The History of Penicillin and Antibiotics

The Drugs That Changed Modern Medicine

Prescription Drugs
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From the Greek—"anti, meaning "against" and bios, meaning "life," an antibiotic is a chemical substance produced by one organism that is destructive to another. The word antibiotic comes from "antibiosis," a term coined in 1889 by a pupil of Louis Pasteur's named Paul Vuillemin to who used it to define a process by which life could be used to destroy life. Antibiotics are natural substances that are released by bacteria and fungi into their environment, as a means of inhibiting other organisms. You can think of it as is chemical warfare on a microscopic scale.

Sir Alexander Fleming

Penicillin is one of the earliest discovered and most widely used antibiotic agents. While Sir Alexander Fleming is credited with its discovery, it was French medical student Ernest Duchesne who first took note of the bacteria in 1896. Fleming's more famous observations would not be made until more than two decades later.

Fleming, a trained bacteriologist, was working St. Mary's Hospital in London when in 1928, he observed a plate culture of Staphylococcus that had been contaminated by a blue-green mold. On closer inspection, he noted that the colonies of bacteria adjacent to the mold were being dissolved.

Curious, Fleming decided to grow the mold in pure culture, from which he was able to see that colonies of the bacterium Staphylococcus aureus were being destroyed by the mold Penicillium notatum, proving, in principle at least, the existence of an antibacterial agent. Fleming named the substance penicillin and published his findings in 1929, noting that his discovery might someday have therapeutic value if it could be produced in quantity, however, it would be years before Fleming's findings would be put into practical, widespread use.

British Research Continues

In 1930, Dr. Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, began experimenting with penicillin for the treatment of infant patients suffering neonatal infections (and later with adults suffering eye infections). After an inauspicious start, he successfully cured his first patient on November 25, 1930, however with only a mild success rate, Dr. Paine's efforts with penicillin were limited to a handful of patients.

In 1939, led by Australian scientist Howard Florey, the work of a team of penicillin researchers at Oxford University’s Sir William Dunn School of Pathology that included Ernst Boris Chain, Edward Abraham, Arthur Duncan Gardner, Norman Heatley, Margaret Jennings, J. Orr-Ewing, and G. Sanders was beginning to show great promise. By the following year, the team was able to demonstrate penicillin's ability to kill infectious bacteria in mice. By 1940, they'd come up with a method for mass-producing penicillin but unfortunately, the output failed to meet expectations.

In 1941, the team began a clinical trial with their first human patient, a policeman named Albert Alexander who was suffering from a severe facial infection. Initially, Alexander’s condition improved but when supplies of penicillin ran out he succumbed to the infection. While subsequent patients were treated successfully, synthesizing the drug in sufficient quantity remained a stumbling block.

Key Research Shifts to the United States

With the increasing demands of World War II putting a huge drain on Great Britain's industrial and governmental resources, the British scientists did not have the means to continue clinical trials on humans at Oxford. Dr. Florey and his colleagues turned to the United States for help and were quickly referred to the Northern Regional Laboratory in Peoria, Illinois, where American scientists were already working on fermentation methods to increase the growth rate of fungal cultures. On July 9, 1941, Dr. Florey and Dr. Norman Heatley came to the United States bearing a vital package containing a small amount of penicillin to begin work.

By pumping air into deep vats containing corn steep liquor (a non-alcoholic by-product of the wet milling process) combined with other key ingredients, researchers were able to induce faster penicillin growth than with any previous methods. Ironically, after a worldwide search, it was a modified strain of penicillin that came from a moldy cantaloupe in a Peoria market produced the largest amount of penicillin when grown in submerged deep-vat conditions.

By November 26, 1941, Andrew J. Moyer, Peoria Lab's expert on the nutrition of molds, had succeeded, with the assistance of Dr. Heatley, in a tenfold increase in the yield of penicillin. After clinical trials were performed in 1943, penicillin was shown to be the most effective antibacterial agent to date.

Mass Production & the Legacy of Penicillin

Meanwhile, simultaneous research being conducted a Pfizer Labs in Brooklyn, New York, helmed by Jasper H. Kane, led to a more practical fermentation method for the mass production of pharmaceutical-grade penicillin. By the time Allied forces hit the beaches on D-Day on June 6, 1944, there was an ample supply of the drug to treat the numerous casualties. Another benefit to mass production was the decrease in cost. Penicillin prices fell from a prohibitively expensive rate in 1940 to $20 per dose in July 1943 to $0.55 per dose by 1946.

The 1945 Nobel Prize for Physiology or Medicine was awarded jointly to Sir Alexander Fleming, Ernst Boris Chain, and Sir Howard Walter Florey "for the discovery of penicillin and its curative effect in various infectious diseases." Dr. Andrew J. Moyer from the Peoria Lab was inducted into the Inventors Hall of Fame and both the British and Peoria Laboratories were designated as International Historic Chemical Landmarks. On May 25, 1948, Dr. Moyer was granted a patent for a method of the mass production of penicillin.

A Timeline of Antibiotics

  • Ancient History—The ancient Egyptians, Chinese, and indigenous tribes of Central America all used various forms of mold to treat infected wounds.
  • Late 1800s–The search for antibiotics begins in the late 1800s with the growing acceptance of the germ theory of disease that linked bacteria and other microbes to the causation of a variety of ailments.
  • 1871—The surgeon Joseph Lister begins research into a phenomenon indicating that urine contaminated with mold inhibited the growth of bacteria.
  • 1890s—German doctors Rudolf Emmerich and Oscar Low are the first to make an effective medication from microbes. While their drug, known as pyocyanase, was the first antibiotic to be used in hospitals, it did not have an effective cure rate.
  • 1928—Sir Alexander Fleming observes that colonies of the bacterium Staphylococcus aureus could be destroyed by the mold Penicillium notatum, demonstrating the principle of antibiotics.
  • 1935—Prontosil, the first sulfa drug, is discovered in 1935 by German chemist Gerhard Domagk.
  • 1942—Howard Florey and Ernst Chain invent a viable manufacturing process for Penicillin G Procaine, which can now be sold as a drug.
  • 1943—Using microbes culled from soil bacteria, American microbiologist Selman Waksman invents streptomycin, the first of a new class of drugs called aminoglycosides that could be used to treat tuberculosis and other infections, however, the side effects of early-stage drugs often outweigh their curative value.
  • 1945—Using advanced X-ray crystallography, Oxford University scientist Dr. Dorothy Crowfoot Hodgkin defines the molecular layout of penicillin, confirming its structure as previously hypothesized and leading to enhanced development of other antibiotics and biomolecular substances, including vitamin B12.
  • 1947—Four years after mass production of penicillin begins, resistant microbes appear, including Staphylococcus aureus. Usually harmless in humans, if allowed to flourish unchecked, Staphylococcus aureus produces toxins that result in illnesses including pneumonia or toxic shock syndrome.
  • 1955—Lloyd Conover receives a patent for Tetracyclin. It soon becomes the most prescribed broad-spectrum antibiotic in the United States.
  • 1957—Nystatin, used to cure many disfiguring and disabling fungal infections, is patented.
  • 1981—SmithKline Beecham patents a semisynthetic antibiotic called Amoxicillin or amoxicillin/clavulanate potassium. The antibiotic debuts in 1998 under the tradenames of Amoxicillin, Amoxil, and Trimox.