The End of the Antibiotic Era?

Recently the BBC published a story about a bacterial strain resistant to a last-resort antibiotic found in China, raising fears that we are close to a post-antibiotic era where common, treatable infections will become untreatable and life-threatening. How did we get to this stage despite the advances of 21st century medicine? Much talk has been made recently regarding the possibility of sending humans to Mars, yet could it really be that humanity may not even get there if we are threatened by the humble terrestrial bacteria?

For most of human existence (around 200,000 years since modern humans appeared), humans have had to rely on their own immune response, as well as the help of some ‘natural remedies’ to help them cure infections. Unbeknown to ancient humans, the natural remedies used such as frog bile with sour milk (Babylonia), warm soil (South American Indians) and mouldy bread (Greece and Serbia) contained the precursors of modern antibiotics. Traditionally, antibiotics are natural chemicals produced by bacteria or fungi to inhibit the growth of other bacteria. Therefore it may not be too surprising if these seemingly strange practices miraculously worked to treat bacterial infections. It was only in 1928, that the modern era of mass-scale production of antibiotics came into being with the discovery of penicillin produced by a contaminating fungus in Alexander Fleming’s laboratory. Since then, many other antibiotics were discovered from the environment and were successfully used to cure many dreaded illnesses such as tuberculosis, scarlet fever and septicaemia. Molecular biology also enabled the screening and tweaking of large numbers of synthetic chemicals that could mimic the action of natural antibiotics. The usage of antibiotics was life-saving and contributed to the rapid decrease in infectious disease burden in the world. We enjoy the increased longevity we now have, in part, due to the ‘re-discovery’ of antibiotics and its subsequent widespread use.

From that stage onwards, one might expect the saying ‘and humanity lived healthily ever after‘ to be emblematic of the state of the human species.

So what happened?

The forces accelerating the rise of resistant bacteria

We all have heard of places where doctors and pharmacists over-prescribe antibiotics, or places (physical or online) where antibiotics could be bought without prescription. As an example, one of the major factors leading to the rise of multi-drug resistant tuberculosis is the abandonment of antibiotic treatment prior to the completion of therapy, leading to the overgrowth of a small population of resistant bacteria, which then gets transmitted to others. In India, the illegal selling of drugs resulted in unregulated usage of antibiotics which subsequently gave rise to resistant strains. Thus, human culture and practice is one major factor that contributes to this problem.

There is, however, another important factor that is discussed less frequently; that of economics. Specifically, the issue lies in the subtle link between the usage and manufacturing of antibiotics to that of monetary profit. By monetary profit, I mean both to increase profit as exemplified by the use of antibiotics to heighten yields in animal agriculture and at the other end of the spectrum, the lack of profitability as viewed from the perspective of the pharmaceutical industry.

The discovery that low doses of antimicrobials had a growth-promoting effect in the late 40s coincided conveniently with the onset of intensive farming practices in the UK with the passing of a new Agriculture Act in 1947. Since then, antibiotics have been used in animal agriculture to counter suboptimum animal growth due to unsanitary conditions and overcrowding, allowing for increased animal densities in farms. Antibiotics were also used preventively during specific periods such as weaning (to separate calves from their mothers) and after transportation, both of which are situations that occur when animals are highly stressed. Stress weakens the immune system making animals more susceptible to infections. Preventively feeding them antibiotics will not do anything to their stress levels but will quickly cure any subsequent infections that develop, thus minimizing loss of profit.

Widespread use of antibiotics in animals creates pressure on bacteria to evolve genes that can resist and survive the onslaught of these antimicrobials. That is exactly the situation that was discovered in China, as reported by the BBC, where the drug of last resort used widely in livestock, colicin, was rendered ineffective by resistant bacteria. Eventually, these resistant bacteria (and residues of antibiotics) will wind up in humans, directly via the consumption of contaminated meat, or via the usage of animal manure in agriculture, finally ending up on your plate. The repercussions of this practice go beyond solely the introduction of resistant bacteria into our bodies, but also towards the perturbation of the human microbiome by antibiotic residues which have been implicated in the rise of obesity as well as allergic diseases.

Whilst antibiotics are used to increase profits in animal agriculture, pharmaceutical industries shy away from the research and production of new antibiotics due to the perceived lack of return from investment. Why invest in the development of an antibiotic that has a net present value of less than $50 million when one can gain more profit in the sales of a new musculoskeletal drug worth more than $1 billion? Almost all the classes of antibiotic used today were discovered between the 1920s and 1970s. Since then, only two new classes have been developed and very few are in the pipeline.

Because bacteria are constantly evolving, resistance genes exist both in the environment where bacteria undergo friendly exchanges as well as due to mutations that occur when the pressure is high for survival, such as with widespread antibiotic usage. Therefore, in order to keep up with the evolving bacteria, research on antimicrobials cannot stall for decades, as has happened, or we will end up in a post-antibiotic world where even simple surgeries may lead to life-threatening consequences. That is where we are heading now, if new efforts to revive antibacterial discovery and re-evaluate the usage of antibiotics are not put in place.

How do we move forward?

Imagine a world where essential drugs such as antimicrobials were made by non-profit organizations that are financed by all governments of the world in a collective action for the good of human health, instead of a world where the health of humans depended on whether or not curing us signifies a good return on investment. Something has clearly gone wrong somewhere in the path of history to have led us to this point of our development as a society.

In 1846, William Morton conducted the first successful surgery using an anaesthetic at the Massachusetts General Hospital in Boston. Following his success, he promptly patented the anaesthetic. His actions at the time generated widespread outrage among the medical establishment who found his actions to control and profit from a life-saving substance to be immoral. No such condemnation exists today as we have gotten used to a new normal where exclusive patents and blockbuster drugs are absolutely acceptable from a capitalistic societal point of view. For most, if not all of us, this model is all that we have ever known.

The prediction and fear of an imminent ‘antibiotic apocalypse’ may just be what is needed to radically change the way businesses are run when it comes to antibiotics and healthcare; similar to the case of climate change, where desperate times require drastic actions. Most countries in the European Union have banned the use of antibiotics in animal feeds though the practice is still widespread worldwide, including the United States. Alternative non-profit drug discovery consortiums have been established though many have turned to collaborating with industry in order to obtain funding. The cost of developing a new drug (at least $300 million) is prohibitively expensive for any non-profit organization to bear, which is why a whole new way of funding such treatments should come into being, such as by pooling together funds from various countries into a common fund for research and drug development for human health. We may also need to look into nature to discover new antibiotics that bacteria have evolved over millennia; though with the unchecked destruction of our ecosystem, these potential therapies may be lost forever before we ever come close to discovering them.

Perhaps it is also time to rethink how we view the fight against infectious diseases by focusing on non-pharmaceutical prevention strategies. Vaccines do not come to mind since it will be impossible and even harmful to our microbiome to create vaccines for every organism on earth that could potentially cause us harm. We need to look into why infections occur in the first place by understanding the dynamics between our environment and our bodies and what we can do to minimize the risk of infections, thus obliterating the need for antibiotics in the first place. This is, in itself, a whole other topic for discussion, so stay tuned!

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