In 1897, a young French medical student named Ernest Duchesne submitted a ground-breaking doctoral thesis titled Contribution to the Study of Vital Competition Between Microorganisms: Antagonism Between Moulds and Microbes. In this work, Duchesne introduced a revolutionary idea that bacteria and moulds are locked in a constant struggle for survival, and this antagonism could be exploited for therapeutic use.
Although the therapeutic properties of fungi and plants in treating infections was known since ancient times, it was Duchesne who showed experimentally that certain moulds destroyed pathogenic bacteria such as Salmonella typhi (which causes typhoid fever) and Escherichia coli in laboratory cultures and when injected into guinea pigs. What Duchesne had discovered was the natural antibiotic penicillin—an achievement typically credited to Scottish physician Alexander Fleming. Duchesne’s work remained largely forgotten until it was rediscovered more than 50 years later, in 1949, four years after Fleming was awarded the prestigious Nobel Prize for his discovery.
Culture of penicillium mould. Photo credit: Wikimedia Commons
Ernest Duchesne was born in Paris in 1874, the son of a chemical engineer who owned a tannery. After completing his secondary education, he was admitted to the military medical school in Lyon (École du Service de Santé Militaire) in 1894. Two years later, Duchesne began his research under the guidance of Gabriel Roux, a professor of microbiology and Director of the Municipal Office of Hygiene in Lyon.
Roux had observed an intriguing phenomenon: despite the abundance of fungal spores in the air, they were absent in tap water and fountain water, though they could be made to grow in distilled water. This led Roux to suspect that certain microorganisms in the water might be inhibiting mould growth. He suggested Duchesne explore this idea as the foundation for his thesis. This observation would prove to be the starting point for Duchesne’s pivotal work on microbial competition, eventually leading to his overlooked discovery of penicillin.
Duchesne conducted a series of experiments in which he cultured Penicillium glaucum in broth, then introduced small amounts of bacteria, Salmonella typhi and Escherichia coli, into the fungal colonies. 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 perished, it might have weakened the bacteria, potentially reducing their virulence and pathogenic properties.
Ernest Duchesne
To test this theory, Duchesne injected guinea pigs with a solution containing an equal mixture of Penicillium glaucum and E. coli. Initially, the animals became seriously ill, but they recovered quickly. Two days after the initial injection, he administered the same mixture again, and the animals showed no ill effects, suggesting they had developed immunity to the E. coli. When guinea pigs were injected with a mixture of S. typhi and P. glaucum, they exhibited a similar immune response.
Duchesne noted that “certain moulds (Penicillum glaucum), inoculated into an animal at the same time as very virulent cultures of some pathogenic microbes (E. coli and typhoid), are capable of reducing to a very considerable degree the virulence of these bacterial cultures.”
Although Duchesne failed to identify the antibiotic produced by the mould Penicillium glaucum, he did correctly conclude about the therapeutic use of fungi:
We hope that the pursuit of these studies on the vital competition for life between fungi and microbes that we have only begun here, and for which we do not pretend to have made more than a small contribution, may result in the discovery of other facts useful and applicable to prophylactic hygiene and therapy.
Duchesne’s thesis earned him a degree, but the novelty of his research failed to intrigue the medical society. Toward the end of 1898, Duchesne was appointed physician to the 2nd Regiment of Hussars based in Senlis. He married in 1901, but his wife died two years later of tuberculosis. He himself became ill with the disease in 1904, and was discharged from the army in 1907. He spent the last years of his life at various sanatoria in the South of France and in Switzerland before dying in 1912 at the age of thirty seven.
Sixteen years later, in 1928, Alexander Fleming experienced a similar discovery to Duchesne’s when his cultures of Staphylococcus aureus were accidentally contaminated with Penicillium mould. Fleming, like Duchesne, observed that the mould was releasing a substance that inhibited bacterial growth. Despite the significance of this finding, Fleming's 1929 paper, published in the British Journal of Experimental Pathology, failed to attract much attention—much like Duchesne’s thesis years earlier.
Alexander Fleming in his laboratory at St Mary's Hospital, London. Photo credit: Wikimedia Commons
Fleming himself was uncertain about the practical medical applications of his discovery. He was more focused on its potential use in bacterial isolation than in treating infections. His chemist colleagues attempted, unsuccessfully, to isolate the active substance—penicillin—leading Fleming to abandon further research on it.
A decade later, in the late 1930s, German-born British biochemist Ernst Boris Chain rediscovered Fleming's overlooked 1929 paper. Recognizing its potential, Chain suggested to Australian scientist Howard Florey that investigating antibacterial substances produced by microorganisms could be a promising line of research. Florey assembled a team of biologists and biochemists at Oxford University, and their collaborative efforts ultimately led to the successful isolation and mass production of penicillin, transforming it into a lifesaving antibiotic. This breakthrough came just in time for widespread use during World War II, changing the course of medicine.
After the curative properties of penicillin became public knowledge, thanks to an editorial in The Times, Alexander Fleming found himself at the center of attention, overshadowing Howard Florey. The media, eager to promote the familiar narrative of a lone scientist making a serendipitous discovery, distorted the facts and attributed the development of penicillin almost entirely to Fleming. Despite the inaccuracies, neither Fleming nor St. Mary's Hospital, where he made his initial observations, made any effort to correct the record. In fact, Fleming later made a statement that hinted at arrogance: “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I suppose that was exactly what I did.”
Howard Florey and Ernst Chain.
In 1945, Fleming, along with Florey and Ernst Boris Chain, was awarded the Nobel Prize in Physiology or Medicine for "the discovery of penicillin and its curative effect in various infectious diseases." Although the prize was shared equally among the three, it was Fleming who continued to receive the lion’s share of public recognition, while Florey and Chain’s crucial roles in developing penicillin into a viable treatment were often overlooked.
Duchesne’s work resurfaced in 1949, thanks to Justin Godart, who presented a paper titled "Le Précurseur Français de l'Action 'Antibiotique' du Penicillium" (The French Forerunner of the Antibiotic Action of Penicillium) before the Académie Nationale de Médecine in February of that year. This marked the beginning of a long-overdue recognition of Duchesne’s contributions.
See: Alexander Fleming’s Microbial Art
In the years that followed, opinions on Duchesne's legacy varied widely. Some claimed unequivocally that Duchesne was the true discoverer of penicillin, having documented its antibacterial properties decades before Fleming. Others contended that while Duchesne was the first to observe the antagonistic relationship between Penicillium and bacteria, his work did not fully reveal the potential for therapeutic use.
In their textbook for first-year chemical and bioprocessing engineering students, Ricardo Simpson and Sudhir K. Sastry argue that “according to the historical background, the person who first noticed the presence of penicillin was not Alexander Fleming, but the French medical student Ernest Duchesne, in 1896.” Similarly, in his acclaimed book Bad Medicine, David Wootton challenges the conventional attribution of the discovery solely to Fleming and instead calls for a more nuanced distribution of credit. He writes, “Thus it would seem fair to say that [Joseph] Lister and Duchesne had both independently discovered penicillin, and had taken it somewhat further than Fleming did, and that there was nothing remarkable in Fleming’s initial identification of penicillium [sic] as an antibiotic.”
Wootton’s assertion underscores the idea that the foundational work of both Lister and Duchesne, long before Fleming, laid the groundwork for what would become the discovery of penicillin. In 1944, botanist Jules Brunel noted that Fleming’s lasting fame was largely due to his coining of the term “penicillin,” rather than his being the first to witness microbial antagonism. Brunel's observation highlights how language and timing often play a critical role in shaping historical recognition, leaving earlier contributors like Duchesne largely overlooked for many years.
There are, however, those who attempt to discredit Duchesne’s work. British scholar Gilbert Shama, for instance, argues that the P. glaucum cultures Duchesne worked with likely did not contain penicillin, since the guinea pigs he injected with the solution survived. Shama points out that guinea pigs are extremely sensitive to penicillin, suggesting that had penicillin been present in Duchesne’s experiments, the animals would have likely died. He further speculates that “the fungal mycelium may have stimulated the animals’ innate defenses, and this may have contributed to their survival,” rather than the presence of an antibiotic substance.
Ultimately, the debate over who truly discovered penicillin may be less significant than recognizing those who advanced it to the point of practical application. While both Duchesne and Fleming made important contributions to understanding microbial antagonism, the real credit for penicillin’s widespread medical use belongs to the scientists, such as Howard Florey, Ernst Boris Chain, and their team, who isolated and developed it into a life-saving drug. It was their work that made penicillin available on a global scale, revolutionizing modern medicine.
The British medical historian Bill Bynum sums this up nicely:
The discovery and development of penicillin is an object lesson of modernity: the contrast between an alert individual (Fleming) making an isolated observation and the exploitation of the observation through teamwork and the scientific division of labour (Florey and his group). The discovery was old science, but the drug itself required new ways of doing science.
References:
# Serge Duckett, Ernest Duchesne and the concept of fungal antibiotic therapy, Lancet
# Gilbert Shama, Deconstructing the fable of the discovery of penicillin by Ernest Duchesne, Endeavour
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