Artuso has outlined the entire process: formulating an appropriate strategy, obtaining biologic extracts, screening those extracts, isolating active compounds, conducting preclinical tests and chemical modification, submitting an Investigational New Drug Application, performing clinical trials, submitting a New Drug Application, and beginning commercial production. Flavopiridol He estimates the entire process would take 10 20 years or more. Using complex mathematical formulae, he discusses what the expected payoff would be relative to such variables as the number of available plant species on earth, the amount of biodiversity in the tropical rain forests, and extinction rates. An element that all estimated projections fail to consider is that any of the 250,000 higher plant species on earth could conceivably produce a new drug, leaving all other criteria, projections, and speculations aside. The reason is that the introduction of novel mechanism based in vitro bioassays is virtually limitless, and therefore any plant, regardless of the extent of prior biologic or chemical study, could prove interesting as a potential new drug source.
For example, from 1960 to 1981 NCI collected and screened approximately 35,000 plant species for anticancer activity. Eventually, NVP-TAE684 all residual extracts from these 35,000 species were destroyed after they were assessed for anticancer activity. Thus, in speculating that about 6% of the 250,000 plant species on earth have been evaluated as a source of drugs, should one count the 35,000 species screened by NCI for anticancer activity within the number of 6%? We think not. Thus, because it is improbable that one could collect all the 250,000 higher plant species to screen for one or more biologic activities, and because the number of bioassays that one could screen these species for is unlimited, one must select judiciously those species most likely to produce useful activity.
In addition, the biologic targets must represent the activities that correlate best with the rationale for plant selection. It would appear that selection of plants based on long term human use in conjunction with appropriate biologic assays that correlate with the ethnomedical uses would be most appropriate. There are advantages and disadvantages of using plants as the starting point in any drug development program. If one elects to use information suggesting that specific plants may yield useful drugs based on long term use by humans one can rationalize that any isolated active compounds from the plants are likely to be safer than active compounds from plants with no history of human use.
Also, plants are a renewable source of starting material in many but not all cases. It is universally believed that plants provide an unlimited source of novel and complex chemical structures that most likely would never be the subject of a beginning synthetic program, e.g, vinblastine, vincristine, taxol, d tubocurarine, digoxin. If the active principles derived from plants have novel structures and useful biologic activity, patent protection can be assured. We have shown here that most useful drugs derived from plants have been discovered by followup of ethnomedical uses. Further, the trend today, especially in an industrial setting, is to seek bioactive compounds from plants that will serve as lead compounds for synthetic or semisynthetic development, to assure patent protection. Thus, this diminishes the need to isolate novel bioactive structures from plants, since the ultimate goal is to use the active compounds to produc