Pharmacology, Biodiversity And

PHARMACOLOGY, BIODIVERSITY AND Paul Alan Cox National Tropical Botanical Garden I. Evolutionary Perspectives including but not limited to iconongraphical repre- II. History sentations, terminologies, names, phrases, legends, III. Modern Chemical Approaches to Drug Discovery methods, and techniques of traditional cultivation, IV. Rational Screens of Biodiversity healing, identification, preparation, and use of bio- V. Nature of Biodiversity-Derived Pharmaceuticals diversity. VI. Biodiversity and Ethics indigenous peoples Peoples who have resided in the same geographical area for many generations and who possess legends, proverbs, geneologies, lan- guages, and other unique cultural features linking GLOSSARY them to the land. phylogeny A family tree of related organisms tracing bioassay A test for pharmaceutical activity in substance their evolutionary history. conducted either in living organisms (in vivo assays) voucher A representative specimen of a plant or animal or in the test tube (in vitro assays). that is properly collected, prepared, and preserved coevolution A heritable response made by a species in a herbarium or museum to facilitate expert identi- through evolutionary time to a different species fication of the species. which is then reciprocated. ethnobotany The study of the uses of plants by different groups of peoples, often indigenous peoples. extremophile A organism that lives and thrives in a PHARMACOLOGY, the science of drugs, studies the habitat characterized by extremes of temperature, ways in which natural products can be employed as acidity, alkalinity, salinity, light, or pressure that medicines. Since ancient times, humans have recog- nized the pharmaceutical properties of certain com- would prove lethal to most other organisms. pounds derived from plants and animals. Current re- fractionation A method of obtaining a pure compound search now also recognizes that biodiversity must be by extracting components of a mixture with solvents maintained in order for the environment to continue of different solubility. herbal A compilation of medicinal plants and their to be a source of such medicinal substances. properties often used in earlier times as a reference for physicians prescribing medical treatments based I. EVOLUTIONARY PERSPECTIVES on plant therapies. indigenous intellectual property rights Rights to intel- Life-forms have evolved a plethora of complex biochem- lectual properties belonging to indigenous peoples, istry to help mediate their interactions with their physi- Encyclopedia of Biodiversity, Volume 4 Copyright 2001 by Academic Press. All rights of reproduction in any form reserved. 523 524 PHARMACOLOGY, BIODIVERSITY AND cal and biotic environments. Some of the resultant mol- the predator or parasite population possess a means of ecules function as materials for membranes and cell detoxifying the defensive chemistry generated by the walls, photosynthetic pigments, energy storage com- plants. The resultant coevolutionary race between two pounds, neurotransmitters (in animals) and hormonal species, sometimes termed a ‘‘red queen race’’ after the signals (in plants as well as in animals), defensive com- never-ending race described by Lewis Carroll in Alice pounds, a variety of protective pigments, and as struc- in Wonderland, has been documented in the interaction tural materials. The resultant juxtaposition of similarity between Passiflora vines and Heliconius butterflies in and diversity of the chemical compounds created by the Neotropics by Larry Gilbert and coworkers at the different life-forms is striking. For example, genetic University of Texas. Other such tight coevolutionary inheritance in all known life-forms is based on nucleic links are the topic of much scientific interest. acids; although some enzymes used in replication differ More common than species–species coevolution is with regard to prokaryotes and eukaryotes, all known what might be termed diffuse chemical coevolution. living organisms use RNA or DNA to transmit their Instead of evolving defensive chemistry against a single genetic information. However, differences in other bio- species of predator or parasite, a plant species generates chemical pathways are profound. These differences re- compounds effective against a wide variety of plant sult in differential vulnerability to toxic compounds, enemies. The presence of toxic compounds in a plant with ranges in LD50s of specific compounds varying cannot, however, be considered prima facie evidence several orders of magnitude between different phyloge- of an evolutionary response to predation. Bioactive mol- netic groups. For example, the concentration of penicil- ecules occur in plants as secondary metabolites as well lin that completely stops cell wall formation and growth as evolved chemical defenses against predation, fungal in Streptococcus bacteria shows little effect when admin- attack, microbial invasion, and viral infection. It is also istered to a centipede or to a geranium, whereas the unlikely that plant compounds known to be toxic to dose of 2,4-D sufficient to kill a geranium would have humans represent evolutionary responses to anthropo- negligible impact on either centipedes or bacteria. genic harvesting; given the omnivorous, generalist for- Throughout the history of life on Earth, such differ- aging patterns of higher primates, it is unlikely (with ences in biochemical vulnerability have generated abun- the possible exception of agricultural weeds) that any dant possibilities for chemical coevolution between dif- plants have evolved a specific biochemical response to ferent species. Even though life on Earth appears to consumption by humans. However, there are hundreds share a common phylogeny, biochemical differences of thousands—perhaps even millions—of bioactive between species leave open the possibility that a muta- molecules in nature resulting from plant chemical war- tion in the biosynthetic pathway of one organism may fare with viruses, bacteria, fungi, and arthropods. Many yield a compound toxic to another. Selection for such of these compounds can be beneficial to humans. protective molecules from predation would likely be The emerging picture of chemical interactions be- greatest in organisms that are unable to flee or lack tween sessile prey and motile predators is compelling: alternative forms of defense, including sessile organisms what might otherwise appear to be a quiet forest glen such as corals, sponges, tunicates, and other marine or a tranquil coral reef may be the evolutionary equiva- invertebrates and nearly all plants. Although poisonous lent of a battlefield rife with chemical warfare. Sessile birds have been found in New Guinea, toxic frogs are prey appear to sequester toxic agents and motile preda- prominent in the Neotropics, and brightly colored toxic tors develop detoxification strategies at a prodigious insects are known to most amateur naturalists, such rate through evolutionary time. Since many of these biochemical protection against predation by motile or- bioactive molecules have relevancy to human disease, ganisms appears to be the exception rather than the rule. a coral reef or forest glen could also be said to resemble A plant species under pressure from a predator or a large pharmaceutical storehouse, perhaps one that is parasite may perish unless individuals in the plant pop- in great disarray. Tens of thousands of vials of pharma- ulation possess, by mutation or some other evolutionary cologically active compounds litter the ground, but the accident, a compound toxic or unpalatable to its ene- labels identifying the contents and their therapeutic mies. If the mutation is heritable, progeny of such plants utility have been lost. How can one determine which will increase in time through population, replacing molecules are useful and for which diseases? those individuals previously lost to predation. If the Eloy Rodriguez and coworkers at Cornell University species of predator or parasite are highly selective in have found evidence that some vertebrates self-dose their choice of prey, they may in turn become imperiled with pharmacologically active compounds produced by by such chemical innovations, unless individuals in plants. Many mammals, including primates, engage in PHARMACOLOGY, BIODIVERSITY AND 525 self-medication when ill. Ongoing pharmacological self- In the first century Padanius Dioscorides, a Greek experimentation by animals may have been observed physician, wrote a seminal work on medicinal plants and mimicked by early humans. Early Polynesian leg- titled De Materia Medica, which describes more than ends indicate that kava, a beverage made from the roots 500 medicinal plants and includes many drawings. Un- and rhizomes of Piper methysticum rich in tranquilizing til the beginning of the Renaissance, Dioscorides’ work sequiterpenes and kava lactones, was discovered by was the final word in medicinal plants for more than watching the calming effect the roots had on rats. Leg- 1000 years. ends from India claim that in ancient times mongooses Such early compilations of folk wisdom concerning were observed to feed on Raulvolfia serpentina before medicinal plants were not confined to the West. In 2000 engaging in combat with cobras. Copying the reputed B.C., the Chinese emperor Chi’en Nung compiled the feeding behavior of the mongoose, local people found Pen Tsao, which is perhaps the earliest known herbal, that the shrub could serve as a potent antidote to snake- whereas in India, Sanskrit texts on medicinal plants are

Load more