THE STORY OF PENICILLIN. (Serendipity to Surreal)



Penicillin, as an antibiotic, was the first great breakthrough in medical research to win a battle between man and germ. Like in many other fields of research there are several actors in this drama of discovery. Lots of people think that scientists invent new things. Far from it: they only unravel the mysteries of Nature in all scientific discoveries and, it is Nature that should rightfully get the Nobel Prize for having invented so many wonders. “This world is a wonderful wonder,” wrote Albert Einstein in the evening of his life. “We always stand on the shoulders of tall men,” was another of Einstein’s quotes, referring to Isaac Newton’s work that propelled his Relativity Theory in the beginning. The drama of penicillin is still more interesting from its human angle.



Louis Pasteur was the first to show that germs and man are, at times, at loggerheads with one another. Man can not live without germs in this universe, but, when the environment changes they could become enemies. However, no germ, in its proper senses, would want to attack man. If the germ wins and man gets any disease, there are two possibilities; both of which are bad for the germ! If man dies of the disease the germ gets burnt or buried deep. If, on the other hand, man wins the battle, man’s immune system kills the germ, anyway. In either case the germ ruins itself by attacking man. They normally co-habit without a proper marriage, though.



Although Paul Ehrlich was the first to think of the horrors of man’s immune system destroying man himself, progress in immunology took a long time. Thanks to the thinking American physician, Theobald Smith, who in 1915 propounded the Grimm’s Law: “while any disease is directly proportionate to the virulence of its cause, it is inversely related the resistance of the host.” This idea, coupled with the “horror auto-toxicus” theory of Paul Ehrlich, laid the foundation for the great science of immunology that has eventually paved the way for organ transplants and what have you.



Robert Koch’s postulates helped research very much but, at the same time, they halted the progress of medical research for nearly one hundred years. People never ever thought of the human immune system because of the cardinal principles of the Koch’s postulates. People have been using germ killers for centuries on the skin surface, but internal use of chemicals to kill germs was thought to be taboo because of the fear of damage inside. Lots of work eventually resulted in arsenic being used in syphilis.



Professor Alexander Fleming was the head of microbiology at the then famous St. Mary’s Medical School in Paddington, London, in the early part of the last century. He was obsessed with the idea that body produces its own germ killers. This thought first occurred to him one day when he inadvertently sneezed on to the culture plate in his laboratory. A very keen observer that he was, he saw that the germs got killed in the area where his nasal mucus had fallen. He was able to later show that it is the lysozyme in the mucus that had killed the germs.

Serendipity enters the story here after. Fleming had gone on a long summer holiday in 1928 August or so. London was exceptionally hot that year, a record that was probably beaten only in the last two summers in London when the temperatures were sky high. In the basement of Fleming’s lab. was the mycology laboratory. The hot air from the basement was coming to the first floor balcony where inside was Fleming’s microbiology unit situated.



Since the professor was on leave, the laboratory assistants forgot to clean the used Petri dishes. When Fleming, the curious observer came back, he was upset that the dirty dishes were still there. He, however, noticed a strange phenomenon. In one of the dishes where there was luxuriant grow of the common germ, staphylococcus, he noticed a large island of clearing. On close observation he saw a fungus growing there. He was able to identify the fungus as penicillium notatum. He found out that this fungus kills staphylococcus. He never realized that it could help mankind. He left his observations there but wanted to get lots of publicity. He was very good at it. He was Knighted by the King in 1929 and had lots of media publicity too.



Away in Oxford was this great brain, a great researcher, an able administrator who got people to work for him and, an innovator par excellence in Professor Howard Florey, an Australian, who was the Chief of the famous William Dunn School of Pathology, at the Oxford University. Florey was working feverishly on lysozyme and other body fluids that had anti-microbial properties for decades. Egged on by Dogmack’s success with sulpha drugs, Florey was looking for some other chemical to use safely in humans against germs. He always appointed the right people for the right job. In his bio-chemistry laboratory he had a brilliant brain in Dr. Ernst Chain, who had fled Hitler’s Germany to England, who was working on all kinds of fungi and was able to extract the active principle in the fungus penicillium notatum. Florey was looking through the voluminous literature to see if anyone had worked on the fungus. After days of search he came up with the work of Alexander Fleming in 1928.



Then on the story moved very fast as there was the governmental pressure on scientists as the war casualties due to gas gangrene and other infections far outnumbered those deaths due to bullets and bombs. Florey had an obsessive personality that helps research. He was also guilty that he had avoided being drafted during the First World War. He knew how to get the funding from the government of the day. He also had nearly twenty people working for him in the lab. with Ernst Chain, Heatley and other technicians. To cut the long story short it was Florey’s group that ultimately discovered penicillin as a drug and got a couple of US scientists from the Agricultural department there, Andrew Moyer and Kenneth Raper, of Peoria in Illinois, to mass produce penicillin for war use. It should be noted here that Howard Florey was a very shy man and was media shy too. He was worried that if he publicized his work, the demand for penicillin would be such that he would not be able to meet the demand. He kept quiet and, in the meantime, the flamboyant Alexander Fleming claimed all credit for discovering penicillin and even bagged the coveted Nobel Prize alone!



When all this was going on, Winston Churchill, the Great War hero, came down with pneumococcal pneumonia, and was in his death bed, partly because of his smoke filled emphysematous lungs and the declining age. The life giver, Alexander Fleming, was quickly summoned and the administration of penicillin saved the great hero’s life! There is a celestial side to this story here. Fleming was the son of a poor farmer in England. One morning his father, the senior Fleming, working in his farm, heard a desperate cry for help from the nearby marshy bushes. When he rushed to look, senior Fleming found a Nobleman’s son drowning there struggling for breath in neck deep marshes. He pulled the boy out and saved his life. The following morning the nobleman was in Fleming’s farm to thank the farmer and offer him financial assistance. The humble farmer did not accept any cash. The nobleman, however, insisted that the farmer send his son to Oxford for which the former would foot the bill. That was how Alexander Fleming became a doctor and an Oxford graduate. The farmer’s son providentially saved the nobleman’s son, Sir Winston Churchill, decades later, a real quirk of fate.



Alexander Fleming was more like the Indian Bolly wood actors or politicians going after publicity, most of the time not deserving though. When he was appointed the Vice Chancellor of the famous Edinburgh University, he agreed to be taken in a large procession through the streets of Edinburgh, carried on the shoulders of tall Scots! If one were to see those pictures they remind one of some victory rally in India or the post Filmfare awards jamboree. He went round the world extolling the virtues of his great discovery while keeping the people in the dark about the whole story. In fact, the whole story is still murky, filled with the drama of missed opportunities and bad luck. Serendipity did smile on many people before Alexander Fleming in this area but no one was there to help like Howard Florey. Florey was very naïve in matters of making money and name from his research. It is unbelievable that he did not even patent penicillin and the two agricultural scientists from the US, who helped him to mass manufacture penicillin patented it and later Florey had to buy penicillin from them! That is bad luck indeed. Read on.



It was Joseph Lister, the great English Surgeon, who found out, way back in 1871, that urine samples from patients did not grow any microbials when contaminated by molds. In the year 1874 another scientist, William Roberts, observed that no germ contaminated his mold cultures. In 1877, Louis Pasteur and Jules Francois Joubert together noticed that the anthrax bacillus culture was inhibited by growth of molds inside the culture plates. None of them went any further. The sad story of young Ernest Duchesne in 1897 who did his PhD thesis on the competition between micro-organisms is there for all of us to see. He studied E.coli being destroyed by Penicillium glucuum and was on the way to extract the active principle. He was then drafted to the First World War and died there. This is misfortune at its best. Bad luck. Luck is the blessing of God without His signature attached to it! Still worse is the story of two poor researchers, Andre Gratia and Sara Dath (?Indian), who in 1920, showed in a paper they read in one of the conferences in England about the suppression of Staphylococcus Aureus by a fungus called penicillium glucuum. But the senior scientists laughed them off and the two left research for ever. They were looking to extract the active principle. That was not to be.



The anticlimax to the whole story is that the dream of the scientific world that anti-biotics will one day rid man of all infections has been belied one hundred percent. Whereas ninety-five percent of staphylococci were sensitive to penicillin to begin with now ninety-five percent of them are resistant. Antibiotic resistance has become a nightmare for doctors and hospitals. The curse of these super-bugs that live on most antibiotics is the dreaded reality. Many hospitals had to close their operation theatres because of these bugs. In the US, in one year, nearly 80,000 people die from nosocomial infections with these bugs! Man had to go back to Nature to fight germs with other living organisms. Maggots have staged a come back in a big way to help man fight the bad germs. This is the irony of fate- the real surreal.



This is the long and short of the penicillin story. It has all the characters of a human drama- daring, keen observation, opportunity, mishaps, jealousy, cheating, pride, super ego, man’s struggle against disease, sacrifice, naivety, God’s will (chance for an atheist), and, of course, the great lessen of humility that Nature is superior to man in any sphere. Howard Florey though, is a national hero in his motherland, Australia for ever. This is not the solitary tale of medical research or, for that matter, any scientific research. In a manner of speaking, what is not in this story, about human qualities of head and heart, is no where.







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