combined with drug accessibility, acceptability, and storage. 7 further the discovery of prototypic drugs.
Conservation here is beyond aesthetical and theoretical issues, since it is likely that in the near future we will benefit in a very concrete way from new plant drugs. The ethnopharmacological approach, a highly valuable process of drug discovery, is now somewhat dependent on our ability to be less arrogant toward non-Western know-how and to consider the fate of the forest and the forest peoples as something to concern us all.
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