Earlier this week, Tyson, killer of about 2 billion chickens every year, announced that it would be phasing out the use of human antibiotics in that poultry by 2017. That declaration makes Tyson the latest in a line of major food processors getting out of antibiotic use, including McDonald's, Perdue, and Chick-fil-A.
In a way, that's all good news, especially for the interest groups that have been pushing for more than a decade to cut antibiotic use in food animals. But their nominal goal---to quell the rising tide of drug-resistant human pathogens that cause an estimated 2 million infections and 23,000 annual deaths in the US each year---isn't as simple as denying amoxicillin to McNuggets. Because scientists don't actually know everything they need to about how and how often antibiotic-resistant bacteria move from livestock to people. And until they get a better handle on the conditions that allow resistant genes to flourish, turning animal pathogens into human ones, they won't be able to determine the best way to combat them.
For sure, the argument against antibiotic use in livestock has a lot of intuitive power. Animals in the United States use at least three times more antibiotics than humans, but usually at subtherapeutic levels, to promote growth or to prevent disease from spreading through crowded facilities. Subtherapeutic dosing---exposing bacteria to a drug but not quite killing it---turns out to be a very good way to create resistant bugs. That which does not kill them does indeed make them stronger. Once those bacteria exist, they can spread to the environment by colonizing farmers, or running into groundwater via feces, or contaminating meat. And those bugs will eventually infect humans.
The last step in that line of logic has a problem, though: Scientists aren't sure just how much movement of resistant bacteria there is from animals to humans. "You can say, unequivocally, that people are colonized and infected by these bacteria from animals," says Lance Price, a genetic epidemiologist at the Milken Institute School of Public Health at George Washington University. "But how often are people colonized and subsequently infected?" Big agriculture companies have clung to that knowledge gap as a way to defend the continued use of antibiotics in their livestock.
Let's be clear: That lack of information isn't an excuse to continue feeding antibiotics to livestock. Scientists have consistently found drug-resistant bacteria in the air and water near concentrated animal feeding operations, or CAFOs, and in the nasal passages of livestock workers. Multiple studies have used genetic fingerprinting to link bacterial strains found in antibiotic-fed animals to the humans who work with them, and antibiotics themselves can end up in food, increasing human exposure and the likelihood of resistance. Resistant bacteria from food animals are definitely colonizing, infecting, and killing humans. "The question is how to quantify it," says Price.
But they can't. The best way to prove and quantify the connection between drug-resistant bugs in animals and humans would be to take bacterial samples from food animals and people and subject them to whole-genome phylogenetic analyses. That doesn't happen in the US, because it'd be super-expensive and because the big-food companies would have to grant access to their animals (don't expect ag companies to welcome researchers into their facilities to hunt for pathogens). The few studies that have proved transmission, like MRSA between pigs and farm workers, happened overseas. US researchers aren't testing groundwater and the air around CAFOs because that's ideal---it's because that's the closest they can get to those operations.
Even the successful studies, the ones done abroad, don't close the loop. They prove that transmission between food animals and humans is happening, but not how---and it's that information that will help guide policies to reduce drug-resistant infections.
The typical explanation for the emergence of antibiotic-resistant bacteria is straightforward: When a chromosomal mutation helps a bacterium survive in the face of a drug, the bug will undergo a series of changes it to make it more fit, and then ultimately it will overtake other bacteria in the environment and proliferate. But genes that encode resistance can also spread in a different way. Bacteria can trade genetic information via plasmids, small, mobile bits of DNA that can replicate independently---and much more promiscuously.
While a single chromosomal mutation can only be passed on by a replicating population, plasmids can instantly transfer between individual bacteria, one-to-one. Plasmids also tend to pick up resistance genes together, so a gene for methicillin resistance might be right next to a gene for tetracycline resistance, which might be next to a gene conferring resistance to other antimicrobial compounds, like zinc or disinfectants. Pass one of those plasmids into a bacteria that's already resistant to a last-line antibiotic, like carbapenem? "That's how you make a superbug," says Tim Johnson, a microbiologist at the University of Minnesota.
That means trouble. Even if every single agribusiness quit using antibiotics, full stop, right now, farmers could still be still selecting for antibiotic resistance. In Denmark, for example, where antibiotics in livestock are outlawed, MRSA is still spreading like wildfire among pigs. How? Farmers are supplementing pig feed with zinc, but bacteria present in those pigs have DNA coding for methicillin resistance next door to a zinc resistance gene. "The zinc supplement was selecting for MRSA," says Price.
All of which makes resistance as much a policy problem as a scientific one. If changes like the ones that Tyson is making are going to really reduce antibiotic-resistant infections, scientists need a system---supported by the federal government---to track the incidence and spread of antibiotic resistance. "We have a retail meat monitoring system. We have a live animal monitoring system," says Johnson. "But they collect very few samples, and we're not following through to track changes as companies make these transitions to lower antibiotic use." That follow-through, across hundreds of farms using different antimicrobial agents, is crucial to understanding which variables select for resistance and which of them will reduce it.
The future isn't completely apocalyptic. In September 2014, the President’s Council of Advisors on Science and Technology issued a report that called for a number of actions to tackle antibiotic resistance. It didn't explicitly set benchmarks for improving knowledge of the connection between livestock resistance and human disease, but the White House's National Strategy for Combating Antibiotic-Resistant Bacteria did better. It asked for additional data to be collected on farm antibiotic use and antibiotic-resistance in live animals on farms, and for a framework to analyze the relationship between antibiotic use in animals and resistance in livestock. It also called for fully sequencing the gut microbiota of a food animal species. The President's proposed 2016 budget puts money behind each of those initiatives.
No matter what, Tyson's decision is a great first step to, as its CEO Donnie Smith said, "responsibly reduce human antibiotics on the farm so these medicines can continue working when they're needed to treat illness." In the absence of more information about the pathway from antibiotic use in animals to drug-resistant disease, less drug use is an obvious goal. But pulling antibiotics out of the food supply will only be worth it if researchers can study the effects of that change, getting better access to bacterial samples from livestock and more funding to complete their work. The future of human---and animal---health depends on it.
