Alexander Fleming, whose accidental 1928 observation gave the world its first true antibiotic, Penicillin. Official photographer, Public domain, via Wikimedia Commons
Pharmacy

Alexander Fleming and Penicillin: The Accidental Discovery That Revolutionized Medicine

How a contaminated petri dish, scientific curiosity, and global collaboration turned a simple mold into one of humanity’s greatest medical breakthroughs.

Vanshika Kalra

Who Was Alexander Fleming?

Early Life and Education

Alexander Fleming was born on August 6, 1881, in Lochfield Farm, Scotland. He was the son of Hugh Fleming and Grace Stirling Morton. He did his schooling in Scotland and later moved to London with his siblings and completed his further education at the Regent Street Polytechnic.

He did not enter medical school immediately, but later using the inheritance left by his uncle John, Fleming pursued medicine and graduated with distinction from St Mary’s Medical School at London University in 1906.¹

The Discovery of Penicillin

The Contaminated Petri Dish

On the morning of Monday, September 3, 1928, Fleming returned to his laboratory at St. Mary’s Hospital after a family holiday. Before leaving, he had been conducting experiments with Staphylococcus aureus, a common and dangerous pathogen. Fleming had left several glass petri dishes on his lab bench with these bacteria growing on solid medium. 1

Known for his meticulous nature, Fleming always examined his experiments before discarding them, even those left for weeks. As he randomly pulled samples from a stack of plates, one dish caught his attention. Upon noticing it, he famously exclaimed, “That’s funny….” 1

In 1928, at St. Mary's Hospital, London, Alexander Fleming discovered penicillin. 2

Fleming's Critical Observation

The plate had been inoculated with a dense bacterial culture but was also contaminated with a microscopic fungus that had formed a large colony on one side. What made this extraordinary was the clear zone surrounding the fungus, an area completely free of bacteria. Today we call this the “zone of inhibition.” It revealed that the fungus was producing something that killed Staphylococcus aureus. 1

Fleming identified the contaminant as a mold of the genus Penicillium, which was producing a substance that killed the bacteria. He initially called this substance ‘mold juice’. 1

He had stumbled upon nature’s biological warfare: microorganisms compete for nutrients by producing substances toxic to their competitors.

From Discovery to Medical Miracle

The Development Challenge

Despite his groundbreaking observation, Fleming faced significant obstacles. He found it extremely difficult to isolate and purify penicillin in large quantities due to its instability. His assistants, Stuart Craddock and Frederick Ridley, could only prepare crude solutions to work with. 2

Fleming published his findings in the British Journal of Experimental Pathology in June 1929, but the scientific community showed little initial enthusiasm. At the time, neither Fleming nor his colleagues fully grasped the discovery’s monumental importance, and penicillin’s potential remained largely unexplored for over a decade. 2

The Oxford Team's Breakthrough

The real transformation came when Howard Florey, Ernst Boris Chain, and their colleagues at Oxford University’s Sir William Dunn School of Pathology took interest in penicillin in 1939. They began intensive work on purification and chemistry, eventually producing enough penicillin for animal experiments and clinical trials. 2

In 1940, Florey conducted crucial experiments proving that penicillin could protect mice from deadly bacterial infections.

Then, on February 12, 1941, a 43-year-old policeman named Albert Alexander became the first human recipient of Oxford-produced penicillin.

He had developed a life-threatening infection after scratching his face while pruning roses. Though he initially showed remarkable recovery, supplies ran out and he tragically died. However, subsequent patients responded better, proving penicillin’s tremendous therapeutic potential. 2

Mass Production of Penicillin during World War II

American Innovation

General chemical structure of penicillin, showing the iconic β-lactam ring in red color.

Recognizing that large-scale production was impossible in war-torn Britain, Florey and Norman Heatley traveled to the United States in 1941 seeking help from the American pharmaceutical industry to produce penicillin on a large scale.

They connected with the U.S. Department of Agriculture’s Northern Regional Research Laboratory (NRRL) in Peoria, Illinois, which became important in making mass production possible.

This contact proved crucial to the project’s success, as the NRRL was a key contributor of innovations that made large-scale production of penicillin possible. 2

Pharmaceutical Industry Collaboration

Major American pharmaceutical companies, including Merck, Pfizer, Squibb, Lilly, and Abbott Laboratories, joined forces to tackle production challenges. They solved complex engineering problems related to deep-tank fermentation, cooling systems, mixing technology, and preventing foam formation.

The cooperative effort represented an unprecedented collaboration between government agencies, academic researchers, and private industry. 2

The Race to D-Day

In 1943, the War Production Board (WBP) took direct responsibility for penicillin production, recognizing its critical importance to the war effort. One of the major goals was ensuring adequate supplies for the proposed D-Day invasion of Normandy scheduled for June 1944. The WPB investigated over 175 companies and selected 21 to participate in an urgent penicillin program, giving them top priority for construction materials and supplies.

Albert Elder, who directed the program, urged manufacturers: "You are urged to impress upon every worker in your plant that penicillin produced today will be saving the life of someone in a few days or curing the disease of someone now incapacitated."

Factories placed slogans encouraging workers and notices in pay envelopes to create enthusiasm for the mission.

Production increased dramatically: from 21 billion units in 1943 to over 6.8 trillion units in 1945.

By D-Day in 1944, there was sufficient penicillin to treat all severe casualties.

On March 1, 1944, Pfizer opened the first commercial plant for large-scale penicillin production in Brooklyn, New York. 2

As Florey observed in 1949, “Too high a tribute cannot be paid to the enterprise and energy with which the American manufacturing firms tackled the large-scale production of the drug. Had it not been for their efforts there would certainly not have been sufficient penicillin by D-Day in Normandy in 1944 to treat all severe casualties, both British and American.” 2

Mechanism of Action of Penicillin

Dr. Disha Mathias, Pharm.D., from Rajiv Gandhi University of Health Sciences, describes the mechanism of action of penicillin as:

"Penicillin works primarily by inhibiting bacterial cell wall synthesis. It targets specific enzymes known as penicillin-binding proteins (PBPs), which aid in the cross-linking of peptidoglycan chains. Penicillin inhibits cell wall formation by binding irreversibly to these enzymes, weakening the walls and causing bacteria to lyse. This mechanism causes bacteria to self-destruct, including the activation of autolytic enzymes that further degrade the cell wall (bactericidal effect)."

This targeted approach makes penicillin highly effective against gram-positive bacteria responsible for diseases including certain types of pneumonia and scarlet fever, while remaining relatively safe for human cells. 3

The Nobel Prize and Recognition

Fleming had been knighted by King George VI in 1944 and later received numerous honorary degrees and awards from around the world.4

The Nobel Prize in Physiology or Medicine 1945 was awarded jointly to Sir Alexander Fleming, Ernst Boris Chain and Sir Howard Walter Florey "for the discovery of penicillin and its curative effect in various infectious diseases"

Fleming was also elected a Fellow of the Royal Society in 1943 and became Emeritus Professor of Bacteriology at the University of London in 1948.

Time magazine later named him one of the 100 most important people of the 20th century, recognizing penicillin’s profound impact on human health and longevity. 4

Fleming's Prophetic Warning: Antibiotic Resistance

During his Nobel Prize acceptance speech in 1945, Fleming issued a prescient warning that remains tragically relevant today. He cautioned that bacteria can adapt very quickly to overcome any hurdle that limits their growth and that the process is fast enough that you can almost see it happening in real time.1

Today, penicillin and its derivatives remain among the most commonly prescribed antibiotics globally, continuing to save lives more than 95 years after Fleming’s accidental discovery.

As Dr. Disha said ,"Penicillin's discovery not only saved millions of lives, but it also accelerated the development of current pharmaceutical production and therapeutic approaches."

Frequently Asked Questions (FAQs) about Penicillin

When did Alexander Fleming discover penicillin?

Alexander Fleming discovered penicillin in 1928, when he first observed its bacteria-killing effect in his London laboratory, a finding that became the foundation for modern antibiotics.

Was the discovery of penicillin truly accidental?

Yes, penicillin was mostly found by chance, and it has transformed medicine all around the world.

- Dr. Disha Mathias

How does penicillin work against bacteria?

"Penicillin works primarily by inhibiting bacterial cell wall synthesis. It targets specific enzymes known as penicillin-binding proteins (PBPs), which aid in the cross-linking of peptidoglycan chains."

- Dr. Disha Mathias

What is penicillin used for?

Penicillin is highly effective against many gram-positive bacteria responsible for diseases including certain types of pneumonia, scarlet fever, some causes of meningitis, and diphtheria, while remaining relatively safe for human cells.

Conclusion

Alexander Fleming’s chance observation of a contaminated petri dish on that September morning in 1928 sparked a medical revolution that continues to save lives today. His discovery, combined with the determination of the Oxford team and the innovative spirit of American researchers and pharmaceutical companies, transformed penicillin from “mold juice” into one of humanity’s most important medicines.

References:

  1. Letek M (2020) Alexander Fleming, The Discoverer of the Antibiotic Effects of Penicillin. Front. Young Minds. 8:159. doi: 10.3389/frym.2019.00159

  2. American Chemical Society International Historic Chemical Landmarks. Discovery and Development of Penicillin. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html (accessed Month Day, Year).

  3. Yip DW, Gerriets V. Penicillin. [Updated 2024 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554560/

  4. Tan SY, Tatsumura Y. Alexander Fleming (1881–1955): Discoverer of penicillin. Singapore Med J. 2015;56(7):366-367. doi:10.11622/smedj.2015105

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