Alexander Fleming and the Discovery of Penicillin

The miraculous mold… Fleming’s Life Saving Discovery lexander Fleming is His famous discovery happened credited with the on the day that Fleming Adiscovery of penicillin; perhaps returned to his laboratory the greatest achievement in having spent August on holiday medicine in the 20th Century. with his family. Before leaving, By Jay Hardy, CLS, SM (NRCM) he had stacked all his cultures Having grown up in Scotland, of staphylococci on a bench in a Fleming moved to London corner of his laboratory. On Jay Hardy is the founder and where he attended medical returning, Fleming noticed that president of Hardy Diagnostics. school. After serving his one culture was contaminated He began his career in country as a medic in World with a fungus, and that the microbiology as a Medical Technologist in Santa Barbara, War I, he returned to London colonies of staphylococci that California. where he began his career as a had immediately surrounded it In 1980, he began manufacturing bacteriologist. There he began had been destroyed, whereas culture media for the local his search for more effective other colonies farther away hospitals. Today, Hardy antimicrobial agents. Having were normal. Diagnostics is the third largest culture media manufacturer in the witnessed the death of many United States. wounded soldiers in the war, he noticed that in many cases the To ensure rapid and reliable turn around time, Hardy Diagnostics use of harsh antiseptics did maintains seven distribution more harm than good. centers, and produces over 3,500 products used in clinical and industrial microbiology By 1928, Fleming was laboratories throughout the world. investigating the properties of staphylococci. He was already well-known from his earlier work, and had developed a reputation as a brilliant Figure 1: Alexander Fleming in his London laboratory. researcher, but his laboratory in the basement of St. Mary’s "When I woke up just after Hospital in London was often untidy. dawn on September 28, 1928, I certainly didn't plan to revolutionize all medicine by Pathology, but little attention Fleming finally abandoned discovering the world's first was paid to his article. penicillin. Not long after he antibiotic, or bacteria killer," did, Howard Florey and Ernst Fleming would later say, "But I Chain at the Radcliffe Infirmary suppose that was exactly what I in Oxford took up researching did.” and mass-producing it with funds from the U.S. and British Fleming grew the mold in a governments. They started mass pure culture and found that it production after the bombing of produced a substance that killed Pearl Harbor. When D-Day a number of pathogenic arrived, they had made enough bacteria. He identified the mold penicillin to treat all the as being from Penicillium wounded Allied forces. notanum, and after some months of calling it "mold Figure 2: Fleming’s photo of the It was Ernst Chain and Edward juice" named the substance it fungus, Penicillium notatum, Abraham who finally developed released penicillin in March of inhibiting Staphylocccus. the method to isolate and 1929. concentrate penicillin. Shortly Fleming continued his after the team published its first investigations, but found that results in 1940, Fleming “…I certainly didn't plan to cultivating penicillium was telephoned Howard Florey, quite difficult. After having revolutionize all medicine by Chain's head of department, to grown the mold, it was even say that he would be visiting discovering the world's first more difficult to isolate the within the next few days. When antibiotic…” antibiotic agent. Chain heard that he was coming, he remarked, "Good Fleming's impression was that He investigated its positive anti- God! I thought he was dead." because of the problem of bacterial effect on many producing it in quantity, and organisms, and noticed that it because its action appeared to affected bacteria such as be rather slow, penicillin would staphylococci and many other not be important in treating Gram positive pathogens that infection. Fleming also became cause scarlet fever, pneumonia, convinced that penicillin would meningitis and diphtheria, but not last long enough in the not typhoid fever or paratyphoid human body (in vivo) to kill fever, which are caused by bacteria effectively. Many Gram-negative bacteria, for clinical tests were inconclusive, which he was seeking a cure at After the team had developed a probably because it had been the time. It also effectively method of purifying penicillin used as a surface antiseptic. In killed Neisseria gonorrhoeae, to an effective first stable form the 1930s, Fleming’s trials although this bacterium is Gram in 1940, several clinical trials occasionally showed more negative. ensued. Their amazing success promise, and he continued until inspired the team to develop 1940 to try to interest a chemist Fleming published his methods for mass production skilled enough to further refine discovery in 1929 in the British and distribution in 1945, which usable penicillin. Journal of Experimental was just in time to be of use in World War II. Fleming was very aware of the ensuing bacterial resistance to his new drug, and he cautioned about the over use of penicillin in his many speeches around the world. He warned not to use penicillin unless there was a properly diagnosed reason for it Figure 3: The chemical structure of to be used, and that if it were penicillin showing the beta-lactam ring. used, never to use too little, or for too short a period, since The structure of the penicillin these are the circumstances Fleming was modest about his under which bacterial resistance part in the development of molecule features the β-Lactam ring, which inhibits the to antibiotics develops. penicillin, describing his fame as the "Fleming Myth" and he formation of the peptidoglycan praised Florey and Chain for cross-links in the bacterial cell transforming the laboratory wall, but has no direct effect on curiosity into a practical drug. cell wall degradation. The In fact, several others reported relatively small size of the the bacteriostatic effects of molecule allows it to deeply Penicillium earlier than penetrate the cell wall. Fleming. The use of bread with a blue mold (it is presumed, In the early days, before resistance developed, penicillin Figure 4: The early days of Penicillium) as a means of Penicillium culturing and penicillin treating infected wounds was a was widely used and effective production at the Dunn School of staple of folk medicine in in treating Staph and Strep Pathology in Oxford, England. Europe since the Middle Ages. infections, as well as syphilis and gonorrhea. It is still highly The challenge of mass- However, Fleming was the first effective against Groups A and producing this drug was to discover the properties of the B Strep infections. daunting. In 1942, the first active substance, giving him the patient was treated for privilege of naming it penicillin. streptococcal septicemia with He also kept, grew and U.S. made penicillin produced distributed the original mold for by Merck & Co. Half of the twelve years, and continued total supply produced at the until 1940 to try to get help time was used on that one from any chemist who had patient. In July 1943, the War enough skill to make penicillin. Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe. Penicillin is actively excreted, Cuter, was also involved in the and about 80% of a penicillin infamous Tuskegee syphilis dose is cleared from the body experiments. within three to four hours of administration. Indeed, during the early penicillin era, the drug was so scarce and so highly valued that it became common to collect the urine from patients being treated, so that the penicillin in the urine could be isolated and reused. In a 1946 to 1948 study in Figure 5: Mass production of Guatemala, U.S. researchers penicillin at Merck & Co. in 1945. used prostitutes to infect prison inmates, insane asylum patients, A moldy cantaloupe in a Peoria, and Guatemalan soldiers with Illinois, market in 1943 was syphilis and other sexually found to contain the best and transmitted diseases, in order to highest-quality penicillin after a test the effectiveness of Since this famous discovery in worldwide search. The penicillin in treating sexually 1928, many more effective discovery of the cantaloupe, and transmitted diseases. They later antimicrobials have been the results of fermentation tried infecting people with developed which retain the beta research on corn steep liquor at "direct inoculations made from lactam ring that is characteristic the Northern Regional Research syphilis bacteria poured into the of penicillin, such as Laboratory at Peoria, Illinois, men's penises and on forearms carbenicillin, methicillin, allowed the United States to and faces that were slightly imipenem, and the produce 2.3 million doses in abraded . or in a few cases cephalosporins. time for the invasion of through spinal punctures.” Normandy in the spring of Approximately 1,300 people For his important life saving 1944. By 1945, over 646 billion were infected as part of the discovery, he shared the Nobel units per year were being study (including orphan Prize in Physiology or Medicine produced. children). This study, now in 1945 with Howard Florey highly criticized for its and Ernst Chain. unethical treatment of its subjects, was sponsored by the Public Health Service, the National Institutes of Health Jay Hardy, CLS, SM (NRCM) and the Pan American Health Santa Maria, California Sanitary Bureau (now the World Health Organization's Pan American Health Organization) and the The information contained in this article is for educational purposes only and is not intended Guatemalan government. The nor recommended as a substitute for medical director of this study, John advice, diagnosis, or treatment.

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