#1 - THE TROPICAL RAINFOREST: A RICH SOURCE OF NATURAL...

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Unformatted text preview: THE TROPICAL RAINFOREST: A RICH SOURCE OF NATURAL MEDICINES Eloy Rodriguez and Jan E. West Cornell University, Ithaca, NY Ref. Proceedings of the 1993 NIGMS Symposium. Atlanta, Georgia The Tropical Rainforest: A Rich? Source Of Natural Medicines "Treat the Earth well. [The Rainforest] was not given to you by your parents. It was loaned to you by your children. " African Proverb (EPA Journal) Introduction No area of the world has undergone a more dramatic change in its popular image than the tropical rainforest. Forty years ago, this region was known as "The Jungle" and was the epitome of the inhospitable nature that confronted many explorers. Today, visits to the tropical rainforest are being sold as ecotoun‘st packages for the affluent, and efforts to preserve the rainforest are in various popular books on the environment. McDonald's restaurants now have prominent displays of posters that tout their efforts to preserve rainforests, and other establishments advertise ice cream flavors with "essences of the tropical rainforest." r a This change in attitude is the result of educational campaigns of phytochemists, environmentalists, anthropologists, ecologists, and other concerned people. Biologists have long been aware of the tremendous diversity of the tropical rainforest. A typical acre of tropical rainforest will contain more than one hundred species of trees, a greater number of species of epiphytes, other smaller plants, as well as thousands of species of insects, and other invertebrates. Charles Darwin's excursion in a tropical rainforest of Brazil was a seminal experience that was critical in his intellectual development and helped lead to the theory of evolution. Other biologists have been similarly impressed by the life of the tropical rainforest and have had experiences in the rainforest that have profoundly influenced their professional development as scientists. What is the Tropical Rainforest? The term was coined by a German scientist, Andrew Franz Wilhelm Schimper, in 1898. According to Schimper, a rainforest consists of evergreen trees living in a warm, humid climate. The trees must be at least 100 feet tall, and the forest must contain a profusion of thick-stemmed vines, and epiphytes (plants that grow on branches of trees). To permit this luxuriant plant growth, rainfall must exceed 80 inches a year and be evenly distributed with high humidity throughout the year. Temperatures must be mild with average temperatures from 70° to 800 with no great diurnal or seasonal fluctuations. These conditions are common in the area 10 degrees north or south of the equator. Here the sun is overhead the whole year, a fact that ensures maximal heating and evaporation of water from the ocean. The heating and evaporation cause atmospheric updrafts and thunderstorms that supply the constant moismre needed by the vegetation. Ocean currents can also carry sufficient moisture to small localized areas as far as 20° north or south of the equator. The largest areas of tropical rainforests are the Amazon region of South America, the éongo river basin of Africa, and large areas in Southeast Asia and adjacent islands such as New Guinea. The total area occupied by rain forest being only one sixteenth of the Earth's surface. Species Diversity In The Tropics Humid and warm conditions of a rain forest are optimal for the growth of living creatures; bacteria, fungi, insects, and plants grow under conditions that can only be duplicated in a greenhouse in temperate regions. The absence of any physical constraints on growth has important biological consequences. First, the absence of seasons relieves the tropical rainforest organisms of the need to evolve adaptations to endure the inclement conditions. The dry season or cold winter makes continued growth impossible for part of the year and forces the organism to go into dormancy (diapause) for that part of the year. It is also imperative that the organism recognize events in the physical world around them that enables it to enter and leave diapause of the appropriate time. As an example, in temperate climates, trees will drop their leaves when the hours of sunshine in a day decrease; consequently, the tree is prepared to survive the cold winter conditions. Subsequently the tree must avoid growth during short winter warm spells that will be folly-yeti. by more cold weather. Organisms that live in areas with distinct seasons must have a complex system of light and temperature receptors that regulate the level of endogenous hormones that control growth. Consequently, the major selection forces in areas with periods of inclement weathery is directed to solve the problems posed by their physical environment. The vast majority of species do not apprear to cope with these conditions, since the number of biological species in areas with severe seasonal constraints is small. Species can exist for thousands or millions of years without the dangers of posed by cold or dry weather. In essence, tropical rainforests can function as vast biological museums. A second biological consequence is an indirect consequence of the from physical constraints. The lack of physical constraints ensures that biological competitipnfwill always be intense, the tropical rainforest is an environment in which any biological innovation such as a new natural chemical (allelochemical), or a a: detoxification mechanism, will confer an immense biological advantage on the species that possesses it. . An allelochemical or secondary metabolite is any organic chemical produced by one organism that confers an advantage on it when it interacts with other organisms. This environment also enables the organisms that inhabit this area to co- cvolve and develop elaborate symbiosis. This large number of species multiplies the number of niches available for new species and this adds even more niches for new species. A typical boreal region of one acre will be dominated by 2 or 3 species of bees; a temperate region forest will contain about a dozen species; and a tropical rainforest will contain over one hundred species of trees. (The maximum recorded being 300 distinct species in one acre of the Amazon rainforest.) The tropical rainforest is the world's richest repository of species. The total number of species of all organisms in the world is estimated by some biologists to be as high as 39 million of which only 1.4 million have been identified, classified, and given scientific names. Approximately half of these species are restricted to the tropical rainforest and will disappear from the world when the rainforests are chopped down. The estimates of the number of species facing extinction with the destruction of the tropical rainforest vary from 3 to 20 million. This extinction will be the greatest destruction of species since the extinction of the dinosaurs at the end of the Cretaceous, 65 million years ago. Why Should We Care? First, the rich biological diversity of the tropical rainforest makes the rainforest the evolutiOnary "hotspot" of the Earth. The complex interactions of species cause more innovation to arise here: The major groups of 'higher plants” and insects first appreared in the tropics; humans are descendants of primates that lived in the tropical rainforest a few million years ago; and the HIV virus was a parasite of primates in the rainforests of Central Africa. It is important for the continued evolution and stability of life on the - Earth that we have {his xomplex of species for the evolution of new life forms. The new species that evolve in'the complex tropical ecosystems make this region important for the long term stability of whole world for the world. This region functions as a flywheel or gyroscope. A simple ecosystem with few species is inherently more unstable than complex ecosystem with many species. One mutation that enables a parasite to destroy a host will have an immense ecological impact if that host species is a dominant part of the ecosystem (the blight that destroyed American Chestnuts, or mutations that confer pesticide resistance in insect pests of agricultural crops). If a species in the temperate zone becomes extinct, a large number of related species in the tropics exists that can evolve to fill this Open niche. An analogous situation occurs with humans and the pathogenic microorganisms that parasitize us. Since the parasites have probably evolved in ironies, the organisms that live in the tropical rainforest have evolved resistance to these pathogens. Hence, scientists travel to the tropics because we know that it is Where we are likely to find the "cure" for the disease. Other Reasons To Conserve The Tropical Rainforest Burning, the rainforests will add a great amount of C02 to the atmosphere and increase giobai warming. Destroying the rainforest will also decrease the amount of water evaporating from the leaves of the forest trees, and this could cause a decrease in the recycling or" moisture in the tropical regions. This could alter the humidity of regions such as the Western Amazon Basin, and this fall in humidity will decrease nubosity (cloudiness) rainfall. This could change the albedo of the regions and cause a serious - in the air currents that carry heat and moisture to regions such as the Anericandvfidwest. (Earlier concerns about a dramatic decrease in oxygen content of the Earth‘s atmosphere after the disappearance of the rainforest is probably an exaggeration.) On a more immediate‘and practical level, the destruction of the rainforests will have a r0 disasnous and. long lasting effect on agricultural productivity. The loss of genome (lie-xerox}! will deprive agricultural scientists of the "new" genes that are needed for crop resistance to pathogens, or higher crop productivity or quality. Nev; genes for existing crops do not appear at random in an agricultural field, but must be introduced from- natural mutations in an existing population. The tropical rainforcst also has a tremendous diversity of plants with edible fruits, oils, or new sources of wood for construction, furniture, or paper. Scientists working in groups such as the Society for Economic Botany have identified hundreds of such plants. Recreation And The Beauty of Nature It is also important to conserve the rainforest to enable ’future generations to have the opportunity to visit these biological museums. Most people do not think a rainforest is a desirable place for vacations because they have seen movies such as "Predator" and "African Queen." Yes, there is humidity, biting insects, and many tropical diseases. However, all visitors to the rainforest have found the rainforest to be awe-inspiring. Henry Walter-Bates, a famous tropical biologist said, "There is something in a tropical rainforest akin to the ocean in its effect on the mind..Man feels so completely his _ insignificance there and the vastness of nature." New Medicines From the Tropical Rainicrest Phytochemists, who have an interest in developing novel pharmaceutical products from plants, have a special interest in tropical plants and are concerned with their continued survival. First, as had been stated earlier, one half of the world species of higher plants are restricted to these forests that occupy only one sixteenth of the Earth's surface area. Secondly, the plants the rainforest are particularly rich in natural products that have biological activity. , Tine tropics have had a stable, benign climate for millionslof years, and this has allowed the development of complex patterns of co—e=;olution and symbiosis. One large tree in the rainforest will have hundreds of other species’including epiphytic plants, insects that eat different parts of the tree or the associated epiphytes, pollinators, and numerous saprophytic and parasitic nematodes, fungi, and bacteria The absence of physical constraints on organisms in the environment ensures that biological competition is mediated by allelochemicals will be more intense. In our earlier research, we had found that the number of different allelochemicals in a plant species varied. with the latitude of the habitat. Species of the genus (Asteraceae) from Wyoming had 2 to 4 major allelochemicals and plants of the same genus from tropical Southern Mexico had 10 to 13 major allelochemicals. 4,... 2‘ '\ Tropical plants have been a major source of drugs for modern medicine. A few of the most famous drugs from tropical plants are listed in Table I and illustrated in Figure 1. However, only about one percent of the plants from the tropical rainforest have received amount of scientific study. The insects, fungi, and bacteria that are associated with these plants, and that will disappear with them, have been studied even less. These organisms also accumulate allelochemicals that give them the biological advantage when they are competing with other organisms. Penicillin, streptomycin, and ’ tetracycline are a few of the medicinal natural products from these groups. of Novel Tropical Allelochemicals The search for novel bioactive natural products that could be used for their pharmacological activity has been a major goal of my research laboratory. Other groups at other universities and private pharmaceutical companies are also conducting similar investigations. The first step of the process is to identify those plants that would be more likely tr, contain bioactive compounds. Consequently, we have collaborative programs with botanists, anthropologists, and anyone else that might give us information to choose ' a good candidate plant. Then we must collect large amounts of the plant, dry it, extract it with solvents, and partially separate the principal chemical constituents into less complex mixtures or fractions. The mixtures are then tested for the capacity to affect a laboratory organism (the bioassay). These organisms used in bioassays are most often simple unicellular organisms, such as bacteria, that can be raised in a petri dish in the laboratory. Very often, there is one particular disease that is being investigated, and a special bioassay must be devised to test the effect of new chemicals on a particular type of cell that has unique characteristics. (As an example, when we are looking for chemicals that affect the nervous system, we must test the chemicals with neurons.) 7 Boch cw . 255:5 805$ 331$ ., mummficg «532$. 05:330.; :ommcouumxm . untamed «SEE :0 m 2:55 mcommmgcov . £5585 «Efimlx 3.55an begin oEo©E< $385 $285 850 aw 0:03.109 53% $635 3585 meflom 28:2 P350 ouofimucxx :50; 2.3.80 Efizgcm ,w V 9:6th ‘ mu<m3 flung—2mg E2415 mazDGmEQQ fixzmmmflmg mag/21E QQUEGMEL 35mm mQZDGQESQ wwwamUmemE m mAfieQL .% $02.6me -mcmEEz dm 528%qu -525an 833850 mmfimfimv‘ .Enozofiu b": \ : £295.:ouzogmzo. z . z / , % x z 0 fo 2 .am 32:3 -3325 mamsnfio $628.6 655:0 . «:38 macESmSmQ -aE.mm_n:_> mzow :oooo _ 05:0 20:8 \ \z ":0 z ( xouuzo w H? to? mwm Mmumgn - mg “a wwmjfignm ngfimflmWQJW m>mmwfiv um flmm gm. mm“. Once a partially purified fraction with a particular type of biological activity is found, we must complete the purification of the chemical constituents. (Any plant will contain thousands of different chemicals.) These purified chemicals are then tested individually to determine which one has the desired type of biological activity. The chemical is then extracted in larger quantities and a variety of chemical spectrometric techniques (Mass Spectrometry and Nuclear Magnetic Resonance) are used to determine the exact structure of the new compound. Subsequently, the purified chemical must be tesrcd exhaustively with a variety of biological systems to fully determine the potential medicinal value. This is a very complex task and will require many years of effort by highly skilled biologists and chemists. A brief overview of the immensity of task is insti'ucn've. The tropical rainforests contain over 100,000 distinct species of higher plants and millions of distinct species of bacteria and fungi. Each plant or fungus species produces a distinct array of natural chemicals (allelochemicals) that are toxic to a particular parasite c:- predators. Each plant or fungus has a few hundred5diéu'nct chemical compounds. The effects of each of the different chemicals from a tree will be different on each type of organism or distinct cell-type in the body. A determination of all the effects of all the different chemicals from one plant on all the types of cells of a human body would. keep millions effscientists busy for thousands of years. Zoopharmacognosy And Ethnopharmacognosy In order to concentrate our efforts on the most promising allelochemicals from the rainforest organisms, we have to devise new methods to identify those plants that are most likely to contain large quantities of medicinal compounds and then concentrate our efforts on them. The most valuable information is the traditional medicinal usage of the plants by human groups that have occupied these forests for thousands of years. The 10 {Gig-fijwti‘lfilttiiing Indians of South America have been observed to use 1,300 species of plants to treat their illnesses. In Southeast Asia, about 6,500 species of plants are used in traditional treatments of diseases, i.e., malaria, ulcers, cancer, colds, and colds. Unfortunately, these native cultures are disappearing even more rapidly than the rainforests. Missionaries, school teachers, and commercial entrepreneurs are actively trying to incorporate these peoples into the predominate cultures of the countries that they inhabit. 227:: South America, the number of rainforest dwelling traditional Indians has gone from own million to less than 20,000 in the last 60 years. To try to preserve some of this vital lgcnowledge and identify new study plants, we haven-established collaborative research programs with Mexican botanists and anthropologists who are studying the folk medicines of the native groups of Southern Mexico. Another program has been established between UCI and scientists in Venezuela who are studying folk medicines used by the native groups of the southern portion of their country (part of the Amazon Rainforcst). Other research activities are being conducted in conjunction with scientists studying traditional herbal remedies in Brazil, Puerto Rico, Ecuador, Colombia, Thailand, and Africa. To further aid the process of discovering new medicines from plants, scientists such as myself, are looking at animal behaviors. Zoopharmacognosy is a new term that is used to describe the process by which animals deliberately select plants or other materials to cure or the symptoms of a disease that is afflicting that animal. The word was coined by Dr. Eloy Rodriguez and Dr. Richard Wrangham, an anthropologist at Harvard. Zoopharmacognosy comes from a combination of zoo, the Greek word for animal, and pharmacognosy, the recognition and study of complex chemical combinations and crude drugs recognized to have medicinal properties. Stimulus for this research comes from 11 the detailed observations of chimpanzees in their natural habitat, observations that were initiated by Jane Goodall in Africa. Observations of peculiar chimpanzee feeding behaviour prompted these anthropologists to collect leaves of these plants (Table 2), and send them to our laboratory at the University of California at Irvine, for chemical analysis. A chemical extraction of the plant material (leaves) yielded several chemical compounds, one major compound being thiarubrine A, an antibiotic compound that is intensely red, and unstable in the presence of light. In vitro experiments have established that a solution of 10 tig/r'il of thiarubrine A is extremely toxic to a roundworm closeiy related to the nematodes that infest humans and chimpanzees. Similar toxicity was observed in laboratory studies with two other species of roundworrns, Caenorhabin's elegant , and Trichostrongyloides columbzfonnis. Other 13 gm experiments have established that these compounds are very effective in treating solid tumors. Research with other plant extracts has established that the plants consumed by chimpanzees are a rich source of medicinal compounds. Table 2. Chimpanzee Plant Medicine. lafint_——~ Plant Part I Piesumed Medicinal Compound M, Ficus exasperata young leaves furanocoumarins Rubia cordifolia young leaves cyclic peptides Aspilia mossambicensis young leaves thiarubrines Vemonia amygdalina pith steroidal glycosides, sesquiterpene lactones MW— 12 Eiluttians have'previously thought that they alone could use medicine, since they alone were thought capable of making a conscious connection between the materials consumed and their physical illness. In contrast, animals were assumed to swallow food or other subs-1"" mere instinct and solely for nutritional purposes. Our research has shown us that animals that eat plants do not randomly swallow every plant that is in front of them, but deliberately and consciously seek out certain plants that contain nutrients and assiduously avoid others that contain toxins. Virtually all animals in warm humid climates are. infested by one or more species of parasitic roundworms, flatworms, or proton: can on occasion cause considerable distress to the animal. Consequently a plant that can alleviate these symptoms will be chosen and consumed for these purposes. Summary The tropical rain forests of the world are still the most diverse and unexplored area for discovering novel medincinal products that are effective against pathogenic bacteria, fungi, viruses, and human tumor cells. We have only begun to investigate the "tip of the rainforest canopy", but the extinctions of the tropical species means that hundreds to thousands of novel driigs are being lost. Extinction, including life saving phytodrugs, is forever. Conservation efforts must focus on the protection of medicinal plants, since such ecomedical systems are essential for the survival of mammals, reptiles, arthropods, and microorganisms. it is indeed ironic that the rainforest we are so eagerly destroying at a maddening pace, contains the pl’iarmaceuticals so badly needed to bring us good health, peace, and spiritual enlightenment. 13 Acknowledgements: We thank Dr. Manuel Aregullin for his assistance on the manuscript, and Mrs. Gloria Reardon for typing and editing: ng (Not all references included) 10. Famolare, L. and Plotkin, Mark (Eds). 1992. Substainable Harvest and Marketing of Rain Forest Products. Conservation International. Island Press, Washington, D.C. McNeely, Jeffrey A. 1988. Economics and Biological Deversity: Developing and Using Economic Incentive to Conserve Biological Resources. International Union for Conservation of Nature and Natural Resources, Switzerland. . Mitchell, Andrew. 1990. Vanishing Paradis: The Tropical Rainforest. The Overlook Press, New York. Myers, Norman. 1992. The Primary Source: Tropical Forests And Our Future. W.W. Norton and Company, New York. Newman, Arnold. 1990. Tropical Rainforest: A World Surgen of our Most Valuable and Endangered Habitat With a Blueprint For Its Survival. Facts On File, New York. Richards, PW. 1952. The Tropical Rain Forest: An Ecological Study. Cambridge University Press, England. Rodriguez, and R. Wrangham. 1993. Zoopharmacognosy: The Use of Medicinal Plants by Animals. (Eds) H.8tafford and K. Downum. Regen; Plenum Press, New York. Rodriguez, E., J. Cavin and J. West. 1982. The Possible Role 6f Amazonian Psychoactive Plants in the Chemotherapy of Parasitic Worms - A Hypothcsc. LQLEthmharmamlgsx 6303-309- Schultes, RE. and RF. Raffouf. 1990. The Healing Forest. Dioscorides Press, Oregon. , Silverberg, Robert 1967. The World of the Rain Forest. Meredith Press, New York. Dr. Eloy Rodriguez Department of Cell Biology University of California Irvine, CA 92717 14 ...
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#1 - THE TROPICAL RAINFOREST: A RICH SOURCE OF NATURAL...

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