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Penicillin was the first antibiotic discovered by man.
Healing effects of penicillin became an impulse for further research, which effected great progress of many different fields like chemistry, bacteriology, pharmacology and medicine. In this article I would like to tell You about some properties, circumstances of discovery of this uncommon substance and the history of its discoverer.
Sir Alexander Fleming was born 06.08.1881 in Lochfield, Scotland. His father was a pharmacist. He attended schools in Louden Moor, Darvel and Academy in Kilmarnock, before he moved to London. There, in 1901, he started medical studies at St. Mary’s Hospital School. As a student he received a medal for his dissertation about sharp bacterial infections. After finishing school with distinction in 1906 he started research work there under the leadership of Sir Almroth Wright – the outstanding expert on vaccines, which lasted till 1914. During World War I Fleming was enlisted to Medical Corps, where he acquired the captain rank. In the army he had many occasions to see infected wounds, which made him discover that many drugs destroy the human organism more than bacteria. After the war in 1918 Fleming returned to Saint Mary’s, where he received the titles of Professor of School and Emeritus Professor of Bacteriology, University of London. Even in his youth, professor Fleming was interested in the influence of bacteria on human organism. Luckily he was able to continue research due to his military career. After demobilization, he started searching for an antibacterial substance that would be non-toxic and could be injected to animals. He was a member of most medical and scientifical societies in the world, he was also awarded a honoris causa doctorate of more that 30 American and European universities and titled as chief Doy-gei-tau of Kiowa tribe (Northern American Indians). In 1943 He was elected as member of the Royal Society. Doctor Alexander Fleming died of heart attack on 11 march 1955 in London and was buried in St. Paul’s cathedral.
Alexander Fleming’s adventure with penicillin started in 1928 from accidental the contamination of a staphylococci bacteria culture with mold. Dr. Fleming noticed, that in some distance from the mold microbes were dispersed. That was so unusual, that it demanded thorough expertise, the Scientist isolated the fungus and domesticated it in different dish. Now he could learn some of the mold’s properties. He found out that this fungus was from Penicillium group. Then it was identified as Penicillium notatum. Fleming decided to grow the mold in another dish and spread many different bacteria radially from the mold. Some of the microbes was growing freely near the mold – but other lived several centimeters away from it. This experiment showed, that the fungus produced a substance, that injured some bacteria, but did not hurt the others. In the same way Dr. Fleming checked many other mold species, but none of them produced that antibacterial substance. Because as he found that substance only in penicillium notatum, he called it penicillinum (penicillin). Penicillin wasn’t the first antibiotic discovered by Dr. Fleming. In the same year he found in human spittle, tears and in egg’s white substance, that he called lysozyme. Lysozyme restrained bacteria from growing, but unfortunately not of those most dangerous to man. With penicillin it was quite different. It destroyed microbes that caused syphilis, gonorrhea, scarlet fever, diphtheria, arthritis, bronchitis, blood, bones and lungs infections, tuberculosis and many more sicknesses.
One of the most important properties of penicillin is that it does not kill leukocytes - white blood corpuscles, as pharmaceuticals used in those days did. Antibacterial remedies used at that time (like phenol) were lethal for leucocytes and microbes quickly gained resistance to them. Penicillin is not toxic, so it cannot be overdosed or you can’t get poisoned with it. What penicillin does, is restraining the cell wall building process in the new bacterias. Penicillin blocks an enzyme – transpeptidase, which is synthesizing bacterial cell wall. This is a very important element of a bacterium. The substances needed for cell to grow are diffused through it and it makes all the microbe’s organs “stay in their place”. If the osmosis (process of diffusion through cell membranes) stops or if the bacteria’s intestines go outside, the cell will die. In some infections dose of 50000 units of penicillin is sufficient, but without care a patient can receive 100 millions units. There is danger however, of giving to small dose!. With dose of penicillin insufficient to kill bacteria they can become resistant very fast. This resistance is meant by possibility of bacteria to produce β-lactamases – enzymes capable of decomposing penicillin. With some people penicillin may cause anaphylactic shock, the cause of which is allergy to this compound. It is true, that penicillin is an amazing cure, but unfortunately till 1940 it could not been mass produced. Then two British chemists: Sir Ernest Boris Chain and Sir Howard Walter Florey worked out a process of acquiring clean penicillin from the mold. This discovery effected in mass scale penicillin production. Great factories was built to grow penicillium notatum. For their discoveries Sir Alexander Fleming, Sir Ernest Boris Chain and Sir Howard Walter Florey were in 1945 honored with Noble Prize for “the discovery of penicillin and its curative effect in various infectious diseases".
From the chemical side, penicillins are all group of chemical compounds, and this most useful is penicillin G. It differs because of the benzyl group.
Penicillin is a single-hydroxide carboxylic acid that contains two heterocyclic rings in its molecule: pentagonal (blue) and tetragonal - -lactam ring (red). Green represents shared elements of both rings. Its systematic name due to International Union of Pure and Applied Chemistry (IUPAC) is: 3,3-dimethyl-7-oxo-6-[(phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Some of penicillin’s G properties:
Today penicillin is produced from penicillium chryzogenum mold.
The advantage of penicillin G is created by adding compounds containing benzyl group to the agar feed, which the fungus will use for synthesis. Thanks to that method it is possible to produce penicillin that contains 95% of penicillin G. Penicillin saved millions of human beings and we may be sure that it will save much more.
Molecule of penicillin G. Legend:
white - hydrogen
yellow - sulfur
red - oxygen
blue - nitrogen
cyan - carbon
Thanks are due to the teachers mgr Ewa Bramora and mgr Barbara Kucharska for their support in consultation.