Fleming, Alexander

(b. Lochfield, Ayrshire, Scotland, 6 August 1881; d. London, England, 11 March 1955)

bacteriology.

Sir Alexander Fleming’s professional career was devoted mainly to investigating the human body’s defenses against bacterial infections. Late in life he achieved retrospective fame for discovering penicillin in 1928.

Descended from Lowland farmers, Alexander was the third of four children born to Grace Morton, second wife of Hugh Fleming. Four children of the first marriage survived. His father died when Alec was seven years old, leaving the widow to manage the farm with her eldest stepson. From age five to ten, the boy attended a tiny moorland school. Then he walked daily to school at Dorval, a small town four miles away. Two years later, he attended Kilmarnock Academy, twelve miles distant, which had exacting standards but meager resources. His basic education was thus hard-earned and rather primitive. He learned early to observe nature intimately, to enjoy simple pleasures, and to appreciate unaffectedness.

When just over thirteen, he followed a stepbrother, already a practicing physician, and his brother John to London. The youngest brother, Robert, soon joined them, and a sister kept house. After attending classes at the Regent Street Polytechnic for two years, Alec became a clerk in a shipping company. In 1900 he enlisted in the London Scottish Regiment, but the Boer War ended before he got overseas. He enjoyed life in the ranks and stayed attached to this regiment until 1914. Fleming was short but sturdy, blue-eyed, fair-haired, good at rifle shooting and water polo. At twenty, he inherited a small legacy and decided to study medicine.

Fleming excelled at competitive examinations. He won a scholarship to St. Mary’s Hospital Medical School, Paddington, and in 1901 began his lifelong connection with that institution. Capturing numerous class prizes and trophies, he obtained the Conjoint Board Diploma in 1906, and two years later graduated M.B., B.S., with honors and a gold medal from the University of London. In 1909 he completed the fellowship examinations of the Royal College of Surgeons of England.

Upon qualifying in 1906, Fleming joined Sir Almroth Wright’s disciples at St. Mary’s Hospital. Although he was Wright’s antithesis—cautious, unpretentious, and laconic—they were closely associated for forty years. Fleming became assistant director of the Inoculation Department in 1921. The department merged with the Institute of Pathology and Research in 1933; it was renamed the Wright-Fleming Institute in 1948. In that year, Fleming retired as professor of bacteriology, University of London, having held the chair since 1928. He retained the principalship of the institute (to which he succeeded when Wright retired in 1946) until January 1955. Two months later he died suddenly from coronary thrombosis in his Chelsea home. He is buried in St. Paul’s Cathedral.

In 1915 Fleming marriéd Sarah Marion McElroy, an Irish farmer’s daughter, who had operated a private nursing home. Despite their dissimilar characters, the marriage was happy. They enjoyed gardening at their Suffolk country house, were very hospitable, and collected antiques. Their only child, Robert, born in 1924, became a physician. Fleming’s wife died in 1949, and in 1953 he married Dr. Amalia Coutsouris-Voureka, a Greek bacteriologist working at the institute.

Fleming upheld and practiced Wright’s doctrine of specific immunization against bacterial infection through vaccine therapy, without necessarily accepting every dictum. His earliest publications (1908) concerned “opsonic index” determinations—Wright’s method of assaying the phagocytic power of a patient’s blood for a particular microorganism. The procedure was of dubious utility and eventually fell out of favor. Fleming was among the first (1909) to treat syphilis with Salvarsan (606), samples of which Ehrlich had entrusted to Wright.

In World War I, Fleming joined the Royal Army Medical Corps as lieutenant, serving under Wright’s colonelcy in a wound-research laboratory at Boulogne. By simple, ingenious techniques, he demonstrated the bactericidal power of pus and the inability of chemical antiseptics to sterilize tortuous wounds. He supported Wright in advocating hypertonic saline solution as a physiological irrigant for septic lacerations. Demobilized with captain’s rank, Fleming resumed studying antibacterial mechanisms at St. Mary’s in 1919.

His best work followed in the next decade. Using “slide cells,” he showed that ordinary germicides damaged the leucocytes in artificially infected blood at dilutions harmless to the bacteria. He therefore condemned the intravenous administration of chemical antiseptics, asserting that ideal therapeutic antibacterial agents should arrest the growth of bacterial invaders without affecting host tissues. Fleming did not systematically search for such entities, but through sharp observation, pertinacious curiosity, and a prepared mind he discovered two outstandingly important antibacterial substances.

In 1921, while inspecting a contaminated culture plate, he observed nasal mucus dissolving a yellowish colony. The bacteriolytic agent was named “lysozyme,” and the susceptible organism (at Wright’s suggestion) Micrococcus lysodeikticus. With V. D. Allison’s collaboration, Fleming detected lysozyme in human blood serum, tears, saliva, and milk; and in such diverse animal and plant substances as leucocytes, egg white, and turnip juice. Since inoffensive airborne bacteria were lyzed more readily than pathogenic species, chemical concentration of the active principle was attempted, without success. (Lysozymes were later crystallized in other laboratories; because of their specific disruptive action on the cell wall of certain gram-positive organisms, these enzymes have proved valuable in studies of bacterial cytology.) Fleming then became engrossed with another lytic agent.

In 1928 he noted a culture plate displaying Penicillium mold surrounded by lyzed colonies of staphylococci. Culture filtrates of the mold (later identified by C. Thom as Penicillium notatum) were antibacterial for many pathogenic species. He reported (1929) that “penicillin” did not interfere with leucocytic function, was nontoxic to laboratory animals, and “may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes.” The intended clinical trials were abandoned because these crude preparations had unpredictable and fleeting potency, which Fleming’s knowledge of chemistry was inadequate to overcome. Although he enlisted aid from junior colleagues and from the biochemist H. Raistrick, the problem remained unsolved. Thereafter, he used the “mold juice” mainly for isolating penicillin-insensitive bacteria from mixed cultures.

Following Domagk’s work on prontosil (1935), Fleming studied the antibacterial properties of sulfonamides. But he never lost confidence that penicillin would be stabilized and purified, and rejoiced when Ernst Chain, Howard Florey, and their co-workers accomplished this at Oxford in 1940. Within two years, the antibiotic’s remarkable powers were established. Mounting war casualties entailed securing the higest priority for its large-scale manufacture, and steps were taken to achieve this in the United States, Britain, and Canada.

As supplies of penicillin expanded and its efficacy became more widely known, tributes and honors showered upon Alexander Fleming. He was elected to fellowship of the Royal Society in 1943; knighted (K.B.) in 1944; received the Nobel Prize in medicine, jointly with Florey and Chain, in 1945; and was awarded numerous foreign decorations and medals, honorary memberships in medical and scientific societies, and doctorates from famous universities. He was elected president of the newly founded Society for General Microbiology (1945) and rector of Edinburg University (1951) and was given the freedom of Dorval, Chelsea, and Paddington—where he had gone to school, lived, and worked. Between 1945 and 1953, despite his limited eloquence, he undertook a succession of speech-making triumphal tours of the United States and other countries.

Fleming at first accepted the honors and acclaim diffidently, but later came to enjoy them. His main Characteristics persisted: the evening game of snooker at the Chelsea Arts Club (where he held a longtreasured honorary membership), the pawky humor, the taciturnity, the basic dedication to the health of mankind.

BIBLIOGRAPHY

I. Original Works. Fleming was sole or senior author of about 100 scientific papers, which appeared mainly in well-known British medical or scientific journals between 1908 and 1954. The majority were reports or reviews of original work on vaccine therapy, wound infection, antiseptics, lysozyme, penicillin, and other antibiotics. Occasionally he described novel techniques or wrote brief biographical memoirs. Philosophical or nonscientific topics were generally beyond his range. He contributed a few individual chapters or sections to composite works and committee reports and was author or coauthor of two books in his own special fields. Among his best papers were those prepared as addresses for endowed lectureships. Certain of these are included in the appended representative list.

No complete bibliography has been printed, but fairly comprehensive lists of his principal publications (containing several minor errors) were appended to Leonard Colebrook’s memoir of Fleming and to the biography by André Maurois. A Collection of his published works and unpublished manuscripts—including letters, diaries, laboratory notebooks, and many other documents relating to Fleming—is deposited with the Sir Alexander Fleming Museum in the Wright-Fleming Institute.

Fleming’s works include “Some Observations on the Opsonic Index, With Special Reference to the Accuracy of the Method and to Some of the Sources of Error,” in Practitioner, 80 (1908). 607–634; “On the Etiology of Acne Vulgaris and Its Treatment by Vaccines,” in Lancet (1909), 1 , 1035–1038; “On the Use of Salvarsan in the Treatment of Syphilis,” ibid. (1911) 1 , 1631–1634, written with L. Colebrook; “On the Bacteriology of Septic Wounds,” ibid. (1915), 2 , 638–643; “The Action of Chemical and Physiological Antiseptics in a Septic Wound,” in British Journal of Surgery, 7 (1919), 99–129, the Hunterian lecture; “On a Remarkable Bacteriolytic Element Found in Tissues and Secretions,” in Proceedings of the Royal Society, 93B (1922) 306–317; “Lysozyme—A Bacteriolytic Ferment Found Normally in Tissues and Secretions,” in Lancet (1929), 1 , 217–220, the Arris and Gale lecture; “The Staphylococci,” in A System of Bacteriology in Relation to Medicine, II (London, 1929), 11–28; “On the Antibacterial Action of Cultures of a Penicillium, With Special Reference to Their Use in the Isolation of B. influenzae,” in British Journal of Experimental Pathology,10 (1929), 226–236; “The Intravenous Use of Germicides,” in Proceedings of the Royal Society of Medicine, 24 (1931), 46–58; Recent Advances in Vaccine and Serum Therapy (London, 1934), written with G. F. Petrie; “Serum and Vaccine Therapy in Combination With Sulphanilamide or M and B 693,” in Proceedings of the Royal Society of Medicine, 32 (1939), 911–920; “The Effect of Antiseptics on Wounds,” ibld., 33 (1940), 487–502; “Streptococcal Meningitis Treated With Penicillin,” in Lancet (1943), 2 , 434–438; “Penicillin: Its Discovery, Development and Uses in the Field of Medicine and Surgery,” in Journal of the Royal Institute of Public Health and Hygiene, 8 (1945), 36–49, 63–71, 93–105, the Harben lectures; “The Morphology and Motility of Proteus vulgaris and Other Organisms Cultured in the Presence of Penicillin,” in Journal of General Microbiology, 4 (1950), 257–269, written with A. Voureka, I. R. H. Kramer, and W. H. Hughes; Penicillin (London, 1946); and “Twentieth Century Changes in the Treatment of Septic Infections,” in New England Journal of Medicine, 248 (1953), 1037–1045, the Shattuck lecture.

II. Secondary Literature. Obituaries include “Sir Alexander Fleming, M.D., D.Sc., F.R.C.P., F.R.C.S., F.R.S.,” in British Medical Journal (1955), 1 , 732–735, unsigned; “Alexander Fleming, Kt., M.B., Lond., F.R.C.P., F.R.C.S., F.R.S.,” in Lancet (1955), 1 , 624–626, unsigned; V. D. Allison, “Sir Alexander Fleming, 1881–1955,” in Journal of General Microbiology, 14 (1956), 1–13; L. Colebrook, “Alexander Fleming, 1881–1955,” in Biographical Memories of Fellows of the Royal Society of London, 2 (1956), 117–127; and R. Cruikshank, “Alexander Fleming, 6th August 1881–11th March 1955,” in Journal of Pathology and Bacteriology, 72 (1956), 697–708.

A biography is André Maurois, The Life of Sir Alexander Fleming, Gerard Hopkins, trans. (London, 1959; Penguin ed., 1963). Lady Fleming persuaded Maurois to undertake this very readable biography, which shows occasional bias and contains some inaccuracies.

Various short appreciations and unusual photographs of Fleming were published in St. Mary’s Hospital Gazette, 61 , no. 3 (1955), 58–74.

Special references are E. P. Abraham, E. Chain, C. M. Fletcher, H. W. Florey, A. D. Gardner, N. G. Heatley, and M. A. Jennings, “Further Observations on Penicillin,” in Lancet (1941), 2 , 177–189; E. Chain, H. W. Florey, A. D. Gardner, N. G. Heatley, M. A. Jennings, J. Orr-Ewing, and A. G. Sanders, ibid. (1940), 2 , 226–228; R. D. Coghill, “Penicillin: Science’s Cinderella,” in Chemical and Engineering News, 22 (1944), 588–593; R. D. Coghill and R. S. Koch, “Penicillin: A Wartime Accomplishment,” ibid., 23 (1945), 2310–2316; L. Colebrook, Almroth Wright: Provocative Doctor and Thinker (London, 1954); R. Hare, The Birth of Penicillin and the Disarming of Microbes (London, 1970); and M. R. J. Salton, “The Properties of Lysozyme and Its Action on Microorganisms,” in Bacteriological Reviews, 21 (1957), 82–99.

Claude E. Dolman

Fleming, Alexander

SCOTTISH BACTERIOLOGIST
1881–1955

Alexander Fleming will always be remembered for turning a laboratory mishap into one of the great medical discoveries of the twentieth century. His discovery of penicillin in 1928 laid the foundation for modern antibiotic therapy and earned him a share of the 1945 Nobel Prize in physiology or medicine.

Fleming was born on August 6, 1881, at Lochfield near Darvel in Ayrshire, Scotland. He attended elementary and secondary school in Scotland and then moved to London to attend the polytechnic school. He graduated with distinction in 1906 from St. Mary's Medical School, London University, received a graduate degree in bacteriology from St. Mary's in 1908, and lectured there until 1914. After serving as a captain in the Army Medical Corps during World War I, Fleming returned to St. Mary's in 1918.

Throughout his career Fleming was intensely interested in naturally occurring antibacterial substances, and penicillin was actually the second antibiotic that he discovered. In 1922 he described the antibacterial properties of lysozyme, a substance found in egg whites, mucus, and tears, which lysed, or dissolved, certain bacteria. Fleming found that lysozyme could turn a thick, milky white suspension of bacteria into a clear solution in a matter of seconds.

Unfortunately, lysozyme failed to destroy bacteria that caused human diseases and was never used as a medicine. Despite the limited utility of lysozyme, Howard Florey and Ernst Boris Chain of Oxford University later determined both its structure and the mechanism by which it destroys bacteria. These two scientists would figure prominently in Fleming's greatest discovery: penicillin.

Fleming freely admitted that he was not looking for a new antibiotic when he discovered penicillin in 1928. In fact, he was working on a problem unrelated to antibiotics when he returned to his lab from a month-long vacation and observed that a blue mold, or fungus, had grown on a discarded culture plate of Staphylococcus aureus (a common bacteria that causes many diseases in humans). Fleming further observed that a bacteria-free zone had developed around the mold. The once thick cultures of bacteria near the mold had become translucent, or almost clear, and evidently a substance produced by the mold had diffused through the culture medium and killed the bacteria.

The extraordinary appearance of the bacteria-free zone interested Fleming, so he set out to isolate the mold in pure culture and to determine some of its properties. Fleming classified the mold as Penicillium rubra, hence, the name penicillin for the active substance.

Fleming tested the purified mold against other bacteria and observed that some bacteria grew right up to the mold, while others grew only to within a few centimeters of it. He tested other molds for their ability to kill sensitive bacteria and found none. Fleming then grew the mold in a liquid medium and determined that the mold excreted penicillin into the culture medium. When he tested the medium against common bacteria, Fleming found that the growth of many disease-causing bacteria was inhibited. He even injected the medium into mice and observed no toxic effects from the new substance.

Although Fleming was convinced that penicillin had enormous potential value in medicine, he was unable to produce enough of it to demonstrate its value to the medical community. He published his findings in 1929, and penicillin seemed destined for obscurity. But in 1938, Florey and Chain began to reinvestigate penicillin and eventually produced enough pure material to demonstrate that Fleming's assertions were correct. Penicillin has indeed had enormous value in the treatment of infections worldwide.

see also Antibiotics; Penicillin.

Thomas M. Zydowsky

Bibliography

Internet Resources

"The Nobel Prize in Physiology or Medicine 1945." Available from <http://www.nobel.se/medicinelaureates/1945/press.html>.

"Penicillin, the Wonder Drug." Available from <http://www.botany.hawaii.edu/faculty/wong>.

"Sir Alexander Fleming—Biography." Available from <http://www.nobel.se/medicinelaureates>.

Fleming, Alexander (1881-1955)

Scottish bacteriologist

With the experienced eye of a scientist, Alexander Fleming turned what appeared to be a spoiled experiment into the discovery of penicillin .

Fleming was born in 1881 to a farming family in Lochfield, Scotland. Following school, he worked as a shipping clerk in London and enlisted in the London Scottish Regiment. In 1901, he began his medical career, entering St. Mary's Hospital Medical School, where he was a prizewinning student. After graduation in 1906, he began working at that institution with Sir Almroth Edward Wright , a pathologist. From the start, Fleming was innovative and became one of the first to use Paul Ehrlich 's arsenic compound, Salvarsan, to treat syphilis in Great Britain.

Wright and Fleming joined the Royal Army Medical Corps during World War I and they studied wounds and infection-causing bacteria at a hospital in Boulogne, France. At that time, antiseptics were used to treat bacterial infections, but Wright and Fleming showed that, especially in deep wounds, bacteria survive treatment by antiseptics while the protective white blood cells in the wound are destroyed. This creates an even worse situation in which infection can spread rapidly. Forever affected by the suffering he saw during the war, Fleming decided to focus his efforts on the search for safe antibacterial substances. He studied the antibacterial power of the body's own leukocytes contained in pus. In 1921, he discovered that a sample of his own nasal mucus destroyed bacteria in a petri dish. He isolated the compound responsible for the antibacterial action, which he called lysozyme, in saliva, blood, tears, pus, milk, and in egg whites.

Fleming made his greatest discovery in 1928. While he was growing cultures of bacteria in petri dishes for experiments, he accidentally left certain dishes uncovered for several days. Fleming found a mold growing in the dishes and began to discard them, when he noticed, to his astonishment, that bacteria near the molds were being destroyed. He preserved the mold, a strain of Penicillium and made a culture of it in a test tube for further investigation. He deduced an antibacterial compound was being produced by the mold, and named it penicillin. Through further study, Fleming found that penicillin was nontoxic in laboratory animals. He described his findings in research journals but was unable to purify and concentrate the substance. Little did he realize that the substance produced by his mold would save millions of lives during the twentieth century.

Fleming dropped his investigation of penicillin and his discovery remained unnoticed until 1940. It was then that Oxford University-based bacteriologists Howard Florey and Ernst Chain stumbled upon a paper by Fleming while researching antibacterial agents. They had better fortune than Fleming, for they were able to purify penicillin and test it on humans with outstanding results. During World War II, the drug was rushed into mass-production in England and the United States and saved thousands of injured soldiers from infections that might otherwise have been fatal.

Accolades followed for Fleming. He was elected to fellowship in the Royal Society in 1943, knighted in 1944, and shared the Nobel Prize with Florey and Chain in 1945. Fleming continued working at St. Mary's Hospital until 1948, when he moved to the Wright-Fleming Institute. Fleming died in London in 1955.

See also Antibiotic resistance, tests for; Antibiotics; Bacteria and bacterial infection; History of the development of antibiotics; History of microbiology; History of public health