The man who broke the mould

The life and achievements of Nobel Prize winner Alexander Fleming

It is hard to imagine a world without penicillin, but until 60 years ago a nasty infection could kill.

One of the people behind this momentous discovery, and one of a trio awarded the Nobel Prize, was Alexander Fleming, who delivered the first SCI Lister Memorial Lecture on Antiseptics to a packed audience in Edinburgh in 1944.

Fleming was born in Scotland in 1881 to a farming family and trained as a doctor at St Mary’s Hospital, London, where he developed a special interest in vaccine therapy. During the First World War, he joined the British Royal Army Medical Corps and tried to find a treatment to prevent soldiers dying from infected wounds, arguing that antiseptics alone were not sufficient.

After the war he returned to St Mary’s where he researched antibacterial substances that would not attack animal tissues, and discovered the antiseptic properties of lysozyme found in tears, body fluids and some plants. By 1928 he was working on the influenza virus, but he also devoted time to his own pet theory, developed after he sneezed into a petri dish, that nasal mucus had antibacterial properties. He was working on this when he left a petri dish of staphylococcus bacteria on his lab bench and went on a two-week holiday.

On his return he discovered that mould was growing in the petri dish and breaking down the bacteria. The mould was Penicillium notatum, a rare type that had floated up from a mycology lab on the floor below. As he described it in the Lister Lecture: ‘A mould colony which appeared as a contamination on a culture plate made such a change in the colonies of staphylococci which were on the plate that something had to be done about it.’

After some experimentation he found the penicillin mould prevented growth of the bacteria, even when greatly diluted. Fleming reported his work in the British Journal of Experimental Pathology the next year, but it was to remain in obscurity for a decade — a great tragedy considering the lives that could have been saved.

Some said that he lacked the chemical expertise to purify penicillin and was unconvinced that drugs could treat serious infections. As Fleming explained in the Lister lecture: ‘We got no further because our amateur efforts at concentration met with little success and because when it [penicillin] was wanted it had frequently become inactive.’ But he freely dispensed samples of the all-important mould to other scientists who asked for it.

Two others, based in Oxford, took up the mantle — Howard Florey, an Australian-born physiologist, and Ernst Boris Chain, a chemist who had fled Nazi Germany. These two, who were to share the Nobel Prize with Fleming, focused on identifying and isolating substances from moulds that could kill bacteria. This was inspired by Gerhard Domagk who, in 1935, showed that a simple compound, Prontosil, could treat streptococcal infections.

By the late 1930s, just as war was breaking out again, the search was on for a drug to combat infection using Fleming’s penicillin mould as a starting point. Florey, Chain and colleagues purified penicillin and successfully treated infected mice. They were equally successful with patients.

As World War Two advanced, the team helped the UK government set up a network of penicillin production. Florey was instrumental in establishing production on a much bigger scale in the US. By D-day there was enough penicillin on hand to treat every soldier who needed it, and the drug saved millions of lives.

Civilian deaths were also prevented on a previously unimaginable scale. Diseases such as tuberculosis, pneumonia, syphilis, gonorrhoea, diphtheria, scarlet fever and childbirth infections could now be treated effectively.

Though Fleming was awarded much of the credit by an adoring public, and clearly enjoyed his success, which included a knighthood and many other awards, he always referred to his adulation as the ‘Fleming myth’. He noted the disadvantages of penicillin as early as 1946, including one flaw that is with us to this day, ‘the administration of too small doses… leads to the production of resistant strains of bacteria’.

Fleming disappeared from the picture after this, though in a somewhat unlikely postscript, he was admitted to the Chelsea Arts Club because of his germ paintings, made using spores of highly-pigmented bacteria. These were invisible while he painted, but when cultured made bright colours; red for Serratia marcescens, purple for Chromobacterium violaceum and yellow for Micrococcus luteus.

He died of a heart attack in 1955 and was buried in St Paul’s Cathedral.