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Monday, 05/28/2018 7:43:02 AM

Monday, May 28, 2018 7:43:02 AM

Post# of 462581
Let's not wait and do this again w/A2-73 etal

Alexander Fleming’s Discovery of Penicillin
Penicillin heralded the dawn of the antibiotic age. Before its introduction there was no effective treatment for infections such as pneumonia, gonorrhea or rheumatic fever. Hospitals were full of people with blood poisoning contracted from a cut or a scratch, and doctors could do little for them but wait and hope.
Antibiotics are compounds produced by bacteria and fungi which are capable of killing, or inhibiting, competing microbial species. This phenomenon has long been known; it may explain why the ancient Egyptians had the practice of applying a poultice of moldy bread to infected wounds. But it was not until 1928 that penicillin, the first true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London.
Returning from holiday on September 3, 1928, Fleming began to sort through petri dishes containing colonies of Staphylococcus, bacteria that cause boils, sore throats and abscesses. He noticed something unusual on one dish. It was dotted with colonies, save for one area where a blob of mold was growing. The zone immediately around the mold—later identified as a rare strain of Penicillium notatum—was clear, as if the mold had secreted something that inhibited bacterial growth.
Fleming found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus and the diphtheria bacillus. He then set his assistants, Stuart Craddock and Frederick Ridley, the difficult task of isolating pure penicillin from the mold juice. It proved to be very unstable, and they were only able to prepare solutions of crude material to work with. Fleming published his findings in the British Journal of Experimental Pathology in June 1929, with only a passing reference to penicillin's potential therapeutic benefits. At this stage it looked as if its main application would be in isolating penicillin-insensitive bacteria from penicillin-sensitive bacteria in a mixed culture. This at least was of practical benefit to bacteriologists, and kept interest in penicillin going. Others, including Harold Raistrick, Professor of Biochemistry at the London School of Hygiene and Tropical Medicine, tried to purify penicillin but failed.
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Penicillin Research at Oxford University
It was Howard Florey, Ernst Chain and their colleagues at the Sir William Dunn School of Pathology at Oxford University who turned penicillin from a laboratory curiosity into a life-saving drug. Their work on the purification and chemistry of penicillin began in earnest in 1939, just when wartime conditions were beginning to make research especially difficult. To carry out a program of animal experiments and clinical trials the team needed to process up to 500 liters a week of mold filtrate. They began growing it in a strange array of culture vessels such as baths, bedpans, milk churns and food tins. Later, a customized fermentation vessel was designed for ease of removing and, to save space, renewing the broth beneath the surface of the mold. A team of "penicillin girls" was employed, at £2 a week, to inoculate and generally look after the fermentation. In effect, the Oxford laboratory was being turned into a penicillin factory.
Meanwhile, biochemist Norman Heatley extracted penicillin from huge volumes of filtrate coming off the production line by extracting it into amyl acetate and then back into water, using a countercurrent system. Edward Abraham, another biochemist who was employed to help step up production, then used the newly discovered technique of alumina column chromatography to remove impurities from the penicillin prior to clinical trials.
In 1940, Florey carried out vital experiments, showing that penicillin could protect mice against infection from deadly Streptococci. Then, on February 12, 1941, a 43-year old policeman, Albert Alexander, became the first recipient of the Oxford penicillin. He had scratched the side of his mouth while pruning roses, and had developed a life-threatening infection with huge abscesses affecting his eyes, face, and lungs. Penicillin was injected and within days he made a remarkable recovery. But supplies of the drug ran out and he died a few days later. Better results followed with other patients though and soon there were plans to make penicillin available for British troops on the battlefield.
War-time conditions made industrial production of penicillin difficult. A number of British companies, including Glaxo (now GlaxoSmithKline) and Kemball Bishop, a London firm later bought by Pfizer, took up the challenge.



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