Penicillin

Introduction — a Petri dish that changed the world

Scotland has given the world many gifts, but few match the humble Petri dish that a quiet Ayrshire farmer's son left on his bench in the late summer of 1928. Alexander Fleming's discovery of penicillin began the antibiotic revolution and ranks among the most important advances in the history of medicine.

Yet the real story is richer — and more honest — than the schoolbook legend. Fleming was the discoverer; an international team made it a medicine; and the whole saga is laced with luck, genius, and a good deal of careful myth-busting.

Early Life: From a Lochfield Hill Farm to London

Alexander Fleming was born on 6 August 1881 at Lochfield Farm, a remote hill farm about four miles north of Darvel in East Ayrshire. He was the third of four children of farmer Hugh Fleming and his second wife, Grace Stirling Morton, the daughter of a neighbouring farmer. Hugh already had four surviving children from his first marriage and was 59 when he married Grace. Hugh died when 'Alec' was just seven, and his mother carried on running the farm. It was, by Fleming's own recollection, a poor but happy childhood spent largely in the open air of the Ayrshire moors — an upbringing of keen observation that would serve him well.

He attended Loudoun Moor School and Darvel School, then won a two-year scholarship to Kilmarnock Academy. At around the age of 13–14 he moved to London to live near his elder brother Tom, already a doctor there. He spent four rather dull years as a clerk in a shipping office before, at 20, inheriting a small legacy from an uncle, John Fleming. Encouraged by Tom, he used it to enter medicine, enrolling at St Mary's Hospital Medical School in Paddington in 1901 and qualifying with distinction in 1906.

At St Mary's, chance — and a rifle club — shaped his career. A keen marksman, Fleming was persuaded to join the research department so the club could keep him on its shooting team, and so he became assistant bacteriologist to Sir Almroth Wright, the pioneer of vaccine therapy. During the First World War, Fleming served as a captain in the Royal Army Medical Corps, working in Wright's wound-research laboratory at Boulogne. There he watched, helpless, as soldiers died not from their wounds but from the bacterial infections that followed — and observed that the antiseptics of the day often did more harm than good, killing the body's own defences while failing to reach bacteria deep in jagged wounds. The experience burned a lifelong purpose into him: to find something that could kill bacteria inside the body without harming the patient.

Fleming's character is essential to the story. Colleagues remembered him as quiet, modest and famously taciturn, but a meticulous observer with a dry, mischievous wit. His instinct never to discard an oddity — to ask 'that's funny' rather than reach for the bin — is precisely what made the difference.

The Discovery: September 1928

The famous moment came in his cramped, cluttered laboratory at St Mary's Hospital, Praed Street, London. In August 1928 Fleming went on holiday to his country home at Barton Mills in Suffolk, leaving a stack of culture plates of Staphylococcus — the bacterium responsible for boils, sore throats and abscesses — piled in a corner of his bench. He returned on 3 September 1928, where his former assistant D. M. Pryce was waiting. As they sorted through the plates, Fleming noticed one whose lid had come off and which had been contaminated by a blue-green mould. Around that mould was a clear 'halo' where the staphylococci had been dissolved away. 'That's funny,' Fleming reportedly remarked.

He identified the contaminant as a Penicillium mould — originally classified as Penicillium notatum, and reclassified in 2011, through genome sequencing, as Penicillium rubens. He grew it in broth, found the 'mould juice' could kill many Gram-positive bacteria — staphylococcus, streptococcus, diphtheria — even when diluted hundreds of times, and on 7 March 1929 named the active substance 'penicillin', to avoid, as he put it, 'the repetition of the rather cumbersome phrase mould broth filtrate'. He published his findings in the British Journal of Experimental Pathology in 1929 to almost total indifference.

A note on dates, because this is where myths breed. Fleming's own famous quote — about waking just after dawn on 28 September 1928 — has led many to give that as the discovery date. The documentary evidence points to his return and first observation on 3 September 1928; the 28 September quotation appears to be a later recollection of his realisation. The Fleming Laboratory Museum at St Mary's itself dates the discovery to 3 September 1928.

Chance Favours the Prepared Mind

This is the perfect illustration of Pasteur's maxim that 'chance favours the prepared mind'. Fleming was characteristically honest about the role of luck: 'Nature makes penicillin; I just found it,' and 'One sometimes finds what one is not looking for.' But he was equally clear that luck alone explained nothing: 'My only merit is that I did not neglect the observation.' Countless scientists had seen mould kill bacteria and thrown the plate away; Fleming, primed by a decade hunting for antibacterials, recognised what he was looking at.

The romantic image of a spore wafting through an open window onto the dish is almost certainly false. Fleming himself gave contradictory accounts. His co-workers, including Pryce, later testified that his laboratory window was kept shut and was awkward to reach. The consensus today — supported by his former assistant Ronald Hare's detailed reconstruction in 1966 — is that the spore most likely drifted up the stairwell from the mycology laboratory one floor directly below, run by the Irish mycologist C. J. La Touche, who was growing large collections of moulds for asthma research. Hare also showed that an unusual cold spell in London in late August–September 1928 created exactly the temperature conditions needed for the mould and bacteria to grow in the sequence that produced Fleming's famous halo — another stroke of luck.

How Penicillin Kills Bacteria

Penicillin works by attacking the one structure that bacteria possess and human cells do not: the cell wall. Bacteria such as Staphylococcus are constantly building and rebuilding a rigid outer wall to contain their high internal pressure. Penicillin binds to the very enzymes — penicillin-binding proteins (PBPs) — that bacteria use to stitch that wall together. With the wall weakened, the bacterium's internal pressure does the rest: the cell swells, ruptures and dies, and the body's immune system clears the debris.

Because human cells have no cell wall, the drug largely spares the patient. That is the secret of its astonishing safety, and the reason penicillin and its descendants — amoxicillin, methicillin, the cephalosporins, the carbapenems — remain workhorses of medicine almost a century after Fleming saw his halo.

From Mould Juice to Medicine

Here the story demands honesty, and Scots should be proud enough of Fleming to tell it. Fleming discovered penicillin, but he did not — and by his own admission could not — turn it into a usable drug. He was a bacteriologist, not a chemist: 'I am a bacteriologist, not a chemist,' he once remarked, and his attempts (with assistants Stuart Craddock and Frederick Ridley) to isolate and stabilise the fragile compound failed. By the early 1930s the chemical work had largely stalled.

The breakthrough came a decade later and 50 miles away, at the Sir William Dunn School of Pathology at the University of Oxford. From 1939, a team led by the Australian pathologist Howard Florey and including the German-Jewish biochemist Ernst Chain — a refugee who had fled Nazi Germany in 1933 — took up Fleming's neglected paper. With Norman Heatley, Edward Abraham, Margaret Jennings and others, they devised methods to grow, extract and purify penicillin, proved it could cure infected mice in 1940, and worked out how to measure and concentrate it.

The first human trial, in February 1941, is one of medicine's most poignant episodes. The patient was Albert Alexander, a 43-year-old Oxford-area policeman with a catastrophic infection of staphylococcus and streptococcus that had cost him an eye and spread across his face and lungs. On 12 February 1941 he was given the precious penicillin and improved dramatically within days. But the Oxford team had so little of the drug that — even after recovering and recycling it from his urine — they ran out. Albert Alexander relapsed and died on 15 March 1941. His case proved penicillin worked in humans; it also proved that without mass production, it was useless.

Wartime Britain could not build that production capacity, so in 1941 Florey and Heatley took penicillin to the United States. There, the breakthroughs in scale came: at the USDA's Northern Regional Research Laboratory in Peoria, Illinois, scientists found that corn-steep liquor and deep-tank fermentation dramatically boosted yields, and a high-yielding mould strain was famously found on a mouldy cantaloupe in a Peoria market. By June 1944, American drug companies were producing vast quantities of penicillin — enough that the antibiotic was carried ashore with Allied troops on D-Day, saving countless soldiers from fatal wound infections. The honest summary: Fleming lit the spark; Florey, Chain and their teams, and American industry, built the fire.

Nobel Prize and a Warning from 1945

Recognition, when it came, was immense. Fleming was elected a Fellow of the Royal Society in 1943 and knighted by King George VI in 1944. In 1945, the Nobel Prize in Physiology or Medicine was awarded jointly to Fleming, Florey and Chain 'for the discovery of penicillin and its curative effect in various infectious diseases'.

It is Fleming's Nobel lecture, delivered on 11 December 1945, that now seems almost eerily prophetic. He warned that misusing penicillin could breed resistant bacteria. In his own words: 'The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.' He concluded with a line that should be carved over every pharmacy door: 'Moral: If you use penicillin, use enough.' Eighty years on, with antimicrobial resistance one of the gravest threats to global health, that warning reads like a message from the future.

Legacy — The Drug That Saved Hundreds of Millions

The scale of Fleming's gift is hard to grasp. According to the New World Encyclopedia, 'It is estimated that penicillin has saved at least 200 million lives since its first use as a medicine in 1942'; Oxford's own Sir William Dunn School of Pathology puts the figure even higher, stating that 'over 500 million lives have now been saved by penicillin.' Either way, it conquered once-deadly scourges including pneumonia, syphilis, gangrene, scarlet fever and meningitis, and made modern surgery, childbirth, cancer therapy and organ transplantation vastly safer.

Fleming died of a heart attack at his London home on 11 March 1955, and his ashes are buried in the crypt of St Paul's Cathedral — a rare honour. His old laboratory at St Mary's is preserved as the Alexander Fleming Laboratory Museum, reconstructed to its 1928 condition. He has never been forgotten in Scotland. In 2009 the Clydesdale Bank put his face on its £5 note as part of its World Heritage series. His Nobel Prize medal was acquired by National Museums Scotland in 1989 and is on public display. In Darvel, a memorial in Hastings Square — featuring a bust of Fleming and a circular flower bed inspired by his Petri dish — honours the town's most famous son, and his birthplace at Lochfield Farm is marked and still stands.

He was named one of Time magazine's 100 Most Important People of the 20th Century, one of the BBC's 100 Greatest Britons, and was voted the third 'greatest Scot' in a 2009 STV poll, behind only Robert Burns and William Wallace. The grandest monument of all is abroad: a bronze bust by Spanish sculptor Emilio Laiz Campos, with a full-length bronze matador saluting Fleming with his montera, was unveiled outside Madrid's Plaza de Toros de Las Ventas on 14 May 1964 — inscribed 'To Dr Fleming with the gratitude of bullfighters', because penicillin had so reduced deaths from goring infections in the ring.

The deepest irony of all is the one Fleming himself foresaw. The man who gave the world its first antibiotic also gave it the first clear warning that we might squander the gift — and the antimicrobial resistance crisis of today proves just how right the quiet Ayrshire farmer's son turned out to be.