Alexander Fleming

Scottish biologist

• Born: August 6, 1881
• Birthplace: Lochfield, Ayrshire, Scotland
• Died: March 11, 1955
• Place of death: London, England

With an exceptional facility for observation and a careful adherence to the basic principles of the scientific method, Fleming discovered lysozyme and penicillin. These discoveries placed him in the vanguard of modern scientists struggling to control infectious diseases among the general population.

Early Life

Alexander Fleming was born in Lochfield, a village located at the junction of the counties of Lanark, Ayr, and Renfrew in Scotland. His mother, Grace Morton, was the second wife of his father, Hugh Fleming, and Alexander was the third of four children resulting from that union. The Flemings were Lowland farmers who made their living from an eight-hundred-acre farm with poor soil. When Alexander was seven, his father died, leaving his mother to manage the farm and head the household. Among the results of this turn of events was the need for the Fleming children to supplement the family diet with fish and game from the nearby moors. In all likelihood, Alexander Fleming’s remarkable powers of observation were developed during his moorland hunting and fishing expeditions.

Fleming’s formal education began in a one-room cottage with a single teacher and fifteen other students. He subsequently attended a larger school in the nearby town of Darvel and then, at the age of twelve, was sent to Kilmarnock Academy. The Kilmarnock schoolmaster was very progressive, insisting that his pupils study two theoretical sciences each year, and Fleming benefited greatly from this early exposure to science. After leaving Kilmarnock, Fleming moved to London, where under the watchful eyes of his brothers, one of whom was a surgeon, he began studying commerce at the Polytechnic School on Regent Street. On completion of his course, Fleming took a post as a clerk with the American Shipping Line Company, but the long hours and small prospects for advancement led him to make a crucial decision. On the advice of his brother Tom, whose surgical practice was thriving, Fleming decided to study medicine. By placing first in the United Kingdom in the medical school entrance examination, Fleming was given his choice of training at any of the twelve hospitals under the control of the University of London. He chose St. Mary’s Hospital in Paddington. He entered St. Mary’s in October, 1901, and spent the next fifty-four years of his life there as a student and member of the staff. When Fleming received his bachelor of medicine degree in 1906, he was asked to stay on at St. Mary’s as a member of the staff working in the Inoculation Department, headed by Sir Almroth Wright. By accepting the offer, he ensured a unique place for himself in the annals of science.

Life’s Work

Fleming’s mentor, Wright, was strong-willed, with a formidable intellect that made him a forbidding character. Famous in medical circles for diagnosing cases of Malta Fever and for his antityphoid fever vaccine, Wright was convinced that the only way to fight infectious disease was through immunotherapy. Because of Wright’s belief in immunotherapy and his strong personality, Fleming began his career as a scientific researcher by laboring to prove the validity of Wright’s theory of the “opsonin index,” which held that the substance he called opsonin prepared bacterial pathogens in the body for destruction by white blood cells. Although loyal to Wright, Fleming slowly became convinced that a more direct method of attacking the causative agents of infectious disease was preferable to relying on the natural defenses of the body.

Any doubts Fleming might have had about using specific medicines to attack pathogenic microorganisms were put to rest in May, 1909, when Paul Ehrlich, a German scientist, revealed his discovery of an arsenic compound called Salvarsan that killed the causative agent of syphilis, Treponema pallidum, without harming the human patient. The first among British physicians to use Salvarsan successfully, Fleming was so impressed by the efficacy of Ehrlich’s “magic bullet” that he determined to devote the rest of his career to finding similar substances for treating other diseases. His quest stretched over decades and included innumerable frustrations, but ultimately his patience and determination were rewarded.

After returning to St. Mary’s after World War I, Fleming made a very important discovery in 1921 when he observed that many human body fluids such as nasal mucus and tears destroyed bacteria in vitro. Extensive experimentation led Fleming to conclude that a substance that he dubbed lysozyme, because it lysed bacteria and had the properties of an enzyme, formed a major part of the body’s defense against invasion by microorganisms. Although he was never able to isolate the substance and use it against disease-causing microbes in vivo, his discovery nevertheless was important. Lysozyme not only was the subject of more than two thousand scientific papers and valuable commercially in protecting packaged foods; its success encouraged Fleming in his search for a substance that could be used therapeutically against microbial diseases.

Quite by accident, Fleming’s greatest achievement came in 1928, when one of his assistants, D. M. Pryce, carelessly exposed some petri dishes with streptococcal cultures to the open air of Fleming’s laboratory in Paddington and contaminated the cultures. Fleming’s initial irritation with Pryce was allayed when he noticed that in one of the petri dishes a colony of mold had begun to grow and appeared to be inhibiting the growth of the streptococci. Too good a scientist to ignore this invaluable observation, Fleming noted the critical connection between the growth of the mold and the inhibition of the pathogen and began to explore the dynamics of the phenomenon. What he soon learned was that the mold, Penicillium notatum, had a natural antibiosis effect, and that gram-positive pathogenic microorganisms were unable to survive in its presence.

Fleming spent the years between 1928 and the outbreak of World War II first trying to prove that the mold could be used in treating disease without harming the patient, then struggling to isolate the active principle of the mold that gave it antibiotic properties. Solutions of the mold “juice” he brewed clearly were effective in controlling infection of superficial wounds, but Fleming’s training in biochemistry and mycology was insufficient to enable him to pursue his discovery to a final and satisfactory conclusion. While he struggled to prove the value of penicillin in fighting disease, he suffered setbacks that would have discouraged someone with less determination. In 1935, a scientist, Gerhard Domagk, working in Hitler’s Germany, produced a drug he called prontosil, one of the sulfonamides (or sulfa drugs), that seemed to accomplish what Fleming had hoped would be the effect of penicillin. Despite that setback, Fleming continued his research, convinced that penicillin was superior in every way to “sulfa,” and in time he was proven correct.

The problem with Fleming’s research was that he could not isolate the active principle of the Penicillium mold because of the limitations of his training and equipment. Fortuitously, two scientists at Oxford, Baron Florey and Ernst B. Chain, were aware of the technical problems attendant on the refining of penicillin, and they developed a technique to produce a substance that was one thousand times more powerful than anything Fleming had been able to use therapeutically. The result of their work was to prove that penicillin was everything that Fleming had claimed it would be in the treatment of diseases caused by gram-positive microbes. At the height of the war, in August, 1942, The Times published an article titled “Penicillium” that gave full credit to Fleming, Florey, and Chain for their respective contributions to the development of the “wonder drug” that saved so many lives during the world conflict. In subsequent years, Fleming received the honors that accompanied his achievement. He was elected to the Royal Society in 1943; the next year, he was honored with a knighthood. In 1945 came the greatest honor of all when he, with Florey and Chain, was awarded the Nobel Prize in Physiology or Medicine for his work in developing penicillin. On March 11, 1955, he died of a heart attack; he was buried in the crypt of St. Paul’s Cathedral.

Significance

Modern scientific accomplishments are commonly the result of team efforts rather than those of individual investigators, and it seems clear that Fleming’s discovery of the antibiotic powers of Penicillium notatum would have remained a laboratory curiosity if Florey and Chain had not managed to isolate the active antibiotic ingredient for use as a medicine. Still, it was Fleming who first noticed the phenomenon of natural antibiosis and his determination, despite many setbacks and frustrations, that finally resulted in production of one of the most powerful weapons in the arsenal of medicine for fighting infectious disease. All modern antibiotic therapy traces its origins to that contaminated petri dish in the cluttered laboratory of Fleming at St. Mary’s Hospital in 1928.

Bibliography

Bud, Robert. Penicillin: Triumph and Tragedy. New York: Oxford University Press, 2007. Describes the discovery and development of penicillin, initially considered a miracle drug until it proved nonresistant to “superbugs.”

Lax, Eric. The Mold in Dr. Florey’s Coat: The Story of the Penicillin Miracle. New York: Henry Holt, 2004. Lax seeks to correct what many believe to be a misconception: that Fleming developed penicillin. In discussing Fleming’s “discovery” of penicillin, Lax describes how Fleming had first abandoned his research, which was then taken up by Baron Florey and other scientists, who, he argues, should be credited with penicillin’s discovery.

Macfarlane, Gwyn. Alexander Fleming: The Man and the Myth. Cambridge, Mass.: Harvard University Press, 1984. Well written, with many penetrating insights, this treatment of Fleming’s life and work is noteworthy both for explaining scientific matters clearly and for providing a balanced view of Fleming in the context of his era. In reference to the subtitle, it should be noted that Fleming kept a scrapbook of everything untrue about him printed in the press, and he titled the scrapbook “The Fleming Myth.”

Maurois, André. The Life of Sir Alexander Fleming. New York: E. P. Dutton, 1959. This work remains the best biography of Fleming purely from the literary perspective. Maurois was a master biographer, and his work is characterized by elegance and a keen understanding of the complexity of his subjects. Maurois’s treatment of Fleming is, however, marred somewhat by his uncritical approach to his subject and his tendency to include errors when dealing with scientific matters.

Pollitt, Ronald, and Herbert Curry. Portraits in British History. Homewood, Ill.: Dorsey Press, 1975. The last of the fifteen original biographical essays in this work is devoted to the life and career of Fleming. A readable, relatively concise essay, it remains the best available treatment of the subject in anything less than a book-length study. It also has the merit of synthesizing all works dealing with Fleming prior to 1975.

Sheehan, John. The Enchanted Ring: The Untold Story of Penicillin. Cambridge, Mass.: MIT Press, 1982. A well-written account of the complex series of events that began with Fleming’s initial discovery and concluded with the practical use of penicillin as an antibiotic. This study includes some particularly impressive scholarly detective work.

Wilson, David. In Search of Penicillin. New York: Alfred A. Knopf, 1976. While it includes all the important factual data about the subject, this study is especially useful in explaining Fleming’s contribution to the development of penicillin by carefully dovetailing his achievements with those of the other scientists who played important roles in refining the drug.