On Christmas day in 1948, a scientist walked into his laboratory outside of New York City to check the results of an experiment. What he found changed the way we raise farm animals and, according to journalist and author Maryn McKenna, set the world on course for crisis.
That crisis is antibiotic resistance, and it began — or at least accelerated — with the discovery 70 years ago that McKenna, the author of “Big Chicken: The Incredible Story of How Antibiotics Created Modern Agriculture and Changed the Way the World Eats,” described Thursday to a packed auditorium at Fred Hutchinson Cancer Research Center.
That scientist discovered that giving tiny doses of antibiotics to chickens sped their growth and protected them from crowding and other unhealthy conditions. Considered both a miracle and a moneymaker, the practice quickly became widespread in pork, beef and other meat production as well. But McKenna said the unintended consequence was that the pervasive use of these drugs put pressure on bacteria to do what they do very well even without encouragement — develop resistance through mutation.
“Whenever we use an antibiotic, we’re taking a risk that the bug will mutate and adapt to the drug designed to kill it. We balance the benefit of the drug versus the risk of resistance,” she said. “Whenever we give animals that are not ill antibiotics, there is no benefit, only risk.”
The well-known science writer — her 2015 TED talk, “What do we do when antibiotics don’t work any more?” has been viewed more than 1.5 million times — spoke at a “Farm to Bedside” symposium on the challenges of antimicrobial resistance in agriculture and human health. Organized by Fred Hutch’s Infectious Disease Sciences Program, it featured a panel of scientists from the Washington State Department of Health, the University of Washington, Washington State University, Seattle Children’s Hospital and Fred Hutch, as well as a lively discussion with an audience that included veterinarians, high school teachers, cheesemakers and infectious disease specialists from across the state.
Resistant microbes don’t stay on the farm. They travel via groundwater, wind, on skin, clothing, and tires, and in meat contaminated in slaughterhouses. They cross borders and oceans.
For years, McKenna said, the public assumed that however bad resistance became, science would always come up with a new and better drug. But the easy drugs already have been discovered, and pharmaceutical companies are wary of investing in drug development when resistance limits its earnings. Today there is an alarming lack of new antibiotics in the drug development pipeline.
“In that endless game of leapfrog between drugs and bugs, the bugs are ahead,” McKenna said.
Today antimicrobial-resistant “superbugs” kill an estimated 700,000 people around the world, 23,000 of them in the United States, according to the U.S. Centers for Disease Control and Prevention. If nothing is done to address the crisis, one study projects that by 2050, resistant pathogens will kill 10 million people a year worldwide — or as McKenna put it — as many as a large passenger plane crashing every 15 minutes.
She also pointed out the less-dramatic effects of a post-antibiotic world, never experienced by those who have been born since the golden age of antibiotics began with the widespread use of penicillin during World War II. Will we begin to fear things we don’t fear anymore, she asked, like a scratch that could lead to an amputation?
“Would you ride a motorcycle? Would you bomb down a ski slope?” she asked. “Would you let your kid slide into home plate? Those are the things that are threatened by our loss of antibiotics that we don’t think about.”
Fred Hutch’s Dr. Steve Pergam, an infectious disease researcher, medical director of infection prevention at Seattle Cancer Care Alliance, and the convener of Thursday’s symposium, said of McKenna’s talk, “I hope her stories scare people so they pay attention to this issue.”
Cancer researchers understand more than most the threat posed by treatment-resistant infections.
“Antibiotic resistance has the potential to not only change cancer therapy but to derail many of the tremendous gains that we’ve made,” said Pergam.
Many of those gains came from learning how to prevent or contain infections that prey on people with immune systems weakened by cancer or treatment, or both.
Fred Hutch has one of the largest groups of infectious disease researchers at any cancer center due to its pioneering work in bone marrow transplantation. Preparing a patient for a transplant means essentially ridding the body of its cancerous immune system and allowing a new one to come in and set up shop. Until the new immune cells take hold, a person’s natural defenses against infections are rendered useless. Threats can come from inside and outside the body. Even microbes that would normally be harmless can wreak havoc.
Other cancer treatments — surgery, radiation and chemotherapy — also increase infection risks. Surgical incisions, as well as central lines for delivering chemotherapy, serve as portals for germs to enter the body. Radiation and chemotherapy can break down cells lining the mouth and the gastrointestinal and respiratory tracts, which ordinarily serve as barriers to germs. And these treatments can weaken the body’s immune system, already burdened by the cancer itself.
Penicillin and newer antibiotics — as well as anti-fungal drugs and antivirals — revolutionized cancer care. The threat that they could lose their livesaving power explains how a cancer center came to convene a panel of experts in antimicrobial resistance.
Pergam and others are quick to point out that agricultural practices aren't the only problem when it comes to inadvertently encouraging resistance. Doctors' prescribing practices share the blame. The panel also explored ways that medicine can be part of the solution.
SCCA and other medical centers are now required by law to have antimicrobial stewardship programs to balance the drugs’ lifesaving good against the threat of resistance. Dr. Scott Weissman, director of antimicrobial stewardship at Seattle Children’s Hospital, called such programs “the last, best hope” of changing overprescribing by physicians: another driver of resistance besides the overuse of antibiotics in animals.
As an expert in pediatric infectious diseases, he knows firsthand the pressure of parents wanting a physician to do something, even if an infection is viral, not bacterial — and thus won’t be helped by an antibiotic. For that matter, he knows that physicians often put that pressure on themselves.
“Prescribing is an emotional behavior, and these are entrenched patterns. We are the fox in our own hen house,” he said, employing an appropriate metaphor for a symposium that began with chickens. “Maybe we should just be prescribing ourselves anti-anxiety medication.”
To panelist Dr. Catherine Liu, director of antimicrobial stewardship at Fred Hutch and SCCA, stewardship programs have an added advantage: In addition to helping stave off resistance, they may help safeguard the microbiome.
Researchers are learning more about how the microbiome — the trillions of bacteria that live in our guts — affects our health. They are also learning how antimicrobials can kill off the good microbes along with the bad, upsetting the balance that allows the good guys to thrive. Preserving that balance becomes one more incentive to use antimicrobials judiciously.
“Antimicrobial agents have transformed the care of cancer and stem cell transplantations,” Liu said. "But they also play a significant role in disrupting gut microbiota, which we’re learning affects graft-vs.-host disease and transplantation outcome.”
Educating physicians — and the public they serve — about the microbiome could help in another way, by lessening the pressure to prescribe antibiotics even when they aren’t medically called for except to calm patients’ worries.
“If we start recognizing how important our microbiome is, we may think twice about taking a drug that’s screwing it up,” said panelist Dr. Peter Rabinowitz, who directs UW’s Center for One Health Research, which explores the links between human, animal and environmental health. “Maybe we’ll start prescribing things that will help the microbiome fight infections.”
Rabinowitz, whose “One Health” center aims to get researchers in human, animal and environmental health out of their silos, called for discussion of and transparency around “organic” and other labels that bar antibiotic use even for animals that are sick and need them.
But he and others also spoke of progress on the agricultural front. McKenna said that the Obama administration in its waning days barred the use of antibiotics as growth promoters in the United States, ending a 40-year stalemate that began when the threat of resistance was first raised during the Carter administration.
“We’re moving in the right direction,” said Dr. Douglas Call, a specialist in food and water-borne diseases and salmon aquaculture and associate director of Washington State University’s Paul G. Allen School for Global Animal Health. He pointed out that even before new guidelines were issued, antibiotic sales dropped from 2015 to 2016, driven largely by consumer demand for antibiotic-free meat.
More good news came from Washington State Department of Health epidemiologist Dr. Marisa D’Angeli, who said that little high-risk resistance has been reported in the Pacific Northwest so far. Still, the state has a rigorous monitoring system in place. "Even though rates are low in Washington, we need to be ready," she said.
But McKenna said that while awareness is at least growing in the United States and Europe, in much of the world prescriptions for antibiotics aren’t even required for humans much less animals. Lack of any regulation begets overuse, misuse — and evermore resistance.
“As economics of emerging nations improve, their new middle classes are buying more meat,” she said. “This is a problem that will not go away. We don’t have much time to get it right. The movement of antibiotic resistance around the world shows us that no one country or ecosystem is separate from the other.”
Mary Engel is a former staff writer at Fred Hutchinson Cancer Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.