Friday, 26 August 2016

THE STORY OF PENICILLIN

Let me, at the very outset, introduce you to this wonderful story-teller. Prof. H.S. Adenwalla is in his late eighties and is one of the most senior Plastic Surgeons in India. He is the Head of Charles Pinto Centre of Cleft Lip, Palate and Cranio-facial Anomalies in Jubilee Mission Medical College & Research Institute in Trichur, Kerala. The learned professor is an encyclopedia of knowledge and yet an epitome of modesty. Trained under the famous Plastic Surgery Guru Charles Pinto in K.E.M. Hospital, Mumbai, when the octogenarian professor chooses to walk down the memory lane, you are distinctly lucky if you are accompanying him! This is one of hise several stories which I am going to share with you all from time to time!
In the history of the growth of science it is difficult to lay any clear watersheds, but we can say that the era of modern medicine roughly started with 1880’s- many good things had happened before, for instance Jenner had begun his war on Small Pox, and Louis Paster had conquered the horrors of Rabies. Dogmack had synthesized salvarsan which was a sulphoamide. But otherwise medicine consisted of purging, bloodletting and starving and more people died of the treatment than the disease. There were a few useful drugs which became the physician’s carthorse, digitalis for the heart, Quinine for malaria, salicylates for fever, sarol for intestinal infections, hexamine for urinary tract infections and opium for pain. Insulin for diabetics, thyroxine for myxoedoema and salvarsan (arsenic) for syphilis, came later.
Our story of Penicillin begins with a young Scottish student of Medicine who wanted to be a surgeon. In 1906 he took a temporary job in the bacteriological department of the St. Mary’s hospital, London under Sir. Almroth Wright, his intention was to stay on the hospital’s rifle shooting team. That as Udwadia says in his book “The forgotten Art of Healing” was a quirk of destiny for both Fleming and the world.
His first discovery of importance was that he proved that there was in tears an enzyme called lysozyme which destroyed organisms that existed in the nasal tract. It showed why the eyes resisted infections so effectively. He then turned to the study of staphylococcus a common organism which infected wounds and caused fatal septicaemia and death.
Now starts a Cinderella story never surpassed in the annals of medicine. Fleming retiring from a holiday found that one of the Petri-dishes that he had left open by chance had been contaminated by a mould, and the bacteria round the mould had been destroyed. He presumed that this mould may have floated up the stairs or through an open window from a laboratory where a research worker was studying fungi. The genius of Fleming was that he did not just throw away the Petri-dish. He was intrigued by the pneumonia and so he studied what lay before him and found that a powerful substance had emanated from the mould that had killed the bacteria. What was this substance? He believed that the mould was Penicillium rublem. It was really Penicillium notatum and hence he called the lethal substance Penicillin. His further research showed that this Penicillin destroyed a whole range of gram positive cocci and a few gram negative ones too. He also showed that Penicillin did not affect healthy tissue or the leucocytes in blood. Why did not Fleming try Penicillin on infected animals? This was because he found that if Penicillin was mixed with blood it lost its potency. He failed to realize that what happens in vitro does not necessarily happen in vivo. Disappointed at this road block he turned to other areas of research. Strange to say other workers who thought Fleming had given up too easily could not duplicate Fleming’s observations. When they dropped penicillium mould on to an agar plate full of colonies of staphylococcus nothing happened. A year later Robert Hare solved the riddle. Robert Hare consulted the meterological records for London at the end of July 1929. When Fleming was away, London had a very cold spell of a week, which favored the growth of the penicillium mould. After that the temperature rose which favored the growth of the staphylococcus. Robert Hare succeeded in duplicating Fleming’s experiment in conditions of controlled temperature. But there the research died. It must be noted here that without that cool period when Fleming went on leave he would not have discovered penicillin at all.
For six years no one spoke or heard of penicillin. In 1935 Howard Florey a brilliant Australian who headed the Dunn School of pathology at Oxford hired a German Jew who had just escaped from the Nazis in Germany, he was a biochemist, they both set out to find a powerful antibacterial substance. By chance they stumbled upon a paper by Alexander Fleming on penicillin but they just could not isolate the active substance from the mould. It was Norma Heatley another biochemist on the team who succeeded. On Sunday the 25th of May 1940 Florey’s team inoculated 8 mice with lethal doses of streptococci four were then put on penicillin. By 1.45 AM the next morning the mice who were not treated with penicillin died the other four survived. Florey exclaimed “This gentleman looks like a miracle.”
The Second World War was going badly for Britain. France had already capitulated. Florey then made a desperate decision, he decided to convert his department into a manufacturing plant for penicillin. Heately was put in-charge and he at last had enough penicillin for a human trial. A police man Albert Alexander had developed septicaemia following a scratch while pruning roses. Dr. Charles Fricher on the 12th of February 1941 administered penicillin three hourly to the patient. By the fourth day the patient’s temperature dropped and he became lucid but unfortunately they ran out of penicillin and Alexander died. They had no doubt that if they had enough Penicillin Alexander would have lived.
Florey appealed to the British pharmaceutical industries for help but they said they were too busy due to the war, so in July 1941 Florey and Heatley flew to the USA to get the help of Andrew J. Moyer. Moyer it is said sapped Heatley of all his knowledge but gave nothing in return. Moyer succeeded in manufacturing penicillin in large amounts.
Now in 1942 Fleming asked for some penicillin for a dying friend, he has given the drug and his friend survived. This was reported in the Times. It was then that Almroth Wright wrote to the Times giving credit to his pupil Fleming for the discovery of Penicillin. Fleming, Florey and Chain shared the Nobel Prize for Medicine. As often happens in life Norman Heatley and Robert Hare were forgotten. Penicillin became the wonder drug which opened up the phenomenal era of antibiotic therapy. For a moment man thought that he had conquered diseases caused by infective organisms but it was not to be, nature always has the upper hand and as Udwadia says “Microbes like man evolve, when threatened they mutate to form resistant strains. And so the battle for survival goes on.”