I have a clear memory of sitting on a Toronto-area park bench in 1985 as my dad—a computer executive and jack-of-all-trades—explained the arms race between our cells and a new virus called HIV. The military metaphor worked for me, an 11-year-old burgeoning physician-scientist with a fascination for jets and Transformers. I thought, Wow, there’s a battle going on inside us, and we have to find the right weapon to win it. That analogy hung on through my adult years and graduate work in microbiology, where I studied phages: tiny, bacteria-destroying viruses alternately known as “nanobot soldiers,” “viral smart bombs” and “the perfect predators.”
Phages, or bacteriophages, get their name from the Greek word for “devour,” and their food of choice is bacteria. In nature, there are more phages than any other entity; these microbes live in soil, seawater and our bodies. (For reference, there are billions of phages in the human gut alone.) Their main objective is to replicate, which they achieve by injecting their DNA into nearby bacteria with the help of external receptors. The bacteria explode and die, expelling up to 300 new phages, which then search for their next target.
More than a century ago, a Franco-Canadian scientist named Félix d’Hérelle—previously known for making whiskey from maple syrup—discovered that these little killing machines could be used to cure infections like shigellosis, which affects the intestines. In its 1930s heyday, phage therapy—which involves phages being applied topically or orally—caught the attention of experts at France’s Pasteur Institute, the pharma company Eli Lilly and several American universities. But once that magic drug penicillin came along, Western medicine sent phage therapy to the fringes and leaned into antibiotics, which could be mass-produced and were more widely effective and, therefore, more profitable. In doing so, we inadvertently started another arms race.
Antimicrobial resistance, also called AMR, has led to the rise of drug-resistant superbugs. It’s the new pandemic, albeit a silent one. We saw resistance to penicillin as early as 1942, but thanks in part to doctors prescribing antibiotics like candy for decades, the problem is now becoming catastrophic. I am already hearing about patients undergoing radical surgery or hospitals paying tens of thousands of dollars to ship end-of-the-line antibiotics over the border from the U.S because we’ve run out of effective ones up here. And by 2050, more people are expected to die annually from AMR than from cancer. They will also die from complications following very straightforward procedures, like knee replacements. Usually, those surgeries come with a one per cent chance of infection. If that infection is drug-resistant, your seemingly simple joint surgery could become a death sentence.
Others may die from simple skin infections. Madonna, a high-profile case, visited the ICU with a serious bacterial infection back in June. Years ago, my own mother died of a drug-resistant urinary tract infection that she contracted in a long-term care facility.
In search of alternative treatments, many Canadian medical professionals are looking, once again, to phages. Health Canada has deemed phages safe enough to spray on food products like meat to knock down bacteria counts, but at the moment, they’re not approved in health-care settings, except in clinical trials. Meanwhile, phage therapy is flourishing in other countries. After antibiotics went mainstream, Félix d’Hérelle headed to the Soviet Union to continue his research and later helped to found the Eliava Phage Therapy Center in Tbilisi, Georgia, a country where you can receive phage-filled ampoules over the counter for as little as $2. The centre shares its innovations with other European countries, like the Netherlands and Belgium. Since 2000, Belgium has treated 150 patients with phage therapy; Canada, which has almost four times the population, has treated two.
Earlier this year, my clinic at St. Joseph’s Health Centre in Toronto completed the first Canadian trial to successfully use phages to treat a drug-resistant urinary tract infection. For years, our patient’s particular strain of E. coli thwarted all of the half-dozen antibiotics prescribed to her and cost her a kidney. Because Canada’s phage ecosystem is still relatively underdeveloped, we had to send a sample of the patient’s bacteria to a lab at the Baylor College of Medicine in Houston, Texas, which matched her strain with three phages and mailed us the winning cocktail. The patient’s condition began to improve 48 hours after we gave her an oral dose of phages. But importing phages isn’t sustainable. That one shipment cost us roughly the equivalent of a cab ride to Texas.
Even with all the new enthusiasm around personalized medicine—which phage therapy very much is—we’re still years away from seeing this treatment in Canadian clinics and hospitals. Right now, there’s no way for patients to charge insurance for phage therapy, and randomized control trials are hard to do when infections require a blend of targeted phages tailored to treat each individual case. What Canada can do in the meantime is become a major market for phage production, supplying researchers here and abroad. The University of Laval is in the process of expanding its phage depot, and the University of Toronto (where I work) is establishing an accelerator that’ll fund grants for phage therapy research for human and animal care.
Phage-centric startups are popping up, too: Qeen BioTechnologies, located just outside Ottawa, supplies phages for international clinical trials and compassionate cases and is aiming to have a full production facility up and running by this coming December. Winnipeg’s Cytophage is working on treatments that might one day replace antibiotics used for growth and disease prevention in livestock—such as broiler chickens—as well as new SARS vaccines.
One of the biggest hurdles to making this treatment mainstream, aside from regulation, is a lack of awareness around phage therapy’s life-saving potential. My goal is to make phage therapy a topic of discussion everywhere from our dinner tables to the highest levels of government. We should never underestimate the power of a single case—or a single phage—to move the needle: since my team’s UTI trial wrapped in the spring, I’ve received roughly 40 calls from Canadians contending with superbugs who want to give phage therapy a go.
I often think about an analogy from my colleague Jon Iredell, an infectious-disease physician and microbiologist in Australia. He often compares medicine’s infection-fighting strategy to a three-legged table. One leg is antibiotics (appropriately used), another leg is vaccines and another is phage therapy. (In my opinion, the fourth, invisible leg is our own immune systems.) For simple skin ulcers or UTIs, I’d say try phages first, while more complicated infections might merit stronger antibiotics. Antimicrobial resistance is a battle that can’t be won on one front. It’s going to take every weapon we’ve got.