IN THE PAST 12 MONTHS ALONE, MORE THAN 1000 NEW species were identified. Some were found in Earth’s most remote locations, such as the Weddell Sea off Antarctica or central Australia’s Simpson Desert, where 3 species of carnivorous sponges and a new microbat species were found, respectively. In addition, nearly 100 previously unknown species of bacteria were found to be inhabiting human epidermis. When it comes to biodiversity—a term that describes the variety of life on the planet—the more scientists look, the more they find. But these discoveries represent far more than just novelty. In them can be found a major engine of advancement for medicine and biomedical research and a new lens with which to look on human health and disease. A Canadian scientific expedition to Easter Island in 1964 provides an example of how biodiversity can benefit medicine. In a remarkable stroke of luck, the scientists brought home a scoop of soil containing Streptomyces hygroscopicus, the bacterial source of sirolimus, a drug that has revolutionized the treatment of solid organ transplant rejection. Sirolimus and its derivatives have also shown promise in the treatment of brain, lung, endometrial, and kidney tumors and as a coating for arterial stents to prevent restenosis. Serendipity of this sort has arisen not only in exotic places but also in familiar ones. For example, Chromobacterium violaceum was cultured from the Pine Barrens of New Jersey, leading to the discovery of aztreonam, a principal antibiotic used in the treatment of gram-negative infections. Science has routinely appropriated microbial compounds for human use, ranging from old stalwarts such as penicillin, aminoglycosides, and tetracyclines to the new lipopeptides (eg, daptomycin) and antifungals (eg, caspofungin). But the reliance on natural products in drug development extends far beyond antimicrobial applications. Studies involving snakes, sea squirts, sponges, and snails have led to the discovery of angiotensin-converting enzyme inhibitors, trabectedin (a new treatment for soft tissue sarcomas), the antivirals azidothymidine and acyclovir, and ziconotide, respectively. Despite enormous investment into synthetic drug development, about half of the 100 most prescribed medications in the United States and about half of the new drugs approved by the Food and Drug Administration in the past 25 years derive directly or indirectly from nature (TABLE). Natural products compose a superb resource for drug discovery because they have evolved, in some cases during millions of years, to exploit fundamental biological pathways often shared by humans. In addition, the random aspect of the evolutionary process gives rise to products with unforeseen, and perhaps unforeseeable, biological actions, allowing for the development of pharmaceuticals with novel mechanisms of action. For example, paclitaxel (discovered in the bark of the Pacific yew tree), a mainstay of chemotherapy for a variety of cancers, was the first drug shown to inhibit microtubule breakdown during mitosis. The ability of nature to devise novel approaches to biological challenges has proven especially valuable to biomedical research. To survive in the extremely hot water of Yellowstone Park’s Mushroom Spring, the bacterium Thermus aquaticus has enzymes that remain functional at high temperature. One of its heat-stable enzymes, DNA polymerase, was instrumental in the development of the polymerase chain reaction, for which the Nobel Prize was awarded in 1993. Another Nobel Prize was awarded in 2006 for a discovery involving a common flower. Intending to produce more intensely colored petals, researchers introduced extra copies of a pigment gene into petunias. The resulting flowers were, against expectation, partially or totally white. The molecular basis for this effect was found to be RNA interference, a fundamental biological mechanism for inhibiting gene expression that has great potential to treat neurodegenerative disease, cancer, infection, and other medical conditions. A number of scientific breakthroughs have come from studies involving some of the 100 000 or more venomous peptides produced by sea snails of the genus Conus. These slow-moving predators, which live on or near coral reefs (among the most endangered habitats on earth), subdue fish with a precise chemical assault directed at their prey’s nervous system, leading to rapid paralysis. Peptides isolated from Conus species bind many molecular targets, including ion
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Oct 1, 2009
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