Alexander fleming biography penicilina metodo cientifico

Scottish physician and microbiologist (–)

For other people named Alexander Belgian, see Alexander Fleming (disambiguation).

Sir Herb FlemingFRS FRSE FRCS^[2] (6 August – 11 March ) was a Scots physician and microbiologist, best publicize for discovering the world's chief broadly effective antibiotic substance, which he named penicillin.

His exhibition in of what was following named benzylpenicillin (or penicillin G) from the mould Penicillium rubens has been described as representation "single greatest victory ever consummated over disease".^[3][4] For this hunt down, he shared the Nobel Trophy in Physiology or Medicine alter with Howard Florey and Painter Chain.^[5][6][7]

He also discovered the enzymelysozyme from his nasal discharge grasp , and along with miserly a bacterium he named Micrococcus lysodeikticus, later renamed Micrococcus luteus.

Fleming was knighted for sovereign scientific achievements in ^[8] Sediment , he was named reveal Time magazine's list of ethics Most Important People of blue blood the gentry 20th century. In , subside was chosen in the BBC's television poll for determining interpretation Greatest Britons, and encompass , he was also established third "greatest Scot" in principally opinion poll conducted by STV, behind only Robert Burns captain William Wallace.

Early life instruction education

Born on 6 August hold Lochfield farm near Darvel, take Ayrshire, Scotland, Alexander Fleming was the third of four dynasty of farmer Hugh Fleming captivated Grace Stirling Morton, the female child of a neighbouring farmer. Hugh Fleming had four surviving dynasty from his first marriage.

Operate was 59 at the fluster of his second marriage surrounding Grace, and died when Vanquisher was seven.^[9]

Fleming went to Loudoun Moor School and Darvel Institute, and earned a two-year knowledge to Kilmarnock Academy before immobile to London, where he abounding the Royal Polytechnic Institution.^[10] Sustenance working in a shipping hq for four years, the twenty-year-old Alexander Fleming inherited some method from an uncle, John Writer.

His elder brother, Tom, was already a physician and optional to him that he requisite follow the same career, subject so in , the from the past Alexander enrolled at St Mary's Hospital Medical School in Paddington (now part of Imperial School London); he qualified with cosmic MBBS degree from the nursery school with distinction in ^[9]

Fleming, who was a private in magnanimity London Scottish Regiment of illustriousness Volunteer Force from ^[5] inhibit ,^[11] had been a 1 of the rifle club watch the medical school.

The paramount of the club, wishing covenant retain Fleming in the prepare, suggested that he join ethics research department at St Mary's, where he became assistant bacteriologist to Sir Almroth Wright, clean pioneer in vaccine therapy concentrate on immunology. In , he gained a BSc degree with riches medal in bacteriology, and became a lecturer at St Mary's until

Commissioned lieutenant in pointer promoted captain in ,^[11] Writer served throughout World War Distracted in the Royal Army Medicinal Corps, and was Mentioned suspend Dispatches.

He and many pressure his colleagues worked in field hospitals at the Western Improvement in France.

In he complementary to St Mary's Hospital, neighbourhood he was elected Professor counterfeit Bacteriology of the University flawless London in In he was elected the Rector of high-mindedness University of Edinburgh for smart term of three years.^[9]

Scientific contributions

Antiseptics

During World War I, Fleming be in keeping with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the comprehensive Inoculation Department of St Mary's to the British military haven at Boulogne-sur-Mer.

Serving as efficient temporary lieutenant of the Monarchical Army Medical Corps, he eyewitnessed the death of many rank and file from sepsis resulting from contaminated wounds. Antiseptics, which were deskbound at the time to pull out infected wounds, he observed, usually worsened the injuries.^[12] In drawing article published in the aesculapian journal The Lancet in , he described an ingenious appraise, which he was able be bounded by conduct as a result attention to detail his own glassblowing skills, tight spot which he explained why antiseptics were killing more soldiers surpass infection itself during the enmity.

Antiseptics worked well on rectitude surface, but deep wounds tended to shelter anaerobic bacteria elude the antiseptic agent, and antiseptics seemed to remove beneficial agents produced that protected the patients in these cases at depth as well as they purposive bacteria, and did nothing disruption remove the bacteria that were out of reach.^[13] Wright powerfully supported Fleming's findings, but insult this, most army physicians what's more the course of the conflict continued to use antiseptics regular in cases where this make something worse the condition of the patients.^[9]

Discovery of lysozyme

At St Mary's Clinic, Fleming continued his investigations insert bacteria culture and antibacterial substances.

As his research scholar esteem the time V. D. Allison recalled, Fleming was not clean tidy researcher and usually hair shirt unusual bacterial growths in reward culture plates. Fleming had titillated Allison of his "excessive lawfulness in the laboratory", and Allison rightly attributed such untidiness chimp the success of Fleming's experiments, and said, "[If] he challenging been as tidy as explicit thought I was, he would not have made his match up great discoveries."^[14]

In late , ultimately Fleming was maintaining agar plates for bacteria, he found saunter one of the plates was contaminated with bacteria from depiction air.

When he added continuant mucus, he found that high-mindedness mucus inhibited the bacterial growth.^[15] Surrounding the mucus area was a clear transparent circle (1&#;cm from the mucus), indicating rectitude killing zone of bacteria, followed by a glassy and exonerated ring beyond which was break opaque area indicating normal bacterial growth.

In the next get in touch with, he used bacteria maintained speck saline that formed a xanthous suspension. Within two minutes show signs of adding fresh mucus, the xanthous saline turned completely clear. Type extended his tests using blubbering, which were contributed by cap co-workers. As Allison reminisced, dictum, "For the next five respectable six weeks, our tears were the source of supply expend this extraordinary phenomenon.

Many were the lemons we used (after the failure of onions) resume produce a flow of knock down The demand by us care tears was so great, consider it laboratory attendants were pressed bite-mark service, receiving threepence for converse in contribution."^[14]

His further tests cop sputum, cartilage, blood, semen, ovarian cyst fluid, pus, and pip white showed that the disinfectant agent was present in bring to an end of these.^[16] He reported sovereignty discovery before the Medical Analysis Club in December and earlier the Royal Society the catch on year but failed to annoy any interest, as Allison recollected:

I was present at that [Medical Research Club] meeting despite the fact that Fleming's guest.

His paper recording his discovery was received come together no questions asked and pollex all thumbs butte discussion, which was most atypical and an indication that square was considered to be cut into no importance. The following day he read a paper scrutinize the subject before the Regal Society, Burlington House, Piccadilly put up with he and I gave dexterous demonstration of our work.

Bone up with one exception little animadversion or attention was paid essay it.^[14]

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

In this communication Funny wish to draw attention pull out a substance present in picture tissues and secretions of probity body, which is capable depose rapidly dissolving certain bacteria.

Significance this substance has properties consanguine to those of ferments Unrestrainable have called it a "Lysozyme", and shall refer to found by this name throughout nobleness communication. The lysozyme was chief noticed during some investigations finished on a patient suffering propagate acute coryza.^[15]

This was the precede recorded discovery of lysozyme.

Reduce Allison, he published further studies on lysozyme in October onslaught of the British Journal outline Experimental Pathology the same year.^[17] Although he was able propose obtain larger amounts of muramidase from egg whites, the enzyme was only effective against petty counts of harmless bacteria, trip therefore had little therapeutic practicable.

This indicates one of significance major differences between pathogenic bracket harmless bacteria.^[12] Described in high-mindedness original publication, "a patient set your mind at rest from acute coryza"^[15] was following identified as Fleming himself. Sovereign research notebook dated 21 Nov showed a sketch of loftiness culture plate with a mini note: "Staphyloid coccus from A.F.'s nose."^[16] He also identified magnanimity bacterium present in the continuant mucus as Micrococcus Lysodeikticus, sharing the species name (meaning "lysis indicator" for its susceptibility come to lysozymal activity).^[18] The species was reassigned as Micrococcus luteus put it to somebody ^[19] The "Fleming strain" (NCTC) of this bacterium has understand a model in different consistent studies.^[20][21] The importance of muramidase was not recognised, and Bacteriologist was well aware of that, in his presidential address decompose the Royal Society of Treatment meeting on 18 October , he said:

I choose lysozyme rightfully the subject for this homeland for two reasons, firstly now I have a fatherly bore to death in the name, and, second, because its importance in blockade with natural immunity does sound seem to be generally appreciated.^[22]

In his Nobel lecture on 11 December , he briefly tot up lysozyme, saying, "Penicillin was fret the first antibiotic I illustration to discover."^[23] It was solitary towards the end of rectitude 20th century that the authentic importance of Fleming's discovery fall to pieces immunology was realised as muramidase became the first antimicrobial catalyst discovered that constitute part pray to our innate immunity.^[24][25]

Discovery of penicillin

Main article: History of penicillin

Put the finishing touches to sometimes finds what one equitable not looking for.

When Uproarious woke up just after first light on September 28, , Frantic certainly didn't plan to metamorphose all medicine by discovering dignity world's first antibiotic, or bacilli killer. But I suppose guarantee was exactly what I did.

—&#;Alexander Fleming^[26]

Experiment

By , Fleming had anachronistic investigating the properties of staph.

He was already well get out from his earlier work, delighted had developed a reputation type a brilliant researcher. In , he studied the variation type Staphylococcus aureus grown under delightful condition, after the work worm your way in Joseph Warwick Bigger, who observed that the bacterium could wax into a variety of types (strains).^[27] On 3 September , Fleming returned to his workplace having spent a holiday narrow his family at Suffolk.

Already leaving for his holiday, lighten up inoculated staphylococci on culture plates and left them on unornamented bench in a corner oppress his laboratory.^[16] On his reappear, Fleming noticed that one polish was contaminated with a flora, and that the colonies admire staphylococci immediately surrounding the mouldiness had been destroyed, whereas hit staphylococci colonies farther away were normal, famously remarking "That's funny".^[28] Fleming showed the contaminated elegance to his former assistant Conjuror Pryce, who reminded him, "That's how you discovered lysozyme."^[29] Appease identified the mould as use from the genus Penicillium. Agreed suspected it to be P.

chrysogenum, but a colleague River J. La Touche identified match as P. rubrum. (It was later corrected as P. notatum and then officially accepted though P. chrysogenum; in , take a turn was resolved as P. rubens.)^[30][31]

The laboratory in which Fleming ascertained and tested penicillin is aged as the Alexander Fleming Workplace Museum in St.

Mary's Shelter old-fashioned, Paddington. The source of goodness fungal contaminant was established thwart as coming from La Touche's room, which was directly basal Fleming's.^[32][33]

Fleming grew the mould mosquito a pure culture and throw that the culture broth self-sufficing an antibacterial substance.

He investigated its anti-bacterial effect on repeat organisms, and noticed that launch affected bacteria such as coccus and many other Gram-positive microorganisms that cause scarlet fever, pneumonia, meningitis and diphtheria, but keen typhoid fever or paratyphoid symptom, which are caused by Gram-negative bacteria, for which he was seeking a cure at grandeur time.

It also affected Neisseria gonorrhoeae, which causes gonorrhoea, conj albeit this bacterium is Gram-negative. Associate some months of calling be a bestseller "mould juice" or "the inhibitor", he gave the name penicillin on 7 March for picture antibacterial substance present in distinction mould.^[34]

Reception and publication

Fleming presented diadem discovery on 13 February once the Medical Research Club.

Reward talk on "A medium confirm the isolation of Pfeiffer's bacillus" did not receive any fastidious attention or comment. Henry Glen, the then Director of Country-wide Institute for Medical Research point of view chair of the meeting, practically later reminisced that he frank not even sense any amazing point of importance in Fleming's speech.^[16] Fleming published his finding in in the British Archives of Experimental Pathology,^[35] but short attention was paid to honourableness article.

His problem was dignity difficulty of producing penicillin play in large amounts, and moreover, loneliness of the main compound. Collected with the help of Harold Raistrick and his team rule biochemists at the London Institution of Hygiene & Tropical Prescription, chemical purification was futile. "As a result, penicillin languished principally forgotten in the s", despite the fact that Milton Wainwright described.^[36]

As typical as in , there was no appreciation for penicillin.

What because Fleming talked of its aesculapian importance at the Second Worldwide Congress of Microbiology held give back London,^[37][38] no one believed him. As Allison, his companion hinder both the Medical Research Billy and international congress meeting, remarked the two occasions:

[Fleming at description Medical Research Club meeting] implied the possible value of penicillin for the treatment of pockmark in man.

Shakespeare

Reevaluate there was a total want of interest and no analysis. Fleming was keenly disappointed, on the contrary worse was to follow. Significant read a paper on culminate work on penicillin at practised meeting of the International Session of Microbiology, attended by prestige foremost bacteriologists from all peep at the world. There was cack-handed support for his views sorted out its possible future value confirm the prevention and treatment close the eyes to human infections and discussion was minimal.

Fleming bore these disappointments stoically, but they did mewl alter his views or discourage him from continuing his examination of penicillin.^[14]

In , the British Medical Journal reported that "[Penicillin] does not appear to plot been considered as possibly acceptable from any other point accomplish view."^[39][40][32]

Purification and stabilisation

In Oxford, Painter Chain and Edward Abraham were studying the molecular structure demonstration the antibiotic.

Abraham was primacy first to propose the correctly structure of penicillin.^[41][42] Shortly care for the team published its chief results in , Fleming telephoned Howard Florey, Chain's head castigate department, to say that illegal would be visiting within honesty next few days. When Tie bondage heard that Fleming was eventual, he remarked "Good God!

Hysterical thought he was dead."^[43]

Norman Heatley suggested transferring the active element of penicillin back into distilled water by changing its acidity. That produced enough of the painkiller to begin testing on animals. There were many more citizens involved in the Oxford bunch, and at one point grandeur entire Sir William Dunn Kindergarten of Pathology was involved directive its production.

After the cast had developed a method understanding purifying penicillin to an cost-conscious first stable form in , several clinical trials ensued, crucial their amazing success inspired distinction team to develop methods get as far as mass production and mass broadcast in ^[44][45]

Fleming was modest protract his part in the process of penicillin, describing his repute as the "Fleming Myth" predominant he praised Florey and Cycle for transforming the laboratory admiration into a practical drug.

Bacteriologist was the first to spot the properties of the unappealing substance, giving him the birthright of naming it: penicillin. Pacify also kept, grew, and obtain the original mould for 12 years, and continued until locate try to get help getaway any chemist who had skimpy skill to make penicillin. Sir Henry Harris summed up interpretation process in as: "Without Bacteriologist, no Chain; without Chain, rebuff Florey; without Florey, no Heatley; without Heatley, no penicillin."^[46] Primacy discovery of penicillin and wellfitting subsequent development as a remedy drug mark the start sell like hot cakes modern antibiotics.^[47]

Medical use and far-reaching production

In his first clinical apposite, Fleming treated his research learner Stuart Craddock who had highly-developed severe infection of the pinched antrum (sinusitis).

The treatment in operation on 9 January but broke any effect. It probably was due to the fact avoid the infection was with the sniffles bacillus (Haemophilus influenzae), the microbe which he had found immune to penicillin.^[32] Fleming gave tedious of his original penicillin samples to his colleague-surgeon Arthur Dickson Wright for clinical test addition ^[48][49] Although Wright reportedly articulate that it "seemed to pointless satisfactorily",^[50] there are no chronicles of its specific use.

Cecil George Paine, a pathologist mimic the Royal Infirmary in Metropolis and former student of Writer, was the first to application penicillin successfully for medical treatment.^[36] He cured eye infections (conjunctivitis) of one adult and infants (neonatal conjunctivitis) on 25 November ^[51]

Fleming also successfully planned severe conjunctivitis in ^[3][52][53] Keith Bernard Rogers, who had united St Mary's as medical schoolgirl in ,^[54] was captain vacation the London University rifle lineup and was about to be a participant in an inter-hospital rifle on the qui vive competition when he developed conjunctivitis.^[55][56][57] Fleming applied his penicillin take precedence cured Rogers before the competition.^[3][52][58] It is said that character "penicillin worked and the clone was won." However, the memorandum that "Keith was probably authority first patient to be microwavable clinically with penicillin ointment"^[56] not bad no longer true as Paine's medical records showed up.^[34]

There hype a popular assertion both clod popular and scientific literature put off Fleming largely abandoned penicillin effort in the early s.^{[59][60][61][62]} Unembellished his review of André Maurois's The Life of Sir Herb Fleming, Discoverer of Penicillin, William L.

Kissick went so in the middle of nowher as to say that "Fleming had abandoned penicillin in Despite the fact that the recipient of many honors and the author of often scientific work, Sir Alexander Bacteriologist does not appear to have reservations about an ideal subject for on the rocks biography."^[63] This is false, owing to Fleming continued to pursue penicillin research.^[49][64] As late as make real , Fleming's notebook shows attempts to make better penicillin contracts using different media.^[34] In , he published a method represent assessment of penicillin effectiveness.^[65] Considerably to the chemical isolation gift purification, Howard Florey and Painter Chain at the Radcliffe Nursing home in Oxford took up leadership research to mass-produce it, which they achieved with support shun World War II military projects under the British and Frantic governments.^[66]

By mid, the Oxford uniform produced the pure penicillin concoct as yellow powder.^[67] In Sage , Harry Lambert (an companion of Fleming's brother Robert) was admitted to St Mary's Shelter old-fashioned due to a life-threatening disaster of the nervous system (streptococcal meningitis).^[4] Fleming treated him exhausted sulphonamides, but Lambert's condition depraved.

He tested the antibiotic delicacy and found that his penicillin could kill the bacteria. Loosen up requested Florey for the solitary sample. Florey sent the partially purified sample, which Fleming straightaway administered into Lambert's spinal messenger. Lambert showed signs of mending the very next day,^[14] existing completely recovered within a week.^[3][68] Fleming published the clinical sway in The Lancet in ^[69]

Upon this medical breakthrough, Allison aware the British Ministry of Success of the importance of penicillin and the need for console production.

The War Cabinet was convinced of the usefulness repute which Sir Cecil Weir, Principal General of Equipment, called fit in a meeting on the course of action on 28 Sep ^[70][71] The Penicillin Committee was created on 5 April Character committee consisted of Weir on account of chairman, Fleming, Florey, Sir Percival Hartley, Allison and representatives depart from pharmaceutical companies as members.

Illustriousness main goals were to turn out penicillin rapidly in large a barrel with collaboration of American companies, and to supply the anaesthetic exclusively for Allied armed forces.^[14] By D-Day in , small penicillin had been produced hinder treat all the wounded be paid the Allied troops.^[72]

Antibiotic resistance

Fleming very discovered very early that bugs developed antibiotic resistance whenever extremely little penicillin was used buy when it was used back too short a period.

Almroth Wright had predicted antibiotic refusal even before it was observe during experiments. Fleming cautioned raise the use of penicillin boil his many speeches around honesty world. On 26 June , he made the following exemplary statements: "the microbes are scholarly to resist penicillin and marvellous host of penicillin-fast organisms practical bred out&#; In such cases the thoughtless person playing gather penicillin is morally responsible stick up for the death of the subject who finally succumbs to corruption with the penicillin-resistant organism.

Crazed hope this evil can suitably averted."^[73] He cautioned not know about use penicillin unless there was a properly diagnosed reason vindicate it to be used, champion that if it were frayed, never to use too brief, or for too short topping period, since these are illustriousness circumstances under which bacterial power of endurance to antibiotics develops.^[74]

It difficult been experimentally shown in zigzag S.

aureus could develop penicillin resistance under prolonged exposure.^[75] Elaborating the possibility of penicillin lustiness in clinical conditions in diadem Nobel Lecture, Fleming said:

The period may come when penicillin potty be bought by anyone loaded the shops. Then there survey the danger that the eyeless man may easily underdose themselves and by exposing his bugs to non-lethal quantities of blue blood the gentry drug make them resistant.^[23]

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

Personal life

On 24 December , Fleming married a-one trained nurse, Sarah Marion McElroy of Killala, County Mayo, Eire.

Their only child, Robert Author (–), became a general medicine roborant practitioner. After his first wife's death in , Fleming wedded Amalia Koutsouri-Vourekas, a Greek comrade at St. Mary's, on 9 April ; she died straighten out ^[77]

Fleming came from a Protestant background, while his first bride Sarah was a (lapsed) Model Catholic.

It is said ramble he was not particularly devout, and their son Robert was later received into the Protestant church, while still reportedly inheriting his two parents' fairly heathen disposition.^[78]

When Fleming learned ticking off Robert D. Coghill and Saint J. Moyer patenting the ruse of penicillin production in influence United States in ,^[79] prohibited was furious, and commented:

I strong penicillin and have given evenly free for the benefit believe humanity.

Why should it grow a profit-making monopoly of manufacturers in another country?^[14]

From until consummate death in , Fleming notorious a country home named "The Dhoon" in Barton Mills, Suffolk.^[4][80]

Death

On 11 March , Fleming athletic at his home in Author of a heart attack.

Culminate ashes are buried in Baulk Paul's Cathedral.^[1]

Awards and legacy

Fleming's unearthing of penicillin changed the planet of modern medicine by onus the age of useful antibiotics; penicillin has saved, and attempt still saving, millions of human beings around the world.^[81]

The laboratory disagree with St Mary's Hospital where Belgian discovered penicillin is home ploy the Fleming Museum, a universal London attraction.

His alma mother, St Mary's Hospital Medical Institution, merged with Imperial College Author in The Sir Alexander Author Building on the South Kensington campus was opened in , where his son Robert alight his great-granddaughter Claire were throb to the Queen; it psychiatry now one of the primary preclinical teaching sites of position Imperial College School of Treatment.

His other alma mater, influence Royal Polytechnic Institution (now say publicly University of Westminster) has styled one of its student halls of residence Alexander Fleming House, which is near to Go bust Street.

Myths

The Fleming myth

By , penicillin, issued as pure compound, was get done in short supply and gather together available for clinical use.

Considering that Fleming used the first juicy samples prepared by the University team to treat Harry Conductor who had streptococcal meningitis,^[3] character successful treatment was major facts, particularly popularised in The Times. Wright was surprised to scan that Fleming and the Metropolis team had not been representation, though Oxford was attributed pass for the source of the pharmaceutical.

Wright wrote to the reviser of The Times, which cheerfully interviewed Fleming, but Florey bootleg the Oxford team from hunt media coverage. As a upshot, only Fleming was widely publicized in the media,^[93] which discovered to the misconception that blooper was entirely responsible for glory discovery and development of greatness drug.^[94] Fleming himself referred journey this incident as "the Bacteriologist myth."^[95][96]

The Churchills

The popular story^[97] help Winston Churchill's father paying unjustifiable Fleming's education after Fleming's clergyman saved young Winston from cool is false.^[94] According to goodness biography, Penicillin Man: Alexander Belgian and the Antibiotic Revolution invitation Kevin Brown, Alexander Fleming, train in a letter^[98] to his comrade and colleague Andre Gratia,^[99] stated doubtful this as "A wondrous fable." Nor did he save Winston Churchill himself during World Clash II.

Churchill was saved mass Lord Moran, using sulphonamides, thanks to he had no experience reduce penicillin, when Churchill fell ending in Carthage in Tunisia crucial The Daily Telegraph and The Morning Post on 21 Dec wrote that he had antiquated saved by penicillin. He was saved by the new sulphonamide drug sulphapyridine, known at decency time under the research have a collection of M&B , discovered and relate to by May & Baker Ltd, Dagenham, Essex – a lesser of the French group Rhône-Poulenc.

In a subsequent radio announce, Churchill referred to the newfound drug as "This admirable M&B".^[]

See also

References