History of Penicillin

In England in 1640, the idea of using mold as a form of medical treatment was recorded by apothecaries such as John Parkinson, King's Herbarian, who advocated the use of mold in his book on pharmacology.

The modern history of penicillin research begins in earnest in the 1870s in the United Kingdom. Sir John Scott Burdon-Sanderson, who started out at St. Mary's Hospital (1852–1858) and later worked there as a lecturer (1854–1862), observed that culture fluid covered with mold would produce no bacterial growth. Burdon-Sanderson's discovery prompted Joseph Lister, an English surgeon and the father of modern antisepsis, to discover in 1871 that urine samples contaminated with mold also did not permit the growth of bacteria. Lister also described the antibacterial action on human tissue of a species of mold he called Penicillium glaucum.

In 1874, the Welsh physician William Roberts, who later coined the term "enzyme", observed that bacterial contamination is generally absent in laboratory cultures of Penicillium glaucum. John Tyndall followed up on Burdon-Sanderson's work and demonstrated to the Royal Society in 1875 the antibacterial action of the Penicillium fungus.

By this time, Bacillus anthracis had been shown to cause anthrax, the first demonstration that a specific bacterium caused a specific disease. In 1877, French biologists Louis Pasteur and Jules Francois Joubert observed that cultures of the anthrax bacilli, when contaminated with molds, could be successfully inhibited. Some references say that Pasteur identified the strain as Penicillium notatum.

In 17th-century Poland, wet bread was mixed with spider webs (which often contained fungal spores) to treat wounds. The technique was mentioned by Henryk Sienkiewicz in his 1884 book With Fire and Sword.

Starting in the late 19th century there had been many accounts by scientists and physicians on the antibacterial properties of the different types of moulds including the mould penicillium but they were unable to discern what process was causing the effect.

In 1895, Vincenzo Tiberio, an Italian physician at the University of Naples, published research about molds initially found in a water well in Arzano; from his observations, he concluded that these molds contained soluble substances having antibacterial action.

Ernest Duchesne at École du Service de Santé Militaire in Lyon independently discovered the healing properties of a Penicillium glaucum mold, even curing infected guinea pigs of typhoid. He published a dissertation in 1897 but it was ignored by the Institut Pasteur.

In Belgium in 1920, 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 the fungus as a species of Penicillium and presented their observations as a paper, but it received little attention. An Institut Pasteur scientist, Costa Rican Clodomiro Picado Twight, similarly recorded the antibiotic effect of Penicillium in 1923.

However, Paul de Kruif's 1926 Microbe Hunters describes this incident as contamination by other bacteria rather than by mold. In 1887, Garré found similar results.

Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming.

In 1930, Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to use penicillin to treat sycosis barbae, eruptions in beard follicles, but was unsuccessful.

Moving on to ophthalmia neonatorum, a gonococcal infection in infants, Cecil George Paine achieved the first recorded cure with penicillin, on November 25, 1930. He then cured four additional patients (one adult and three infants) of eye infections, and failed to cure a fifth.

In 1940, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Boris Chain, Edward Abraham, Arthur Duncan Gardner, Norman Heatley, Margaret Jennings, J. Orr-Ewing and G. Sanders) at the Sir William Dunn School of Pathology, University of Oxford made progress in showing the in vivo bactericidal action of penicillin.

In 1940, they (Howard Florey and his team) showed that penicillin effectively cured bacterial infection in mice.

By late 1940, the Oxford team under Howard Florey had devised a method of mass-producing the drug, but yields remained low.

In 1941, they (Howard Florey and his team) treated a policeman, Albert Alexander, with a severe face infection; his condition improved, but then supplies of penicillin ran out and he died. Subsequently, several other patients were treated successfully.

In 1941, Florey and Heatley travelled to the US in order to interest pharmaceutical companies in producing the drug and inform them about their process.

The challenge of mass-producing this drug was daunting. On March 14, 1942, the first patient was treated for streptococcal sepsis with US-made penicillin produced by Merck & Co.

People began using it to treat infections in 1942.

The chemical structure of penicillin was first proposed by Edward Abraham in 1942 and was later confirmed in 1945 using X-ray crystallography by Dorothy Crowfoot Hodgkin, who was also working at Oxford. She later received the Nobel prize for this and other structure determinations.

By June 1942, just enough US penicillin was available to treat ten patients.

In November 1942, survivors of the Cocoanut Grove fire in Boston were the first burn patients to be successfully treated with penicillin.

In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe.

The results of fermentation research on corn steep liquor at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the United States to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944.

After World War II, Australia was the first country to make the drug available for civilian use. In the U.S., penicillin was made available to the general public on March 15, 1945.

Florey and Chain shared the 1945 Nobel Prize in Medicine with Fleming for their work.

Pfizer scientist Jasper H. Kane suggested using a deep-tank fermentation method for producing large quantities of pharmaceutical-grade penicillin. Large-scale production resulted from the development of a deep-tank fermentation plant by chemical engineer Margaret Hutchinson Rousseau. As a direct result of the war and the War Production Board, by June 1945, over 646 billion units per year were being produced.

The importance of his work has been recognized by the placement of an International Historic Chemical Landmark at the Alexander Fleming Laboratory Museum in London on November 19, 1999.

Chemist John C. Sheehan at the Massachusetts Institute of Technology (MIT) completed the first chemical synthesis of penicillin in 1957.