Picture credits: https://www.historyextra.com/period/20th-century/a-big-day-in-history-alexander-fleming-discovers-penicillin/
To envision a world where the tiniest cut could kill is frightening, and we owe that to the discovery of antibiotics. These revolutionary medicines enabled a plethora of scientific advancements in the 20th century and combatted diseases we now render manageable - but not for long. Being brought up in an era where antibiotics are ubiquitous to most has made us take them for granted, hastening antibiotic resistance - the ever-growing threat that could revive the horrors of our pre-antibiotic past.
Before the 20th century, infectious diseases were rampant, responsible for the top three causes of deaths: pneumonia, tuberculosis and gastrointestinal infections. Nowadays, these diseases account for a few per cent of deaths at most, and pneumonia can even be cured within two weeks thanks to the availability of antibiotics, powerful medicines that target bacterial infections.
How do antibiotics work?
Bactericidal antibiotics such as penicillin kill bacteria by interfering with their cell contents or cell wall formation. When the cell wall is weakened, it makes the cell prone to rupturing easily. Daptomycin is another example of a bactericidal antibiotic which functions by disrupting the bacterium’s cell membrane, thereby killing the bacterium as its ions and molecules leak out of the cell. On the other hand, bacteriostatic antibiotics such as tetracycline inhibit bacterial growth by interfering with their DNA replication, protein production and other aspects of their metabolism. Antibiotics can also be classified according to their efficacy against a range of bacteria. Broad-spectrum antibiotics target a wide range of bacteria while narrow-spectrum antibiotics do the opposite.
The history behind antibiotics
Picture credits: https://api.time.com/wp-content/uploads/2016/03/fleming.jpeg?quality=85&w=1024&h=512&crop=1
Sir Alexander Fleming is arguably one of the world’s most well-known scientists, pioneering the ground-breaking discovery of antibiotics. However, long before the time of Fleming, archaeological findings have proved that the usage of antibiotics can actually be traced back to ancient times! Traces of tetracycline were found in ancient Nubians from 350-550 CE because tetracycline gets deposited into bones, and the presence of this antibiotic likely stems from an antibiotic-laced beer they brew. George Armelagos, co-author of this study notes, ”We tend to associate drugs that cure diseases with modern medicine. But it's becoming increasingly clear that this prehistoric population was using empirical evidence to develop therapeutic agents. I have no doubt that they knew what they were doing."
Other ancient civilisations also share a similar practice of using antibiotics from natural sources, such as moulds and plant extracts, but whether they understood the mechanism behind it is unknown. For example, ancient Egyptians would apply mouldy bread to infected wounds.
However, the discovery of penicillin wasn’t made until 1928.
1928 was the year Alexander Fleming left a culture plate of Staphylococcus aureus (a common pathogen) uncovered and kickstarted the antibiotic revolution. Fleming noticed bacteria-free zones around a fungus colony (zones of inhibition) that contaminated the culture plate, identified as Penicillium notatum, and discovered its ability to inhibit bacterial growth. He proceeded to isolate and grow the mould in pure culture, and noticed its wondrous efficacy even at low concentrations - after 800 dilutions, the mould could still successfully prevent Staphylococcus growth. This is arguably the most significant discovery in medicine as it led to the creation of penicillin, the first antibiotic that perfected treatments for bacterial infections such as syphilis and tuberculosis.
Thus, Fleming laid the foundation for further pivotal antibiotic developments and treatments of previously life-threatening diseases. In WW2, penicillin saved millions of soldiers, earning its nickname “the wonder drug”. Antibiotics play an indispensable role in medicine today, without which common surgeries such as c-sections would become extremely unethical to perform due to the high susceptibility of surgical site infections, and chemotherapy treatments would become infeasible.
Antibiotic resistance
Unfortunately, there is a vast imbalance of antibiotic consumption across nations. In low-income countries, inaccessibility to antibiotics results in the loss of a child’s life every three minutes and accounts for 10% of maternal deaths due to bacterial infections. This all happens while most countries continue to overuse antibiotics, encouraging bacteria to build up resistance against bacteria in turn.
In other words, we are losing control. We are losing our control over treating bacterial infections. We are losing momentum in the arms race against bacteria, a problem caused by the reduction in new antibiotics being produced. A problem further exacerbated by the over-use of antibiotics.
As genius of a scientist Fleming was, I argue that he had a secret talent for predicting the future. Ironically enough, Fleming had warned us of this very problem 75 years ago, stating "the thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.
Antibiotic resistance falls under Antimicrobial resistance (AMR), an ever-accelerating problem that causes 700,000 deaths globally. Alarmingly, this number could rise up to 10 million in 2050 if the thriving of bacteria successfully overrides our efforts of curbing it. Antibiotic resistance is a slow, natural process we are accelerating it to dangerous extents by our misuse and overuse of antibiotics. Notably, this is compounded by the meat industry. Antibiotics are needed as most animals are kept in unhygienic and cramped conditions, the perfect catalyst for infectious diseases to blossom. Additionally, extensive amounts of antibiotics are fed to animals in order to promote their growth and achieve a higher yield, further contributing to the crisis.
Antibiotic resistance relies on a mechanism known as natural selection. Bacteria genetically mutate randomly and develop resistance mechanisms, from breaking antibiotics down with enzymes to simply ejecting them using pumps in their cell walls. As a result, bacteria susceptible to antibiotics are killed, reducing competition which allows for resistant bacteria to flourish. They can survive and reproduce, passing on the resistant alleles onto more and more generations. To make matters worse, immunity is spreading at an alarming rate as resistance genes transfer between all bacteria in plasmids, even across species, and not solely through inheritance. This whole process is dramatically sped up by the overuse of antibiotics.
Picture credits: https://www.cdc.gov/drugresistance/images/about/how-resistance-happens/how-germs-fight-antibiotics-pic.png
Picture credits: https://ichef.bbci.co.uk/news/640/cpsprodpb/14F6D/production/_103996858_explainerchart.png
The unabated rise of bacteria has therefore led to the creation of strains resistant to multiple antibiotics called superbugs, an issue further exacerbated by the halt in developing new antibiotics owing mostly to inadequate funding and regulatory burden. “The costs of trials are so high and society is not willing to pay the high price for antibiotics; so that is the paradox,” Mahesh Patel, director of drug discovery research at Wockhardt, says. Methicillin-resistant Staphylococcus aureus (MRSA), a superbug unresponsive to multiple antibiotics, claims 11,000 lives every year in the US alone. It has particularly nasty effects, ranging from skin infections to pneumonia, or even bloodstream infections.
However, the situation can still be salvaged if action is taken expeditiously. Personal changes must be made, such as only taking necessary antibiotics and finishing prescription; education towards the public is needed to discard misconceptions surrounding antibiotics, such as antibiotics being effective against viral infections as well, preventing misuse. The extensive use of antibiotics in agriculture must be more closely restricted and monitored. Lastly, our support for organisations (e.g. APUA) that fight antibiotic resistance is crucial.
Among the myriad of issues we are facing globally, one that is often overlooked is the silent growing strength of bacteria. The increasing urgency of the situation may have irreversible implications on our healthcare and world. Fleming had once said, “One sometimes finds what one is not looking for.” Perhaps we will be fortunate enough to stumble upon another discovery that would be the perfect solution like he did. But before that happens, we cannot let society fall into complacency knowing that most antibiotics are still on our side. It would truly be a shame if we allow our ignorance to cost us our life-saving medicines, and subsequently decades of scientific advancement.
Sources:
https://kids.frontiersin.org/article/10.3389/frym.2019.00159 (more on Fleming's Penicillin discovery!)
https://www.wired.com/2010/09/antibiotic-beer/ (study on ancient Nubians, Tetracycline and antibiotic-laced beer)
Read more about the history of antibiotics:
Videos I watched:
What causes antibiotic resistance? - Kevin Wu
The Antibiotic Apocalypse Explained - Kurzgesagt
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