What do we do when antibiotics don’t work?

MARYN MCKENNA: This is my great-uncle, my father’s father’s younger brother. His name was Joe McKenna. He was a young husband and semi-pro basketball player, and a fireman in New York City. Family history says he loved being a fireman and so, in 1938, on one of his days off, he elected to hang out at the firehouse. To make himself useful that day, he started polishing all the brass, the railings on the fire truck, the fittings on the walls. And one of the fire-hose nozzles, a giant, heavy piece of metal, toppled off a shelf and hit him. A few days later, his shoulder started to hurt. Two days after that, he spiked a fever. The fever climbed and climbed. His wife was taking care of him, but nothing she did made a difference, and when they got the local doctor in, nothing he did mattered either. They flagged down a cab and took him to the hospital. The nurses there recognised right away that he had an infection, what at the time they would have called blood poisoning. And though they probably didn’t say it, they would have known right away that there was nothing they could do.

There was nothing they could do because the things we use now to cure infections didn’t exist yet. The first test of penicillin, the first antibiotic, was three years in the future. People who got infections either recovered, if they were lucky, or they died. My great-uncle was not lucky. He was in the hospital for a week, shaking with chills, dehydrated and delirious, sinking into a coma as his organs failed. His condition grew so desperate that the people from his firehouse lined up to give him transfusions, hoping to dilute the infection surging through his blood. Nothing worked. He died. He was 30 years old.

If you look back through history, most people died the way my great-uncle died. Most people didn’t die of cancer or heart disease, the lifestyle diseases that afflict us in the West today. They didn’t die of those diseases because they didn’t live long enough to develop them. They died of injuries—being gored by an ox, shot on a battlefield, crushed in one of the new factories of the Industrial Revolution—and most of the time from infection, which finished what those injuries began.

All of that changed when antibiotics arrived. Suddenly, infections that had been a death sentence became something you recovered from in days. It seemed like a miracle. And ever since, we have been living inside the golden epoch of the miracle drugs. And now, we are coming to an end of it.

My great-uncle died in the last days of the pre-antibiotic era. We stand today on the threshold of the post-antibiotic era. In the earliest days of a time when simple infections, such as the one Joe had, will kill people once again. In fact, they already are. People are dying of infections again because of a phenomenon called antibiotic resistance. Briefly, it works like this. Bacteria compete against each other—for resources, for food—by manufacturing lethal compounds that they direct against each other. Other bacteria, to protect themselves, evolve defences against that chemical attack. When we first made antibiotics, we took those compounds into the lab and made our own versions of them, and bacteria responded to our attack the way they always had.

Here is what happened next.

Penicillin was distributed in 1943, and widespread penicillin resistance arrived by 1945. Vancomycin arrived in 1972, vancomycin resistance in 1988. Imipenem in 1985, and resistance to it in 1998. Daptomycin, one of the most recent drugs, in 2003, and resistance to it just a year later in 2004. For 70 years, we played a game of leapfrog—our drug, and their resistance, and then another drug, and then resistance again—and now the game is ending.

Bacteria develop resistance so quickly that pharmaceutical companies have decided making antibiotics is not in their best interest. So there are infections moving across the world for which, out of the more than 100 antibiotics available on the market, two drugs might work, with side effects, or one drug, or none. This is what that looks like.

In 2000, the Centers for Disease Control and Prevention, the CDC, identified a single case in a hospital in North Carolina of an infection resistant to all but two drugs. Today, that infection, known as KPC, has spread to every state but three, and to South America, Europe and the Middle East. In 2008, doctors in Sweden diagnosed a man from India with a different infection resistant to all but one drug that time. The gene that creates that resistance, known as NDM, has now spread from India into China, Asia, Africa, Europe, and Canada, and the United States. 

It would be natural to hope that these infections are extraordinary cases. But in fact, in the United States and Europe, 50,000 people a year die of infections which no drugs can help. A project chartered by the British government known as the Review on Antimicrobial Resistance estimates that the worldwide toll right now is 700,000 deaths a year. That is a lot of deaths. And yet, the chances are good that you don’t feel at risk. That you imagine these people were hospital patients in intensive care units or nursing-home residents near the ends of their lives. People whose infections are remote from us, in situations we can’t identify with. What you didn’t think about, none of us do, is that antibiotics support almost all of modern life.

If we lost antibiotics, here’s what else we’d lose. First, any protection for people with weakened immune systems—cancer patients, AIDs patients, transplant recipients, premature babies. Next, any treatment that installs foreign objects in the body. Stents for stroke, pumps for diabetes, dialysis, joint replacements. How many athletic baby boomers need new hips and knees? A recent study estimates that without antibiotics, one out of every six would die. Next, we’d probably lose surgery. Many operations are preceded by prophylactic doses of antibiotics. Without that protection, we’d lose the ability to open the hidden spaces of the body. So no heart operations, no prostate biopsies, no caesarean sections. We’d have to learn to fear infections that now seem minor. Strep throat used to cause heart failure. Skin infections led to amputations. Giving birth killed, in the cleanest hospitals, almost one woman out of every 100. Pneumonia took three children out of every 10. More than anything else, we’d lose the confident way we live our everyday lives. If you knew that any injury could kill you, would you ride a motorcycle, bomb down a ski slope, climb a ladder to hang your Christmas lights, let your kid slide into home plate? After all, the first person to receive penicillin, a British policeman named Albert Alexander, who was so ravaged by infection that his scalp oozed pus and doctors had to take out an eye, was infected by doing something very simple. He walked into his garden and scratched his face on a thorn. 

That British project I mentioned which estimates that the worldwide toll right now is 700,000 deaths a year also predicts that if we can’t get this under control by 2050, not long, the worldwide toll will be 10 million deaths a year.

How did we get to this point, where what we have to look forward to is those terrifying numbers? The difficult answer is, we did it to ourselves. Resistance is an inevitable biological process, but we bear the responsibility for accelerating it. We did this by squandering antibiotics with a heedlessness that now seems shocking. Penicillin was sold over the counter until the 1950s. In much of the developing world, most antibiotics still are. In the United States, 50 per cent of the antibiotics given in hospitals are unnecessary. Forty-five per cent of the prescriptions written in doctor’s offices are for conditions that antibiotics cannot help. And that’s just in health care. On much of the planet, most meat animals get antibiotics every day of their lives, not to cure illnesses, but to fatten them up and to protect them against the factory-farm conditions they are raised in. In the United States, possibly 80 per cent of the antibiotics sold every year go to farm animals—not to humans—creating resistant bacteria that move off the farm, in water, in dust, in the meat the animals become. Aquaculture depends on antibiotics too, particularly in Asia, and fruit-growing relies on antibiotics to protect apples, pears, citrus, against disease. And because bacteria can pass their DNA to each other, like a traveller handing off a suitcase at an airport, once we have encouraged that resistance into existence, there is no knowing where it will spread.

This was predictable. In fact, it was predicted by Alexander Fleming, the man who discovered penicillin. He was given the Nobel Prize in 1945 in recognition and, in an interview shortly after, this is what he said: ‘The thoughtless person playing with penicillin treatment is morally responsible for the death of a man who succumbs to infection with a penicillin-resistant organism’. He added, ‘I hope this evil can be averted’.

Can we avert it?

There are companies working on novel antibiotics, things the superbugs have never seen before. We need those new drugs, badly. And we need incentives. Discovery grants, extended patents, prizes, to lure other companies into making antibiotics again. But that probably won’t be enough. Here’s why. Evolution always wins.

Bacteria birth a new generation every 20 minutes. It takes pharmaceutical chemistry 10 years to derive a new drug. Every time we use an antibiotic, we give the bacteria billions of chances to crack the codes of the defences we’ve constructed. There’s never yet been a drug they could not defeat. 

This is asymmetric warfare. But—we can change the outcome. We could build systems to harvest data to tell us automatically and specifically how antibiotics are being used. We could build gatekeeping into drug order systems so that every prescription gets a second look. We could require agriculture to give up antibiotic use. We could build surveillance systems to tell us where resistance is emerging next. Those are the tech solutions. They probably aren’t enough either. Unless we help. 

Antibiotic resistance is a habit. We all know how hard it is to change a habit. But as a society, we’ve done that in the past. People used to toss litter into the streets, used to not wear seatbelts, used to smoke inside public buildings. We don’t do those things anymore. We don’t trash the environment, or court devastating accidents, or expose others to the possibility of cancer, because we decided those things were expensive, destructive, not in our best interest. We changed social norms. We could change social norms around antibiotic use too.

I know that the scale of antibiotic resistance seems overwhelming, but if you’ve ever bought a fluorescent light bulb because you were concerned about climate change, or read the label on a box of crackers because you think about the deforestation from palm oil, you already know what it feels like to take a tiny step to address an overwhelming problem. We could take those kinds of steps for antibiotic use too. We could forgo giving an antibiotic if we’re not sure it’s the right one. We could stop insisting on a prescription for our kid’s ear infection before we’re sure what caused it. We could ask every restaurant, every supermarket, where their meat comes from. We could promise each other never again to buy chicken or shrimp or fruit raised with routine antibiotic use, and if we did those things, we could slow down the arrival of the post-antibiotic world. But we have to do it soon. Penicillin began the antibiotic era in 1943. In just 70 years, we walked ourselves up to the edge of disaster. We won’t get 70 years to find our way back out again. Thank you very much.