The History of the Antibiotic

While modern medical researchers get the awards, ancient people were already in the know

Antibiotics and other antimicrobials have been used since ancient times but more recent iterations have transformed medicine. Depicted is an illustration by Robert Thom (1957) detailing an ancient Egyptian doctor administering medicine to a patient. (Public Domain)
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By Peter Weiss

While many people believe that penicillin was the first antibiotic, they would be wrong by only a few thousand years. Various molds and plant extracts have been used as “antibiotics” throughout history.

Ancient Egyptians would apply moldy bread onto infected wounds, while examinations of skeletal remains from ancient Sudanese Nubia dating as far back as A.D. 350 showed traces of tetracycline. These people must have had foods with tetracycline material in their diets since tetracycline is absorbed into bone when ingested. Beer brewed at the time is thought to be a source. The same was found in examining skeletal remains from the Roman period, however, there was no mention of beer.

Tetracycline is still used today, but avoided in young children since it can permanently damage teeth and can be incorporated into the mineral of bones. Tetracycline was first discovered in 1948 and was produced from actual bacterial cells of streptomyces and actinobacteria. The historical origins still remain a mystery though.

Honey has long been known to have antimicrobial properties and has a well-documented use in wound care and medicine since ancient times. The antimicrobial properties of honey have to do with the enzymatic production of hydrogen peroxide. There are some kinds of honey that don’t produce hydrogen peroxide but still act as antimicrobials due to their high sugar content and low pH, both of which hinder bacterial growth.

Traditional Chinese medicine has used antimicrobials for a millennia. Artemisinin (qinghaosu), a potent antimalarial drug, is derived from the artemisia plants used in Chinese medicine to treat malaria for thousands of years.

Pyocyanase, a mixture of “antibiotics” obtained from pseudomonas aeruginosa, was probably the first “antibiotic” to be used to treat human infections. In the 1890s, Rudolf Emmerich and Oscar Löw discovered that this green discharge isolated from injured patients’ bandages inhibited the growth of other microbes. They used this concoction as a paste over infections to limited success.

Until the beginning of the 20th century, infections were the leading cause of death worldwide. Infections such as pneumonia, influenza, and tuberculosis took scores of lives.

In 1904, the treatment of syphilis involved the use of inorganic mercury salts. This treatment had severe side effects, such as skin rashes, mental disturbances, memory loss, and weakness—side effects similar to the symptoms of syphilis itself. This treatment also wasn’t very effective.

In 1909, a German physician, Dr. Paul Erlich discovered a chemical, arsphenamine, that was used successfully to treat syphilis. He didn’t call it an antibiotic but chemotherapy, since a chemical was used as therapy.

Erlich wanted to find specific treatments for specific infections. He developed a derivative of a highly toxic drug Atoxyl and after the 600th series tested, he found a somewhat effective treatment against syphilis. A more soluble and less toxic form, neosalvarsan, was developed and was the most prescribed drug until the advent of penicillin.

Dr. Selman Waksman is credited with the term antibiotic some 30 years later. He was a Russian emigrant to America who discovered some 15 antibiotics including streptomycin, which was the first effective treatment for tuberculosis. Until then, many lives were lost from the TB epidemic. He was awarded a Nobel Prize in 1952 for his work. Meanwhile, Dr. Alexander Fleming, an Englishman, was given the somewhat mistaken accolades of discovering the first antibiotic.

Fleming, a somewhat disorganized scientist, returned from a Scottish vacation to find his laboratory a complete mess. He had several colonies of staphylococcus Aureus in several Petri dishes throughout his lab. He looked at them under a microscope and found that the penicillium mold had contaminated his staphylococcal Petri dishes, and was amazed to find that there was no evidence of any staphylococcus wherever the penicillium mold was.

He was astute enough to recognize the importance and wrote a letter about that date, Sept. 28, 1928, as the day he discovered what he called the first antibiotic. While he stopped working on penicillin in 1935, his work had been taken up by two others in 1929. It took some 14 years of development by other scientists, Dr. Howard Florey and Dr. Ernst Chaim, to isolate and help mass-produce pure penicillin.

All three would share the Nobel Prize in 1945 for their work.

In March 1942, Anne Miller in Connecticut was the first civilian to be successfully treated with penicillin after she developed life-threatening sepsis following a miscarriage.

An interesting note is that while Fleming wasn’t the first to discover the benefits of penicillium mold, he helped isolate the more pure penicillin. In 1870, Sir John Scott Burden Sanderson described how culture fluid covered in mold prevented bacteria from growing. It also was known for some time that Arab stable boys would treat saddle sores with mold formed on their saddles.

Penicillin, which was mass-produced during World War II, has been credited with saving many thousands of lives, especially for the Allies, who had plenty of the antibiotic while the Germans didn’t. The Germans had to rely on less effective sulfonamides, which were first recognized as antimicrobial in the 1930s by Gerhard Domagk, who was working at Bayer AG. He eventually used it to save his daughter from an arm amputation due to a serious staphylococcal infection.

He noticed that a sulfonamide dye, prontosil, could effectively kill bacteria by changing into an antibacterial form, sulfanilamide. In 1938, it was used to treat pneumonia, and later bladder infections, for which a more advanced form is still used today. It was a wonder drug until penicillin came along, which was more effective and had fewer side effects.

Back to Anne Miller. She was 33 years old, and her physician had connections with someone spearheading the development of penicillin as a mass-produced drug. He was able to get 5.5 grams of this penicillin from Merck Pharmaceuticals in New Jersey, sent to him in Connecticut. Miller started recovering within 24 hours of receiving the penicillin. She eventually died in 1990 at the age of 90.

So you can see that antibiotics have come a long way, but they also have a very long history.

Fleming said it best: “Nature makes penicillin; I just found it.”

Dr. Peter Weiss has been a frequent guest on local and national TV, newspapers, and radio. He was an assistant clinical professor of OB/GYN at the David Geffen School of Medicine at UCLA for 30 years, stepping down so he could provide his clinical services to those in need when the COVID pandemic hit. He was also a national health care adviser for Sen. John McCain’s 2008 presidential campaign.

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