History Part 1 : Phage Therapy and its discovery by Felix d'Hérelle

Félix d’Hérelle: The Forgotten Father of Phage Therapy

Picture of Félix d'Hérelle (Pasteur Institute)

A Visionary in the Shadows of History

In the annals of microbiology, certain names are carved into stone — Pasteur, Koch, Fleming. But among them, one figure remains unjustly obscured: Félix d’Hérelle, a self-taught microbiologist who, in 1917, discovered the existence of bacteriophages — viruses that infect and destroy bacteria. Through meticulous experimentation and bold clinical application, d’Hérelle not only identified a new biological entity, but pioneered one of the most promising alternatives to antibiotics: phage therapy.

A Self-Made Scientist

Born in 1873 in Montreal, d’Hérelle had no formal degree in science. Instead, he was an intellectual adventurer — multilingual, well-read, and ferociously curious. After working in Guatemala and Mexico on fermentation and agricultural microbiology, he returned to France where he joined the Pasteur Institute in Paris as an unpaid researcher. There, he conducted much of the work that would define his legacy.

D’Hérelle’s strength was not in academic conformity, but in empirical rigor. He trusted what he could observe, measure, and reproduce. And it was exactly this mindset that led him to challenge conventional wisdom in one of the most significant microbiological discoveries of the 20th century.

The 1917 Discovery: Bacteriophages

While investigating outbreaks of bacillary dysentery during World War I, d’Hérelle analyzed stool samples from infected soldiers. He noticed that when these samples were filtered — removing all visible bacteria — and then applied to fresh bacterial cultures of Shigella, they produced clear plaques, small zones where the bacteria had lysed.

Crucially, this agent:

• Passed through Chamberland filters (0.2 μm), meaning it was smaller than bacteria;

• Was reproducible, causing the same lysis pattern in subsequent bacterial cultures;

• Replicated in the presence of the host bacterium, amplifying its effect;

• Showed host specificity, lysing only certain bacterial strains.

From this, d’Hérelle deduced the existence of an obligate bacterial parasite — an invisible entity that infected and destroyed specific bacteria. He named it the bacteriophage, or “bacteria eater.”

A Methodical Experimental Framework

What distinguished d’Hérelle’s work was the precision and consistency of his experimental design. He introduced concepts that would later become foundational in virology:

• Plaque assays to quantify phage particles;

• Serial dilutions to determine phage concentration;

• The idea that bacteriophages multiply inside bacteria, a form of intracellular parasitism.

He firmly rejected the notion — popular at the time — that bacterial lysis was caused by autocatalysis or enzymatic degradation. His experiments showed that the lytic activity was transferable, amplifiable, and contagious, consistent only with a replicating infectious agent.

First Clinical Application: Treating Dysentery in 1919

D’Hérelle was not just a theorist; he was a man of action. In 1919, he administered a phage preparation to a 12-year-old boy at the Hôpital des Enfants-Malades in Paris who was suffering from severe, treatment-resistant dysentery. Within 24 hours, the child’s symptoms improved dramatically. The recovery was fast, complete, and — most strikingly — achieved without any toxicity.

This marked the first documented therapeutic use of bacteriophages in humans.

Encouraged, d’Hérelle published his results and launched further clinical applications — in chickens with Salmonella, in humans with Staphylococcus and Streptococcus infections, and later in regions ravaged by cholera and typhoid.

Global Reach: From Paris to Tbilisi

D’Hérelle’s success caught the attention of scientists worldwide. In 1923, he travelled to Egypt during a cholera outbreak and reported rapid reductions in mortality after phage administration. Later, he collaborated with Soviet researchers and co-founded the George Eliava Institute of Bacteriophages in Tbilisi, Georgia, which would become a hub for phage research throughout the 20th century.

In every location, d’Hérelle emphasized reproducibility, field testing, and clinical trials. His approach was strikingly modern — blending microbiological insight with translational science. At a time when antibiotics had not yet entered the scene, phage therapy appeared to be a miracle solution.

Scientific Controversies and Isolation

Despite his achievements, d’Hérelle faced fierce opposition. Some contemporaries, including members of the Pasteur Institute, questioned the viral nature of phages. Others dismissed his therapeutic claims as anecdotal or insufficiently controlled. This skepticism — combined with his abrasive personality and political outspokenness — contributed to his scientific marginalization in Western Europe.

Meanwhile, the rise of antibiotics in the 1940s — notably penicillin — rapidly eclipsed interest in phage therapy in the West. D’Hérelle’s contributions, once celebrated, were increasingly forgotten.

Legacy and Reappraisal

Today, as the global threat of antibiotic resistance intensifies, the scientific community is rediscovering d’Hérelle’s work with fresh eyes. His methods — from host-specific therapy to personalized phage cocktails — are now being explored in precision medicine and bioengineered phage design.

Modern molecular tools (such as CRISPR-based phage editing, phage display, and metagenomic screening) have validated many of his core assumptions. Where his contemporaries saw speculation, we now see vision.

Personal Advice : A Prophet of Targeted Medicine

Félix d’Hérelle’s discovery of bacteriophages was not a historical curiosity — it was the seed of a biomedical revolution that is only now beginning to flourish. He envisioned a world where natural viral predators could be used to restore microbial balance, treat infections without harming commensal flora, and evolve alongside bacterial threats.

Though forgotten by history for decades, d’Hérelle stands today not only as the father of phage therapy, but as one of the first scientists to embrace what we now call biological precision therapeutics.

Sources :

https://rochepro.fr/pharmaciens/expertise-pui/toute-actualite/phagotherapie-quand-virus-viennent-a-bout-bacteries.html

https://www.pasteur.fr/en/institut-pasteur/notre-histoire/felix-herelle-decouvreur-bacteriophages

https://pdf.sciencedirectassets.com/272288/1-s2.0-S0399077X08X00095/1-s2.0-S0399077X0800173X/main.pdf

https://en.wikipedia.org/wiki/F%C3%A9lix_d%27H%C3%A9relle