Bacteriophage therapy
non-uniform progression within the host but also for its ability to evolve with treatment and demonstrate adaptive behaviour. 4
Bacteriophage therapy (phage therapy in short) refers to the therapeutic use of bacterial viruses (i.e., bacteriophages, phages in short) to treat bacterial infections. Bacteriophages have been exploited for their range of applications since their discovery in 1915. 5 Phage therapy was immediately recognized as a therapeutic approach to treat bacterial infections, and the therapeutic use of phages was first officially reported by French- Canadian microbiologist Félix d’Hérelle in 1919. 6 In the 1940s, the advent of broad-spectrum antibiotics, which were widely regarded as the almighty panacea, signalled the inevitable decline of phage therapy in the western world. On the other side of the Iron Curtain, however, phage therapy survived as an established treatment. 7 Although the practice has been undergoing great struggles to develop over the decades of neglect in the west, it is currently witnessing a return of renewed interest, both academically and clinically, with the growing demand for phage therapy for terminally ill patients with antibiotic-resistant superbug infections. A small number of successful intravenous (IV) phage therapy have been recently reported. 8 It is generally agreed that common antibiotics are immutable and usually unspecific chemicals that target a range of bacteria, whereas phages are considered as living, dynamic, and specific entities continually evolving following the co-evolution patterns during the interaction with their hosts. 9 Apart from treating bacterial infections, phages have also exhibited their therapeutic potential as efficient platforms for precise therapeutic delivery, including delivering chemotherapeutic agents and genes for cancer treatment. 10 Nevertheless, challenges persist as phages are not suited to any commonly accepted existing regulatory categories, norms or development models for their evolving identity. Apart from the residual socio- political scepticism of a practice generally perceived to be associated with the Soviets, the long- established dominance of antibiotics has also given rise to an epistemological infrastructure that acts as a serious impediment to the seeming rise of phage therapy in the west. 11
A brief history of phage therapy
The evolutionary battle for survival between phages and their hosts, bacteria, has been non-stop since time immemorial. The predator and prey relationship in the microscopic world had been kept behind the veil of nature as a secret until the year 1896 when English bacteriologist Ernest Hankin observed the antiseptic action of the waters of the Ganges and Jamuna rivers in India against vibrio cholerae . 12 The presence of this report was long neglected and lay fallow until the 1915 publication of Frederick Twort, in which he described the mysterious microbe as ‘a transparent bacteriolytic agent of enzymatic nature that dissolved up the micrococci’ and hypothes ized that the dissolving effect was caused by ultra- microscopic viruses. 13 Two years later, Félix d’Hérelle also independently discovered and isolated the invisible microbe with antagonistic properties against the pathogenic bacilli from the stool of dysentery
4 Sanmukh & Felisbino, 2017. 5 Twort 1915.
6 D’Hérelle, 1931. 7 Häusler, 2008. 8 Dedrick et al. 2019; Schooley et al. 2017. 9 Williams 2009. 10 Sanmukh & Felisbino 2017. 11 Brives & Pourraz 2020. 12 Hankin 1896. 13 Twort 1915.
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