Alexander Fleming (1881-1955): A noble life in science Winner in 1945 of the Nobel Prize in Physiology or Medicine with Howard W. Florey and Ernst B. Chain "for the discovery of penicillin and its curative effect in various infectious diseases". Enlarged image         Nobel Prize Certificate, 1945 British Library Add. MS 56213Copyright © The British Library Board   Scientific creativity takes various forms. One of these is serendipity - discovering phenomena while diverting from intended research: pursuing a passing intuition; detecting the significance of a seemingly unexceptional and inconsequential occurrence. Fleming was one of the great exponents of intelligent serendipity, making two outstanding discoveries involving antibiotics. Henry Dale, Nobel Laureate of 1936, commented: "I can assure you that the elegance and beauty of his observations just as a naturalist observer of the phenomenon of lysozyme and of penicillin, as he presented it, did make a great impression and everybody remembered these things". Fleming quite deliberately did not clean his petri dishes each day, but would look at them weeks later; and although his laboratory was focussed on immunotherapy, he did not disregard chemotherapy. Alexander Fleming's scientific success lay in his open, enquiring mind, his strong technical intuition, and his penchant for naturalistic observation. And, as he explained: "I was situated so that I could leave my previous line of work and follow the track which fate had indicated for me". 1881-1900 Childhood Alec Fleming was the son of a Scottish farming family, born in Loudon, a village in the moorlands of Ayrshire, on 6 August 1881. In 1895 he and other family members moved to London, where he continued his schooling at Regent Street Polytechnic. 1901-1913 Medical education and first research At St Mary's Hospital Medical School, he excelled, quickly showing his manual dexterity and inventiveness; so much so that for a while it looked as if a future in surgery beckoned until he was drawn to the attractions of bacteria hunting and therapeutic sleuthing. He completed his degrees at the University of London in 1908, and stayed on at the renowned Inoculation Laboratory of Almroth Wright. 1914-1918 War wounds Just when Fleming was at risk of becoming known only as the 'Pox Doctor' on account of his work with venereal diseases, the Great War intervened and he and Wright found themselves in France at a military hospital in Boulogne. Fleming's research there showed that the bacteria responsible for gas gangrene and tetanus - two great scourges of the trenches - were able to grow in the anaerobic depths of the terrible wounds; moreover, antiseptics did not reach these areas, sometimes exacerbating the condition by harming cells that defend the body. The recommendation that diseased tissues should be cut away was controversial. Enlarged image Enlarged image   Letter from C.A. Pannett to Lady Fleming, 1956; mentions Paul Ehrlich, Nobel Laureate of 1908, and his offer of the new antiseptic salvarsan British Library Add. MS 56215, f.181v & f.181rCopyright © The British Library Board   Medical scientific report on "Cressy's Hole" (war wound), 28 July 1917 British Library Add. MS 56148, f.51  Copyright © The British Library Board 1919-1937 One discovery leads to another: lysozyme and penicillin After the war Fleming returned to St Mary's Hospital, where one day, suffering from a heavy cold, curiosity inspired him to culture his nasal mucus on agar jelly. After some weeks, in November 1921 he looked again at the petri dish, and made the discovery that would be a prelude to that of penicillin, seven years later. Although there was a healthy population of bacteria growing on the culture, those near the mucus had been inhibited or destroyed. Fleming had found lysozyme, an antibacterial enzyme that occurs naturally in tissues and secretions: mucus, tears and egg-white (protecting the embryonic bird). Unfortunately this substance has little effect on the more notoriously harmful bacteria. Nonetheless it had alerted Fleming to the power of natural biological antibiotics. In 1928 history repeated itself, in a more fortuitous way. On returning to the laboratory after some weeks in his country home in Suffolk, he picked up a culture plate of the Staphylococcus bacteria that he had left on the bench. A contaminating mould had grown on the dish and around it for some distance the bacterial colonies were absent or dead. Subsequent research by Fleming revealed that the 'mould juice' was effective against a wide range of bacterial strains including many that are highly pathogenic to humans. A major remaining hurdle was the production of the active substance Fleming had named 'penicillin', in significant quantities and concentrations, and in a stable form. Enlarged image Enlarged image   Notes for the discovery of lysozyme, antiseptic in nasal mucus capable of dissolving bacteria, 21 November 1921 British Library Add. MS 56154, ff.134v-135r Copyright © The British Library Board   Inhibition by moulds including penicillin, with notes and red highlights, 11 December 1928 British Library Add. MS 56162, f.26  Copyright © The British Library Board 1938-1944 The penicillin revolution The fresh impetus emerged from Oxford University. Biochemists Howard Florey, Ernst Chain, Norman Heatley and others were searching for germicides to analyse chemically. By the end of the 1930s penicillin had been deemed the best candidate based on Fleming's published findings and mould culture. The group devised a suitable assay standard for measuring the strength of a penicillin preparation, as well as means of extracting and purifying it. The process was later industrialised by researchers in the USA, with the assistance of Heatley. The Oxford group conducted in May 1940 the first intravenous injections of penicillin into infected mice, demonstrating the powerful efficacy of penicillin as an antibiotic. Its significance to the war was now so evident that Florey and his colleagues smeared spores of the mould into their suit linings in case they needed to escape quickly following invasion. In early 1941 penicillin was injected, with initial success, into an Oxford policeman afflicted with septicaemia. Sadly he died when the available penicillin was exhausted. It was not until 1942 that a supply of penicillin from British sources enabled otherwise terminally ill patients to be cured in significant numbers. 1945-1955 Recognition In 1945 Sir Alexander Fleming, along with Sir Howard Florey and Ernst Chain, was awarded the Nobel Prize; a notable omission was Norman Heatley (as only three winners are allowed). For Fleming, a quiet personality, 10 years of worldwide fame and travel followed, until on 11 March 1955 he died, an international hero. His ashes were interred in St Paul's Cathedral, London. Enlarged image Enlarged image   First intrathecal injection of penicillin: graph of temperature, pulse rate etc. of Fleming's patient Harry Lambert, August 1942 British Library Add. MS 56183, f.282Copyright © The British Library Board