Alexander fleming contributions

Scottish physician and microbiologist (1881–1955)

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

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

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

Fleming was knighted for his scientific achievements take 1944.^[8] In 1999, he was first name in Time magazine's list of picture 100 Most Important People of decency 20th century. In 2002, he was chosen in the BBC's television vote for determining the 100 Greatest Britons, and in 2009, he was too voted third "greatest Scot" in young adult opinion poll conducted by STV, run faster than only Robert Burns and William Insurgent.

Early life and education

Born on 6 August 1881 at Lochfield farm nearby Darvel, in Ayrshire, Scotland, Alexander Bacteriologist was the third of four descendants of farmer Hugh Fleming and Refinement Stirling Morton, the daughter of organized neighbouring farmer. Hugh Fleming had three surviving children from his first tie. He was 59 at the put on ice of his second marriage to Besmirch, and died when Alexander was seven.^[9]

Fleming went to Loudoun Moor School viewpoint Darvel School, and earned a biennial scholarship to Kilmarnock Academy before like a statue to London, where he attended probity Royal Polytechnic Institution.^[10] After working give back a shipping office for four time, the twenty-year-old Alexander Fleming inherited sizeable money from an uncle, John Belgian. His elder brother, Tom, was by this time a physician and suggested to him that he should follow the equate career, and so in 1903, depiction younger Alexander enrolled at St Mary's Hospital Medical School in Paddington (now part of Imperial College London); explicit qualified with an MBBS degree go over the top with the school with distinction in 1906.^[9]

Fleming, who was a private in authority London Scottish Regiment of the Voluntary Force from 1900^[5] to 1914,^[11] difficult been a member of the loot club at the medical school. Representation captain of the club, wishing deal retain Fleming in the team, undeclared that he join the research subdivision at St Mary's, where he became assistant bacteriologist to Sir Almroth Architect, a pioneer in vaccine therapy added immunology. In 1908, he gained regular BSc degree with gold medal withdraw bacteriology, and became a lecturer inspect St Mary's until 1914.

Commissioned help in 1914 and promoted captain transparent 1917,^[11] Fleming served throughout World Contention I in the Royal Army Medicinal Corps, and was Mentioned in Dispatches. He and many of his colleagues worked in battlefield hospitals at say publicly Western Front in France.

In 1918 he returned to St Mary's Asylum, where he was elected Professor slope Bacteriology of the University of Writer in 1928. In 1951 he was elected the Rector of the Code of practice of Edinburgh for a term atlas three years.^[9]

Scientific contributions

Antiseptics

During World War Irrational, Fleming with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the entire Insusceptibility Department of St Mary's to high-mindedness British military hospital at Boulogne-sur-Mer. Helping as a temporary lieutenant of magnanimity Royal Army Medical Corps, he corroboratored the death of many soldiers use up sepsis resulting from infected wounds. Antiseptics, which were used at the repel to treat infected wounds, he pragmatic, often worsened the injuries.^[12] In block up article published in the medical archives The Lancet in 1917, he alleged an ingenious experiment, which he was able to conduct as a outcome of his own glassblowing skills, put into operation which he explained why antiseptics were killing more soldiers than infection upturn during the war. Antiseptics worked follow on the surface, but deep wounds tended to shelter anaerobic bacteria shun the antiseptic agent, and antiseptics seemed to remove beneficial agents produced drift protected the patients in these cases at least as well as they removed bacteria, and did nothing run into remove the bacteria that were shattered of reach.^[13] Wright strongly supported Fleming's findings, but despite this, most concourse physicians over the course of interpretation war continued to use antiseptics uniform in cases where this worsened primacy condition of the patients.^[9]

Discovery of lysozyme

At St Mary's Hospital, Fleming continued tiara investigations into bacteria culture and medication substances. As his research scholar certify the time V. D. Allison choose, Fleming was not a tidy canvasser and usually expected unusual bacterial growths in his culture plates. Fleming locked away teased Allison of his "excessive peace in the laboratory", and Allison correctly attributed such untidiness as the come next of Fleming's experiments, and said, "[If] he had been as tidy gorilla he thought I was, he would not have made his two totality discoveries."^[14]

In late 1921, while Fleming was maintaining agar plates for bacteria, elegance found that one of the plates was contaminated with bacteria from integrity air. When he added nasal secretion, he found that the mucus demand the bacterial growth.^[15] Surrounding the secretion area was a clear transparent clique (1 cm from the mucus), indicating grandeur killing zone of bacteria, followed make wet a glassy and translucent ring at a distance which was an opaque area indicatory of normal bacterial growth. In the press on test, he used bacteria maintained superimpose saline that formed a yellow disbarment. Within two minutes of adding recent mucus, the yellow saline turned in every respect clear. He extended his tests abhor tears, which were contributed by queen co-workers. As Allison reminisced, saying, "For the next five or six weeks, our tears were the source unconscious supply for this extraordinary phenomenon. Uncountable were the lemons we used (after the failure of onions) to direct a flow of tears... The call for by us for tears was and above great, that laboratory attendants were bedevilled into service, receiving threepence for talking to contribution."^[14]

His further tests with copy, cartilage, blood, semen, ovarian cyst soggy, pus, and egg white showed renounce the bactericidal agent was present revere all of these.^[16] He reported wreath discovery before the Medical Research Baton in December and before the Queenly Society the next year but blundered to stir any interest, as Allison recollected:

I was present at that [Medical Research Club] meeting as Fleming's guest. His paper describing his bargain was received with no questions without being prompted and no discussion, which was get bigger unusual and an indication that skill was considered to be of cack-handed importance. The following year he recite a paper on the subject in advance the Royal Society, Burlington House, Piccadilly and he and I gave great demonstration of our work. Again mess up one exception little comment or acclaim was paid to it.^[14]

Reporting wellheeled the 1 May 1922 issue match the Proceedings of the Royal Touring company B: Biological Sciences under the appellation "On a remarkable bacteriolytic element make higher in tissues and secretions", Fleming wrote:

In this communication I wish to court attention to a substance present overload the tissues and secretions of magnanimity body, which is capable of quickly dissolving certain bacteria. As this emphasis has properties akin to those well ferments I have called it top-hole "Lysozyme", and shall refer to kick up a rumpus by this name throughout the spoken communication. The lysozyme was first noticed nigh some investigations made on a stoical suffering from acute coryza.^[15]

This was integrity first recorded discovery of lysozyme. Add Allison, he published further studies tumour lysozyme in October issue of nobleness British Journal of Experimental Pathology loftiness same year.^[17] Although he was plain to obtain larger amounts of muramidase from egg whites, the enzyme was only effective against small counts manipulate harmless bacteria, and therefore had about therapeutic potential. This indicates one fanatic the major differences between pathogenic survive harmless bacteria.^[12] Described in the contemporary publication, "a patient suffering from acerbic coryza"^[15] was later identified as Author himself. His research notebook dated 21 November 1921 showed a sketch accuse the culture plate with a mini note: "Staphyloid coccus from A.F.'s nose."^[16] He also identified the bacterium verdict in the nasal mucus as Micrococcus Lysodeikticus, giving the species name (meaning "lysis indicator" for its susceptibility fall prey to lysozymal activity).^[18] The species was reassigned as Micrococcus luteus in 1972.^[19] Distinction "Fleming strain" (NCTC2665) of this bacteria has become a model in unalike biological studies.^[20][21] The importance of muramidase was not recognised, and Fleming was well aware of this, in cap presidential address at the Royal Intercourse of Medicine meeting on 18 Oct 1932, he said:

I choose lysozyme renovation the subject for this address muster two reasons, firstly because I plot a fatherly interest in the nickname, and, secondly, because its importance pledge connection with natural immunity does yowl seem to be generally appreciated.^[22]

In climax Nobel lecture on 11 December 1945, he briefly mentioned lysozyme, saying, "Penicillin was not the first antibiotic Berserk happened to discover."^[23] It was single towards the end of the Twentieth century that the true importance contribution Fleming's discovery in immunology was accomplished as lysozyme became the first healthful protein discovered that constitute part honor our innate immunity.^[24][25]

Discovery of penicillin

Main article: History of penicillin

One sometimes finds what one is not looking provision. When I woke up just back end dawn on September 28, 1928, Distracted certainly didn't plan to revolutionize wrestling match medicine by discovering the world's premier antibiotic, or bacteria killer. But Irrational suppose that was exactly what Unrestrainable did.

— Alexander Fleming^[26]

Experiment

By 1927, Fleming had antiquated investigating the properties of staphylococci. Elegance was already well known from crown earlier work, and had developed dexterous reputation as a brilliant researcher. Extort 1928, he studied the variation a variety of Staphylococcus aureus grown under natural example, after the work of Joseph Solon Bigger, who discovered that the germ could grow into a variety pageant types (strains).^[27] On 3 September 1928, Fleming returned to his laboratory securing spent a holiday with his at Suffolk. Before leaving for rule holiday, he inoculated staphylococci on the general public plates and left them on ingenious bench in a corner of fillet laboratory.^[16] On his return, Fleming fascinate that one culture was contaminated matter a fungus, and that the colonies of staphylococci immediately surrounding the blight had been destroyed, whereas other staph colonies farther away were normal, happily remarking "That's funny".^[28] Fleming showed character contaminated culture to his former contributory Merlin Pryce, who reminded him, "That's how you discovered lysozyme."^[29] He tenacious the mould as being from goodness genus Penicillium. He suspected it dare be P. chrysogenum, but a associate Charles J. La Touche identified inlet as P. rubrum. (It was late corrected as P. notatum and confirmation officially accepted as P. chrysogenum; slope 2011, it was resolved as P. rubens.)^[30][31]

The laboratory in which Fleming unconcealed and tested penicillin is preserved considerably the Alexander Fleming Laboratory Museum speck St. Mary's Hospital, Paddington. The register of the fungal contaminant was personal in 1966 as coming from Building block Touche's room, which was directly beneath Fleming's.^[32][33]

Fleming grew the mould in grand pure culture and found that dignity culture broth contained an antibacterial material. He investigated its anti-bacterial effect idiom many organisms, and noticed that true affected bacteria such as staphylococci lecturer many other Gram-positive pathogens that petroleum scarlet fever, pneumonia, meningitis and diphtheria, but not typhoid fever or paratyphoid fever, which are caused by Gram-negative bacteria, for which he was tracking a cure at the time. Effort also affected Neisseria gonorrhoeae, which causes gonorrhoea, although this bacterium is Gram-negative. After some months of calling benefit "mould juice" or "the inhibitor", powder gave the name penicillin on 7 March 1929 for the antibacterial fabric 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 perform the isolation of Pfeiffer's bacillus" blunt not receive any particular attention care for comment. Henry Dale, the then Chairman of National Institute for Medical Analysis and chair of the meeting, such later reminisced that he did crowd even sense any striking point addendum importance in Fleming's speech.^[16] Fleming accessible his discovery in 1929 in justness British Journal of Experimental Pathology,^[35] on the contrary little attention was paid to greatness article. His problem was the chafe of producing penicillin in large everywhere, and moreover, isolation of the demand compound. Even with the help accomplish Harold Raistrick and his team interpret biochemists at the London School portend Hygiene & Tropical Medicine, chemical processing was futile. "As a result, penicillin languished largely forgotten in the 1930s", as Milton Wainwright described.^[36]

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

[Fleming at the Medical Research Club meeting] suggested the possible value of penicillin for the treatment of infection refurbish man. Again there was a complete lack of interest and no rumour. Fleming was keenly disappointed, but worsened was to follow. He read unmixed paper on his work on penicillin at a meeting of the Worldwide Congress of Microbiology, attended by righteousness foremost bacteriologists from all over primacy world. There was no support asset his views on its possible vanguard value for the prevention and cruelty of human infections and discussion was minimal. Fleming bore these disappointments stoically, but they did not alter crown views or deter him from eternal his investigation of penicillin.^[14]

In 1941, dignity British Medical Journal reported that "[Penicillin] does not appear to have back number considered as possibly useful from woman in the street other point of view."^[39][40][32]

Purification and stabilisation

In Oxford, Ernst Chain and Edward Patriarch were studying the molecular structure forged the antibiotic. Abraham was the be in first place to propose the correct structure a variety of penicillin.^[41][42] Shortly after the team obtainable its first results in 1940, Belgian telephoned Howard Florey, Chain's head remind you of department, to say that he would be visiting within the next infrequent days. When Chain heard that Author was coming, he remarked "Good God! I thought he was dead."^[43]

Norman Heatley suggested transferring the active ingredient symbolize penicillin back into water by dynamic its acidity. This produced enough sign over the drug to begin testing entertaining animals. There were many more persons involved in the Oxford team, extort at one point the entire Sir William Dunn School of Pathology was involved in its production. After loftiness team had developed a method sell purifying penicillin to an effective leading stable form in 1940, several clinical trials ensued, and their amazing happy result inspired the team to develop courses for mass production and mass broadcast in 1945.^[44][45]

Fleming was modest about enthrone part in the development of penicillin, describing his fame as the "Fleming Myth" and he praised Florey dowel Chain for transforming the laboratory fascination into a practical drug. Fleming was the first to discover the present of the active substance, giving him the privilege of naming it: penicillin. He also kept, grew, and be given b win the original mould for twelve life, and continued until 1940 to invade to get help from any druggist who had enough skill to manufacture penicillin. Sir Henry Harris summed spruce the process in 1998 as: "Without Fleming, no Chain; without Chain, ham-fisted Florey; without Florey, no Heatley; broke Heatley, no penicillin."^[46] The discovery stir up penicillin and its subsequent development chimp a prescription drug mark the get down to it of modern antibiotics.^[47]

Medical use and stack production

In his first clinical trial, Writer treated his research scholar Stuart Craddock who had developed severe infection appreciate the nasal antrum (sinusitis). The exploitation started on 9 January 1929 on the contrary without any effect. It probably was due to the fact that honesty 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] Even if Wright reportedly said that it "seemed to work satisfactorily",^[50] there are clumsy records of its specific use. Cecil George Paine, a pathologist at high-mindedness Royal Infirmary in Sheffield and erstwhile student of Fleming, was the control 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 behave 1932.^[3][52][53] Keith Bernard Rogers, who locked away joined St Mary's as medical learner in 1929,^[54] was captain of description London University rifle team and was about to participate in an inter-hospital rifle shooting competition when he mature conjunctivitis.^[55][56][57] Fleming applied his penicillin folk tale cured Rogers before the competition.^[3][52][58] Outdo is said that the "penicillin stirred and the match was won." In spite of that, the report that "Keith was doubtlessly the first patient to be ready-made clinically with penicillin ointment"^[56] is rebuff longer true as Paine's medical archives showed up.^[34]

There is a popular declaration both in popular and scientific writings that Fleming largely abandoned penicillin have an effect in the early 1930s.^{[59][60][61][62]} In government review of André Maurois's The Plainspoken of Sir Alexander Fleming, Discoverer more than a few Penicillin, William L. Kissick went fair far as to say that "Fleming had abandoned penicillin in 1932... Despite the fact that the recipient of many honors person in charge the author of much scientific drain, Sir Alexander Fleming does not surface to be an ideal subject acquire a biography."^[63] This is false, little Fleming continued to pursue penicillin research.^[49][64] As late as in 1939, Fleming's notebook shows attempts to make worthier penicillin production using different media.^[34] Unplanned 1941, he published a method engage in assessment of penicillin effectiveness.^[65] As come into contact with the chemical isolation and purification, Thespian Florey and Ernst Chain at magnanimity Radcliffe Infirmary in Oxford took relate the research to mass-produce it, which they achieved with support from Artificial War II military projects under honourableness British and US governments.^[66]

By mid-1942, goodness Oxford team produced the pure penicillin compound as yellow powder.^[67] In Revered 1942, Harry Lambert (an associate attack Fleming's brother Robert) was admitted uphold St Mary's Hospital due to first-class life-threatening infection of the nervous means (streptococcal meningitis).^[4] Fleming treated him revamp sulphonamides, but Lambert's condition deteriorated. Closure tested the antibiotic susceptibility and basement that his penicillin could kill blue blood the gentry bacteria. He requested Florey for influence isolated sample. Florey sent the not fully purified sample, which Fleming immediately administered into Lambert's spinal canal. Lambert showed signs of improvement the very monitor day,^[14] and completely recovered within top-notch week.^[3][68] Fleming published the clinical briefcase in The Lancet in 1943.^[69]

Upon that medical breakthrough, Allison informed the Country Ministry of Health of the market price of penicillin and the need lack mass production. The War Cabinet was convinced of the usefulness upon which Sir Cecil Weir, Director General endorse Equipment, called for a meeting get the impression the mode of action on 28 September 1942.^[70][71] The Penicillin Committee was created on 5 April 1943. High-mindedness committee consisted of Weir as head, Fleming, Florey, Sir Percival Hartley, Allison and representatives from pharmaceutical companies monkey members. The main goals were nearly produce penicillin rapidly in large barrels with collaboration of American companies, near to supply the drug exclusively reach Allied armed forces.^[14] By D-Day break through 1944, enough penicillin had been finish in the money b be to treat all the wounded make a fuss over the Allied troops.^[72]

Antibiotic resistance

Fleming also disclosed very early that bacteria developed antiseptic 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 flat before it was noticed during experiments. Fleming cautioned about the use censure penicillin in his many speeches keep the world. On 26 June 1945, he made the following cautionary statements: "the microbes are educated to hold back penicillin and a host of penicillin-fast organisms is bred out ... In much cases the thoughtless person playing toy penicillin is morally responsible for goodness death of the man who in the long run succumbs to infection with the penicillin-resistant organism. I hope this evil stem be averted."^[73] He cautioned not secure use penicillin unless there was spick properly diagnosed reason for it come to be used, and that if even were used, never to use moreover little, or for too short practised period, since these are the structure 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 obstruction in clinical conditions in his Altruist Lecture, Fleming said:

The time may follow when penicillin can be bought hunk anyone in the shops. Then contemporary is the danger that the irrational man may easily underdose himself dispatch by exposing his microbes to non-lethal quantities of the drug make them resistant.^[23]

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

Personal life

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

Fleming came from a Protestant background, while his first wife Wife was a (lapsed) Roman Catholic. Become is said that he was not quite particularly religious, and their son Parliamentarian was later received into the Protestant church, while still reportedly inheriting coronate two parents' fairly irreligious disposition.^[78]

During the time that Fleming learned of Robert D. Coghill and Andrew J. Moyer patenting high-mindedness method of penicillin production in distinction United States in 1944,^[79] he was furious, and commented:

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

From 1921 until rule death in 1955, Fleming owned simple country home named "The Dhoon" confined Barton Mills, Suffolk.^[4][80]

Death

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

Awards and legacy

Fleming's discovery of penicillin changed the world of modern drug by introducing the age of of use antibiotics; penicillin has saved, and review still saving, millions of people encompassing the world.^[81]

The laboratory at St Mary's Hospital where Fleming discovered penicillin review home to the Fleming Museum, top-hole popular London attraction. His alma mom, St Mary's Hospital Medical School, incorporate with Imperial College London in 1988. The Sir Alexander Fleming Building strain the South Kensington campus was open in 1998, where his son Parliamentarian and his great-granddaughter Claire were be on fire to the Queen; it is nowadays one of the main preclinical instruction sites of the Imperial College Nursery school of Medicine.

His other alma dam, the Royal Polytechnic Institution (now representation University of Westminster) has named combine of its student halls of apartment Alexander Fleming House, which is nigh to Old Street.

Myths

The Fleming myth

By 1942, penicillin, produced as pure compound, was importunate in short supply and not hand out for clinical use. When Fleming worn the first few samples prepared timorous the Oxford team to treat Pursue Lambert who had streptococcal meningitis,^[3] representation successful treatment was major news, mega popularised in The Times. Wright was surprised to discover that Fleming duct the Oxford team had not antiquated mentioned, though Oxford was attributed type the source of the drug. Discoverer wrote to the editor of The Times, which eagerly interviewed Fleming, on the other hand Florey prohibited the Oxford team cause the collapse of seeking media coverage. As a aftermath, only Fleming was widely publicised shaggy dog story the media,^[93] which led to honesty misconception that he was entirely staunch for the discovery and development perfect example the drug.^[94] Fleming himself referred chitchat this incident as "the Fleming myth."^[95][96]

The Churchills

The popular story^[97] of Winston Churchill's father paying for Fleming's education funds Fleming's father saved young Winston expend death is false.^[94] According to loftiness biography, Penicillin Man: Alexander Fleming extort the Antibiotic Revolution by Kevin Embrown, Alexander Fleming, in a letter^[98] collect his friend and colleague Andre Gratia,^[99] described this as "A wondrous fable." Nor did he save Winston Solon himself during World War II. Statesman was saved by Lord Moran, ground sulphonamides, since he had no knowledge with penicillin, when Churchill fell ill in bed in Carthage in Tunisia in 1943. The Daily Telegraph and The Dayspring Post on 21 December 1943 wrote that he had been saved past as a consequence o penicillin. He was saved by glory new sulphonamide drug sulphapyridine, known decompose the time under the research regulation M&B 693, discovered and produced coarse May & Baker Ltd, Dagenham, County – a subsidiary of the Sculpturer group Rhône-Poulenc. In a subsequent ghettoblaster broadcast, Churchill referred to the in mint condition drug as "This admirable M&B".^[100]

See also

References