In 1954, just a few years after the widespread introduction of antibiotics, doctors were already aware of the problem of resistance. Natural selection meant that using these new medicines gave an advantage to the microbes that could survive the assault – and a treatment that worked today could become ineffective tomorrow. A British doctor put the challenge in military terms: “We may run clean out of effective ammunition. Then how the bacteria and moulds will lord it.”
More than 70 years later, that concern looks prescient. The UN has called antibiotic resistance “one of the most urgent global health threats”. Researchers estimate that resistance already kills more than a million people a year, with that number forecast to grow. And new antibiotics are not being discovered fast enough; many that are essential today were discovered more than 60 years ago.
The thing to remember is that antibiotics are quite unlike other medicines. Most drugs work by manipulating human biology: paracetamol relieves your headache by dampening the chemical signals of pain; caffeine blocks adenosine receptors and as a result prevents drowsiness taking hold. Antibiotics, meanwhile, target bacteria. And, because bacteria spread between people, the challenge of resistance is social: it’s as if every time you took a painkiller for your headache, you increased the chance that somebody else might have to undergo an operation without anaesthetic.
That makes resistance more than simply a technological problem. But like that British doctor in 1954, we still often talk as if it is: we need to invent new “weapons” to better defend ourselves.
What this framing overlooks is that the extraordinary power of antibiotics is not due to human ingenuity. In fact, the majority of them derive from substances originally made by bacteria and fungi, evolved millions of years ago in a process of microbial competition.
This is where I can’t help thinking about another natural resource that helped create the modern world but has also been dangerously overused: fossil fuels. Just as Earth’s geological forces turned dead plants from the Carboniferous era into layers of coal and oil that we could burn for energy, so evolution created molecules that scientists in the 20th century were able to recruit to keep us alive.
Both have offered an illusory promise of cheap, miraculous and never-ending power over nature – a promise that is now coming to an end. If we thought of antibiotics as the “fossil fuels” of modern medicine, might that change how we use them? And could it help us think of ways to make the fight against life-threatening infections more sustainable?
The antibiotic era is less than a century old. Alexander Fleming first noticed the activity of a strange mould against bacteria in 1928, but it wasn’t until the late 1930s that the active ingredient – penicillin – was isolated. A daily dose was just 60mg, about the same as a pinch of salt. For several years it was so scarce it was worth more than gold. But after production was scaled up during the second world war, it ended up costing less than the bottle it came in.
This abundance did more than tackle infectious diseases. Just as the energy from fossil fuels transformed society, antibiotics allowed the entire edifice of modern medicine to be built. Consider surgery: cutting people open and breaking the protective barrier of the skin gives bacteria the chance to swarm into the body’s internal tissues. Before antibiotics, even the simplest procedures frequently resulted in fatal blood poisoning. After them, so much more became possible: heart surgery, intestinal surgery, transplantation. Then there’s cancer: chemotherapy suppresses the immune system, making bacterial infections one of the most widespread complications of treatment.
The effects of antibiotics have rippled out even further: they made factory farming possible, both by reducing disease among animals kept in close quarters, and by increasing their weight through complex effects on metabolism. They’re one of the reasons for the huge increase in meat consumption since the 1950s, with all its concomitant welfare and environmental effects.
Despite the crisis of resistance, antibiotics remain cheap compared with other medicines. Partly – as with fossil fuels – this is because the negative consequences of their use (so-called externalities) are not priced in. And like coal, oil and gas, antibiotics lead to pollution. One recent study estimated that 31% of the 40 most used antibiotics worldwide enter rivers. Once they’re out there, they increase levels of resistance in environmental bacteria: one study of soil from the Netherlands showed that the incidence of some antibiotic-resistant genes had increased by more than 15 times since the 1970s. Another source of pollution is manufacturing, particularly in countries such as India. In Hyderabad, where factories produce huge amounts of antibiotics for the global market, scientists have found that the wastewater contains levels of some antibiotics that are a million times higher than elsewhere.
Like the climate crisis, antibiotic resistance has laid global inequalities bare. Some high-income countries have taken steps to decrease antibiotic use, but only after benefiting from their abundance in the past. That makes it hard for them to take a moral stand against their use in other places, a dilemma that mirrors the situation faced by post-industrial nations urging developing nations to forgo the economic benefits of cheap energy.
This may be where the similarities end. While we look forward to the day when fossil fuels are phased out completely, that’s clearly not the case with antibiotics, which are always going to be part of medicine’s “energy mix”. After all, most deaths from bacterial disease worldwide are due to lack of access to antibiotics, not resistance. What we are going to need to do is make our approach to development and use much more sustainable. Currently, many pharmaceutical companies have abandoned the search for new antibiotics: it’s hard to imagine a more perfect anti-capitalist commodity than a product whose value depletes every time you use it.
That means we need alternative models. One proposal is for governments to fund an international institute that develops publicly owned antibiotics, rather than relying on the private sector; another is to incentivise development with generously funded prizes for antibiotic discovery. And to address the issue of overuse, economists have suggested that health authorities could run “subscription” models that remove the incentive to sell lots of antibiotics. In one pilot scheme in England, two companies are being paid a set amount per year by the NHS, regardless of how much of their product is actually used.
Finally, we have to remember that antibiotics aren’t the only game in town. Supporting other, “renewable” approaches means we get to use the ones we do have for longer. Vaccines are vital to disease prevention – with every meningitis, diphtheria or whooping cough vaccine meaning a potential course of antibiotics forgone. And the 20th century’s largest reductions in infectious disease occurred not because of antibiotics, but thanks to better sanitation and public health. (Even in the 2000s, the threat of MRSA was addressed with tried-and-tested methods such as handwashing and cleaning protocols – not new antibiotics.) Given that antibiotics themselves emerged unexpectedly, we should also be investing more in blue-skies research.
Just as we no longer burn coal without a thought for the consequences, the era of carefree antibiotic use is now firmly in the past. In both cases, the idea that there wouldn’t be a reckoning was always an illusion. But as with our slow waking up to the reality of the climate crisis, coming to appreciate the limits of our love affair with antibiotics may ultimately be no bad thing.
Liam Shaw is a biologist at the University of Oxford, and author of Dangerous Miracle (Bodley Head).
Further reading
Being Mortal: Medicine and What Matters in the End by Atul Gawande (Profile, £11.99)
Infectious: Pathogens and How We Fight Them by John S Tregoning (Oneworld, £10.99)
Deadly Companions: How Microbes Shaped our History by Dorothy H Crawford (Oxford, £12.49)