The Oceans - A Storehouse of Undiscovered Drugs and Medicines The health of human populations requires a wide variety of chemical and physical supports from both local ecosystems and from the global ecosystem. The subject of this paper is the indirect relationship between biodiversity and human health, particularly with regard to coral reef ecosystems. Coral reefs are the most diverse ecosystems in the sea. “High diversity density gives rise to intense species competition and the subsequent organism capability to construct exotic defensive and offensive chemicals, many with pharmacological value” (Adey 2000). It is estimated that less than ten percent of reef biodiversity is currently known, and only a small fraction of that percentage has been tested for active compounds. However, coral reefs face numerous hazards and threats, both natural and anthropogenic. “Current estimates note that ten percent of all coral reefs are degraded beyond recovery. Thirty percent are in critical condition and may die within ten to twenty years. Experts predict that if current pressures are allowed to continue unabated, sixty percent of the world‟s coral reefs may die completely by 2050” (Hazards to Coral Reefs). Many species that exist only in coral reef ecosystems will likely become extinct in the coming decades, and the pharmacological potential that these species hold will be lost forever. Most of the drugs in use today have come from nature. Three common examples include aspirin, morphine, and penicillin. “„In the old days you could wander around a corn field or up in a forest, take little dirt samples, bring them back to the lab—and what do you know? You‟d found microorganisms that produce streptomycin, or actinomycin, or vancomycin‟” says William Fenical, director of the Scripps Center for Marine Biotechnology and Biomedicine” (Mestel 1999). Today when you do that you find the same things. “Of everything you find, 98 percent turns out to be something you‟ve found before. It‟s costly; it‟s inefficient” (Mestel 1999). In addition, drug discovery is going down and drug resistance is going up; new drugs are needed to combat the growing list of currently incurable diseases. The most effective way to search for new compounds is to go to a place that is rich in biodiversity and gather what has not been studied before. Coral reefs are the perfect place to look. “„Of the 27 diverse phyla of life, only 17 occur on land, yet 27 of the 27 occur in the ocean…There are one million cells in one milliliter of seawater and they‟re all different, yet we know something about only one or two percent of those. The oceans are a huge resource for drugs” (Rayl, “Oceans” 1999). The best sources of pharmacologically active compounds are bacteria, cyanobacteria, fungi, sponges, soft corals, gorgonians, sea hares, nudibranches, bryozoans, and tunicates. It is important to pay attention to the ecology of the reef when searching for new compounds. For example, sponges are often brightly colored and obvious members of a reef. Predators could certainly benefit by consuming these sponges, but they are generally untouched. Why? The sponges protect themselves through chemical warfare. Sponges feed by filtering sea water through their bodies, and sea water has a high concentration of bacteria, so in order to survive the sponges must produce antibiotics. In addition, space is very limited on a coral reef. Marine invertebrates frequently grow in an encrusting form by producing sheets of tissue. When one organism grows into its neighbor, it must either overgrow the neighbor or be overgrown. In this instance, the organism with the most toxic chemical wins. This chemical must effectively kill the rapidly dividing cells of the neighboring organism. This is exactly what chemotherapy does to the cancerous cells in a human body. “Anticancer drugs often act by killing the rapidly dividing cells of a tumor but generally do not harm „normal‟ healthy cells” (Kerr). On the other hand, studying hard corals would not lead to any groundbreaking discoveries. They have no need to produce powerful toxins to protect themselves because these species use their hardness as a defensive measure. “Today the list of novel potential anticancer drugs at the National Cancer Institute‟s Natural Products Branch includes more candidates from the ocean than from the land” (Mestel 1999). The NCI is conducting Phase I, Phase II, and Phase III trials on several exciting compounds such as Bryostatin 1 (“a compound isolated from the bryozoan Bugula neritina, an organism that attaches itself to the bottoms of boats off the coast of California, primarily for use as a treatment of melanoma, non-Hodgkin‟s lymphoma, and renal cancer” (Rayl, “Oceans” 1999)), Dolostatin 10 (“a linear peptide derivative isolated from the sea hare Dolabella auricularia from the Indian Ocean, for use in the treatment of breast and liver cancers, solid tumors, and leukemia” (Rayl, “Oceans” 1999)), and AE941 (“a shark cartilage preparation…for use in treatment of various tumors” (Rayl, “Oceans” 1999). The private sector has generally been slow to invest in pharmaceutical research related to the world‟s oceans. “It appears, not too surprisingly, to be a dollars and cents issue as much as anything” (Rayl, “Oceans” 1999). The reason is because marine drug development takes longer to do and pharmaceutical companies are under tremendous economic pressure to produce new compounds quickly. Another reason involves Rio Convention issues; in other words, if a private firm discovers something in another country‟s waters, will that firm be allowed to develop it? Some countries are controlling all research in their waters, which means that outside researchers are excluded from the research process. The Philippines has recently done this. However, some smaller firms have been conducting research on marine based pharmaceuticals. PharmaMar, a Spanish firm, is currently in Phase II trials with Ecteinascidin-743 (ET743). ET743 is a compound derived from a Caribbean tunicate, and it has been effective in fighting ovarian cancer and other tumors. Estee Lauder has also introduced a skin care product that includes the anti-inflammatory compound Pseudopterogorgia elisabethae. This commercial application has proven to be the first true test of large scale harvesting of a marine invertebrate, with over 10,000 pounds of gorgonians already harvested. “The gorgonians, which occur between 45 and 75 feet deep, are pruned by hand along an approximately 60 mile length of the Bahamas coastline. Diving is limited to 60 feet, allowing the deep water specimens to provide a reservoir of breeding stock” (Faulkner 2000). The population has already been pruned four times, and researchers are optimistic that the P. elisabethae populations can be harvested indefinitely in a sustainable manner. “Since the demand for the product is probably five times the current supply, expanded but properly managed harvesting of gorgonians could provide an economic incentive for community based conservation of coral reefs in other nations in the Caribbean” (Faulkner 2000). Clearly, supplying sufficient material for the large scale production of drugs is a daunting task for the pharmaceutical industry. The yield for ET743, for example, is one gram per ton of tunicate. Harvesting tons and tons of tunicates is not economically or biologically feasible. The two major options for overcoming this problem are synthesis and aquaculture. “The commercial source of choice for the pharmaceutical industry is synthesis, which allows the company to control all aspects of production. This is the best solution for relatively simple compounds but many bioactive marine natural products are extremely complex and require multi step syntheses of heroic proportions. For these more complex molecules, it seems best to elucidate the mechanism of action and identify the pharmacophore so that simpler compounds can be synthesized” (Faulkner 2000). If synthesis is not possible, aquaculture can produce the necessary compounds. Small et al. show that coral reef systems can be close cultured long term successfully, and these systems can be maintained at the very large scale (many acres) necessary for a successful aquaculture operation. Moreover, CalBioMarine Technologies, a California based biotechnology firm, has shown that the aquacultural production of bryostatin is possible in a commercial setting (Rayl, “Reaping” 1999). To conclude, coral reef ecosystems are threatened and are already showing signs of degradation. This directly translates into large, irreversible biodiversity losses around the world. As human health standards increase in step with drug resistance, pharmaceutical research and development must be increased as well. “The world‟s oceans are a storehouse of undiscovered new drugs and new products of many types including enzymes, agrochemicals, and gene products. It is our last major natural resource; we need to realize its importance and plan for the future” (Marine Pharmaceuticals). Since large scale harvesting of these new products from the oceans is not economically or biologically feasible, synthesis and aquaculture techniques must be improved if society is to benefit from the amazing opportunities that these compounds provide. However, “The time scale of effective coral reef conservation and reef based drug development is beyond the supply and demand capabilities of the commercial world. An extraordinary international effort is required on a proportionally short time frame to bring together a mutually supportive effort to preserve and enhance the health of both human society and coral reef ecosystems”.
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