Is This the End for Antibiotics?

Feb 68 min read

Since Alexander Fleming stumbled upon penicillin nearly a century ago, antibiotics have saved hundreds of millions of lives. They’re so widely used that it’s easy to forget that they’re among the most revolutionary medical breakthroughs in history.

But we now face a grave problem: they’re becoming less effective and may soon stop working altogether. This is because bacteria are becoming increasingly resistant. Does this rise of “superbugs” threaten to return us to an era of untreatable diseases?

In this short explainer video, I explore why this is happening and what we can do about it:

The accidental discovery that changed the world

Scottish scientist Alexander Fleming was an untidy and forgetful man who kept his lab in a filthy state.

In the late summer of 1928, he set off for a two-week holiday, locking up his premises in Paddington, London, without bothering to clean up first. It was an act of slovenliness that led to the most significant life-saving medical breakthrough of the 20th century.

On 3rd September, Fleming returned to work and prepared to wash up the stacks of Petri dishes he’d left lying around. But he noticed something unusual.

A grayscale image of Alexander Fleming working in his lab.

Before going on holiday, Fleming had been studying Staphylococcus, a common bacteria that causes abscesses, boils, and sore throats.

He was now surprised to see that mould had developed on one of the bacteria-covered samples. Most significantly, this growth was surrounded by a clear buffer zone. Whatever this thing was, it had stopped the bacteria from growing.

The sample, it seemed, had been contaminated by something sweeping in through a window Fleming had forgotten to close.

After further investigation, it turned out that this strange new compound could kill a range of harmful bacteria. Fleming eventually identified it as being from the genus Penicillium and called his new solution penicillin. The era of antibiotics was born.

From lab to lifesaver

During the First World War, Fleming served in the Royal Army Medical Corps. In the grim conditions of field hospitals, he was surrounded by soldiers dying – some from significant injuries, but others from infected wounds. As a bacteriologist, his job was to stop bacterial infections like gangrene from becoming fatal.

So, the significance of this fortuitous 1928 discovery wasn’t lost on him. However, it took another decade – and the outbreak of the Second World War – for its potential to be fully realised.

The start of a new global conflict sparked an urgent demand for effective treatments and a coordinated multinational effort to make penicillin scalable.¹

A cartoon depiction of a penicillin molecule and bacteria under a magnifying glass.

A team at Oxford University developed a method to purify and stabilise Fleming’s discovery, while pharmaceutical companies in the UK and the US collaborated to scale up production. By the time the war ended in 1945, more than 1 million people had been treated with this “miracle drug” – saving countless soldiers from amputations or death.

Fleming shared the 1945 Nobel Prize in Physiology or Medicine with Oxford University’s Howard Florey and Ernst Boris Chain. Together, they revolutionised medicine. More than 100 new antibiotics were discovered in the next few decades, giving doctors a powerful new arsenal for tackling infectious diseases.

The impact was astonishing. By the end of the 20th century, average life expectancy had doubled – a feat unprecedented in human history. In 1900, two in every five children died before their fifth birthday. By 2000, that measure of child mortality had reduced to around two in 28. Previously fatal diseases like scarlet fever and diphtheria became easily treatable conditions. Sore throats, minor cuts and dental infections went from being potential death sentences to relatively minor inconveniences.

Fleming’s messy lab discovery saved hundreds of millions of lives.

Fleming’s terrible prophecy

I would like to sound one note of warning. Penicillin is to all intents and purposes non-poisonous so there is no need to worry about giving an overdose and poisoning the patient. There may be a danger, though, in underdosage. It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body. The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.

– Alexander Fleming’s 1945 Nobel Lecture

Fleming’s nightmare scenario has come true. While penicillin isn’t sold freely in shops, the widespread misuse of antibiotics has had the same effect.

A cartoon depiction of Alexander Fleming making a speech about penicillin whilst receiving his Nobel Prize.

GPs often overprescribe to meet patient expectations, resulting in people taking antibiotics unnecessarily for illnesses not caused by bacteria. (Antibiotics have no effect on viral, fungal, or parasitic infections.) Meanwhile, almost half of people in the US admit to ‘underdosing’ by stopping their course of antibiotics too early.

Our reliance on these drugs has continued to rocket. Around 49.3 billion daily doses were consumed in 2023. And that’s just human usage. Two-thirds of antibiotics are used in agriculture, where they are indiscriminately dished out to livestock to reduce the risk of disease and promote growth.

With the advent of deadly superbugs like MRSA, we have reached a crisis point. Bacteria have become resistant and the old medicines are no longer working.

“Antimicrobial resistance could unwind 100 years of medical progress, making infections that are easily treatable today a death sentence.” That was the stark warning last year from the World Health Organization’s director general Tedros Adhanom Ghebreyesus.

1.9 million people died from antibiotic-resistant infections in 2019. A review commissioned by the UK government estimated that by 2050, this could rise to 10 million per year.

Bacteria develop resistance to antibiotics through natural selection. Following the discovery of penicillin, we entered an arms race with these tiny foes, developing new antibiotics each time bacteria evolved to resist the old ones.

But in this game of genetic whack-a-mole, the odds were always stacked against us. Bacteria can quickly adapt and mutate thanks to their incredible reproduction speed: some replicate every 20 minutes!

In contrast, our efforts to stay on top have almost ground to a halt. The golden age of antibiotic discovery ended a generation ago. No new effective antibiotics have made it out of the lab since 1987.

Two graphs side by side showing "Effectiveness" with a downward trend, and "Innovation" with an upward trend.

Five potential solutions

So, with superbugs running rampant and the World Health Organization warning of an existential threat to humanity, where is a solution going to come from? A century on from Fleming’s messy lab discovery, we need a new breakthrough. Here are five potential answers:

1. Find new antibiotics

The first and most obvious solution is to add to our artillery of antibiotics. By some accounts, we’ve discovered only 1% of the antibiotics the natural world has to offer. Ordinary soil is a potential treasure trove of microorganisms with antibiotic potential. And there have been some encouraging recent developments.

Clovibactin, discovered in 2023, could be a game-changer. It attacks bacteria from the inside out, dismantling its ability to build protective walls and develop resistance.

AI is accelerating the search for new antibiotics, rapidly sifting through millions of candidate compounds to find promising treatments. In 2019, a machine learning model was used to discover a new antibiotic for the first time. Researchers at MIT named the substance halicin, after the artificial intelligence system in 2001: A Space Odyssey.

However, with a long, uncertain road of clinical trials ahead, we're unlikely to be adding these new drugs to our medical toolkit any time soon.

2. Phage therapy

An old technique gaining renewed attention, phage therapy uses carefully selected viruses that attack specific bacteria to infect the infection. Doctors were using phages more than a century ago to treat infectious diseases, but this method was soon eclipsed by the emergence of penicillin. Phages require an accurate diagnosis of the disease being treated and the isolation of a virus that will attack precisely the right kind of bacteria. This complexity was considered a weakness compared with the low-risk, low-cost convenience of traditional antibiotics. But, in the future, this accuracy may lead to its re-emergence. Trials of phage therapies in the U.S. and Australia have yielded promising results in treating superbug infections resistant to antibiotics.

3. Nanomedicine

A more high-tech approach uses nanoparticles about a million times smaller than a grain of sand to attack a bacteria's cell walls, DNA, or other weak points. It's been suggested these can be delivered through gels for the skin, inhaling them into the lungs for pneumonic infections, or via contact lenses for eye infections. Some nanoparticles can be activated under light, offering pinpoint precision without the risk of harming healthy tissues. Still, nanoparticles need more research before we can be sure they’re safe to use.

4. Halting evolution

What if, instead of trying to outpace the evolution of bacteria, we could effectively stop them from developing resistance? That’s the thinking behind a promising new strategy being developed by researchers at Oxford University. They’ve discovered that a single gene is largely responsible for how quickly a dangerous bacteria can evolve resistance to certain antibiotics. Even more excitingly, they found that by targeting this gene with inhibitors, they could prevent it from developing resistance altogether. This ‘anti-evolution’ approach could represent a huge breakthrough in combatting superbugs – if it works in clinical trials.

5. Probiotics

The human body plays host to literally trillions of bacteria. In recent years, we’ve developed a better understanding of our microbiome and now know that many bacteria play a crucial role in digestion and our overall health. One drawback of antibiotics is that they try to kill all bacteria they come into contact with – even the “good” ones. Probiotics – live bacteria and yeasts that help nurture good bacteria in our bodies – have been around for some time, but there’s still a lot we don’t know about them. Scientists are now studying whether probiotic-based therapies could help tackle resistance, boost immunity and ultimately reduce our reliance on antibiotics. The theory is that if we can crowd out “bad” bacteria with the “good” ones, then the harmful organisms won’t be able to thrive.

Beyond antibiotics

Anyone who’s taken antibiotics has likely experienced an upset stomach – an unintended consequence of the same Achilles’ heel that drives antimicrobial resistance. Antibiotics are a blunt tool. They may have helped clear up that ear infection you were struggling with, but they also indiscriminately attacked lots of other cells on the way – including the good bacteria in your gut.²

As microbiologist Roy Robins-Browne explains:

If you consume an antibiotic for an infection in your foot, it does not magically go to your foot alone, but is distributed throughout the body, affecting some of the ‘good’ bacteria that live on and in us. For this reason, many of the 100 trillion bacteria that live in each of us have become resistant to commonly used antibiotics. These ‘good’ bacteria can then transfer resistance to their disease-causing companions.In order to control antibiotic resistance we need to think about antimicrobial therapy in new ways.

Put simply, we need to do things differently. The continuing search for new antibiotics may help in the short term, but really, it’s just upping the ante in the same losing game.

Fleming’s discovery revolutionised medicine, helping us all lead healthier and longer lives. As we face the resistance crisis he predicted 80 years ago, the greatest breakthroughs of our time may not be new antibiotics – but alternatives that make us less reliant on the 20th century’s “miracle drugs”.

In the meantime, we can all play our part in keeping antibiotics effective for as long as possible by treating them as the precious resources they are – and using them wisely.