Words by Hollen Singleton.

Illustrations by Subin Yang

This story is brought to you by our partner Activated Probiotics.

In 2013, the Australian Government Office of the Chief Scientist released a paper that warned, “Only one antibiotic that works in a novel way has been discovered and developed for use in humans, in the last 50 years.”

Fast forward to today and the news on superbugs is almost Hitchcockian: nearly a quarter of Australian silver gulls have been found to be carrying life-threatening E coli bacteria that is resistant to various antibiotics. We could all be swiftly approaching the end of an era, what some have called the ‘golden age of antibiotics’. But what does this mean for medicine? How did we get here, and what comes next?

In the 1940s, Australian pharmacologist Howard Florey and his German colleague, Ernst Chain, were responsible for developing a manufacturing process for penicillin that meant it could be produced on a grand scale. Such antimicrobial treatments remain, arguably, the most critical invention of modern medicine. Penicillin and other antibiotics changed the world. They have annihilated many diseases that today seem mundane or venial but that, pre-1940s, were often fatal.

However, these antibiotics largely operate in an analogous way: they work because they affect bacterial cells in the essential ways that they differ from human cells. Penicillin, for example, prevents a bacterium from producing a cell wall (a thing that human cells do not have). Antibiotics are said to block the bacteria’s ability to make the literal stuff of life.

Even when suffering from severe infection, the human body is not only populated with that bug’s bacteria. Our bodies rely on and benefit from a synergistic relationship with our microbiome: a community of helpful bacteria in our gut. Antibiotics can disturb the balance of this community, which can cause opportunistic infections (those quick enough to multiply before the healthy balance can be restored).

The other concern with this blanket microbe-killing approach is that nature is crafty. Even when taken correctly, antibiotics can leave behind a lingering contingent of bacteria that happen to be resistant. These bacteria might be able to, as an example, prevent the drug from passing through the cell wall; this naturally selected trait may be effective for that bacteria to survive many types of similar antibiotics. And this is where the issue with similarly working antibiotics kicks in: if a bacterium is able to survive one kind of antibiotic, it is likely to survive others. Bacteria can pass this trait on in a familiar reproductive way, but they are also able to transfer the trait to other kinds of bacteria through mobile genetic elements such as plasmids. This is one way we get to a multi-drug-resistant strain of an illness – a ‘superbug’.

In 2014, nearly half of the Australian population was prescribed at least one course of antibiotics (more than 30 million prescriptions for PBS-listed antibiotics were offered). Overconsumption and misuse of antibiotics (which could be prescription for viruses, for an incorrect duration, or too broad-spectrum) is a growing concern among certain groups. In the words of Dr Margaret Chan, former Director-General of the World Health Organisation, “Things as common as strep throat or a child’s scratched knee could once again kill.” Without antibiotics, other treatments, such as surgery and chemotherapy, may become too risky. The World Health Organization predicts that by the year 2050, antibiotic-resistant bacteria will overtake cancer as a leading cause of death, globally.

Superbugs, those infectious strains of bacteria and fungus, be they deadly or non-deadly, have been appearing around the world for decades. Scientists have warned of their dangers since their invention: Alexander Fleming, the inventor of penicillin, upon accepting his Nobel Prize alongside Howard Florey in 1945, spoke to the threat of resistant microbes emerging through what he imagined to be “ignorant” usage.

In the United States, the CDC released a report this year stating that antibiotic-resistant infections kill about 35,000 people annually. In Australia, there were two diagnosed cases of multi-drug resistant gonorrhoea in 2018. This strain resists all routine antibiotics. While it currently may be abated through complex treatment, the increasingly common appearance of gonorrhoea resistant to one or more antibiotics presents somewhat apocalyptic concerns. While gonorrhoea may be asymptomatic (80 percent of women have no symptoms), complications of the STI can be severe; in women, it can cause pelvic inflammatory disease, which can lead to chronic pain and infertility.

Across the world, and basically down to human actions, resistant bacteria are on the rise. There is, however, a lot that humans can do to combat this subtle yet seismic shift. Much is not yet monitored or is under-enforced in the realm of animal agriculture, which is where over 70% of antibiotics are used. This wild usage is prophylactic (prevention rather than treatment of infection), particularly as a means of enabling less-than-wholesome conditions in industrial farming. They are also routinely used for growth stimulation purposes. In 2016, plasmid-mediated colistin resistance was found in a pig farm. Plasmids, as mentioned before, are mobile genetic elements that enable genes to travel horizontally to other bacteria. And colistin is considered a last-resort antibiotic. Livestock cultivation and animal agricultural practices are a known vector for epidemics. Investigation and regulation could be crucial to restricting the spread of zoonotic resistant bacteria.

Evolved bacteria have disincentivised the development of new antibiotics by pharmaceutical companies.

Australia has encouragingly shown signs of improvement regarding the consumption of antibiotics, with the last five years showing the first decline in usage for two decades. However, broad-spectrum antibiotics are being used as a first response to illnesses that may benefit from other therapies or simply run their own course. Seasonal fluctuations in prescription demonstrate that many antibiotics prescribed to patients in Australia are going towards fighting viral infections that cannot be successfully treated with antibiotics.

Treatments and bolsters for the immune system, eliminating or reducing the need for antibiotics, are also going to be a vital part of the perhaps-post-antibiotic future. Contrarily, studies are demonstrating that probiotics fight infection and shorten the duration of illness. A recent meta-analysis (a review of multiple scientific studies in the same field) found that evidence suggests probiotic supplementation also reduces the likelihood of antibiotic prescription in children.

The future of treatment may look to creative, new ways to extinguish dangerous bacteria. A team in Adelaide have developed a gel, a compound that looks like iron: the favourite snack of ravenous bacteria. This poison starves them of that life-giving element. This treatment is currently on its way from the laboratory to trials on those with sinus infections. There has also been a renewed interest in bacteriophages and phage therapy, the use of a virus that eats up specific bacteria. Their use actually predates antibiotics. If antibiotics are a bomb for bacteria, phages are more like assassins. Phage therapy mostly fell by the wayside, due to the finesse of antibiotics, but it could be due for an intensively researched return.

Evolved bacteria have disincentivised the development of new antibiotics by pharmaceutical companies. As they are drugs taken for a short duration, and superbugs are currently winning the battle to eliminate their usage, they seem like a less desirable investment for R&D companies. If we are to have antibiotics that work in new ways—which is very much needed—we require something other than the free market to decide what medicines have value.

It is difficult not to draw many comparisons to current situation when thinking of Fleming’s warning at the Nobel Banquet in Stockholm, how that call-to-carefulness went unheeded for decades. Howard Florey, speaking at the same event in 1945 addressed how the inventions of that time were causing the most existential terror. He spoke directly to those listening, over plates of potage aux champignons and bombe-glacée, that on those present “rests not only the responsibility for furthering the immediate interests of science but also that of ensuring that those who control our destinies are fully informed of the tremendous forces with which they deal.” While Florey and Fleming spoke to their peers, they were also addressing politicians and heads of state. They petitioned for a safeguarded future, for the intervention by governments on behalf of a broader human interest and for a wellbeing extending beyond the present moment.

We’re proud to partner with Activated Probiotics. The probiotic strains in Activated Probiotic products are chosen for their unique ability to improve the symptoms of complex conditions and maintain health and wellbeing during key life stages.

Hollen Singleton is a writer for business and pleasure. They are the features and community editor for Going Down Swinging.