Evolutionary Biology and Drug Development

Abstract

Evolution is the unifying framework in biology and scales to all living systems. It is the central organizing concept to explain seemingly disparate biological phenomena; from the very small (individual molecules) to the very large (ecosystems), from the rise and spread of molecular variants to the behavior and body shapes of elephants. In recent times, our appreciation for evolution in medicine has gained momentum. Individuals have championed the cause, dedicated journals have emerged, and new books on the subject are frequently published (“The Evolution and Medicine Review” is an excellent web-based resource providing updated information on the subject, http://evmedreview.com). This union between evolution and medicine has already advanced our understanding of pathological processes (Maccullum, 2007, Nesse & Stearns, 2008). Drug development and therapeutic strategies are areas in which evolutionary principles may be particularly helpful. The avalanche of bioinformatic methods, genomic data and subsequent emergence of evolutionary genomics in the last few decades means that integrating these fields in drug design is now a possibility. Incorporating evolutionary information is not only helpful a posteriori when we may hope to understand why resistance to a particular compound emerged. It is also valuable a priori, to design more efficacious drugs, suggest potential resistance profiles and conceptualize novel treatment strategies. Many allopathic treatments, particularly those for chronic non-infectious diseases, relate to the manipulation of cellular functions within one individual’s lifespan, for example, developing a drug aimed at a particular cardiac disorder. In these instances, evolutionary biology may explain why a particular disease arose, the evolutionary relationships between genes in the animal model and human or which pathological processes should be targeted. From an evolutionary perspective populations of reproducing individuals are the material on which evolution acts. Adaptive and non-adaptive changes occur over successive generations, and infectious organisms and cancer are therefore the premier examples to illustrate the role of evolution in drug development. In the current age it is almost unthinkable that evolutionary theory, the only scientific framework for studying ultimate causality in biology, doesn’t already form the starting point for developing therapeutic interventions affecting evolving populations. Here we wish to illustrate the role of evolution in allopathic medicine. A brief overview of the typical drug development pipeline is provided, followed by a discussion of relevant evolutionary questions. We discuss in greater detail the molecular evolutionary processes impacting on the emergence of drug resistance and offer suggestions to limit the problem.