History Part 2 : The grasshopper experiment and its clinical applications

From Discovery to Remedy: The Early Therapeutic Applications of Phage Therapy by Félix d’Hérelle

Félix d'Hérelle, grasshopper and phages (artist view)

Félix d’Hérelle's 1917 identification of bacteriophages marked a conceptual breakthrough — but it was in the immediate years that followed that his work took on an audacious, revolutionary dimension: the deliberate use of phages to treat bacterial infections in animals and humans. Long before the advent of antibiotics, d’Hérelle believed he had uncovered a natural, precise, and replicable antiviral weapon against bacteria — and he wasted no time proving it.

From Observation to Experiment: Animal Trials

After returning to Paris from his work in Tunisia, d’Hérelle turned his full attention to bacteriophages. He believed that these invisible bacterial parasites could be cultivated and administered as therapeutic agents. His first challenge: to prove their efficacy in living organisms.

One of his earliest controlled experiments was carried out on chickens suffering from Salmonella infections — specifically, Salmonella gallinarum, the cause of fowl typhoid, a devastating disease for poultry farmers. In a series of trials, d’Hérelle administered phage preparations to infected chickens and observed a sharp decline in mortality rates compared to untreated controls. In several flocks, death rates dropped from over 80% to under 5%.

Crucially, phage-treated birds not only survived but showed no adverse effects, reinforcing d’Hérelle’s claim that phages were both highly specific and non-toxic. For a world yet to discover antibiotics, this was a stunning finding: the first demonstration that bacterial infections could be cured by a viral agent.

1919: The First Documented Human Phage Therapy

D’Hérelle’s leap from veterinary to human medicine came in 1919, and it was as bold as it was historic. At the Hôpital des Enfants-Malades in Paris, he encountered a 12-year-old boy suffering from acute bacillary dysentery. The disease, caused by Shigella dysenteriae, was common among soldiers and civilians alike — highly contagious and frequently fatal in its severe form.

D’Hérelle administered a bacteriophage preparation orally. The patient recovered rapidly — within 24 hours, the symptoms had dramatically subsided, and the infection resolved within days.

While modern standards would require randomized, placebo-controlled trials, for 1919, this was a medical milestone. D’Hérelle had treated a bacterial infection in a human with a viral agent — and succeeded.

In the years that followed, he replicated this success in other human cases, including:

• Cholera patients in India and Egypt;

• Typhoid fever in French North Africa;

• Staphylococcal and streptococcal infections in European clinics.

Wherever he worked, he emphasized rigorous observation, pre-treatment bacteriological identification, and individualized phage preparation — a methodology that eerily resembles personalized medicine a century later.

Beyond Paris: Expanding Therapeutic Use Across Continents

In the early 1920s, d’Hérelle's reputation spread quickly. He collaborated with military doctors, field physicians, and Pasteurian researchers in deploying phage therapy to epidemic zones. In India, working with Lieutenant-Colonel John Morison of the British Indian Medical Service, d’Hérelle participated in trials where phage preparations were used to treat and prevent cholera during seasonal outbreaks.

Field results suggested that communities given prophylactic phage treatment experienced significantly reduced mortality compared to those untreated. These early efforts, though not always conducted under modern trial conditions, laid the groundwork for what we now recognize as population-level biological interventions.

In Egypt, during a 1927 cholera outbreak in Alexandria, d’Hérelle worked with local doctors to apply phage therapy in field hospitals. Patients given oral phage solutions often recovered within two days, with far fewer complications than traditional therapies allowed.

In Brazil, researchers from the Oswaldo Cruz Institute — inspired by d’Hérelle’s publications — began using phages to treat dysentery, with reports of full recovery in as little as 48 hours.

A Global Movement and Industrial Production

By the late 1920s, d’Hérelle’s work had sparked industrial interest. Pharmaceutical companies including L’Oréal in France, Eli Lilly and Parke-Davis in the United States, and several Soviet biomedical institutes began producing bacteriophage preparations for diseases such as:

• Dysentery

• Cholera

• Typhoid

• Staphylococcal skin infections

• Septicemia

These preparations were sold in ampoules or tablets, often under proprietary names. While not always standardized (and sometimes contaminated), they marked the first mass production of virus-based therapeutics in modern medicine.

Scientific Methodology Ahead of Its Time

What is remarkable is not just the breadth of d’Hérelle’s applications, but the scientific methodology that underpinned them:

• Strain-specific diagnosis: Before treatment, he often isolated the pathogenic strain and tested phage susceptibility.

• Bespoke therapy: He custom-prepared phage solutions tailored to the identified pathogen.

• Quantitative dosing: He introduced titration using plaque-forming units (PFUs), a concept that still forms the basis of viral quantification today.

• No collateral damage: Unlike the antibiotics that would follow, phages left the commensal microbiota untouched — a concept only now being fully appreciated in microbiome medicine.

Conclusion : The Proof Before Penicillin

In the decade following the 1917 discovery, Félix d’Hérelle accomplished what most scientists only dream of: he identified a new class of biological entity, elucidated its life cycle, and deployed it successfully in veterinary and human medicine across multiple continents. His work demonstrated that viral therapy could treat bacterial infections safely, rapidly, and with strain-level precision.

Long before antibiotics reached clinical use, d’Hérelle’s phage therapy was already saving lives. Though it would later be eclipsed by penicillin and other wonder drugs, these early therapeutic advances remain not just a historical curiosity, but a prophetic glimpse of the future of medicine — one in which natural biological agents are repurposed to fight resistant pathogens with exquisite specificity.

Sources : 

Summers, W. C. (1999). Félix d’Hérelle and the Origins of Molecular Biology.

Ackermann, H.-W., & DuBow, M. S. (1987). Viruses of Prokaryotes. Volume I: General Properties of Bacteriophages.

Chanishvili, N. (2012). Phage Therapy—History from Twort and d’Hérelle through Soviet Experience to Current Approaches.

Sulakvelidze, A., Alavidze, Z., & Morris, J. G. Jr. (2001). Bacteriophage Therapy

Dublanchet, A., & Bourne, S. (2007). The Epic of Bacteriophage Therapy.

Parasion, S., Kwiatek, M., Gryko, R., Mizak, L., & Malm, A. (2014). Bacteriophages as an alternative strategy for fighting biofilm development..