In Archives From Antibiotics’ Earliest Days, Scientists Find Bacteria Already Evolved Resistance

Scientists suspect the farm use of penicillin was to blame.
A technician preparing penicillin in 1943.

It took nearly three decades after Alexander Fleming discovered penicillin for other scientists to develop a version of the drug that worked against E. coli and Salmonella, but it took less than two years after that for the first outbreak of antibiotic-resistant food poisoning to show up. Beecham Research Laboratories in Surrey, England, began mass-producing ampicillin in 1961. The first ampicillin-resistant Salmonella outbreak happened in the later half of 1962.

How did Salmonella learn to evade its killer so quickly? It might have gotten a head start on farms, according to a new study. The study found three samples of amipicillin-resistant Salmonella, taken from people sometime between 1959 and 1960. The research also showed that it’s possible for bacteria to become resistant to ampicillin if they grow up in environments with low levels of penicillin. Farmers in Europe often put penicillin into their livestock feed before the practice was banned in 1969. With the new study, researchers think it’s possible that penicillin that made its way into cow patties and soil helped armor bacteria against ampicillin even before they ever encountered the newer antibiotic.

“Our findings suggest that antibiotic residues in farming environments such as soil, waste water, and manure may have a much greater impact on the spread of resistance than previously thought,” Francois-Xavier Weill, a bacteriologist at the Institut Pasteur in France who worked on the study, said in a statement. The results bolster scientists’ calls for farms to stop using antibiotics so much, for fear of rendering life-saving drugs useless.

To trace the origins of ampicillin resistance, Weill and his team analyzed 288 Salmonella samples, gathered between 1911 and 1969 and stored in various French research institutes. Most of the historical samples were susceptible to all of the antibiotics the scientists tested on them, but 11 turned out to be resistant to ampicillin. (Seven of those were resistant to at least one other kind of antibiotic as well.) By sequencing the DNA in their samples, the team learned that ampicillin-resistant Salmonella evolved at least three separate times in the late ’50s and early ’60s: Resistant bugs taken from one person in France in 1959, from two people in Tunisia in 1960, and from folks who became ill in the United Kingdom in 1962 and 1964 all had different origins.

Individual countries and the United Nations have made some moves to counter antibiotic resistance recently. In 2016, the U.N. adopted a plan to combat antibiotic resistance that includes monitoring farms and limiting their antibiotic use. In the United States, the Food and Drug Administration released voluntary guidelines that suggest farms only use “medically important” antibiotics on their animals to treat them when they’re sick—instead of feeding the drugs to healthy animals to fatten them—and that farmers consult a veterinarian when they do use antibiotics. While the guidelines aren’t legally enforceable, many major producers have pledged to follow them.

Scientists have long sounded the alarm about farms’ antibiotic use, even in the drugs’ early days. Fleming famously warned about antibiotic resistance in the speech he gave after winning the Nobel Prize in 1945. Meanwhile, Pacific Standard found a newspaper article, published in the U.K.-based Birmingham Daily Post in 1966, that sounds eerily similar to modern news stories about the consequences of widespread antibiotic use. “Doctors are now asking,” the story reads, “is it right to use the drugs among animals, use which may increase the risk of spreading resistant strains through the community?”

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