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in treating. While he found the agent to increase urine volume and, thus, to have diuretic properties, he commented in his thesis that the drug had a powerful action on the motion of the heart and thus recognized its cardiotonic action years before it was actually proven. Withering was a masterful botanist (he chronicled the plants of Great Britain later in his life). He was an exemplary clinical pharmacologist and demonstrated the best in botanical drug discovery and testing, given the skills of his day. But Withering's observations may not be unique. The effect of the foxglove on disease is known to be part of European plant folklore. The use of the glycoside yielding plants and the use of the skin of the toad for medicinal purposes goes back to ancient Egypt, as well as being mentioned in Chinese herbal writings. Confucius talks of glycoside plants for edematous states and cardiac glycosides are a significant component of Chinese herbal medications. While Withering's observations were a defining moment for modern medicine, botanicals of similar action were used over 2000 years ago. Clearly botanicals have been important to therapeutic advances. Whether we are discussing digitalis or atropine or any number of other drugs, plants have contributed much to drug discovery. The use of quinidine in atrial fibrillation and quinine to treat malaria are other examples of the important role botanicals have played in therapeutics. In fact, in the 1700s and 1800s botanicals were the only source of drugs for development. Anti-infective agents have depended on extracts from molds and fungus for a very long time. Recent therapies are derived from nature with some chemical modifications to improve activity. We often think of the age of botanicals as one that has gone by, but even though the use of botanicals was the first step in drug discovery and development, it continues to this day to play a major role. While reserpine was used for 1000 years in India and parts of China, it was only in the 1950s that it was purified and used as an effective antihypertensive agent. The recent use of taxol in oncology is an example of a botanical that was in very short supply. Until a synthetic pathway for commercial production was developed, the bark of the Yew tree became a very valuable commodity and caused the Yew tree to be endangered. In fact, some companies like Schaman Pharmaceuticals have made it their corporate purpose to discover and develop pharmaceuticals from botanical sources. We read of Merck and Company and Pfizer, to name two of the corporate giants, who have formed special alliances with botanical gardens, countries in South America or Africa, or both, to find new drug products. Is this a denial of the evolution of drug discovery, a last chance for the botanical pioneers, or a shrewd business decision? I would venture to say a bit of each. The biodiversity of the planet, the potential to find new antibacterials and other potentially useful pharmaceuticals is great. However, the need to assay so many compounds for a host of disease states and the imperfect capacity of our assays makes the odds of success much less than one might first estimate. Another critical aspect to the drug development process |
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