Alexander Fleming

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Sir Alexander Fleming (7 August 1881 – 11 March 1955) was a Scottish biologist and pharmacologist. He discovered the enzyme lysozyme in 1922, and in 1928 isolated the antibiotic substance penicillin from the fungus Penicillium notatum, for which he shared a Nobel Prize with Howard Florey and Ernst Chain.[1]

Birth and education

Alexander Fleming was born on a farm at Lochfield near Darvel in East Ayrshire, went to the local school, and then for two years at the Kilmarnock Academy. In 1901 he enrolled at St Mary's Hospital, London, qualifying with distinction in 1906. By chance, he had been a member of the rifle club; 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. He gained M.B. and then B.Sc. with Gold Medal in 1908, and became a lecturer at St. Mary's until 1914. He served throughout World War I as a captain in the Army Medical Corps, and was mentioned in dispatches. He worked in battlefield hospitals at the Western Front in France. In 1918 he returned to St.Mary's Hospital, which was a teaching hospital, and was elected Professor of Bacteriology there in 1928.

Work before penicillin

After the war, Fleming searched for anti-bacterial agents having witnessed the death of many soldiers from septicemia resulting from infected wounds. Unfortunately antiseptics killed the patient's immunological defences more effectively than they killed the invading bacteria. In an article he submitted to the medical journal The Lancet during World War I, Fleming described an ingenious experiment, which he was able to conduct as a result of his own glass blowing skills, in which he explained why antiseptics were actually killing more soldiers than infection itself. 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. Sir Almroth Wright strongly supported Fleming's findings, but despite this, most army physicians over the course of World War I continued to use antiseptics even in cases where this worsened the condition of the patients.

In 1922, Fleming discovered lysozyme, the "body's own antibiotic", and that it has a weak anti-bacterial property.[2][3]

Accidental discovery

See also: Discovery of penicillin

Fleming was the first to notice the antibiotic properties of molds and fungi.

By 1928, he was investigating the properties of staphylococci. He had developed a reputation as a brilliant researcher, but a quite careless lab technician; cultures that he worked on he often forgot, and his lab in general was usually in chaos. After returning from a long holiday, Fleming noticed that many of his culture dishes were contaminated with a fungus and he threw the dishes in disinfectant. But on one occasion, he had to show a visitor what he had been researching, and so he retrieved some of the unsubmerged dishes that he would have otherwise discarded; he then noticed a zone around an invading fungus where the bacteria could not seem to grow. Fleming proceeded to isolate an extract from the mould, correctly identified it as being from the penicillium family, and therefore named it penicillin.

He investigated its positive anti-bacterial effect on many organisms, and noticed that it affected bacteria such as staphylococci, and indeed all Gram-positive pathogens (scarlet fever, pneumonia, gonorrhea, meningitis, diphtheria ) but unfortunately not typhoid or paratyphoid, for which he was seeking a cure at the time.

Fleming published his discovery in 1929 in the British Journal of Experimental Pathology, but little attention was paid to his article. Fleming continued his investigations, but found that cultivating penicillium was quite difficult, and that after having grown the mould, it was even more difficult to isolate the antibiotic agent. Fleming's impression was that because of the problem of producing it in quantity, and because its action appeared to be rather slow, penicillin would not be important in treating infection. Fleming also became convinced that penicillin would not last long enough in the human body (in vivo) to kill bacteria effectively. Many clinical tests were inconclusive, probably because it had been used as a surface antiseptic. In the 1930s, Fleming’s trials occasionally showed more promise,[4] and he continued, until 1940, to try and interest a chemist skilled enough to further refine usable penicillin.

Purification to a stable form and industrial scale production

Ernst Chain worked out how to isolate and concentrate penicillin. He also correctly theorized the structure of penicillin. Shortly after the team published its first results in 1940, Fleming telephoned Florey, Chain's head of department to say that he would be visiting within the next few days. When Chain heard that he 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.

Sir Henry Harris said in 1998: "Without Fleming, no Chain or Florey; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin."

There were many more people involved in the Oxford team, and at one point the entire Dunn School 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 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 isolate the active substance, giving him the privilege of naming it. He also kept, grew and distributed the original mould for twelve years, and continued until 1940 to try to get help from any chemist that had enough skill to make a stable form of it for mass production. There were many failed attempts around Fleming towards stabilising the substance before Florey organized his large and very skilled biochemical research team in 1938 at Oxford to undertake the immense and innovative work that had to be done to produce a stable 'mass produce-able' penicillin.

Antibiotics

Fleming's accidental discovery and isolation of penicillin in September 1928 marks the start of modern antibiotics.

Fleming also discovered very early that bacteria developed antibiotic resistance whenever too little penicillin was used or when it was used for too short a period of time. Almroth Wright had predicted the antibiotic resistance even before it was noticed during experiments. Fleming cautioned about the use of penicillin in his many speeches around the world. 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 antibiotic resistance in bacteria develop.

Accolades

  • Fleming, Florey, and Chain jointly received the Nobel Prize in Medicine in 1945. According to the rules of the Nobel committee a maximum of three people may share the prize.
  • Fleming was knighted in 1944.
  • Florey received the greater honour of a peerage for his monumental work in making penicillin available to the public and saving millions of lives in World War II, becoming a Baron.
  • The discovery of penicillin was ranked as the most important discovery of the millennium when the year 2000 was approaching by at least 3 large Swedish magazines.[5] It is impossible to know how many lives have been saved by this discovery, but some of these magazines placed their estimate near 200 million lives.
  • Kevin Brown's biography contains a list with hundreds of prizes and honours given to Fleming.

Other information

In 1915, Fleming married Sarah Marion McElroy of Killala, Ireland, who died in 1949. Their son became a general medical practitioner. Fleming married Dr Amalia Koutsouri-Voureka, a Greek colleague at St. Mary's in 1953.

Fleming was long a member of the Chelsea Arts Club, a private club for artists of all genres, founded in 1891 at the suggestion of the painter James McNeil Whistler. Fleming was admitted to the club after he made "germ paintings," in which he drew with a culture loop using spores of highly pigmented bacteria. The bacteria were invisible while he painted, but when cultured made bright colours.

Fable

The popular story of Winston Churchill's father's paying for Fleming's education after Fleming's father saved young Winston's life is false. Nor did he save Winston Churchill during WWII. Churchill was saved by Lord Moran, using sulphonamides when Churchill fell ill in Carthage in Tunisia in 1943. The Daily Telegraph and The Morning Post both reported, on 21 December 1943, that he had been saved by penicillin; as sulphonamide was a German discovery, it may be that patriotic pride had some part in this misreporting.

Death

Fleming died in 1955 of a heart attack in London. His discovery of penicillin had changed modern medicine by introducing the age of antibiotics; penicillin has saved hundreds of millions and is still saving millions of people today. His widow presented his Nobel Prize medal to the Savage Club (a London Gentlemen's club), where Fleming was a member. The Medal is still displayed among the Club's artifacts.

References

  1. Sir Alexander Fleming – Biography, Nobel, 1945-12-11.
  2. Fleming A (1922) On a remarkable bacteriolytic substance found in secretions and tissues Proc Roy Soc B 93:306
  3. Fleming A (1922) Observations on a bacteriolytic substance (Lysozyme) found in secretions and tissues Brit J Exp Path 3:252
  4. Keith Bernard Rogers, who worked with Fleming, was treated with penicillin during their research.
  5. Greatest Hero of the Millennium, Ny Teknik, 1999-12-16.