Penicillin: How a Mould Became the First Antibiotic

In 1900 a scratch from a rose thorn could kill you. Infected wounds, pneumonia, blood poisoning and childbirth fever were ordinary causes of death, and doctors could do little about them. Then a mould drifted onto a laboratory dish, a curious scientist noticed, and a team in Oxford turned an unstable mould juice into a drug. This guide tells the whole story: the chance observation, the years of hard chemistry, the wartime factories, the way penicillin actually works, and the resistance problem that follows every antibiotic.

Life before antibiotics

Before the 1940s, bacterial infections were deadly because doctors had few effective drugs. Soldiers in the First World War often died of infected wounds rather than the injuries themselves. Pneumonia, scarlet fever, meningitis and blood poisoning killed children and adults. Surgery was risky because infection could follow any operation, and giving birth carried the danger of puerperal fever. The best tools were cleanliness, rest, and hoping the patient’s own body would win.

The accident that was not quite an accident

In September 1928 the Scottish bacteriologist Alexander Fleming returned to St Mary’s Hospital in London after a holiday. He had been studying Staphylococcus bacteria, and a culture dish left on his bench had been contaminated by a mould. Around the mould, the bacteria had disappeared, leaving a clear ring.

Plenty of researchers might have thrown the dish away. Fleming looked closer. He grew more of the mould, identified it as a Penicillium, and found that the liquid it produced killed many kinds of bacteria. In 1929 he published his findings and called the active substance penicillin.

Luck mattered, since mould spores landed in the right place at the right time, but Fleming’s training mattered too. Fleming had already discovered lysozyme, an antibacterial substance in tears, and he was primed to notice a substance that kills bacteria. He did not manage to purify penicillin, though, and it broke down quickly. For a decade it remained a laboratory curiosity.

How penicillin works

Bacteria are surrounded by a tough cell wall that stops them bursting under their own internal pressure. The wall is built from a mesh of sugar and protein chains that must be cross-linked as the cell grows. Penicillin contains a four-membered ring of atoms, the beta-lactam ring, which jams the enzymes that do this cross-linking.

Turning mould juice into a medicine

In the late 1930s, at the University of Oxford, Howard Florey (an Australian pathologist) led a team that included the biochemist Ernst Chain and the technician Norman Heatley. They set out to purify penicillin and test whether it worked in animals. Heatley devised ways to extract the fragile substance from the mould broth, using different solvents and changes in acidity. In 1940 they tested it on mice infected with a deadly dose of streptococci: the treated mice lived, and the untreated ones died.

In early 1941 they gave penicillin to a human patient, Albert Alexander, a policeman suffering from a severe infection. He improved dramatically, but the team did not have enough drug to finish the treatment, and he died. The lesson was clear: penicillin worked, but it had to be made in vastly greater quantities.

Mass production in wartime

With Britain at war and its industry under pressure, Florey and Heatley travelled to the United States in 1941 to interest American laboratories. At the US Department of Agriculture lab in Peoria, Illinois, scientists found that growing the mould in deep tanks, with corn steep liquor as food, gave far higher yields. A laboratory worker known as “Moldy Mary” brought in a rotting cantaloupe in 1943, and its mould, Penicillium chrysogenum, proved to produce much more penicillin than Fleming’s original strain. Further selection and mutation raised yields again.

By D-Day in June 1944 there was enough penicillin to treat Allied wounded. A drug that had been a few precious grams in 1941 was being manufactured by the kilogram. In 1945 Fleming, Florey and Chain shared the Nobel Prize in Physiology or Medicine. The same year, Dorothy Hodgkin worked out the molecular structure of penicillin, a step that later allowed chemists to make new variants.

Try it: how fast bacteria multiply

One reason infections are dangerous is that bacteria multiply by doubling. In good conditions, some bacteria divide every 20 minutes or so. Drag the slider to see what exponential growth does.

Resistance: a toy model in Python

Any large population of bacteria contains a few cells that happen to be resistant. When a drug kills the susceptible majority, the resistant few take over. This toy model shows how quickly that happens. It is a simplification, not a clinical prediction.

resistant = 1e-6          # fraction of bacteria already resistant
kill_susceptible = 0.999  # share of susceptible bacteria killed per course

for course in range(0, 5):
    print(f"After {course} courses: {resistant * 100:9.4f}% resistant")
    survivors_susceptible = (1 - resistant) * (1 - kill_susceptible)
    resistant = resistant / (resistant + survivors_susceptible)

Output:

After 0 courses:    0.0001% resistant
After 1 courses:    0.0999% resistant
After 2 courses:   50.0000% resistant
After 3 courses:   99.9001% resistant
After 4 courses:   99.9999% resistant

The lesson is selection: each course of treatment kills the weak and leaves the strong. In real life the dynamics are more complex, with mutation, gene swapping between bacteria and the patient’s own immune system, but the direction is the same. Fleming himself warned in 1945 that using too little penicillin could teach bacteria to resist it.

Penicillin in India

India set up its first large-scale antibiotics factory soon after independence. Hindustan Antibiotics Limited was established at Pimpri near Pune on 10 March 1954, and the plant was commissioned in 1955-56. It was India’s first manufacturer to make antibiotics, including penicillin and streptomycin, on a commercial scale. The company has struggled financially since the 1990s, but it marked the start of an Indian pharmaceutical industry that is now among the world’s largest suppliers of generic medicines.

Today India also faces a heavy burden of resistant infections. Antibiotics are widely used, and in some places they are bought without prescription. India published a National Action Plan on antimicrobial resistance in 2017, and regulators mark many prescription-only antibiotics with a red line on the packaging so that buyers know not to take them without medical advice. Doctors and public-health experts keep stressing one message: use the right drug, at the right dose, only when needed.

Mind map: penicillin at a glance

Common myths

• Myth: Fleming made penicillin into a drug. He discovered it; the Oxford team and American factories made it usable.
• Myth: It was pure accident. Chance played a part, but Fleming’s alert eye and earlier work mattered.
• Myth: Antibiotics treat colds and flu. Those are viral infections, and antibiotics do not act on viruses.
• Myth: Resistance means your body is resistant. It is the bacteria that become resistant, not you.

Frequently asked questions

Keep exploring

Sources

• Penicillin, Encyclopaedia Britannica
• Alexander Fleming, Encyclopaedia Britannica
• Antibiotic, Encyclopaedia Britannica
• Sir Alexander Fleming: facts, Nobel Prize Outreach
• Sir Howard Florey: facts, Nobel Prize Outreach
• Hindustan Antibiotics Limited, Department of Pharmaceuticals, Government of India
• Antimicrobial resistance, World Health Organization

Featured image: Image: Ministry of Information Photo Division Photographer, via Wikimedia Commons, Public domain. This guide is for general education and is not medical advice.