Alexander Fleming
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Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician and
microbiologist A microbiologist (from Greek ) is a scientist who studies microscopic life forms and processes. This includes study of the growth, interactions and characteristics of microscopic organisms such as bacteria, algae, fungi, and some types of par ...
, best known for discovering the world's first broadly effective
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
substance, which he named
penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
. His discovery in 1928 of what was later named
benzylpenicillin Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis, diphtheria, gas gangrene, leptospiro ...
(or penicillin G) from the mould ''
Penicillium rubens ''Penicillium rubens'' is a species of fungus in the genus ''Penicillium'' and was the first species known to produce the antibiotic penicillin. It was first described by Philibert Melchior Joseph Ehi Biourge in 1923. For the discovery of penicil ...
'' has been described as the "single greatest victory ever achieved over disease". For this discovery, he shared the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
in 1945 with
Howard Florey Howard Walter Florey, Baron Florey, (; 24 September 1898 – 21 February 1968) was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Chain and Sir Alexander Fleming for his ro ...
and
Ernst Chain Sir Ernst Boris Chain (19 June 1906 – 12 August 1979) was a German-born British biochemist and co-recipient of the Nobel Prize in Physiology or Medicine for his work on penicillin. Life and career Chain was born in Berlin, the son of Marg ...
. He also discovered the
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
lysozyme Lysozyme (, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside hydrolase ...
from his
nasal discharge Rhinorrhea (American English), also spelled rhinorrhoea or rhinorrhœa (British English), or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is an extremely common condition. It is a common symptom of allergie ...
in 1922, and along with it a bacterium he named ''Micrococcus lysodeikticus'', later renamed '' Micrococcus luteus''. Fleming was
knighted A knight is a person granted an honorary title of a knighthood by a head of state (including the pope) or representative for service to the monarch, the church, or the country, especially in a military capacity. The concept of a knighthood ...
for his scientific achievements in 1944. In 1999, he was named in ''
Time Time is the continuous progression of existence that occurs in an apparently irreversible process, irreversible succession from the past, through the present, and into the future. It is a component quantity of various measurements used to sequ ...
'' magazine's list of the 100 Most Important People of the 20th century. In 2002, he was chosen in the BBC's television poll for determining the ''
100 Greatest Britons ''100 Greatest Britons'' is a television series that was broadcast by the BBC in 2002. It was based on a television poll conducted to determine who the British people at that time considered the greatest Britons in history. The series included i ...
'', and in 2009, he was also voted third "greatest Scot" in an opinion poll conducted by STV, behind only
Robert Burns Robert Burns (25 January 1759 – 21 July 1796), also known familiarly as Rabbie Burns, was a Scottish poet and lyricist. He is widely regarded as the List of national poets, national poet of Scotland and is celebrated worldwide. He is the be ...
and
William Wallace Sir William Wallace (, ; Norman French: ; 23 August 1305) was a Scottish knight who became one of the main leaders during the First War of Scottish Independence. Along with Andrew Moray, Wallace defeated an English army at the Battle of St ...
.


Early life and education

Born on 6 August 1881 at Lochfield farm near
Darvel Darvel (, ) is a town in East Ayrshire, Scotland. It is at the eastern end of the Loudoun, Irvine Valley and is sometimes referred to as "The Lang Toon" (). The town's Latin motto, , means "Not for ourselves, but for others". History Prehis ...
, in
Ayrshire Ayrshire (, ) is a Counties of Scotland, historic county and registration county, in south-west Scotland, located on the shores of the Firth of Clyde. The lieutenancy areas of Scotland, lieutenancy area of Ayrshire and Arran covers the entirety ...
, Scotland, Alexander Fleming was the third of four children of farmer Hugh Fleming and Grace Stirling Morton, the daughter of a neighbouring farmer. Hugh Fleming had four surviving children from his first marriage. He was 59 at the time of his second marriage to Grace, and died when Alexander was seven. Fleming went to
Loudoun Loudoun () is a parish in East Ayrshire, Scotland and lies between five and ten miles east of Kilmarnock. The parish roughly encompasses the northern half of the Upper-Irvine Valley and borders Galston parish, Galston Parish (which encompasses ...
Moor School and Darvel School, and earned a two-year scholarship to
Kilmarnock Academy Kilmarnock Academy (Scottish Gaelic: ''Acadamaidh Chille Mheàrnaig''), formerly Kilmarnock Burgh School, is an 11–17 co-educational state-funded secondary school in Kilmarnock, Scotland, currently serving in its third location on Sutherland D ...
before moving to London, where he attended the
Royal Polytechnic Institution The University of Westminster is a public university based in London, United Kingdom. Founded in 1838 as the Royal Polytechnic Institution, it was the first polytechnic A polytechnic is an educational institution that primarily focuses on vo ...
. After working in a shipping office for four years, the twenty-year-old Alexander Fleming inherited some money from an uncle, John Fleming. His elder brother, Tom, was already a physician and suggested to him that he should follow the same career, and so in 1903, the younger Alexander enrolled at St Mary's Hospital Medical School in
Paddington Paddington is an area in the City of Westminster, in central London, England. A medieval parish then a metropolitan borough of the County of London, it was integrated with Westminster and Greater London in 1965. Paddington station, designed b ...
(now part of
Imperial College London Imperial College London, also known as Imperial, is a Public university, public research university in London, England. Its history began with Prince Albert of Saxe-Coburg and Gotha, Prince Albert, husband of Queen Victoria, who envisioned a Al ...
); he qualified with an
MBBS A Bachelor of Medicine, Bachelor of Surgery (; MBBS, also abbreviated as BM BS, MB ChB, MB BCh, or MB BChir) is a medical degree granted by medical schools or universities in countries that adhere to the United Kingdom's higher education tradi ...
degree from the school with distinction in 1906. Fleming, who was a
private Private or privates may refer to: Music * "In Private", by Dusty Springfield from the 1990 album ''Reputation'' * Private (band), a Denmark-based band * "Private" (Ryōko Hirosue song), from the 1999 album ''Private'', written and also recorded ...
in the
London Scottish Regiment The London Scottish was a Army Reserve (United Kingdom), reserve infantry regiment then a Company (military unit), company of the British Army. In its final incarnation it was A (The London Scottish) Company, the London Regiment (1993), Londo ...
of the
Volunteer Force The Volunteer Force was a citizen army of part-time rifle, artillery and engineer corps, created as a Social movement, popular movement throughout the British Empire in 1859. Originally highly autonomous, the units of volunteers became increa ...
from 1900 to 1914, had been a member of the rifle club at the medical school. The captain of the club, wishing to retain Fleming in the team, suggested that he join the research department at St Mary's, where he became assistant bacteriologist to Sir
Almroth Wright Sir Almroth Edward Wright (10 August 1861 – 30 April 1947) was an English bacteriologist and immunologist. He is notable for developing a system of anti-typhoid fever inoculation, recognizing early on that antibiotics would create resistan ...
, a pioneer in
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
therapy and immunology. In 1908, he gained a BSc degree with gold medal in
bacteriology Bacteriology is the branch and specialty of biology that studies the Morphology (biology), morphology, ecology, genetics and biochemistry of bacteria as well as many other aspects related to them. This subdivision of microbiology involves the iden ...
, and became a lecturer at St Mary's until 1914. Commissioned lieutenant in 1914 and promoted captain in 1917, Fleming served throughout
World War I World War I or the First World War (28 July 1914 – 11 November 1918), also known as the Great War, was a World war, global conflict between two coalitions: the Allies of World War I, Allies (or Entente) and the Central Powers. Fighting to ...
in the
Royal Army Medical Corps The Royal Army Medical Corps (RAMC) was a specialist corps in the British Army which provided medical services to all Army personnel and their families, in war and in peace. On 15 November 2024, the corps was amalgamated with the Royal Army De ...
, and was
Mentioned in Dispatches To be mentioned in dispatches (or despatches) describes a member of the armed forces whose name appears in an official report written by a superior officer and sent to the high command, in which their gallant or meritorious action in the face of t ...
. He and many of his colleagues worked in battlefield hospitals at the Western Front in France. In 1918 he returned to St Mary's Hospital, where he was elected Professor of Bacteriology of the
University of London The University of London (UoL; abbreviated as Lond or more rarely Londin in Post-nominal letters, post-nominals) is a collegiate university, federal Public university, public research university located in London, England, United Kingdom. The ...
in 1928. In 1951 he was elected the Rector of the
University of Edinburgh The University of Edinburgh (, ; abbreviated as ''Edin.'' in Post-nominal letters, post-nominals) is a Public university, public research university based in Edinburgh, Scotland. Founded by the City of Edinburgh Council, town council under th ...
for a term of three years.


Scientific contributions


Antiseptics

During World War I, Fleming with Leonard Colebrook and Sir Almroth Wright joined the war efforts and practically moved the entire Inoculation Department of St Mary's to the British military hospital at
Boulogne-sur-Mer Boulogne-sur-Mer (; ; ; or ''Bononia''), often called just Boulogne (, ), is a coastal city in Hauts-de-France, Northern France. It is a Subprefectures in France, sub-prefecture of the Departments of France, department of Pas-de-Calais. Boul ...
. Serving as a temporary lieutenant of the Royal Army Medical Corps, he witnessed the death of many soldiers from
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
resulting from infected
wound A wound is any disruption of or damage to living tissue, such as skin, mucous membranes, or organs. Wounds can either be the sudden result of direct trauma (mechanical, thermal, chemical), or can develop slowly over time due to underlying diseas ...
s.
Antiseptic An antiseptic ( and ) is an antimicrobial substance or compound that is applied to living tissue to reduce the possibility of sepsis, infection, or putrefaction. Antiseptics are generally distinguished from ''antibiotics'' by the latter's abil ...
s, which were used at the time to treat infected wounds, he observed, often worsened the injuries. In an article published in the medical journal ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...
'' in 1917, he described an ingenious experiment, which he was able to conduct as a result of his own
glassblowing Glassblowing is a glassforming technique that involves inflating molten glass into a bubble (or parison) with the aid of a blowpipe (or blow tube). A person who blows glass is called a ''glassblower'', ''glassmith'', or ''gaffer''. A '' lampworke ...
skills, in which he explained why antiseptics were killing more soldiers than infection itself during the war. Antiseptics worked well on the surface, but deep wounds tended to shelter
anaerobic bacteria An anaerobic organism or anaerobe is any organism that does not require molecular oxygen for growth. It may react negatively or even die if free oxygen is present. In contrast, an aerobic organism (aerobe) is an organism that requires an oxygenat ...
from the antiseptic agent, and antiseptics seemed to remove beneficial agents produced that protected the patients in these cases at least as well as they removed bacteria, and did nothing to remove the bacteria that were out of reach. Wright strongly supported Fleming's findings, but despite this, most army physicians over the course of the war continued to use antiseptics even in cases where this worsened the condition of the patients.


Discovery of lysozyme

At St Mary's Hospital, Fleming continued his investigations into bacteria culture and antibacterial substances. As his research scholar at the time V. D. Allison recalled, Fleming was not a tidy researcher and usually expected unusual bacterial growths in his culture plates. Fleming had teased Allison of his "excessive tidiness in the laboratory", and Allison rightly attributed such untidiness as the success of Fleming's experiments, and said, " fhe had been as tidy as he thought I was, he would not have made his two great discoveries." In late 1921, while Fleming was maintaining agar plates for bacteria, he found that one of the plates was contaminated with bacteria from the air. When he added nasal mucus, he found that the mucus inhibited the bacterial growth. Surrounding the mucus area was a clear transparent circle (1 cm from the mucus), indicating the killing zone of bacteria, followed by a glassy and translucent ring beyond which was an opaque area indicating normal bacterial growth. In the next test, he used bacteria maintained in saline that formed a yellow suspension. Within two minutes of adding fresh mucus, the yellow saline turned completely clear. He extended his tests using tears, which were contributed by his co-workers. As Allison reminisced, saying, "For the next five or six weeks, our tears were the source of supply for this extraordinary phenomenon. Many were the lemons we used (after the failure of onions) to produce a flow of tears... The demand by us for tears was so great, that laboratory attendants were pressed into service, receiving threepence for each contribution." His further tests with sputum, cartilage, blood, semen, ovarian cyst fluid, pus, and egg white showed that the bactericidal agent was present in all of these. He reported his discovery before the Medical Research Club in December and before the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
the next year but failed to stir any interest, as Allison recollected:
I was present at this edical Research Clubmeeting as Fleming's guest. His paper describing his discovery was received with no questions asked and no discussion, which was most unusual and an indication that it was considered to be of no importance. The following year he read a paper on the subject before the Royal Society, Burlington House, Piccadilly and he and I gave a demonstration of our work. Again with one exception little comment or attention was paid to it.
Reporting in the 1 May 1922 issue of the '' Proceedings of the Royal Society B: Biological Sciences'' under the title "On a remarkable bacteriolytic element found in tissues and secretions", Fleming wrote:
In this communication I wish to draw attention to a substance present in the tissues and secretions of the body, which is capable of rapidly dissolving certain bacteria. As this substance has properties akin to those of ferments I have called it a "
Lysozyme Lysozyme (, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside hydrolase ...
", and shall refer to it by this name throughout the communication. The lysozyme was first noticed during some investigations made on a patient suffering from acute coryza.
This was the first recorded discovery of lysozyme. With Allison, he published further studies on lysozyme in October issue of the ''British Journal of Experimental Pathology'' the same year. Although he was able to obtain larger amounts of lysozyme from egg whites, the enzyme was only effective against small counts of harmless bacteria, and therefore had little therapeutic potential. This indicates one of the major differences between
pathogenic In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term ...
and harmless bacteria. Described in the original publication, "a patient suffering from acute coryza" was later identified as Fleming himself. His research notebook dated 21 November 1921 showed a sketch of the culture plate with a small note: "Staphyloid coccus from A.F.'s nose." He also identified the bacterium present in the nasal mucus as ''Micrococcus Lysodeikticus'', giving the species name (meaning "lysis indicator" for its susceptibility to lysozymal activity). The species was reassigned as '' Micrococcus luteus'' in 1972. The "Fleming strain" (NCTC2665) of this bacterium has become a model in different biological studies. The importance of lysozyme was not recognised, and Fleming was well aware of this, in his presidential address at the
Royal Society of Medicine The Royal Society of Medicine (RSM) is a medical society based at 1 Wimpole Street, London, UK. It is a registered charity, with admission through membership. Its Chief Executive is Michele Acton. History The Royal Society of Medicine (R ...
meeting on 18 October 1932, he said:
I choose lysozyme as the subject for this address for two reasons, firstly because I have a fatherly interest in the name, and, secondly, because its importance in connection with natural immunity does not seem to be generally appreciated.
In his Nobel lecture on 11 December 1945, he briefly mentioned lysozyme, saying, "Penicillin was not the first antibiotic I happened to discover." It was only towards the end of the 20th century that the true importance of Fleming's discovery in immunology was realised as lysozyme became the first antimicrobial protein discovered that constitute part of our
innate immunity The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...
.


Discovery of penicillin


Experiment

By 1927, Fleming had been investigating the properties of
staphylococci ''Staphylococcus'', from Ancient Greek σταφυλή (''staphulḗ''), meaning "bunch of grapes", and (''kókkos''), meaning "kernel" or " Kermes", is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillale ...
. He was already well known from his earlier work, and had developed a reputation as a brilliant researcher. In 1928, he studied the variation of ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'' grown under natural condition, after the work of Joseph Warwick Bigger, who discovered that the bacterium could grow into a variety of types (strains). On 3 September 1928, Fleming returned to his laboratory having spent a holiday with his family at Suffolk. Before leaving for his holiday, he inoculated staphylococci on culture plates and left them on a bench in a corner of his laboratory. On his return, Fleming noticed that one culture was contaminated with a fungus, and that the colonies of staphylococci immediately surrounding the fungus had been destroyed, whereas other staphylococci colonies farther away were normal, famously remarking "That's funny". Fleming showed the contaminated culture to his former assistant Merlin Pryce, who reminded him, "That's how you discovered lysozyme." He identified the mould as being from the genus ''
Penicillium ''Penicillium'' () is a genus of Ascomycota, ascomycetous fungus, fungi that is part of the mycobiome of many species and is of major importance in the natural environment, in food spoilage, and in food and drug production. Some members of th ...
.'' He suspected it to be ''P. chrysogenum,'' but a colleague Charles J. La Touche identified it as ''P. rubrum.'' (It was later corrected as ''P. notatum'' and then officially accepted as ''P. chrysogenum''; in 2011, it was resolved as ''P. rubens.'') The laboratory in which Fleming discovered and tested penicillin is preserved as the Alexander Fleming Laboratory Museum in St. Mary's Hospital,
Paddington Paddington is an area in the City of Westminster, in central London, England. A medieval parish then a metropolitan borough of the County of London, it was integrated with Westminster and Greater London in 1965. Paddington station, designed b ...
. The source of the fungal contaminant was established in 1966 as coming from La Touche's room, which was directly below Fleming's. Fleming grew the mould in a pure culture and found that the culture broth contained an antibacterial substance. He investigated its anti-bacterial effect on many organisms, and noticed that it affected bacteria such as staphylococci and many other
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain is ...
pathogens that cause
scarlet fever Scarlet fever, also known as scarlatina, is an infectious disease caused by ''Streptococcus pyogenes'', a Group A streptococcus (GAS). It most commonly affects children between five and 15 years of age. The signs and symptoms include a sore ...
,
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
,
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
and
diphtheria Diphtheria is an infection caused by the bacteria, bacterium ''Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild Course (medicine), clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs a ...
, but not
typhoid fever Typhoid fever, also known simply as typhoid, is a disease caused by '' Salmonella enterica'' serotype Typhi bacteria, also called ''Salmonella'' Typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often th ...
or
paratyphoid fever Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of three types of '' Salmonella enterica''. Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever. Often, a gradu ...
, which are caused by
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
bacteria, for which he was seeking a cure at the time. It also affected ''
Neisseria gonorrhoeae ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular) or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria first isolated by Albert Ludwig Sigesmund Neisser, Albert Neisser in 1879. An obligate human pathog ...
,'' which causes gonorrhoea, although this bacterium is Gram-negative. After some months of calling it "mould juice" or "the inhibitor", he gave the name
penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
on 7 March 1929 for the antibacterial substance present in the mould.


Reception and publication

Fleming presented his discovery on 13 February 1929 before the Medical Research Club. His talk on "A medium for the isolation of Pfeiffer's bacillus" did not receive any particular attention or comment. Henry Dale, the then Director of
National Institute for Medical Research The National Institute for Medical Research (NIMR), was a medical research institute based in Mill Hill, on the outskirts of north London, England. It was funded by the Medical Research Council (MRC); In 2016, the NIMR became part of the new F ...
and chair of the meeting, much later reminisced that he did not even sense any striking point of importance in Fleming's speech. Fleming published his discovery in 1929 in the ''British Journal of Experimental Pathology,'' but little attention was paid to the article. His problem was the difficulty of producing penicillin in large amounts, and moreover, isolation of the main compound. Even with the help of Harold Raistrick and his team of biochemists at the
London School of Hygiene & Tropical Medicine The London School of Hygiene & Tropical Medicine (LSHTM) is a public research university in Bloomsbury, central London, and a member institution of the University of London that specialises in public health and tropical medicine. The institu ...
, chemical purification was futile. "As a result, penicillin languished largely forgotten in the 1930s", as
Milton Wainwright Milton Wainwright (born 23 February 1950) is a British microbiologist who is known for his research into what he claims could be extraterrestrial life found in the stratosphere. Biography Wainwright graduated from the University of Nottingham i ...
described. As late as in 1936, there was no appreciation for penicillin. When Fleming talked of its medical importance at the Second International Congress of Microbiology held in London, no one believed him. As Allison, his companion in both the Medical Research Club and international congress meeting, remarked the two occasions:
leming at the Medical Research Club meetingsuggested the possible value of penicillin for the treatment of infection in man. Again there was a total lack of interest and no discussion. Fleming was keenly disappointed, but worse was to follow. He read a paper on his work on penicillin at a meeting of the International Congress of Microbiology, attended by the foremost bacteriologists from all over the world. There was no support for his views on its possible future value for the prevention and treatment of human infections and discussion was minimal. Fleming bore these disappointments stoically, but they did not alter his views or deter him from continuing his investigation of penicillin.
In 1941, the ''
British Medical Journal ''The BMJ'' is a fortnightly peer-reviewed medical journal, published by BMJ Publishing Group Ltd, which in turn is wholly-owned by the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world ...
'' reported that " enicillindoes not appear to have been considered as possibly useful from any other point of view."


Purification and stabilisation

In Oxford,
Ernst Chain Sir Ernst Boris Chain (19 June 1906 – 12 August 1979) was a German-born British biochemist and co-recipient of the Nobel Prize in Physiology or Medicine for his work on penicillin. Life and career Chain was born in Berlin, the son of Marg ...
and
Edward Abraham Sir Edward Penley Abraham, (10 June 1913 – 8 May 1999) was an English biochemist instrumental in the development of the first antibiotics penicillin and cephalosporin. Early life and education Abraham was born on 10 June 1913 at 47 South V ...
were studying the molecular structure of the antibiotic. Abraham was the first to propose the correct structure of penicillin. Shortly after the team published its first results in 1940, Fleming telephoned
Howard Florey Howard Walter Florey, Baron Florey, (; 24 September 1898 – 21 February 1968) was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Chain and Sir Alexander Fleming for his ro ...
, Chain's head of department, to say that he would be visiting within the next few days. When Chain heard that Fleming was coming, he remarked "Good God! I thought he was dead." Norman Heatley suggested transferring the active ingredient of penicillin back into water by changing its acidity. This produced enough of the drug to begin testing on animals. There were many more people involved in the Oxford team, and at one point the entire
Sir William Dunn School of Pathology The Sir William Dunn School of Pathology is a department within the University of Oxford. Its research programme includes the cellular and molecular biology of pathogens, the immune response, cancer and cardiovascular disease. It teaches undergr ...
was involved in its production. After the team had developed a method of purifying penicillin to an effective first stable form in 1940, several clinical trials ensued, and their amazing success inspired the team to develop methods for mass production and mass distribution in 1945. Fleming was modest about his part in the development of penicillin, describing his fame as the "Fleming Myth" and he praised Florey and Chain for transforming the laboratory curiosity into a practical drug. Fleming was the first to discover the properties of the active substance, giving him the privilege of naming it: penicillin. He also kept, grew, and distributed the original mould for twelve years, and continued until 1940 to try to get help from any chemist who had enough skill to make penicillin. Sir Henry Harris summed up the process in 1998 as: "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin." The discovery of penicillin and its subsequent development as a prescription drug mark the start of modern
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
.


Medical use and mass production

In his first clinical trial, Fleming treated his research scholar Stuart Craddock who had developed severe infection of the nasal antrum (
sinusitis Sinusitis, also known as rhinosinusitis, is an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure ...
). The treatment started on 9 January 1929 but without any effect. It probably was due to the fact that the infection was with influenza bacillus (''Haemophilus influenzae''), the bacterium which he had found unsusceptible to penicillin. Fleming gave some of his original penicillin samples to his colleague-surgeon Arthur Dickson Wright for clinical test in 1928. Although Wright reportedly said that it "seemed to work satisfactorily", there are no records of its specific use. Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield and former student of Fleming, was the first to use penicillin successfully for medical treatment. He cured eye infections (
conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...
) of one adult and three infants (
neonatal conjunctivitis Neonatal conjunctivitis is a form of conjunctivitis (inflammation of the outer eye) which affects newborn babies following birth. It is typically due to neonatal bacterial infection, although it can also be non-infectious (e.g. chemical exposure) ...
) on 25 November 1930. Fleming also successfully treated severe conjunctivitis in 1932. Keith Bernard Rogers, who had joined St Mary's as medical student in 1929, was captain of the London University rifle team and was about to participate in an inter-hospital rifle shooting competition when he developed conjunctivitis. Fleming applied his penicillin and cured Rogers before the competition. It is said that the "penicillin worked and the match was won." However, the report that "Keith was probably the first patient to be treated clinically with penicillin ointment" is no longer true as Paine's medical records showed up. There is a popular assertion both in popular and scientific literature that Fleming largely abandoned penicillin work in the early 1930s. In his review of André Maurois's ''The Life of Sir Alexander Fleming, Discoverer of Penicillin,'' William L. Kissick went so far as to say that "Fleming had abandoned penicillin in 1932... Although the recipient of many honors and the author of much scientific work, Sir Alexander Fleming does not appear to be an ideal subject for a biography." This is false, as Fleming continued to pursue penicillin research. As late as in 1939, Fleming's notebook shows attempts to make better penicillin production using different media. In 1941, he published a method for assessment of penicillin effectiveness. As to the chemical isolation and purification,
Howard Florey Howard Walter Florey, Baron Florey, (; 24 September 1898 – 21 February 1968) was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Chain and Sir Alexander Fleming for his ro ...
and
Ernst Chain Sir Ernst Boris Chain (19 June 1906 – 12 August 1979) was a German-born British biochemist and co-recipient of the Nobel Prize in Physiology or Medicine for his work on penicillin. Life and career Chain was born in Berlin, the son of Marg ...
at the
Radcliffe Infirmary The Radcliffe Infirmary was a hospital in central north Oxford, England, located at the southern end of Woodstock Road on the western side, backing onto Walton Street. Closed in 2007, after refurbishment the building was re-opened in October ...
in Oxford took up the research to mass-produce it, which they achieved with support from World War II military projects under the British and US governments. By mid-1942, the Oxford team produced the pure penicillin compound as yellow powder. In August 1942, Harry Lambert (an associate of Fleming's brother Robert) was admitted to St Mary's Hospital due to a life-threatening infection of the nervous system (streptococcal
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
). Fleming treated him with sulphonamides, but Lambert's condition deteriorated. He tested the antibiotic susceptibility and found that his penicillin could kill the bacteria. He requested Florey for the isolated sample. Florey sent the incompletely purified sample, which Fleming immediately administered into Lambert's
spinal canal In human anatomy, the spinal canal, vertebral canal or spinal cavity is an elongated body cavity enclosed within the dorsal bony arches of the vertebral column, which contains the spinal cord, spinal roots and dorsal root ganglia. It is a pro ...
. Lambert showed signs of improvement the very next day, and completely recovered within a week. Fleming published the clinical case in ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...
'' in 1943. Upon this medical breakthrough, Allison informed the British Ministry of Health of the importance of penicillin and the need for mass production. The War Cabinet was convinced of the usefulness upon which Sir
Cecil Weir Cecil James Mullo Weir (4 December 1897 – 4 March 1995) was a Scottish academic and theologian, who was Professor of Hebrew and Semitic Languages, Glasgow, Professor of Hebrew and Semitic Languages at the University of Glasgow from 1937 until ...
, Director General of Equipment, called for a meeting on the mode of action on 28 September 1942. The Penicillin Committee was created on 5 April 1943. The committee consisted of Weir as chairman, Fleming, Florey, Sir Percival Hartley, Allison and representatives from pharmaceutical companies as members. The main goals were to produce penicillin rapidly in large quantities with collaboration of American companies, and to supply the drug exclusively for Allied armed forces. By
D-Day The Normandy landings were the landing operations and associated airborne operations on 6 June 1944 of the Allied invasion of Normandy in Operation Overlord during the Second World War. Codenamed Operation Neptune and often referred to as ...
in 1944, enough penicillin had been produced to treat all the wounded of the Allied troops.


Antibiotic resistance

Fleming also discovered very early that bacteria developed
antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...
whenever too little penicillin was used or when it was used for too short a period. Almroth Wright had predicted antibiotic resistance even before it was noticed during experiments. Fleming cautioned about the use of penicillin in his many speeches around the world. On 26 June 1945, he made the following cautionary statements: "the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out ... In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted." He cautioned not to use penicillin unless there was a properly diagnosed reason for it to be used, and that if it were used, never to use too little, or for too short a period, since these are the circumstances under which bacterial resistance to antibiotics develops. It had been experimentally shown in 1942 that ''S. aureu''s could develop penicillin resistance under prolonged exposure. Elaborating the possibility of penicillin resistance in clinical conditions in his Nobel Lecture, Fleming said:
The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.
It was around that time that the first clinical case of penicillin resistance was reported.


Personal life

On 24 December 1915, Fleming married a trained nurse, Sarah Marion McElroy of
Killala Killala () is a village in County Mayo in Ireland, north of Ballina. The railway line from Dublin to Ballina once extended to Killala. To the west of Killala is the townland of Townsplots West (known locally as Enagh Beg), which contains a num ...
, County Mayo, Ireland. Their only child, Robert Fleming (1924–2015), became a general medical practitioner. After his first wife's death in 1949, Fleming married Amalia Koutsouri-Vourekas, a
Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...
colleague at St. Mary's, on 9 April 1953; she died in 1986. Fleming came from a
Presbyterian Presbyterianism is a historically Reformed Protestant tradition named for its form of church government by representative assemblies of elders, known as "presbyters". Though other Reformed churches are structurally similar, the word ''Pr ...
background, while his first wife Sarah was a (lapsed) Roman Catholic. It is said that he was not particularly religious, and their son Robert was later received into the
Anglican church Anglicanism, also known as Episcopalianism in some countries, is a Western Christianity, Western Christian tradition which developed from the practices, liturgy, and identity of the Church of England following the English Reformation, in the ...
, while still reportedly inheriting his two parents' fairly irreligious disposition. When Fleming learned of Robert D. Coghill and Andrew J. Moyer patenting the method of penicillin production in the United States in 1944, he was furious, and commented:
I found penicillin and have given it free for the benefit of humanity. Why should it become a profit-making monopoly of manufacturers in another country?
From 1921 until his death in 1955, Fleming owned a country home named "The Dhoon" in Barton Mills, Suffolk.


Death

On 11 March 1955, Fleming died at his home in London of a heart attack. His ashes are buried in
St Paul's Cathedral St Paul's Cathedral, formally the Cathedral Church of St Paul the Apostle, is an Anglican cathedral in London, England, the seat of the Bishop of London. The cathedral serves as the mother church of the Diocese of London in the Church of Engl ...
.


Awards and legacy

Fleming's discovery of penicillin changed the world of modern medicine by introducing the age of useful
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s; penicillin has saved, and is still saving, millions of people around the world. The laboratory at St Mary's Hospital where Fleming discovered penicillin is home to the Fleming Museum, a popular London attraction. His alma mater, St Mary's Hospital Medical School, merged with
Imperial College London Imperial College London, also known as Imperial, is a Public university, public research university in London, England. Its history began with Prince Albert of Saxe-Coburg and Gotha, Prince Albert, husband of Queen Victoria, who envisioned a Al ...
in 1988. The ''Sir Alexander Fleming Building'' on the
South Kensington South Kensington is a district at the West End of Central London in the Royal Borough of Kensington and Chelsea. Historically it settled on part of the scattered Middlesex village of Brompton. Its name was supplanted with the advent of the ra ...
campus was opened in 1998, where his son Robert and his great-granddaughter Claire were presented to the Queen; it is now one of the main preclinical teaching sites of the
Imperial College School of Medicine Imperial College School of Medicine (ICSM) is the undergraduate medical school of Imperial College London in England and one of the United Hospitals. It is part of the college's Imperial College Faculty of Medicine, Faculty of Medicine and was ...
. His other alma mater, the Royal Polytechnic Institution (now the
University of Westminster The University of Westminster is a public university, public university based in London, United Kingdom. Founded in 1838 as the Royal Polytechnic Institution, it was the first Polytechnic (United Kingdom), polytechnic to open in London. The Po ...
) has named one of its student halls of residence ''Alexander Fleming House'', which is near to Old Street.


Myths


The Fleming myth

By 1942, penicillin, produced as pure compound, was still in short supply and not available for clinical use. When Fleming used the first few samples prepared by the Oxford team to treat Harry Lambert who had streptococcal meningitis, the successful treatment was major news, particularly popularised in ''
The Times ''The Times'' is a British Newspaper#Daily, daily Newspaper#National, national newspaper based in London. It began in 1785 under the title ''The Daily Universal Register'', adopting its modern name on 1 January 1788. ''The Times'' and its si ...
''. Wright was surprised to discover that Fleming and the Oxford team had not been mentioned, though Oxford was attributed as the source of the drug. Wright wrote to the editor of ''The Times'', which eagerly interviewed Fleming, but Florey prohibited the Oxford team from seeking media coverage. As a consequence, only Fleming was widely publicised in the media, which led to the misconception that he was entirely responsible for the discovery and development of the drug. Fleming himself referred to this incident as "the Fleming myth."


The Churchills

The popular story of Winston Churchill's father paying for Fleming's education after Fleming's father saved young Winston from death is false. According to the biography, ''Penicillin Man: Alexander Fleming and the Antibiotic Revolution'' by Kevin Brown, Alexander Fleming, in a letter to his friend and colleague Andre Gratia, described this as "A wondrous fable." Nor did he save Winston Churchill himself during
World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...
. Churchill was saved by Lord Moran, using sulphonamides, since he had no experience with penicillin, when Churchill fell ill in
Carthage Carthage was an ancient city in Northern Africa, on the eastern side of the Lake of Tunis in what is now Tunisia. Carthage was one of the most important trading hubs of the Ancient Mediterranean and one of the most affluent cities of the classic ...
in Tunisia in 1943. ''
The Daily Telegraph ''The Daily Telegraph'', known online and elsewhere as ''The Telegraph'', is a British daily broadsheet conservative newspaper published in London by Telegraph Media Group and distributed in the United Kingdom and internationally. It was found ...
'' and ''
The Morning Post ''The Morning Post'' was a conservative daily newspaper published in London from 1772 to 1937, when it was acquired by ''The Daily Telegraph''. History The paper was founded by John Bell. According to historian Robert Darnton, ''The Morning ...
'' on 21 December 1943 wrote that he had been saved by penicillin. He was saved by the new sulphonamide drug sulphapyridine, known at the time under the research code M&B 693, discovered and produced by May & Baker Ltd,
Dagenham Dagenham () is a town in East London, England, within the London Borough of Barking and Dagenham. Dagenham is centred east of Charing Cross. It was historically a rural parish in the Becontree Hundred of Essex, stretching from Hainault Fo ...
, Essex – a subsidiary of the French group Rhône-Poulenc. In a subsequent radio broadcast, Churchill referred to the new drug as "This admirable M&B".''A History of May & Baker 1834–1984'', Alden Press 1984.


See also

* Fleming Prize Lecture * People on Scottish banknotes


References


Further reading


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


External links


Alexander Fleming Obituary
* including the Nobel Lecture, 11 December 1945 ''Penicillin''
Some places and memories related to Alexander Fleming
* {{DEFAULTSORT:Fleming, Alexander 1881 births 1955 deaths Military personnel from East Ayrshire People from Darvel People educated at Kilmarnock Academy 20th-century British biologists British Army personnel of World War I Alumni of Imperial College London Alumni of the University of Westminster Academics of Imperial College London Academics of the University of London Burials at St Paul's Cathedral Honorary Fellows of the Royal Society of Edinburgh Fellows of the Royal Society Fellows of the Royal College of Physicians of Edinburgh Fellows of the Royal College of Physicians Fellows of the Royal College of Surgeons of England Members of the Pontifical Academy of Sciences Knights Bachelor Nobel laureates in Physiology or Medicine Recipients of the Civil Order of Alfonso X, the Wise Rectors of the University of Edinburgh Royal Army Medical Corps officers Scottish bacteriologists 20th-century Scottish biologists Scottish inventors Scottish knights 20th-century Scottish medical doctors Scottish microbiologists Scottish Nobel laureates British Nobel laureates Scottish pharmacologists London Scottish soldiers Territorial Force soldiers Scottish surgeons Alumni of St Mary's Hospital Medical School People from Forest Heath (district) Physicians of Guy's Hospital Physicians of St Mary's Hospital, London