Alexander Fleming

Sir Alexander Fleming was a Scottish physician and microbiologist. He shared the 1945 Nobel Prize in Physiology or Medicine with Howard Florey and Ernst Chain "for the discovery of penicillin and its curative effect in various infectious diseases".
This was the first antibiotic substance discovered. His discovery in 1928 of what was later named benzylpenicillin from the mould Penicillium rubens has been described as the "single greatest victory ever achieved over disease".
He also discovered the enzyme lysozyme from his nasal discharge in 1922, and along with it a bacterium he named Micrococcus lysodeikticus, later renamed Micrococcus luteus.
Fleming was knighted for his scientific achievements in 1944. In 1999, he was named in Time magazine's list of the 100 Most Important People of the 20th century. In 2002, he was included in the BBC's television poll of the 100 Greatest Britons, and in 2009, he was also voted third "greatest Scot" in an opinion poll conducted by STV, behind only Robert Burns and William Wallace.

Early life and education

Born on 6 August 1881 at Lochfield farm near Darvel, in Ayrshire, 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 Moor School and Darvel School, and earned a two-year scholarship to Kilmarnock Academy before moving to London, where he attended the Royal Polytechnic Institution. 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 ; he qualified with an MBBS degree from the school with distinction in 1906.
Fleming, who was a private in the London Scottish Regiment of the Volunteer Force 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, a pioneer in vaccine therapy and immunology. In 1908, he gained a BSc degree with gold medal in bacteriology, 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 in the Royal Army Medical Corps, and was Mentioned in Dispatches. 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 in 1928.

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. Serving as a temporary lieutenant of the Royal Army Medical Corps, he witnessed the death of many soldiers from sepsis resulting from infected wounds. Antiseptics, 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 in 1917, he described an ingenious experiment, which he was able to conduct as a result of his own glassblowing 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 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, " he 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, 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 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 next year but failed to stir any interest, as Allison recollected:

I was present at this meeting 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", 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 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. The species was reassigned as Micrococcus luteus in 1972. The "Fleming strain" 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 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.

Discovery of penicillin

Experiment

By 1927, Fleming had been investigating the properties of staphylococci. 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 grown under natural condition, after the work of Joseph Warwick Bigger, who discovered that the bacterium could grow into a variety of types. 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. He suspected it to be P. chrysogenum, but a colleague Charles J. La Touche identified it as P. rubrum.
The laboratory in which Fleming discovered and tested penicillin is preserved as the Alexander Fleming Laboratory Museum in St. Mary's Hospital, Paddington. 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 pathogens that cause scarlet fever, pneumonia, meningitis and diphtheria, but not typhoid fever or paratyphoid fever, which are caused by Gram-negative bacteria, for which he was seeking a cure at the time. It also affected Neisseria gonorrhoeae, 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 on 7 March 1929 for the antibacterial substance present in the mould.