In September 1928, at St Mary's Hospital in London, the Scottish physician Alexander Fleming noticed that a mould growing on one of his bacterial culture plates had stopped the bacteria around it from growing. Turning that observation into a usable drug took more than a decade: a team at Oxford led by Howard Florey, with Ernst Chain, purified the substance and proved it could cure infections, and American scientists and companies worked out how to make it in bulk during the Second World War. Fleming, Florey and Chain shared the 1945 Nobel Prize in Physiology or Medicine.
Fleming's contaminated plate
Before leaving for his summer holiday at the end of July 1928, Fleming set aside several plates seeded with Staphylococcus aureus. When he returned on 3 September, one plate had been contaminated by a blue-green mould, and the bacteria near it had failed to grow. He cultured the mould and found that it released something that killed certain bacteria, including staphylococci, streptococci and the diphtheria bacillus, but not, for example, the typhoid bacterium. On 7 March 1929 he named the active mould broth "penicillin". The mould, long known as Penicillium notatum or P. chrysogenum, was shown by genome analysis in 2011 to be Penicillium rubens.
Trained as a bacteriologist rather than a chemist, Fleming relied on his assistants, but Stuart Craddock and Frederick Ridley failed to isolate the active substance. His paper, submitted to the British Journal of Experimental Pathology on 10 May 1929, attracted little notice, and Fleming seemed more interested in using penicillin to isolate bacteria in the laboratory than as a medicine. Work on it at St Mary's ended that year.
The Oxford team
In 1939, at the Sir William Dunn School of Pathology in Oxford, Chain drew Florey's attention to Fleming's largely forgotten paper. Florey assembled a team that included Norman Heatley, Edward Abraham, Ethel Florey and Margaret Jennings, funded at first by the Medical Research Council and then by a Rockefeller Foundation grant of US$5,000 a year. Producing enough penicillin was the central problem. The mould was grown on liquid in shallow vessels, including purpose-made ceramic containers modelled on bedpans; Heatley devised a "reverse extraction" to move penicillin from solvent back into water, and Chain proposed freeze-drying to obtain it as a powder.
Mice and the first patients
On 25 May 1940 Florey infected eight mice with a virulent streptococcus and then treated four of them with penicillin. By the early hours of the next day all four untreated mice were dead, while the treated ones were still alive. The team published its results in The Lancet on 24 August 1940. Human trials followed. In February 1941 an Oxford policeman, Albert Alexander, with a severe facial infection, improved dramatically, but the supply ran out and he relapsed and died on 15 March. Later patients, including children who needed smaller doses, recovered.
Mass production
British firms were slow to help, so on 27 June 1941 Florey and Heatley flew to the United States. They were directed to the Department of Agriculture's Northern Regional Research Laboratory in Peoria, Illinois, where Andrew Moyer found that adding corn steep liquor raised yields tenfold. Researchers there developed growth in deep tanks rather than shallow pans, and a mould from a cantaloupe bought in a Peoria market in 1943 yielded a strain that, once mutated with X-rays and ultraviolet light, produced far more penicillin. The company Pfizer opened the first deep-tank production plant on 1 March 1944. American output climbed from 21 billion units in 1943 to 1,663 billion the following year, and the price of a million units fell from $200 to $6 by 1945. In Britain a War Cabinet Penicillin Committee was set up on 5 April 1943.
Credit
When newspapers took up the story in 1942, they cast Fleming as the lone discoverer, while Florey shunned the press. The 1945 Nobel Prize recognised both the discovery and the development of the drug.
On our maps
Our 1930 map shows the United Kingdom where Fleming made his discovery, and the 1945 map shows the world at the end of the war, by which time the United States was producing penicillin on an industrial scale.