The "Three Amigos" pose in the Bahamas
Amanda HaidetCosta Rica Research Paper
From the early days of crude teas to the sophisticated drugs made from extraction today, plants have long been used by humans as a medicinal source. Given that more than half of the world’s plant species reside in the tropical forests, it is reasonable to assume that the greatest chance for discovering medicinal plants is in the rainforest (Soejarto 2). In fact, Costa Rica alone holds five percent of the entire world’s species but only 16 percent are known to humans (National Biodiversity Inventory 1). Additionally, the 20 best-selling drugs worth about six billion a year currently come from natural sources (Yoon 23) and 25 percent of prescription drugs also have ingredients that come from plants (Balck, Elisabetsky, and Laird 5). Despite the promise of the rainforest for holding the cure to many diseases today, fewer than five percent of all tropical plants have been investigated for medicinal value (Saving what remains 1). Therefore in the past ten years, considerable time and money has been spent on researching organisms in the rainforest. These studies have a variety of motives such as the chance to discover cures to cancer, AIDS, and other diseases. Others use the prospect of finding important drugs in the rainforest as a political cause to help save the rainforest. However, many would agree that all of these efforts have had a considerable effect on the pharmaceutical industry and will most likely continue to for some time.
While searching for medicine in the rainforest may seem like a good idea due to the number of species present, the high level of biodiversity also creates the problem of where to start looking. There are several different philosophies concerning this issue which have all been somewhat successful. The first collection technique and probably the most widely used is the biodiversity-based approach (Soejarto 4). Basically, this technique involves rando collection of as many different species as possible to be screened. While this approach may seem like looking for a needle in a haystack, it is actually not completely random as collectors avoid many plants already tested or widely known (Soejarto 4). Probably the most prominent association that began utilizing the biodiversity approach is the National Cancer Institute (NCI) in the United States between 1960 and 1980. The NCI’s program employs a variety of organizations and universities who actually collect the samples from places like Africa, Central America, and Southeast Asia (Soejarto 4). The NCI has collected over 60,000 plant and marine organisms for screening and has achieved considerable results (Questions and answers about NCI's natural products branch 1). Several different anti-cancer agents were found including Taxol, a derivative from the bark of the Pacific yew, which has shown effective in treating ovarian and breast cancer (Soejarto 4). However, while the biodiversity-based approach has yielded good results, it is the most expensivemethod of collection and the chances of discovery based on the number of specimens collected is very low (Soejarto 4).
Another philosophy which is the next step up from random collection combines using observations of interactions between organisms and chemotaxic relationships between organisms to narrow the group of specimens collected. Collectors search for plants who produce secondary metabolites that help defend the plant from predators or pathogens (Soejarto 5). In fact, it hasbeen shown that many plant chemicals used to ward off insects have considerable bio-activity in humans (Saving 1). In addition, collectors may look for an organism with known biological power, such as snake venom, or a plant whose fallen leaves resist growing mold during decomposition (Yoon 22). This type of collection process led to the discovery of kaempferol rhamnoside, which is an antifungal flavonoid (Soejarto 5). The other part of this collection approach involves searching for plants that have similar taxonomic relationships with other plants already known to contain a biologically active compound. The more closely the plants are related, the greater the chance for discovering a related compound (Soejarto 5). Probably the most important example of this approach is the history of quinine, a compound used to fight malaria. Once quinine was determined to have considerable effects on malaria, the search was on to find the species in the Cinchona plant group that produced the highest yield of quinine. Expeditions led by Hasskarl and Markham in the early 20th century found that the species Cinchona ledgeriana produced the highest amount of quinine (Soejarto 5). An example of an organization that utilizes this combination technique is the Inventario Nacional de Biodiversidad (INBIO), or the National Inventory of Biodiversity in Costa Rica (Yoon 22). This organization holds 23 biodiversity stations across Costa Rica and so far has collected over 52,000 plant specimens and an even greater number of insect specimens (National Biodiversity Inventory 1). Once the specimens are identified, many are sent to Merck & Co., a pharmaceutical company whohas paid one million dollars in order to get the first look at these newly identified species (Yoon 23). Although only one in 10,000 will most likely turn out to be marketable, the discovery of a new drug can generate tens of millions of dollars annually (Yoon 23). INBIO also works in collaboration with the National Cancer Institute by allowing for their collected compounds to bescreened for anticancer and AIDS fighting potential (Questions 2). The only drawback to the chemotaxic approach for collection is that the chances for discovering new compounds that are biologically active is relatively low (Soejarto 6).
The final major collection approach which has gained much speed in recent years is the ethnobotanical approach. This philosophy marries anthropology and botany by using the knowledge of traditional medicine men or shamans to identify plants of medicinal value (Carr and Pedersen 12). Historically, these shamans have amassed a wealth of knowledge about a wide range of rainforest plants and it is estimated that 80 percent of indigenous peoples in developingcountries still use traditional medicine for primary health care needs (Medicinal treasures of the rainforest 1). In fact, the indigenous people of Southeast Asian forests use more than 6,500 species and the people of Northwest Amazonia use 1,300 species for medicine (Saving 1). The scientist, R.E. Schultes, wraps it up best claiming “each time a medicine man dies, it is as if a library has been burned down” (Schultes 24). The ethnobotanical approach uses the knowledge of shamans to cut down on the number of species tested for biological activity. Many of the plants used by traditional medicine men have proven to actually have medicinal value. One study in Samoa found that a whopping 86 percent of the plants used by local shamans had a biologicaleffect in humans (Saving 1). Nevertheless, some categories of plant-based medicines have shown to be more successful than others such as traditional drugs used for antibacterial, antifungal, and antiviral purposes. In contrast, those plants with supposed traditional antifertility, anticancer, and anti-HIV agents have had a lower success rate (Soejarto 3). While there are several organizations that utilize the ethnobotanical approach, the most well-known one is probably Shaman Pharmaceuticals, Inc. which has discovered products such as Provir for respiratory viral infections and Virend, a treatment for the herpes simplex virus (Carr and Pedersen 16). In fact, out of 262 plants screened for biological activity, 192 were found to be active, yielding a 73 percent successrate (Carr and Pedersen 17). Despite the attractiveness of the ethnobotanical approach, there are both restrictions and ethical considerations. First, the field collector must not only know the language and customs of the native shaman, but must also be accepted into the cultural group in order for the shaman to share such privileged information (Soejarto 3). If a collector is able to cross this line, there is still the issue of ownership of the information provided. In the modern world, literature-based information is the claim for patents and thus the orally-passed knowledge of shamans presents legal problems (Soejarto 3). In other words, most of the third-world countries possess the greatest number of traditional shaman, but the most industrialized countries dominate the majority of drug research (Saving 2). For example, the US is involved in a legal battle over the patent of a hallucinogenic medicine called Yage made from a combination of plants in the Amazon. An American took a sample of Yage without permission and is developing psychiatric and cardiac drugs in the US. The US Senate has refused to approve a UN agreement which gives recognitionto the intellectual property rights of shamans and other traditional medicine men (Saving 2). However, some drug companies such as Shaman Pharmaceuticals have tried to award the native people for their knowledge of medicinal plants. Shaman Pharmaceuticals donated 13,333 shares of its stock to a nonprofit organization to go toward the health care of the native people of thecountry where medicines have been discovered (Carr and Pedersen 14). Hopefully in years to come, better agreements can be formed between shamans and drug companies in order to use their extensive knowledge to benefit the rest of the world.
Once the plant or animal specimens are collected, they are frozen or most often dried to prepare for shipment. Upon arrival at pharmaceutical laboratories, they are ground up and extracted. The plant “soups” are then finally screened for anti-cancer, antiviral, or antifungal properties and if they show potential, chemists will isolate the active chemicals (Questions 5). Before these chemicals are advanced to preclinical and clinical trials, they must first be tested for toxicity (Questions 5). Lastly, if the chemicals make it all the way through preclinical and clinical trials, they must still be approved by the Federal Drug Association (FDA) before they can be put on the market. Many times scientists can use these compounds discovered as templates to chemically synthesize a drug on a large scale. For example, the template for aspirin comes from a compound in a willow tree in the rainforest although it is now completely synthesized in the lab (Medicinal treasures 1). However, many of the compounds discovered are very complex and it is actually much cheaper and easier to simply extract them from plants than to synthesize them(Medicinal treasures 1).
Many important drugs today have been found using this process including several cancer drugs. Taxol, a compound extracted from the Pacific Yew tree, is now the drug of choice for several types of breast and ovarian cancer (Taylor 8). In addition, vincristine and vinblastine were extracted from the now extinct rosy periwinkle in Madagascar and are now chemically synthesized. Vinblastine has amazingly raised the survival rate for childhood leukemia by 80 percent while vincristine gives Hodgkin’s disease sufferers a 58 percent chance of lifetime remission (Taylor 8). Besides these, many more promising natural products are currently on their way to the market for cancer treatment. From the Camptotheca acuminata tree in China comes Topotecan which is currently in clinical trials for the treatment of ovarian and small cell lung cancer. Also from this same tree comes Irinotecan for metastatic colorectal cancer and 9AC for ovarian, stomach cancer, and T-cell lymphoma. These two drugs are also currently in clinical trials and have already been approved by the FDA (Taylor 7). In addition to compounds extracted from plants, several microbial sources, such as the Streptomyces species, have yielded compounds for treatment of solid tumors, lymphomas, hematogic cancers, and leukemia that are now in both preclinical and clinical trials. Even tropical marine organisms such as the sea hare, tunicates, bryozoans, and sponges have produced compounds that are now in preclinical and clinical trials for the treatment of cancer (Taylor 8). The National Cancer Institute claims that 70 percent of the plants identified as having anti-cancer properties are found in the rainforest (Questions 1). With all of this promise from tropical plants and organisms, the fight to save the biodiversity of the rainforest seems even more crucial.
Not only does the rainforest yield a variety of anti-cancer plants and animals, but it also bears many promising AIDS drugs. For example, the drug Prostialin was isolated in 1984 from a tree in Samoa and has shown activity in fighting HIV (Saving 2). Currently, the most promising natural AIDS products are (+)-Calanolide A and (-)-Calanolide B which are found in the Calophyllum lanigerum and Calophyllum teysmanii, two species of trees found in Malaysia. Conocurovone, found in a shrub from Western Australia, is also in preclinical and clinical development for its AIDS fighting potential (Questions 7). In addition, there are a myriad of phytomedicines which come from plants that can help fight the associated infections many AIDS suffers experience. For example, bitter kola was discovered from traditional medicine men in Africa and is used to treat bronchitis and throat infections. Likewise, a drug called grains of paradise has shown incredible antimicrobial and antifungal properties (Iwu, Duncan, and Okunji 460). Many other promising antimicrobial drugs exist and are currently in preclinical and clinical trials.
Besides the discoveries of AIDS and anti-cancer drugs, the rainforest has shown to hold many other types of medicines as well from everyday pain killers like aspirin to important cardiac drugs. In fact, plant derived medicines are commonly used for fever, fungal infections, burns, gastrointestinal problems, pain, respiratory problems, and wound treatment (Balck, Elisabetsky, and Laird 63). Some examples of common everyday drugs derived from plant sources are thepainkiller codeine from the opium poppy (Yoon 24), the vomit-inducing Ipecac from the Cephaelis ipeccuanha plant (Taylor 1), and diosgenin from the Mexican yam used as the active ingredient in birth control pills (Carr and Pedersen 17). Furthermore, an estimated 4,000 plant species have been indicated as having contraceptive possibilities (Medicinal treasures 1). Also mentioned earlier was the use of quinine from the bark of the Cinchona tree to treat malaria and the painkiller aspirin from willow trees of the rainforest. Additionally, many complex drugs have been discovered from rainforest plants including the tranquilizer reserpine from the serpentine root, the cardiac stimulant digitoxin from the common foxglove, ergonovine from the plant fungus smut-of-rye for treatment of migraine headaches (Yoon 23), and d-turbocuarine from the poisonous bark of some curare lianas to treat multiple sclerosis, Parkinson’s disease, and other muscular disorders (Medicinal treasures 1). Plants, fungi, and other microbes have also long been known as excellent sources of antimicrobial agents. Some common examples include penicillin, streptomycin, aureomycin, and chlorobycetin (Iwu, Duncan, and Okunji 457). Since infectious disease is the number one cause of death in the world today and antibiotic resistance is growing, finding new antimicrobial agents is becoming crucial, especially to third-world countries (Iwu, Duncan, and Okunji 457).
While many recognize the drug potential of the rainforest, some are still skeptical and believe that the prospect of finding drugs in the rainforest could actually endanger plants and animals. For example, the complete synthesis of Taxol, a popular anti-cancer drug, is not feasible in the laboratory and in 1993 alone, about 12,000 tons of dried Pacific yew bark were needed to supply enough Taxol for clinical use (Soejarto 2). At this time, the Pacific yew was actually an endangered species although since then a semisynthetic route for Taxol production has been developed (Tulp and Bohlin 29). This example still presents the question of what would happen if an endangered species was found to contain a highly successful anti-cancer drug that could not be synthesized in the lab. In addition, many feel that combinational chemistry can synthesize compounds faster and cheaper in the lab than searching for natural resources in the field. This is due to the fact that the process of natural discovery can be long and exhausting from actuallycollecting the plants to making separate extracts that can be screened. In comparison, combinational chemistry can synthesize tens of thousands or even millions of compounds at once using robotic technology (Service 186). However, there is no substitute for the unique three-dimensional compounds found in nature. Therefore, it is unlikely tropical forests will be abandoned in the search for new drugs.
Taking into consideration some of the limitations of discovering medicine in natural sources, the rainforest still holds the greatest amount of biodiversity in the world, possessing an essentially limitless number of new possibilities for drugs. Through several different methods of collections, many plants and other tropical organisms have already been investigated and found to have biologically active agents. These compounds range in ability from easing the everyday headache to curing childhood leukemia. However, unlike most avenues of research, this field produces the unlikely bond between the dollar-motivated pharmaceutical companies and environmental conservationists. It allows for businesses to make millions of dollars marketing novel natural medicines, providing this segment of the population with a crucial motive for fighting to save the rainforest. Conversely, many scientists who believe the rainforest should be preserved solely for its biodiversity and aesthetic quality are working hard to classify new plants and other organisms in order to keep pharmaceutical companies supplied with a variety of new compounds. Basically, if the rainforest is destroyed for logging or farming, both pharmaceuticalcompanies and conservationists lose. For example, Peter Principe of the US Environmental Protection Agency calculated that if the given retail value of plant-based medicines is about eight billion per year, the probability of 5 in 10,000 plants can be made into a marketable drug, and the current rates of extinction are taken into account, then the lost value of drug products in 1992alone was a whopping $150 million (Carr and Pedersen 22). Since over two percent of the world’s rainforests are irreparably destroyed each year, not only are pharmaceutical companies losing billions of dollars, but we may have also just cut down the only few trees that can cure a brain tumor or prevent the development of Alzheimer’s disease. Considering these kind of implications, we need to realize that chemical technology can only get us so far in the development of new medicines and therefore, preserving pristine rainforests including their indigenous peoples is crucial to the continuing advancement of medicine.
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