The Ancient History of Antibiotics

Here is a paper I wrote in February of 2018 about the little known ancient history of antibiotics. When most people think about the history of antibiotics, they think were invented only about a century ago, but they actually go back thousands of years. I hope you enjoy learning about the ancient history of antibiotics and let me know what you think or if you have any questions or ideas for further research (for the latter two, we’d appreciate a comment in the forum).


Abram Leyzorek

2/14/2018

The Ancient History of Antibiotics

            Names like Alexander Fleming and Paul Ehrlich come to mind when we think of the origin of antibiotics. It was Alexander Fleming’s accidental discovery of the antibiotic mold penicillin in 1929, that seemed, at the time, to overcome humanity’s age-old adversary, the bacterial infection. Paul Ehrlich’s research led to an effective treatment of syphilis via antibiotics. These pioneers ushered in the modern age of antibiotics that has saved countless human lives. (1).

            Little is known, however, about an even earlier use of antibiotics by Emmerich and Low in 1899. They used a compound known as Pyacyonase derived from Pseudomonas aeruginosa in an attempt to cure various bacterial diseases, but soon found the substance to be unfeasible due to excessive toxicity. (1).

            Even less is known is known about certain discoveries that show the use of natural antibiotics by ancient humans; Tetracycline has been found in the bones of Sudanese Nubians dating back to 350-550 AD. Late-Roman skeletons from the Dakhleh Oasis, Egypt were found to contain markers that indicated the regular intake of tetracycline. The red soils of Jordan have long been used as a cheap alternative to prescribed antibiotics that treat skin infections and were found to contain an actinomycete1 bacterium that produces the antibiotics actinomycin C2 and actinomycin C3. Many herbs in the tradition of Chinese medicine have antimicrobial2 properties, including the artemisia, or the mugworts, from which a potent, anti-malarial drug, qinghaosu or artemisinin, was extracted. (1).

            This tradition goes back thousands of years, but the arms race between bacteria and antibiotics has been ongoing for millions of years, long before humans joined in. The phylogeny3 of certain genes for antibiotic resistance against natural antibiotics, reveals that they developed long ago; the serine and metallo-β-lactamases enzymes, for example, developed two billion years ago. They have been present in plasmids4 for millions of years. (1).

            Modern humans are making big waves in the world of microbes with new, synthetic antibiotics, but they were not, as is commonly believed, the first organisms to use antibiotics. Pre-modern humans used antibiotics extensively, and before them, microorganisms secreted antibiotics. The microbiota inside of animals that consumed plants and soils containing natural antibiotics needed to develop resistance.  (1).

            Humans are suffering today from antibiotic resistant microorganisms, but we have only been mass producing antibiotics for the biological blink-of-an-eye. Much of the resistances have developed over the millions of years that microorganisms were exposed to natural antibiotics. (1).

            But they are capable of extremely rapid mutation to evade our best efforts to exterminate them. Most of the antibiotics that we have developed are already ineffective and the golden age of new antibiotic discovery is long passed. All of the “new” antibiotics developed today are actually just modifications on previous compounds. Their is a delicate equilibrium between the rate at which humans develop “new” treatments, and the rate at which microorganisms develop new resistances. Our rate of discovery seems to be slowing down. Humans may be losing the battle. (1).

            But a new discovery may warrant new hope: researchers at the Rockefeller University in New York have discovered what could be a genuinely new class of antibiotics. They have called it malacidin, short for metagenomic5. acidic lipoprotein6 antibiotic cidin7. It was found in soil samples containing calcium dependent genes; the researches were searching for new treatments related to an exceptionally effective and long-lasting antibiotic called daptomycin, which uses calcium to rupture the cell walls of bacteria. But, in the long run, the microorganisms will always mutate and we will need new treatments. (2).


Footnotes

1.  Actinomycetes are filamentous, rod shaped bacteria of the order Actinomycetales. (3).

2.  Antimicrobial and antibiotic are essentially synonymous, and both have an adjectival form. But here, to avoid confusion, “antimicrobial” describes things that kill microbes, and “antibiotic” refers to drugs that do this. (4) (5).

3. Phylogeny is the evolutionary development of a species or higher taxonomic group. (6).

4.  A plasmid is a genetic cellular structure capable of replication independent from the chromosomes. (7).

5. Describes things associated with the metagenome, the collective genome of all the microorganisms in an environment. (8).

6. Proteins  that combine with and transport lipids in blood plasma. (9).

7. Comes from Latin root cid- meaning cut. (10). In English it has come to mean death or kill, e.g. infanticide, herbicide, etc.


References.

  1. Aminov, R. I. (2010). “A Brief History of the Antibiotic Era: Lessons Learned and Challenges for the Future.” NCBI. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109405/. Date-accessed: 2/14/2018.
  2. Healy, M. (2018). “In soil-dwelling bacteria, scientists find a new weapon to fight drug-resistant superbugs.” Los Angleses Times. http://www.latimes.com/science/sciencenow/la-sci-sn-new-antibiotic-soil-20180213-story.html. Date-accessed: 2/14/2018.
  3. “Actinomycetes.” (2018). Merriam Webster. https://www.merriam-webster.com/dictionary/actinomycete. Date-accessed: 2/14/2018.
  4. “Antibiotic.” (2018). Merriam Webster. https://www.merriam-webster.com/dictionary/antibiotic. Date-accessed: 2/14/2018.
  5. “Antimicrobial.” (2018). Merriam Webster. https://www.merriam-webster.com/dictionary/antimicrobial. Date-accessed: 2/14/2018.
  6. “Phylogeny.” (2018). Merriam Webster. https://www.merriam-webster.com/dictionary/phylongeny. Date-accessed: 2/14/2018.
  7. “Plasmid.” (2018). Merriam Webster. https://www.merriam-webster.com/dictionary/plasmid. Date-accessed: 2/14/2018.
  8. Hover, Bradley M. et. al. (2018). “Metagenomics.” Nature. https://www.nature.com/subjects/metagenomics. Date-accessed: 2/14/2018.
  9. “Lipoprotien.” (n.d.). Google dictionary. https://www.google.com/search?client=opera&q=define+lipoprotein&sourceid=opera&ie=UTF-8&oe=UTF-8. Date-accessed: 2/14/2018.
  10. Schodde, Carla. (2013). “Far too many Latin words for kill.” Found in Antiquity. https://foundinantiquity.com/2013/07/20/far-too-many-latin-words-for-kill/. Date-accessed: 2/14/2018.