Scientific Knowledge and Technology, Animal Experimentation, and Pharmaceutical Development.

Human discovery of pharmacologically active substances is arguably the oldest of the biomedical sciences with origins >3500 years ago. Since ancient times, four major transformations have dramatically impacted pharmaceutical development, each driven by advances in scientific knowledge, technology, and/or regulation: (1) anesthesia, analgesia, and antisepsis; (2) medicinal chemistry; (3) regulatory toxicology; and (4) targeted drug discovery. Animal experimentation in pharmaceutical development is a modern phenomenon dating from the 20th century and enabling several of the four transformations. While each transformation resulted in more effective and/or safer pharmaceuticals, overall attrition, cycle time, cost, numbers of animals used, and low probability of success for new products remain concerns, and pharmaceutical development remains a very high risk business proposition. In this manuscript we review pharmaceutical development since ancient times, describe its coevolution with animal experimentation, and attempt to predict the characteristics of future transformations.