Alexander Fleming

Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician and microbiologist. He shared the 1945 Nobel Prize in Physiology or Medicine…

Sir Alexander Fleming (6 August 1881 – 11 March 1955), a distinguished Scottish physician and microbiologist, was a co-recipient of the 1945 Nobel Prize in Physiology or Medicine. He shared this prestigious award with Howard Florey and Ernst Chain for their seminal contributions to "the discovery of penicillin and its curative effect in various infectious diseases." This substance represented the inaugural antibiotic ever identified. His 1928 discovery of what was subsequently named benzylpenicillin (or penicillin G), isolated from the mold Penicillium rubens, has been lauded as the "single greatest victory ever achieved over disease."

Sir Alexander Fleming (6 August 1881 – 11 March 1955) 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 (or penicillin G) from the mould Penicillium rubens has been described as the "single greatest victory ever achieved over disease".

In 1922, he also identified the enzyme lysozyme, isolated from his own nasal discharge. Concurrently, he named an associated bacterium Micrococcus lysodeikticus, which was subsequently reclassified as Micrococcus luteus.

Fleming was knighted in 1944 for his profound scientific achievements. His legacy was further acknowledged in 1999 when Time magazine listed him among the 100 Most Important People of the 20th Century. In 2002, he was included in the BBC's television poll, "100 Greatest Britons," and by 2009, an STV opinion poll recognized him as the third "greatest Scot," surpassed only by Robert Burns and William Wallace.

Early Life and Education

Alexander Fleming was born on 6 August 1881, at Lochfield farm near Darvel, Ayrshire, Scotland. He was the third of four children born to farmer Hugh Fleming and Grace Stirling Morton, the daughter of a neighboring farmer. Hugh Fleming had four surviving children from his initial marriage. He was 59 years old at the time of his second marriage to Grace and died when Alexander was seven.

Fleming attended Loudoun Moor School and Darvel School, subsequently earning a two-year scholarship to Kilmarnock Academy. He then moved to London, where he enrolled at the Royal Polytechnic Institution. After four years of working in a shipping office, the twenty-year-old Alexander Fleming inherited funds from his uncle, John Fleming. His elder brother, Tom, already a physician, suggested he pursue a similar career path. Thus, in 1903, Alexander matriculated at St Mary's Hospital Medical School in Paddington (now part of Imperial College London), from which he graduated with an MBBS degree with distinction in 1906.

From 1900 to 1914, Fleming served as a private in the London Scottish Regiment of the Volunteer Force and was an active member of the medical school's rifle club. The club's captain, keen to retain Fleming, suggested he join the research department at St Mary's. There, he became an assistant bacteriologist to Sir Almroth Wright, a pioneer in vaccine therapy and immunology. In 1908, Fleming earned a BSc degree with a gold medal in bacteriology and subsequently lectured at St Mary's until 1914.

Commissioned as a lieutenant in 1914 and promoted to captain in 1917, Fleming served with the Royal Army Medical Corps throughout World War I, earning a Mention in Dispatches. He and many of his colleagues were stationed in battlefield hospitals on the Western Front in France.

In 1918, he returned to St Mary's Hospital, and in 1928, he was appointed Professor of Bacteriology at the University of London.

Scientific Contributions

Antiseptics

During World War I, Fleming, in collaboration with Leonard Colebrook and Sir Almroth Wright, contributed to the war effort by relocating the entire Inoculation Department of St Mary's to the British military hospital at Boulogne-sur-Mer. Serving as a temporary lieutenant in the Royal Army Medical Corps, he observed numerous soldier fatalities resulting from sepsis in infected wounds. He noted that antiseptics, then commonly used for wound treatment, frequently exacerbated these injuries. In a 1917 article published in the medical journal The Lancet, Fleming described an ingenious experiment, made possible by his glassblowing skills, which explained why antiseptics were causing more fatalities than the infections themselves during the war. He posited that while antiseptics were effective on superficial wounds, deep wounds often shielded anaerobic bacteria from the antiseptic agent. Moreover, antiseptics appeared to eliminate beneficial protective agents produced by the body, at least as effectively as they removed bacteria, and were ineffective against bacteria beyond their reach. Although Wright strongly supported Fleming's findings, most army physicians continued to employ antiseptics throughout the war, even when this practice worsened patient conditions.

Discovery of Lysozyme

At St Mary's Hospital, Fleming persisted in his research on bacterial cultures and antimicrobial agents. His contemporary research scholar, V. D. Allison, noted Fleming's unconventional research habits, often anticipating unexpected bacterial formations on his culture plates. Fleming frequently jested about Allison's "excessive tidiness in the laboratory," a characteristic Allison later credited as instrumental to Fleming's experimental breakthroughs, stating, "Had he been as meticulous as he perceived me to be, he would not have achieved his two monumental discoveries."

In late 1921, during his maintenance of bacterial agar plates, Fleming observed airborne bacterial contamination on one particular plate. Upon applying nasal mucus, he noted a significant inhibition of bacterial proliferation. A distinct, transparent halo, approximately 1 cm from the mucus application, encircled the area, signifying a bacterial killing zone. This was succeeded by a glassy, translucent ring, beyond which normal bacterial growth was evident in an opaque region. Subsequent experiments involved bacteria suspended in saline, forming a yellow solution. The addition of fresh mucus rapidly clarified the yellow saline within two minutes. Fleming expanded his investigations to include tears, which were supplied by his colleagues. Allison recounted the extensive efforts to obtain samples: "For the subsequent five to six weeks, our tears served as the primary source for this remarkable phenomenon. Numerous lemons were employed (following the ineffectiveness of onions) to stimulate tear production... The substantial demand for tears even led to laboratory attendants being enlisted, receiving threepence for each donation."

Further analyses of sputum, cartilage, blood, semen, ovarian cyst fluid, pus, and egg white confirmed the ubiquitous presence of this bactericidal agent. Despite presenting his findings to the Medical Research Club in December and subsequently to the Royal Society the following year, the discovery garnered minimal attention, as Allison later recalled:

Allison, present as Fleming's guest at the Medical Research Club meeting, observed that Fleming's presentation detailing his discovery elicited no questions or discussion, an unusual reception that suggested its perceived insignificance. The subsequent year, Fleming delivered a paper on the topic at the Royal Society, Burlington House, Piccadilly, where he and Allison also provided a demonstration of their research. However, with only one exception, the work again received scant comment or attention.

In the May 1, 1922, issue of the Proceedings of the Royal Society B: Biological Sciences, Fleming published his findings under the title "On a remarkable bacteriolytic element found in tissues and secretions," stating:

In this communication, I aim to highlight a substance found within bodily tissues and secretions that possesses the capacity to rapidly dissolve specific bacteria. Given its properties, which resemble those of ferments, I have designated this substance "Lysozyme" and will refer to it by this nomenclature throughout this paper. The initial observation of lysozyme occurred during investigations conducted on a patient afflicted with acute coryza.

This marked the inaugural documented discovery of lysozyme. Collaborating with Allison, Fleming published additional research on lysozyme in the October issue of the British Journal of Experimental Pathology that same year. Despite successfully extracting substantial quantities of lysozyme from egg whites, the enzyme demonstrated efficacy only against limited populations of non-pathogenic bacteria, thereby possessing minimal therapeutic utility. This observation highlighted a fundamental distinction between pathogenic and non-pathogenic bacterial species. The "patient suffering from acute coryza," as referenced in the original publication, was subsequently identified as Fleming himself. His research notebook, dated November 21, 1921, contained a sketch of the culture plate accompanied by the note: "Staphyloid coccus from A.F.'s nose." Fleming further identified the bacterium within the nasal mucus as Micrococcus Lysodeikticus, a species name signifying "lysis indicator" due to its susceptibility to lysozymal action. In 1972, the species was reclassified as Micrococcus luteus. The "Fleming strain" (NCTC2665) of this bacterium has since become a significant model organism in various biological investigations. The broader significance of lysozyme remained unacknowledged, a fact Fleming himself recognized, as evidenced by his presidential address at the Royal Society of Medicine meeting on October 18, 1932, where he stated:

The speaker selected lysozyme for this address due to a personal affinity for the name and the perceived underappreciation of its significance in natural immunity.

During his Nobel lecture on December 11, 1945, Fleming briefly referenced lysozyme, stating, "Penicillin was not the first antibiotic I happened to discover." The profound immunological significance of Fleming's discovery was not fully recognized until the late 20th century, when lysozyme was identified as the inaugural antimicrobial protein contributing to innate immunity.

Discovery of Penicillin

Serendipitous discoveries often occur. Upon awakening shortly after dawn on September 28, 1928, the intention was not to revolutionize medicine by identifying the world's inaugural antibiotic, or bactericidal agent. However, this outcome precisely materialized.

Experimental Procedure

By 1927, Fleming had been engaged in research concerning the characteristics of staphylococci, having already established a distinguished reputation as an exceptional investigator through his prior work. In 1928, he investigated the phenotypic variations of Staphylococcus aureus cultivated under natural conditions, building upon the findings of Joseph Warwick Bigger, who had demonstrated the bacterium's capacity to develop into diverse strains. On September 3, 1928, following a family vacation in Suffolk, Fleming returned to his laboratory. Prior to his departure, he had inoculated staphylococci onto culture plates and left them on a laboratory bench. Upon his return, Fleming observed that one culture plate was contaminated with a fungus, and the staphylococcal colonies immediately adjacent to the fungus had been lysed, while more distant colonies remained unaffected. He famously commented, "That's funny." Fleming presented the contaminated culture to his former assistant, Merlin Pryce, who remarked, "That's how you discovered lysozyme." Fleming identified the mold as belonging to the genus Penicillium. Initially, he hypothesized it was P. chrysogenum, but his colleague Charles J. La Touche identified it as P. rubrum. (Subsequent reclassifications identified it as P. notatum and then officially as P. chrysogenum; in 2011, it was definitively resolved as P. rubens.)

The laboratory where Fleming discovered and conducted initial tests on penicillin is now preserved as the Alexander Fleming Laboratory Museum, located within St. Mary's Hospital, Paddington. In 1966, the origin of the fungal contamination was determined to be La Touche's room, situated directly beneath Fleming's laboratory.

Fleming cultivated the mold in a pure culture and subsequently determined that the resulting broth contained an antibacterial compound. He investigated its antimicrobial efficacy against numerous organisms, observing its inhibitory effect on bacteria such as staphylococci and various other Gram-positive pathogens responsible for conditions like scarlet fever, pneumonia, meningitis, and diphtheria. Notably, it did not affect typhoid fever or paratyphoid fever, which are caused by Gram-negative bacteria, and for which he was actively seeking a treatment. However, it did demonstrate activity against Neisseria gonorrhoeae, the causative agent of gonorrhea, despite this bacterium being Gram-negative. After several months of referring to it as "mould juice" or "the inhibitor," Fleming formally named the antibacterial substance "penicillin" on March 7, 1929.

Initial Reception and Publication

Fleming formally presented his discovery to the Medical Research Club on February 13, 1929. His presentation, titled "A medium for the isolation of Pfeiffer's bacillus," garnered no significant attention or commentary. Henry Dale, then Director of the National Institute for Medical Research and chairman of the meeting, later recalled perceiving no particularly striking aspect of importance in Fleming's address. Fleming subsequently published his findings in 1929 in the British Journal of Experimental Pathology, yet the article received minimal notice. A primary challenge was the formidable difficulty in producing penicillin in substantial quantities and, furthermore, isolating its active compound. Even with the assistance of Harold Raistrick and his team of biochemists at the London School of Hygiene & Tropical Medicine, chemical purification efforts proved unsuccessful. Consequently, as Milton Wainwright observed, "penicillin languished largely forgotten in the 1930s."

Even by 1936, penicillin's potential remained unrecognized. When Fleming presented its medical significance at the Second International Congress of Microbiology in London, his assertions were met with skepticism. Allison, who accompanied Fleming at both the Medical Research Club and the international congress, later recounted these two events:

[At the Medical Research Club meeting, Fleming] proposed penicillin's potential efficacy in treating human infections. Once more, his presentation garnered no interest and minimal discussion. Fleming experienced profound disappointment, yet further setbacks awaited him. Subsequently, he presented a paper detailing his penicillin research at the International Congress of Microbiology, an event attended by leading bacteriologists globally. His perspectives on its prospective utility for preventing and treating human infections received no endorsement, and the ensuing discussion was negligible. Despite these significant disappointments, Fleming stoically maintained his convictions and remained undeterred in his ongoing investigation of penicillin.

By 1941, the British Medical Journal observed that "it appeared that penicillin's utility had not been contemplated from any other perspective."

Purification and Stabilization

At Oxford, Ernst Chain and Edward Abraham commenced investigations into the antibiotic's molecular structure. Abraham subsequently became the first to accurately delineate penicillin's chemical structure. Following the team's initial publication of results in 1940, Fleming contacted Howard Florey, Chain's departmental head, to announce an impending visit. Upon learning of Fleming's imminent arrival, Chain reportedly exclaimed, "Good God! I thought he was dead."

Norman Heatley proposed a method for re-extracting penicillin's active compound into an aqueous solution by modifying its pH. This technique yielded a sufficient quantity of the drug for initial animal trials. The Oxford research group comprised numerous additional contributors, with the entire Sir William Dunn School of Pathology eventually participating in the production efforts. Following the team's successful development of a purification method yielding an initial stable and effective form of penicillin in 1940, subsequent clinical trials demonstrated remarkable success, prompting the team to devise strategies for mass production and distribution by 1945.

Fleming exhibited humility regarding his role in penicillin's development, referring to his renown as the "Fleming Myth" and crediting Florey and Chain with transforming a laboratory curiosity into a viable therapeutic agent. As the initial discoverer of the active substance's properties, Fleming was accorded the prerogative of naming it penicillin. Furthermore, he maintained, cultivated, and disseminated the original mold for a period of twelve years, persistently seeking assistance from skilled chemists to produce penicillin until 1940. In 1998, Sir Henry Harris succinctly summarized the collaborative process: "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin." The discovery of penicillin and its subsequent evolution into a prescription medication signify the genesis of modern antibiotics.

Medical Applications and Mass Production

Fleming's initial clinical application involved treating his research scholar, Stuart Craddock, who presented with a severe infection of the nasal antrum (sinusitis). Commencing on January 9, 1929, this treatment proved ineffective. This likely resulted from the infection being caused by Haemophilus influenzae, a bacterium Fleming had previously identified as resistant to penicillin. In 1928, Fleming provided samples of his original penicillin to his surgical colleague, Arthur Dickson Wright, for clinical evaluation. While Wright reportedly stated that it "seemed to work satisfactorily," no specific records of its application exist. Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield and a former student of Fleming, achieved the first documented successful medical application of penicillin. On November 25, 1930, he successfully treated conjunctivitis in one adult and three infants (neonatal conjunctivitis).

In 1932, Fleming also achieved a successful treatment for severe conjunctivitis. Keith Bernard Rogers, a medical student at St Mary's since 1929 and captain of the London University rifle team, developed conjunctivitis shortly before an inter-hospital rifle shooting competition. Fleming administered his penicillin, which resulted in Rogers' recovery prior to the event. Anecdotal accounts suggest that "the penicillin worked and the match was won." However, the assertion that "Keith was probably the first patient to be treated clinically with penicillin ointment" has since been disproven by the emergence of Paine's medical records.

A prevalent assertion in both popular and scientific discourse suggests that Fleming largely discontinued his work on penicillin during the early 1930s. William L. Kissick, in his review of André Maurois's The Life of Sir Alexander Fleming, Discoverer of Penicillin, even stated 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 claim is inaccurate, as Fleming consistently pursued penicillin research. His notebooks from as late as 1939 document efforts to enhance penicillin production through the use of various culture media. Furthermore, in 1941, he published a methodology for evaluating penicillin's efficacy. Regarding the chemical isolation and purification, Howard Florey and Ernst Chain at the Radcliffe Infirmary in Oxford subsequently undertook the research to enable mass production, a goal they achieved with backing from World War II military initiatives supported by the British and US governments.

By mid-1942, the Oxford research team had successfully synthesized pure penicillin, which manifested as a yellow powder. In August 1942, Harry Lambert, an associate of Fleming's brother Robert, was hospitalized at St Mary's Hospital with a life-threatening streptococcal meningitis infection of the nervous system. Fleming initially treated Lambert with sulphonamides, but the patient's condition worsened. Upon testing antibiotic susceptibility, Fleming determined that his penicillin was effective against the causative bacteria. He then requested an isolated sample from Florey, who provided an incompletely purified preparation. Fleming promptly administered this sample directly into Lambert's spinal canal. Lambert exhibited signs of improvement by the following day and achieved a full recovery within a week. Fleming subsequently published this clinical case in The Lancet in 1943.

Following this significant medical breakthrough, Allison apprised the British Ministry of Health of penicillin's critical importance and the imperative for its mass production. The War Cabinet, convinced of the drug's utility, prompted Sir Cecil Weir, Director General of Equipment, to convene a meeting on 28 September 1942, to discuss its mechanism of action. The Penicillin Committee was subsequently established on 5 April 1943. This committee comprised Weir as chairman, alongside Fleming, Florey, Sir Percival Hartley, Allison, and representatives from various pharmaceutical companies. Its primary objectives were to facilitate the rapid, large-scale production of penicillin through collaboration with American companies and to ensure its exclusive supply to the Allied armed forces. By D-Day in 1944, sufficient penicillin had been manufactured to treat all wounded personnel among the Allied troops.

Antibiotic Resistance

Fleming made an early discovery that bacteria developed antibiotic resistance when penicillin was administered in insufficient quantities or for excessively brief durations. Almroth Wright had, in fact, predicted the phenomenon of antibiotic resistance even before its experimental observation. Fleming frequently issued warnings regarding penicillin usage in numerous addresses delivered globally. On 26 June 1945, he articulated the following cautionary remarks: "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 advised against the use of penicillin unless a precise diagnostic rationale supported its application, and emphasized that, if used, it should never be administered in inadequate amounts or for insufficient periods, as these conditions foster the development of bacterial resistance to antibiotics.

Experimental evidence from 1942 demonstrated that S. aureus could acquire penicillin resistance following prolonged exposure. In his Nobel Lecture, Fleming further elaborated on the potential for penicillin resistance to emerge in clinical settings, stating:

This statement highlights a potential future risk: the widespread availability of penicillin could lead to individuals self-administering insufficient dosages, thereby exposing microorganisms to sub-lethal concentrations of the drug and fostering antimicrobial resistance.

Coincident with these concerns, the initial clinical instance of penicillin resistance was documented.

Personal Life

On December 24, 1915, Fleming entered into marriage with Sarah Marion McElroy, a qualified nurse from Killala, County Mayo, Ireland. Their sole offspring, Robert Fleming (1924–2015), subsequently pursued a career as a general medical practitioner. Following the demise of his first wife in 1949, Fleming remarried on April 9, 1953, to Amalia Koutsouri-Vourekas, a Greek colleague from St. Mary's, who passed away in 1986.

Fleming's upbringing was rooted in a Presbyterian tradition, whereas his first wife, Sarah, identified as a lapsed Roman Catholic. Accounts suggest that Fleming himself was not notably devout. Their son, Robert, was later admitted into the Anglican church, yet he reportedly maintained a largely irreligious inclination, consistent with his parents' dispositions.

Fleming expressed considerable indignation upon discovering that Robert D. Coghill and Andrew J. Moyer had patented the penicillin production method in the United States in 1944, remarking:

I discovered penicillin and freely offered it for the betterment of humanity. Why should it transform into a profit-driven monopoly for manufacturers in a different nation?

From 1921 until his passing in 1955, Fleming maintained ownership of a rural residence known as "The Dhoon," situated in Barton Mills, Suffolk.

Demise

Fleming passed away from a cardiac arrest at his London residence on March 11, 1955. His cremated remains are interred within St Paul's Cathedral.

Accolades and Enduring Influence

Fleming's groundbreaking discovery of penicillin revolutionized modern medicine, inaugurating the era of effective antibiotics. This compound has demonstrably preserved, and continues to preserve, the lives of millions globally.

The laboratory at St Mary's Hospital, where Fleming made his pivotal penicillin discovery, now houses the Fleming Museum, a prominent London attraction. His alma mater, St Mary's Hospital Medical School, integrated with Imperial College London in 1988. The Sir Alexander Fleming Building, located on the South Kensington campus, was inaugurated in 1998, an event at which his son Robert and great-granddaughter Claire were presented to the Queen. This facility currently serves as a primary preclinical teaching location for the Imperial College School of Medicine.

The Royal Polytechnic Institution, another of his alma maters, now known as the University of Westminster, has designated one of its student residential halls as Alexander Fleming House, situated in proximity to Old Street.

Misconceptions

The Fleming Narrative

By 1942, penicillin, even in its purified compound form, remained scarce and inaccessible for widespread clinical application. When Fleming administered the initial samples, prepared by the Oxford team, to treat Harry Lambert, who suffered from streptococcal meningitis, the successful outcome garnered significant media attention, notably popularized in The Times. Wright expressed astonishment upon realizing that neither Fleming nor the Oxford team had been explicitly acknowledged, despite Oxford being credited as the drug's origin. Wright subsequently corresponded with the editor of The Times, which promptly interviewed Fleming. However, Florey had forbidden the Oxford team from engaging with media outlets. Consequently, Fleming alone received extensive public recognition, fostering the erroneous belief that he was solely accountable for the drug's discovery and subsequent development. Fleming himself termed this phenomenon "the Fleming myth."

The Churchills

The widely circulated narrative asserting that Winston Churchill's father funded Fleming's education because Fleming's father had saved a young Winston from a fatal incident is unsubstantiated. In a letter to his colleague Andre Gratia, Alexander Fleming himself characterized this account as "A wondrous fable," as documented in Kevin Brown's biography, Penicillin Man: Alexander Fleming and the Antibiotic Revolution. Furthermore, Fleming did not personally save Winston Churchill during World War II. Churchill's recovery from an illness in Carthage, Tunisia, in 1943, was facilitated by Lord Moran, who administered sulphonamides, as Moran lacked experience with penicillin. Despite reports in The Daily Telegraph and The Morning Post on December 21, 1943, attributing Churchill's recovery to penicillin, he was actually treated with sulphapyridine, a novel sulphonamide drug identified by its research code M&B 693. This drug was developed and manufactured by May & Baker Ltd of Dagenham, Essex, a subsidiary of the French conglomerate Rhône-Poulenc. Churchill later publicly acknowledged the medication in a radio broadcast, referring to it as "This admirable M&B."

Fleming Prize Lecture

Fleming Prize Lecture
Individuals Featured on Scottish Banknotes

References

Maurois, André. The Life Of Sir Alexander Fleming. Jonathan Cape, 1959.

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