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27 June 2023

The legacy of penicillin’s first patient

Albert Alexander’s story should inspire us to renew humanity’s struggle against antimicrobial resistant infections.

By Michael Barrett

On 3 July, in Glasgow at the Scottish Event Campus (SEC), Sheila LeBlanc, visiting from California will be introduced to the World Congress of Pharmacology and members of the public attending a special session on antimicrobial drugs. Sheila, who is now 90, is the daughter of constable Albert Alexander, the first patient ever treated with penicillin. Tragically the first batch of drug ran out before Alexander had fully recovered, although the treatment had been going remarkably well. He died in March 1941. After his death, his wife, Edith, and two young children, Brian and Sheila, had to depart their police house. The children moved to an orphanage. After the war Sheila met and fell in love with an American serviceman, Lieutenant Colonel Lee LeBlanc. They married and later moved back to the US and a gruelling military existence criss-crossing the Atlantic before settling in California in the 1970s, where Sheila has been living ever since. Accompanied by her daughters, she will be flying back to the UK late in June and visit her father’s grave in Newbury and the old family home in Wootton, south of Oxford, before heading up to the congress in Glasgow, where Professor Dame Sally Davies, the UK’s special envoy for antimicrobial resistance, will lead the symposium’s summary of global efforts to deal with the growing crisis in antimicrobial drug resistance that provides an existential threat to humanity today. Antimicrobial resistance, according to Davies, is the global pandemic to worry about. Its impacts will dwarf those of Covid-19 if we don’t act deisively, and soon.

Our “fight” against bacterial disease is often depicted in the vocabulary of war. Man against microbes. The discovery and development of penicillin owed a great deal to necessity born through world war. It was the Scottish doctor, Alexander Fleming, from Darvel, East Ayrshire, who discovered the drug while he was working at St Mary’s hospital in London in 1928. “Flem” as his colleagues called him, had been seeking antimicrobial drugs ever since he’d served as a medic in France during the First World War, where the constant stream of soldiers dying from gangrenous infections acquired at the front horrified him. After discovering lysosome, an antibacterial protein in his own nasal secretions, he was well set to appreciate the meaning of a serendipitous discovery he made returning to his lab after a holiday in the summer of 1928. Some mould, which he identified as Penicillium notatum, had landed on one of his bacteriological plates and lysed the bacteria in its vicinity. It was secreting an agent, which he named penicillin, that killed bacteria. Unfortunately, he didn’t have the requisite skills to purify the agent and could only hope others might have more luck.

At the start of the Second World War interest in Fleming’s work was rekindled by a group of brilliant scientists in Oxford. Howard Florey, an Australian pathologist, had assembled a team that included a number of individuals with those skills in chemical purification that Fleming had lacked. One, Ernst Chain, was a refugee from Hitler’s Germany. Another, Norman Heatley, was a mild-mannered Englishman who had only stayed in Florey’s group when the war prevented his travel to Denmark where he had been due to take up a post. Their combined ingenuity allowed them to purify penicillin. By 26 May 1940 they had enough to show that mice, infected with bacteria, could be cured. This was the same day that the evacuation of the British Expeditionary Force from the beach at Dunkirk had begun. Defeat to Hitler appeared inevitable. However, the Oxford team appreciated that a drug capable of preventing the bacterial infections that killed more soldiers that the immediate effects of battlefield wounds could have a huge impact on the war. Florey converted the Dunn School of Pathology into a makeshift penicillin factory, and a team of six local women, “the penicillin girls”, worked round the clock to harvest the mould from which the chemists produced the drug.

By early 1941 Florey reckoned they had enough drug to test in humans. A terminally ill cancer patient was first given penicillin to confirm it didn’t cause dangerous side effects. All was fine. Dr Charles Fletcher then proposed that Albert Alexander, a police constable who lay “desperately and pathetically ill” in the John Radcliffe infirmary in Oxford, would be an ideal candidate. “There was all to gain for him in a trial of penicillin and nothing to lose” because bacterial sepsis was ebbing his life away. Alexander had picked up a minor wound while seconded to Southampton during the Blitz late in 1940. His treatment began on 12 February 1941. The drug had to be given by intravenous injection every three hours because it was excreted so quickly. After five days Alexander was showing a remarkable recovery, but tragically stocks of penicillin ran out before the cure was complete. He relapsed and died, aged 43, on 15 March 1941.

[See also: The NHS’s decline will have political consequences]

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However, the recovery had shown what could happen if only enough drug were available. In a flurry of activity Florey and Heatley flew on a secret mission to America where they persuaded the US government and a handful of pharmaceutical companies to increase production. By 1944 enough penicillin was available to keep wounded Allied serviceman fighting and the drug is often said to have turned the tide in the Allies’ favour. The antibiotic era had begun.

What of the Germans? They tried to get their hands on penicillin, but a series of heroic interventions by scientists in the Nazi occupied countries thwarted their efforts; scientists provided strains of mould that didn’t produce the drug while concealing the useful Penicillium strains. At Ravensbrück concentration camp the Nazis undertook a series of unspeakably cruel experiments on captive Polish women. Gashes sliced deep into their limbs were filled with a cocktail of lethal gangrene-causing bacteria, along with shards of broken glass, sawdust and soil to mimic battlefield wounds before being treated with another class of sulphur-based antibiotic discovered in pre-war Germany. The drugs didn’t work in those circumstances. The infected subjects generally either died of the disease or were shot once it was clear the drugs had failed.

The medical history books usually conclude the initial work in Oxford with the death of Albert Alexander. But what of his family? It was only in the 1960s when a German journalist turned up at Edith’s house requesting a photograph of Albert that the family had the faintest inkling that he had played a pivotal role in showing penicillin’s potential.

I heard of Sheila’s story from my aunt, who had been friends with her in the 1950s. As I work on antimicrobial drugs I was naturally intrigued by her story and that of her father. The textbooks had created a myth that his lethal infection had come about when he pricked himself on a rose bush while out pruning. This may have been wartime propaganda to disguise the lethal impact of a German bomb. It has been difficult to discover the origin of the rose bush apocrypha, although Sheila recalls the police house did have a beautiful rose garden. Last summer I visited Wootton, a quintessential English village at the foot of Boars Hill, famed for its views across to the “dreaming spires” of Oxford and a former home for poets including Matthew Arnold, John Masefield, Robert Graves and favourite haunt of the painter Paul Nash. I’d hoped to find the old police house, but had no joy. However, I was put in touch with the village history society. Some probing research at their end led to the discovery of Albert Alexander’s wartime ration book and an address that is still there (but no longer a police house) beside the Bystander pub, his local.

Sheila LeBlanc was one of the last of a generation for whom bacterial diseases were a constant and deadly risk. Antibiotics offered the potential to confine bacterial disease to history. Unfortunately, bacteria that resist the lethal effects of antibiotics have emerged. Globally, today, over a million people each year die from antimicrobial resistant infections and the problem is getting worse. Ten million a year will die from antibiotic resistant bugs by 2050 if things aren’t turned around. And yet the pharmaceuticals industry has largely abandoned developing new antibiotics, focusing on more lucrative conditions like cancer and heart disease instead. The antimicrobials symposium at the World Congress of Pharmacology will address the issues confronting progress. It could be that Sheila’s story will remind us of just how deadly bacteria can be and, just like her father did, galvanise a renewed effort to regain the upper hand in humanity’s struggle against contagion.

[See also: The family doctor knows best]

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