Drug Development

Man has been using natural products for therapeutic use for thousands of years. Drugs extracted from plants and animals remain some of the most potent and widely used drugs today. For example, morphine from the opium poppy (Papaver somniferum), digitalis from the foxglove (Digitalis purpurea), curare from the bark of a South American tree, and quinine from another bark (Cinchona species) (Fig 1).

Raw extracts from plants and animals often contain a mixture of active ingredients. Early efforts at drug development focused on identifying the most important and purifying them. It is usually easier to control the effects of a drug, both beneficial and adverse, if one is dealing with a single molecule (or a small number of molecules) rather than a complex mixture. For example, McLeod, Banting, and Best performed a series of experiments on dogs and identified that removal of the pancreas rendered the dogs diabetic. Further work with a biochemist, Collip, allowed them to identify and purify insulin from the pancreas. The first insulin extracted in this way was given to a boy with diabetes in 1922.

This source of potential new medicines is far from exhausted. Plants and animals are seen as particularly important sources for novel antibacterial drugs. However, molecules extracted from plants and animals are often large and complex, making them difficult to manufacture. Adequate drug supply can be a limiting factor in early drug development, For example, paclitaxel, the first of the taxane class of chemotherapeutic drugs, was originally extracted from the bark of the Pacific yew tree (Taxus brevifolia). If this drug were produced by extraction, it would take 2000 mature yew trees to produce 1 Kg of paclitaxel. Therefore, in many cases, the natural compound is used as a template for further exploratory chemistry aimed at simplifying it.