Guest Blog: Phage Therapy - The Other Antibiotic Treatment

by G.W. (Bill) Riedel, PhD, MCIC

If I suggested that a cure for the cholera outbreak in Haiti could be found in the same rivers thought to be responsible for the outbreak in the first place, most people would consider me crazy. But they’d be wrong.

In 1896 the British bacteriologist, Ernest Hankin discovered marked antibacterial activity – against Vibrio cholerae, the bacterium that causes cholera – in the waters of the Ganges and Jumna rivers in India. He suggested that an unidentified substance (which passed through fine porcelain filters and was destroyed by heat) was responsible for this phenomenon and for limiting the spread of cholera epidemics.

It wasn’t until 1917, though, that French-Canadian microbiologist Felix D’Herelle – working at the Pasteur Institute – realized that the antibacterial activity discovered by Hankin was due to viruses that preyed on bacteria. D’Herelle named these viruses “bacteriophages” (phages for short).

Bacteriophages are viruses that are parasitic to bacteria and cannot multiply independently. Each phage can only infect a specific bacterial host, as it has to be able to link with special structures on the surface of the bacterial cell. Once attached, the phage injects its DNA into the host cell. The phage DNA hijacks the reproductive mechanism of the bacterial cell, causing the infected bacterium to produce 50 to 200 daughter phages in as little as 30 minutes. Finally, the infected cell bursts – releasing the new crop of phages and starting another cycle of infection and phage reproduction.

Prior to the discovery of the electron microscope in 1940, no one could see bacteriophages, even with high-powered conventional microscopes. Early studies of phage behavior and reproduction depended on adding phages to liquid cultures in which bacteria had grown, and observing the clearing of the turbid broth and destruction of the bacteria. In other experiments, scientists observed and counted clear zones in layers of bacterial growth on solid culture media.

Soon after he discovered and named bacteriophages, D’Herelle began to experiment with the possibility of using phages to cure, and even prevent, bacterial infections. The fruits of his efforts survive to this day in Tbilisi, Georgia at the Phage Therapy Center, which welcomes patients from all over the world.

In Poland, at The Hirszfeld Institute and of Immunology and Experimental Therapy, phage therapy is carried out under medical experimentation, ethical and compassionate use regulatory provisions similar to those that exist in most countries. A broad range of infections have been treated since the initial anti-staphylococcal treatment in 1925. The Institute requires that all patients treated must have previously been treated – unsuccessfully – with conventional methods such as antibiotics. Since the 1980s, their work with phages has been published in English language scientific journals. Very high success rates – 85% on average – have been obtained for infections caused by bacteria such as Escherichia, Klebsiella, Proteus, Enterobacter, Pseudomonas, and Staphylococcus aureus. Their success rates for treating Pseudomonas aeruginosa and Staphylococcus aureus, including MRSA strains, have been reported to be even higher than 85%.

Phage biology was not well understood in D’Herelle’s time, and results from early attempts at phage therapy treatments were inconsistent. Once antibiotics appeared, interest in phage therapy in the West waned – until antibiotic-resistance and superbugs rekindled research efforts. As of this writing, Phase I trials of phage therapy treatments are being planned or have been completed in the United Kingdom, Belgium, Australia and India.

In the USA, “phage therapy” (a.k.a. biocontrol) has received the most attention – and the greatest acceptance – in non-clinical applications. The FDA recognizes a bacteriophage preparation made by Intralytix as a safe antimicrobial for control of Listeria monocytogenes on ready-to-eat meat and poultry products. Another phage preparation, Agriphage, a phage product that is commercially available from Omnilytics, is used primarily to treat bacterial damage of tomatoes and peppers, and has been recognized as being compatible with organic food production. The status of clinical phage therapy in the US was laid out clearly in a March 31, 2009 Popular Science article, The Next Phage.

Is it absurd that phage biocontrol products are accepted in the West for prevention or treatment of contamination in food, but not available to patients suffering from antibiotic-resistant infections? I, for one, think so. If you are interested in learning more and forming your own opinion, the following resources will be helpful.

• Thomas Haeusler. 2006. Viruses vs. Superbugs, a solution to the antibiotics crisis?
• Monk, et al. 2010. Bacteriophage applications: where are we now? Letters in Applied Microbiology, 51, 363-369.
• Kutter, et al. 2010. Phage therapy in clinical practice: Treatment of human infections, Current Pharmaceutical Biotechnology, 11, 69-86.
• Bacteriophages in the Control of Food- and Waterborne Pathogens, Editors: Parviz M. Sabour and Mansel W. Griffiths, ASM Press, 2010.
• Killer Cure: The Amazing Adventures of Bacteriophage (Canadian-made movie)

About the author: Before his retirement from Health Canada, G.W. (Bill) Riedel, PhD., MCIC, was Chief, Program Development and Evaluation Division, in Health Canada’s Field Operations Directorate. Bill organized and moderated a symposium entitled "Phage therapy as it applies to food public health bacteriology" at the 2003 Annual Meeting of the Institute of Food Technologists in Chicago, and he has given a number of presentations on phage therapy.