Paul Turner on the Next Decade of Phage Therapy: Clinical Trials, Engineered Phages and Global Access

The interview begins from a simple premise: phage therapy is old, but the problem it is now being asked to solve has changed. Bacteriophages were used therapeutically before antibiotics became dominant in Western medicine, and the basic concept remains the same — exploiting viruses that naturally infect bacteria to eliminate bacterial pathogens. What has changed is the scale of antimicrobial resistance and the availability of modern genomics, synthetic biology and clinical infrastructure capable of turning phages into far more controlled biological medicines.

Turner argues that the renewed interest in phage therapy is directly linked to the declining effectiveness of antibiotics against some bacterial infections. His expectation is that interest will continue growing globally as antibiotic resistance creates increasing pressure for alternatives and adjuncts. At the same time, he distinguishes countries where phage therapy has historically been used in clinical practice from jurisdictions such as the United States, where access remains largely experimental or based on expanded-access mechanisms rather than routine approval as a general medicinal product.

This regulatory distinction is central to his view of the next decade. Turner does not argue that phages should bypass the conventional clinical development process. On the contrary, he emphasizes that countries seeking broadly approved phage medicines will need robust clinical trial data demonstrating safety and efficacy. He expects the coming five to ten years to bring an increasing number of trials directed at defined indications, including respiratory and urinary tract infections.

That position is consistent with the situation at Yale, where phage therapy has already been used under FDA expanded-access pathways for patients with severe multidrug-resistant infections. Yale’s Center for Phage Biology & Therapy has worked on such cases since 2013, while also building phage libraries and investigating personalized approaches for difficult infections.

One of the most interesting sections of the interview concerns the future balance between naturally isolated and genetically engineered bacteriophages. Turner does not dismiss natural phages; many can be isolated from the environment, sequenced and used effectively. But he argues that engineering offers a potential advantage because researchers can increasingly define exactly what a therapeutic phage contains and what it is designed to do.

The issue is particularly important because phages are biological entities rather than chemically fixed small molecules. Natural phage genomes may contain genes whose functions are poorly characterized, and some candidates may carry undesirable genetic elements. Whole-genome sequencing can identify many known risks, but Turner stresses that scientists still do not understand the function of every phage gene. For therapeutic development, this creates an incentive to simplify and deliberately design phage genomes, removing unnecessary or potentially problematic elements where feasible.

That concept is already moving from theory into experimental systems. Turner’s group and researchers at New England Biolabs, including Greg Lohman and colleagues, recently reported a fully synthetic Golden Gate assembly system for engineering a Pseudomonas aeruginosa phiKMV-like phage. The work illustrates precisely the kind of platform Turner describes in the interview: moving from simply finding useful natural phages toward technologies that allow researchers to build, modify and understand therapeutic phages more systematically.

For Turner, this does not mean that engineered phages will automatically replace natural isolates. Rather, the distinction may become less important as the field develops reliable engineering platforms. Natural phages can provide powerful starting scaffolds, while synthetic biology can remove unwanted components, modify host range or optimize therapeutic properties. The broader objective is greater control over the biological drug.

The interview also addresses safety, but Turner frames the issue carefully. Phages are already abundant components of human-associated microbial ecosystems, including the gut and skin, and humans are continuously exposed to them. This provides biological context for why therapeutic phage administration has generally shown favorable safety profiles. Nevertheless, he emphasizes that introducing a selected or engineered phage into a complex microbiome cannot be treated as if the virus were operating in isolation.

The question may therefore be less about whether phages are intrinsically dangerous and more about whether their therapeutic activity changes when they encounter complex microbial communities. A phage that behaves predictably against a single bacterial strain in vitro may encounter competing bacteria, alternative hosts, biofilms, immune factors and ecological interactions in a patient. These variables may alter treatment efficacy and must increasingly be incorporated into preclinical testing.

Turner also highlights the role of collaboration between academic laboratories and biotechnology companies. He specifically describes the partnership between his laboratory and New England Biolabs, particularly Greg Lohman’s group, as an example of how fundamental phage biology can connect with tool development and industrial translation. Academic laboratories may identify mechanisms and answer basic biological questions, whereas companies can turn those discoveries into standardized technologies that other researchers can actually use.

This interface could become increasingly important as phage engineering matures. A major limitation in the field is that sophisticated engineering methods often remain restricted to laboratories with extensive expertise in individual phage–host systems. Turner argues that generalized tools capable of engineering phages through well-characterized surrogate systems could make the technology accessible to many more laboratories.

His longer-term view also extends far beyond human medicine. Phage applications in veterinary medicine, plant disease, agriculture and aquaculture may face different regulatory pathways and could potentially be translated more rapidly. These sectors are themselves under increasing pressure from antibiotic resistance, particularly where bacterial outbreaks can disrupt large-scale food production systems.

This is where Turner frames phage therapy explicitly within a global context. Phage production itself can be relatively inexpensive compared with many advanced biologics, although large-scale manufacturing, purification and quality control add substantial costs. That creates an opportunity for researchers and physicians in low- and middle-income countries to develop locally relevant phage solutions rather than waiting for therapies optimized exclusively for diseases prioritized in wealthier countries.

Turner points to strong interest in phage research across Africa, South America and other regions where access to expensive antimicrobial innovation may be limited but local microbiological expertise is growing. His argument is not that phage therapy is automatically a low-cost solution, but that its biological and manufacturing characteristics could make decentralized development more feasible than some other therapeutic platforms.

The interview ultimately presents a field moving simultaneously in several directions. Personalized therapy remains important because individual bacterial strains can differ dramatically in phage susceptibility. At the same time, standardized products and broader-host-range cocktails are needed if phage therapy is to become routine rather than exceptional. Natural phages will continue to be used, while engineered phages may offer greater control. Compassionate-use cases will continue generating experience, but clinical trials will be required to establish efficacy convincingly.

Turner’s own research illustrates this convergence of evolutionary biology and translational medicine. His work has long focused on how bacteria evolve resistance to phages and whether that evolutionary response can itself be exploited therapeutically. One strategy is to select phages whose bacterial receptors are also important for virulence or antibiotic resistance, so that resistance to the phage may impose a cost on the pathogen. Yale has continued exploring such evolutionary trade-offs in difficult infections, including respiratory disease.

This evolutionary perspective also explains why Turner resists describing phage therapy as a simple replacement for antibiotics. Phages replicate, mutate and interact with evolving bacterial populations. Their therapeutic behavior depends on both ecology and evolution, which creates opportunities unavailable to conventional drugs but also introduces additional complexity into manufacturing, dosing and clinical prediction.

Perhaps the clearest message from the interview is that the next phase of phage therapy will depend less on demonstrating that phages can kill bacteria — that has been known for more than a century — and more on transforming that biological fact into reproducible medicine. That means better engineering tools, defined manufacturing standards, rigorous clinical trials, improved understanding of microbiome interactions and stronger connections between academia, industry and clinical practice.

Turner expects the field to continue accelerating over the next five to ten years, but his argument is not one of inevitable success. Regulatory approval will depend on demonstrating efficacy. Engineered phages will require careful characterization. Personalized medicine must become more scalable. And global adoption will depend on whether the technology can be made accessible outside a handful of highly specialized centers.

The significance of the current moment is therefore that several pieces are beginning to converge at once: rapidly advancing phage engineering, expanding clinical experience, growing antimicrobial resistance, increased industrial involvement and a larger international research community. Whether these developments finally move phage therapy from exceptional treatment to a widely available antimicrobial platform will largely be determined by the clinical and technological work performed during the coming decade.

Sources :

New England Biolabs — NEB Podcast #83: Interview with Paul Turner: Putting Bacteriophage to Work, September 2026.
https://www.neb.com/fr-fr/podcasts/podcast-83-interview-with-paul-turner

Yale School of Medicine — Paul Turner, PhD. https://medicine.yale.edu/profile/paul-turner/

Turner Lab, Yale University. https://turnerlab.yale.edu/

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