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Editorial: Howard Florey and the penicillin story

Journal of Orthopaedic Surgery, Dec 1997 by Bauze, Robert

This year (1998) marks the centenary of the birth of Howard Florey, the man whose development of the clinical use of penicillin ushered in the antibiotic era, saving countless millions of lives and making possible the treatment of serious orthopaedic infections and the major joint replacement surgery that we perform today.

In 1945, with Alexander Fleming and Ernst Chain, Howard Florey was awarded the Nobel Prize in Medicine and Physiology, the world's greatest honour for a medical scientist.

In a memorial service in Westminster Abbey after Florey's death in 1968, Lord Adrian, the great physiologist and a Nobel Laureate himself, described Florey as 'one of the great leaders of medical science millions owe their very lives to him and for what he did - Florey is to be honoured as were Pasteur, Jenner and Lister.'

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Howard Florey was born in Adelaide on 24 September 1898, the son of an English immigrant, a successful shoemaker, Joseph Florey and his wife Bertha. At high school he developed a love of science and a feeling for chemistry as well as skill in athletics and other sports, particularly tennis.

At the age of 13, in his first year of high school, at St Peter's Adelaide, he announced to his older sister, Hilda, then a medical student, that he wished to devote his life to research. As medicine offered the possibility of a research career, on graduating as Dux of the School, he entered the Faculty of Medicine at the University of Adelaide in 1916.

At that time the Adelaide Medical School was oriented to producing general practitioners. So after a very distinguished academic career, in 1922 when he was awarded the Rhodes Scholarship for Australia to the University of Oxford, England, he proceeded to pursue a career as a medical scientist.

Florey was probably fortunate to settle into physiology under the direction of the famous pioneering neurophysiologist, Sir Charles Sherrington, and he subsequently graduated with first class honours in physiology at the University of Oxford. From there he was appointed to the Department of Pathology in Cambridge where he proceeded to apply physiological principles to pathology. His experimental work included cerebral circulation, vessel response to injury, mesenteric blood flow and lymphathic vessels. Florey also pursued his interests in lysozyme, an enzyme in mucous (and many other natural secretions and products) which causes bacterial cells to breakdown or lyse. He noted an earlier publication by Alexander Fleming, a London microbiologist, on mucous lysozyme. Thus, more than 10 years before penicillin, the scientific lives of Florey and Fleming crossed paths. (Incidentally, Florey had developed an interest in lysozymes because of his own digestive disorders.)

In 1926 he married a fellow Adelaide medical student, Ethel Reed. She was the only women graduate of her year and she subsequently was in charge of the first clinical trials of penicillin.

His next appointment was in 1931, as Professor of Pathology at the University of Sheffield. Subsequently, in 1935 he was appointed to the University of Oxford as Professor in the Sir William Dunn School of Pathology, where he did his most famous work. In Oxford, Florey continued his studies on lysozyme and built up a large research team, helped by a benefaction to Oxford by Lord Nuffield (of Morris Cars, MGs and Nuffield Orthopaedic Centre). From Cambridge, Florey recruited a biochemist, Ernst Chain, a Jewish refugee from Nazi Germany.

Chain and Florey searched the scientific literature and found the report of an observation by Alexander Fleming in 1929 of the antibacterial activity of the mould Penicillium notatum.

The story of Fleming's observation is interesting. Fleming was a bacteriologist working at St Mary's Hospital, Paddington, London, England. He had observed an accidental occurrence. Some bacterial culture plates were left in his laboratory sink over a weekend. One of the plates, which had been growing staphylococcus, had been contaminated by a mould. Around the mould was an area where the bacteria had not grown. Something had stopped them growing. It is not known how the mould contaminated the bacterial culture plate. It was just an accident. Fleming identified the mould as Penicillium notatum, and its secretion which prevented bacterial growth and which he called 'penicillin'. It was very unstable and Fleming believed that it was of no practical use in medicine. However, he carefully documented the observation and published it in The Lancet. It was this report that Florey and Chain decided to investigate further.

Chain subsequently worked on the purification of penicillin and its stability and Florey did further biological tests. Heatley, one of the two sole survivors of Howard Florey's Oxford team reports as follows:

'... the first mouse protection experiment was started... on Saturday, 25 May 1940, and proved to be a watershed. Eight white mice were injected intraperitoneally with a lethal dose of Streptococcus pyogenes which had been passaged to make it more mouse-virulent. One hour later, two mice were given a single intramuscular dose of 10 mg of a penicillin preparation. Two other mice were given 25 mg of the same preparation, in four divided doses, at roughly twohour intervals, and four mice were given no penicillin. At 3.30 am on 26 May (within 17 hours), the four control mice were all dead. Of the treated animals, one survived for six weeks and was reckoned to have been cured. The others survived for four, six and 13 days. (MJA 1998,169:316-7)'

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Editorial: Howard Florey and the penicillin story

Journal of Orthopaedic Surgery, Dec 1997 by Bauze, Robert

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