Definitions

herbarian

Discovery of penicillin

Alexander Fleming was the first to suggest that the Penicillium mould must have an antibacterial substance, and the first to isolate the active substance which he named penicillin, but he was not the first to use its properties.

Year Location Descriptions
Ancient times Greece & India Many ancient cultures, including the ancient Greeks and ancient India, already used moulds and other plants to treat infection. This worked because some moulds produce antibiotic substances. However, they couldn’t distinguish or distill the active component in the moulds.
“traditional medicine” Serbia & Greece There are many old remedies where mould is involved. In Serbia and in Greece, mouldy bread was a traditional treatment for wounds and infections.
“traditional” Russia Russian peasants used warm soil as treatment for infected wounds.
c. 150 BC Sri Lanka Soldiers in the army of king Dutugemunu (161 BC – 137 BC) are recorded to have stored oil cakes (a traditional Sri Lankan sweetmeat) for long periods in their hearth lofts before embarking on their campaigns, in order to make a poultice of the cakes to treat wounds. It is assumed that the oil cakes served the dual function of desiccant and antibacterial.
1640 England The idea of using mould as a form of treatment was recorded by apothecaries, such as John Parkington, King’s Herbarian, who advocated the use of mould in his 1640 book on pharmacology.
1870 England Sir John Scott Burdon-Sanderson, who started out at St. Mary’s Hospital 1852–1858 and as lecturer there 1854–1862 observed in 1870 that culture fluid covered with mould would produce no bacteria.
1871 England Joseph Lister, an English surgeon and the father of modern antisepsis, was prompted by Burdon-Sandersons discovery to investigate and describes in 1871 that urine samples contaminated with mould did not allow the growth of bacteria and he also described the antibacterial action on human tissue on what he called Penicillium Glaucum. A nurse at King's College Hospital, whose wounds did not respond to any antiseptic, was then given another substance which cured her, and Lister’s registrar informed her that it was called Penicillium.
1874 England William Roberts observed in 1874 that bacterial contamination is generally absent in cultures of the mould Penicillium glaucum.
1875 England John Tyndall followed up on Burdon-Sanderson’s work and demonstrated to the Royal Society the antibacterial action of the penicillium fungus in 1875.
1875 Bacillus anthracis is shown to cause anthrax. This was the first demonstration that a specific bacterium caused a specific disease.
1877 France Louis Pasteur and Jules Francois Joubert in 1877 had observed that cultures of the anthrax bacilli, when contaminated with moulds, became inhibited. Some references say that Pasteur identified the strain as Penicillium notatum.
1887 France Garré in 1887 found similar results.
1895 Italy Vicenzo Tiberio of Naples made extracts of Penicillium mould and injected them into animals with virulent bacteria, with inconclusive results in 1895.
1897 France Ernest Duchesne at École du Service de Santé Militaire in Lyons then independently discovered healing properties of a penicillium glaucum mould, even curing infected guinea pigs from typhoid and published a dissertation in 1897 but this was ignored by the Institut Pasteur. However Duchesne was himself using a discovery made by Arab stable boys, who were using moulds to cure sores on horses. He did not claim that the mould contained any antibacterial substance, but simply claimed that the mould somehow protected the animals.
  • Duchesne cured typhoid, but the penicillin isolated by Fleming does not cure typhoid.
  • Duchesne injected a mould with the fungus penicillium glaucum. In contrast, Fleming isolated the substance penicillin from a mould containing penicillium notatum.
  • The term penicillium glaucum was used as a catch-all phrase at the time for different fungi, but not for penicillium notatum and the mould was unfortunately not preserved, which makes it impossible to be certain today which fungus might have been responsible for the cure, and consequently even less certain which substance was responsible.

1920 Belgium In the 1920s, Andre Gratia and Sara Dath observed a fungal contamination in one of their Staphylococcus aureus cultures that was inhibiting the growth of the bacterium. They identified this as a species of Penicillium and presented their observations as a paper. There was little attention to this paper.
1923 Costa Rica An Institut Pasteur scientist, Costa Rican Clodomiro Picado Twight recorded the antibiotic effect of Penicillium in 1923.
1928 England Fleming noticed a halo of inhibition of bacterial growth around a contaminant blue-green mould on a Staphylococcus plate culture. He concluded that the mould was releasing a substance that was inhibiting bacterial growth. He grew a pure culture of the mould and discovered that it was Penicillium notatum. With help from a chemist he isolated what he later named “penicillin”. During the next twelve years, he grew and distributed the original mould, unsuccessfully trying to get help from any chemist that had enough skill to make a stable form of it for mass production.
1930 England Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to treat sycosis - eruptions in beard follicles - but was unsuccessful, probably because the drug did not get deep enough. Moving on to opthalmia neonatorum, a gonococcal infection in babies, he achieved the first cure on 25th November 1930. He cured four patients (one adult, the others babies) of eye infections, although a fifth patient was not so lucky.
1938 England In Oxford, Howard Walter Florey organized his large and very skilled biochemical research team, notable among them Ernst Boris Chain and Norman Heatley, to undertake the innovative work to produce a stable penicillin.
1941 - 1943 USA Peoria, Illinois: Moyer, Coghill and Raper at the USDA Northern Regional Research Laboratory (NRRL) developed methods for industrialized penicillin production and isolated higher-yielding strains of the Penicillium fungus.
1941 - 1944 USA Brooklyn, New York: Jasper Kane and other Pfizer scientists develop the practical, deep-tank fermentation method for production of large quantities of pharmaceutical-grade penicillin.

References

  • “History of Antiobiotics” from a course offered at Princeton University.
  • Penicillin Man: Alexander Fleming and the Antibiotic Revolution, by Kevin Brown, St Mary's Trust Archivist and Alexander Fleming Laboratory Museum Curator. (2004) ISBN 0-7509-3152-3 (Most of the information in this article comes from this book)

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