What began as a means of increasing the productivity of livestock farming has grown into one of the burgeoning health crises of our era. Maryn McKenna explains the imminent threat of antibiotic resistance.
On Christmas Day 1948, a British-American biologist named Thomas Jukes walked into a laboratory outside New York City to check the results of an experiment.
What he found that day reshaped agriculture as it was then known. It created the ability to grow livestock inexpensively in enormous numbers, simultaneously sparking a worldwide human health threat that would emerge from the vast farms facilitated by his discovery.
The threat was, and is, antibiotic resistance; the ability of pathogens to protect themselves against the drugs intended to kill them. According to the Review on Antimicrobial Resistance, chartered by former British Prime Minister David Cameron, drug-resistant infections currently kill an estimated 700,000 people per year worldwide and may come to kill 10 million per year by 2050. Cameron called that “an almost unthinkable scenario where… we are cast back into the dark ages of medicine.”
The contribution that Jukes made to that problem — and that intensive agriculture enthusiastically adopted after him — is the routine administration of antibiotics to livestock on most of the days of their lives. This gives birth to resistant bacteria that cause human illness far away from farms.
Jukes was a biologist at the pharmaceutical firm Lederle Laboratories, which had just patented the drug aureomycin, the first of the tetracycline class of antibiotics. Antibiotics were new — penicillin, the first of them, had only been released to the public in 1944 — and wildly popular. The firms that were rushing to make them were angling for any advantage that would deliver a sliver more market share to their products over those of their competitors’.
“From the start of the antibiotic era in the 1940s, scientists warned that allowing bacteria to adapt to antibiotics would lead to the drugs losing their power.”
The experiment that Jukes was running was designed to carve out one such sliver. He was looking for a supplement that livestock farmers could use to augment the inexpensive feed they had adopted after the guaranteed market of provisioning troops went away with the Second World War’s end. To feed so many soldiers, sailors and workers, the meat industry had invested heavily in new capacity; when those guaranteed sales went away, the industry felt compelled to cut costs sharply to keep from total collapse.
Switching to cheaper feed — grains, instead of high-protein fishmeal — was one way to cut costs, but cheaper feed was also less nutritious. Farmers needed an abundantly available supplement that would cost them little money. Jukes’ experiment — a bunch of baby chicks divided into groups, one per supplement, with one group held back as a control — revealed that the most potent supplement available to him was tiny doses of his company’s antibiotic, contained in the leftover growth medium in which the drug had been brewed. The net result was money for nothing: a substance with a price that farmers could afford, made from a material that the manufacturer had intended to discard.
“By 1955, American farmers were giving their livestock 500,000 pounds of antibiotics per year. Now, globally, the total is estimated to be 131,109 tons, predicted to rise to 200,235 tons by 2030.”
Jukes called the effect created by his company’s drug “growth promotion.” Within a year, Lederle had patented the drug for that use. Within two years it had wangled a drug approval from the US Food and Drug Administration. Shortly afterward, additional research revealed that slightly larger doses of antibiotics could also protect livestock from becoming infected with any diseases that circulated in barns and feedlots, and that use was patented and licensed too. Growth promotion in particular was fantastically successful, conferring at least a 5% and up to a 12% saving on the amount of food it took to get an animal to market weight. No wonder then that by 1955, American farmers were giving their livestock 500,000 pounds of antibiotics per year.
Now, globally, the total is estimated to be 131,109 tons, predicted to rise to 200,235 tons by 2030. The quantity administered to each animal is not uniform across the globe; if you calculate how much antibiotic a country uses across the number of animals it raises, the range goes from Norway (8 milligrams per kilogram of livestock produced) to China (318 milligrams per kilogram). On a relative basis, livestock receive approximately as much antibiotics by weight as are given to humans — but with the crucial difference that antibiotics given to humans are intended to cure illness. Most of the livestock that receive antibiotics are not sick.
From the start of the antibiotic era in the 1940s, scientists warned that allowing bacteria to adapt to antibiotics, and develop defences against their fatal effects, would lead to the drugs losing their power. Sir Alexander Fleming, who discovered penicillin, famously warned against that possibility in his 1945 Nobel Medicine Prize acceptance speech, saying: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them.”
No one seems to have noticed that the burgeoning use of antibiotics in agriculture represented just what Fleming had warned against. Jukes’ growth promotion used doses that were too small to kill bacteria, but the right size to affect the microbiome in animals’ intestines. This shifted the mix of gut flora toward organisms that more efficiently extracted nutrition from feed, but increased the proportion that were resistant. No one noticed, either, that the ability to grow animals more quickly, and to keep them healthy while they grew, was encouraging the meat industry to pack increasing numbers of animals onto farms, creating exactly the right conditions for newly resistant bacteria to circulate from one animal to another. That those bacteria were in animals’ guts was a crucial clue to what happened next.
“When animals were slaughtered and disassembled, their gut contents splashed onto the whole carcass, and the resistant bacteria from the guts traveled on the meat into restaurants and home kitchens.”
Antibiotic-resistant foodborne illness — a thing that had never before existed in the world — began to occur in outbreaks, first in small clusters of illness and then increasingly large ones. The cause was meat. When animals were slaughtered and disassembled, their gut contents splashed onto the whole carcass. This was then butchered and sold to consumers, and the resistant bacteria from the guts traveled on the meat into restaurants and home kitchens.
There was a risk from live animals, too. The resistant bacteria they defecated washed away from farms in storm runoff or blew away on the wind, sending resistant DNA out into the world to be picked up by other bacteria with no obvious farm connection.
Precisely because so many outbreaks of resistant illness have been foodborne — from the 15 children killed by drug-resistant E. coli in the Yorkshire town of Middlesbrough in 1967, to the 638 people sickened by a resistant Salmonella outbreak in the United States in 2013 and 2014 — the connection with farm antibiotic use hasn’t been hard to make.
Over the decades, researchers have also confirmed links that were harder to tease out than those between animal husbandry and meat consumption. Among them: an epidemic of drug-resistant staph, MRSA, which crossed from pigs to pig farmers in the Netherlands — not from meat, but from bacteria on the animals’ skin and in their noses — and which sparked an outbreak in Dutch hospitals. There was also the discovery in 2015 that Chinese agriculture had caused resistance to a last-resort antibiotic called colistin. This was occurring simultaneously in pigs, retail pork and people, and had escaped the Chinese agricultural system to move around the globe.
And, in several states in America, the revelation that people living near large farms were at greater risk of drug-resistant infections, even if they had no personal or family contact with the farms.
Science has always been confident of the connection between farm antibiotic use and antibiotic resistance; at this point, hundreds of studies have confirmed it. However, it took a while for policy-makers to agree. The first ban on some forms of farm antibiotic use was enacted by the British Parliament in 1971. The European Union acted in 2005. The United States, not until 2017. Much of the developing world has no curbs on farm antibiotic use at all.
The challenge has been quantifying just how much of the global epidemic of antibiotic resistance can be attributed to farms. That’s problematic because, in most countries outside the European Union, record keeping of what is sold for farm use is sparse, quite different from the close tracking of pharmaceuticals for human use. Surveillance for resistant bacteria arising in animals is robust in a few countries, but patchy in many and nonexistent in many more.
Still, policymakers are taking the connection seriously, to the point that in 2015, the World Health Assembly adopted a comprehensive plan on antibiotic resistance that included agricultural reform. The United Nations devoted a day of its General Assembly in 2016 to examining resistance, and all of its member governments committed to working out national policies that include reforming agriculture. The World Organization for Animal Health, a UN agency, is now pressing countries to develop better data for how big their national flocks and herds have grown and how many antibiotics they consume.
It’s important to do that quickly, because meat consumption is growing, driven by the increased spending power and appetite for flesh in the new middle classes of the developing world. A report published in January 2018 for the meeting of the World Economic Forum estimates that global meat production, which was about 45 million tonnes per year in 1960, is currently 263 million tonnes, and is headed towards 445 million tonnes by 2050. This is a tenfold increase driven entirely by the intensification of production in the kinds of farms that require antibiotics to operate.
The appetite for meat seems hardwired into humans, but there are some positive signs that meat production may be able to break its antibiotic habit. In 2014, the American corporation Perdue Farms Inc., the fourth- largest poultry company in the country, abruptly announced that it was relinquishing most of its antibiotic use, forcing the rest of the US industry to scramble to catch up. Before the announcement, Perdue had cannily conducted a lengthy experiment on its contract farms, evaluating whether birds continued to do better on antibiotic-laced feed, and discovered that the drugs were no longer necessary. Whatever deficits in farming had existed back in the 1950s, better hygiene and precision nutrition now made them an unnecessary expense.
The ability to change isn’t confined to the United States. In 2010, the Dutch government asked its agricultural sector to collaborate in reducing antibiotic use; in three years, the country reduced its farm-antibiotic consumption by half. And in 2016, the central government of China, embarrassed by the worldwide spread of colistin resistance emerging from its agriculture, banned the drug from use on its farms, unilaterally taking 8,000 tons of it off the market.
It’s important to acknowledge the power of consumers to support such changes. In the United States, where regulation of growth promoters arrived a decade after it did in Europe, political change was preceded by meat buyers rejecting products raised with routine antibiotic use. Healthcare organisations and school systems led the charge, telling wholesalers they would refuse to buy meat raised in this way. Chefs’ organisations and parents groups followed, voting with their food dollars for “no antibiotics ever” chicken, and making companies like Perdue feel that changing their practices would not cause them to lose customers.
As potent as it is, consumer action isn’t enough. Governments have to act to tamp down the risk of antibiotic resistance emerging from farms — and it’s not clear that they will. Late last year, the World Health Organization asked all its member governments to commit to more extensive regulations than any of them had made so far. It wanted them to ban preventive use on farms, reserving antibiotics only for the treatment of sick animals. One of the first governments to react to the plea was the new Trump Administration. It said no.