Transmission electron microscopy (TEM) images of bacteriophages: From left to right, images 1–4 captured by the late Hans-Wolfgang Ackermann (formerly Université Laval) and Image 5 by David Goulding (Wellcome Sanger Institute) with samples provided by Evelien Adriaenssens (Quadram Institute) and Rob Lavigne (KU Leuven).

“I never planned to end up in the world of bacteriophages (viruses that infect and kill bacteria). Like most microbiologists, I started out fascinated by bacteria, not the viruses that hunt them. But once you meet phages, it’s hard to look away. They are ancient, precise, and relentless.

Discovered over a century ago by Frederick Twort and Félix d’Hérelle, phages were once hailed as miracle cures. Then came antibiotics, and phage research was quietly sidelined, thriving mainly in Eastern Europe while fading into obscurity elsewhere.

Now, facing a global crisis of antimicrobial resistance, we’re looking at phages with fresh eyes. But to maximise their potential, we need to move beyond simple binaries. Phages defy easy black and white labels like “natural” or “engineered,” “precise” or “broad.”: the interesting truths lie in many shades of grey.

Grey #1 The myth of the “natural”phage

It’s tempting to divide phages into two camps: the “natural” ones found in nature, and the versions engineered in labs. But the reality is far more collaborative. Even natural phage therapy requires human touch; isolating, purifying, and testing phages before they ever reach a patient.

And “engineered” phages aren’t necessarily synthetic overhauls. Sometimes, a single, precise change like swapping the tail fibres a phage uses to latch onto its prey can turn a dud into a lifesaver. Take the case of a patient with a devastating Mycobacterium abscessus infection: researchers used a cocktail of natural phages, but genetically tweaked one to enhance its activity.

Grey #2 Precision of bacteriophages is a gift and a challenge

Phages are celebrated for their narrow host range, that is, their ability to target a specific bacterial strain without wiping out the rest of the microbiome. This precision is a huge advantage, but it’s also a practical hurdle.

To use bacteriophages effectively, you need to know exactly which bacterium you’re fighting. The solution isn’t to wish for broader phages, but to be strategic. By combining several narrow-targeting phages into a cocktail, we can create a therapy that’s both precise and comprehensive.

Grey #3 One-size-fits-all or personalised medicine?

Should phage therapy look like an antibiotic prescription, standardised and mass-produced, or more like personalised cancer treatment, tailored to the individual? The answer is: both.

For common, well-understood infections, standardised cocktails are the most practical.

For rare or stubborn infections, a personalised approach might be the only hope.

The future of bacteriophage treatments likely holds a flexible model, a library of approved, standard phages, with the ability to create custom blends when needed.

Grey #4 Breaking the “last resort” mindset for using bacteriophages as treatments

Stories like Tom Patterson’s whose infection was cured in a last-ditch effort by phage therapy have cemented the idea of phages as a heroic last resort. But waiting until a patient is septic and out of options creates a high-stakes, desperate scenario. It also ignores a more powerful, preventive potential. What if we used phages earlier in treatment?

In chronic conditions like cystic fibrosis, for instance, proactively managing Pseudomonas lung infections with phages could prevent catastrophic damage and preserve lung function. A 2025 study in Nature Medicine reported just that: Cystic Fibrosis patients receiving phage therapy showed reduced bacterial burdens and clinical improvement.

Using phages as precision gardeners to tend a problematic microbiome, rather than as bulldozers after a collapse, could fundamentally change patient outcomes.

Grey #5 Bacteriophages are partners, not replacements for antibiotics

We often frame phages as potential replacements for antibiotics, but their real promise may lie in partnership.

When bacteria evolve resistance to a phage, they often pay a price, sometimes losing their resistance to antibiotics in the process. This evolutionary trade-off is a therapeutic goldmine.

Research has shown that some Pseudomonas aeruginosa strains , when pressured by phages, can become resensitised to drugs they once ignored. Phages don’t just add to our arsenal; they can help reclaim weapons we thought we’d lost.

Grey #6 Bacteriophages role in the gut ecosystem

In the gut, phages regulate bacterial populations by selectively infecting and lysing specific strains. This “predator-prey” dynamic maintains balance—preventing any one bacterial group from dominating and preserving overall diversity.

Studies using metagenomic sequencing have shown that shifts in the gut phage population, or “phageome,” closely mirror changes in bacterial composition and even correlate with diseases such as inflammatory bowel disease and type 2 diabetes.

Embracing the greys of bacteriophages

If we cling to a polarised thinking, seeing phages only as a last-ditch effort or a direct antibiotic replacement, we’ll keep missing the point. Phage therapy doesn’t fit neatly into the frameworks we’ve built for other treatments. It’s alive, it evolves, and it demands a regulatory and clinical mindset that embraces flexibility.

That, in many ways, is the frontier where my own PhD work resides. I am trying to understand phages not just as agents of infection or therapy, but as participants in a vast biological dialogue. By studying how bacteria and phages interact at the genetic level, and how these interactions shift over time, we can begin to see the underlying language of their relationship and perhaps learn to speak it ourselves.

At the Quadram Institute, our research into phages, the microbiome, and antimicrobial resistance continues to illuminate these many shades, revealing not just how phages work, but how we might work with them to build a more resilient microbial future.

Let’s see phages for what they truly are—complex, adaptable, and alive with possibility.

Do you have any thoughts, case studies, or regulatory experiences to share? I’d love to hear them. The greys get clearer when more people add their colour.”