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Penicillin: World War II Infections and Howard Florey

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Penicillin: World War II Infections and Howard Florey In Focus Penicillin: World War II infections and Howard Florey The results were dramatic – the control mice rapidly succumbed, while all of the treated mice survived. These results attracted great interest from the scientific and military communities because, if Ian Gust replicated in humans, the drug had the potential to influence the Department of Microbiology and outcome of WWII. Immunology University of Melbourne It took Florey and 16 colleagues several months to produce suffi- Parkville, Vic. 3010, Australia Tel: +61 3 8344 3963 cient material to treat a handful of patients. The team worked under Fax: +61 3 8344 6552 fi fi Email: [email protected] dif cult circumstances with a lack of funding and equipment; at rst penicillin was made using old dairy equipment. Hospital bedpans were later used to grow the mould and the liquid containing fi Howard Florey is celebrated for his major contributions to penicillin drained from beneath the growing mould and ltered the large-scale production of the fungal product, penicillin, through parachute silk. during World War II (WWII), leading to life-saving outcomes The first patient they treated was a policeman, in whom an infected for many more than those with war wounds. scratch had developed into a life threatening infection. He was given Howard Florey was born in South Australia in 1898. After studying penicillin, and within a day began to recover. Unfortunately Florey’s medicine at the University of Adelaide he was awarded a Rhodes team only had sufficient drug for 5 days of treatment and when Scholarship to work in Oxford under Sir Charles Sherrington. After their efforts to recycle penicillin from the patient’s urine failed, subsequently undertaking a PhD at Cambridge and a brief period he relapsed and died. Because of this experience, the team then as Professor of Physiology at The University of Sheffield, he was concentrated their effects on sick children, who did not require such appointed to a chair in the Sir William Dunn School of Pathology at large quantitates of the drug, demonstrating its value in a child with Oxford, where he remained until his retirement. septicaemia and another with meningitis. In the 1930sbacterial infections were anunimportant cause ofillness By mid-1941 the drug’s potential was widely recognised and it was and death in civilian populations were untreatable. In civilian life, clear that the team needed the help of industry to produce it at large diseases such as meningitis and pneumonia were frequently fatal, scale. Companies in Britain were unable to help out because of the minor wounds could result in cellulitis or life threatening septicae- war, so later that year Florey and Heatley took a dangerous flight mia and sexually transmitted diseases such as syphilis and gonor- to the United States in a blacked-out plane. Penicillin production fi rhoea were serious conditions. On the battle eld it is estimated that was declared a war project and given high priority. Florey convinced up to one-third of lives lost were due to secondary infections. four major pharmaceutical companies (Pfizer, Abbott, Merck and Florey became interested in the use of natural substances to combat Lederle) and many smaller players to become involved. infections and in 1938, with biochemist Ernst Chain, began a During these meetings Florey encountered a scientist from the systematic study of the antibacterial properties of substances pro- Department of Agriculture who was searching for a new use for a duced by bacteria and fungi. They selected penicillin, a substance thick liquid that was a by product from the milling of corn. When this produced by the fungus Penicillium notatum, which had been liquid was used, as a substrate the yield of penicillin was increased described by Alexander Fleming almost a decade earlier, for further 10-fold. A further boost was given when Mary Hunt (known as study. Chain and his colleague Norman Heatley were able to devise Mouldy Mary) found a species of penicillin growing on a moulding extraction and purification techniques which enabled them to cantaloupe (P. chrysogenum) was almost 200 times as successful obtain sufficient penicillin to test its efficacy in laboratory animals. again in producing penicillin as P. notatum. Further modifications On 25 May 1940, a batch of laboratory mice were injected with resulted in strains almost 1000 times as productive as Fleming’s a lethal dose of streptococci and half then treated with penicillin. original cultures. MICROBIOLOGY AUSTRALIA * SEPTEMBER 2014 10.1071/MA14042 177 In Focus By late 1943 mass production of the drug had commenced in 25,000 A paper that he wrote played a seminal role in the decision to gallon aerated metal tanks, a process that Pfizer devised and made establish the Australian National University and during 1947–1958 available to its rivals and later that year Florey was able to test the he was closely associated with development of the John Curtin drug in soldiers in North Africa, with dramatic results especially in School of Medical Research, effectively acting as its non-resident the treatment of gonorrhoea. Production continued to rise so that head and declining several offers of the Directorship. some 2 million doses were available for the D-day landings in June Florey was an excellent experimentalist, a gifted writer and a strong 1944. The results were dramatic, the survival rate for wounded and effective administrator who had the knack of getting things soldiers rising from 4 per 100 (WWI) to around 50 per 100 and the done. His last major role, that of President of the Royal Society was death rate from pneumonia, falling from 18% to less than 1%. By the outstandingly successful, resulting in major reforms. end of the war, many laboratories were manufacturing the drug, including Australia’s Commonwealth Serum Laboratories. Florey was an excellent sportsman, who excelled at tennis. He loved to travel, was an enthusiastic photographer and found pleasure in In 1943, the public health worker, Bill Keogh, convinced the war gardening. cabinet that Australia needed to be self-sufficient in penicillin and identified a young vet, Val Bazely, who was serving in an armoured Once the importance of penicillin was recognised, Florey received regiment in New Guinea, as the man for the job. Bazely was ordered many honours. He became a member of the Royal Society in 1941, back to Melbourne and almost immediately sent to the US. He spent was knighted in 1944, received the Nobel Prize in 1945, the French three months visiting major manufacturers and returned in Decem- Legion d’honneur in 1946 and the US Medal of Merit in 1948. In 1965 ber with a great deal of new knowledge, most of it in his head. he was created Baron Florey of Adelaide and later appointed to the Order of Merit. Bazely set himself the heroic target of producing penicillin within six weeks and worked day and night to achieve it. He produced As one of Australia’s greatest scientists, Florey has been rightly specifications and working drawings, designed purification process- celebrated. His likeness adorns Australia’s $50 note, and his name es, identified suppliers and fabricators, commandeered equipment lives on – both a suburb in Canberra and a major research institute in and scrounged for scarce raw material. To obtain efficient staff, he Melbourne are named after him. persuaded soldiers who were awaiting discharge to assist him. By February, 1944, 10 weeks after his return, a sizable quantity of Biography material had been produced and, by April, CSL became the first Professor Ian Gust A.O., is a medical virologist with advanced company in the world able to provide penicillin to both soldiers training in pathology and infectious diseases. In 1986 he established and civilians. the Burnet Institute (1986) and became its founding director. In Despite living in Britain for all his working life, Florey took a great 1990 he became the R&D Director at CSL Ltd. More recently he has interest in Australia, hosting many young post-docs in his labora- assisted public and private sector organisations, either as a board tories and visiting regularly. member or scientific advisor. International Symposium on the Biology of Actinomycetes Kusadasi, Aydin - Turkey 8–12 October 2014 Register at www.isba17.com 178 MICROBIOLOGY AUSTRALIA * SEPTEMBER 2014.
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