What was the Golden Age of Antibiotics, and how can we spark a new one?

Antibiotic-like treatments date back thousands of years, with records of moldy bread and medicinal soil used to treat wounds in ancient Egypt, Greece and China. We now know they may contain antibiotic compounds.¹

But the journey of modern science began in the early 20th century. Scientists gradually began to discover antibiotics from both synthetic sources, such as dyes, and natural sources, such as bacteria and fungi.

In the 1940s, the development of antibiotics advanced rapidly, and many 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 the reasons for the slowdown in antibiotic development. I also offer some ideas on how to reinvigorate the development of antibiotics today so that we can overcome antibiotic resistance and continue using effective antibiotics in the future.

In the early 1900s, microbiologist Paul Ehrlich studied dyes for staining bacteria. He looks for potential drugs that can target microbes without harming human cells.

In 1910, after testing hundreds of compounds, he made a breakthrough and identified Salvasan ——This became the first effective treatment method syphilis Also the first synthetic antibiotic used in medicine. It’s an aphenamine, the second type of antibiotic at the top of the timeline.¹

Another milestone came in 1928 when Alexander Fleming observed that fungal mold could kill bacteria on contaminated petri dishes. he found penicillin. Unfortunately, it took several years for penicillin production to scale up, as shown in the timeline below. This is the fourth class of antibiotics from the top.²

The story of penicillin is important because it also influenced the development of other antibiotics during this period.

Researchers at the University of Oxford collaborated with Fleming to purify penicillin and sought assistance and funding to produce it on a large scale. They contacted the U.S. Office of Scientific Research and Development (OSRD), which oversaw U.S. national science funding during World War II.³

Infections were the leading cause of death among soldiers and civilians at the time.⁴ Because of this, OSRD recognized the potential of penicillin and launched a global search with the United States Department of Agriculture (USDA) to find another fungal strain capable of producing penicillin in higher yields. Eventually, this strain was discovered, growing on cantaloupes.⁵

The U.S. War Production Board subsequently coordinated efforts to improve fermentation, organize clinical trials, promote collaboration, share data, and lift patent restrictions, accelerating development. By 1943, they were available to the military and some civilians in sufficient quantities to become widely available to the American public by 1945.⁶

During this period, the knowledge, manufacturing processes, and techniques that laboratories gained while scaling up penicillin made it easier for them to study other antibiotics.⁷

Meanwhile, there was another key breakthrough: scientist Selman Waksman discovered Actinomycetesa group of soil bacteria that are prolific producers of antibiotics. Through repeated screening, Waxman and then-doctoral student Albert Schatz discovered Streptomycineffective treatment of tuberculosis. More antibiotics from Actinomycetes followed by bacteria, including Tetracyclines and macrolides. Repeated screening can help identify more antibiotics from other organisms.⁸

As the timeline above shows, the turnaround time between discovery and introduction was often very fast during this period. Some antibiotics, such as tetracyclines, macrolides, and pyridinamides, were introduced in the same year that they were discovered.

The period from the early 1940s to the mid-1960s is known as the “Golden Age of Antibiotics,” with intensive research into natural and synthetic compounds leading to the rapid discovery of many new antibiotics.

The timeline below is now organized by year of clinical introduction for each antibiotic drug class.

It shows that almost two-thirds of antibiotic drug classes were developed during the Golden Age of Antibiotics. Most are still in use today.

By the 1970s, antibiotic research and development slowed dramatically. Since 1970, only 8 new classes have been approved.⁹

One reason is that pharmaceutical companies are shifting their focus to more profitable chronic disease treatments, which can provide stable, long-term revenue compared with antibiotics, which are typically shorter-lived and less expensive.¹⁰

Rising antibiotic resistance It also reduces the need for new antibiotics, which are often used to treat serious, drug-resistant infections – a relatively small market. Furthermore, efforts to identify new antibiotics by screening organisms for their antibiotic activity often result in the re-identification of the same compounds that others have already discovered.¹¹

These challenges, coupled with high development costs and low margins, have squeezed many large pharmaceutical companies out of the market, leaving smaller companies struggling with limited resources.

In recent decades, scientific and economic efforts have reinvigorated antibiotic drug discovery.

One approach is through synthetic biology and “genome mining” – a technique that identifies antibiotic genes hidden in microorganisms that are not expressed by the microorganisms under standard laboratory conditions. Several potential new antibiotics have been discovered through these efforts, but they are currently still in clinical testing.¹²

Research shows that we have only identified a small fraction of the world’s bacterial species. Therefore, another approach is to culture bacteria in natural environments such as soil, or to explore currently undiscovered bacteria in extreme ecosystems such as oceans and deserts, to reveal the antibiotic compounds they may produce in these environments. ¹³

Finally, drug discovery could focus on combining different antibiotics to prevent the development of resistance: this is possible when resistance to one antibiotic makes bacteria more susceptible to another antibiotic.¹⁴

At the root of the problem, however, is the lack of economic incentives that are critical to driving innovation and manufacturing.

Antibiotics are unique: Their use typically lasts only a few days or weeks, and new antibiotics are rarely used to slow resistance. This means that antibiotic innovation generates far less revenue than drugs for many other diseases.

To overcome this problem, governments and organizations are using new financing models. For example, Advance Market Commitments can reward companies that successfully bring new antibiotics to market with guaranteed payments if they meet approval criteria.¹⁵

Another idea being trialled in the UK is to use a “subscription model”, where health agencies or the country 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 utilization rates low.¹¹

Collaborative funding efforts, e.g. CARB-X and gadepuSupporting programs to tackle drug-resistant infections can also help close the gap. These initiatives provide developers with more financial stability, reduce risk, and ensure that essential new antibiotics are developed for those who need them most.¹¹

The golden age of antibiotics was the result of coordinated efforts, incentives, priorities, and new technologies.

Since then, antibiotic development has slowed. But it doesn’t have to be this way.

Rapid advances in genome sequencing and synthetic biology may allow more antibiotics to be discovered and developed. Many yet-to-be-discovered bacteria may be sources of new antibiotics, but there is currently limited economic incentive to study them.

With better incentives and research efforts, a new era of antibiotic discovery and development could be ignited.

Continue reading our world of data

Saloni Dattani (2024) - “What was the Golden Age of Antibiotics, and how can we spark a new one?” Published online at OurWorldinData.org. Retrieved from: 'https://ourworldindata.org/golden-age-antibiotics' [Online Resource]

@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}
}