How was penicillin discovered and made into a medicine?

Penicillin was noticed by chance in 1928 by Alexander Fleming in London, but he could not purify it. A team at Oxford led by Howard Florey and Ernst Chain isolated it and showed it worked in animals and then in a person around 1939 to 1941. Researchers in the United States then scaled up production with deep fermentation tanks and a better mould strain, so that by 1943 there was enough for the Allied armed forces. [1] [2]

In 1928 Fleming, a bacteriologist at St. Mary's Hospital, returned from a holiday and found mould growing on a dish of Staphylococcus bacteria, with the bacteria failing to grow around it. He identified the mould as a Penicillium and named its active substance penicillin. He published in 1929 and found it acted against staphylococci and other gram-positive bacteria. [1] [2]

The compound proved unstable, and chemists he recruited could not purify it. One of them, the biochemist Harold Raistrick, called production for therapeutic use almost impossible. Fleming's peers showed little interest, and penicillin came to be seen as a laboratory curiosity, though Fleming kept sending the mould to anyone who asked for it. [1] [2]

Chain found Fleming's article and proposed isolating the compound to Florey. Florey assembled a team that included Norman Heatley, who worked on growing the mould in quantity, and Chain, who purified the drug. On 25 May 1939, according to the CDC journal, eight mice were infected with Streptococcus and four were given penicillin. By the next morning all the untreated mice were dead and the treated ones were alive. The Science Museum dates a similar mouse experiment to 1940, so the sources differ on the year. The results were published in The Lancet in August 1940. [2] [1]

Output was the bottleneck. Gallons of mould broth yielded only a fingernail's worth of penicillin, and the team improvised with containers such as bedpans and milk churns. Heatley designed semi-automatic apparatus to extract and purify the drug. In February 1941 an Oxford policeman with severe infection was the first person treated. He improved markedly, but the supply ran out and he died weeks later. [1] [3] [2]

British drug companies were tied up with wartime commitments, so Florey and Heatley travelled to the US in June 1941. At the Department of Agriculture's laboratory in Peoria, Illinois, researchers added corn steep liquor, a cornstarch by-product, to the broth, which greatly increased yields. They also used deep-tank fermentation, in which air is bubbled through large tanks while the mixture is stirred. [2] [1]

A search for better strains ended with a mould on a cantaloupe from a local market, found by Mary Hunt, which produced six times more penicillin than Fleming's strain. In 1941 the US had too little penicillin to treat one patient. By the end of 1942 it had enough for fewer than 100, and by September 1943 enough for the Allied armed forces. Penicillin reached the British public in 1946. [2] [1]