General knowledge · Inventions & discoveries

Penicillin

1928 (observed); 1941 (first clinical use)

Discovery — medicine

In September 1928 Alexander Fleming returned from holiday to a cluttered laboratory at St Mary's Hospital, Paddington, and found a stray mould on a staphylococcus plate with a clear ring around it where the bacteria had dissolved. He named the active substance after the mould but could not purify it, and the observation lay largely unused for a decade. The drug was made real by Howard Florey's team at Oxford, who purified it, proved it in mice in 1940 and in patients from 1941, and drove mass production in wartime America; the three-way Nobel Prize of 1945 went to Fleming, Florey and Ernst Chain.

How to spot them

▸A contaminated culture plate at St Mary's Hospital, Paddington, on 3 September 1928
▸The Dunn School at Oxford; bedpans used as culture vessels; a policeman who improved and then died
▸A mouldy cantaloupe from Peoria, Illinois, and a lab assistant nicknamed 'Mouldy Mary'
▸The beta-lactam ring, whose structure Dorothy Hodgkin worked out by X-ray crystallography

Key facts

A contaminated culture plate at St Mary's, Paddington, 3 September 1928 (1928)

Staphylococci had dissolved in a ring around a stray blue-green mould; the discoverer at first called the liquid 'mould juice'

Albert Alexander, the Oxford policeman treated in February 1941 (1941)

He rallied dramatically, then died when supplies ran out; the drug was recovered from his urine and re-used

Bedpans pressed into service as culture vessels at the Dunn School

Norman Heatley's improvised production line, using porcelain vessels of his own design

A mouldy cantaloupe from a market in Peoria, Illinois

It yielded the high-yielding Penicillium strain behind wartime mass production; the assistant who hunted such samples was nicknamed 'Mouldy Mary' Hunt

Dorothy Hodgkin's X-ray work revealed its four-membered ring (1945)

The beta-lactam ring, which blocks bacterial cell-wall construction

The Nobel Prize in Physiology or Medicine 1945, shared three ways (1945)

Fleming, Florey and Chain; Norman Heatley was left out, and received an honorary Oxford doctorate of medicine in 1990

Its discoverer used his Nobel lecture to warn about resistance (1945)

He warned that under-dosing could educate microbes to resist the drug

Key ideas

It works by blocking the enzymes that cross-link peptidoglycan, so a growing bacterium cannot finish its cell wall and bursts; human cells have no cell wall, which is why the drug is so well tolerated
Resistance usually comes from beta-lactamase enzymes that cut the four-membered ring open, which is why it is often paired with an inhibitor such as clavulanic acid

Quick-fire facts

•The mould was identified as Penicillium notatum, now reclassified as Penicillium rubens; it may have drifted up from the mycology lab on the floor below
•Fleming published in 1929 in the British Journal of Experimental Pathology and got almost no response
•The mouse protection experiment by Florey, Chain and Heatley on 25 May 1940 was the turning point
•Heatley travelled to the United States in 1941; production was scaled up at the Northern Regional Research Laboratory in Peoria using corn steep liquor
•Deep-tank fermentation took output from trickles to millions of doses in time for the D-Day landings in June 1944
•Fleming, Florey and Chain shared the 1945 Nobel Prize in Physiology or Medicine
•Fleming had earlier discovered the enzyme lysozyme, in 1922
•Florey was Australian, born in Adelaide; Chain was a German-Jewish refugee from Berlin
•Dorothy Hodgkin determined the structure in 1945 and won her own Nobel Prize, in Chemistry, in 1964
•Ernest Duchesne had described the antibacterial power of a Penicillium mould in his 1897 Lyon thesis, which went unnoticed

Drill it — 10 cards

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Sources

Science Museum — How was penicillin developed?
The Nobel Foundation — The Nobel Prize in Physiology or Medicine 1945