Understanding Medical History: What is the Oldest Antibiotic?

October 6, 2025 •

3 min read

Ancient Nubian skeletons dating back to 350-550 CE contain traces of the antibiotic tetracycline, suggesting some form of early, potentially unknowing, use of antibiotic-producing bacteria. However, the question of what is the oldest antibiotic in the modern medical context is far more complex, with different claims depending on the definition used.

Quick Summary

The identity of the oldest antibiotic varies depending on if you consider ancient remedies, early scientific isolation, or the first clinically effective and widely distributed drugs.

Key Points

Ancient remedies predate modern discovery: Archaeological evidence shows early civilizations unknowingly used natural antibiotic sources like moldy bread and tetracycline-producing bacteria for thousands of years.
Mycophenolic acid was the first isolated antibiotic: Isolated in 1893 by Bartolomeo Gosio from Penicillium glaucum, this was the first scientifically isolated antibiotic, though it did not achieve clinical use for its antibacterial properties at the time.
Salvarsan was the first synthetic antibacterial: Developed by Paul Ehrlich in 1910, Salvarsan was a groundbreaking synthetic drug used to treat syphilis, representing a major step in chemotherapy.
Sulfonamides were the first broad-spectrum systemic drugs: Prontosil and its active metabolite sulfanilamide, developed in the 1930s, became the first widely used and effective broad-spectrum systemic antimicrobial agents.
Penicillin was the revolutionary 'wonder drug': While discovered in 1928, penicillin's purification and mass production in the 1940s transformed medicine and marked the true beginning of the modern antibiotic era.

The search for the oldest antibiotic is not a straightforward one, as the answer depends on whether one is referring to ancient remedies, early isolated compounds, or the first modern, mass-produced medicines. While many point to penicillin, a closer look reveals a layered history with multiple significant milestones.

Ancient Discoveries and Natural Remedies

Evidence suggests ancient cultures utilized natural substances with antimicrobial properties. Notably, skeletons from ancient Nubia contained high levels of tetracycline, believed to be consumed through fermented beer made with Streptomyces. Other historical examples include the use of moldy bread on wounds in ancient Egypt and mold-based poultices in other cultures. Early scientific observations of one microorganism inhibiting another were also recorded in the late 19th century.

The First Isolated Antibiotic: Mycophenolic Acid

In 1893, Italian physician Bartolomeo Gosio isolated mycophenolic acid from the mold Penicillium glaucum, identifying it as the first scientifically isolated antibiotic from a natural source. Gosio demonstrated its ability to inhibit Bacillus anthracis. However, his findings were largely overlooked, and mycophenolic acid was later developed for use as an immunosuppressant.

The First Synthetic Antibacterial: Salvarsan

Prior to natural antibiotic purification, the first modern antibacterial treatment was the synthetic drug Salvarsan (arsphenamine). Inspired by selective staining techniques, Paul Ehrlich developed the concept of a "magic bullet" and, with Sahachirō Hata, discovered compound '606' to treat syphilis. Introduced in 1910, Salvarsan was the standard treatment for syphilis for nearly four decades.

The Rise of Clinical Antibiotics

The mid-20th century saw the introduction of the first widely effective antimicrobial drugs.

Sulfanilamide and the Sulfonamides

Gerhard Domagk discovered in 1932 that the dye prontosil had antibacterial effects. French scientists later found that prontosil converted to the active compound sulfanilamide in the body. Sulfonamides became the first effective and broad-spectrum systemic antimicrobials used in clinical settings.

Penicillin: The Serendipitous Revolution

While often considered the first antibiotic, Alexander Fleming's 1928 discovery of penicillin was preceded by others. Fleming observed that Penicillium notatum mold inhibited Staphylococcus growth. He named the active agent penicillin but struggled with its isolation. A decade later, the Oxford team of Howard Florey and Ernst Chain successfully purified penicillin, leading to its mass production during WWII and revolutionizing medicine.

Comparing Key Early Antibiotics

The timeline of early antibiotic-related discoveries and drugs includes several significant entries:


Antibiotic	Type	Year of Discovery	Discoverer	Initial Clinical Use?	Key Facts
Tetracycline (in Nubian bones)	Natural (accidental consumption)	350–550 CE	Ancient Nubians	Yes (unwittingly)	The earliest documented evidence of antibiotic-like substances ingested by humans.
Mycophenolic Acid	Natural (isolated)	1893	Bartolomeo Gosio	No (initially)	First scientifically isolated antibiotic, but discovery was overlooked.
Salvarsan (Arsphenamine)	Synthetic (chemically designed)	1910	Paul Ehrlich	Yes	First synthetic antibacterial drug, effective against syphilis but toxic.
Prontosil (Sulfanilamide)	Synthetic (chemically designed)	1932	Gerhard Domagk	Yes	First effective broad-spectrum systemic antimicrobial drug.
Penicillin	Natural (purified)	1928 (discovered), 1940s (purified)	Alexander Fleming (discovered), Florey and Chain (purified)	Yes	The first "wonder drug," revolutionized medicine, but discovered after earlier agents.

Conclusion: Defining the "Oldest"

Defining what is the oldest antibiotic is complex. It involves considering ancient practices, the first isolated compound, the first synthetic drug, and the first widely available clinical treatments. While ancient evidence and early isolation efforts were important, the modern antibiotic era began with the first effective and broadly used systemic drugs, notably the sulfonamides and penicillin.

For more on the development of antibiotics, see this overview from Nature: "A brief history of antibiotics and select advances in their discovery and development".

The Modern Impact of Antibiotics

Antibiotics have significantly impacted modern medicine by treating infectious diseases and enabling complex medical procedures. However, the rise of antibiotic resistance presents a critical challenge today.

Frequently Asked Questions

No, penicillin was not the first antibiotic discovered. Earlier discoveries include mycophenolic acid in 1893 and the synthetic drug Salvarsan in 1910. However, penicillin's purification and widespread availability in the 1940s cemented its place as the first revolutionary 'wonder drug'.

Ancient civilizations used various natural remedies with antimicrobial properties. Evidence suggests ancient Nubians unknowingly consumed tetracycline through fermented beer. The ancient Egyptians used moldy bread on infections, and cultures in China, Serbia, and Greece also used mold-based poultices.

Natural antibiotics, like penicillin, are produced by microorganisms such as fungi or bacteria. Synthetic antibiotics, like Salvarsan and sulfonamides, are chemically designed and manufactured in a laboratory. Many modern antibiotics are semi-synthetic, meaning they are chemically modified versions of naturally derived compounds.

The first synthetic antibacterial drug, arsphenamine (Salvarsan), was developed by Paul Ehrlich and his team and introduced for treating syphilis in 1910.

The initial discovery of penicillin was a serendipitous event by Scottish bacteriologist Alexander Fleming in 1928, who observed its effects on a moldy petri dish. However, the mass production and clinical use of penicillin were developed by a team of Oxford scientists, including Howard Florey and Ernst Chain, in the 1940s.

Prontosil was a prodrug discovered by Gerhard Domagk in 1932 that contained the active antibacterial compound sulfanilamide. It was the first effective broad-spectrum systemic antimicrobial drug used clinically and heralded the era of sulfonamide antibiotics.

Understanding the history of antibiotics is crucial for recognizing the immense medical progress made and for addressing modern challenges like antibiotic resistance. Studying past discoveries, including early observations and the development of different classes of drugs, helps inform ongoing research and highlights the need for responsible use.