The story of penicillin, like numerous other discoveries, involves a chain of observations, discoveries and researches involving several different people.


The Players

 
Alexander Fleming; born in 1881 in Darvel, Ayrshire, Scotland. He moved to London when he was 13 and later trained there as a doctor. After the First World War he joined St Mary's Hospital in London as a research assistant in the innoculation department.

Ernst Chain; a German Jewish refugee working in Oxford. He was the first to separate penicillin following up Fleming's observations. His initial interests were scientific not medical.



Howard Florey; born in Adelaide, Australia. Appointed as Professor of Pathology at Oxford University in 1935. He led the efforts in Oxford to separate penicillin and to make enough to carry out the first medical trials.

The Story

Alexander Fleming returned from the First World War and went back to his research work at St Mary's Hospital, London. His experiences during the war had shown him the importance of being able to treat infection in wounded patients, and his subsequent work at the hospital involved him in researching agents which might help fight infection.

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In 1922, Fleming discovered lysozyme, an enzyme found in human tears, which is capable of destroying bacteria. However, while the new discovery was effective at inhibiting the growth of harmless bacteria, it proved ineffective against those that caused disease.

In 1928 Felming made an interesting observation while he was looking at a pile of neglected petri dishes which he had rediscovered in the general untidiness of his lab. The dishes had originally been been cultured with Staphylococcus bacteria (known to cause wounds to go septic) but the agar had gone mouldy. However, Fleming was surprised to notice that, in the areas around the mould, the colonies of Staphylococcus had stopped growing. It appeared that something produced by the mould was inhibiting the growth of the bacteria. After further testing, Fleming was able to identify the inhibitory substance and name in penicillin. (More information...)

This agar plate shows the effect Penicillium mould has on the growth of different bacteria.

If you look carefully, you can see that the feint lines of bacteria in the brown agar do not grow close to the grey/white mould.

 

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The medicine : mould to pill


 

Building on Alexander Fleming's initial observations, Howard Florey and Ernst Chain took the discovery of penicillin towards the development of the drugs that we know as antibiotics.

 

 

The overwhelming casualties during the Second World War led Florey and Chain to look at resurrecting Fleming's work. After much refinement they were able to develop a powdered form of penicillin.

In 1941 the first human was treated. Penicillin was given to Reserve Constable Albert Alexander who was dying of blood poisoning from a small cut. The drug proved successful but Alexander died 5 days later, when the supply of the drug ran out.

With World War II raging in Europe, Florey and one of his assistants moved to the United States to continue their work with penicillin. When the United States also entered the war, it gave added incentive to the penicillin project, which was declared a war project and given top priority. Penicillin was a wartime asset kept secret by the allies. British and US supplies were for military use only. Wounded troops benefited and much early penicillin was used to treat venereal disease which was the scourge of the North Africa Campaign.

With the development of new production methods, it became possible to make larger quantities of penicillin. By the end of the Second World War, enough penicillin was produced to treat seven million patients a year. After 1945, British and US civilians were also treated with penicillin, while the rest of Europe depended on a flourishing black market.

 

The Structure of the Drug

Scientists initially believed that, once they knew the chemical structure of penicillin, they would soon be making synthetic penicllin themselves. But a satisfactory process for artificial synthesis was never found.

Penicillin V, which is effective when administered to patients by mouth, was produced by altering the mould's growing conditions. In 1957 the central , unchanging part of the penicillin molecule was isolated. Scientists used this to create new semi-synthetic penicillins.

SEE THE MOLECULE
If you have used Rasmol programmes you will be able to down load molecule and manipulate it using the right mouse button otherwise go to the web site http://www.recipnet.indiana.edu/  or to http://www.recipnet.indiana.edu/common/Drugs_stimulants/indexpage.htm

J Deacon,
University of Edinburgh

 

 

The success story of penicillin led pharmaceutical firms to search for more antibiotics. Moulds and fungi are common in soil, so thousands of soil samples were screened in the 40s and 50s with several positive outcomes. The cephalosporins, now the biggest selling broad-spectrum antibiotics in the world , were found in sewage in Sardinia.

Nowadays, new antibiotics are often made by chemical manipulation of known ones in laboratories.

 

Recognising Achievements

Although Fleming was the discoverer of the medical effects of penicillin, he could not separate the drug or test it. However, in 1944, he was knighted along with Howard Florey, and a year later was awarded the Nobel Prize in Physiology and Medicine along with Florey and Chain.

See them receiving their prize(download video)

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