The Pioneers of Phage Virology

One of the most surprising things for me in starting my ‘phage journey’ was just how long we have known about bacteriophages and their potential.  And yet we still have so much to learn!  It made me curious as to who discovered phages in the first place, and how.  In reading the blog posts from previous Massey University Phage Hunters I really enjoyed the variety of content, especially posts that explored a particular area of interest for that student. So, I decided to look into the history of phage discovery, and add my ‘slice to the pie’.  I hope you enjoy it.

Todar - Electron Micrograph (left) and model (right) of bacteriophage T4

Electron micrograph (left) and model (right) of bacteriophage T4 (Todar, 2012)

Ernest Hanbury Hankin was a bacteriologist working in India, who in 1896 discovered that cholera bacteria were susceptible to an organism in the Ganga and Yamuna rivers (Wittebole, Roock, & Opal, 2014).  The nature of the organism was unknown, but it was small enough to be able to permeate millipore filters used to retain bacteria in solution.  He didn’t know what it was, or how to see it, but he knew it was there.

In 1915, Frederick William Twort was trying to grow a viral strain on agar when he observed not only colonies resulting from bacterial contamination of his sample, but a strange morphology of what he assessed to be colonies of different bacterial strains (Kutter & Sulakvelidze, 2004).  They appeared either entirely or semi-transparent, and Twort realised that these ‘colonies’ were actually areas of bacterial cell degeneration.  Twort hypothesised that this could be due to an enzyme or virus too small to be seen by microscope.

Now remember, every time one of your fellow students is disappointed at returning to the lab and finding no plaques, despite the care and consideration that went into their method, you can tell them that over 100 years ago, ol’ Freddy got them without even trying.  Not only that, but they were the result of what would today be considered poor lab technique.  Some people get all the luck.

Stent - A picaresque genius

Felix d’Herelle (Stent, 2000)

Two years after Twort’s happy accident, microbiologist Felix d’Herelle made the independent discovery of a microorganism which appeared to utilise and destroy bacteria in the process of its own reproduction, resulting in cleared areas of cell death on bacterial lawns.  He called the cleared areas ‘plaques’, and concluded that they were the result of a virus that attacked bacteria (Kutter & Sulakvelidze, 2004).  These characteristics were the basis for d’Herelle naming this type of virus Bacteriophage.

I tried to figure out how d’Herelle knew that these strange little bacteria-assassins were viruses, but access to a published copy of his work that is accessible either online or in little ol’ New Zealand, and also conveniently published in English, may take a little more digging to come by.  I don’t think it’s unreasonable to assume that viruses were at the forefront of every microbiologist’s mind back then, having been only recently discovered in the late 1890’s (Zimmer, 2015).  I try to imagine what their thought process would have been to reach the conclusions that they did.  I suppose that despite a lack of knowledge, it may have been an easier process to discover new evidence, rather than have a wealth of education as a resource to search for the answer to a specific question.

The concept of ‘phage therapy’ was also introduced by d’Herelle (Fruciano & Bourne, 2007); he was one of several microbiologists who worked to isolate bacteriophages that targeted several known bacterial pathogens, and began to experiment in treating disease with phage therapy.  These treatments were successfully involved in the combat of multiple staphlycoccal, intestinal and systemic infections.

Lipman - vials of phage from Georgia, Eurasia

Vials of phage from Georgia, Eurasia (Lipman & Ferguson, 2015)

Phage therapy was not widely embraced by Western countries, though it is practiced extensively in Russia, Poland and Georgia as a result of previously restricted access to antibiotics (Reardon, 2014).  Its relative safety and predicted longevity in comparison to antibiotic treatments have many touting it as the way forward in a time when the growing antibiotic resistance of many bacteria is a rising threat.  If this is where we stand after 100 years of limited bacteriophage research, imagine what we could potentially achieve in the future with more widespread involvement.

 

References:

Fruciano, D. E., & Bourne, S. (2007). Phage as an antimicrobial agent: d’Herelle’s heretical theories and their role in the decline of phage prophylaxis in the West. The Canadian Journal of Infectious Diseases & Medical Microbiology, 18(1), 19–26.

Kutter, E., & Sulakvelidze, A. (Eds.) (2004). Bacteriophages: Biology and Applications. Florida: CRC Press.

Lipman, M., & Ferguson, A. (2015). Bacteriophage: Good Guys of the Virus World. Evergreen Magazine, Spring/Summer.

Reardon, S. (2014). Phage therapy gets revitalized. Nature, 510, 15-16.

Stent, G. S. (2000). A picaresque genius. Nature, 403, 827-828.

Todar, K. (2012). Bacteriophage. Todar’s Online Textbook of Bacteriology.  Retrieved from http://textbookofbacteriology.net/phage.html

Wittebole, X., Roock, S. D., & Opal, S. M. (2014). A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens. Virulence, 5(1), 226-235. doi:10.4161/viru.25991

Zimmer, C. (2015). A Planet of Viruses: Second Edition. Chicago: The University of Chicago Press.

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About jcturnbullnz

BSc Genetics student and novice phage hunter
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