Eisenberg et al. Identification of natural product-based leads for Western drug discovery has usually resulted from screening of extracts or compounds from diverse biological sources, generally without regard to preexisting knowledge of the therapeutic utility of the producing plant. A good example is the remarkable portfolio of hundreds of thousands of natural products and extracts amassed by the United States National Cancer Institute(NCD) since the inception of its natural product-based efforts in 1955[23]. Between 1960 and 1982, the NCI screened extracts of 35,000 plant species in collaboration with the U.S. Department of Agriculture (USDA). The strategy adopted was largely one of random selection of a broad range of natural product sources as opposed to selection based on medicinal use, i.e. ethnomedicine 4]. To a large extent, the driving force for NCI's efforts was biological and geographic diversity rather than pre-existing knowledge of therapeutic utility. Focusing on biological and geographic diversity is a typical paradigm of most natural product drug discovery successes, meaning that the use of natural products for Western drug discovery has largely been one of trial and error. This approach has been referred to as "bio-prospecting Paclitaxel, vinblastine and camptothecin were discovered using this approach. Interestingly, Verpoorte has pointed out that there are an estimated 250,000 flowering plant species on earth while as of 2000, fewer than 15,000(6%)had been screened for biological activity [24] n contrast, many cultures around the world have developed ethnomedical traditions based on therapeutic utility of selected local plants and animals. Such empirical traditions are often hundreds if not thousands of years old, as in the case of TCM for which written records exist going back over 2000 years. Unfortunately, the potential value of ethnomedicines has often been discounted by Western medicine and science, with several identifiable factors accounting for this. First, medical diagnoses in TCM and other ethnomedical systems are often portrayed in ways that are not readily understood by Western clinicians. Second, TCM and other ethnomedicines are often viewed as fundamentally lacking in the mechanistic scientific bases that usually underpin claims of Western medical efficacy. Third, there has been a lack of rigorous, well-controlled clinical trials demonstrating clinical efficacy(and mechanisms)of TCM and other ethnomedicines. Fourth, existing scientific and clinical studies of TCM have often utilized plants that have been quality compromised, may be contaminated with pesticides or heavy metals, may have been botanically misidentified, or are lacking a consistent and reproducible resupply chain. As such, and as noted earlier, prior udies have frequently been compromised by quality control and botanical authentication ues, as well as lot-to-lot variability and lack of knowledge of precise growing locations nd conditions, factors that have too often limited reproducibility. Finally, resupply of herbs for confirmation and follow-up studies is frequently problematic. The limiting factors mentioned earlier fall into two main categories: variables related to starting materials, and ariables related to execution or interpretation of scientific and clinical studies. While the two are interdependent, without addressing the former, there is little value in pursuing the From the vantage point of ethnobotany, researchers have highlighted the difficulties 9 replicating the biological activity of a given plant when attempts are made to repeat an experiment after subsequent recollection[25]. As such, the challenge of reproducibility remains a formidable one here are also challenges in terms of sourcing plant species to be studied. These include collecting them according to traditional techniques, documenting the precise collection sites using GPS technology, authenticating them visually, chemically and, through DNA sequencing, processing and extracting them according to established, traditional and reproducible techniques, storing them properly and so on AuthoIdentification of natural product-based leads for Western drug discovery has usually resulted from screening of extracts or compounds from diverse biological sources, generally without regard to preexisting knowledge of the therapeutic utility of the producing plant. A good example is the remarkable portfolio of hundreds of thousands of natural products and extracts amassed by the United States National Cancer Institute (NCI) since the inception of its natural product-based efforts in 1955 [23]. Between 1960 and 1982, the NCI screened extracts of 35,000 plant species in collaboration with the U.S. Department of Agriculture (USDA). The strategy adopted was largely one of random selection of a broad range of natural product sources as opposed to selection based on medicinal use, i.e. ethnomedicine [4]. To a large extent, the driving force for NCI’s efforts was biological and geographic diversity rather than pre-existing knowledge of therapeutic utility. Focusing on biological and geographic diversity is a typical paradigm of most natural product drug discovery successes, meaning that the use of natural products for Western drug discovery has largely been one of trial and error. This approach has been referred to as “bio-prospecting.” Paclitaxel, vinblastine and camptothecin were discovered using this approach. Interestingly, Verpoorte has pointed out that there are an estimated 250,000 flowering plant species on earth while as of 2000, fewer than 15,000 (6%) had been screened for biological activity [24]. In contrast, many cultures around the world have developed ethnomedical traditions based on therapeutic utility of selected local plants and animals. Such empirical traditions are often hundreds if not thousands of years old, as in the case of TCM for which written records exist going back over 2000 years. Unfortunately, the potential value of ethnomedicines has often been discounted by Western medicine and science, with several identifiable factors accounting for this. First, medical diagnoses in TCM and other ethnomedical systems are often portrayed in ways that are not readily understood by Western clinicians. Second, TCM and other ethnomedicines are often viewed as fundamentally lacking in the mechanistic, scientific bases that usually underpin claims of Western medical efficacy. Third, there has been a lack of rigorous, well-controlled clinical trials demonstrating clinical efficacy (and mechanisms) of TCM and other ethnomedicines. Fourth, existing scientific and clinical studies of TCM have often utilized plants that have been quality compromised, may be contaminated with pesticides or heavy metals, may have been botanically misidentified, or are lacking a consistent and reproducible resupply chain. As such, and as noted earlier, prior studies have frequently been compromised by quality control and botanical authentication issues, as well as lot-to-lot variability and lack of knowledge of precise growing locations and conditions, factors that have too often limited reproducibility. Finally, resupply of herbs for confirmation and follow-up studies is frequently problematic. The limiting factors mentioned earlier fall into two main categories: variables related to starting materials, and variables related to execution or interpretation of scientific and clinical studies. While the two are interdependent, without addressing the former, there is little value in pursuing the latter. From the vantage point of ethnobotany, researchers have highlighted the difficulties in replicating the biological activity of a given plant when attempts are made to repeat an experiment after subsequent recollection [25]. As such, the challenge of reproducibility remains a formidable one. There are also challenges in terms of sourcing plant species to be studied. These include: collecting them according to traditional techniques, documenting the precise collection sites using GPS technology, authenticating them visually, chemically and, through DNA sequencing, processing and extracting them according to established, traditional and reproducible techniques, storing them properly and so on. Eisenberg et al. Page 5 Fitoterapia. Author manuscript; available in PMC 2012 January 1. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript