Penicillin – The World’s Greatest Collab?

Friday 28 September 1928. Scottish scientist Alexander Fleming would walk into his Imperial College laboratory on the morning of this day to find a petri dish containing staphylococcus bacteria to be contaminated by mold. The mold seemed to inhibit the growth of bacteria, leading Fleming to conclude that it had produced a substance harbouring anti-bacterial properties. The events that would conspire in the following years would arguably be the biggest success story the world has ever witnessed.

This post is about the discovery and subsequent mass production efforts that accelerated the delivery of penicillin to the millions who needed it most. For the synthesis and mechanism of action, check out the Wiki on beta-lactam antibiotics.

Discovery

Although many had already observed the antibacterial properties of mold since ancient times, Alexander Fleming is credited for its discovery as he was the first to isolate and grow a pure culture of the mold, which he found to be Penicillium – and he named the filtered broth penicillin. He was, however, unable extract the antibacterial compound found in the filtrate, which was finally done so by the Australian Howard Florey and his team at Oxford in 1939.

Florey, with German-born Jew Ernst Boris Chain and Englishman Edward Abraham – both members of his research team – went on to discover penicillin’s therapeutic action and its chemical composition. Chain and Florey isolated and concentrated the bactericidal agent in penicillin, while Abraham was involved in theorising the beta-lactam structure of penicillin in 1942. The chemical structure of penicillin was ultimately confirmed using X-ray crystallography by Dorothy Hodgkin in 1945.

penchemstruc
Chemical structure of penicillin, with the beta-lactam ring highlighted in red. The variable R group is shown.

Mass Production

If there is a single catalyst that the mass production of penicillin can be attributed to, it has to be Norman Heatley – another prominent member of Florey’s team. Realizing the importance of quickly producing the drug but hampered by wartime efforts – which in 1940 was now in full swing – Heatley designed and proposed his idea of using ceramic vessels instead of glass to grow cultures of penicillin. This was accepted by James MacIntyre and Co. at Stoke-on-Trent, a town in the English Midlands known as The Potteries for their fine tableware.

By the summer of 1941, there was no doubt about the effectiveness of the antibiotic but efforts to improve yields had stalled.  The Rockefeller Foundation based in New York, which had been supporting Florey’s research, urged him to visit the United States to seek help from pharmaceutical companies. Florey and Heatley flew to Portugal and from there boarded a Pan-Am Clipper seaplane to New York.

1200px-Boeing_314_Yankee_Clipper_1939
Pan-Am Clipper being all fancy and all.

Florey and Heatley went on to acquire the help of the USDA, along with pharmaceutical giants Pfizer and Merck & Co. that all made noticeable contributions to perfecting penicillin production. Large scale production truly began once a fermentation plant was constructed in Brooklyn, overseen by chemical engineer Margaret Hutchinson Rousseau.

Legacy

The introduction of penicillin for wider use was not only felt by those at the front – the use of the antibiotic reduced Allied casualties by a substantial amount as it was delivered in time for the invasion of Normandy – its effects would also be felt by the general population. After World War II, Australia was the first country to make the drug available for civilian use. In the U.S., penicillin was made available to the general public on March 15, 1945.

This meant that sulfonamides – the existing antibiotic treatment overused to the point of ineffectiveness – were replaced and almost overnight, Penicillin changed the face of medicine forever.

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1957 Fermentation ‘Reactor’ – Flickr