Bacteriophage Clinical Use as Antibacterial "Drugs": Utility and Precedent.

For phage therapy-the treatment of bacterial infections using bacterial viruses-a key issue is the conflict between apparent ease of clinical application, on the one hand, and on the other hand, numerous difficulties that can be associated with undertaking preclinical development. These conflicts between achieving efficacy in the real world versus rigorously understanding that efficacy should not be surprising because equivalent conflicts have been observed in applied biology for millennia: exploiting the inherent, holistic tendencies of useful systems, e.g., of dairy cows, inevitably is easier than modeling those systems or maintaining effectiveness while reducing such systems to isolated parts. Trial and error alone, in other words, can be a powerful means toward technological development. Undertaking trial and error-based programs, especially in the clinic, nonetheless is highly dependent on those technologies possessing both inherent safety and intrinsic tendencies toward effectiveness, but in this modern era we tend to forget that ideally there would exist antibacterials which could be thus developed, that is, with tendencies toward both safety and effectiveness, and which are even relatively inexpensive. Consequently, we tend to demand rigor as well as expense of development even to the point of potentially squandering such utility, were it to exist. In this review I lay out evidence that in phage therapy such potential, in fact, does exist. Advancement of phage therapy unquestionably requires effective regulation as well as rigorous demonstration of efficacy, but after nearly 100 years of clinical practice, perhaps not as much emphasis on strictly laboratory-based proof of principle.