title: The reductionist paradox: are the laws of chemistry and physics sufficient for the discovery of new drugs?
abstract: Reductionism is alive and well in drug-discovery research. In that tradition, we continually improve experimental and computational methods for studying smaller and smaller aspects of biological systems. Although significant improvements continue to be made, are our efforts too narrowly focused? Suppose all error could be removed from these methods, would we then understand biological systems sufficiently well to design effective drugs? Currently, almost all drug research focuses on single targets. Should the process be expanded to include multiple targets? Recent efforts in this direction have lead to the emerging field of polypharmacology. This appears to be a move in the right direction, but how much polypharmacology is enough? As the complexity of the processes underlying polypharmacology increase will we be able to understand them and their inter-relationships? Is "new" mathematics unfamiliar in much of physics and chemistry research needed to accomplish this task? A number of these questions will be addressed in this paper, which focuses on issues and questions not answers to the drug-discovery conundrum.
authors.affiliation: Department of Pharmacology & Toxicology, College of Pharmacy and BIO5 Institute, University of Arizona, Tucson, USA. gerry.maggiora@gmail.com
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Maggiora
mesh_terms: D055808:Drug Discovery; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D049490:Systems Biology