History Part 7 : The Rise of Penicillin and the Fall of Phages: A Forgotten Chapter in Medical History

Penicillin and the Eclipse of Phage Therapy in Western Medicine (1928–1950)

Abstract:
The period between the late 1920s and the mid-20th century witnessed a fundamental transformation in antimicrobial therapeutics. Bacteriophage therapy, once a promising solution to bacterial infections, saw increasing use in European clinics during the interwar years. However, the discovery and mass production of penicillin during World War II radically shifted clinical priorities. This article examines the rise of penicillin and the scientific, clinical, and industrial dynamics that led to the displacement of phage therapy in Western medical practice by 1950.

Introduction: A Divided Therapeutic Landscape

In the interwar period, Western medicine faced a crisis of infectious disease without a universal remedy. While chemical antiseptics and arsenical compounds like Salvarsan were used for certain infections, many remained untreatable. Bacteriophage therapy emerged as a candidate solution, particularly in parts of Europe, where clinical trials were undertaken for diseases like dysentery, wound infections, and puerperal sepsis. Laboratories in France, Romania, and Poland produced bespoke phage preparations, administered based on presumed bacterial etiology.

Despite promising anecdotal outcomes, enthusiasm for phage therapy remained tempered by the empirical nature of its practice, variability in results, and a lack of rigorous biological understanding. Into this therapeutic uncertainty entered penicillin—a compound that would fundamentally redefine medical treatment of bacterial disease.

The Discovery and Early Promise of Penicillin

Artisitic view

In 1928, Alexander Fleming, working at St. Mary’s Hospital in London, serendipitously observed that a contaminant mold inhibited the growth of Staphylococcus aureus. He identified the mold as Penicillium notatum and reported its bactericidal properties the following year. However, Fleming’s penicillin was unstable and difficult to purify, and the discovery languished for a decade.

The turning point came in 1938 when a team at the University of Oxford, led by Howard Florey and Ernst Boris Chain, succeeded in isolating and stabilizing penicillin in a form suitable for therapeutic use. Initial animal studies were promising, and by 1941, the first human trials showed remarkable efficacy in treating septicemia, pneumonia, and surgical infections. A patient with life-threatening Streptococcus septicemia experienced rapid recovery after receiving intravenous penicillin—a result unheard of with earlier therapies.

Wartime Mobilization and Industrial Scale-Up

Recognizing its potential, the British and U.S. governments launched an unprecedented effort to mass-produce penicillin. The U.S. War Production Board collaborated with pharmaceutical firms such as Pfizer and Merck to optimize fermentation processes. By 1944, penicillin production had scaled from milligram to metric ton quantities.

This effort culminated in the drug’s deployment during the D-Day invasion, where it was used to treat battlefield injuries, syphilis, and postoperative infections. Penicillin’s success among Allied forces was seen as both a medical and symbolic triumph. The U.S. produced over 650 billion units of penicillin in 1945 alone, making it widely accessible to civilians after the war.

Comparative Advantages Over Phage Therapy

The swift adoption of penicillin in clinical practice highlighted multiple comparative advantages over phage therapy:

1) Broad-spectrum efficacy: Penicillin was effective against most Gram-positive pathogens, including Streptococcus and Staphylococcus species, eliminating the need for pathogen-specific matching.

2) Standardized production: Pharmaceutical-grade penicillin could be manufactured with consistent potency and quality—unlike phage preparations, which were often variable, locally produced, and lacked standardized titration.

3) Ease of administration: Penicillin could be administered intravenously or orally, required no specialized microbiological expertise, and yielded reproducible therapeutic outcomes.

Phage therapy, by contrast, required isolation of the infecting bacterial strain, matching with a specific phage or phage cocktail, and careful monitoring of bacterial resistance. In most Western hospitals—pressed for resources and seeking generalizable treatments—these complexities were deemed impractical.

Decline of Phage Research and Clinical Use

By the late 1940s, phage therapy had largely vanished from the clinical literature in North America and Western Europe. Major journals such as The Lancet and JAMA published few, if any, phage studies after 1945. A landmark 1934 review by Eaton and Bayne-Jones, published in Bacteriological Reviews, concluded that phage therapy lacked sufficient clinical evidence and consistency to be widely recommended.

Academic interest waned as penicillin—and subsequently streptomycin (1943), chloramphenicol (1947), and tetracycline (1948)—dominated antimicrobial research. Pharmaceutical companies redirected funding and infrastructure toward antibiotic discovery and commercialization, abandoning phage development programs.

Government and military medical systems, impressed by antibiotics’ role in wartime medicine, embedded them into standard treatment protocols. By 1950, the therapeutic use of bacteriophages in the West had effectively ended.

Conclusion: A Paradigm Shift by 1950

Between 1928 and 1950, the trajectory of antimicrobial therapy in Western medicine underwent a dramatic shift. From a landscape of fragmented approaches—including phage therapy—clinicians moved rapidly to embrace antibiotics as a universal, reliable solution. The discovery, refinement, and wartime mobilization of penicillin eclipsed phage therapy not through disproof of its potential, but through the unmatched speed, efficacy, and scalability of this new class of drugs.

This paradigm shift marked the end of the first era of phage therapy in the West. While phages continued to be investigated in the Soviet Union and select Eastern European institutions, they would remain absent from mainstream Western practice for decades to come.

Sources : 

1. Fleming, A. (1929). On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. influenzae. British Journal of Experimental Pathology, 10(3), 226–236.

2. Chain, E., Florey, H. W., Gardner, A. D., Heatley, N. G., Jennings, M. A., Orr-Ewing, J., & Sanders, A. G. (1940). Penicillin as a Chemotherapeutic Agent. The Lancet, 236(6104), 226–228.

3. Eaton, M. D., & Bayne-Jones, S. (1934). Bacteriophage: Review of the Literature and Summary of Investigations Made at the Naval Medical School. Bacteriological Reviews, 1(1), 1–78.

4. Bud, R. (2007). Penicillin: Triumph and Tragedy. Oxford University Press.

5. Ligon, B. L. (2004). Penicillin: Its Discovery and Early Development. Seminars in Pediatric Infectious Diseases, 15(1), 52–57.