History
Fleming
Alexander Fleming at St. Mary’s Hospital Medical School in London during 1928 noticed something growing on a culture plate of bacteria. It was dotted with colonies, except for one area where a blob of mold was emerging. The zone immediately around the mold—identified incorrectly by Fleming as a rare strain of Penicillium notatum, but later identified correctly as Penicillum rubens—was clear, showing the mold had secreted something that inhibited bacterial growth. This was during the time of WWI, and Fleming's
battlefront experience had shown him how serious of a killer bacteria could be and his quest for an antibacterial drug began.
Fleming had already discovered lysozyme, an enzyme occurring in many body fluids that had a natural antibacterial effect, but not against the strongest infectious agents. After his encounter with Penicillium, Fleming presented his findings in 1929, but they raised little interest. He published a report on penicillin and its potential uses in the British Journal of Experimental Pathology. Fleming worked with the mold for some time, but refining and growing it was a difficult process better suited to a chemist. The work was taken over by a team of chemists and mold specialists, among them was Howard Florey.
battlefront experience had shown him how serious of a killer bacteria could be and his quest for an antibacterial drug began.
Fleming had already discovered lysozyme, an enzyme occurring in many body fluids that had a natural antibacterial effect, but not against the strongest infectious agents. After his encounter with Penicillium, Fleming presented his findings in 1929, but they raised little interest. He published a report on penicillin and its potential uses in the British Journal of Experimental Pathology. Fleming worked with the mold for some time, but refining and growing it was a difficult process better suited to a chemist. The work was taken over by a team of chemists and mold specialists, among them was Howard Florey.
Howard Florey, Professor of Pathology at Oxford in 1935, with the help of Norman Heatley, a biochemist who became Florey’s research associate in 1940, were able to test the activity of samples of
penicillin they themselves produced . They needed a good method to extract the penicillin from cultures of the Penicillium mold leading Heatley to devise a new technique to measure the activity of a sample of penicillin; a method called back-extraction to isolate the organism by extracting it into amyl acetate and then back into water, using a countercurrent system. Another biochemist, Edward Abraham, then used the newly discovered technique of alumina column chromatography to remove impurities from the penicillin prior to clinical trials. |
By 25 May 1940, the team had reached a point where they could carry out a new experiment that would test
whether penicillin could be an important antibacterial drug. 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 the mold in different vessels such as baths, bedpans, milk churns, and food tins. Then, 8 mice were given lethal doses of Streptococci and 4 of the mice were given injections of penicillin. The next morning only the mice that had received the injection of penicillin had survived. |
At this point, the biggest problem became the production of enough penicillin since it was hard and expensive to accomplish. Florey and another researcher traveled to the U.S. and visited an agricultural research center and chemical manufacturers in Peoria, Illinois. Here, an excellent technique of fermentation had been developed. (Fermentation is a process needed
for penicillin growth). The nutrient base for the penicillin grown there was corn (maize), which was not commonly grown in Britain - the penicillin yielded almost 500 times as much as it had before. More vigorous and productive strains of the mold were sought, and one of the best came from a rotting cantaloupe. |
With this result, Florey realized the need to expand production – an effective treatment for infection could be a valuable contribution to Britain’s war effort. He turned the Dunn School into something of a penicillin factory. A team of young girls was employed, at £2 a week, to inoculate and generally look after the fermentation; these ‘penicillin girls’ were taken on to maintain production in 700 newly designed vessels which were
continuously in use. By February 1941, Florey felt he had enough penicillin to begin trials in humans. |
On 12 February 1941, with the help of Charles Fletcher, a young doctor at the Radcliffe Infirmary, Albert Alexander, a 43-year-old policeman, became the first patient to be treated with penicillin. He had scratched his face on a rose bush, the wound had become infected and the infection had spread. Fletcher injected
him with penicillin regularly over four days, and the next day his condition had improved considerably. Other human trials took place immediately after; of the next five patients, four recovered from their infections after a treatment with penicillin. The other, a child of four, was cured of his infection but tragically died of a brain hemorrhage. The results were published in The Lancet in August 1941 |
These results had great implications considering the political conditions of the time. War-time conditions made industrial production of penicillin difficult. A number of British companies, took up the challenge. Other similarly impressive results from larger trials began to emerge consequently. Companies in the US and then the in the UK began to start production of penicillin on an industrial scale. Supplies of penicillin accompanied the troops making the D-day landings in June 1944, and the death toll from infected wounds during the campaign was dramatically reduced. Penicillin inspired massive efforts to discover other new drugs that could conquer the many diseases still threatening the world. Further antibiotics soon followed.
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Antibiotics have seen a dramatic change in the figures for deaths and illness from infectious diseases. Antibiotics have also provided safe and effective treatments for the wide range of infections that were a daily problem in hospitals and general practice.
Fleming, Florey and Chain were jointly awarded the Nobel Prize for physiology or medicine in 1945, recognizing the tremendous contribution of penicillin to human welfare. |
Image 1 Source :http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-bio.html
Image 2 Source: http://en.wikipedia.org/wiki/File:Howard_Walter_Florey_1945.jpg
Image 3 Source: http://news.bbc.co.uk/local/oxford/hi/people_and_places/history/newsid_8828000/8828836.stm
Image 4 Source: http://www.scienceclarified.com/scitech/Bacteria-and-Viruses/Fighting-an-Invisible-Enemy.html#blsbv_0001_0001_0_img0014.jpg
Image 5 Source: http://www.onearth.org/blog/antibiotic-resistance-and-the-bacterial-arms-race
Image 6 Source: http://pubs.acs.org/cen/coverstory/83/8325/8325penicillin.html
Image 7 Source: http://www.ox.ac.uk/research/medical_sciences/projects/penicillin.html
Donald J. Tipper and Jack L. Strominger. "Mechanism of Action of Penicillins: A Proposal Based on their Structural Similarity to Acyl-D-alanyl-D-alanine." Proceedings of the National Academy of
Sciences of the United States of America. 1965. Page 1133.
Houbraken, J., Frisvad, J.C., Samson, R.A. "Fleming's penicillin producing strain is not Penicillin chryosgenum but P. rubens." <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317369/>
"A Science Odyssey: People and Discoveries: Fleming discovered penicillin." <http://www.pbs.org/wgbh/aso/databank/entries/dm28pe.html>
University of Oxford. "The Story of Penicillin." <http://www.ox.ac.uk/research/medical_sciences/projects/penicillin.html>
Image 2 Source: http://en.wikipedia.org/wiki/File:Howard_Walter_Florey_1945.jpg
Image 3 Source: http://news.bbc.co.uk/local/oxford/hi/people_and_places/history/newsid_8828000/8828836.stm
Image 4 Source: http://www.scienceclarified.com/scitech/Bacteria-and-Viruses/Fighting-an-Invisible-Enemy.html#blsbv_0001_0001_0_img0014.jpg
Image 5 Source: http://www.onearth.org/blog/antibiotic-resistance-and-the-bacterial-arms-race
Image 6 Source: http://pubs.acs.org/cen/coverstory/83/8325/8325penicillin.html
Image 7 Source: http://www.ox.ac.uk/research/medical_sciences/projects/penicillin.html
Donald J. Tipper and Jack L. Strominger. "Mechanism of Action of Penicillins: A Proposal Based on their Structural Similarity to Acyl-D-alanyl-D-alanine." Proceedings of the National Academy of
Sciences of the United States of America. 1965. Page 1133.
Houbraken, J., Frisvad, J.C., Samson, R.A. "Fleming's penicillin producing strain is not Penicillin chryosgenum but P. rubens." <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317369/>
"A Science Odyssey: People and Discoveries: Fleming discovered penicillin." <http://www.pbs.org/wgbh/aso/databank/entries/dm28pe.html>
University of Oxford. "The Story of Penicillin." <http://www.ox.ac.uk/research/medical_sciences/projects/penicillin.html>