The Man Who Turned Antibiotics Into Animal Feed
THE MAN WHO TURNED ANTIBIOTICS INTO ANIMAL FEED
The food industry and the medical community have fought bitterly, and for decades, over the widespread practice of adding antibiotics to livestock feed to make animals grow faster. Banning the practice would be an agricultural disaster, food companies predict—or at least the end of affordable meat. Medical researchers say the disaster is already happening: With agriculture now consuming 80 percent of all U.S. antibiotics, the food business bears much of the blame, they say, for an epidemic of antibiotic-resistant infections that kills 63,000 Americans each year.
But the debate also raises a more basic question: How did antibiotics get into our food supply in the first place? That is, how did U.S. food companies get to the point of adding almost 13 million kilograms of antibiotics to livestock feed every year, about 300 milligrams for every kilogram of meat produced?
The discovery that farmers could make livestock grow faster by dosing their feed with antibiotics was largely the work of a remarkable biologist named Thomas H. Jukes (1903-1999). Jukes, an old school environmentalist, was a life member of the Sierra Club, an enthusiastic outdoorsman, and in later years, when he was a professor at the University of California at Berkeley, a pioneer in the new science of molecular biology. He was also an ardent defender of science, or at least his view of science. He wrote hundreds of opinion pieces, often polemical, on topics of the day, and, among other achievements, fought effectively to prevent the introduction of creationism into California schools. He also campaigned against Laetrile and other quack cancer cures, and lambasted Linus Pauling for touting massive vitamin doses as a panacea.
But Jukes had formed his ideas in an age of medical miracles, and firmly believed in the power of science to conquer sickness and hunger. So he also defended use of DDT against malaria in the strongest possible language—in one instance calling attempts to ban the insecticide “unquestionably genocidal.” When the prescription drug DES, or diethylstilbestrol, became notorious in the 1970s for causing birth defects and cancers in humans, Jukes argued for its continued use as a growth promoter in cattle, saying the risk to consumers was minuscule. He took what he saw as a rigorous, evidence-based approach to such questions, in contrast to the supposedly “emotional” language of the emerging environmental movement. He often quoted the Renaissance medical writer Paracelsus, who believed that everything and nothing is poisonous, or as Jukes put it: “The dose alone makes the poison.”
But his fierce opposition to environmental critics also undoubtedly reflected his own career history. Before moving to Berkeley in 1963, Jukes had spent his most productive years, from his mid-30s to his late 50s, in the pharmaceutical industry. He worked as a biochemist for Lederle Laboratories, a division of American Cyanamid, in Pearl River, New York, and there, his own writing indicates, he was considerably less rigorous about insisting on detailed experimental evidence.
In particular, his 1985 memoir of how antibiotics first came to be used in livestock feed is often startling, for a modern reader, because of the casual and freewheeling nature of the pharmaceutical business then. Jukes wrote the article under a headline that seemed, uncharacteristically, to discourage attention, “Some Historical Notes on Chlortetracycline,” and in a publication that was well off the beaten path, Reviews of Infectious Diseases. The article made it clear that he regarded the unfettered environment in the industry in the mid-twentieth century as a key to that era’s genius for invention. He and other pioneers “retain a warm spot for those early days,” he wrote.
The discovery that antibiotics could play a useful role in the livestock industry happened by accident. Benjamin Duggar, a botanist who worked mainly on plant diseases caused by fungi, had joined Lederle as a full-time consultant after reaching mandatory retirement age at the University of Wisconsin. At first, he worked on developing a new treatment for malaria, a critical problem for U.S. troops fighting in the Pacific. But with the end of World War II, Lederle assigned him instead to the search for antibiotics. This new class of drugs had just helped win the war, by preventing deaths from infected wounds among Allied troops. Antibiotics were now also making their mark as wonder drugs in civilian health care, too. Duggar’s long interest in microbes soon paid off
“It was a few months later,” Jukes recalled, “that he wrote me that they were having good results, so much so that his assistants and others were ‘stealing’ portions of the crude extracts to cure their colds.” Duggar was working with a bacteria species he had collected from the soil at an experimental agronomy plot belonging to the University of Missouri. In culture, the fungus not only demonstrated powerful antibiotic effects, but also produced a yellow pigment for which Duggar named it Streptomyces auriofaciens, or “the gold-bearing streptomyces.”
The name had an apt double meaning. When the president of the company showed off a vial of the stuff to his research committee, he boasted that it “would make a million dollars for Lederle.” This quickly turned out to be a wild underestimate. By the end of 1948, the antibiotic was on the market under the name aureomycin. It was the first of the tetracycline antibiotics, and a genuine miracle drug, effective against a much broader spectrum of pathogens than the other leading antibiotics on the market, penicillin and streptomycin. Doctors found it particularly useful, The New York Times soon reported, against viral pneumonia, whooping cough, Rocky mounted spotted fever, eye infections, typhus, amoebic dysentery, and both streptococcus and staphylococcus infections. (Children also liked it because it was the first antibiotic administered orally, rather than by injection.)
That December, Jukes received a sample to test on chickens. The poultry industry had lately begun to feed its animals soybean meal as a cheaper substitute for fishmeal. But soybeans lacked an essential ingredient for survival, the elusive “animal protein factor” or “anti-pernicious anemia factor.” In human patients, pernicious anemia had until recently been routinely fatal; it had killed Alexander Graham Bell, Annie Oakley, and Madame Curie, among many others. In the 1920s, researchers found a lifesaving cure in the form of raw liver, at a rate of a half-pound daily. A concentrated liver extract became available in the 1940s. But for the poultry industry, switching to soybeans was mainly about cost, and “no one could afford to feed concentrated liver extract to chickens,” Jukes wrote.
A few months before he began his work with aureomycin, competing researchers at Glaxo in England and at Merck just down the road in Rahway, New Jersey, had identified the key ingredient in liver, and the animal protein factor thereafter became known as vitamin B12.. Merck didn’t say so at the time, but it had managed to extract B12 from a microbe, Streptomyces griseus, meaning that it could now mass produce the precious “animal protein factor” in huge fermentation vats.
Lederle must have felt the competitive pressure. It was also searching for a microbial source of animal protein factor, Jukes later wrote, “because it was known to be present in cow manure and chicken litter,” indicating that it was not a product of animal meat, as the name suggested, but of microorganisms in an animal’s gut. For his experiments with aureomycin, Jukes and a colleague, Robert Stokstad, used hens given just enough feed to allow their eggs to hatch. The resulting “depleted” chicks were generally doomed to die within two weeks unless they got more of the critical animal protein factor. Soon after their experiments began, though, the researchers realized that they had stumbled upon something unexpected. The chicks being fed aureomycin weren’t just growing as fast as chicks supplied with animal protein factor alone. They were growing faster. Something about the antibiotic promoted growth.
Jukes tested groups of a dozen young birds with aureomycin added to their feed, versus other groups supplemented with liver extract (for animal protein factor, or B12) penicillin, or nothing at all. “The record shows,” Jukes wrote, “that I weighed the chicks on Christmas Day, 1948.” The subordinate who would normally have done that job was home for the holiday with his family. Not only had 11 of 12 chicks survived on aureomycin, the same as on the highest dose of liver extract, but the chicks that got more aureomycin significantly outweighed their liver-fed counterparts. No one understood why this was so. But the evidence that antibiotics could somehow cause animals to put on meat more rapidly did not encourage the researchers to ask many questions.
Looking back almost 35 years later, Jukes wrote, “If such a discovery were made at Cyanamid in 1985, there would be round after round of committee meetings, and plans would be made to cope with various U.S. Food and Drug Administration (FDA) roadblocks. Long-term and short-term toxicity tests would be started. Metabolites and residues would be isolated and identified. Above all, the product would be tested for carcinogenicity. Finally, the FDA would refuse permission to market it.
“None of these things took place in 1949. Instead, we were told that we could have no more of the product because it was needed for the extraction of the antibiotic for use in human medicine.”
Jukes and his staff soon figured out that they could get the same growth-promoting effect by feeding chicks on the waste products from the aureomycin fermentation process, no doubt because some of the antibiotic inevitably got left behind in the fermentation liquid. Lederle used acetone to extract the aureomycin from the fermentation liquid, and Jukes referred to the waste product as “acetone cake,” which needed to be dried out and pulverized for further use.
Though it sounds oddly Dickensian for the mid-twentieth century, the Pearl River facility at that time had a “tank house,” where horse carcasses were routinely dehydrated over an open flame, presumably to be ground up for fertilizer or animal feed. Jukes recalled that when he proposed dehydrating the acetone cake there, he was asked whether, given the volatile nature of acetone, it “would explode and blow up the tank house, and although I assumed the responsibility for such a possible disaster, it fortunately never happened.” At one point, he added, the researchers were so desperate for byproducts of the aureomycin fermentation process that they “dug residues out of the Lederle dump and sifted out the Coke bottles.” The dump would later become an EPA Superfund site.
Lederle sent out samples for testing at universities and agricultural experimental stations. A University of Florida researcher got “the most spectacular results” -- a tripling of the growth rate in young pigs. The company quickly began selling the product, not waiting to complete toxicity testing or routine assays on animals. Lederle marketed it at first as a source of vitamin B12,, Jukes wrote, and was thus “able to avoid any registration problems as to its antibiotic content.” It sold by the tanker car, and demand was intense, particularly in the Midwestern states, where the aureomycin content also cured an epidemic of bloody diarrhea in pigs. A U.S. Senator from Nebraska was soon complaining that his state wasn't getting its fair share of this miraculous product. A Minnesota pharmacist bought it in bulk, repackaged it, and sold it at such a high markup that he supposedly retired to Florida on the profits.
When the FDA finally found out a year later that American livestock were being fed large quantities of antibiotics, an official there merely asked "what level of aureomycin should be authorized for use as an animal feed supplement," and the company told him.
The New York Times broke the news on its front page on April 10, 1950, under the headline, “’Wonder Drug’ Aureomycin Found to Spur Growth 50%.” Science writer William L. Laurence quoted a Lederle report arguing that this “spectacular” discovery would “hold enormous long-range significance for the survival of the human race in a world of dwindling resources and expanding populations.” The article concluded, “No undesirable side effects have been observed, it is said.”
Other studies in that era suggested that adding antibiotics to animal feed could produce a gain in the 4-12 percent range, not 50 percent. But that still represented a significant advantage in the business of getting more meat to market less expensively. By eliminating certain chronic diseases, the daily antibiotic regimen also made it possible to raise animals in highly concentrated facilities—which would become the central feature of modern industrial agriculture. The innovation by Jukes and his colleagues soon spread worldwide, and the era of antibiotics devoted primarily to meat production, rather than to human health, had begun.
Twelve years later, in June of 1962, Rachel Carson’s Silent Spring began to appear in The New Yorker, attacking the uncontrolled use of DDT and other pesticides, and also raising questions about blind reliance on technological solutions more generally. Jukes promptly responded in Chemical Week with a portrait of a more natural world, in which women had no time to be “writers of science fiction horror stories” because they were too busy “squashing black beetles; beating the clothes moths out of the winter woolens; scraping the mold from the fatback pork; and wondering if they could afford the luxury of a chicken for their Sunday dinner.”
That last line hints that he foresaw the eventual attack on the use of antibiotics as growth promoters in livestock. It came just three years later, when a Salmonella strain that was resistant to multiple antibiotics killed six people in the United Kingdom. The British government’s “Swann Report” subsequently concluded that the disease organisms “acquired their resistance through the use of antibiotics in animals.” Jukes responded that this remained to be proved. He seemed worried mainly that the press would now “threaten us with the propaganda device of a new Silent Spring.”
When Jukes died in 1999, his friends and colleagues remembered him as a brilliant scientist and polemicist (“cantankerous” but “usually right and always honest”). They also celebrated a decent, well-rounded man, who loved to take his family on hikes into the mountains, was a careful reader of the novels of Aldous Huxley, listened to Bach and Beethoven, could quote Shakespeare at will, held season tickets to Berkeley’s “Cal Bear” football games, and, though he had grown up in England, enjoyed few things more than watching Oakland A’s pitcher Dennis Eckersley striking out the other side in the ninth inning of a close game.
An obituary called Jukes “one of the giants of 20th-Century biological science.” But he may also have been one of its greatest failures. During the long fight over antibiotics in livestock feed, he always focused on the benefits and minimized the risks. When another deadly outbreak of antibiotic resistant Salmonella occurred in 1985, for instance, he noted in Science that “feeding antibiotics to animals has increased meat production by millions of pounds annually for 30 years.” That was what mattered—feeding a hungry world.
Elsewhere, Jukes often stated that he and his fellow researchers at Lederle had always foreseen the danger that feeding antibiotics to livestock would make bacterial strains resistant to antibiotics. But he also discounted the idea that antibiotic resistance would spill over to affect human health. Resistance would occur within the guts of animals receiving the antibiotics. That mattered to him, he suggested around the time of the Swann Report, mainly on the narrow, practical grounds of “whether the effect of antibiotics on improving growth … in farm animals would disappear in a year or two because of the emergence of resistance. If this were the case, we would indeed be doing more harm than good by temporarily alleviating a problem only to replace it with a more intractable one.” Then he added this chilling sentence: "The experiment to provide the answer was under way on a gigantic scale by 1951 and is still in progress.”
Researchers continue to argue today about the consequences of this willy-nilly global experiment. But the evidence in recent years has increasingly indicated that antibiotics in livestock feed bear much of the blame for a genuinely intractable problem: The medical world’s wonder drug antibiotics no longer work against an array of virulent pathogens, notably including Salmonella, E. coli, MRSA (methicillin-resistant Staphylococcus aureus) and the totally drug-resistant variety of tuberculosis that recently appeared in India.
If he were alive today, Jukes might still deny that turning antibiotics into animal feed had anything to do with this problem. But given his public record, the remarkable thing is that he encouraged the pharmaceutical industry’s “gigantic” experiment to go forward in the first place. In arguing with his critics, he always insisted that they back up their words with hard scientific evidence. But in his own work at Lederle, with his tantalizing new discovery ready to go to market largely untested, Jukes had behaved as if all the rules of basic science somehow did not apply. It was an extraordinary act of hubris. And, if those who oppose the practice of feeding antibiotics to livestock are correct, the terrible consequence is that tens of thousands of people now pay for it every year with their lives.