The Forgotten Inventor of Antibiotics

In 1897, a young French medical student named Ernest Duchesne submitted a doctoral thesis entitled A Contribution to the Study of the Competition for Life among Microorganisms: Antagonism between Molds and Bacteria. In this thesis, Duchesne put forward the revolutionary idea that bacteria and molds are constantly engaged in a struggle for existence and that humans can exploit this antagonism to treat diseases, according to Amusing Planet.

Although the medicinal properties of fungi and plants in treating infectious diseases had been known since ancient times, it was Duchesne who experimentally demonstrated that certain molds destroyed pathogenic bacteria such as Salmonella typhi (which causes typhoid fever) and Escherichia coli in the laboratory when injected into guinea pigs. What Duchesne discovered was the natural antibiotic penicillin, an achievement often associated with the Scottish physician Alexander Fleming. Duchesne’s research was largely forgotten until it was rediscovered more than 50 years later, in 1949, four years after Fleming was awarded the Nobel Prize.

Ernest Duchesne was born in Paris in 1874, the son of a chemical engineer who owned a tannery. After finishing high school, he was admitted to the military medical school in Lyon (École du Service de Santé Militaire) in 1894. Two years later, Duchesne began his studies under the guidance of Gabriel Roux, professor of microbiology and director of the Provincial Sanitary Service in Lyon.

Roux observed an interesting phenomenon. Although fungal spores were abundant in the air, they were absent from tap and fountain water, although they could grow in distilled water. This led Roux to suspect that some microorganisms in the water might inhibit mold growth. He suggested that Duchesne explore this idea as the basis for his dissertation. That observation was the starting point for Duchesne’s pivotal research on competition with bacteria, which eventually led to his discovery of penicillin.

Duchesne conducted a series of experiments in which he cultured Penicillium glaucum in meat broth, then introduced small amounts of Salmonella typhi and Escherichia coli bacteria into the fungal population. Each time, the fungal spores died. He concluded that in the struggle for survival, the bacteria had the upper hand. However, Duchesne speculated that before the Penicillium died, it might weaken the bacteria, thereby reducing their virulence and disease-causing properties.

To test this hypothesis, Duchesne injected guinea pigs with a solution containing equal amounts of Penicillium glaucum and E. coli. The mice initially became very ill, but recovered quickly. Two days after the first injection, he injected them with the same dose. The mice showed no signs of illness, indicating that they had developed resistance to the E. coli. When guinea pigs were injected with a mixture of S. typhi and P. glaucum, they also had a similar immune response.

Duchesne found that mold (Penicillium glaucum), injected into animals at the same time as certain bacteria such as S. typhi and E. coli, could significantly reduce their virulence. Although Duchesne could not identify the antibiotic produced by Penicillium glaucum, he was correct in his conclusions about how molds could be used to treat disease.

Duchesne’s thesis earned him a doctorate, but his ideas failed to gain traction in the medical community. By the end of 1898, Duchesne was commissioned as a physician in the Second Cavalry Regiment stationed at Senlis. He married in 1901, but his wife died two years later of tuberculosis. He himself contracted the disease in 1904 and was discharged from the army in 1907. He spent his final years in various sanatoriums in southern France and Switzerland before dying in 1912 at the age of 37.

In 1928, 16 years later, Alexander Fleming made a discovery similar to Duchesne’s when his culture of Staphylococcus aureus was accidentally contaminated with the fungus Penicillium. Like Duchesne, Fleming observed that the fungus secreted compounds that inhibited bacterial growth. Despite the importance of his discovery, Fleming’s paper published in the British journal Experimental Pathology did not attract much attention, as had Duchesne’s thesis many years earlier.

Fleming himself was uncertain about the practical medical applications of his discovery. He was more focused on its potential use in isolating bacteria rather than treating infectious diseases. His fellow chemists attempted to isolate the active compound penicillin but were unsuccessful, prompting Fleming to abandon further research.

A decade later, in the late 1930s, British biochemist Ernst Boris Chain rediscovered Fleming’s overlooked 1929 paper. Recognizing its potential, Chain suggested that Australian scientist Howard Florey investigate antibacterial compounds secreted by microorganisms. Florey assembled a team of biologists and biochemists at Oxford University. Their collaboration eventually led to the successful isolation and mass production of penicillin, turning it into a life-saving antibacterial agent. The breakthrough came in time for widespread use during World War II, transforming medicine.

Once the therapeutic properties of penicillin became widely known, Alexander Fleming became the center of attention, even overshadowing Howard Florey. In 1945, Fleming, along with Florey and Ernst Boris Chain, were awarded the Nobel Prize in Physiology or Medicine for “the discovery of penicillin and its therapeutic effect in many infectious diseases.” Although the prize was split between the three, Fleming continued to receive public recognition, while Florey and Chain’s pivotal roles in developing penicillin into a viable treatment were often overlooked.