History of Phage Therapy

Phage therapy is not a recent discovery; it dates back to the early 20th century, with two scientists making impactful discoveries within two years of each other. But research priorities shifted toward antibiotics to treat bacterial infections, leaving bacteriophages behind. However, as scientists recognise the growing antimicrobial resistance problem, phages are receiving increasing attention.

1900-1930s

Frederick Twort

Frederick Twort was a British biologist working at the Brown Institution in London. Whilst studying the smallpox vaccine virus, Twort noticed something strange; some bacterial colonies became glassy, transparent and stopped growing. He found that even after passing this through a porcelain filter, small enough to trap bacteria, it still remained. Twort proposed three possible explanations: either an enzyme, a self-replicating virus, or a product of bacterial metabolism. He leaned towards the virus hypothesis, publishing his work in the Lancet in 1915. However, his research was cut short by World War I and a lack of funding.

Félix d’Hérelle

In 1917, Félix d’Hérelle, a French-Canadian microbiologist, was working at the Pasteur Institute in Paris. While investigating outbreaks of dysentery among soldiers, d’Hérelle observed that filtrates from recovering patients could kill Shigella dysenteriae. He concluded this was due to a virus that infects bacteria, which he named ‘bacteriophage’ (literally ‘bacteria-eater’). d’Hérelle immediately began therapeutic trials using phages to treat dysentery and cholera in India, publishing extensively and publicising his results.

During the 1920s and 1930s, phage therapy spread rapidly across the world as researchers and physicians began using bacteriophages to treat a range of bacterial infections, including dysentery, cholera, and staphylococcal skin infections. Pharmaceutical companies such as Eli Lilly in the US commercialised phage preparations, and clinical trials were conducted in several countries. However, the results were often inconsistent and unreliable. At the time, scientists had a limited understanding of phage biology, and preparations were typically impure, poorly characterised, and lacked standardisation. As a result, treatment outcomes varied widely, which ultimately undermined confidence in phage therapy despite its early promise.

1940-1970s

Despite this early enthusiasm, the discovery of penicillin by Alexander Fleming in 1928 shifted global attention toward antibiotics. Antibiotics were broader-spectrum, easier to produce, and simpler to standardise, making them far more appealing to clinicians.

As a result, interest in phage therapy waned across much of Europe and North America, whilst phage research and clinical use persisted in Eastern Europe and the Soviet Union. Countries like Georgia and Poland maintained phage therapy as a viable treatment option, particularly for chronic and antibiotic-resistant bacterial infections, during a period when it had largely disappeared elsewhere.

2000s-2020s

However, Western reliance on antibiotics eventually led to the growing problem of antimicrobial resistance (AMR), prompting scientists and clinicians to reconsider phage therapy as a potential alternative.

By the 2000s and 2010s, advances in molecular biology and genomics had transformed scientific understanding of bacteriophages, enabling researchers to better characterise their biology, specificity, and safety. This renewed interest led to the first modern clinical evaluations, the most significant being the EU-funded Phagoburn trial, which assessed the tolerance and efficacy of phage cocktails for treating wound infections in burn patients. Although the study faced challenges with phage stability, it demonstrated the feasibility of conducting regulated phage therapy trials in Europe. Around the same time, compassionate-use cases in Europe, Asia and the United States (such as Tom Patterson) successfully used phages to treat otherwise untreatable, antibiotic-resistant infections.

By the 2020s, phage therapy had entered the era of personalised medicine, where specific phages are matched to patients’ bacterial isolates. New regulatory frameworks began to emerge, such as Belgium’s ‘magistral phage’ model, which allows the production of custom-made phage medicines under controlled conditions.

In the United Kingdom, the rise of antimicrobial resistance (AMR) drove a resurgence of interest in phage research and therapy. A landmark case in 2019 saw NHS doctors, in collaboration with US researchers, successfully use compassionate phage therapy to treat a teenager with cystic fibrosis infected by Mycobacterium abscessus, the first case of its kind in the UK. Research universities launched dedicated phage research programs, like the Phage Collection Project.

Conclusion

Phages have captured varying levels of research attention over the last century, but their potential as a treatment for antibiotic-resistant infections is once again drawing global interest. You could even play a part in this research. The Phage Collection Project are asking for citizens for environmental and toilet samples, which our researchers will use to hunt for potential therapeutic phages. If you are interested, you can find information in the ‘Get Involved’ tab on the website. Who knows, the next life-saving phage may be hidden in your back garden?

The information and opinions expressed in this blog post represent those of the original author of the blog. They do not necessarily reflect and represent the views and opinions of the Phage Collection Project or its staff.