This Winnipeg scientist is using viruses to fight drug-resistant superbugs

Article By Karen Pauls Published December 28, 2023
Article Source: This Winnipeg scientist is using viruses to fight drug-resistant superbugs | CBC News

Cutting-edge bacteriophage research has human and animal applications

Steven Theriault is convinced he has the solution to an urgent global public health threat — antibiotic resistance.

But he can't get his bacteria-killing viruses approved through what he calls Canada's rigid and outdated regulatory system.

"The next big focus in science is actually genetics and live organisms. … I think we're going to create some really interesting therapies and technologies," he said during a recent CBC News visit to his lab.

"Hopefully in the future, the Canadian government will ... change the regulatory process, because this is actually something that will save lives in Canada as well as treat our animal flocks in Canada. And right now, we can't use it."

Theriault is a former paramedic who got his PhD in molecular genetics and virology and then spent 15 years working on projects like the Ebola vaccine at Canada's only Level 4 National Microbiology Lab in Winnipeg. He left in 2018 to start his own biotech company, Cytophage.

His research involves phages — or viruses of bacteria — which work by binding themselves to a bacteria and injecting their genetic information inside, creating more of themselves until they burst out of the bacteria, looking for more hosts to kill.

Phages were discovered in 1915 and were used to treat cholera during the 1927 epidemic, but the emergence of antibiotics in the 1940s eclipsed them. That is, until the rise of antibiotic-resistant bacteria.

The problem is, they are highly targeted — individual phages are very specific to their hosts. That's where Theriault and his team come in: they have been able to modify and genetically engineer phages that will attack a range of bacteria. 

Winnipeg scientist Steven Theriault and his team have genetically engineered phages that will attack a range of bacteria. While that may sound frightening, Theriault says there's no known way to perform gain of function research that would enable bacteriophages to cause disease in people.  

"It can only be weaponized against bacteria; cannot be weaponized against humans," he explained. "Doesn't infect human cells, doesn't infect animal cells. And you probably have about 100 trillion of them all over you right now."

Theriault believes bacteriophages are an answer to antibiotic resistance, which the World Health Organization (WHO) says is one of the biggest threats to global health, food security and development, associated with nearly five million deaths in 2019.

An era of drug-resistant pathogens

He's not the only one who believes that. Research being done at places like the University of Toronto, UC San Diego and the U.S. National Institutes of Health suggests "phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments" and may be an alternative to antibiotics in the era of drug-resistant pathogens.

The main cause of this resistance is antibiotic overuse in humans and animals, which kills some bacteria but allows others to mutate and develop defence mechanisms. A growing number of infections, including pneumonia, tuberculosis, gonorrhea and salmonella, are becoming more difficult to treat as the antibiotics are less effective on resistant superbugs. 

An estimated 70 per cent of all antibiotics around the world is used in animals. Until recent regulatory changes, Canadian producers gave antibiotics to livestock and poultry as a preventative measure. It had the side-effect of helping them gain weight, but also got into the groundwater and traces remained in the meat itself, such that the animals and people who consumed them started to harbour antibiotic-resistant bacteria. 

A Winnipeg biotech company has developed a cocktail of viruses that kill E. coli and salmonella in chickens. Also known as phages, it's believed the cocktail could be used to treat antibiotic-resistant bacteria that infect people.

Theriault and his team started their work on the resistance problem for humans, but soon expanded into agriculture.

They have developed and tested a product called FarmPhage, a cocktail of bacteriophages that kills E.coli and salmonella in chickens. In trials at the University of Saskatchewan's Vaccine and Infectious Disease Organization, the survival rate of chickens infected with E.coli was 92 per cent, compared to eight per cent of untreated birds.

In Bangladesh, their research found that when treated with FarmPhage, the chicken's protein content increased by 22 per cent, the amount of food they needed to grow decreased by 12 per cent and they reached their target size and weight two days sooner.  

Theriault said the birds are also healthier. When a flu swept through their barns, the chickens in Bangladesh getting FarmPhage survived better than those in the control barn.

Seeking approval in U.S.

He believes their product could also be adapted to treat people who have infections caused by drug-resistant superbugs.

Theriault has submitted FarmPhage for approval in the U.S. and hopes to start selling into that market in 2024. He's also looking to the European Union and Australia, which are developing regulatory frameworks for use there.

Theriault has not submitted it to Health Canada, because he said existing drug regulations are meant for chemical drugs, not products like bacteriophages, so it's impossible to fulfil all the requirements.

For example, Health Canada would require a field trial with a large number of chickens that can't enter the food chain after being given an unapproved drug. They would have to be slaughtered, something Theriault said is unacceptable from an animal welfare perspective.

This is a concern for other Canadian biotech companies as well, said Lauren Carde, vice-president of operations and regulatory affairs at Paul Dick and Associates, an animal health consulting company based in Guelph, Ont. It helps start-ups and multinational companies wade through government regulations, get products approved and then to market.

"The way that our regulatory system is set up is if you have a product that has an anti-microbial mode of action or is making therapeutic claims — so, claiming to treat, prevent, mitigate disease — that puts you into the drug category," she said.

Lobbying to change 'outdated' rules

In a statement, Health Canada said bacteriophages can be regulated differently depending on their purpose. For example, if it's used to prevent food from spoiling, it may be classified as a processing aid. If it's intended to prevent or treat disease in an animal, it may be classified as a drug. Products used to clean or deodorize animals may be considered consumer products.

Health Canada said it works closely with other regulators, including in the U.S., U.K., New Zealand and Australia, but is not aware of any approvals for the use of bacteriophages for the prevention or treatment of an animal disease or disorder in a "trusted" regulatory jurisdiction. It has not received a submission for FarmPhage or any other bacteriophage product for use in animals.

"Health Canada has been working with producer associations and veterinary groups over the last few years to understand their veterinary product needs, and work together on innovative and flexible ways to bring products to the Canadian market. However, we cannot compel a drug manufacturer to submit their product for authorization," the statement said.

Carde understands the role of Canada's regulatory system is to make sure any product being administered to animals is safe for them, doesn't pose a risk to environmental safety and is also safe for people eating meat products from that animal. But she said FarmPhage is one of the safest products she has worked with, because the animals don't absorb bacteriophages. There are no residues in the meat. The bacteriophages don't leave the gut until they are excreted as feces.

Given the pressure to reduce antibiotic use, Carde says Canada needs to change its rules to allow the use of bacteriophages as non-drug products. 

Health Canada is "outdated and I don't think they're keeping pace" with innovation and scientific breakthroughs, she said. "There needs to be room to be agile, to be flexible and to really be a catalyst to bring these products in."  

Carde worries small companies such as Cytophage will abandon Canada because of the small market size and high regulatory burden, putting Canadian producers at a disadvantage.

'Multiple opportunities in our industry'

Canadian producers are watching all of this closely. 

"We are very aware of the product, and in fact, we have helped Cytophage gather samples from farms as well as participated in trials," said Wayne Hiltz, executive director of the Manitoba Chicken Producers. "Once the technology receives approval, I think there are multiple opportunities in our industry where we can utilize the technology."

In the meantime, Theriault and his team have found a way to freeze-dry their FarmPhage cocktail and package it into doses that poultry producers can add to a chicken's drinking water.

"The reason we're doing that is because it gives it a forever lifespan. So then I can create these packets, we can send them to Bangladesh or to Africa, and they can use them and there's no fridge or no cold chain needed," he said, adding that by spring, the goal is to treat 25 million chickens in Bangladesh every month. "[To] save lives and feed them."