Nov 17, 2023

U of T Scientists discover a century of safe and effective use of Phage Therapy

Programs: Postgraduate, Programs: Undergraduate, Research: Genetics, Genomics & Proteomics, Research: Infectious diseases & immunopathology, Impactful research, Disruptive Innovation, Dynamic Collaboration, Alumni
Jonathan Cook and Greg German
L-R: Dr. Jonathan Cook and Dr. Greg German
By Jenni Bozec

“Phage therapy is an effective way to treat bacterial infections, without some of the drawbacks of antibiotics”, says Dr. Greg German. Not currently available as a treatment in Canada, scientists and physicians are currently fighting to raise awareness of this method as an adjunct to standard antibiotic therapy. 

Leading this effort is Dr. German, Assistant Professor in the Department of Laboratory Medicine (LMP) and Pathobiology, and Physician/Medical Microbiologist at Unity Health Toronto. Together with LMP medical microbiology resident, Dr. Jonathan Cook, they have recently published a comprehensive systematic review that uncovers how widespread and safe Phage therapy actually is. They hope with this evidence, to have set the stage for modern clinical trials that will prove efficacy and reduce regulatory barriers and ensure it becomes a treatment option for Canadians.

Phages are a bacterial virus that preys on bacteria. It targets a particular bacterium, then injects it with DNA to take it over and make more Phages. The bacteria explode and die, expelling up to 300 new Phages, which then search for their next target. We shouldn’t be concerned about introducing Phages into our bodies as we are already full of them - there are over a billion of them in every pea-sized amount of stool. 

“We can select the Phages we want, read their DNA code to confirm safety, and when necessary, train them with serial passage or edit them with molecular scissors to be more effective. In this modern way we can create a very targeted, specific treatment for a particular bacterium, and it will only affect that bacteria so side effects are very low, unlike with antibiotics,” explains German.

The team conducted a very broad, global, systematic review investigating all scientific studies that included Phages for the treatment of Urinary Tract Infections (UTIs). UTIs are a problem worldwide, affecting almost half a billion people each year. They looked at studies in all languages and all species with no time restriction. Payton Hooey, who completed the LMP Summer Undergraduate Research Program (SURE), in German’s lab co-authored the paper with Amany Al-Anany from McMasters University. Julia Martyniuk from the U of T library and Dr. Alexander Hynes and Dr. Lori Burrows also from McMaster, all contributed to the paper. 

“Up until recently it was believed there had been only a handful of cases, but through our systematic review we have identified more than 1,400 unique human cases of Phage therapy to treat urinary tract infections since 1926. Overall, the success rate was at 50-80% and only 1% had side effects. Typically, around 5-6% of people have side effects from antibiotics . That’s been the magic of this study – to find out that we've been using Phages safely for a long time, and now we should be looking at it much more closely from a regulatory standpoint,” explains German.

Phage therapy was widely used in the 1920s as  Eli Lilly and Company, Stanford University, Baylor College of Medicine and Yale University, amongst others, had strong Phage programs. With the lucrative and successful introduction of antibiotics during World War Two, Western countries largely abandoned Phage therapy to focus on developing antibiotic. A few countries in Eastern Europe, have maintained their programs and still use Phage therapy today.

Cook adds, “There is an urgency for new and innovative medicines to fight against antimicrobial resistance which makes Phage therapy a very exciting field. As this technology has taken a backseat to antibiotic development, we find ourselves now trying to catch up as a discipline but we're making progress. Once the technology fully matures, we'll be able to develop on demand medicines to treat otherwise untreatable infections. There are drawbacks with any medicine, but what we have found through our literature review is that the safety profile of Phage therapy is impressive compared to any broad-spectrum antibiotic.”

German and his colleagues are involved in many groups and initiatives trying to raise the profile of Phages as an alternative, or complementary, treatment. “We are running out of tools and often the tools that are available are not making it to Canada. Only three out of 18 recently approved antibiotic drugs in the global context are currently available in Canada which is a tragedy. We need more alternatives to stop killer bacteria and harnessing bacteria’s natural enemy is increasingly considered a safe, cost-effective tool that we need to move forward in this country”.

Read the full paper in Phage

Dr. Greg German's faculty profile

The LMP Summer Undergraduate Research Experience (SURE)

Read more on phage therapy

Driving a new era of Phage Therapy research and innovation

Greg German writes in Maclean's Superbugs are overpowering antibiotics. We should fight them with phage therapy

More on microbiology

Residency training in Medical Microbiology (for MDs)

Postdoctoral Diploma Program in Clinical Microbiology (for PhDs)

Dr. Tony Mazzulli, Medical and Clinical Microbiology Program Director, answers our 'Humans of LMP' Q&A

Donate to Bacteriophage Therapy Research and Innovation

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This story showcases the following pillars of the LMP strategic plan: Dynamic Collaboration (pillar 2), Impactful Research (pillar 3), Disruptive Innovation (pillar 4) and Agile Education (pillar 5).