The Ethnobotanical Approach to Drug Discovery Medicinal plants discovered by traditional societies are proving to be an important source of potentially therapeutic drugs by Paul Alan Cox and Michael J. Balick n 1785 William Withering, a British A decade ago this story would proba- 25 percent of all prescriptions issued physician, reported that ingestion bly have been regarded as nothing more every year in North America. Many of I of dried leaves from the foxglove than a historical anecdote, of little rele- these agents are now synthesized in the plant eased dropsy, an accumulation of vance to contemporary drug discovery. laboratory, but others are still isolated ßuid now known to be caused by the By the mid-1980s most pharmaceutical from plants. Most were discovered by heartÕs failure to pump adequately. With- manufacturers had abandoned explor- studying indigenous uses of plants. ering credited an unexpected source for ing folk uses of plants in their search his information. ÒI was told,Ó he wrote, for new drugs. Now, however, the pen- or instance, the drug reserpine, that this use of foxglove (a member of dulum is beginning to swing back to- which is still occasionally pre- the genus Digitalis) Òhad long been kept ward an appreciation that plants used F scribed in the U.S. for hyperten- a secret by an old woman in Shrop- in traditional medicine can serve as a sion, was isolated from the root of the shire, who had sometimes made cures source of novel therapeutic agents. climbing shrub RauvolÞa serpentina (In- after the more regular practitioners Such appreciation has emerged in dian snakeroot) after scientists began had failed.Ó part because of recent discoveries made analyzing Ayurvedic remediesÑthe tra- Digitalis has been helping cardiac pa- by a small but growing group of ethno- ditional treatments used by the peoples tients ever since. Today two of its com- botanistsÑresearchers who study the of India. Other examples include aspi- ponentsÑthe glycosides digoxin and relationships between plants and peo- rin, opiates, pilocarpine (prescribed for digitoxinÑare prescribed to hundreds ple. Fieldwork exploring the medicinal glaucoma and dry-mouth syndrome) of thousands of people throughout the uses of plants by indigenous peoples in and two cancer treatmentsÑvincristine world every year. Indeed, these glyco- remote parts of the world, coupled with and vinblastine. Vincristine and vinblas- sides currently serve as the treatments the introduction of sophisticated assays tine, both of which are still extracted of choice for rapid atrial Þbrillation, a able to determine whether plants exert from Catharanthus roseus (rosy peri- dangerous cardiac irregularity. Given a biological eÝect, has facilitated the winkle), have been prescribed for pedi- the importance of Digitalis, we have no discovery of bioactive molecules made atric leukemia and HodgkinÕs disease, doubt that many readers of ScientiÞc by medicinal plants. Some of these mol- respectively, since the 1960s. American are alive in 1994 because ecules show promise as possible thera- Plants have been a rich source of Withering investigated the secret reme- pies for a range of diseases, including medicines because they produce a host dy of Òan old woman in Shropshire.Ó AIDS and cancer. of bioactive molecules, most of which In the U.S. the drug development probably evolved as chemical defenses process is a long and arduous one, de- against predation or infection. Never- signed to ensure that therapies released theless, several forces conspired by the PAUL ALAN COX and MICHAEL J. to market are eÝective and safe. It can close of the 1970s to cause plants to BALICK met in the late 1970s, when they thus easily take many years for a sub- lose much of their appeal as drug sourc- were doctoral students at Harvard Uni- stance to become commercially avail- es for the pharmaceutical industry. Mi- versity. Cox is dean of general education able as a drug. There seems little doubt, croorganisms and fungi that inhabit and honors and professor of botany at however, that within a decade several soil, which are easy to collect and cul- Brigham Young University. He is also president of the Society for Economic new agents derived from ethnobotani- ture, had provided a dazzling array of Botany. Balick is Philecology Curator of cal research will be introduced. We can- antibiotics. Advances in synthetic chem- Economic Botany and director of the In- not claim that most drugs of the future istry and molecular biology promised to stitute for Economic Botany of the New will be found in this way. Yet the strat- supply new means for designing drugs York Botanical Garden in Bronx, N.Y. He egy, as will be seen, has many merits. in the laboratory. And few major dis- is also past president of the Society for Until the 1950s, almost all pharma- coveries of plant-derived drugs had fol- Economic Botany. Cox and Balick, who ceutical research relied heavily on vas- lowed the identiÞcation of vincristine are collaborating on a book about ethno- botany for W. H. Freeman and Company, cular plants as sources of medicines. and vinblastine. Given these conditions, serve as advisers to a variety of govern- Flowering plants and ferns (as opposed many pharmaceutical Þrms simply mental, academic and industrial research to microscopic organisms and fungi) stopped searching for therapeutic com- groups and foundations. have given rise to about 120 commer- pounds in higher plants. cially sold drugs and account for some In spite of this discouraging state 82 SCIENTIFIC AMERICAN June 1994 Copyright 1994 Scientific American, Inc. of aÝairs, in the late 1970s and early Food and Drug Administration ap- program, with varying degrees of ener- 1980s several groups of scientists inde- proved taxol, derived from Taxus brev- gy, since 1960. (Today the NCI employs pendently set oÝ to diÝerent corners ifolia (the PaciÞc yew tree), as a treat- several plant-gathering strategies. It also of the world for the express purpose of ment for ovarian cancer and in 1994 ap- examines specimens not only for their Þnding innovative drugs through eth- proved it for treating metastatic breast anticancer eÝects but also for their abil- nobotanical research. Some of the re- cancer unresponsive to other therapies. ity to impede the functioning of the hu- searchers, such as Gunnar Samuelsson Taxol was found in the course of a ran- man immunodeÞciency virus, or HIV, and Lars Bohlin of the University of dom-screening program conducted by which causes AIDS.) Uppsala, were former students of the the National Cancer Institute (NCI), Other plant-collecting methods, in- distinguished Swedish ethnobotanist which has maintained a plant-screening cluding the ethnobotanical approach, Finn Sandberg. A number of American researchers trace much of their inspi- ration to another leading ethnobota- nist, Richard Evans Schultes of Harvard University. The two of us are among that latter group. When we were graduate students at Harvard in the late 1970s, Schultes encouraged us to continue our studies of traditional uses of plants in remote regions of the earth. Balick, in his doc- toral work, extended SchultesÕs pioneer- ing ethnobotanical research in the Ama- zon. Meanwhile Cox, who had been a missionary in Samoa for the Mormon church during his undergraduate years, returned to the South PaciÞc to study the ecology of the rain forest and the uses of plants by the Samoan people. After receiving our degrees, we contin- ued to investigate herbal medicine in two culturally and geographically dis- tinct areas: Central America (Balick) and Polynesia (Cox). Both of us have stud- ied intensively with indigenous healers. he ethnobotanical approach is ac- tually one of several methods that T can be applied in choosing plants for pharmacological studies. It is esti- mated that 265,000 ßowering species grace the earth. Of these, less than half of 1 percent have been studied exhaus- tively for their chemical composition and medicinal value. In a world with limited Þnancial resources, it is impos- sible to screen each of the remaining species for biological activity. Some kind of collection strategy is needed. Investigators, for example, can gath- er vegetation randomly in an area sup- porting rich biological diversity. Unfor- tunately, random searches yield rela- tively few new drug possibilities. One notable exception is taxol. In 1992 the ANDREW RAMCHARAN, a healer living in Belize, Central America, is collecting the leaves and flowers of the plant Cor- nutia pyramidata to include in a mixture used for skin rashes. Ethnobotanists in- terested in drug discovery often rely on healers to identify plants that are likely to contain potent bioactive chemicals. There is some urgency to this work: many healers are elderly and lack ap- prentices. As they die, much of their knowledge of local vegetation dies, too. Copyright 1994 Scientific American, Inc. Drugs Discovered from Ethnobotanical Leads The well-established drugs listed below are among doz- stance, Western researchers isolated reserpine in 1952 ens that were developed after scientists began to analyze from the climbing shrub Rauvolfia serpentina (photo- the chemical constituents of plants used by traditional graph), which has been employed in India for many cen- peoples for medicinal or other biological effects. For in- turies to treat snakebite and mental illness. DRUG MEDICAL USE PLANT SOURCE Aspirin Reduces pain and inflammation Filipendula ulmaria Codeine Eases pain; suppresses coughing Papaver somniferum Ipecac Induces vomiting Psychotria ipecacuanha Pilocarpine Reduces pressure in the eye Pilocarpus jaborandi Pseudoephedrine Reduces nasal congestion Ephedra sinica Quinine Combats malaria Cinchona pubescens Reserpine Lowers blood pressure Rauvolfia serpentina Scopolamine Eases motion sickness Datura stramonium Theophylline Opens bronchial passages Camellia sinensis Rauvolfia serpentina Vinblastine Combats Hodgkin’s disease Catharanthus roseus INDIAN SNAKEROOT Filipendula ulmaria Papaver somniferum Datura stramonium Cinchona pubescens Catharanthus roseus MEADOWSWEET OPIUM POPPY JIMSON WEED FEVER TREE ROSY PERIWINKLE are more targeted.