MAN VS MICROBE: THE BEGINNING


Till the middle of the 1930s the only effective anti-infective drugs were quinine against malaria, arsenicals (and to a lesser extent mercury) against syphilis, and antimony against schistosomiasis. Then came a major breakthrough in 1935 with the discovery of sulphonamide

The drug could however cause dangerous side-effects and the micro-organisms could become resistant to the drug. The never-ending, never-to-be-won war between man and microbes had begun.

The next great step in the fight against infection was the discovery of penicillin by Sir Alexander Fleming, a Scottish microbiologist at St Mary's Hospital in London. The improbable chain of events that led Alexander Fleming to discover penicillin in 1928 is the stuff of which scientific legends are made. Fleming, a young Scottish research scientist had accidently left a culture plate smeared with Staphylococcus bacteria on his lab bench while he went on a two-week holiday.

When he returned, he noticed a clear halo surrounding the yellow-green growth of a mould that had accidentally contaminated the plate. Seeing that halo was Fleming's "Eureka" moment. He correctly deduced that the mould must have released a substance that inhibited the growth of the bacteria. The active ingredient in that mould, which Fleming named 'penicillin', turned out to be an infection-fighting agent of enormous potency.

Curiously, however, when other scientists tried to replicate the accidental method by which Fleming had made his discovery - by dropping some penicillum mould on to a plate of staphylococci - they were quite unable to do so.

Fleming's former assistant, Ronald Hare, then investigated the matter in detail. He found that the growth of the penicillium mould occurred at a different temperature (20 degree Celsius) than the staphylococcus, which grows best at a temperature of around 35 degree Celsius. Fleming did not, prior to going on holiday, place the dish in the incubator but left it out on the laboratory bench. Consulting the meteorological records for London at the end of July in 1928, Ronald Hare discovered that while Fleming was away there had been an exceptionally cool nine-day period - which would have favoured the growth of the penicillium mould. Thus, without the 'nine cool days' in London in the summer of 1928, Fleming, would have never discovered penicillin.

Fleming failed to pursue the possibilities of penicillin because of the common belief that any compound capable of destroying bacteria would necessarily harm the person to whom it was given.

The discovery of penicillin would have remained buried in the archives of medical journals had it not been for a brilliant Australian pathologist, Howard Florey. Howard Florey teamed with a biochemist Ernst Chain and after going through over 200 papers came across the work of Fleming.

In a classic experiment on May 25, 1940, Florey and his colleagues inoculated eight mice with lethal doses of streptococci; four were then given penicillin. The next morning, the mice that had not received the drug had died, but the four who had received the penicillin were alive and well. The scientists realized the great potential of penicillin for treating infections and, in particular, the wounded of the Second World War.

After the publication of the results of this experiment in The Lancet on August 24, 1940, Florey hoped that one of the pharmaceutical companies would become sufficiently interested to produce penicillin on a large scale. However, in the desperate moments of the World War II, this was not to be. Florey then decided to commit the puny resources of his laboratory in Oxford to make enough penicillin to test in humans. The hallmark of Florey's university laboratory-turned-penicillin factory was improvisation, the penicillium moulds being grown on hospital bedpans and precious fluid extracted and stored in milk jugs.

On 12th February 1941, a 43-year old policeman, Albert Alexander who had scratched his face on a rose bush (and the scratches had turned septic), became the first person to be treated with penicillin. However, the supply of penicillin was exhausted on the fifth day of treatment, and hence his condition deteriorated and he died a month later. When more supplies of penicillin became available, four more patients were treated successfully. More than fifty years later, the use of penicillin had lost none of its power to amaze.

By the middle of the century, Fleming's discovery spawned a huge pharmaceutical industry, churning out synthetic penicillins that would conquer some of mankind's most ancient scourges, including syphilis, gangrene and tuberculosis. In 1945, Alexander Fleming, Howard Florey and Ernst Chain shared the Nobel Prize for the discovery of penicillin.

The story of penicillin, and the other antibiotics that followed, is perceived as a triumph of science and rationalism in the conquest of illness. The antibiotic revolution had finally made a mark in fighting diseases, which used to decimate humankind at frequent intervals. While the seesaw battle against the wily microorganism continues, the penicillin story continues to inspire.

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