History of Antibiotics and Penicillin

Germ theory, established by Louis Pasteur and Robert Koch, made it plausible that particular organisms caused particular diseases, and that targeted interventions might follow. That framework is traced in Germ Theory and the Remaking of Medicine.

Paul Ehrlich gave the search its name and its goal. He coined the term "chemotherapy" and sought a "magic bullet" (Zauberkugel) that would destroy a pathogen without damaging the host. His laboratory's arsphenamine, marketed as Salvarsan and introduced in 1910, became the first effective treatment for syphilis and the model for selective antimicrobial therapy. See the Salvarsan timeline entry.

For two decades, Salvarsan and its derivative Neosalvarsan were the only chemical therapies for bacterial infection. The next breakthrough came with the sulfonamides: the dye Prontosil, found active against streptococcal infection in the 1930s, and the active compound sulfanilamide identified in 1935. Sulfonamides were the first antimicrobials to save lives at scale, and they created the clinical expectation that a chemical could decisively treat a specific infection.

In 1928, Alexander Fleming, a bacteriologist at St Mary's Hospital in London, noticed that a contaminating mold of the genus Penicillium had cleared the bacteria around it on an agar plate. He isolated the mold, extracted its active substance, and named it penicillin. He published the observation in 1929 in the British Journal of Experimental Pathology.

Fleming showed that penicillin inhibited staphylococci and other gram-positive bacteria, but he could not purify the unstable compound in sufficient quantity. For about a decade, no one took the work further; Fleming sent his mold to researchers who asked for it, but interest had waned. The observation remained a laboratory curiosity rather than a drug.

The penicillin timeline entry and the profile of Alexander Fleming examine this moment and its later reputation.

In 1939, the pathologist Howard Florey read Fleming's 1929 paper and, with the biochemist Ernst Chain and the pharmacologist Norman Heatley, began a programme at Oxford to recover penicillin as a usable substance. They developed methods of cultivation, extraction, and purification, and in 1940 showed in mouse experiments that penicillin could clear infections.

In 1941 the team began the first human trials at the Radcliffe Infirmary in Oxford. The best-known early patient was Albert Alexander, a city councillor who had developed a severe infection after injuring his face; he improved dramatically after treatment began on 12 February, but the scarce supply ran out and he died on 15 March 1941. The Oxford team's clinical results were published in the Lancet in August 1941.

The Oxford work established that penicillin was clinically powerful, but it also showed the central problem: the material was too scarce and too expensive to be a general treatment. Turning it into a standard medicine required industrial production.

In 1941 Florey and Heatley visited the United States, where the problem was taken up by government laboratories and pharmaceutical companies. The USDA's Northern Regional Research Laboratory in Peoria, Illinois, developed deep-tank fermentation, and a high-yielding strain of Penicillium chrysogenum made large-scale production feasible. Wartime cooperation between Britain and the United States was, by 1943, "incredibly successful," according to later historical accounts.

By the time of the Normandy landings in 1944, penicillin had been stockpiled for military use, and it became a standard part of wartime surgical and trauma care. That connection links antibiotics to military medicine.

In 1945 Fleming, Florey, and Chain were awarded the Nobel Prize in Physiology or Medicine. The British government also decided to make penicillin widely available rather than tightly patented, and after the war production in the Netherlands and elsewhere increased supply and lowered prices. Penicillin had become ordinary.

The microbiologist Selman Waksman, who coined the term "antibiotic" in 1942, led the search for further compounds. His laboratory at Rutgers found streptomycin in 1943, which became the first effective treatment for tuberculosis and opened a new class of drugs. Waksman received the 1952 Nobel Prize; his graduate student Albert Schatz, who had isolated streptomycin, was not included, a priority dispute that remains a cautionary episode in the history of scientific credit.

Streptomycin's success against tuberculosis showed that antibiotics could reach diseases that had long resisted treatment. In the following years, chloramphenicol (1947), the tetracyclines (from 1948), and ampicillin, a broad-spectrum semisynthetic penicillin introduced in 1961, joined the family. By the 1960s, dozens of antibiotics were in clinical use, each with a different target and spectrum.

Which compounds became therapies depended on pharmaceutical screening, fermentation, medicinal chemistry, patents, and global supply. That industrial and commercial dimension is part of the broader history traced in From Materia Medica to Modern Drugs.

Penicillin-resistant staphylococci were reported as early as 1943, only a few years after the first clinical use. Bacterial variation, selection, transmission, and incomplete treatment meant that resistance was an expected consequence of use, not an accident.

World Health Organization expert reports were addressing antibiotic resistance by the 1960s, and the organization has since treated resistance as a global health threat. In the 1980s, methicillin-resistant Staphylococcus aureus (MRSA) became a well-known hospital problem.

In 2015 WHO launched its first Global Action Plan on antimicrobial resistance, and in 2016 the independent Review on Antimicrobial Resistance chaired by Jim O'Neill projected that, without action, drug-resistant infections could cause about 10 million deaths a year by 2050. WHO first published its bacterial priority-pathogens list in 2017 and issued an updated list in 2024 to guide research and investment.

Current estimates remain large and uncertain: WHO's 2026 fact sheet reports that bacterial resistance was associated with more than 4.7 million deaths globally in 2021, and that about one in six laboratory-confirmed bacterial infections worldwide was resistant to an antibiotic in 2023. Resistance therefore belongs to the wider history of epidemics and public health.

Start with the penicillin timeline entry and the profile of Alexander Fleming. For the background that made antibiotics possible, read Germ Theory and the Remaking of Medicine, Louis Pasteur, Robert Koch, Paul Ehrlich, and the Salvarsan timeline entry.

For the surgical and institutional context, follow antiseptic surgery, Surgery Through the Ages, History of Military Medicine, and History of Tuberculosis. For the credit and priority questions, see Who Gets Credit for Medical Discovery?.