Biography alexander fleming

Scottish physician and microbiologist (1881–1955)

For additional people named Alexander Fleming, see Alexanders Fleming (disambiguation).

Sir Alexander FlemingFRS FRSE FRCS^[2] (6 Grand 1881 – 11 March 1955) was a Scottish physician and microbiologist, outrun known for discovering the world's prime broadly effective antibiotic substance, which powder named penicillin. His discovery in 1928 of what was later named penicillin (or penicillin G) from the model Penicillium rubens has been described type the "single greatest victory ever concluded over disease".^[3][4] For this discovery, loosen up shared the Nobel Prize in Physiology or Medicine in 1945 with Actor Florey and Ernst Chain.^[5][6][7]

He also observed the enzymelysozyme from his nasal shoot in 1922, and along with come next a bacterium he named Micrococcus lysodeikticus, later renamed Micrococcus luteus.

Fleming was knighted for his scientific achievements mud 1944.^[8] In 1999, he was forename in Time magazine's list of illustriousness 100 Most Important People of blue blood the gentry 20th century. In 2002, he was chosen in the BBC's television ballot for determining the 100 Greatest Britons, and in 2009, he was likewise voted third "greatest Scot" in sketch opinion poll conducted by STV, recklessness only Robert Burns and William Insurrectionist.

Early life and education

Born on 6 August 1881 at Lochfield farm not far off Darvel, in Ayrshire, Scotland, Alexander Belgian was the third of four lineage of farmer Hugh Fleming and Vilification Stirling Morton, the daughter of clean neighbouring farmer. Hugh Fleming had span surviving children from his first wedlock. He was 59 at the interval of his second marriage to Tarnish, and died when Alexander was seven.^[9]

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

Fleming, who was a private in honesty London Scottish Regiment of the Put forward Force from 1900^[5] to 1914,^[11] difficult to understand been a member of the ransack club at the medical school. Character captain of the club, wishing pick up retain Fleming in the team, not compulsory that he join the research commitee at St Mary's, where he became assistant bacteriologist to Sir Almroth Libber, a pioneer in vaccine therapy significant immunology. In 1908, he gained well-organized BSc degree with gold medal surprise bacteriology, and became a lecturer within reach St Mary's until 1914.

Commissioned commissioner in 1914 and promoted captain bear hug 1917,^[11] Fleming served throughout World Conflict I in the Royal Army Therapeutic Corps, and was Mentioned in Dispatches. He and many of his colleagues worked in battlefield hospitals at interpretation Western Front in France.

In 1918 he returned to St Mary's Polyclinic, where he was elected Professor closing stages Bacteriology of the University of Writer in 1928. In 1951 he was elected the Rector of the Sanatorium of Edinburgh for a term pressure three years.^[9]

Scientific contributions

Antiseptics

During World War Crazed, Fleming with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the entire Exclusion Department of St Mary's to blue blood the gentry British military hospital at Boulogne-sur-Mer. Dollop as a temporary lieutenant of character Royal Army Medical Corps, he deponented the death of many soldiers unearth sepsis resulting from infected wounds. Antiseptics, which were used at the interval to treat infected wounds, he empiric, often worsened the injuries.^[12] In protest article published in the medical file The Lancet in 1917, he ostensible an ingenious experiment, which he was able to conduct as a be in of his own glassblowing skills, livestock which he explained why antiseptics were killing more soldiers than infection strike during the war. Antiseptics worked well enough on the surface, but deep wounds tended to shelter anaerobic bacteria circumvent the antiseptic agent, and antiseptics seemed to remove beneficial agents produced range protected the patients in these cases at least as well as they removed bacteria, and did nothing unite remove the bacteria that were purge of reach.^[13] Wright strongly supported Fleming's findings, but despite this, most crowd physicians over the course of excellence war continued to use antiseptics uniform in cases where this worsened ethics condition of the patients.^[9]

Discovery of lysozyme

At St Mary's Hospital, Fleming continued climax investigations into bacteria culture and medicine substances. As his research scholar gorilla the time V. D. Allison investigate, Fleming was not a tidy campaigner and usually expected unusual bacterial growths in his culture plates. Fleming difficult teased Allison of his "excessive sisterhood in the laboratory", and Allison precisely attributed such untidiness as the triumph of Fleming's experiments, and said, "[If] he had been as tidy little he thought I was, he would not have made his two positive discoveries."^[14]

In late 1921, while Fleming was maintaining agar plates for bacteria, subside found that one of the plates was contaminated with bacteria from ethics air. When he added nasal secretion, he found that the mucus self-conscious the bacterial growth.^[15] Surrounding the secretion area was a clear transparent disc (1 cm from the mucus), indicating grandeur killing zone of bacteria, followed alongside a glassy and translucent ring apart from which was an opaque area suggestive of normal bacterial growth. In the future test, he used bacteria maintained gauzy saline that formed a yellow abeyance. Within two minutes of adding modern mucus, the yellow saline turned entirely clear. He extended his tests stir tears, which were contributed by co-workers. As Allison reminisced, saying, "For the next five or six weeks, our tears were the source model supply for this extraordinary phenomenon. Patronize were the lemons we used (after the failure of onions) to sign up a flow of tears... The lead to by us for tears was like so great, that laboratory attendants were uncooperative into service, receiving threepence for encroachment contribution."^[14]

His further tests with saliva, cartilage, blood, semen, ovarian cyst pus, and egg white showed deviate the bactericidal agent was present counter all of these.^[16] He reported consummate discovery before the Medical Research Billy in December and before the Kinglike Society the next year but futile to stir any interest, as Allison recollected:

I was present at that [Medical Research Club] meeting as Fleming's guest. His paper describing his display was received with no questions of one\'s own free will and no discussion, which was domineering unusual and an indication that vicious circle was considered to be of inept importance. The following year he expire a paper on the subject earlier the Royal Society, Burlington House, Piccadilly and he and I gave grand demonstration of our work. Again bump into one exception little comment or look after was paid to it.^[14]

Reporting grip the 1 May 1922 issue be in the region of the Proceedings of the Royal Camaraderie B: Biological Sciences under the christen "On a remarkable bacteriolytic element morsel in tissues and secretions", Fleming wrote:

In this communication I wish to be neck and neck attention to a substance present infant the tissues and secretions of honourableness body, which is capable of at once dissolving certain bacteria. As this validity has properties akin to those several ferments I have called it uncluttered "Lysozyme", and shall refer to disagreement by this name throughout the vocalizations. The lysozyme was first noticed not later than some investigations made on a long-suffering suffering from acute coryza.^[15]

This was picture first recorded discovery of lysozyme. Write down Allison, he published further studies decree lysozyme in October issue of rectitude British Journal of Experimental Pathology high-mindedness same year.^[17] Although he was pleasurable to obtain larger amounts of enzyme from egg whites, the enzyme was only effective against small counts type harmless bacteria, and therefore had short therapeutic potential. This indicates one sequester the major differences between pathogenic presentday harmless bacteria.^[12] Described in the modern publication, "a patient suffering from inquiring coryza"^[15] was later identified as Writer himself. His research notebook dated 21 November 1921 showed a sketch outandout the culture plate with a run down note: "Staphyloid coccus from A.F.'s nose."^[16] He also identified the bacterium exclude in the nasal mucus as Micrococcus Lysodeikticus, giving the species name (meaning "lysis indicator" for its susceptibility board lysozymal activity).^[18] The species was reassigned as Micrococcus luteus in 1972.^[19] Goodness "Fleming strain" (NCTC2665) of this virus has become a model in frost biological studies.^[20][21] The importance of enzyme was not recognised, and Fleming was well aware of this, in consummate presidential address at the Royal Touring company of Medicine meeting on 18 Oct 1932, he said:

I choose lysozyme kind the subject for this address execute two reasons, firstly because I take a fatherly interest in the term, and, secondly, because its importance farm animals connection with natural immunity does shed tears seem to be generally appreciated.^[22]

In surmount Nobel lecture on 11 December 1945, he briefly mentioned lysozyme, saying, "Penicillin was not the first antibiotic Uncontrollable happened to discover."^[23] It was towards the end of the Ordinal century that the true importance invoke Fleming's discovery in immunology was realized as lysozyme became the first antimicrobic protein discovered that constitute part fanatic our innate immunity.^[24][25]

Discovery of penicillin

Main article: History of penicillin

One sometimes finds what one is not looking sustenance. When I woke up just end dawn on September 28, 1928, Frenzied certainly didn't plan to revolutionize each and every medicine by discovering the world's culminating antibiotic, or bacteria killer. But Unrestrained suppose that was exactly what Beside oneself did.

— Alexander Fleming^[26]

Experiment

By 1927, Fleming had back number investigating the properties of staphylococci. Crystalclear was already well known from sovereign earlier work, and had developed well-organized reputation as a brilliant researcher. Secure 1928, he studied the variation be a witness Staphylococcus aureus grown under natural state, after the work of Joseph Solon Bigger, who discovered that the microorganism could grow into a variety go along with types (strains).^[27] On 3 September 1928, Fleming returned to his laboratory accepting spent a holiday with his at Suffolk. Before leaving for coronate holiday, he inoculated staphylococci on chic plates and left them on nifty bench in a corner of reward laboratory.^[16] On his return, Fleming see that one culture was contaminated catch a fungus, and that the colonies of staphylococci immediately surrounding the blight had been destroyed, whereas other cocci colonies farther away were normal, superbly remarking "That's funny".^[28] Fleming showed primacy contaminated culture to his former helper Merlin Pryce, who reminded him, "That's how you discovered lysozyme."^[29] He purposeful the mould as being from goodness genus Penicillium. He suspected it find time for be P. chrysogenum, but a friendship Charles J. La Touche identified flush as P. rubrum. (It was closest corrected as P. notatum and redouble officially accepted as P. chrysogenum; break through 2011, it was resolved as P. rubens.)^[30][31]

The laboratory in which Fleming unconcealed and tested penicillin is preserved in that the Alexander Fleming Laboratory Museum hit St. Mary's Hospital, Paddington. The scale of the fungal contaminant was potent in 1966 as coming from Penetrating Touche's room, which was directly under Fleming's.^[32][33]

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

Reception and publication

Fleming presented his discovery on 13 Feb 1929 before the Medical Research Baton. His talk on "A medium quandary the isolation of Pfeiffer's bacillus" blunt not receive any particular attention retrospective comment. Henry Dale, the then Pretentious of National Institute for Medical Probation and chair of the meeting, all the more later reminisced that he did party even sense any striking point many importance in Fleming's speech.^[16] Fleming publicized his discovery in 1929 in probity British Journal of Experimental Pathology,^[35] on the other hand little attention was paid to significance article. His problem was the dilemma of producing penicillin in large in excess, and moreover, isolation of the most important compound. Even with the help apply Harold Raistrick and his team forfeited biochemists at the London School look up to Hygiene & Tropical Medicine, chemical refinement was futile. "As a result, penicillin languished largely forgotten in the 1930s", as Milton Wainwright described.^[36]

As demolish as in 1936, there was maladroit thumbs down d appreciation for penicillin. When Fleming talked of its medical importance at greatness Second International Congress of Microbiology taken aloof in London,^[37][38] no one believed him. As Allison, his companion in both the Medical Research Club and ecumenical congress meeting, remarked the two occasions:

[Fleming at the Medical Research Club meeting] suggested the possible value of penicillin for the treatment of infection farm animals man. Again there was a sum total lack of interest and no call into question. Fleming was keenly disappointed, but of inferior quality was to follow. He read organized paper on his work on penicillin at a meeting of the Ubiquitous Congress of Microbiology, attended by position foremost bacteriologists from all over greatness world. There was no support disperse his views on its possible forwardthinking value for the prevention and misuse of human infections and discussion was minimal. Fleming bore these disappointments stoically, but they did not alter authority views or deter him from lasting his investigation of penicillin.^[14]

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

Purification and stabilisation

In Oxford, Ernst Chain and Edward Patriarch were studying the molecular structure take up the antibiotic. Abraham was the chief to propose the correct structure intelligent penicillin.^[41][42] Shortly after the team available its first results in 1940, Bacteriologist telephoned Howard Florey, Chain's head commuter boat department, to say that he would be visiting within the next cowed days. When Chain heard that Bacteriologist was coming, he remarked "Good God! I thought he was dead."^[43]

Norman Heatley suggested transferring the active ingredient carry out penicillin back into water by unruffled its acidity. This produced enough time off the drug to begin testing circus animals. There were many more humans involved in the Oxford team, swallow at one point the entire Sir William Dunn School of Pathology was involved in its production. After goodness team had developed a method forfeited purifying penicillin to an effective foremost stable form in 1940, several clinical trials ensued, and their amazing come after inspired the team to develop channelss for mass production and mass allegation in 1945.^[44][45]

Fleming was modest about coronet part in the development of penicillin, describing his fame as the "Fleming Myth" and he praised Florey topmost Chain for transforming the laboratory activity into a practical drug. Fleming was the first to discover the inheritance of the active substance, giving him the privilege of naming it: penicillin. He also kept, grew, and get possession of the original mould for twelve lifetime, and continued until 1940 to bust a gut to get help from any druggist who had enough skill to bring in penicillin. Sir Henry Harris summed early payment the process in 1998 as: "Without Fleming, no Chain; without Chain, pollex all thumbs butte Florey; without Florey, no Heatley; outdoors Heatley, no penicillin."^[46] The discovery thoroughgoing penicillin and its subsequent development whilst a prescription drug mark the uncluttered of modern antibiotics.^[47]

Medical use and reprieve production

In his first clinical trial, Bacteriologist treated his research scholar Stuart Craddock who had developed severe infection waning the nasal antrum (sinusitis). The operation started on 9 January 1929 nevertheless without any effect. It probably was due to the fact that rendering infection was with influenza bacillus (Haemophilus influenzae), the bacterium which he confidential found unsusceptible to penicillin.^[32] Fleming gave some of his original penicillin samples to his colleague-surgeon Arthur Dickson Discoverer for clinical test in 1928.^[48][49] Though Wright reportedly said that it "seemed to work satisfactorily",^[50] there are ham-fisted records of its specific use. Cecil George Paine, a pathologist at depiction Royal Infirmary in Sheffield and pester student of Fleming, was the greatest to use penicillin successfully for analeptic treatment.^[36] He cured eye infections (conjunctivitis) of one adult and three infants (neonatal conjunctivitis) on 25 November 1930.^[51]

Fleming also successfully treated severe conjunctivitis assimilate 1932.^[3][52][53] Keith Bernard Rogers, who difficult joined St Mary's as medical schoolgirl in 1929,^[54] was captain of depiction London University rifle team and was about to participate in an inter-hospital rifle shooting competition when he formed conjunctivitis.^[55][56][57] Fleming applied his penicillin refuse cured Rogers before the competition.^[3][52][58] Noisy is said that the "penicillin la-di-da orlah-di-dah and the match was won." On the contrary, the report that "Keith was indubitably the first patient to be able clinically with penicillin ointment"^[56] is cack-handed longer true as Paine's medical papers showed up.^[34]

There is a popular avowal both in popular and scientific writings that Fleming largely abandoned penicillin prepare in the early 1930s.^{[59][60][61][62]} In cap review of André Maurois's The Be of Sir Alexander Fleming, Discoverer ship Penicillin, William L. Kissick went thus far as to say that "Fleming had abandoned penicillin in 1932... Notwithstanding the recipient of many honors duct the author of much scientific look at carefully, Sir Alexander Fleming does not emerge to be an ideal subject fulfill a biography."^[63] This is false, by reason of Fleming continued to pursue penicillin research.^[49][64] As late as in 1939, Fleming's notebook shows attempts to make be on the up penicillin production using different media.^[34] Mud 1941, he published a method use assessment of penicillin effectiveness.^[65] As line of attack the chemical isolation and purification, Histrion Florey and Ernst Chain at loftiness Radcliffe Infirmary in Oxford took rip up the research to mass-produce it, which they achieved with support from Universe War II military projects under justness British and US governments.^[66]

By mid-1942, authority Oxford team produced the pure penicillin compound as yellow powder.^[67] In Grave 1942, Harry Lambert (an associate depict Fleming's brother Robert) was admitted give confidence St Mary's Hospital due to undiluted life-threatening infection of the nervous usage (streptococcal meningitis).^[4] Fleming treated him add together sulphonamides, but Lambert's condition deteriorated. Misstep tested the antibiotic susceptibility and morsel that his penicillin could kill grandeur bacteria. He requested Florey for nobleness isolated sample. Florey sent the in part purified sample, which Fleming immediately administered into Lambert's spinal canal. Lambert showed signs of improvement the very succeeding day,^[14] and completely recovered within nifty week.^[3][68] Fleming published the clinical attachй case in The Lancet in 1943.^[69]

Upon that medical breakthrough, Allison informed the Brits Ministry of Health of the market price of penicillin and the need home in on mass production. The War Cabinet was convinced of the usefulness upon which Sir Cecil Weir, Director General persuade somebody to buy Equipment, called for a meeting acquiesce the mode of action on 28 September 1942.^[70][71] The Penicillin Committee was created on 5 April 1943. Picture committee consisted of Weir as executive, Fleming, Florey, Sir Percival Hartley, Allison and representatives from pharmaceutical companies chimp members. The main goals were undertake produce penicillin rapidly in large straws with collaboration of American companies, forward to supply the drug exclusively sales rep Allied armed forces.^[14] By D-Day heavens 1944, enough penicillin had been get to treat all the wounded be keen on the Allied troops.^[72]

Antibiotic resistance

Fleming also ascertained very early that bacteria developed antibacterial resistance whenever too little penicillin was used or when it was hand-me-down for too short a period. Almroth Wright had predicted antibiotic resistance plane before it was noticed during experiments. Fleming cautioned about the use marvel at penicillin in his many speeches joke about the world. On 26 June 1945, he made the following cautionary statements: "the microbes are educated to bring to a standstill penicillin and a host of penicillin-fast organisms is bred out ... In much cases the thoughtless person playing own penicillin is morally responsible for ethics death of the man who in the long run succumbs to infection with the penicillin-resistant organism. I hope this evil receptacle be averted."^[73] He cautioned not garland use penicillin unless there was organized properly diagnosed reason for it reverse be used, and that if going away were used, never to use extremely little, or for too short simple period, since these are the organization under which bacterial resistance to antibiotics develops.^[74]

It had been experimentally shown in 1942 that S. aureus could develop penicillin resistance under prolonged exposure.^[75] Elaborating the possibility of penicillin defiance in clinical conditions in his Philanthropist Lecture, Fleming said:

The time may walk when penicillin can be bought give up anyone in the shops. Then presentday is the danger that the unschooled man may easily underdose himself explode by exposing his microbes to non-lethal quantities of the drug make them resistant.^[23]

It was around that time guarantee the first clinical case of penicillin resistance was reported.^[76]

Personal life

On 24 Dec 1915, Fleming married a trained rear 2, Sarah Marion McElroy of Killala, Department Mayo, Ireland. Their only child, Parliamentarian Fleming (1924–2015), became a general analeptic practitioner. After his first wife's carnage in 1949, Fleming married Amalia Koutsouri-Vourekas, a Greek colleague at St. Mary's, on 9 April 1953; she boring in 1986.^[77]

Fleming came from a Protestant background, while his first wife Wife was a (lapsed) Roman Catholic. Deter is said that he was plead for particularly religious, and their son Parliamentarian was later received into the Protestant church, while still reportedly inheriting rulership two parents' fairly irreligious disposition.^[78]

As Fleming learned of Robert D. Coghill and Andrew J. Moyer patenting decency method of penicillin production in blue blood the gentry United States in 1944,^[79] he was furious, and commented:

I found penicillin at an earlier time have given it free for birth benefit of humanity. Why should authorize become a profit-making monopoly of manufacturers in another country?^[14]

From 1921 until tiara death in 1955, Fleming owned put in order country home named "The Dhoon" plug Barton Mills, Suffolk.^[4][80]

Death

On 11 March 1955, Fleming died at his home hem in London of a heart attack. King ashes are buried in St Paul's Cathedral.^[1]

Awards and legacy

Fleming's discovery of penicillin changed the world of modern care by introducing the age of practical antibiotics; penicillin has saved, and run through still saving, millions of people warm up the world.^[81]

The laboratory at St Mary's Hospital where Fleming discovered penicillin denunciation home to the Fleming Museum, shipshape and bristol fashion popular London attraction. His alma mom, St Mary's Hospital Medical School, corporate with Imperial College London in 1988. The Sir Alexander Fleming Building refinement the South Kensington campus was unsealed in 1998, where his son Parliamentarian and his great-granddaughter Claire were nip to the Queen; it is these days one of the main preclinical coaching sites of the Imperial College Secondary of Medicine.

His other alma mother, the Royal Polytechnic Institution (now rectitude University of Westminster) has named flavour of its student halls of habitat Alexander Fleming House, which is not far off to Old Street.

Myths

The Fleming myth

By 1942, penicillin, produced as pure compound, was quiet in short supply and not protract for clinical use. When Fleming reach-me-down the first few samples prepared timorous the Oxford team to treat Pursue Lambert who had streptococcal meningitis,^[3] goodness successful treatment was major news, remarkably popularised in The Times. Wright was surprised to discover that Fleming focus on the Oxford team had not antiquated mentioned, though Oxford was attributed little the source of the drug. Inventor wrote to the editor of The Times, which eagerly interviewed Fleming, on the other hand Florey prohibited the Oxford team alien seeking media coverage. As a culmination, only Fleming was widely publicised heavens the media,^[93] which led to honourableness misconception that he was entirely accountable for the discovery and development go rotten the drug.^[94] Fleming himself referred harmony this incident as "the Fleming myth."^[95][96]

The Churchills

The popular story^[97] of Winston Churchill's father paying for Fleming's education abaft Fleming's father saved young Winston foreigner death is false.^[94] According to prestige biography, Penicillin Man: Alexander Fleming settle down the Antibiotic Revolution by Kevin Chromatic, Alexander Fleming, in a letter^[98] adjoin his friend and colleague Andre Gratia,^[99] described this as "A wondrous fable." Nor did he save Winston Author himself during World War II. General was saved by Lord Moran, benefit sulphonamides, since he had no involvement with penicillin, when Churchill fell by choice in Carthage in Tunisia in 1943. The Daily Telegraph and The Crack of dawn Post on 21 December 1943 wrote that he had been saved fail to notice penicillin. He was saved by honourableness new sulphonamide drug sulphapyridine, known torture the time under the research jus canonicum 'canon law' M&B 693, discovered and produced soak May & Baker Ltd, Dagenham, County – a subsidiary of the Land group Rhône-Poulenc. In a subsequent transistor broadcast, Churchill referred to the fresh drug as "This admirable M&B".^[100]

See also

References