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Wikipedia

Alexander Fleming

Sir Alexander Fleming FRS FRSE FRCS[1] (6 August 1881 – 11 March 1955) was a Scottish physician and microbiologist, best known for discovering the world's first broadly effective antibiotic substance, which he named penicillin. His discovery in 1928 of what was later named benzylpenicillin (or penicillin G) from the mould Penicillium rubens has been described as the "single greatest victory ever achieved over disease".[3][4] For this discovery, he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain.[5][6][7]


Alexander Fleming

Fleming in his laboratory, c. 1943
Born(1881-08-06)6 August 1881
Darvel, Ayrshire, Scotland
Died11 March 1955(1955-03-11) (aged 73)
London, England
Resting placeSt Paul's Cathedral
Alma mater
Known forDiscovery of penicillin and lysozyme
Spouses
Sarah Marion McElroy
(m. 1915; died 1949)
(m. 1953)
Awards
Scientific career
Fields
Signature

He also discovered the enzyme lysozyme from his nasal discharge in 1922, and along with it a bacterium he named Micrococcus lysodeikticus, later renamed Micrococcus luteus.

Fleming was knighted for his scientific achievements in 1944.[8] In 1999, he was named in Time magazine's list of the 100 Most Important People of the 20th century. In 2002, he was chosen in the BBC's television poll for determining the 100 Greatest Britons, and in 2009, he was also voted third "greatest Scot" in an opinion poll conducted by STV, behind only Robert Burns and William Wallace.

Early life and education

Born on 6 August 1881 at Lochfield farm near Darvel, in Ayrshire, Scotland, Alexander Fleming was the third of four children of farmer Hugh Fleming (1816–1888) and Grace Stirling Morton (1848–1928), the daughter of a neighbouring farmer. Hugh Fleming had four surviving children from his first marriage. He was 59 at the time of his second marriage to Grace, and died when Alexander was seven.[9]

Fleming went to Loudoun Moor School and Darvel School, and earned a two-year scholarship to Kilmarnock Academy before moving to London, where he attended the Royal Polytechnic Institution.[10] After working in a shipping office for four years, the twenty-year-old Alexander Fleming inherited some money from an uncle, John Fleming. His elder brother, Tom, was already a physician and suggested to him that he should follow the same career, and so in 1903, the younger Alexander enrolled at St Mary's Hospital Medical School in Paddington (now part of Imperial College London); he qualified with an MBBS degree from the school with distinction in 1906.[9]

Fleming, who was a private in the London Scottish Regiment of the Volunteer Force from 1900[5] to 1914,[11] had been a member of the rifle club at the medical school. The captain of the club, wishing to retain Fleming in the team, suggested that he join the research department at St Mary's, where he became assistant bacteriologist to Sir Almroth Wright, a pioneer in vaccine therapy and immunology. In 1908, he gained a BSc degree with gold medal in Bacteriology, and became a lecturer at St Mary's until 1914.

Commissioned lieutenant in 1914 and promoted captain in 1917,[11] Fleming served throughout World War I in the Royal Army Medical Corps, and was Mentioned in Dispatches. He and many of his colleagues worked in battlefield hospitals at the Western Front in France. In 1918 he returned to St Mary's Hospital, where he was elected Professor of Bacteriology of the University of London in 1928. In 1951 he was elected the Rector of the University of Edinburgh for a term of three years.[9]

Scientific contributions

Antiseptics

During World War I, Fleming with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the entire Inoculation Department of St Mary's to the British military hospital at Boulogne-sur-Mer. Serving as a temporary lieutenant of the Royal Army Medical Corps, he witnessed the death of many soldiers from sepsis resulting from infected wounds. Antiseptics, which were used at the time to treat infected wounds, he observed, often worsened the injuries.[12] In an article published in the medical journal The Lancet in 1917, he described an ingenious experiment, which he was able to conduct as a result of his own glassblowing skills, in which he explained why antiseptics were killing more soldiers than infection itself during the war. Antiseptics worked well on the surface, but deep wounds tended to shelter anaerobic bacteria from the antiseptic agent, and antiseptics seemed to remove beneficial agents produced that protected the patients in these cases at least as well as they removed bacteria, and did nothing to remove the bacteria that were out of reach.[13] Wright strongly supported Fleming's findings, but despite this, most army physicians over the course of the war continued to use antiseptics even in cases where this worsened the condition of the patients.[9]

Discovery of lysozyme

At St Mary's Hospital, Fleming continued his investigations into bacteria culture and antibacterial substances. As his research scholar at the time V. D. Allison recalled, Fleming was not a tidy researcher and usually expected unusual bacterial growths in his culture plates. Fleming had teased Allison of his "excessive tidiness in the laboratory", and Allison rightly attributed such untidiness as the success of Fleming's experiments, and said, "[If] he had been as tidy as he thought I was, he would not have made his two great discoveries."[14]

In late 1921, while he was maintaining agar plates for bacteria, he found that one of the plates was contaminated with bacteria from the air. When he added nasal mucus, he found that the mucus inhibited the bacterial growth.[15] Surrounding the mucus area was a clear transparent circle (1 cm from the mucus), indicating the killing zone of bacteria, followed by a glassy and translucent ring beyond which was an opaque area indicating normal bacterial growth. In the next test, he used bacteria maintained in saline that formed a yellow suspension. Within two minutes of adding fresh mucus, the yellow saline turned completely clear. He extended his tests using tears, which were contributed by his co-workers. As Allison reminisced, saying, "For the next five or six weeks, our tears were the source of supply for this extraordinary phenomenon. Many were the lemons we used (after the failure of onions) to produce a flow of tears... The demand by us for tears was so great, that laboratory attendants were pressed into service, receiving threepence for each contribution."[14]

His further tests with sputum, cartilage, blood, semen, ovarian cyst fluid, pus, and egg white showed that the bactericidal agent was present in all of these.[16] He reported his discovery before the Medical Research Club in December and before the Royal Society the next year but failed to stir any interest, as Allison recollected:

I was present at this [Medical Research Club] meeting as Fleming's guest. His paper describing his discovery was received with no questions asked and no discussion, which was most unusual and an indication that it was considered to be of no importance. The following year he read a paper on the subject before the Royal Society, Burlington House, Piccadilly and he and I gave a demonstration of our work. Again with one exception little comment or attention was paid to it.[14]

Reporting in the 1 May 1922 issue of the Proceedings of the Royal Society B: Biological Sciences under the title "On a remarkable bacteriolytic element found in tissues and secretions", Fleming wrote:

In this communication I wish to draw attention to a substance present in the tissues and secretions of the body, which is capable of rapidly dissolving certain bacteria. As this substance has properties akin to those of ferments I have called it a "Lysozyme", and shall refer to it by this name throughout the communication. The lysozyme was first noticed during some investigations made on a patient suffering from acute coryza.[15]

This was the first recorded discovery of lysozyme. With Allison, he published further studies on lysozyme in October issue of the British Journal of Experimental Pathology the same year.[17] Although he was able to obtain larger amounts of lysozyme from egg whites, the enzyme was only effective against small counts of harmless bacteria, and therefore had little therapeutic potential. This indicates one of the major differences between pathogenic and harmless bacteria.[12] Described in the original publication, "a patient suffering from acute coryza"[15] was later identified as Fleming himself. His research notebook dated 21 November 1921 showed a sketch of the culture plate with a small note: “Staphyloid coccus from A.F.'s nose."[16] He also identified the bacterium present in the nasal mucus as Micrococcus Lysodeikticus, giving the species name (meaning "lysis indicator" for its susceptibility to lysozymal activity).[18] The species was reassigned as Micrococcus luteus in 1972.[19] The "Fleming strain" (NCTC2665) of this bacterium has become a model in different biological studies.[20][21] The importance of lysozyme was not recognised, and Fleming was well aware of this, in his presidential address at the Royal Society of Medicine meeting on 18 October 1932, he said:

I choose lysozyme as the subject for this address for two reasons, firstly because I have a fatherly interest in the name, and, secondly, because its importance in connection with natural immunity does not seem to be generally appreciated.[22]

In his Nobel lecture on 11 December 1945, he briefly mentioned lysozyme, saying, "Penicillin was not the first antibiotic I happened to discover."[23] It was only towards the end of the 20th century that the true importance of Fleming's discovery in immunology was realised as lysozyme became the first antimicrobial protein discovered that constitute part of our innate immunity.[24][25]

Discovery of penicillin

 
An advertisement advertising penicillin's "miracle cure"

One sometimes finds what one is not looking for. When I woke up just after dawn on September 28, 1928, I certainly didn't plan to revolutionize all medicine by discovering the world's first antibiotic, or bacteria killer. But I suppose that was exactly what I did.

— Alexander Fleming[26]

Experiment

By 1927, Fleming had been investigating the properties of staphylococci. He was already well known from his earlier work, and had developed a reputation as a brilliant researcher. In 1928, he studied the variation of Staphylococcus aureus grown under natural condition, after the work of Joseph Warwick Bigger, who discovered that the bacterium could grow into a variety of types (strains).[27] On 3 September 1928, Fleming returned to his laboratory having spent a holiday with his family at Suffolk. Before leaving for his holiday, he inoculated staphylococci on culture plates and left them on a bench in a corner of his laboratory.[16] On his return, Fleming noticed that one culture was contaminated with a fungus, and that the colonies of staphylococci immediately surrounding the fungus had been destroyed, whereas other staphylococci colonies farther away were normal, famously remarking "That's funny".[28] Fleming showed the contaminated culture to his former assistant Merlin Pryce, who reminded him, "That's how you discovered lysozyme."[29] He identified the mould as being from the genus Penicillium. He suspected it to be P. chrysogenum, but a colleague Charles J. La Touche identified it as P. rubrum. (It was later corrected as P. notatum and then officially accepted as P. chrysogenum; in 2011, it was resolved as P. rubens.)[30][31]

 
Commemorative plaque marking Fleming's discovery of penicillin at St Mary's Hospital, London

The laboratory in which Fleming discovered and tested penicillin is preserved as the Alexander Fleming Laboratory Museum in St. Mary's Hospital, Paddington. The source of the fungal contaminant was established in 1966 as coming from La Touche's room, which was directly below Fleming's.[32][33]

Fleming grew the mould in a pure culture and found that the culture broth contained an antibacterial substance. He investigated its anti-bacterial effect on many organisms, and noticed that it affected bacteria such as staphylococci and many other Gram-positive pathogens that cause scarlet fever, pneumonia, meningitis and diphtheria, but not typhoid fever or paratyphoid fever, which are caused by Gram-negative bacteria, for which he was seeking a cure at the time. It also affected Neisseria gonorrhoeae, which causes gonorrhoea, although this bacterium is Gram-negative. After some months of calling it "mould juice" or "the inhibitor", he gave the name penicillin on 7 March 1929 for the antibacterial substance present in the mould.[34]

Reception and publication

Fleming presented his discovery on 13 February 1929 before the Medical Research Club. His talk on "A medium for the isolation of Pfeiffer's bacillus" did not receive any particular attention or comment. Henry Dale, the then Director of National Institute for Medical Research and chair of the meeting, much later reminisced that he did not even sense any striking point of importance in Fleming's speech.[16] Fleming published his discovery in 1929 in the British Journal of Experimental Pathology,[35] but little attention was paid to the article. His problem was the difficulty of producing penicillin in large amounts, and moreover, isolation of the main compound. Even with the help of Harold Raistrick and his team of biochemists at the London School of Hygiene and Tropical Medicine, chemical purification was futile. "As a result, penicillin languished largely forgotten in the 1930s", as Milton Wainwright described.[36]

As late as in 1936, there was no appreciation for penicillin. When Fleming talked of its medical importance at the Second International Congress of Microbiology held in London,[37][38] no one believed him. As Allison, his companion in both the Medical Research Club and international congress meeting, remarked the two occasions:

[Fleming at the Medical Research Club meeting] suggested the possible value of penicillin for the treatment of infection in man. Again there was a total lack of interest and no discussion. Fleming was keenly disappointed, but worse was to follow. He read a paper on his work on penicillin at a meeting of the International Congress of Microbiology, attended by the foremost bacteriologists from all over the world. There was no support for his views on its possible future value for the prevention and treatment of human infections and discussion was minimal. Fleming bore these disappointments stoically, but they did not alter his views or deter him from continuing his investigation of penicillin.[14]

In 1941, the British Medical Journal reported that "[Penicillin] does not appear to have been considered as possibly useful from any other point of view."[39][40][32]

Purification and stabilisation

 
3D-model of benzylpenicillin

In Oxford, Ernst Boris Chain and Edward Abraham were studying the molecular structure of the antibiotic. Abraham was the first to propose the correct structure of penicillin.[41][42] Shortly after the team published its first results in 1940, Fleming telephoned Howard Florey, Chain's head of department, to say that he would be visiting within the next few days. When Chain heard that Fleming was coming, he remarked "Good God! I thought he was dead."[43]

Norman Heatley suggested transferring the active ingredient of penicillin back into water by changing its acidity. This produced enough of the drug to begin testing on animals. There were many more people involved in the Oxford team, and at one point the entire Sir William Dunn School of Pathology was involved in its production. After the team had developed a method of purifying penicillin to an effective first stable form in 1940, several clinical trials ensued, and their amazing success inspired the team to develop methods for mass production and mass distribution in 1945.[44][45]

Fleming was modest about his part in the development of penicillin, describing his fame as the "Fleming Myth" and he praised Florey and Chain for transforming the laboratory curiosity into a practical drug. Fleming was the first to discover the properties of the active substance, giving him the privilege of naming it: penicillin. He also kept, grew, and distributed the original mould for twelve years, and continued until 1940 to try to get help from any chemist who had enough skill to make penicillin. Sir Henry Harris summed up the process in 1998 as: "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin."[46] The discovery of penicillin and its subsequent development as a prescription drug mark the start of modern antibiotics.[47]

Medical use and mass production

In his first clinical trial, Fleming treated his research scholar Stuart Craddock who had developed severe infection of the nasal antrum (sinusitis). The treatment started on 9 January 1929 but without any effect. It probably was due to the fact that the infection was with influenza bacillus (Haemophilus influenzae), the bacterium which he had found unsusceptible to penicillin.[32] Fleming gave some of his original penicillin samples to his colleague-surgeon Arthur Dickson Wright for clinical test in 1928.[48][49] Although Wright reportedly said that it "seemed to work satisfactorily",[50] there are no records of its specific use. Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield and former student of Fleming, was the first to use penicillin successfully for medical treatment.[36] He cured eye infections (conjunctivitis) of one adult and three infants (neonatal conjunctivitis) on 25 November 1930.[51]

 
Fleming in his laboratory in 1943

Fleming also successfully treated severe conjunctivitis in 1932.[3][52][53] Keith Bernard Rogers, who had joined St Mary's as medical student in 1929,[54] was captain of the London University rifle team and was about to participate in an inter-hospital rifle shooting competition when he developed conjunctivitis.[55][56][57] Fleming applied his penicillin and cured Rogers before the competition.[3][52][58] It is said that the "penicillin worked and the match was won." However, the report that "Keith was probably the first patient to be treated clinically with penicillin ointment"[56] is no longer true as Paine's medical records showed up.[34]

There is a popular assertion both in popular and scientific literature that Fleming largely abandoned penicillin work in the early 1930s.[59][60][61][62] In his review of André Maurois's The Life of Sir Alexander Fleming, Discoverer of Penicillin, William L. Kissick went so far as to say that "Fleming had abandoned penicillin in 1932... Although the recipient of many honors and the author of much scientific work, Sir Alexander Fleming does not appear to be an ideal subject for a biography."[63] This is false, as Fleming continued to pursue penicillin research.[49][64] As late as in 1939, Fleming's notebook shows attempts to make better penicillin production using different media.[34] In 1941, he published a method for assessment of penicillin effectiveness.[65] As to the chemical isolation and purification, Howard Florey and Ernst Boris Chain at the Radcliffe Infirmary in Oxford took up the research to mass-produce it, which they achieved with support from World War II military projects under the British and US governments.[66]

By mid-1942, the Oxford team produced the pure penicillin compound as yellow powder.[67] In August 1942, Harry Lambert (an associate of Fleming's brother Robert) was admitted to St Mary's Hospital due to a life-threatening infection of the nervous system (streptococcal meningitis).[68] Fleming treated him with sulphonamides, but Lambert's condition deteriorated. He tested the antibiotic susceptibility and found that his penicillin could kill the bacteria. He requested Florey for the isolated sample. Florey sent the incompletely purified sample, which Fleming immediately administered into Lambert's spinal canal. Lambert showed signs of improvement the very next day,[14] and completely recovered within a week.[3][69] Fleming published the clinical case in The Lancet in 1943.[70]

Upon this medical breakthrough, Allison informed the British Ministry of Health of the importance of penicillin and the need for mass production. The War Cabinet was convinced of the usefulness upon which Sir Cecil Weir, Director General of Equipment, called for a meeting on the mode of action on 28 September 1942.[71][72] The Penicillin Committee was created on 5 April 1943. The committee consisted of Weir as chairman, Fleming, Florey, Sir Percival Hartley, Allison and representatives from pharmaceutical companies as members. The main goals were to produce penicillin rapidly in large quantities with collaboration of American companies, and to supply the drug exclusively for Allied armed forces.[14] By D-Day in 1944, enough penicillin had been produced to treat all the wounded of the Allied troops.[73]

Antibiotic resistance

 
Modern antibiotics are tested using a method similar to Fleming's discovery.

Fleming also discovered very early that bacteria developed antibiotic resistance whenever too little penicillin was used or when it was used for too short a period. Almroth Wright had predicted antibiotic resistance even before it was noticed during experiments. Fleming cautioned about the use of penicillin in his many speeches around the world. On 26 June 1945, he made the following cautionary statements: "the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out ... In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted."[74] He cautioned not to use penicillin unless there was a properly diagnosed reason for it to be used, and that if it were used, never to use too little, or for too short a period, since these are the circumstances under which bacterial resistance to antibiotics develops.[75]

It had been experimentally shown in 1942 that S. aureus could develop penicillin resistance under prolonged exposure.[76] Elaborating the possibility of penicillin resistance in clinical conditions in his Nobel Lecture, Fleming said:

The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.[23]

It was around that time that the first clinical case of penicillin resistance was reported.[77]

Personal life

 
Grave of Sir Alexander Fleming in the crypt of St Paul's Cathedral, London

On 24 December 1915, Fleming married a trained nurse, Sarah Marion McElroy of Killala, County Mayo, Ireland. Their only child, Robert Fleming (1924–2015), became a general medical practitioner. After his first wife's death in 1949, Fleming married Amalia Koutsouri-Vourekas, a Greek colleague at St. Mary's, on 9 April 1953; she died in 1986.[78]

Fleming came from a Presbyterian background, while his first wife Sarah was a (lapsed) Roman Catholic. It is said that he was not particularly religious, and their son Robert was later received into the Anglican church, while still reportedly inheriting his two parents' fairly irreligious disposition.[79]

When Fleming learned of Robert D. Coghill and Andrew J. Moyer patenting the method of penicillin production in the United States in 1944,[80] he was furious, and commented:

I found penicillin and have given it free for the benefit of humanity. Why should it become a profit-making monopoly of manufacturers in another country?[14]

From 1921 until his death in 1955, Fleming owned a country home named "The Dhoon" in Barton Mills, Suffolk.[4][81]

Death

On 11 March 1955, Fleming died at his home in London of a heart attack. His ashes are buried in St Paul's Cathedral.[2]

Awards and legacy

 
Display of Fleming's awards, including his Nobel Prize. Also shows a sample of penicillin and an example of an early apparatus for preparing it.
 
Sir Alexander Fleming (centre) receiving the Nobel prize from King Gustaf V of Sweden (right) in 1945
 
Faroe Islands postage stamp commemorating Fleming
 
Barcelona to Sir Alexander Fleming (1956), by Catalan sculptor Josep Manuel Benedicto. Barcelona: jardins del Doctor Fleming.

Fleming's discovery of penicillin changed the world of modern medicine by introducing the age of useful antibiotics; penicillin has saved, and is still saving, millions of people around the world.[82]

The laboratory at St Mary's Hospital where Fleming discovered penicillin is home to the Fleming Museum, a popular London attraction. His alma mater, St Mary's Hospital Medical School, merged with Imperial College London in 1988. The Sir Alexander Fleming Building on the South Kensington campus was opened in 1998, where his son Robert and his great-granddaughter Claire were presented to the Queen; it is now one of the main preclinical teaching sites of the Imperial College School of Medicine.

His other alma mater, the Royal Polytechnic Institution (now the University of Westminster) has named one of its student halls of residence Alexander Fleming House, which is near to Old Street.

Myths

The Fleming myth

By 1942, penicillin, produced as pure compound, was still in short supply and not available for clinical use. When Fleming used the first few samples prepared by the Oxford team to treat Harry Lambert who had streptococcal meningitis,[3] the successful treatment was a major news, particularly popularised in The Times. Wright was surprised to discover that Fleming and the Oxford team were not mentioned, though Oxford was attributed as the source of the drug. Wright wrote to the editor of The Times, which eagerly interviewed Fleming, but Florey prohibited the Oxford team from seeking media coverage. As a consequence, only Fleming was widely publicised in the media,[94] which led to the misconception that he was entirely responsible for the discovery and development of the drug.[95] Fleming himself referred to this incident as "the Fleming myth."[96][97]

The Churchills

The popular story[98] of Winston Churchill's father paying for Fleming's education after Fleming's father saved young Winston from death is false.[95] According to the biography, Penicillin Man: Alexander Fleming and the Antibiotic Revolution by Kevin Brown, Alexander Fleming, in a letter[99] to his friend and colleague Andre Gratia,[100] described this as "A wondrous fable." Nor did he save Winston Churchill himself during World War II. Churchill was saved by Lord Moran, using sulphonamides, since he had no experience with penicillin, when Churchill fell ill in Carthage in Tunisia in 1943. The Daily Telegraph and The Morning Post on 21 December 1943 wrote that he had been saved by penicillin. He was saved by the new sulphonamide drug sulphapyridine, known at the time under the research code M&B 693, discovered and produced by May & Baker Ltd, Dagenham, Essex – a subsidiary of the French group Rhône-Poulenc. In a subsequent radio broadcast, Churchill referred to the new drug as "This admirable M&B".[101] It is highly probable that the correct information about the sulphonamide did not reach the newspapers because, since the original sulphonamide antibacterial, Prontosil, had been a discovery by the German laboratory Bayer, and as Britain was at war with Germany at the time, it was thought better to raise British morale by associating Churchill's cure with a British discovery, penicillin.[citation needed]

See also

References

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Further reading

  • The Life Of Sir Alexander Fleming, Jonathan Cape, 1959. Maurois, André.
  • Nobel Lectures, the Physiology or Medicine 1942–1962, Elsevier Publishing Company, Amsterdam, 1964
  • An Outline History of Medicine. London: Butterworths, 1985. Rhodes, Philip.
  • The Cambridge Illustrated History of Medicine. Cambridge, England: Cambridge University Press, 1996. Porter, Roy, ed.
  • Penicillin Man: Alexander Fleming and the Antibiotic Revolution, Stroud, Sutton, 2004. Brown, Kevin.
  • Alexander Fleming: The Man and the Myth, Oxford University Press, Oxford, 1984. Macfarlane, Gwyn
  • Fleming, Discoverer of Penicillin, Ludovici, Laurence J., 1952
  • The Penicillin Man: the Story of Sir Alexander Fleming, Lutterworth Press, 1957, Rowland, John.

External links

  • Alexander Fleming Obituary
  • Alexander Fleming on Nobelprize.org   including the Nobel Lecture, 11 December 1945 Penicillin
  • Some places and memories related to Alexander Fleming
  • Newspaper clippings about Alexander Fleming in the 20th Century Press Archives of the ZBW
Academic offices
Preceded by Rector of the University of Edinburgh
1951–1954
Succeeded by

alexander, fleming, other, people, named, disambiguation, frse, frcs, august, 1881, march, 1955, scottish, physician, microbiologist, best, known, discovering, world, first, broadly, effective, antibiotic, substance, which, named, penicillin, discovery, 1928, . For other people named Alexander Fleming see Alexander Fleming disambiguation Sir Alexander Fleming FRS FRSE FRCS 1 6 August 1881 11 March 1955 was a Scottish physician and microbiologist best known for discovering the world s first broadly effective antibiotic substance which he named penicillin His discovery in 1928 of what was later named benzylpenicillin or penicillin G from the mould Penicillium rubens has been described as the single greatest victory ever achieved over disease 3 4 For this discovery he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain 5 6 7 SirAlexander FlemingFRS FRSE FRCSFleming in his laboratory c 1943Born 1881 08 06 6 August 1881Darvel Ayrshire ScotlandDied11 March 1955 1955 03 11 aged 73 London EnglandResting placeSt Paul s CathedralAlma materRoyal Polytechnic Institution St Mary s Hospital Medical SchoolKnown forDiscovery of penicillin and lysozymeSpousesSarah Marion McElroy m 1915 died 1949 wbr Amalia Koutsouri Vourekas m 1953 wbr AwardsFRS 1943 1 Knight Bachelor 1944 Cameron Prize for Therapeutics of the University of Edinburgh 1945 Nobel Prize 1945 2 FRSE FRCS Eng Scientific careerFieldsBacteriologyimmunologySignatureHe also discovered the enzyme lysozyme from his nasal discharge in 1922 and along with it a bacterium he named Micrococcus lysodeikticus later renamed Micrococcus luteus Fleming was knighted for his scientific achievements in 1944 8 In 1999 he was named in Time magazine s list of the 100 Most Important People of the 20th century In 2002 he was chosen in the BBC s television poll for determining the 100 Greatest Britons and in 2009 he was also voted third greatest Scot in an opinion poll conducted by STV behind only Robert Burns and William Wallace Contents 1 Early life and education 2 Scientific contributions 2 1 Antiseptics 2 2 Discovery of lysozyme 2 3 Discovery of penicillin 2 3 1 Experiment 2 3 2 Reception and publication 2 3 3 Purification and stabilisation 2 3 4 Medical use and mass production 2 3 5 Antibiotic resistance 3 Personal life 4 Death 5 Awards and legacy 6 Myths 6 1 The Fleming myth 6 2 The Churchills 7 See also 8 References 9 Further reading 10 External linksEarly life and educationBorn on 6 August 1881 at Lochfield farm near Darvel in Ayrshire Scotland Alexander Fleming was the third of four children of farmer Hugh Fleming 1816 1888 and Grace Stirling Morton 1848 1928 the daughter of a neighbouring farmer Hugh Fleming had four surviving children from his first marriage He was 59 at the time of his second marriage to Grace and died when Alexander was seven 9 Fleming went to Loudoun Moor School and Darvel School and earned a two year scholarship to Kilmarnock Academy before moving to London where he attended the Royal Polytechnic Institution 10 After working in a shipping office for four years the twenty year old Alexander Fleming inherited some money from an uncle John Fleming His elder brother Tom was already a physician and suggested to him that he should follow the same career and so in 1903 the younger Alexander enrolled at St Mary s Hospital Medical School in Paddington now part of Imperial College London he qualified with an MBBS degree from the school with distinction in 1906 9 Fleming who was a private in the London Scottish Regiment of the Volunteer Force from 1900 5 to 1914 11 had been a member of the rifle club at the medical school The captain of the club wishing to retain Fleming in the team suggested that he join the research department at St Mary s where he became assistant bacteriologist to Sir Almroth Wright a pioneer in vaccine therapy and immunology In 1908 he gained a BSc degree with gold medal in Bacteriology and became a lecturer at St Mary s until 1914 Commissioned lieutenant in 1914 and promoted captain in 1917 11 Fleming served throughout World War I in the Royal Army Medical Corps and was Mentioned in Dispatches He and many of his colleagues worked in battlefield hospitals at the Western Front in France In 1918 he returned to St Mary s Hospital where he was elected Professor of Bacteriology of the University of London in 1928 In 1951 he was elected the Rector of the University of Edinburgh for a term of three years 9 Scientific contributionsAntiseptics Main article Antiseptic During World War I Fleming with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the entire Inoculation Department of St Mary s to the British military hospital at Boulogne sur Mer Serving as a temporary lieutenant of the Royal Army Medical Corps he witnessed the death of many soldiers from sepsis resulting from infected wounds Antiseptics which were used at the time to treat infected wounds he observed often worsened the injuries 12 In an article published in the medical journal The Lancet in 1917 he described an ingenious experiment which he was able to conduct as a result of his own glassblowing skills in which he explained why antiseptics were killing more soldiers than infection itself during the war Antiseptics worked well on the surface but deep wounds tended to shelter anaerobic bacteria from the antiseptic agent and antiseptics seemed to remove beneficial agents produced that protected the patients in these cases at least as well as they removed bacteria and did nothing to remove the bacteria that were out of reach 13 Wright strongly supported Fleming s findings but despite this most army physicians over the course of the war continued to use antiseptics even in cases where this worsened the condition of the patients 9 Discovery of lysozyme Main article Lysozyme At St Mary s Hospital Fleming continued his investigations into bacteria culture and antibacterial substances As his research scholar at the time V D Allison recalled Fleming was not a tidy researcher and usually expected unusual bacterial growths in his culture plates Fleming had teased Allison of his excessive tidiness in the laboratory and Allison rightly attributed such untidiness as the success of Fleming s experiments and said If he had been as tidy as he thought I was he would not have made his two great discoveries 14 In late 1921 while he was maintaining agar plates for bacteria he found that one of the plates was contaminated with bacteria from the air When he added nasal mucus he found that the mucus inhibited the bacterial growth 15 Surrounding the mucus area was a clear transparent circle 1 cm from the mucus indicating the killing zone of bacteria followed by a glassy and translucent ring beyond which was an opaque area indicating normal bacterial growth In the next test he used bacteria maintained in saline that formed a yellow suspension Within two minutes of adding fresh mucus the yellow saline turned completely clear He extended his tests using tears which were contributed by his co workers As Allison reminisced saying For the next five or six weeks our tears were the source of supply for this extraordinary phenomenon Many were the lemons we used after the failure of onions to produce a flow of tears The demand by us for tears was so great that laboratory attendants were pressed into service receiving threepence for each contribution 14 His further tests with sputum cartilage blood semen ovarian cyst fluid pus and egg white showed that the bactericidal agent was present in all of these 16 He reported his discovery before the Medical Research Club in December and before the Royal Society the next year but failed to stir any interest as Allison recollected I was present at this Medical Research Club meeting as Fleming s guest His paper describing his discovery was received with no questions asked and no discussion which was most unusual and an indication that it was considered to be of no importance The following year he read a paper on the subject before the Royal Society Burlington House Piccadilly and he and I gave a demonstration of our work Again with one exception little comment or attention was paid to it 14 Reporting in the 1 May 1922 issue of the Proceedings of the Royal Society B Biological Sciences under the title On a remarkable bacteriolytic element found in tissues and secretions Fleming wrote In this communication I wish to draw attention to a substance present in the tissues and secretions of the body which is capable of rapidly dissolving certain bacteria As this substance has properties akin to those of ferments I have called it a Lysozyme and shall refer to it by this name throughout the communication The lysozyme was first noticed during some investigations made on a patient suffering from acute coryza 15 This was the first recorded discovery of lysozyme With Allison he published further studies on lysozyme in October issue of the British Journal of Experimental Pathology the same year 17 Although he was able to obtain larger amounts of lysozyme from egg whites the enzyme was only effective against small counts of harmless bacteria and therefore had little therapeutic potential This indicates one of the major differences between pathogenic and harmless bacteria 12 Described in the original publication a patient suffering from acute coryza 15 was later identified as Fleming himself His research notebook dated 21 November 1921 showed a sketch of the culture plate with a small note Staphyloid coccus from A F s nose 16 He also identified the bacterium present in the nasal mucus as Micrococcus Lysodeikticus giving the species name meaning lysis indicator for its susceptibility to lysozymal activity 18 The species was reassigned as Micrococcus luteus in 1972 19 The Fleming strain NCTC2665 of this bacterium has become a model in different biological studies 20 21 The importance of lysozyme was not recognised and Fleming was well aware of this in his presidential address at the Royal Society of Medicine meeting on 18 October 1932 he said I choose lysozyme as the subject for this address for two reasons firstly because I have a fatherly interest in the name and secondly because its importance in connection with natural immunity does not seem to be generally appreciated 22 In his Nobel lecture on 11 December 1945 he briefly mentioned lysozyme saying Penicillin was not the first antibiotic I happened to discover 23 It was only towards the end of the 20th century that the true importance of Fleming s discovery in immunology was realised as lysozyme became the first antimicrobial protein discovered that constitute part of our innate immunity 24 25 Discovery of penicillin Main article History of penicillin nbsp An advertisement advertising penicillin s miracle cure One sometimes finds what one is not looking for When I woke up just after dawn on September 28 1928 I certainly didn t plan to revolutionize all medicine by discovering the world s first antibiotic or bacteria killer But I suppose that was exactly what I did Alexander Fleming 26 Experiment By 1927 Fleming had been investigating the properties of staphylococci He was already well known from his earlier work and had developed a reputation as a brilliant researcher In 1928 he studied the variation of Staphylococcus aureus grown under natural condition after the work of Joseph Warwick Bigger who discovered that the bacterium could grow into a variety of types strains 27 On 3 September 1928 Fleming returned to his laboratory having spent a holiday with his family at Suffolk Before leaving for his holiday he inoculated staphylococci on culture plates and left them on a bench in a corner of his laboratory 16 On his return Fleming noticed that one culture was contaminated with a fungus and that the colonies of staphylococci immediately surrounding the fungus had been destroyed whereas other staphylococci colonies farther away were normal famously remarking That s funny 28 Fleming showed the contaminated culture to his former assistant Merlin Pryce who reminded him That s how you discovered lysozyme 29 He identified the mould as being from the genus Penicillium He suspected it to be P chrysogenum but a colleague Charles J La Touche identified it as P rubrum It was later corrected as P notatum and then officially accepted as P chrysogenum in 2011 it was resolved as P rubens 30 31 nbsp Commemorative plaque marking Fleming s discovery of penicillin at St Mary s Hospital LondonThe laboratory in which Fleming discovered and tested penicillin is preserved as the Alexander Fleming Laboratory Museum in St Mary s Hospital Paddington The source of the fungal contaminant was established in 1966 as coming from La Touche s room which was directly below Fleming s 32 33 Fleming grew the mould in a pure culture and found that the culture broth contained an antibacterial substance He investigated its anti bacterial effect on many organisms and noticed that it affected bacteria such as staphylococci and many other Gram positive pathogens that cause scarlet fever pneumonia meningitis and diphtheria but not typhoid fever or paratyphoid fever which are caused by Gram negative bacteria for which he was seeking a cure at the time It also affected Neisseria gonorrhoeae which causes gonorrhoea although this bacterium is Gram negative After some months of calling it mould juice or the inhibitor he gave the name penicillin on 7 March 1929 for the antibacterial substance present in the mould 34 Reception and publication Fleming presented his discovery on 13 February 1929 before the Medical Research Club His talk on A medium for the isolation of Pfeiffer s bacillus did not receive any particular attention or comment Henry Dale the then Director of National Institute for Medical Research and chair of the meeting much later reminisced that he did not even sense any striking point of importance in Fleming s speech 16 Fleming published his discovery in 1929 in the British Journal of Experimental Pathology 35 but little attention was paid to the article His problem was the difficulty of producing penicillin in large amounts and moreover isolation of the main compound Even with the help of Harold Raistrick and his team of biochemists at the London School of Hygiene and Tropical Medicine chemical purification was futile As a result penicillin languished largely forgotten in the 1930s as Milton Wainwright described 36 As late as in 1936 there was no appreciation for penicillin When Fleming talked of its medical importance at the Second International Congress of Microbiology held in London 37 38 no one believed him As Allison his companion in both the Medical Research Club and international congress meeting remarked the two occasions Fleming at the Medical Research Club meeting suggested the possible value of penicillin for the treatment of infection in man Again there was a total lack of interest and no discussion Fleming was keenly disappointed but worse was to follow He read a paper on his work on penicillin at a meeting of the International Congress of Microbiology attended by the foremost bacteriologists from all over the world There was no support for his views on its possible future value for the prevention and treatment of human infections and discussion was minimal Fleming bore these disappointments stoically but they did not alter his views or deter him from continuing his investigation of penicillin 14 In 1941 the British Medical Journal reported that Penicillin does not appear to have been considered as possibly useful from any other point of view 39 40 32 Purification and stabilisation nbsp 3D model of benzylpenicillinIn Oxford Ernst Boris Chain and Edward Abraham were studying the molecular structure of the antibiotic Abraham was the first to propose the correct structure of penicillin 41 42 Shortly after the team published its first results in 1940 Fleming telephoned Howard Florey Chain s head of department to say that he would be visiting within the next few days When Chain heard that Fleming was coming he remarked Good God I thought he was dead 43 Norman Heatley suggested transferring the active ingredient of penicillin back into water by changing its acidity This produced enough of the drug to begin testing on animals There were many more people involved in the Oxford team and at one point the entire Sir William Dunn School of Pathology was involved in its production After the team had developed a method of purifying penicillin to an effective first stable form in 1940 several clinical trials ensued and their amazing success inspired the team to develop methods for mass production and mass distribution in 1945 44 45 Fleming was modest about his part in the development of penicillin describing his fame as the Fleming Myth and he praised Florey and Chain for transforming the laboratory curiosity into a practical drug Fleming was the first to discover the properties of the active substance giving him the privilege of naming it penicillin He also kept grew and distributed the original mould for twelve years and continued until 1940 to try to get help from any chemist who had enough skill to make penicillin Sir Henry Harris summed up the process in 1998 as Without Fleming no Chain without Chain no Florey without Florey no Heatley without Heatley no penicillin 46 The discovery of penicillin and its subsequent development as a prescription drug mark the start of modern antibiotics 47 Medical use and mass production In his first clinical trial Fleming treated his research scholar Stuart Craddock who had developed severe infection of the nasal antrum sinusitis The treatment started on 9 January 1929 but without any effect It probably was due to the fact that the infection was with influenza bacillus Haemophilus influenzae the bacterium which he had found unsusceptible to penicillin 32 Fleming gave some of his original penicillin samples to his colleague surgeon Arthur Dickson Wright for clinical test in 1928 48 49 Although Wright reportedly said that it seemed to work satisfactorily 50 there are no records of its specific use Cecil George Paine a pathologist at the Royal Infirmary in Sheffield and former student of Fleming was the first to use penicillin successfully for medical treatment 36 He cured eye infections conjunctivitis of one adult and three infants neonatal conjunctivitis on 25 November 1930 51 nbsp Fleming in his laboratory in 1943Fleming also successfully treated severe conjunctivitis in 1932 3 52 53 Keith Bernard Rogers who had joined St Mary s as medical student in 1929 54 was captain of the London University rifle team and was about to participate in an inter hospital rifle shooting competition when he developed conjunctivitis 55 56 57 Fleming applied his penicillin and cured Rogers before the competition 3 52 58 It is said that the penicillin worked and the match was won However the report that Keith was probably the first patient to be treated clinically with penicillin ointment 56 is no longer true as Paine s medical records showed up 34 There is a popular assertion both in popular and scientific literature that Fleming largely abandoned penicillin work in the early 1930s 59 60 61 62 In his review of Andre Maurois s The Life of Sir Alexander Fleming Discoverer of Penicillin William L Kissick went so far as to say that Fleming had abandoned penicillin in 1932 Although the recipient of many honors and the author of much scientific work Sir Alexander Fleming does not appear to be an ideal subject for a biography 63 This is false as Fleming continued to pursue penicillin research 49 64 As late as in 1939 Fleming s notebook shows attempts to make better penicillin production using different media 34 In 1941 he published a method for assessment of penicillin effectiveness 65 As to the chemical isolation and purification Howard Florey and Ernst Boris Chain at the Radcliffe Infirmary in Oxford took up the research to mass produce it which they achieved with support from World War II military projects under the British and US governments 66 By mid 1942 the Oxford team produced the pure penicillin compound as yellow powder 67 In August 1942 Harry Lambert an associate of Fleming s brother Robert was admitted to St Mary s Hospital due to a life threatening infection of the nervous system streptococcal meningitis 68 Fleming treated him with sulphonamides but Lambert s condition deteriorated He tested the antibiotic susceptibility and found that his penicillin could kill the bacteria He requested Florey for the isolated sample Florey sent the incompletely purified sample which Fleming immediately administered into Lambert s spinal canal Lambert showed signs of improvement the very next day 14 and completely recovered within a week 3 69 Fleming published the clinical case in The Lancet in 1943 70 Upon this medical breakthrough Allison informed the British Ministry of Health of the importance of penicillin and the need for mass production The War Cabinet was convinced of the usefulness upon which Sir Cecil Weir Director General of Equipment called for a meeting on the mode of action on 28 September 1942 71 72 The Penicillin Committee was created on 5 April 1943 The committee consisted of Weir as chairman Fleming Florey Sir Percival Hartley Allison and representatives from pharmaceutical companies as members The main goals were to produce penicillin rapidly in large quantities with collaboration of American companies and to supply the drug exclusively for Allied armed forces 14 By D Day in 1944 enough penicillin had been produced to treat all the wounded of the Allied troops 73 Antibiotic resistance nbsp Modern antibiotics are tested using a method similar to Fleming s discovery Fleming also discovered very early that bacteria developed antibiotic resistance whenever too little penicillin was used or when it was used for too short a period Almroth Wright had predicted antibiotic resistance even before it was noticed during experiments Fleming cautioned about the use of penicillin in his many speeches around the world On 26 June 1945 he made the following cautionary statements the microbes are educated to resist penicillin and a host of penicillin fast organisms is bred out In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin resistant organism I hope this evil can be averted 74 He cautioned not to use penicillin unless there was a properly diagnosed reason for it to be used and that if it were used never to use too little or for too short a period since these are the circumstances under which bacterial resistance to antibiotics develops 75 It had been experimentally shown in 1942 that S aureus could develop penicillin resistance under prolonged exposure 76 Elaborating the possibility of penicillin resistance in clinical conditions in his Nobel Lecture Fleming said The time may come when penicillin can be bought by anyone in the shops Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non lethal quantities of the drug make them resistant 23 It was around that time that the first clinical case of penicillin resistance was reported 77 Personal life nbsp Grave of Sir Alexander Fleming in the crypt of St Paul s Cathedral LondonOn 24 December 1915 Fleming married a trained nurse Sarah Marion McElroy of Killala County Mayo Ireland Their only child Robert Fleming 1924 2015 became a general medical practitioner After his first wife s death in 1949 Fleming married Amalia Koutsouri Vourekas a Greek colleague at St Mary s on 9 April 1953 she died in 1986 78 Fleming came from a Presbyterian background while his first wife Sarah was a lapsed Roman Catholic It is said that he was not particularly religious and their son Robert was later received into the Anglican church while still reportedly inheriting his two parents fairly irreligious disposition 79 When Fleming learned of Robert D Coghill and Andrew J Moyer patenting the method of penicillin production in the United States in 1944 80 he was furious and commented I found penicillin and have given it free for the benefit of humanity Why should it become a profit making monopoly of manufacturers in another country 14 From 1921 until his death in 1955 Fleming owned a country home named The Dhoon in Barton Mills Suffolk 4 81 DeathOn 11 March 1955 Fleming died at his home in London of a heart attack His ashes are buried in St Paul s Cathedral 2 Awards and legacy nbsp Display of Fleming s awards including his Nobel Prize Also shows a sample of penicillin and an example of an early apparatus for preparing it nbsp Sir Alexander Fleming centre receiving the Nobel prize from King Gustaf V of Sweden right in 1945 nbsp Faroe Islands postage stamp commemorating Fleming nbsp Barcelona to Sir Alexander Fleming 1956 by Catalan sculptor Josep Manuel Benedicto Barcelona jardins del Doctor Fleming Fleming s discovery of penicillin changed the world of modern medicine by introducing the age of useful antibiotics penicillin has saved and is still saving millions of people around the world 82 The laboratory at St Mary s Hospital where Fleming discovered penicillin is home to the Fleming Museum a popular London attraction His alma mater St Mary s Hospital Medical School merged with Imperial College London in 1988 The Sir Alexander Fleming Building on the South Kensington campus was opened in 1998 where his son Robert and his great granddaughter Claire were presented to the Queen it is now one of the main preclinical teaching sites of the Imperial College School of Medicine His other alma mater the Royal Polytechnic Institution now the University of Westminster has named one of its student halls of residence Alexander Fleming House which is near to Old Street Fleming Florey and Chain jointly received the Nobel Prize in Medicine in 1945 According to the rules of the Nobel committee a maximum of three people may share the prize Fleming s Nobel Prize medal was acquired by the National Museums of Scotland in 1989 and is on display after the museum re opened in 2011 83 Fleming was a member of the Pontifical Academy of Sciences 5 Fleming was elected a Fellow of the Royal Society FRS in 1943 1 Fleming was awarded the Hunterian Professorship by the Royal College of Surgeons of England Fleming was knighted as a Knight Bachelor by king George VI in 1944 84 85 Fleming was awarded the Medal for Merit by the President of the United States 11 Fleming was made a Grand Cross of the Legion of Honour by the French Republic 11 Fleming was made a Grand Cross of the Order of the Phoenix of Greece 11 He was made a Knight Grand Cross of the Order of Alfonso X the Wise Spain in 1948 86 In 1999 Time magazine named Fleming one of the 100 Most Important People of the 20th century stating It was a discovery that would change the course of history The active ingredient in that mould which Fleming named penicillin turned out to be an infection fighting agent of enormous potency When it was finally recognized for what it was the most efficacious life saving drug in the world penicillin would alter forever the treatment of bacterial infections By the middle of the century Fleming s discovery had spawned a huge pharmaceutical industry churning out synthetic penicillins that would conquer some of mankind s most ancient scourges including syphilis gangrene and tuberculosis 87 The importance of his work was recognized by the placement of an International Historic Chemical Landmark plaque at the Alexander Fleming Laboratory Museum in London on 19 November 1999 88 When 2000 was approaching at least three large Swedish magazines ranked penicillin as the most important discovery of the millennium In 2002 Fleming was named in the BBC s list of the 100 Greatest Britons following a nationwide vote 89 A statue of Alexander Fleming stands outside the main bullring in Madrid Plaza de Toros de Las Ventas 90 It was erected by subscription from grateful matadors as penicillin greatly reduced the number of deaths in the bullring 90 Flemingovo namesti is a square named after Fleming in the university area of the Dejvice community in Prague A secondary school is named after him in Sofia Bulgaria In Athens a small square in the downtown district of Votanikos is named after Fleming and bears his bust There are also a number of Streets in greater Athens and other towns in Greece named after either Fleming or his Greek second wife Amalia In mid 2009 Fleming was commemorated on a new series of banknotes issued by the Clydesdale Bank his image appears on the new issue of 5 notes 91 In 2009 Fleming was voted third greatest Scot in an opinion poll conducted by STV behind only Scotland s national poet Robert Burns and national hero William Wallace 92 91006 Fleming an asteroid in the Asteroid Belt is named after Fleming Fleming station on the Thessaloniki Metro system takes its name from Fleming Street on which it is located Sir Alexander Fleming College a British school in Trujillo northern PeruFleming and Howard Florey were jointly awarded the Cameron Prize for Therapeutics of the University of Edinburgh in 1945 Rue Alexander Fleming in the borough of Saint Laurent in Montreal is named in his honour The Fleming crater on the moon is named after Alexander Fleming and the Scottish astronomer Williamina Fleming Mount Fleming in New Zealand s Paparoa Range was named after him in 1970 by the Department of Scientific and Industrial Research 93 MythsThe Fleming myth By 1942 penicillin produced as pure compound was still in short supply and not available for clinical use When Fleming used the first few samples prepared by the Oxford team to treat Harry Lambert who had streptococcal meningitis 3 the successful treatment was a major news particularly popularised in The Times Wright was surprised to discover that Fleming and the Oxford team were not mentioned though Oxford was attributed as the source of the drug Wright wrote to the editor of The Times which eagerly interviewed Fleming but Florey prohibited the Oxford team from seeking media coverage As a consequence only Fleming was widely publicised in the media 94 which led to the misconception that he was entirely responsible for the discovery and development of the drug 95 Fleming himself referred to this incident as the Fleming myth 96 97 The Churchills The popular story 98 of Winston Churchill s father paying for Fleming s education after Fleming s father saved young Winston from death is false 95 According to the biography Penicillin Man Alexander Fleming and the Antibiotic Revolution by Kevin Brown Alexander Fleming in a letter 99 to his friend and colleague Andre Gratia 100 described this as A wondrous fable Nor did he save Winston Churchill himself during World War II Churchill was saved by Lord Moran using sulphonamides since he had no experience with penicillin when Churchill fell ill in Carthage in Tunisia in 1943 The Daily Telegraph and The Morning Post on 21 December 1943 wrote that he had been saved by penicillin He was saved by the new sulphonamide drug sulphapyridine known at the time under the research code M amp B 693 discovered and produced by May amp Baker Ltd Dagenham Essex a subsidiary of the French group Rhone Poulenc In a subsequent radio broadcast Churchill referred to the new drug as This admirable M amp B 101 It is highly probable that the correct information about the sulphonamide did not reach the newspapers because since the original sulphonamide antibacterial Prontosil had been a discovery by the German laboratory Bayer and as Britain was at war with Germany at the time it was thought better to raise British morale by associating Churchill s cure with a British discovery penicillin citation needed See alsoFleming Prize Lecture People on Scottish banknotesReferences a b c Colebrook L 1956 Alexander Fleming 1881 1955 Biographical Memoirs of Fellows of the Royal Society 2 117 126 doi 10 1098 rsbm 1956 0008 JSTOR 769479 S2CID 71887808 a b Sir Alexander Fleming Biography Nobel Foundation Retrieved 25 October 2011 a b c d e Bennett Joan W Chung King Thom 2001 Alexander Fleming and the discovery of penicillin Advances in Applied Microbiology Elsevier 49 163 184 doi 10 1016 s0065 2164 01 49013 7 ISBN 978 0 12 002649 4 PMID 11757350 Retrieved 17 October 2020 a b Ligon B Lee 2004 Sir Alexander Fleming Scottish researcher who discovered penicillin Seminars in Pediatric Infectious Diseases 15 1 58 64 doi 10 1053 j spid 2004 02 002 PMID 15175996 a b c Alexander Fleming Biography Les Prix Nobel The Nobel Foundation 1945 Archived from the original on 30 January 2011 Retrieved 27 March 2011 Hugh T B 2002 Howard Florey Alexander Fleming and the fairy tale of penicillin The Medical Journal of Australia 177 1 52 53 author 53 53 doi 10 5694 j 1326 5377 2002 tb04643 x PMID 12436980 S2CID 222048204 Cruickshank Robert 1955 Sir Alexander Fleming F R S Nature 175 4459 355 6 Bibcode 1955Natur 175 663C doi 10 1038 175663a0 PMC 1023893 PMID 13271592 McIntyre N 2007 Sir Alexander Fleming Journal of Medical Biography 15 4 234 doi 10 1258 j jmb 2007 05 72 PMID 18615899 S2CID 77187550 a b c d Mazumdar P M 1984 Fleming as Bacteriologist Alexander Fleming Science 225 4667 1140 1141 Bibcode 1984Sci 225 1140C doi 10 1126 science 225 4667 1140 PMID 17782415 Brown Kevin 2004 Penicillin man Alexander Fleming and the antibiotic revolution Stroud Sutton ISBN 978 0 7509 3152 6 Retrieved 11 September 2015 a b c d e Kelly s Handbook to the Titled Landed and Official Classes 1955 Kelly s p 802 a b Tan S Y Tatsumura Y July 2015 Alexander Fleming 1881 1955 Discoverer of penicillin Singapore Medical Journal 56 7 366 367 doi 10 11622 smedj 2015105 PMC 4520913 PMID 26243971 Fleming Alexander September 1917 The Physiological and Antiseptic Action of Flavine With Some Observations on the Testing of Antiseptics The Lancet 190 4905 341 345 doi 10 1016 S0140 6736 01 52126 1 a b c d e f g Allison V D 1974 Personal recollections of Sir Almroth Wright and Sir Alexander Fleming The Ulster Medical Journal 43 2 89 98 PMC 2385475 PMID 4612919 a b c Fleming A 1922 On a remarkable bacteriolytic element found in tissues and secretions Proceedings of the Royal Society B 93 653 306 317 Bibcode 1922RSPSB 93 306F doi 10 1098 rspb 1922 0023 a b c d Lalchhandama Kholhring 2020 Reappraising Fleming s snot and mould Science Vision 20 1 29 42 doi 10 33493 scivis 20 01 03 Fleming Alexander Allison V D 1922 Observations on a Bacteriolytic Substance Lysozyme Found in Secretions and Tissues British Journal of Experimental Pathology 3 5 252 260 PMC 2047739 Salton M R J 1957 The properties of lysozyme and its action on micororganisms Bacteriological Reviews 21 2 82 100 doi 10 1128 MMBR 21 2 82 100 1957 PMC 180888 PMID 13436356 Schleifer K H Kloos W E Moore A 1972 Taxonomic Status of Micrococcus luteus Schroeter 1872 Cohn 1872 Correlation Between Peptidoglycan Type and Genetic Compatibility International Journal of Systematic Bacteriology 22 4 224 227 doi 10 1099 00207713 22 4 224 Young Michael Artsatbanov Vladislav Beller Harry R Chandra Govind Chater Keith F Dover Lynn G Goh Ee Been Kahan Tamar Kaprelyants Arseny S Kyrpides Nikos Lapidus Alla 2010 Genome Sequence of the Fleming Strain of Micrococcus luteus a Simple Free Living Actinobacterium Journal of Bacteriology 192 3 841 860 doi 10 1128 JB 01254 09 PMC 2812450 PMID 19948807 Canada Environment and Climate Change 23 February 2018 Final Screening Assessment of Micrococcus luteus strain ATCC 4698 aem Retrieved 17 October 2020 Fleming Alexander 1932 Lysozyme Proceedings of the Royal Society of Medicine 26 2 71 84 doi 10 1177 003591573202600201 S2CID 209362460 a b Fleming A 1945 The Nobel Prize in Physiology or Medicine 1945 Penicillin Nobel Lecture NobelPrize org Retrieved 17 October 2020 Gallo Richard L 2013 The birth of innate immunity Experimental Dermatology 22 8 517 doi 10 1111 exd 12197 PMID 23879811 S2CID 23482849 Ragland Stephanie A Criss Alison K 2017 From bacterial killing to immune modulation Recent insights into the functions of lysozyme PLOS Pathogens 13 9 e1006512 doi 10 1371 journal ppat 1006512 PMC 5608400 PMID 28934357 Haven Kendall F 1994 Marvels of Science 50 Fascinating 5 Minute Reads Littleton Colo Libraries Unlimited p 182 ISBN 1 56308 159 8 Bigger Joseph W Boland C R O meara R A Q 1927 Variant colonies ofStaphylococcus aureus The Journal of Pathology and Bacteriology 30 2 261 269 doi 10 1002 path 1700300204 Brown K 2004 Penicillin Man Alexander Fleming and the Antibiotic Revolution 320 pp Sutton Publishing ISBN 0 7509 3152 3 Hare R The Birth of Penicillin Allen amp Unwin London 1970 Houbraken Jos Frisvad Jens C Samson Robert A 2011 Fleming s penicillin producing strain is not Penicillium chrysogenum but P rubens IMA Fungus 2 1 87 95 doi 10 5598 imafungus 2011 02 01 12 PMC 3317369 PMID 22679592 Hibbett David S Taylor John W 2013 Fungal systematics is a new age of enlightenment at hand Nature Reviews Microbiology 11 2 129 133 doi 10 1038 nrmicro2963 PMID 23288349 S2CID 17070407 a b c Hare R 1982 New light on the history of penicillin Medical History 26 1 1 24 doi 10 1017 s0025727300040758 PMC 1139110 PMID 7047933 Curry J 1981 Obituary C J La Touche Medical Mycology 19 2 164 doi 10 1080 00362178185380261 a b c Diggins FW 1999 The true history of the discovery of penicillin with refutation of the misinformation in the literature British Journal of Biomedical Science 56 2 83 93 PMID 10695047 Fleming Alexander 1929 On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B influenzae British Journal of Experimental Pathology 10 3 226 236 PMC 2041430 PMID 2048009 Reprinted as Fleming A 1979 On the antibacterial action of cultures of a Penicillium with special reference to their use in the isolation of B influenzae British Journal of Experimental Pathology 60 1 3 13 PMC 2041430 a b Wainwright Milton 1993 The Mystery of the Plate Fleming s Discovery and Contribution to the Early Development of Penicillin Journal of Medical Biography 1 1 59 65 doi 10 1177 096777209300100113 PMID 11639213 S2CID 7578843 International Congress of Microbiology British Medical Journal 2 3944 307 310 1936 doi 10 1136 bmj 2 3943 253 PMC 2457049 Dixon Bernard 1986 A Salute to the Pioneers of Microbiology Nature Biotechnology 4 8 681 doi 10 1038 nbt0886 681 S2CID 37941905 Annotations British Medical Journal 2 4208 310 2 August 1941 doi 10 1136 bmj 2 4208 310 PMC 2162429 PMID 20783842 Fleming A September 1941 Penicillin British Medical Journal 2 4210 386 doi 10 1136 bmj 2 4210 386 PMC 2162878 in October 1943 Abraham proposed a molecular structure which included a cyclic formation containing three carbon atoms and one nitrogen atom the b lactam ring not then known in natural products This structure was not immediately published due to the restrictions of wartime secrecy and was initially strongly disputed by Sir Robert Robinson among others but it was finally confirmed in 1945 by Dorothy Crowfoot Hodgkin using X ray analysis Oxford Dictionary of National Biography Abraham Sir Edward Penley Lowe Gordon 13 May 1999 Obituary Sir Edward Abraham The Independent London Archived from the original on 4 October 2013 Yanes Javier 6 August 2018 Fleming and the Difficult Beginnings of Penicillin Myth and Reality OpenMind Retrieved 7 June 2020 Moberg C 1991 Penicillin s forgotten man Norman Heatley Science 253 5021 734 735 Bibcode 1991Sci 253 734M doi 10 1126 science 1876832 PMID 1876832 Norman Heatley The Independent 23 January 2004 Archived from the original on 16 November 2020 Retrieved 7 June 2020 Henry Harris Howard Florey and the development of penicillin a lecture given on 29 September 1998 at the Florey Centenary 1898 1998 Sir William Dunn School of Pathology Oxford University sound recording 1 Conly J M Johnston B L 2005 Where are all the new antibiotics The new antibiotic paradox Canadian Journal of Infectious Diseases and Medical Microbiology 16 3 159 160 doi 10 1155 2005 892058 PMC 2095020 PMID 18159536 Wainwright M Swan H T 1987 The Sheffield penicillin story Mycologist 1 1 28 30 doi 10 1016 S0269 915X 87 80022 8 a b Wainwright Milton 1990 Besredka s antivirus in relation to Fleming s initial views on the nature of penicillin Medical History 34 1 79 85 doi 10 1017 S0025727300050286 PMC 1036002 PMID 2405221 Wainwright M 1987 The history of the therapeutic use of crude penicillin Medical History 31 1 41 50 doi 10 1017 s0025727300046305 PMC 1139683 PMID 3543562 Wainwright M Swan HT January 1986 C G Paine and the earliest surviving clinical records of penicillin therapy Medical History 30 1 42 56 doi 10 1017 S0025727300045026 PMC 1139580 PMID 3511336 a b Howie J 1986 Penicillin 1929 40 British Medical Journal Clinical Research Ed 293 6540 158 159 doi 10 1136 bmj 293 6540 158 PMC 1340901 PMID 3089435 Glover J 1986 The MRC and informed consent British Medical Journal 293 6540 157 158 doi 10 1136 bmj 293 6540 157 PMC 1340900 PMID 3089434 Heaman Elsbeth A 2003 St Mary s The History of a London Teaching Hospital Montreal Que McGill Queen s University Press p 212 ISBN 978 0 7735 7086 3 OCLC 144085272 Marko Vladimir 2020 Penicillin From Aspirin to Viagra Stories of the Drugs that Changed the World Springer pp 105 106 doi 10 1007 978 3 030 44286 6 5 ISBN 978 3 030 44286 6 OCLC 1164582807 S2CID 241636139 a b Rossiter Peter 2005 Keith Bernard Rogers BMJ 331 7516 579 doi 10 1136 bmj 331 7516 579 c PMC 1200632 Maurois Andre 1963 The Life of Sir Alexander Fleming Discoverer of Penicillin Penguin Books p 156 ISBN 1 199 30814 5 Aronson J K 1992 Penicillin European Journal of Clinical Pharmacology 42 1 1 9 doi 10 1007 BF00314911 PMID 1541305 S2CID 62877498 Kyle Robert A Steensma David P Shampo Marc A 2015 Howard Walter Florey Production of Penicillin Mayo Clinic Proceedings 90 6 e63 64 doi 10 1016 j mayocp 2014 12 028 PMID 26046419 Shama Gilbert 2017 Miracle near 34th street Wartime Penicillin Research at St John s University NY Endeavour 41 4 217 220 doi 10 1016 j endeavour 2017 09 003 PMID 29055651 Morin Robert B Gorman Marvin 2014 Penicillins and Cephalosporins Academic Press pp xxii ISBN 978 1 4832 7719 6 Ward John W Warren Christian 2006 Silent Victories The History and Practice of Public Health in Twentieth Century America Oxford University Press p 50 ISBN 978 0 19 974798 6 Kissick William L 1959 The Life of Sir Alexander Fleming Discoverer of Penicillin The Yale Journal of Biology and Medicine 32 2 140 PMC 2604061 Wainwright Milton 2002 Fleming s unfinished Perspectives in Biology and Medicine 45 4 529 538 doi 10 1353 pbm 2002 0065 PMID 12388885 S2CID 32684352 Fleming A 1942 In vitro Tests of Penicillin Potency The Lancet 239 6199 732 733 doi 10 1016 S0140 6736 00 70368 0 Bickel L Florey The Man Who Made Penicillin Sun Books Melbourne 1972 https trove nla gov au work 21266280 Abraham EP Chain E Holiday ER 1942 Purification and Some Physical and Chemical Properties of Penicillin British Journal of Experimental Pathology 23 3 103 119 PMC 2065494 Ligon B Lee 2004 Sir Alexander Fleming Scottish researcher who discovered penicillin Seminars in Pediatric Infectious Diseases 15 1 58 64 doi 10 1053 j spid 2004 02 002 PMID 15175996 Cairns H Lewin W S Duthie E S Smith Honor V 1944 Pneumococcal Meningitis Treated with Penicillin The Lancet 243 6299 655 659 doi 10 1016 S0140 6736 00 77085 1 Fleming Alexander 1943 Streptococcal Meningitis treated With Penicillin The Lancet 242 6267 434 438 doi 10 1016 S0140 6736 00 87452 8 Mathews John A 2008 The Birth of the Biotechnology Era Penicillin in Australia 1943 80 Prometheus 26 4 317 333 doi 10 1080 08109020802459306 S2CID 143123783 Baldry Peter 1976 The Battle Against Bacteria A Fresh Look CUP Archive p 115 ISBN 978 0 521 21268 7 Richards A N 1964 Production of penicillin in the United States 1941 1946 Nature 201 4918 441 445 Bibcode 1964Natur 201 441R doi 10 1038 201441a0 PMID 14164615 S2CID 4296757 Fishman Neil Infectious Diseases Society of America Pediatric Infectious Diseases Society April 2012 Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America SHEA the Infectious Diseases Society of America IDSA amp the Pediatric Infectious Diseases Society PIDS PDF Infection Control amp Hospital Epidemiology 33 4 322 327 doi 10 1086 665010 PMID 22418625 S2CID 24828623 Archived PDF from the original on 9 October 2022 Rosenblatt Farrell Noah 2009 The Landscape of Antibiotic Resistance Environmental Health Perspectives 117 6 244 150 doi 10 1289 ehp 117 a244 PMC 2702430 PMID 19590668 Rammelkamp Charles H Maxon Thelma 1942 Resistance of Staphylococcus aureus to the Action of Penicillin Proceedings of the Society for Experimental Biology and Medicine 51 3 386 389 doi 10 3181 00379727 51 13986 S2CID 87530495 Plough Harold H 1945 Penicillin Resistance of Staphylococcus Aureus and its Clinical Implications American Journal of Clinical Pathology 15 10 446 451 doi 10 1093 ajcp 15 10 446 PMID 21005048 Biographical Index of Former Fellows of the Royal Society of Edinburgh 1783 2002 PDF The Royal Society of Edinburgh July 2006 ISBN 0 902198 84 X Archived from the original PDF on 24 January 2013 Retrieved 9 May 2016 Penicillin Man Alexander Fleming and the Antibiotic Revolution The History Press September 2005 ISBN 0 7509 3153 1 US 2423873 Coghill Robert D amp Moyer Andrew J Method for production of increased yields of penicillin published 15 July 1947 BartonMills net local history Retrieved 17 October 2016 Roberts Michael Ingram Neil 2001 Biology 2 illustrated ed Nelson Thornes p 105 ISBN 0 7487 6238 8 Retrieved 4 March 2012 Penicillin is just one of a very large number of drugs which today are used by doctors to treat people with diseases 100 000 visitors in 6 days National Museums Scotland 3 August 2011 Archived from the original on 23 February 2012 Retrieved 4 March 2012 No 36544 The London Gazette Supplement 2 June 1944 p 2566 People of the century P 78 CBS News Simon amp Schuster 1999 Santesmases Maria Jesus 18 December 2017 The Circulation of Penicillin in Spain Health Wealth and Authority Springer p 39 ISBN 978 3 319 69718 5 Retrieved 7 July 2020 Alexander Fleming Time 100 People of the Century Time 29 March 1999 Archived from the original on 16 October 2007 Discovery and Development of Penicillin International Historic Chemical Landmarks American Chemical Society Retrieved 21 August 2018 BBC Great Britons Top 100 Internet Archive Archived from the original on 4 December 2002 Retrieved 19 July 2017 a b Edward Lewine 2007 Death and the Sun A Matador s Season in the Heart of Spain p 123 Houghton Mifflin Harcourt 2007 Banknote designs mark Homecoming BBC News 14 January 2008 Archived from the original on 25 January 2009 Retrieved 20 January 2009 Robert Burns voted Greatest Scot STV Group 30 November 2009 Archived from the original on 6 November 2018 Retrieved 7 February 2016 Place name detail Mount Fleming New Zealand Gazetteer New Zealand Geographic Board Retrieved 21 August 2022 Gaynes Robert 2017 The Discovery of Penicillin New Insights After More Than 75 Years of Clinical Use Emerging Infectious Diseases 23 5 849 853 doi 10 3201 eid2305 161556 PMC 5403050 a b Dufour Heloise D Carroll Sean B 2013 History Great myths die hard Nature 502 7469 32 33 doi 10 1038 502032a PMID 24137644 Ho David 29 March 1999 Bacteriologist Alexander Fleming Time ISSN 0040 781X Retrieved 17 October 2020 Selwyn Sydney 1980 Howard Florey the making of a great scientist Journal of Medical Microbiology 13 3 483 doi 10 1099 00222615 13 3 483 e g The Philadelphia Inquirer 17 July 1945 Brown Penicillin Man note 43 to Chapter 2 14 November 1945 British Library Additional Manuscripts 56115 Brown Penicillin Man note 44 to Chapter 2 see Wikipedia Discovery of penicillin article entry for 1920 A History of May amp Baker 1834 1984 Alden Press 1984 Further readingThe Life Of Sir Alexander Fleming Jonathan Cape 1959 Maurois Andre Nobel Lectures the Physiology or Medicine 1942 1962 Elsevier Publishing Company Amsterdam 1964 An Outline History of Medicine London Butterworths 1985 Rhodes Philip The Cambridge Illustrated History of Medicine Cambridge England Cambridge University Press 1996 Porter Roy ed Penicillin Man Alexander Fleming and the Antibiotic Revolution Stroud Sutton 2004 Brown Kevin Alexander Fleming The Man and the Myth Oxford University Press Oxford 1984 Macfarlane Gwyn Fleming Discoverer of Penicillin Ludovici Laurence J 1952 The Penicillin Man the Story of Sir Alexander Fleming Lutterworth Press 1957 Rowland John External links nbsp Wikiquote has quotations related to Alexander Fleming nbsp Wikimedia Commons has media related to Alexander Fleming Alexander Fleming Obituary Alexander Fleming on Nobelprize org nbsp including the Nobel Lecture 11 December 1945 Penicillin Some places and memories related to Alexander Fleming Newspaper clippings about Alexander Fleming in the 20th Century Press Archives of the ZBWAcademic officesPreceded byAlastair Sim Rector of the University of Edinburgh1951 1954 Succeeded bySydney Smith Retrieved from https en wikipedia org w index php title Alexander Fleming amp oldid 1195587091, wikipedia, wiki, book, books, library,

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