How a Winnipeg entrepreneur is using Mother Nature’s deadly weapon to fight antibiotic-resistant superbugs
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Steven Theriault was enjoying steak and mashed potatoes at a restaurant near Toronto’s Pearson International Airport when somebody at the table mentioned a photograph of his right foot. The prompt sent the French-Canadian microbiologist and chief executive of Winnipeg-based Cytophage Technologies Inc. scrolling through his smartphone in search of a photo he took after a mishap, involving a pair of scissors and the family dog, that left him with a nasty gash on the aforementioned appendage.
Within a week, the cut had bloomed into a sore, suppurating mess. Theriault sent a picture of it to his father-in-law, an emergency room doctor, who recommended antibiotics. It was sound medical advice, offered from a place of wisdom and caring. But instead of following doctor’s orders, the scientist followed his curiosity, using his infected foot as a guinea pig.
“We were goofing around in the lab,” he said. “What we wanted to determine was whether we could create a bacteriophage that would treat the infection in my foot and use it instead of antibiotics.”
Bacteriophages, or phages for short, are Mother Nature’s ultimate assassins: good guy viruses, existing everywhere and too numerous to count, that evolved over the millennia to kill bacteria. (Loosely translated from its Greek root, bacteriophage means bacteria eater.) To kill bacteria, a phage must be matched to it, making them apex predators — think: lions to zebras — though of a highly specialized sort.
Some people think phages could be the solution to the growing crisis in antibiotics, chiefly that hospital-born superbugs are proving to be drug-resistant, putting patients at extreme risk of dying from infections once cured by popping pills. Theriault, in toying around with phages, has positioned himself at the cutting edge of a potential bio-medical revolution, making him one to watch and, for those laid low by runaway infections, perhaps one to root for.
It is good thing then that the 45-year-old isn’t just some amateur scientist with a home chemistry kit and a dream. Theriault holds a doctorate in molecular genetics and virology from the University of Manitoba and is the former head of applied biosafety programs at the federal government’s National Microbiology Laboratory in Winnipeg, in addition to being an infectious disease adviser to the World Health Organization. He was also a contributing researcher to the made-in-Canada Ebola vaccine deployed against the killer virus in West Africa.
In sum: he has some serious scientific chops.
“Most exotic viruses, I’ve touched,” he said.
Three years ago, the 45-year-old left his government job to found Cytophage, a biomedical startup with the potential, he believes, “to become the Apple of infectious disease control.” It is an ambitious boast, even coming from a pitchman with a PhD.
But Theriault is not the first French-Canadian to view phages as an answer to the bacterium that increasingly ails society at an exorbitant cost, both health-wise and economic.
Earlier this year, the Council of Canadian Academies released a 268-page report with an ominous title: When Antibiotics Fail. Scarier still were the facts in the report, such as: approximately 5,400 Canadians in 2018 died as a direct result of so-called superbugs, while the hit to the economy, due to deaths and illnesses associated with drug-resistant infections, rang in at $2 billion.
Projecting forward, the numbers will get worse, with more bugs, more deaths, more money spent and, in the world beyond the experts, a presumably growing fear among the general, otherwise healthy public that being in hospital is a dangerous place to be.
“By 2050, a total of 256,000 lives could be lost in Canada,” the report warns.
It is an apocalyptic public health vision Felix d’Herelle might have appreciated were he still alive today. The globetrotting, self-trained Montreal scholar, with a quick temper and a penchant for ticking off Nobel laureates, is credited with discovering phages, and was the first to use them medically as a treatment for dysentery in 1919.
Among d’Herelle’s other projects was being commissioned by the Canadian government to make schnapps out of maple syrup, an experiment, alas, that failed. Word got around, however, of what he was up to with phages, ushering in a golden age of phage research/experimentation in the pre-penicillin years when a cut leg could lead to amputation, and contracting pneumonia was often a death sentence.
Phage therapy boomed, albeit with mixed results, while d’Herelle bounced from place to place, including the Soviet Union, where he dedicated a book he wrote to Joseph Stalin.
By the time of d’Herelle’s death in 1949, penicillin had emerged as a wonder drug, and the way of the future. Phage therapy, outside the former Soviet Union, slid to the fringes, until another Canadian — this time an Anglophone from east-end Toronto — surfaced with a miraculous story to tell.
Steffanie Strathdee first heard the term phage during a virology lecture at the University of Toronto in the mid-1980s. Thirty years later, that lecture would bubble to mind as her husband, Tom Patterson, lay dying in a San Diego hospital bed; comatose, with failing organs and a body shot through with a superbug infection.
“I thought, I know what phages are,” said Strathdee, an infectious disease epidemiologist and co-director of the new centre for Innovative Phage Applications and Therapeutics (IPATH) at the University of California San Diego (UCSD).
In a last-ditch attempt to save her spouse, Strathdee began hunting for phages, sourcing a batch from the United States Navy, and another from a researcher at Texas A&M University. Chip Schooley, chief of infectious diseases at UCSD’s school of medicine, pumped billions of the bacteria killers into Patterson’s bloodstream.
No one knew what to expect next.
Three days later, Patterson woke up. Three months later, his body-wide infection had been wiped out.
Strathdee told her story to journalists and later wrote a book, The Perfect Predator: A Scientist’s Race to Save Her Husband from a Deadly Superbug. Meanwhile, phages had a viral moment, publicly, so much so that a forgotten treatment method, discovered a century ago by an egomaniac French-Canadian, entered the conversation around how best to combat bacterial infections in the age of compromised antibiotics.
“I have kind of made it my mission not only to raise awareness about superbugs, but also to resurrect a 100-year-old forgotten cure,” Strathdee said, stressing, as Steven Theriault readily does, that there is much “science” — not to mention rigorous clinical trials — to be done if phages are to shift from the alternative medicine cabinet to a mainstream treatment option.
Brett Finlay, chair of the expert panel behind the When Antibiotics Fail report, and a world-renowned microbiologist, describes phage therapy as a “cool” concept with “lots of promise,” but one “that hasn’t been clinically proven in most cases.”
Most exotic viruses, I’ve touched
In ways, Theriault is both the perfect and a perfectly unlikely scientist/entrepreneur to pick up the torch d’Herelle initially lit.
For starters, his background is more blue collar than lab coat. His parents ran gas stations around northern Ontario, hopping from town to town. Their son would come home from school, drop his books, grab his BB gun and head out hunting, something he still enjoys doing today — either with a bow or rifle — at the 59-acre farm outside Winnipeg he shares with his wife, Natasha, two young daughters and two dogs.
The family grows its own food and is famous among a small circle of people for their canned sour cherries, as well as the garlic-flavoured pepperette sticks Theriault prepares from deer meat.
“I grew up in the woods,” he said.
For kicks, Theriault rock climbs; for rest, he sleeps three hours a night, waking to a cup of tea, a ritual followed by a workout on his climbing wall, next to the lab in his home. (His away-from-home lab is Cytophage’s Winnipeg headquarters, near the university campus).
The outdoorsman wound up in Manitoba studying microbiology after a stint as an air ambulance paramedic in Thunder Bay, Ont. His abundant energy and varied interests were soon evident to Deborah Court, a professor he studied under.
“Steven has imagination, he can see all sorts of niches where things could work,” Court said, adding that she was not surprised to see her former pupil walk away from a good job with a secure pension at a government lab to strike out on his own.
“Steven was always very willing to try the next thing and to go forward quite fearlessly,” she said.
Philosophically, Theriault always wanted to be part of something big, and Ebola was huge, but at the same time limited in scope. It is a terrifying virus, with about a 50-per-cent mortality rate, and yet it has only killed about 15,000 people globally since first being identified in 1976.
Comparing Ebola to superbugs is apples to oranges. What drew Theriault to phage therapy was that it presented both a puzzle to be solved, and a potential weapon in the fight against superbugs. For someone looking to grab hold of something big, phage therapy, in theory, was it.
“I didn’t get into this to get rich,” Theriault said. “I want to help people.”
Earnest as the scientist may be, helping people has a way of paying off. Canadians filled 24 million drug prescriptions in 2017, according to government figures, while the domestic pharmaceuticals market is an annual $20-billion-plus business. As a nation, we are addicted to drugs, and now some of those drugs are faltering, creating a substantial market opportunity for the rise of something new or, in this case, something old.
I didn’t get into this to get rich. I want to help people
Phages, of course, are not a cure-all. One of things that keeps Theriault, never a big sleeper anyway, awake is their pickiness as predators. To kill bacteria, a phage has to be a match, and finding matches in nature can be like finding a needle in a haystack. To shortcut the search, Theriault and his team have developed synthetic phages — lab-made bacteria killers — that allow him to produce phages à la carte, as per need.
“What Steven is doing is the future,” Strathdee said. “It is terribly exciting.”
Notwithstanding the excitement, North American consumers needn’t bother inquiring about the bacteria-killing wonders at their local drugstore anytime soon. It is early days, and Theriault is the first to say so.
Lately, he has been preoccupied with chickens, specifically, a bunch of hatchlings at the Vaccine and Infectious Disease Organization facility at the University of Saskatchewan in Saskatoon. He bombed the birds with a lethal dose of E. coli before treating them with a synthetic phage, instead of antibiotics.
The survival rate of the treated birds, according to Theriault, was 92 per cent, while only eight per cent of the untreated birds pulled through.
Cytophage’s near-term business plan (he was in Toronto meeting with investors) is to break into the poultry market, prove phage therapy works, gain momentum as a company and, ultimately, pivot to humans, which should lead to more conversations about the company founder’s infected right foot.
And about that foot: after not taking his father-in-law’s advice, Theriault began swabbing the wound with his phage concoction. Ten days later, there was no trace of infection left.
“It worked,” he said.
It is a compelling yarn, related over lunch, and, its storyteller cautions, a one-man clinical trial is statistically insignificant.
“We have a lot of science to do,” Theriault said. “But if everything we are working on as a company comes to fruition, think of the biggest pharmaceutical company. We could be that big.”