Penicillin

In myth and legend, Alexander Fleming is said to be first to suggest that the Penicillium mould must secrete an antibacterial substance, and the first to concentrate the active substance which he named penicillin. But in fact,  he was definitely not the first to observe this feature of penicillin, nor use its properties in medicine.

 

Ancient times

 

Greece & India

 

Many ancient cultures, including the ancient Greeks and ancient India, already used moulds and other plants to treat infection.1 This worked because some moulds produce antibiotic substances. However, they could not 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.citation needed

 

 

 

"traditional"

 

Russia

 

Russian peasants used warm soil as treatment for infected wounds.citation needed

 

 

 

c. 150 BC

 

Sri Lanka

 

Soldiers in the army of king Dutugemunu (161–137 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.citation needed It is assumed that the oil cakes served the dual functions of desiccant and antibacterial.

 

 

 

1600s

 

Poland

 

Wet bread was mixed with spider webs (containing spores) to treat wounds. The technique was mentioned by Henryk Sienkiewicz in his 1884 book With Fire and Sword.

 

 

 

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.citation needed

 

 

 

1870

 

United Kingdom

 

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

 

United Kingdom

 

Joseph Lister, an English surgeon and the father of modern antisepsis, was prompted by Burdon-Sanderson's discovery to investigate and describe in 1871 that urine samples contaminated with mould did not allow the growth of bacteria. He also described the antibacterial action on human tissue of 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 that cured her, and Lister's registrar informed her that it was called Penicillium.

 

 

 

1874

 

United Kingdom

 

William Roberts observed in 1874 that bacterial contamination is generally absent in cultures of the mould Penicillium glaucum.

 

 

 

1875

 

United Kingdom

 

John Tyndall followed up on Burdon-Sanderson's work and demonstrated to the Royal Society the antibacterial action of the Penicillium fungus in 1875.2

 

 

 

1875

 

 

Bacillus anthracis was 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 observed that cultures of the anthrax bacilli, when contaminated with moulds, became inhibited. Some references say that Pasteur identified the strain as Penicillium notatum.citation needed

 

 

 

1887

 

France

 

Garré in 1887 found similar results.

 

 

 

1895

 

Italy

 

Vincenzo Tiberio, physician of the University of Naples published a research about a mould in a water well that had an antibacterial action.34

 

 

 

1897

 

France

 

Ernest Duchesne at École du Service de Santé Militaire in Lyons independently discovered healing properties of a Penicillium glaucum mould, even curing infected guinea pigs from typhoid. He published a dissertation5 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, only 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 the mould 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.

 

 

 

1928

 

United Kingdom

 

Scottish biologist Sir Alexander 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 concentrated 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

 

United Kingdom

 

Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to treat sycosis (eruptions in beard follicles) with penicillin but was unsuccessful, probably because the drug did not penetrate deep enough. Moving on to opthalmia neonatorum, a gonococcal infection in babies, he achieved the first cure on 25 November 1930. He cured four patients (one adult, the others babies) of eye infections, although a fifth patient was not so lucky.6

 

 

 

1938

 

United Kingdom

 

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 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.78

 

 

 

1941–1944

 

USA

 

Brooklyn, New York: Jasper Kane and other Pfizer scientists developed the practical, deep-tank fermentation method for production of large quantities of pharmaceutical-grade penicillin.9

 

 

 

1945

 

United Kingdom

 

Oxford: Using X-ray crystallographic analysis, Dorothy Hodgkin elucidated the correct chemical structure of penicillin.10

 

 

 

1952

 

Austria

 

Kundl, Tyrol: Hans Margreiter and Ernst Brandl of Biochemie (now Sandoz) developed the first acid-stable penicillin for oral administration, Penicillin V.11

 

 

 

1957

 

USA

 

Chemist John C. Sheehan at the Massachusetts Institute of Technology (MIT) completed the first chemical synthesis of penicillin in 1957.12

 

 

Referencesedit

 

1.Jump up

Douglas Allchin. "Penicillin & Chance". SHiPS Resource Center. Retrieved 2010-02-09.

 

 3.Jump up

Salvatore De Rosa, Introduttore: Fabio Pagan. "Vincenzo Tiberio, vero scopritore degli antibiotici - Festival della Scienza" (in (Italian)). Festival2011.festivalscienza.it. Retrieved 2012-07-13

 

 5.Jump up

Wainwright M, Swan HT (January 1986). "C.G. Paine and the earliest surviving clinical records of penicillin therapy". Med Hist 30 (1): 42–56. doi:10.1017/S0025727300045026. PMC 1139580. PMID 3511336.

 

7.Jump up

"Historic Peoria, Illinois". Northern Regional Research Lab.

 

 9.Jump up

Curtis, Rachel; Jones, John (2007). "Robert Robinson and penicillin: an unnoticed document in the saga of its structure". Journal of Peptide Science 13: 769–775. doi:10.1002/psc.888.

 

11.Jump up

E. J. Corey; John D. Roberts. "Biographical Memoirs: John Clark Sheehan". The National Academy Press. Retrieved 28 January 2013.

 

 

External linksedit

 “History of Antibiotics”, archived from the original on 14 May 2002, retrieved 6 August 2013 -- from a course offered at Princeton University.

 Brown, Kevin W. (St Mary's Trust Archivist and Alexander Fleming Laboratory Museum Curator) (2004). Penicillin man: Alexander Fleming and the antibiotic revolution. Scarborough, Ont: Sutton Pub. ISBN 0-7509-3152-3.

 (Most of the information in this article comes from this book)

 Debate in the House of Commons on the history and the future of the discovery