The story of penicillin

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The development of antibiotics was one of the greatest medical advances of the 20th century. But few know the story of what was involved. It took the vision and persistence of an Oxford University team to make penicillin and its successors universally available.

It was Alexander Fleming at St Mary’s Hospital Medical School who noticed a mould growing on a culture plate of bacteria one day in September 1928. Around the Penicillium notatum mould was a clear area where the colonies of bacteria appeared to have been dissolved. Fleming set about establishing the identity of the substance that was killing the bacteria, giving it the name ‘penicillin’. But Fleming only continued to study penicillin for a year or so, and he never got to the stage of  purifying and testing its effects against bacterial infections when injected into a living animal or patient.

Professor Howard FloreyHoward Florey became Professor of Pathology at Oxford in 1935, moving into a splendid new department, the Sir William Dunn School of Pathology. Florey quickly recruited Ernst Chain to work with him, and they began to look at a range of substances that might have an effect on bacteria.

Around the time Britain declared war on Germany, Chain and Florey came to the conclusion that penicillin was far more effective in combating bacteria than the other candidates. But there was no simple means of testing the activity of the samples of penicillin they produced. And they needed a good method to extract the penicillin from cultures of the Penicillium mould.

With Norman Heatley, a biochemist who became Florey’s research associate in 1940, the team solved both these problems. Heatley devised a new technique to measure the activity of a sample of penicillin and came up with a method called back-extraction to isolate the penicillin. He managed to automate this procedure using a set up consisting of bottles, milk churns, yards of glass and rubber tubing.

By 25 May 1940, the team had reached a point where they could carry out a new experiment that would test whether penicillin could be an important antibacterial drug. Eight mice were given lethal doses of streptococci. Four of the mice were then given injections of penicillin. By the next morning all the untreated mice were dead while those that had received penicillin survived for days to weeks.

With this result, Florey realised that he needed to expand production – an effective treatment for infection could be a valuable contribution to Britain’s war effort. He turned the Dunn School into something of a penicillin factory. Six ‘penicillin girls’ were taken on to maintain production in 700 newly designed vessels which were continuously in use. By February 1941 Florey felt he had enough penicillin to begin trials in humans.

The Dunn School became a factory to produce enough penicillin for trials in humans

With the help of Charles Fletcher, a young doctor at the Radcliffe Infirmary, on 12 February 1941, Albert Alexander, a 43-year-old policeman, became the first patient to be treated with penicillin. He had scratched his face on a rose bush, the wound had become infected and the infection had spread. Fletcher injected him with penicillin regularly over four days, and within 24 hours he was greatly improved. But supplies of the new drug ran out before his cure was complete. He relapsed at the beginning of March, and died two weeks later.

Of the next five patients, four recovered from their infections after a course of penicillin. The other, a child of four, was cured of his infection but tragically died of a brain haemorrhage. The results were published in The Lancet in August 1941.

As similarly impressive results from larger trials began to come in, companies in the US and then the UK began to start production of penicillin on an industrial scale. Supplies of penicillin accompanied the troops making the D-day landings in June 1944, and the death toll from infected wounds during the campaign was dramatically reduced.

Penicillin inspired massive efforts to discover other new drugs that could conquer the many diseases still threatening the world. Further antibiotics soon followed, including streptomycin, chloramphenicol, the tetracylines, and erythromycin. Another important family of antibiotics, the cephalosporins, were developed from research at Oxford.

Antibiotics have seen a dramatic change in the figures for deaths and illness from infectious diseases. Antibiotics have also provided safe and effective treatments for the wide range of infections that were a daily problem in hospitals and general practice.

Fleming, Florey and Chain were jointly awarded the Nobel Prize for physiology or medicine in 1945, recognising the tremendous contribution of penicillin to human welfare.

The research team that worked on penicillin in the early war years