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This month in pharma: Discovery of penicillin

Exploring the industry's most important dates, we recall September 1928: the discovery of penicillin

A calendar dated September 1928 - the discovery of penicillinSometimes time away from work can be the best means for an innovative idea to develop, for it was only after a two-week holiday that Scottish research scientist and future knight, Dr Alexander Fleming, came to make one of medicine's greatest discoveries – that penicillin could be used to treat bacterial infections.

It was a breakthrough that "would change the course of history" according to AIDS research pioneer David Ho in his tribute to Fleming as part of Time magazine's list of the 100 most important people of the 20th century.

It is a statement against which it is hard to argue, considering the countless lives the antibiotic has saved, especially during periods of conflict such as World War II, where the drug became an essential part of Allied supplies for the Normandy landings to prevent amputations and death.

Indeed, it was partly Fleming's own experience working in a battlefield hospital in World War I and observing soldiers dying from such diseases as septicaemia, tetanus and gangrene caused by simple infections that first inspired him to research better alternatives to the antiseptics used at the time.

The fungus Penicillium, from which penicillin is derived, had previously been noted for its abilities to treat wounds. For example, Arab stable boys would use mould to nurse the sores of horses and French physician Ernest Duchesne had carried out related work.

However, Fleming was the first to isolate the active antibiotic of penicillin and realise its potential to treat infections.

The path to discovery was something of a fortunate series of circumstances, however, with Fleming enrolling at St Mary's Hospital Medical School, London, on the suggestion of his brother, the physician Tom Fleming, and choosing to research bacteriology.

This was due, in part, to the insistence of the captain of St Mary's rifle club who knew that Fleming was a talented shot and did notwant to lose him to another school to study surgery.

Fleming spent the rest of his working life at St Mary's, with his first major achievement being the 1923 discovery of lysozyme, an enzyme occurring in human tears that had an antiseptic effect.

It was in 1928, however, that Fleming took his fortuitous holiday in the middle of his antibacterial research, only to return and discover something unusual had happened to a culture plate smeared with Staphylococcus bacteria, a common cause of infection, that he had left on a laboratory bench.

The plate had accidentally been contaminated by a growth of mould from a mycology laboratory nearby, which had grown during Fleming's absence. The bacteria had also grown, managing to cover the entire plate, except the area where the mould was situated.

Reminded by his assistant Merlin Price that it was in a similar way he had discovered lysozyme, Fleming deduced that the mould must have released a substance that inhibited the growth of the bacteria. He went on to grow the mould in a pure culture and named the active substance penicillin.

Fleming conducted further experiments with the substance in an attempt to create an effective antibiotic, but little progress was made over the next 10 years.

It took a team of scientists at the University of Oxford, led by Dr Howard Florey, to develop penicillin further, showing its effectiveness in mice. The difficulty of obtaining the substance hindered their research though, and Florey was unable to experiment effectively on human subjects.

In 1941, with the ongoing war demanding an effective antibiotic, Florey travelled to the US to take his team's ideas to several pharmaceutical companies, including Merck, Squibb, Eli Lilly and Pfizer, all of whom showed minor interest in helping with further research.

However, it was not until a more effective way of producing penicillin was developed by Dr Andrew J Moyer that these companies became more confident in the drug's potential, and at a Committee on Medical Research (CMR) conference in December 1941, just days after the Japanese attack on Pearl Harbor, George W Merck committed his company to developing penicillin.

Merck went on to collaborate with Squibb and Pfizer, treating the first patient in March 1942, before large-scale production was introduced and, by June 1945, over 646 billion units of penicillin were being made annually.

In the same year, Fleming, Florey and fellow researcher Ernst Boris Chain were all awarded the Nobel Prize for Medicine for their contributions to a drug that some estimate to have saved 200 million lives across the world.

What good a holiday can do!

Tom Meek

The Author
Tom Meek
is web editor of PMLiVE.

12th September 2011


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