History of penicillin
While working at St Mary's Hospital in London in 1928, Scottish physician Alexander Fleming was the first to experimentally determine that a Penicillium mould secretes an antibacterial substance, which he named "penicillin".
It was discovered that adding penicillin to animal feed increased weight gain, improved feed-conversion efficiency, promoted more uniform growth and facilitated disease control.
Many ancient cultures, including those in Australia, China, Egypt, Greece and India, independently discovered the useful properties of fungi and plants in treating infections.
[5] Joseph Lister, an English surgeon and the father of modern antisepsis, observed in November 1871 that urine samples contaminated with mould also did not permit the growth of bacteria.
Nor is it due to the utilization of the available foodstuff by the more quickly growing organisms, rather there is an antagonism caused by the secretion of specific, easily diffusible substances which are inhibitory to the growth of some species but completely ineffective against others.
[17] Two years later, Ernest Duchesne at École du Service de Santé Militaire in Lyon independently discovered the healing properties of a P. glaucum mould, even curing infected guinea pigs of typhoid.
He prepared a culture method from which he could obtain the mould juice, which he called "penicillin" on 7 March 1929, "to avoid the repetition of the rather cumbersome phrase 'mould broth filtrate'.
Charles John Patrick La Touche, an Irish botanist, had recently joined St Mary's as a mycologist, and he identified the specimen as Penicillium rubrum, the identification used by Fleming in his publication.
[86] The Oxford team reported their results in the 24 August 1940 issue of The Lancet, a prestigious medical journal, as "Penicillin as a Chemotherapeutic Agent" with names of the seven joint authors listed alphabetically.
[90][91] The Columbia team presented the results of their penicillin treatment of the four patients at the annual meeting of the American Society for Clinical Investigation in Atlantic City, New Jersey, on 5 May 1941.
[94] Fletcher next identified an Oxford policeman, Albert Alexander, who had a severe facial infection involving streptococci and staphylococci which had developed from a small sore at the corner of his mouth.
Weaver arranged for the Rockefeller Foundation to fund a three-month visit to the United States for Florey and a colleague to explore the possibility of production of penicillin there.
Harrison referred Florey to Thom, the chief mycologist at the Bureau of Plant Industry of the United States Department of Agriculture (USDA) in Beltsville, Maryland, and the man who had identified the mould reported by Fleming.
Pfizer scientists Jasper H. Kane, G. M. Shull, E. M. Weber, A. C. Finlay and E. J. Ratajak worked on the fermentation process while R. Pasternak, W. J. Smith, V. Bogert and P. Regna developed extraction techniques.
Keogh summoned Captain Percival Bazeley, with whom he had worked at the Commonwealth Serum Laboratories (CSL) before the war, and Lieutenant H. H. Kretchmar, a chemist, and directed them to establish a production facility by Christmas.
[130] During his visit to North America in August 1941, Howard Florey approached the Connaught Laboratories at the University of Toronto, where he met with the director, R. D. Defries, and Ronald Hare.
The results of clinical trials caused a change of heart, and in August 1943 the Canadian government asked the Connaught Laboratories to initiate mass production of penicillin.
[134] Three vials of penicillin captured by the Afrika Korps reached Germany in 1943 and one was sent to Heinz Öppinger at Hoechst in Frankfurt, and he began conducting experiments with moulds.
[138][d] Much of Germany's penicillin came from Czechoslovakia, where research was carried out at Charles University in Prague and the Fragner Pharmaceutical Company by a team that included chemist Karel Wiesner.
[140] In 1946 and 1947, penicillin factories were established in Belarus, Ukraine, Poland, Italy and Yugoslavia with plant and expertise from Canada through the United Nations Relief and Rehabilitation Administration (UNRRA), of which Canadian Lester B. Pearson was the head of its supply committee.
[142] Manfred Kiese [de] at the Pharmacological Institute in Berlin published a survey of literature on antibiotics in the 7 August 1943 issue of Klinische Wochenschrift that included the Oxford team's publications.
[154][153] The chairman of the NRC committee on chemotherapy, Chester Keefer was responsible for administering the equitable distribution of penicillin for civilian use on behalf of the CMR.
On 29 June he was joined by Hugh Cairns, another Rhodes Scholar from Adelaide, who now held the rank of brigadier in the British Army, and was in charge of the Military Hospital for head injuries in Oxford, who brought with him a stockpile of 40 million units of penicillin.
[164] Florey considered that the source of infection in many cases was from the hospital rather than the battlefield, and advocated changes to the way that patients were treated to take advantage of the properties of penicillin.
[190][191] In April 1945, the British firm Glaxo signed agreements with Squibb and Merck under which it paid 5 per cent royalties on its sales of penicillin for five years in return for the use of their deep submergence fermentation techniques.
The secretary of the Nobel committee, Göran Liljestrand, made an assessment of Fleming and Florey in the same year, but little was known about penicillin in Sweden at the time, and he concluded that more information was required.
[201] The Nobel Assembly at the Karolinska Institute did consider awarding half to Fleming and one-quarter each to Florey and Chain, but in the end decided to divide it equally three ways.
[199] On 25 October 1945, it announced that Fleming, Florey and Chain equally shared the 1945 Nobel Prize in Physiology or Medicine "for the discovery of penicillin and its curative effect in various infectious diseases.
[217] Research conducted by the American Cyanamid laboratories in the late 1940s and early 1950s demonstrated that adding penicillin to chicks' feed increased their weight gain by 10 per cent.
After the Food and Drug Administration approved the use of penicillin as feed additives for poultry and livestock in 1951, the pharmaceutical companies ramped up production to meet the demand.
