Sir Alexander Fleming, Nobel Prize in Physiology or Medicine, 1945

SIR ALEXANDER FLEMING (1881-1955)

Scottish biologist, pharmacologist and botanist. His best-known discoveries are the enzyme lysozyme in 1923 and the antibiotic substance benzylpenicillin (Penicillin G) from the mould Penicillium notatum in 1928, for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain

Sir Alexander Fleming is the first cousin, twice removed, of Margaret Strang Craig Gilmour the wife of James Coats Reid of Wester Kittochside (1908-1988). A drop-line pedigree chart for the Fleming family and their Gilmour cousins was among the personal possessions she left behind when she gifted Wester Kittochside Farm to the National Trust for Scotland. The name of the researcher who drew-up this chart is not known but it seems reasonable to give the author credit for this work by highlighting Sir Alec's relationship with Margaret Strang Craig Gilmour, Mrs. James Coats Reid of Wester Kittochside.

Sir Alexander Fleming was born on 6 August 1881 at Lochfield Farm, near Darvel in Ayrshire, Scotland, the third of the four children of Hugh Fleming (1816–1888), from his second marriage to Grace Stirling Morton (1848–1928). Hugh Fleming had four surviving children from his first marriage. He was 59 at the time of his second marriage, and died when Alexander (known as Alec) was seven [https://en.wikipedia.org/wiki/Alexander_FlemingWikipedia: Alexander Fleming]

He was a Scottish biologist and pharmacologist. He wrote many articles on bacteriology, immunology and chemotherapy. His best-known discoveries are the discovery of the enzyme lysozyme in 1923 and the antibiotic substance penicillin from the mold Penicillium notatum in 1928, for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Chain.

In 1999, Time Magazine named Fleming one of the 100 Most Important People of the 20th Century for his discovery of penicillin, and stated: It was a discovery that would change the course of history. The active ingredient in that mould, which Fleming named penicillin, turned out to be an infection-fighting agent of enormous potency. When it was finally recognised for what it was, the most efficacious life-saving drug in the world, penicillin would alter forever the treatment of bacterial infections. By the middle of the century, Fleming's discovery had spawned a huge pharmaceutical industry, churning out synthetic penicillins that would conquer some of mankind's most ancient scourges, including syphilis, gangrene and tuberculosis.

Fleming went to Louden Moor School and Darvel School, and though the two before were modest schools at best, 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 Fleming inherited some money from an uncle, John Fleming. His elder brother, Tom, was already a physician and suggested to his younger sibling that he follow the same career, and so in 1903, the younger Alexander enrolled at St Mary's Hospital, Paddington, London. He qualified for the school with distinction in 1906 and had the option of becoming a surgeon.

By chance, however, he had been a member of the rifle club (he had been an active member of the Volunteer Force since 1900). 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 an M.B. and then a B.Sc. with Gold Medal in 1908, and became a lecturer at St. Mary's until 1914. On 23 December 1915, Fleming married a trained nurse, Sarah Marion McElroy of Killala, County Mayo, Ireland.

Fleming served throughout World War I as a captain 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, which was a teaching hospital. He was elected Professor of Bacteriology in 1928.

After the war Fleming actively searched for anti-bacterial agents, having witnessed the deaths of many soldiers from septicemia resulting from infected wounds. Antiseptics killed the patients' immunological defences more effectively than they killed the invading bacteria. In an article he submitted for 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 killing more soldiers than infection itself during World War I. 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 the war continued to use antiseptics even in cases where this worsened the condition of the patients.

By 1928, Fleming was investigating the properties of staphylococci. He was already well-known from his earlier work, and had developed a reputation as a brilliant researcher, but his laboratory was often untidy. On 3 September 1928, Fleming returned to his laboratory having spent August on holiday with his family. Before leaving he had stacked all his cultures of staphylococci on a bench in a corner of his laboratory. On returning, Fleming noticed that one culture was contaminated with a fungus, and that the colonies of staphylococci that had immediately surrounded it had been destroyed, whereas other colonies further away were normal. Fleming showed the contaminated culture to his former assistant Merlin Price who said "That's how you discovered lysozyme." Fleming identified the mould that had contaminated his culture plates as being from the Penicillium genus, and, after some months of calling it "mould juice" named the substance it released penicillin on 7 March 1929.

He investigated its positive 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.

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, and he continued, until 1940, to try to interest a chemist skilled enough to further refine usable penicillin.

Fleming finally abandoned penicillin, and not long after Florey and Chain Ernst Chain worked out how to isolate and concentrate penicillin. He also correctly theorised the structure of penicillin. Shortly after the team published its first results in 1940, Fleming telephoned Howard 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. 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 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 said in 1998: "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin." 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. 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. 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.

The popular story of Winston Churchill's father's 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. Churchill was saved by Lord Moran, using sulphonamides, since he had no experience with penicillin, when Churchill fell ill in Carthage in Tunisia in 1943. The Daily Telegraph and the Morning Post 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, 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." It is highly probable that the correct information about the sulphonamide did not reach the newspapers because, since this drug had been a discovery by the German laboratory Bayer and Britain was at war with Germany at the time, it was thought better to raise British morale by associating Churchill's cure with the British discovery, penicillin.

Fleming married twice. He was married first to Sarah Marion McElroy of Killala, Ireland, in 1915, and they had one son, Robert Fleming, who is a general medical practitioner. Sarah Marion McElroy died in 1949 and on 9 April 1953 Fleming married Dr. Amalia Koutsouri-Vourekas, a Greek colleague at St.Mary's. She died in 1986 [ Dr. Amalia Koutsouri-Vourekas ]. Sir Alexander Fleming died of a heart attack in 1955. He was cremated and his ashes were interred in St Paul's Cathedral one week later.

Project note: Fleming was a Freemason and a member of London Scottish Rifles Lodge No. 2310.

Other References

• Biographical index of former fellows of the Royal Society of Edinburgh, 1783-2002, pt. 1. A-J, page 317
• Hogg, Bruce; Freemasons and the Royal Society ed 2; Library and Museum of Freemasonry; January 2012; page 43
• "Alexander (Sir) Fleming", Munk's Roll, Royal College of Physicians of London

https://www.familysearch.org/tree/person/details/L8G7-LHW