What was the Golden Age of Antibiotics, and how can we spark a new one?
Many antibiotics were developed during the “Golden Age of Antibiotics”. How did it happen, why has antibiotic development slowed down since then, and what can we do to reignite it?
Antibiotic-like remedies date back millennia, with records of moldy bread and medicinal soil being used to treat wounds in ancient Egypt, Greece, and China. We now know they are likely to have contained antibiotic compounds.1
But the modern scientific journey began in the early 20th century. Scientists gradually began discovering antibiotics from synthetic sources, such as dyes, and natural sources, such as bacteria and fungi.
In the 1940s, antibiotic development took off, and a wide range of new antibiotics were discovered. This led to the “Golden Age of Antibiotics” from the early 1940s to the mid-1960s.
In this article, I visualize the history of antibiotics, describe how they were developed, and explain why antibiotic development has slowed down. I also give some ideas on how to reignite antibiotic development today so we can overcome antibiotic resistance and continue to have effective antibiotics in the future.
The discovery and development of antibiotics
In the early 1900s, the microbiologist Paul Ehrlich worked on dyes that stained bacteria. He searched for potential medicines that could target microbes without harming human cells.
In 1910, after testing hundreds of compounds, he made a breakthrough and identified salvarsan — which became the first effective treatment for syphilis and the first synthetic antibiotic used in medicine. It’s a type of arsphenamine, the second antibiotic class from the top of the timeline.1
Another milestone came in 1928 when Alexander Fleming observed fungal mold that killed bacteria on a contaminated Petri dish. He had discovered penicillin. Unfortunately, scaling up penicillin production took years, as shown in the timeline below. It’s the fourth antibiotic class from the top.2
Penicillin’s story is important because it influenced the development of other antibiotics during this period as well.
Researchers at the University of Oxford, who worked with Fleming to purify penicillin, sought help and funding to mass manufacture it. They approached the Office of Scientific Research and Development (OSRD) in the United States, which oversaw national science funding in America during World War II.3
Infections were a major cause of death among soldiers and civilians at the time.4 Because of this, the OSRD recognized the potential of penicillin and launched a global search with the United States Department of Agriculture (USDA) to find another fungal strain that could produce it with a higher yield. Eventually, the strain was found, growing on a cantaloupe.5
The US War Production Board then coordinated efforts to improve fermentation, organize clinical trials, foster collaboration, share data, and lift patent restrictions — which sped up development. In 1943, they provided sufficient quantities to the military and some civilians, and by 1945, enough to make it widely available to the American public.6
The knowledge, manufacturing processes, and technologies that labs gained while scaling up penicillin during this time made it easier for them to work on other antibiotics.7
There was another pivotal breakthrough around this time as well: the scientist Selman Waksman discovered the potential of actinomycetes, a group of soil-dwelling bacteria that are prolific producers of antibiotics. Through repetitive screening, Waksman and then-PhD student Albert Schatz discovered streptomycin, which effectively treated tuberculosis. Many more antibiotics from actinomycetes bacteria followed, including tetracyclines and macrolides. Repetitive screening helped identify many more antibiotics from other organisms.8
As the timeline above shows, there were often very rapid turnaround times between discovery and introduction during this period. Some antibiotics, like tetracyclines, macrolides, and pyridinamides, were introduced in the same year they were discovered.
The Golden Age of Antibiotics
The period between the early 1940s and the mid-1960s is called “the Golden Age of Antibiotics”, as intense research into natural and synthetic compounds led to the rapid discovery of many new antibiotics.
The timeline below is now arranged by the year of clinical introduction for each antibiotic drug class.
It shows that almost two-thirds of all antibiotic drug classes were developed during the Golden Age of Antibiotics. Most are still used today.
By the 1970s, the antibiotic pipeline slowed dramatically. Since 1970, only 8 new classes have been approved.9
One reason was that pharmaceutical companies shifted focus to more profitable chronic disease treatments, which offered steady, long-term revenue compared to antibiotics, which are typically used for short durations and sold at low prices.10
Rising antibiotic resistance also reduced the demand for new antibiotics, which are typically reserved for severe drug-resistant infections — a relatively small market. In addition, efforts to identify new antibiotics, by screening organisms for antibiotic activity, often led to reidentifying the same compounds already discovered by others.11
These challenges, along with high development costs and low profitability, pushed many large pharmaceutical companies out of the market, leaving smaller firms struggling with limited resources.
How can we reignite antibiotic drug discovery?
In recent decades, there have been scientific and economic efforts to reignite antibiotic drug discovery.
One approach has been through synthetic biology and “genome mining” — a technique that identifies antibiotic genes hidden in microbes that are not expressed by them in standard laboratory conditions. Some potential new antibiotics have been found through these efforts, but they’re currently still in clinical testing.12
Research suggests that we’ve only identified a small fraction of the bacterial species in the world. So another approach is to cultivate bacteria in their natural environments, such as soil, or explore currently undiscovered bacteria in extreme ecosystems like oceans and deserts to reveal antibiotic compounds they might produce in those environments. 13
Finally, drug discovery could focus on combining different antibiotics to prevent resistance from developing: this would be possible when resistance to one antibiotic makes bacteria more vulnerable to another.14
Underlying the problem, however, is the lack of economic incentives, which are critical to drive innovation and manufacturing.
Antibiotics are unique: their usage often lasts only days or weeks, and new antibiotics are used sparingly to slow down resistance. This means that antibiotic innovation generates far less revenue than drugs for many other conditions.
To overcome this, governments and organizations are using new funding models. For example, “Advance Market Commitments” could reward companies for successfully bringing new antibiotics to market by guaranteeing payments if they meet approval standards.15
Another idea, piloted in the UK, is to use “subscription models” where health institutions or countries would pay an annual fee for access to antibiotics rather than paying based on volume. This could reward medical innovation and compensate manufacturers while keeping usage low.11
Collaborative funding efforts like CARB-X and GARDP, which support projects tackling drug-resistant infections, also help bridge the gap. These initiatives provide more financial stability to developers, reduce risks, and ensure essential new antibiotics are developed for people who need them most.11
The Golden Age of Antibiotics resulted from coordinated efforts, incentives, prioritization, and new technologies.
Since then, antibiotic development has slowed down. But it doesn’t have to be this way.
Rapid advances in genome sequencing and synthetic biology could allow more antibiotics to be discovered and developed. Many as-yet-undiscovered bacteria could be sources of new antibiotics, but current economic incentives to work on them are limited.
With better incentives and research efforts, a new age of antibiotic discovery and development could be ignited.
Acknowledgments
I’m grateful to Edouard Mathieu and Max Roser for providing feedback on this article.
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Endnotes
Hutchings, M. I., Truman, A. W., & Wilkinson, B. (2019). Antibiotics: Past, present and future. Current Opinion in Microbiology, 51, 72–80. https://doi.org/10.1016/j.mib.2019.10.008
Gaynes, R. (2017). The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerging Infectious Diseases, 23(5), 849–853. https://doi.org/10.3201/eid2305.161556
Gaynes, R. (2017). The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerging Infectious Diseases, 23(5), 849–853. https://doi.org/10.3201/eid2305.161556
Why We Should Reexamine the “Golden Age” of Antibiotics in Social Context. (2024). AMA Journal of Ethics, 26(5), E418-428. https://doi.org/10.1001/amajethics.2024.418
Infectious diseases were the second-most common cause of hospital admissions in the US Army during World War II. The death rate from infectious diseases had been declining for many decades before WWII and declined further during the war as antibiotics became widely available.
Medical Department, US Army (1975). Medical Statistics in World War II. Available online.
Cirillo, V. J. (2008). Two Faces of Death: Fatalities from Disease and Combat in America’s Principal Wars, 1775 to Present. Perspectives in Biology and Medicine, 51(1), 121–133. https://doi.org/10.1353/pbm.2008.0005
Gaynes, R. (2017). The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerging Infectious Diseases, 23(5), 849–853. https://doi.org/10.3201/eid2305.161556
US Department of Agriculture. (nd.) The Enduring Mystery of “Moldy Mary”. Available online.
Sampat, B. N. (2023). Second World War and the Direction of Medical Innovation. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.4422261
Gaynes, R. (2017). The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use. Emerging Infectious Diseases, 23(5), 849–853. https://doi.org/10.3201/eid2305.161556
Why We Should Reexamine the “Golden Age” of Antibiotics in Social Context. (2024). AMA Journal of Ethics, 26(5), E418-428. https://doi.org/10.1001/amajethics.2024.418
Baxter, J. P. (1946). Scientists Against Time (Vol. 1, Ch. 22). Little Brown. Available online.
Sampat, B. N. (2023). Second World War and the Direction of Medical Innovation. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.4422261
Waksman, S. A., & Schatz, A. (1945). Streptomycin–Origin, Nature, and Properties*††Journal Series Paper of the Department of Microbiology of the New Jersey Agricultural Experiment Station, Rutgers University. Journal of the American Pharmaceutical Association (Scientific Ed.), 34(11), 273–291. https://doi.org/10.1002/jps.3030341102
Hutchings, M. I., Truman, A. W., & Wilkinson, B. (2019). Antibiotics: Past, present and future. Current Opinion in Microbiology, 51, 72–80. https://doi.org/10.1016/j.mib.2019.10.008
As of 2023.
Hutchings, M. I., Truman, A. W., & Wilkinson, B. (2019). Antibiotics: Past, present and future. Current Opinion in Microbiology, 51, 72–80. https://doi.org/10.1016/j.mib.2019.10.008
Årdal, C., Balasegaram, M., Laxminarayan, R., McAdams, D., Outterson, K., Rex, J. H., & Sumpradit, N. (2020). Antibiotic development—Economic, regulatory and societal challenges. Nature Reviews Microbiology, 18(5), 267–274. https://doi.org/10.1038/s41579-019-0293-3
Årdal, C., Balasegaram, M., Laxminarayan, R., McAdams, D., Outterson, K., Rex, J. H., & Sumpradit, N. (2020). Antibiotic development—Economic, regulatory and societal challenges. Nature Reviews Microbiology, 18(5), 267–274. https://doi.org/10.1038/s41579-019-0293-3
As an example, “humimycins” were discovered through genome mining efforts.
Chu, J., Vila-Farres, X., Inoyama, D., Ternei, M., Cohen, L. J., Gordon, E. A., Reddy, B. V. B., Charlop-Powers, Z., Zebroski, H. A., Gallardo-Macias, R., Jaskowski, M., Satish, S., Park, S., Perlin, D. S., Freundlich, J. S., & Brady, S. F. (2016). Discovery of MRSA active antibiotics using primary sequence from the human microbiome. Nature Chemical Biology, 12(12), 1004–1006. https://doi.org/10.1038/nchembio.2207
Hutchings, M. I., Truman, A. W., & Wilkinson, B. (2019). Antibiotics: Past, present and future. Current Opinion in Microbiology, 51, 72–80. https://doi.org/10.1016/j.mib.2019.10.008
Kolter, R., & Van Wezel, G. P. (2016). Goodbye to brute force in antibiotic discovery? Nature Microbiology, 1(2), 15020. https://doi.org/10.1038/nmicrobiol.2015.20
Kolter, R., & Van Wezel, G. P. (2016). Goodbye to brute force in antibiotic discovery? Nature Microbiology, 1(2), 15020. https://doi.org/10.1038/nmicrobiol.2015.20
Baym, M., Stone, L. K., & Kishony, R. (2016). Multidrug evolutionary strategies to reverse antibiotic resistance. Science, 351(6268), aad3292. https://doi.org/10.1126/science.aad3292
Kremer, M., Levin, J., & Snyder, C. M. (2020, May). Advance market commitments: insights from theory and experience. In AEA Papers and Proceedings (Vol. 110, pp. 269-273). Available online.
Renwick, M. J., Brogan, D. M., & Mossialos, E. (2016). A systematic review and critical assessment of incentive strategies for discovery and development of novel antibiotics. The Journal of Antibiotics, 69(2), 73–88. https://doi.org/10.1038/ja.2015.98
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@article{owid-golden-age-antibiotics,
author = {Saloni Dattani},
title = {What was the Golden Age of Antibiotics, and how can we spark a new one?},
journal = {Our World in Data},
year = {2024},
note = {https://ourworldindata.org/golden-age-antibiotics}
}
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