Introducing yesterday‘s phage Therapy in today‘s Medicine

Abstract

The worldwide emergence of ‘superbugs’ and a dry antibiotic pipeline threaten modern society with a return to the preantibiotic era. Phages – the viruses of bacteria – could help fight antibiotic-resistant bacteria. Phage therapy was first attempted in 1919 by Felix d’Herelle and was commercially developed in the 1930s before being replaced by antibiotics in most of the western world. The current antibiotic crisis fueled a worldwide renaissance of phage therapy. The inherent potential of phages as natural biological bacterium controllers can only be put to use if the potential of the coevolutionary aspect of the couplet phage–bacterium is fully acknowledged and understood, including potential negative consequences. We must learn from past mistakes and set up credible studies to gather the urgently required data with regard to the efficacy of phage therapy and the evolutionary consequences of its (unlimited) use. Unfortunately, our current pharmaceutical economic model, implying costly and time-consuming medicinal product development and marketing, and requiring strong intellectual property protection, is not compatible with traditional sustainable phage therapy. A specific framework with realistic production and documentation requirements, which allows a timely (rapid) supply of safe, tailor-made, natural bacteriophages to patients, should be developed. Ultimately, economic models should be radically reshaped to cater for more sustainable approaches such as phage therapy. This is one of the biggest challenges faced by modern medicine and society as a whole.

Predation in Homogeneous and Heterogeneous Phage Environments Affects Virulence Determinants of Pseudomonas aeruginosa

“…At an estimated total of 10 31 , bacteriophages are the most abundant biological agent on earth (16) and, based on their prevalence and effects on prokaryotic communities, they can play a significant role in bacterial survival, activity, and evolution (17). The rise of variants in the presence of lytic phage has been one of the foundations for evolution studies (18)(19)(20)(21)(22)(23)(24)(25); however, this is also one of the reasons why phage therapy has always been considered with skepticism by the medical community (26). The current rise of antibiotic-resistant bacteria is forcing researchers to look for alternative treatments, and phage therapy has proven to be promising in several animal case studies (27)(28)(29)(30)(31), as well as in human clinical trials (32,33).…”

Viruses That Can Cure, When Antibiotics Fail...

“…A specific European regulatory frame with realistic production and documentation requirements, which allows a timely (rapid) supply of safe, tailor-made, natural bacteriophages to patients, is a must [13]. Fundamental changes of mentality in the medical and pharmaceutical environment are essential for a successful re-introduction of bacteriophage therapy into modern Western medicine [53].…”

Re-establishing a place for Phage Therapy in Western Medicine

“…A number of companies are pursuing phage therapy preclinical research, serve as suppliers of existing products or function as facilitators of phage-therapy services for those individuals who are able and willing to travel [15]. Notwithstanding the extensive need, interest, experience and reported successes of phage therapy, typical western approaches to biomedical research and implementation are poorly adapted to motivate, regulate or assess such nonstandard approaches to antibacterial therapy [5,16].…”

“…Today, in the west, phage therapy suffers from insufficient credibility, patient and physician unfamiliarity and related limited product availability. This ties in with a very challenging regulatory environment that, although in many ways supportive of phage therapy development, is both expensive and poorly suited to harnessing the power of what could be an abundance of relatively inexpensive, diverse and safe antibacterial agents [5,6,16,18].…”