By Petra Dreiser

It has emerged as one of the major challenges to modern medicine and healthcare globally: antibiotic resistance. According to the WHO, more than a million deaths result directly from drug resistance to bacterial infections every year, and almost 5 million more are associated with it. How can we counter this increasingly pernicious development? 

“It’s at base an evolutionary problem,” says Nicole Mideo, an associate professor in the Department of Ecology & Evolutionary Biology (EEB) who studies patterns of evolution in infectious disease. With time, bacteria adapt to the medications meant to destroy them, selecting for variations that neutralize the treatments. The prevalent use of antibiotics over the past century has contributed to the emergence of multidrug-resistant “superbugs,” which render conventional therapeutic approaches ineffective.  

To researchers like Mideo, however, evolutionary principles don’t just form the foundation of antibiotic resistance; they also hold the promise of solving this potentially catastrophic issue. “It makes sense to find evolutionary solutions to an evolutionary problem,” she says.  

“It makes sense to find evolutionary solutions to an evolutionary problem.”

One colleague who could not agree more is Paul Turner, Rachel Carson Professor of Ecology & Evolutionary Biology at Yale University, and Microbiology faculty member at the Yale School of Medicine. His proposed solution for a viable antimicrobial alternative: phage therapy.  

It was the topic of his 2026 Martin Lecture, hosted by EEB and titled “Leveraging Evolutionary Trade-Offs in the Development of Phage Therapy.” Turner, whose work examines viruses as malleable agents in evolving bacterial systems and the impact of those interactions on infectious disease and antibiotic resistance, presented his research to an audience of almost 200 at Innis Town Hall, before joining a panel discussion with Mideo and two additional colleagues from the University of Toronto: Greg German (UHN, Phage Canada, and Laboratory Medicine & Pathobiology, Temerty Faculty of Medicine) and Arjumand Siddiqi (Dalla Lana School of Public Health and SickKids). 

“Paul Turner’s work—initiating a conceptual shift with practical consequences—has reshaped how we understand viruses,” remarked EEB chair Joel Levine in his introduction. “This research perspective, linking evolutionary approaches to public health issues,” he emphasized, “resonates strongly within the Canadian scientific tradition.” In that vein, the event proffered the beginnings of intensified collaboration in EEB on research at the intersections of antimicrobial resistance and emerging infectious disease.  

Why phage therapy?  

A phage, short for “bacteriophage,” is a type of virus that specifically infects and destroys bacteria through what is called a lytic infection cycle: the phage attaches to a bacterium’s surface receptors, injects its own genetic material, and then hijacks the the host’s internal machinery to replicate and, ultimately, make the bacterium burst and die (lysis), expelling hundreds of new phages in search of their next target.  

As the most abundant natural entities on earth, phages exist in almost unlimited supply: “There’s a big, beautiful world of phage biodiversity out there,” says Turner, creating “an immense, and efficient, discovery space.” And it’s not just the numbers that recommend phages; it’s also their specificity. Unlike antibiotics, which attack bacteria rather indiscriminately, phages often target only a particular strain of bacteria, leaving their beneficial bacterial neighbours intact.  

“Antibiotics have saved countless lives,” Turner knows, but they come with what he calls “some automatic liabilities: they can kill flora that should be there. Phages don’t tend to do that.” Phage specificity of course has its own disadvantages, like having to find, combine, or synthesize phages for individual, highly particular bacterium strains, but based on his and others’ research, including German’s, Turner “feels optimism” regarding the issue.  

“There’s a big, beautiful world of phage biodiversity out there.”

The idea of fighting bacterial infections with their natural predators is not new. In 1915 and 1917, the microbiologists Frederik Twort and Félix d’Hérelle independently discovered phages, and the latter scientist soon recognized the therapeutic potential of his discovery. Although research into, and treatment with, phages continued from that point on, the discovery of penicillin in 1928 by Alexander Fleming would change the course of modern medicine, sidelining phage therapy in the West (though not elsewhere in the world), for a host of reasons, including antibiotics’ broader effectiveness and the ability to  mass-produce them.  

Fast-forward to today: Across the globe, extant antibiotic drugs increasingly encounter the evolution of resistance in their target pathogens. Reasons are nuanced, but researchers agree that the mis- and overuse of antibiotics in healthcare and agriculture have contributed. Paired with the slowed pace in recent decades of antibiotic discovery—finding or synthesizing safe and effective new drugs—this growing resistance has encouraged greater creativity in the search for solutions among scientists. Or, in some ways, a look back to what Turner calls “a longstanding tradition in controlling bacterial infections.” 

Of course, phages cannot themselves escape evolutionary principles. When phages attack bacteria, they enter into a kind of arms race of adaptation: the two entities co-evolve to keep up with one another’s resistances. As Turner’s work has shown, a phage might attach to a molecular pump that a bacterium uses to expel antibiotic drugs. When the bacterium then develops resistance to the phage, it often does so by altering the pump—the doorway to its own destruction, if you will—an adaptation that in turn makes the bacterium more vulnerable to antibiotic therapy again.  

This evolutionary trade-off—the cost to the bacterium of developing phage resistance—for Turner opens up the possibility of designing phage treatment protocols that exploit the inevitable processes of evolution to “steer” outcomes in a beneficial, and pre-planned, direction. In other words, phages deployed might be chosen or synthesized to effect a specific evolutionary response in the bacteria involved in an infection. For now, such treatments, available only in individual, compassionate cases, rely on phage therapy alongside more traditional interventions like antibiotics. 

Phages cannot themselves escape evolutionary principles.

“Much more work lies ahead” before phage therapy could become more widely available, Turner knows, potentially helping stave off a global health crisis and more easily and cost-efficiently making treatments available to communities around the world who need them most.  

German, for one, suggests that a “bold narrative makeover” for phage therapy might help move it toward clinical trials. “People don’t know about phage therapy’s life-saving potential,” he says; “we need to make it dinner-table conversation.” Siddiqi cautions that this narrative must also take into consideration “the disproportionate effects of infectious disease on marginalized groups,” as well as historical precedents of medical abuse against underserved and excluded communities. “We need consideration of equity from the start,” she insists, “not as an afterthought once therapies are developed.” This includes acknowledging and tackling the structural causes of inequity. 

In all of this, broad-based education seems key, also about the meaningful contributions evolutionary thinking more generally can make to solving public health challenges. The conversation has only just begun. 

The Martin Lecture Series, held annually at the Faculty of Arts & Science at the University of Toronto, welcomes top thinkers and researchers in astronomy & astrophysics, ecology & evolutionary biology, physics, and public policy. The Martin Lecture Series recognizes the generosity of the late Mary Louise and Ronald Laidlaw Martin. It was established alongside the Martin Graduate Scholarships in the Faculty of Arts & Science at U of T, illustrating the Martin family’s deep commitment to supporting student success in a variety of fields. We are deeply grateful.