History Part 5 : A large-scale experiment in Tunisia that lays the foundations of modern medicine !

Félix d’Hérelle’s Phage Therapy Trials in Tunisia: A Forgotten Milestone in Medical Experimentation

Illustration of Félix d'Hérelle with patients in Tunisia (artist's impression)

In the early 1920s, the arid hospital wards of French Tunisia became the site of one of the earliest large-scale clinical applications of bacteriophage therapy in human patients. Led by Félix d’Hérelle—microbiologist, iconoclast, and self-styled bacteriophage evangelist—this episode stands as a largely overlooked but pivotal moment in the history of therapeutic microbiology.

At a time when the mechanisms of bacterial disease were only partially understood and antibiotics had yet to transform modern medicine, d’Hérelle’s ambition was radical: to cure deadly infections using living viruses that specifically target and destroy bacterial pathogens. His experiments in North Africa were not preliminary lab trials, but structured medical interventions on infected patients in real clinical settings.

The Setting: Tunisia’s Colonial Hospitals

Following his initial therapeutic success treating dysentery in a Parisian hospital in 1919, d’Hérelle sought broader validation. Tunisia, a French protectorate with a diverse population and high incidence of enteric diseases, offered both epidemiological opportunity and imperial infrastructure. The colonial hospitals in places like Tunis and Sfax were sites where infectious diseases—particularly bacillary dysentery and typhoid fever—routinely ravaged civilian and military populations alike.

D’Hérelle obtained permission to administer phage preparations to infected patients under the oversight of colonial medical authorities. These trials were notable not only for their scale, but for their rigor relative to the time.

Methodology and Execution

The phages used in Tunisia were isolated directly from sewage and stool samples of dysentery patients, then purified using porcelain filters to remove bacterial debris. D’Hérelle maintained that the preparations were sterile of any living bacteria, containing only the lytic agent—what we now know as bacteriophages.

Patients selected for treatment were suffering from severe bacillary dysentery, confirmed by the presence of Shigella in stool cultures. The phage solution was administered orally or rectally, depending on the severity of the illness.

Crucially, d’Hérelle conducted comparative trials: some patients received phage treatment, while others received conventional therapies of the time, including hydration and mild antiseptics. In numerous documented cases, patients receiving the phage therapy showed rapid improvement within 24 to 48 hours: fever subsided, stools normalized, and cultures of Shigella often became negative within days.

D’Hérelle recorded a notably lower mortality rate among the phage-treated cohort compared to those receiving standard care. He also emphasized the absence of adverse reactions, interpreting this as evidence of both specificity and safety—an advantage he often contrasted with the toxicity of chemical antiseptics.

Scientific Impact and Legacy

While these results would not meet the randomized, double-blind standards of contemporary clinical trials, they were unprecedented at the time. D’Hérelle’s Tunisian studies represented the first sustained attempt to demonstrate that bacteriophages could be systematically deployed in the clinic to treat life-threatening infections.

The work caught the attention of the French Academy of Medicine and international observers, though many remained skeptical. Critics questioned the reproducibility of results and the precise nature of the “filtrable virus.” But d’Hérelle was undeterred: he published his findings widely and used the Tunisian data as proof of concept to promote phage therapy worldwide.

A Milestone in Biomedical History

Though ultimately overshadowed by the antibiotic revolution, d’Hérelle’s trials in Tunisia deserve renewed attention. They mark one of the first instances in which a viral agent—deliberately selected, amplified, and administered—was used to cure a bacterial disease in a human population at scale.

As modern medicine rediscovers phage therapy in the face of antimicrobial resistance, the Tunisian experiments of the 1920s stand not as an eccentric footnote, but as a foundational chapter in the therapeutic use of viruses. Long before genomics and synthetic biology, a French-Canadian scientist in colonial North Africa pioneered a vision of precision antimicrobials—guided not by chemistry, but by ecology, evolution, and the invisible predators of the microbial world.

Sources : 

- Abedon, S. T., Kuhl, S. J., Blasdel, B. G., & Kutter, E. M. (2011). Phage treatment of human infections. Bacteriophage, 1(2), 66–85. https://doi.org/10.4161/bact.1.2.15845

- Berghmans, P. (1930). La phagothérapie en Tunisie. Archives de l’Institut Pasteur de Tunis.

- Chanishvili, N. (2012). Phage therapy—History from Twort and d’Hérelle through Soviet experience to current approaches. In M. Łobocka & W. Borysowski (Eds.), Advances in Virus Research (Vol. 83, pp. 3–40). Academic Press. https://doi.org/10.1016/B978-0-12-394438-2.00001-4

-  d’Hérelle, F. (1921). Sur un microbe invisible antagoniste des bacilles dysentériques. Comptes Rendus de l’Académie des Sciences, 165, 373–375.

- d’Hérelle, F. (1926). The bacteriophage: Its role in immunity. Baltimore: Williams & Wilkins.

-  Kutter, E., De Vos, D., Gvasalia, G., Alavidze, Z., Gogokhia, L., Kuhl, S., & Abedon, S. T. (2010). Phage therapy in clinical practice: Treatment of human infections. Current Pharmaceutical Biotechnology, 11(1), 69–86. https://doi.org/10.2174/138920110790725401

- Miller, R. V., & Sulakvelidze, A. (Eds.). (2005). Bacteriophage therapy in the 21st century. Washington, DC: ASM Press.

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Summers, W. C. (1999). Félix d’Hérelle and the origins of molecular biology. New Haven: Yale University Press.