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The history of bacteriophage therapy
1895
Ernest Hanbury Hankin observed that Chlora bacteria living in the Ganges and Yamuna rivers in India, were killed by something. However, the cause could not be further identified (E. H. Hankin, 1895).
1905
After many years of research, Ernest Hanbury Hankin was able to describe the phenomenon and published a paper entitled “On the Epidemiology of Plaque” (Hankin, 1905).
1915
The English bacteriologist Frederick W. Twort described an “ultramicroscopic virus” as a “transparent material,” which was able to destroy bacteria but could not multiply without them. Moreover, it showed no pathogenicity in infection experiments with laboratory animals (Frederick W. Twort, 1915).
1917
Felix d’Herelle named these bacterial killers “bacteriophages” and proved that they could be used as a therapeutic agent against dysentery-causing bacteria (Felix d’Herelle, 1917).
1923
Georgi Eliava Institute of Bacteriophages, Microbiology and Virology founded in Tibilisi, Georgia, by microbiologist Georgi Eliava (Chanishvili et al., 2022).
1933
Felix d’Herelle worked at the Georgi Eliava Institute (Chanishvili et al., 2022).
1939
Visualization of phages through the work of Helmut Ruska in Berlin (Ruska, 1942).
1941
Rejection of phage therapy by the physicians Monroe D. Eaton and Stanhope Bayne-Jones. Interest in bacteriophages was lost with the discovery of antibiotics (Eaton and Bayne-Jones, 1934; Krueger and Scribner E. Jane, 1941).
Today
The worldwide emergence of multidrug-resistant bacteria as causative agents of deadly infections has renewed the interest in phage therapy. Currently, work is in progress on an addition to the European Pharmacopoeia – general paragraphs (General Chapter) – to regulate the magisterial preparation and the therapeutic use of phages in human and veterinary medicine.
The basis for this is the General Monograph, Phage Active Pharmaceutical Ingredients, from Belgium. Already in 2016, Belgium was the first country in the EU to approve individual human therapy with magisterially produced phage suspensions. Annex II to Regulation (EC) 2019/6 also contains the EMA’s first guidelines on quality requirements for the use of bacteriophages.
References
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Chanishvili, N., Myelnikov, D., and Blauvelt, T. K. (2022). Professor Giorgi Eliava and the Eliava Institute of Bacteriophage. Phage (New Rochelle) 3, 71–80. doi: 10.1089/phage.2022.0016
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E. H. Hankin (1895). Observations on Cholera in India. Ind Med Gaz.
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Eaton, M. D., and Bayne-Jones, S. (1934). Bacteriophage Therapy. JAMA 103, 1769. doi: 10.1001/jama.1934.72750490003007
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Felix d’Herelle (1917). On an invisible microbe antagonistic to dysentery bacilli.
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Florian Georg Leupold (2018). Die Geschichte des VEB Serum-Werk Bernburg von 1954 bis 1990 unter besonderer Berücksichtgung biogener Arzneistoffe.
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Frederick W. Twort (1915). An investigation on the nature of ultra-microscopic viruses.
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Hankin, E. H. (1905). On the Epidemiology of Plague. J. Hyg. 5, 48–83. doi: 10.1017/s0022172400002357
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Krueger, A. P., and Scribner E. Jane (1941). The Bacteriophage. JAMA 116, 2269. doi: 10.1001/jama.1941.62820200013011
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Ruska, H. (1942). “Morphologische Befunde bei der bakteriophagen Lyse,” in Morphologische Befunde bei der bakteriophagen Lyse (Springer, Berlin, Heidelberg), 345–387.