The full story
This is the episode's narration, word for word. Headings jump to that point in the video.
The question 0:00
Before the nineteen-forties, a scratch could kill you. The first antibacterial drugs, the sulfa drugs, had only arrived in the mid-thirties, and hospitals were still full of people with blood poisoning from a cut. In 1928, a mould was seen killing bacteria on a plate in London. But it wasn't until 1941 that it was injected into a patient to fight an infection. Why did it take so long? And what does a boy from Adelaide have to do with it?
The plate 0:32
In September 1928, the bacteriologist Alexander Fleming came back from holiday to a stack of culture plates growing Staphylococcus, a common cause of boils and abscesses. One had been spoiled by a mould. Around the mould, the bacterial colonies had gone see-through. They were bursting open, a process called lysis. Something was leaking out of the mould and killing them.
Why would a mould do that? 1:02
That's less strange than it sounds. In nature, microbes are surrounded by rivals, and many make chemicals that hold those rivals back. Bacteriologists saw one microbe inhibiting another all the time. What made this one special was its target. It hit some of the germs behind our most common infections.
What Fleming showed 1:26
Fleming grew the mould in broth, and named the active substance penicillin, after the mould, Penicillium. Even diluted a thousand times, the broth still stopped Staphylococcus growing. He published all this in 1929. So why didn't it become a medicine?
Why it stalled 1:49
In Fleming's own words, penicillin "is easily destroyed". His team tried to concentrate it and failed. "We were bacteriologists, not chemists," he said. His few trials on patients gave "favourable results but nothing miraculous". And there was a step Fleming never took: infecting an animal and seeing whether penicillin could cure it. So for about ten years, penicillin was mostly a laboratory tool.
The boy from Adelaide 2:21
Howard Florey was born in Adelaide in 1898, the son of a boot manufacturer. He studied medicine at the University of Adelaide, then left for Oxford as a Rhodes scholar in 1921. By 1935 he ran Oxford's Sir William Dunn School of Pathology. So let's be honest about the Australian part. Florey was Australian-born, and stayed Australian in accent and outlook, but this work was done in England. It was paid for partly by America's Rockefeller Foundation.
The team 2:55
Ernst Chain, a Jewish biochemist, had fled Berlin in 1933. It was Chain who dug up Fleming's overlooked paper. Norman Heatley, a young Cambridge biochemist, had joined in 1936. From 1938 to 1939, Florey and Chain began testing natural antibacterial substances, and they chose penicillin. Florey's team grew to about a dozen scientists and technicians, including the chemist Edward Abraham.
Getting it out 3:30
Step one was getting the penicillin out of the broth. It was already known that in acid, penicillin moves out of water into a solvent like ether. Heatley's trick was the return trip. Shake that solvent with water that isn't acidic, and the penicillin moves back into the clean water. Why? Penicillin is a weak acid. In acid it's mostly uncharged, and it prefers the oily solvent. In neutral water it carries a charge, and charged molecules prefer water. Most of the junk doesn't make the same round trip, so the penicillin comes out cleaner.
How little there was 4:11
And there was very little to get. Oxford's broth held only about one to two units of penicillin per millilitre, and a unit turned out to be just over half a millionth of a gram. That's roughly one gram of penicillin in a tonne of broth.
Eight mice 4:28
On Saturday the twenty-fifth of May, 1940, they ran the test Fleming never did. Eight mice were injected with a lethal dose of streptococcus bacteria. An hour later, four of them got penicillin. The other four got nothing. Those four are the controls. Same mice, same bacteria, so any difference has to come from the penicillin. Heatley stayed up. By about half past three in the morning, all four untreated mice were dead. All four treated mice were alive.
"Of practical importance" 5:07
Heatley wrote in his diary that it "really looks as if penicillin may be of practical importance". He also noted that he'd put his underpants on back to front in the dark. They published in The Lancet that August. But a person is about three thousand times heavier than a mouse, and needs about three thousand times as much penicillin.
Bedpans 5:30
British drug companies, stretched by the war, wouldn't take it on, so the Dunn School became a penicillin factory, running around the clock. The mould needs air, so it grows on the surface of the broth. They used whatever was wide and shallow: baths, pie dishes, biscuit tins, and hospital bedpans. Heatley designed a better vessel, a tray holding one litre at less than two centimetres deep. Pyrex wanted six months to make it.
Christmas in the Potteries 6:02
So Heatley tried pottery instead. A firm in Stoke-on-Trent, James Macintyre and Company, made ceramic versions almost at once. On the twenty-third of December 1940, Heatley borrowed a van and brought back the first 174. On Christmas Day, he seeded them with mould. A small team of young women, hired at two pounds a week and nicknamed the penicillin girls, tended the cultures.
Albert Alexander 6:32
The first patient given Oxford's penicillin to fight an infection was Albert Alexander, a forty-three-year-old policeman. An infection had spread across his face and scalp, and he had already lost an eye. The usual story blames a scratch from a rose bush. But an old police pamphlet suggests he was hurt in a bombing raid, and his hospital notes don't say which. From the twelfth of February 1941, he was given penicillin, and within a day he was much better. There was so little that they recovered it from his urine to reuse. Then it ran out. He relapsed and died on the fifteenth of March.
Proof, and a promise 7:16
Alexander's death showed the problem was supply, not the drug. Florey vowed always to have enough penicillin to finish a treatment. Of the next seriously ill patients, four recovered, among them a fifteen-year-old boy with an infected wound. Florey's wife Ethel, also an Adelaide-trained doctor, took part in the clinical trials that followed. But Oxford's first month of production came to only about a hundred thousand units, around sixty milligrams of the pure drug.
America and a rockmelon 7:48
In July 1941, Florey and Heatley flew to America. At a government lab in Peoria, Illinois, Andrew Moyer added corn-steep liquor, a waste product from processing corn, to the broth, and yields jumped tenfold. Then they moved from trays to deep tanks, stirred and bubbled with air, so the mould grows all through the liquid. Fleming's mould did poorly in tanks, so they searched the world for a better one. The winner came from a mouldy cantaloupe, what we'd call a rockmelon, from a Peoria market. In the best-known account, a lab technician, Mary Hunt, found it, but even that is uncertain.
From milligrams to tonnes 8:33
In March 1944, Pfizer opened the first commercial plant making penicillin in deep tanks. American output went from twenty-one billion units in 1943 to more than six point eight trillion in 1945. That's about four tonnes of pure penicillin. Florey said that without the American companies, there wouldn't have been enough penicillin by D-Day. Back home, the army pathologist Bill Keogh appointed P. L. Bazeley to supervise Australian production, and Australia became one of the first countries to use penicillin widely.
Who gets the credit? 9:14
In 1945, the Nobel Prize in Physiology or Medicine went to Fleming, Chain and Florey, in equal shares. Fleming became the famous one, partly because he talked to the press and Florey wouldn't. Heatley wasn't included. A Nobel can be shared by at most three people, and one Oxford historian has asked whether that rule alone is why he missed out. In 1990, Oxford gave him an honorary medical doctorate, the first for a non-medic in eight hundred years. And Florey never patented penicillin.
How it kills 9:53
So how does penicillin actually work? Most bacteria wrap themselves in a wall called peptidoglycan, long sugar chains tied together by short cross-links. As a bacterium grows, an enzyme keeps tying new links. Penicillin has a small, strained four-sided ring, the beta-lactam ring, that looks like the piece the enzyme normally grabs. The enzyme grabs penicillin instead, and gets stuck. The wall weakens, water pushes in, and the bacterium bursts. That's the lysis Fleming saw on his plate. Our own cells have no peptidoglycan, so the target isn't there.
The bacteria fight back 10:40
Resistance showed up almost at once. In December 1940, before Alexander was treated, Chain and Abraham reported a bacterial enzyme that destroys penicillin. It cuts that ring open. Bacteria were evolving defences against each other's chemicals long before we came along. Use an antibiotic, and the few resistant bacteria survive and multiply, and they can even pass resistance genes to others. By the late nineteen-sixties, more than eighty per cent of staph strains resisted penicillin. In 2019, resistant infections directly caused an estimated one point two seven million deaths.
Fleming's warning 11:23
Fleming saw this coming. In his Nobel lecture, he warned that exposing microbes to "concentrations not sufficient to kill them" could make them resistant. He imagined a man who takes "not enough to kill the streptococci but enough to educate them to resist penicillin". Today, scientists see misuse and overuse as the big drivers, and how to use antibiotics is a question for your doctor, not this video.
Seeing inside 11:54
Penicillin let doctors fight what they couldn't see. Next time, an Australian team helps them see it. How do you make a picture of the inside of a body using nothing but sound?
Sources
Every factual claim in the episode is tied to one of these. Spotted an error? Tell us.
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Image credits
- Fleming, Br. J. Exp. Pathol. 1929 · Wellcome Collection L0007150 · CC BY 4.0 · via Wikimedia Commons · licence: https://creativecommons.org/licenses/by/4.0/
- Howard Florey, Dunn School, Oxford, 1944 · Ministry of Information · IWM D 17803 · public domain · via Wikimedia Commons
- Ernst Chain, Dunn School, Oxford, 1944 · Ministry of Information · IWM D 17806 · public domain · via Wikimedia Commons
- Early penicillin equipment: glass flasks and milk churns (Ernst Chain papers) · Wellcome Collection L0015392 · CC BY 4.0 · via Wikimedia Commons · licence: https://creativecommons.org/licenses/by/4.0/
- Wartime poster 'We are United Nations: Miracles of Medicine' (series by Life) · No Copyright – United States · Hennepin County Library / DPLA · via Wikimedia Commons
- Norman Heatley's blue plaque, Old Marston · photo Bill Nicholls · CC BY-SA 2.0 · via Wikimedia Commons · licence: https://creativecommons.org/licenses/by-sa/2.0/
- Alexander Fleming in his laboratory, St Mary's, 1943 · official photographer · IWM TR 1468 · public domain · via Wikimedia Commons
Researched and scripted with AI assistance, fact-checked claim by claim, with synthetic narration and diagrams drawn in code. How we make episodes.
