A Brief History of Antibiotics

When you think of antibiotics, you likely have the word "penicillin" floating around there somewhere. Penicillin was one of the first widely publicized, mass-produced antibiotics [3,4].

Author: Milica Ristovski

Picture this: you just finished saving the Nakatomi plaza where your wife and her colleagues were being held hostage. You walk out, victorious, but covered in cuts. The paramedics then grab some mouldy bread and dirt and rub it into your cuts.

Just kidding... kind of. 2000 years ago, that might have been the reality if you lived in China, Russia, Serbia, Egypt, or Greece [1].

Why on Earth would anyone do that? One word: antibiotics.

What are antibiotics? The word itself comes from anti, which means ‘against’, and biotikos, which means ‘fit for life’ [2]. The oldest recorded instances crop up in Ancient Serbia, China, Egypt, and Greece, where they would use mouldy bread, either as-is or in the form of a paste, to put on wounds in order to prevent infection. In Ancient Russia, a slightly different approach was taken: "medicinal earth" — but we'll get into that later.

When you think of antibiotics, you likely have the word "penicillin" floating around there somewhere. Penicillin was one of the first widely publicized, mass-produced antibiotics [3,4]. It was deemed the "miracle drug" of WWII [3,4].

There is no doubt that hundreds of thousands of lives were saved by the discovery of antibiotics [5]. Prior to WWII, the number of people who died from sepsis (full body infections) rivaled and greatly surpassed the numbers of those who died from combat [6]. For example, in the Crimean War (1854-1856), 34000 died in combat, 26000 died from wounds, and a whopping 130000 died from infectious diseases [6]. Antibiotics allowed for infections to be slowed and even cured, saving many from amputations that could then be deemed unnecessary [6].

Before we speak about penicillin, let's take a little detour down the Sulfa drug lane. The Sulfa drug was discovered in 1932 by Gerhard Domagk [7]. It was a staple of first aid kits throughout the 1940s, but fell out of favour due to penicillin’s competitive mass production, since penicillin caused fewer adverse side effects [7].

But who discovered penicillin? Where did it come from? Well, remember that mouldy bread mentioned earlier? The same substance was likely at work there: penicillin.

Penicillin was discovered by Sir Alexander Fleming. The 1928 story goes as such, that Fleming went on vacation and he had left agar plates (petri dishes) to grow some bacteria in his absence. When he got back, he discovered that the plates had been contaminated! They were covered in spots of mould; however, there was something else that had also caught his attention: no bacteria grew near the mould [8].

Instead of tossing out the plates, he began running experiments to test the mould’s antibiotic properties. Fast forward slightly over a decade, WWII is in full swing, and soldiers are in dire need of medical attention for their infections. Penicillin swooped in at this point to save countless lives.

After some time, cracks in the miracle drug began to show — In 1940, the first penicillin-resistant bacteria was discovered: staphylococcus. More followed, resistance appearing in various bacteria to follow [9,10]


How does resistance occur? It occurs due to the overuse or incomplete use of antibiotics, both of which result in a non-lethal exposure, allowing some bacteria to survive [11]. The bacteria that survive continue to reproduce so that all of their offspring have the same antibiotic-resistant genes [11].

Worse yet, the end of the 1960s brought about the appearance of superbugs. Superbugs are "bugs", also known as bacteria or fungi, which are resistant to multiple types of antibiotics [11]. Currently, one of the most common is MRSA, or methicillin-resistant Staphylococcus aureus [12].

Does the appearance of superbugs mean the end of all hope? Many scientists disagree.

Remember that "medicinal earth" that the Ancient Russians used? It is likely that the reason it worked was due to tiny viruses called bacteriophages, or phages for short. Phages are tiny viruses that only infect bacteria, and they are found everywhere, from dirt to feces, all over the world [13].

In 1917, two scientists separately observed the same phenomenon: on their agar plates, clear spots would appear among the bacteria. The clear spots would fade out as they got further from the center, and the clear spots were transmissible [14].

English physician Frederick Twort and French-Canadian microbiologist Felix d'Herelle both proposed that there were tiny viruses that infected their experimental bacteria [15]. d'Herelle gave them the name bacteriophages [15].

Fast forward to 2015, Steffanie and Tom Patterson were on vacation in Egypt. After dinner, Tom had a bout of what the Pattersons thought was food poisoning. Unfortunately, it turned out to be much worse. The illness continued spreading, and after being diagnosed with Acinetobacter baumannii in his pancreas, he was flown to San Francisco, where he soon thereafter fell into a coma [15].

Tom was unresponsive to any of the antibiotics given to him. His organs were beginning to fail. Steffanie, determined to save him, promised to "leave no stone unturned". She set off on her search to find a cure. When she was a student at the University of Toronto, Steffanie had learned about bacteriophages.

Phages, unfortunately, have to be exact matches to the bacteria, so she began trying to contact every phage facility she could find. She was eventually able to procure enough bacteriophages to begin the attack on the bacteria taking over Tom. The phages were purified from sewage and then injected into Tom's abdomen and bloodstream. A few days later, he was awake. "Literally he was off life support within two weeks,” said Steffanie.


Now that you have a rough idea of the history of antibiotics, what's next?

One route is certainly phage therapy, as discussed previously. If it interests you, uOttawa has a course called "SEA-PHAGE hunters," open to all students, in which you can find and name your very own phages.

As for other solutions to superbugs, that's up to you to discover.


Editors

Ibrahim Alayche, Rhea Verma

Designer

Web design by Majd Al-Aarg

Additional Credits

Cover photo provided by Myriam Zilles on Unsplash

References

  1. Gould K. Antibiotics: from prehistory to the present day. Journal of Antimicrobial Chemotherapy. 2016;71(3):572-575. Available from: https://doi.org/10.1093/jac/dkv484

  2. Oxford Languages [Internet]. Toronto (ON): Oxford University Press. 2021 [cited 18 January 2021]. Available from: https://languages.oup.com/google-dictionary-en/

  3. Aminov R. A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future. Frontiers in Microbiology. 2010;1. 10.3389/fmicb.2010.00134

  4. Bernard D. [Internet]. 2020 [cited 15 January 2021]. Available from: https://www.washingtonpost.com/history/2020/07/11/penicillin-coronavirus-florey-wwii-infection/

  5. Conniff R. Penicillin: Wonder Drug of World War II [Internet]. HistoryNet. 2020 [cited 15 January 2021]. Available from: https://www.historynet.com/penicillin-wonder-drug-world-war-ii.htm

  6. Pennington H. The impact of infectious disease in war time: a look back at WW1. Future Microbiology. 2019;14(3):165-168. Available from: https://www.futuremedicine.com/doi/full/10.2217/fmb-2018-0323

  7. Encyclopedia Britannica [Internet]. Chicago (IL): The Editors of Encyclopaedia Britannica; 2021. 2021 [cited 16 January 2021]. Available: https://www.britannica.com/science/sulfa-drug

  8. The Nobel Prize [Internet]. Stockholm (SE): NobelPrize.org; 2021. The Nobel Prize in Physiology or Medicine 1945; 2022 [cited 17 January 2021]. Available: https://www.nobelprize.org/prizes/medicine/1945/fleming/biographical/

  9. Davies J, Davies D. Origins and Evolution of Antibiotic Resistance. Microbiology and Molecular Biology Reviews. 2010;74(3):417-433. Available from: 10.1128/MMBR.00016-10

  10. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P T. 2015 Apr;40(4):277-83. PMID: 25859123; PMCID: PMC4378521.

  11. STAT [Internet]. Boston (MA): Carl Zimmer; 2021. The surprising history of the war on superbugs — and what it means for the world today; 2016 [cited 16 January 2021]. Available: https://www.statnews.com/2016/09/12/superbug-antibiotic-resistance-history/

  12. Live Science [Internet]. New York (NY): Mosher D; 2021. What is a Superbug?; 2012 [cited 19 January 2021]. Available: https://www.livescience.com/32370-what-is-a-superbug.html

  13. Clokie M, Millard A, Letarov A, Heaphy S. Phages in nature. Bacteriophage. 2011;1(1):31-45. Available from: 10.4161/bact.1.1.14942

  14. Keen E. A century of phage research: Bacteriophages and the shaping of modern biology. BioEssays. 2014;37(1):6-9. 10.1002/bies.201400152

  15. CTV News [Internet]. Toronto (ON): Favaro A & St. Philip E; 2021. A long forgotten Canadian discovery used to treat superbugs; 2019 [cited 19 January 2021]. Available: https://www.ctvnews.ca/w5/a-long-forgotten-canadian-discovery-used-to-treat-superbugs-1.4706823

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