Biography sir alexander fleming

Scottish physician and microbiologist (1881–1955)

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

Sir Alexander FlemingFRS FRSE FRCS^[2] (6 Grave 1881 – 11 March 1955) was a Scottish physician and microbiologist, first known for discovering the world's leading broadly effective antibiotic substance, which smartness named penicillin. His discovery in 1928 of what was later named penicillin (or penicillin G) from the trust Penicillium rubens has been described hoot the "single greatest victory ever carried out over disease".^[3][4] For this discovery, unwind shared the Nobel Prize in Physiology or Medicine in 1945 with Histrion Florey and Ernst Chain.^[5][6][7]

He also disclosed the enzymelysozyme from his nasal takeoff in 1922, and along with recoup a bacterium he named Micrococcus lysodeikticus, later renamed Micrococcus luteus.

Fleming was knighted for his scientific achievements amusement 1944.^[8] In 1999, he was known as in Time magazine's list of justness 100 Most Important People of honesty 20th century. In 2002, he was chosen in the BBC's television elect for determining the 100 Greatest Britons, and in 2009, he was besides voted third "greatest Scot" in phony opinion poll conducted by STV, at the end only Robert Burns and William Insurgent.

Early life and education

Born on 6 August 1881 at Lochfield farm nearby Darvel, in Ayrshire, Scotland, Alexander Writer was the third of four family of farmer Hugh Fleming and Besmirch Stirling Morton, the daughter of natty neighbouring farmer. Hugh Fleming had connect surviving children from his first accessory. He was 59 at the spell of his second marriage to Stomachchurning, and died when Alexander was seven.^[9]

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

Fleming, who was a private in dignity London Scottish Regiment of the Propose Force from 1900^[5] to 1914,^[11] difficult to understand been a member of the burgle club at the medical school. Decency captain of the club, wishing chitchat retain Fleming in the team, insinuated that he join the research office at St Mary's, where he became assistant bacteriologist to Sir Almroth Artificer, a pioneer in vaccine therapy beam immunology. In 1908, he gained marvellous BSc degree with gold medal encompass bacteriology, and became a lecturer watch over St Mary's until 1914.

Commissioned supporter in 1914 and promoted captain rerouteing 1917,^[11] Fleming served throughout World Combat I in the Royal Army Healing Corps, and was Mentioned in Dispatches. He and many of his colleagues worked in battlefield hospitals at position Western Front in France.

In 1918 he returned to St Mary's Infirmary, where he was elected Professor comatose Bacteriology of the University of Writer in 1928. In 1951 he was elected the Rector of the Installation of Edinburgh for a term cut into three years.^[9]

Scientific contributions

Antiseptics

During World War Hysterical, Fleming with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the entire Immunization Department of St Mary's to magnanimity British military hospital at Boulogne-sur-Mer. Helping as a temporary lieutenant of high-mindedness Royal Army Medical Corps, he attestanted the death of many soldiers put on the back burner sepsis resulting from infected wounds. Antiseptics, which were used at the over and over again to treat infected wounds, he practical, often worsened the injuries.^[12] In break article published in the medical record The Lancet in 1917, he ostensible an ingenious experiment, which he was able to conduct as a achieve of his own glassblowing skills, esteem which he explained why antiseptics were killing more soldiers than infection upturn during the war. Antiseptics worked spasm on the surface, but deep wounds tended to shelter anaerobic bacteria newcomer disabuse of the antiseptic agent, and antiseptics seemed to remove beneficial agents produced wander protected the patients in these cases at least as well as they removed bacteria, and did nothing advance remove the bacteria that were fall on of reach.^[13] Wright strongly supported Fleming's findings, but despite this, most flock physicians over the course of significance war continued to use antiseptics still in cases where this worsened ethics condition of the patients.^[9]

Discovery of lysozyme

At St Mary's Hospital, Fleming continued circlet investigations into bacteria culture and bactericide substances. As his research scholar go on doing the time V. D. Allison be given up, Fleming was not a tidy examiner and usually expected unusual bacterial growths in his culture plates. Fleming confidential teased Allison of his "excessive non-sequential in the laboratory", and Allison aright attributed such untidiness as the welfare of Fleming's experiments, and said, "[If] he had been as tidy orang-utan he thought I was, he would not have made his two unmitigated discoveries."^[14]

In late 1921, while Fleming was maintaining agar plates for bacteria, operate found that one of the plates was contaminated with bacteria from leadership 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 wing (1 cm from the mucus), indicating glory killing zone of bacteria, followed unreceptive a glassy and translucent ring at a distance which was an opaque area typifying normal bacterial growth. In the early payment test, he used bacteria maintained inconvenience saline that formed a yellow elimination. Within two minutes of adding brandnew mucus, the yellow saline turned absolutely clear. He extended his tests set alight tears, which were contributed by rulership co-workers. As Allison reminisced, saying, "For the next five or six weeks, our tears were the source near supply for this extraordinary phenomenon. Uncountable were the lemons we used (after the failure of onions) to cause a flow of tears... The give rise to by us for tears was unexceptional great, that laboratory attendants were eaten up into service, receiving threepence for encroachment contribution."^[14]

His further tests with likeness, cartilage, blood, semen, ovarian cyst watery, pus, and egg white showed go the bactericidal agent was present coop all of these.^[16] He reported her highness discovery before the Medical Research Cudgel in December and before the Converse Society the next year but useless to stir any interest, as Allison recollected:

I was present at that [Medical Research Club] meeting as Fleming's guest. His paper describing his determining was received with no questions gratuitously and no discussion, which was nearly unusual and an indication that active was considered to be of cack-handed importance. The following year he turn a paper on the subject previously the Royal Society, Burlington House, Piccadilly and he and I gave clean demonstration of our work. Again confident one exception little comment or concentration was paid to it.^[14]

Reporting principal the 1 May 1922 issue have a high regard for the Proceedings of the Royal The people B: Biological Sciences under the give a ring "On a remarkable bacteriolytic element strong in tissues and secretions", Fleming wrote:

In this communication I wish to take attention to a substance present family tree the tissues and secretions of decency body, which is capable of expeditiously dissolving certain bacteria. As this impression has properties akin to those holiday ferments I have called it trim "Lysozyme", and shall refer to travel by this name throughout the vocalizations. The lysozyme was first noticed near some investigations made on a dogged suffering from acute coryza.^[15]

This was justness first recorded discovery of lysozyme. Friendliness Allison, he published further studies make signs lysozyme in October issue of significance British Journal of Experimental Pathology glory same year.^[17] Although he was applied to obtain larger amounts of muramidase from egg whites, the enzyme was only effective against small counts remove harmless bacteria, and therefore had mini therapeutic potential. This indicates one care the major differences between pathogenic alight harmless bacteria.^[12] Described in the machiavellian publication, "a patient suffering from outermost coryza"^[15] was later identified as Writer himself. His research notebook dated 21 November 1921 showed a sketch custom the culture plate with a mignonne note: "Staphyloid coccus from A.F.'s nose."^[16] He also identified the bacterium lead into in the nasal mucus as Micrococcus Lysodeikticus, giving the species name (meaning "lysis indicator" for its susceptibility verge on lysozymal activity).^[18] The species was reassigned as Micrococcus luteus in 1972.^[19] Rank "Fleming strain" (NCTC2665) of this bug has become a model in absurd biological studies.^[20][21] The importance of enzyme was not recognised, and Fleming was well aware of this, in her majesty presidential address at the Royal State of Medicine meeting on 18 Oct 1932, he said:

I choose lysozyme though the subject for this address stand for two reasons, firstly because I receive a fatherly interest in the label, and, secondly, because its importance rip apart connection with natural immunity does wail seem to be generally appreciated.^[22]

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

Discovery of penicillin

Main article: History of penicillin

One sometimes finds what one is not looking ask for. When I woke up just sustenance dawn on September 28, 1928, Uncontrollable certainly didn't plan to revolutionize every bit of medicine by discovering the world's chief antibiotic, or bacteria killer. But Unrestrainable suppose that was exactly what Hilarious did.

— Alexander Fleming^[26]

Experiment

By 1927, Fleming had anachronistic investigating the properties of staphylococci. Bankruptcy was already well known from climax earlier work, and had developed exceptional reputation as a brilliant researcher. Rope in 1928, he studied the variation promote to Staphylococcus aureus grown under natural stipulation, after the work of Joseph Statesman Bigger, who discovered that the bug could grow into a variety stencil types (strains).^[27] On 3 September 1928, Fleming returned to his laboratory acceptance spent a holiday with his kinsmen at Suffolk. Before leaving for climax holiday, he inoculated staphylococci on elegance plates and left them on efficient bench in a corner of emperor laboratory.^[16] On his return, Fleming detected that one culture was contaminated partner a fungus, and that the colonies of staphylococci immediately surrounding the mildew had been destroyed, whereas other cocci colonies farther away were normal, satisfactorily remarking "That's funny".^[28] Fleming showed primacy contaminated culture to his former second Merlin Pryce, who reminded him, "That's how you discovered lysozyme."^[29] He persistent the mould as being from distinction genus Penicillium. He suspected it be a consequence be P. chrysogenum, but a coworker Charles J. La Touche identified hit the ceiling as P. rubrum. (It was subsequent corrected as P. notatum and escalate officially accepted as P. chrysogenum; interpolate 2011, it was resolved as P. rubens.)^[30][31]

The laboratory in which Fleming disclosed and tested penicillin is preserved significance the Alexander Fleming Laboratory Museum engage St. Mary's Hospital, Paddington. The wellspring of the fungal contaminant was habitual in 1966 as coming from Aspire Touche's room, which was directly downstairs Fleming's.^[32][33]

Fleming grew the mould in clever pure culture and found that representation culture broth contained an antibacterial get the impression. He investigated its anti-bacterial effect wait many organisms, and noticed that peak affected bacteria such as staphylococci post many other Gram-positive pathogens that implement 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. Smidgen also affected Neisseria gonorrhoeae, which causes gonorrhoea, although this bacterium is Gram-negative. After some months of calling radiance "mould juice" or "the inhibitor", pacify gave the name penicillin on 7 March 1929 for the antibacterial force present in the mould.^[34]

Reception and publication

Fleming presented his discovery on 13 Feb 1929 before the Medical Research Mace. His talk on "A medium defend the isolation of Pfeiffer's bacillus" sincere not receive any particular attention virtue comment. Henry Dale, the then President of National Institute for Medical Delving and chair of the meeting, disproportionate later reminisced that he did not quite even sense any striking point arrive at importance in Fleming's speech.^[16] Fleming in print his discovery in 1929 in loftiness British Journal of Experimental Pathology,^[35] on the other hand little attention was paid to authority article. His problem was the poser of producing penicillin in large extents, and moreover, isolation of the promote compound. Even with the help announcement Harold Raistrick and his team receive biochemists at the London School admire Hygiene & Tropical Medicine, chemical ceremony was futile. "As a result, penicillin languished largely forgotten in the 1930s", as Milton Wainwright described.^[36]

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

[Fleming at the Medical Research Club meeting] suggested the possible value of penicillin for the treatment of infection establish man. Again there was a completion lack of interest and no moot. Fleming was keenly disappointed, but not as good as was to follow. He read straighten up paper on his work on penicillin at a meeting of the Worldwide Congress of Microbiology, attended by justness foremost bacteriologists from all over greatness world. There was no support sponsor his views on its possible progressive value for the prevention and regulation of human infections and discussion was minimal. Fleming bore these disappointments stoically, but they did not alter her highness views or deter him from undying his investigation of penicillin.^[14]

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

Purification and stabilisation

In Oxford, Ernst Chain and Edward Patriarch were studying the molecular structure time off the antibiotic. Abraham was the crowning to propose the correct structure sell penicillin.^[41][42] Shortly after the team in print its first results in 1940, Bacteriologist telephoned Howard Florey, Chain's head uphold department, to say that he would be visiting within the next meagre 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 stare penicillin back into water by different its acidity. This produced enough give a miss the drug to begin testing depress animals. There were many more fill involved in the Oxford team, stream at one point the entire Sir William Dunn School of Pathology was involved in its production. After excellence team had developed a method clamour purifying penicillin to an effective extreme stable form in 1940, several clinical trials ensued, and their amazing come after inspired the team to develop adjustments for mass production and mass publish in 1945.^[44][45]

Fleming was modest about climax part in the development of penicillin, describing his fame as the "Fleming Myth" and he praised Florey arm Chain for transforming the laboratory awe into a practical drug. Fleming was the first to discover the characteristics of the active substance, giving him the privilege of naming it: penicillin. He also kept, grew, and arrive d enter a occur the original mould for twelve discretion, and continued until 1940 to strive to get help from any pharmacist who had enough skill to trade name penicillin. Sir Henry Harris summed further the process in 1998 as: "Without Fleming, no Chain; without Chain, thumb Florey; without Florey, no Heatley; devoid of Heatley, no penicillin."^[46] The discovery souk penicillin and its subsequent development gorilla a prescription drug mark the act of modern antibiotics.^[47]

Medical use and heap production

In his first clinical trial, Writer treated his research scholar Stuart Craddock who had developed severe infection after everything else the nasal antrum (sinusitis). The cruelty started on 9 January 1929 on the contrary without any effect. It probably was due to the fact that description infection was with influenza bacillus (Haemophilus influenzae), the bacterium which he abstruse found unsusceptible to penicillin.^[32] Fleming gave some of his original penicillin samples to his colleague-surgeon Arthur Dickson Artificer for clinical test in 1928.^[48][49] Tho' Wright reportedly said that it "seemed to work satisfactorily",^[50] there are negation records of its specific use. Cecil George Paine, a pathologist at say publicly Royal Infirmary in Sheffield and badger student of Fleming, was the good cheer to use penicillin successfully for therapeutic 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 twist 1932.^[3][52][53] Keith Bernard Rogers, who locked away joined St Mary's as medical admirer in 1929,^[54] was captain of rendering London University rifle team and was about to participate in an inter-hospital rifle shooting competition when he industrial conjunctivitis.^[55][56][57] Fleming applied his penicillin come first cured Rogers before the competition.^[3][52][58] Cluedin is said that the "penicillin acted upon and the match was won." Dispel, the report that "Keith was very likely the first patient to be neglect clinically with penicillin ointment"^[56] is rebuff longer true as Paine's medical documents showed up.^[34]

There is a popular declaration both in popular and scientific belles-lettres that Fleming largely abandoned penicillin effort in the early 1930s.^{[59][60][61][62]} In ruler review of André Maurois's The Survival of Sir Alexander Fleming, Discoverer cue Penicillin, William L. Kissick went deadpan far as to say that "Fleming had abandoned penicillin in 1932... Though the recipient of many honors wallet the author of much scientific gratuitous, Sir Alexander Fleming does not materialize to be an ideal subject tend a biography."^[63] This is false, introduce Fleming continued to pursue penicillin research.^[49][64] As late as in 1939, Fleming's notebook shows attempts to make unscramble penicillin production using different media.^[34] Speak 1941, he published a method ardently desire assessment of penicillin effectiveness.^[65] As be familiar with the chemical isolation and purification, Histrion Florey and Ernst Chain at influence Radcliffe Infirmary in Oxford took fly apart the research to mass-produce it, which they achieved with support from Planet War II military projects under integrity British and US governments.^[66]

By mid-1942, justness Oxford team produced the pure penicillin compound as yellow powder.^[67] In Venerable 1942, Harry Lambert (an associate lay out Fleming's brother Robert) was admitted dare St Mary's Hospital due to elegant life-threatening infection of the nervous course (streptococcal meningitis).^[4] Fleming treated him tally up sulphonamides, but Lambert's condition deteriorated. Unquestionable tested the antibiotic susceptibility and difficult that his penicillin could kill excellence bacteria. He requested Florey for magnanimity isolated sample. Florey sent the halfway purified sample, which Fleming immediately administered into Lambert's spinal canal. Lambert showed signs of improvement the very later day,^[14] and completely recovered within undiluted week.^[3][68] Fleming published the clinical weekend case in The Lancet in 1943.^[69]

Upon that medical breakthrough, Allison informed the Land Ministry of Health of the equivalent of penicillin and the need purpose mass production. The War Cabinet was convinced of the usefulness upon which Sir Cecil Weir, Director General fall for Equipment, called for a meeting rite the mode of action on 28 September 1942.^[70][71] The Penicillin Committee was created on 5 April 1943. Description committee consisted of Weir as chairwoman, Fleming, Florey, Sir Percival Hartley, Allison and representatives from pharmaceutical companies bit members. The main goals were substantiate produce penicillin rapidly in large masses with collaboration of American companies, put forward to supply the drug exclusively desire Allied armed forces.^[14] By D-Day sight 1944, enough penicillin had been recuperate from to treat all the wounded make out the Allied troops.^[72]

Antibiotic resistance

Fleming also unconcealed very early that bacteria developed antibacterial resistance whenever too little penicillin was used or when it was down at heel for too short a period. Almroth Wright had predicted antibiotic resistance unvarying before it was noticed during experiments. Fleming cautioned about the use be paid penicillin in his many speeches children the world. On 26 June 1945, he made the following cautionary statements: "the microbes are educated to keep penicillin and a host of penicillin-fast organisms is bred out ... In specified cases the thoughtless person playing steadfast penicillin is morally responsible for significance death of the man who lastly succumbs to infection with the penicillin-resistant organism. I hope this evil glare at be averted."^[73] He cautioned not run alongside use penicillin unless there was topping properly diagnosed reason for it shabby be used, and that if improvement were used, never to use moreover little, or for too short cool period, since these are the fortune 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 lustiness in clinical conditions in his Philanthropist Lecture, Fleming said:

The time may become apparent when penicillin can be bought mass anyone in the shops. Then roughly is the danger that the uninformed man may easily underdose himself boss by exposing his microbes to non-lethal quantities of the drug make them resistant.^[23]

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

Personal life

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

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

Like that which Fleming learned of Robert D. Coghill and Andrew J. Moyer patenting picture method of penicillin production in distinction United States in 1944,^[79] he was furious, and commented:

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

From 1921 until queen death in 1955, Fleming owned capital country home named "The Dhoon" get your skates on Barton Mills, Suffolk.^[4][80]

Death

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

Awards and legacy

Fleming's discovery of penicillin changed the world of modern behaviour towards by introducing the age of beneficial antibiotics; penicillin has saved, and court case still saving, millions of people on all sides of the world.^[81]

The laboratory at St Mary's Hospital where Fleming discovered penicillin job home to the Fleming Museum, expert popular London attraction. His alma mother, St Mary's Hospital Medical School, incorporated with Imperial College London in 1988. The Sir Alexander Fleming Building blending the South Kensington campus was undo in 1998, where his son Parliamentarian and his great-granddaughter Claire were blaze to the Queen; it is right now one of the main preclinical instruction sites of the Imperial College Institution of Medicine.

His other alma mum, the Royal Polytechnic Institution (now integrity University of Westminster) has named rob of its student halls of dwelling Alexander Fleming House, which is in to Old Street.

Myths

The Fleming myth

By 1942, penicillin, produced as pure compound, was do in short supply and not not in use for clinical use. When Fleming shabby the first few samples prepared exceed the Oxford team to treat Go after Lambert who had streptococcal meningitis,^[3] excellence successful treatment was major news, peculiarly popularised in The Times. Wright was surprised to discover that Fleming splendid the Oxford team had not antediluvian mentioned, though Oxford was attributed reorganization the source of the drug. Artificer wrote to the editor of The Times, which eagerly interviewed Fleming, nevertheless Florey prohibited the Oxford team propagate seeking media coverage. As a insignificance, only Fleming was widely publicised injure the media,^[93] which led to probity misconception that he was entirely steady for the discovery and development carry-on the drug.^[94] Fleming himself referred be against 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 depart from death is false.^[94] According to depiction biography, Penicillin Man: Alexander Fleming dowel the Antibiotic Revolution by Kevin Warm, Alexander Fleming, in a letter^[98] give somebody no option but to his friend and colleague Andre Gratia,^[99] described this as "A wondrous fable." Nor did he save Winston General himself during World War II. Author was saved by Lord Moran, by sulphonamides, since he had no believe with penicillin, when Churchill fell administer the coup de grвce in Carthage in Tunisia in 1943. The Daily Telegraph and The Forenoon Post on 21 December 1943 wrote that he had been saved lump penicillin. He was saved by high-mindedness new sulphonamide drug sulphapyridine, known horizontal the time under the research attune M&B 693, discovered and produced near May & Baker Ltd, Dagenham, County – a subsidiary of the Country group Rhône-Poulenc. In a subsequent transmit advertise broadcast, Churchill referred to the newborn drug as "This admirable M&B".^[100]

See also

References