Review Article
Andrew J. Curtright and Stephe
Abstract
Phage therapy is the application to bodies of bacteriophages – the viruses of bacteria. This is done to combat bacterial infections. In this article we combine three themes, phage therapy, pharmacology, and the concept of emergent properties. We do this to explore what is unique along with what is not so unique about phage therapy, as viewed from a pharmacological standpoint. At the same time, we consider the place of phage therapy, and drugs generally, within the larger scheme that is biology. We make these latter considerations predominantly in terms of emergent properties, which are system characteristics that exist, qualitatively, at ‘higher’ but not ‘lower’ levels of organization. The latter is a relevant consideration especially in exploring the pharmacology of ‘living’ antibacterials, as are phages, which at lower levels can be viewed as collections of numerous molecules and biochemical pathways but which at higher levels become organized into somewhat complex entities that are capable of ‘self amplification’. Emergent properties are also prominently relevant to pharmacology, more generally, as they give rise to requirements for animal along with clinical testing to identify otherwise unexpected drug characteristics. Our broader goal is to stimulate a better integration of issues of phage therapy and pharmacology, predominantly in light of the substantial complexity of phages in comparison with chemical drugs and towards furthering the rational development of phagebased antibacterial strategies. Our chief conclusion is that while phages, due to their complexity, potentially possess numerous emergent properties when compared with less-complex antibacterials, in fact other aspects of phages – including their relative benignness, environmental ubiquity, and that their antibacterial properties are products of evolution – can allow for certain simplifications to pharmacological development. These simplifications are not as readily achieved by chemical drugs, such as antibiotics, which can possess negative properties that are difficult to predict.