A symposium held by the National Academy of Sciences initiated debate concerning the relationship between antibiotics in animal feed and antibiotic resistance in humans.

Antibiotics have been used as animal feed additives since the 1950’s, although there were indications from the start that such additives might contribute to the development of antibiotic-resistant bacteria. Many scientists considered the public health risk of the practice unacceptable and recommended that it be regulated. Antibiotics
Animal feed
Bacteria, drug-resistant[Bacteria, drug resistant]
[kw]Scientists Debate the Addition of Antibiotics to Animal Feed (June, 1967)
[kw]Antibiotics to Animal Feed, Scientists Debate the Addition of (June, 1967)
[kw]Animal Feed, Scientists Debate the Addition of Antibiotics to (June, 1967)
Antibiotics
Animal feed
Bacteria, drug-resistant[Bacteria, drug resistant]
[g]North America;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
[g]United States;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
[c]Health and medicine;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
[c]Agriculture;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
[c]Science and technology;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
[c]Biology;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
[c]Chemistry;June, 1967: Scientists Debate the Addition of Antibiotics to Animal Feed[09300]
Jukes, Thomas H.
Watanabe, Tsutomu
Kennedy, Donald
Holmberg, Scott D.
O’Brien, Thomas
Novick, Richard

In June, 1967, the National Research Council of the National Academy of Sciences National Academy of Sciences, U.S. held an international symposium at the request of the U.S. Food and Drug Administration Food and Drug Administration (FDA) to address growing concerns about the link between the practice of feeding antibiotics to livestock and the development of antibiotic-resistant human pathogens, or disease-producing organisms. Although most participants in the symposium agreed that the addition of antibiotics to feed improved the quality of the meat produced, there was no consensus as to the risks to humans from traces of antibiotics in foods. Two areas of public health that concerned scientists were the emergence of more antibiotic-resistant pathogenic bacteria and adverse allergic reactions in individuals sensitive to particular antibiotics.

In 1949, Thomas H. Jukes, director of nutrition and physiology research at Lederle Laboratories, found that Streptomyces aureofaciens, the bacterium that produces the antibiotic chlortetracycline (Aureomycin) Aureomycin , also produced high concentrations of vitamin B₁₂. Because animal feeds used at that time were vitamin B₁₂-deficient, Jukes thought that the fermentation wastes from the production of chlortetracycline might be a good, inexpensive feed supplement. To his surprise, the chicks and piglets that received the supplement gained significantly more weight than animals fed vitamin B₁₂ from other sources. The weight gains were especially significant among animals that were at risk from bacterial infections or from the stress of overcrowding. Jukes found that although more antibiotic-resistant bacteria were found in treated animals than in untreated ones, the treated animals continued to gain weight and could be fed less. Scientists suspected that maintaining the animals from birth on low concentrations of antibiotics prevented mild, nonsymptomatic diseases and infections that might have been slowing growth, and they assumed that because the animals grew bigger, they were healthier.

Using antibiotics in livestock feed, which became common practice in the 1950’s, created major changes in the way meat is produced. Meat growers could produce larger animals on less food. Even more important from an economic point of view, producers could keep animals in more crowded surroundings, because the likelihood of infectious diseases spreading was diminished. As large-scale production on less land became possible and profitable, small farms where the flocks or herds ranged in large yards or pastures disappeared.

When antibiotics are fed to animals for extended periods of time, there is increased likelihood that antibiotic residues will remain in the meat. It was legal to use chlortetracycline up to the day of slaughter; when tetracycline was combined with other antibacterial drugs, however, the mixture had to be withdrawn fifteen days before slaughter. Even then, it was possible that antibiotic residues or antibiotic-resistant bacteria remained in the meat.

Already in the 1950’s, some scientists were alarmed at the increase of antibiotic-resistant bacteria they observed in the human population. Initially, they believed that overuse of antibiotics in human medicine was the primary reason for the growing resistance. By the 1960’s, however, scientists and clinicians increasingly came to suspect that a contributing factor might be the practice of lacing livestock feed with subtherapeutic doses of antibiotics; subtherapeutic doses are defined as concentrations too low to be effective in treating a disease.

The practice of feeding antibiotics to livestock has two significant consequences. First, antibiotic residues in the meat may contribute to the selection of antibiotic-resistant bacteria in the intestinal tracts of human consumers. Second, resistant bacteria from the animals may transfer their resistance to both pathogenic and nonpathogenic bacteria in humans. Bacteria that become resistant to many antibiotics are a particularly serious problem in the treatment of infectious diseases. Japanese microbiologist Tsutomu Watanabe found that the genes for resistance to antibiotics are often found on small circular pieces of deoxyribonucleic acid Deoxyribonucleic acid;plasmids (DNA) called plasmids Plasmids . Plasmids are separate from the main chromosome of the bacteria and can easily be transferred from one bacterium to another during a process called conjugation. Conjugation Genetics;conjugation is one of the ways that bacteria transfer genes to one another to introduce genetic diversity (and hence adaptability) into a population. Thus, one antibiotic-resistant cell in a population can very quickly convert the entire population to resistance. Plasmids may also contain transposons, DNA sequences that direct the genes adjacent to them to “jump” from one place to another. By this mechanism, a plasmid that already carries the gene for penicillin resistance may acquire an additional gene for tetracycline resistance. Because transposons can mediate the transfer of multiple genes, plasmids that gain two or more antibiotic-resistant genes can be created.

After the discovery of penicillin by Sir Alexander Fleming in 1928, medicine came to rely on antibiotics to treat bacterial infections of all kinds. Many of the diseases caused by bacteria were life-threatening before the availability of antibiotics. As more bacteria become antibiotic-resistant, however, many strategies used throughout the twentieth century for treating diseases were no longer successful. Scientists continued to discover new, effective antibiotics, but new resistant bacterial strains continued to emerge as well.

After an outbreak of antibiotic-resistant infectious diarrhea caused by salmonellae in Great Britain in the mid-1960’s, which began in cattle and spread to humans, the British government appointed a group of scientists to study the problem. The Swann Committee Swann Committee report, issued in 1969, concluded that the subtherapeutic use of antibiotics in animal feed posed a significant health risk to humans and should be restricted. As a result of the Swann Committee’s report, the FDA appointed a task force to study the problem in the United States. There, the greatest concern was for two forms of tetracycline, chlortetracycline and oxytetracycline, and penicillin because of their effectiveness in the treatment of many human diseases. Scientists feared that substantial increases in the numbers of tetracycline- or penicillin-resistant bacteria would have a major adverse effect on public health.

In 1972, the FDA threatened to ban subtherapeutic use of antibacterial agents in animal feed unless the feed-, antibiotic-, and meat-producing industries could show that the agents were safe. In 1977, Donald Kennedy, then FDA commissioner, decided that there was insufficient evidence to conclude that antibiotics were safe and proposed a ban of all subtherapeutic uses of penicillin in feed and most subtherapeutic uses of tetracycline. The Senate and House Committees on Appropriations, Senate Committee on Appropriations
House Committee on Appropriations however, instructed the FDA to conduct additional studies on the issue of safety. A report issued in 1980 by the National Academy of Sciences (NAS) found that the studies existing at that time were all flawed in one way or another. The NAS report indicated that there was not much direct evidence to substantiate a connection between antibiotic residues in meat and resulting antibiotic-resistant bacteria in humans, but it did recommend further studies. A bill to require the FDA to regulate antibiotic use in feeds was proposed in the House in 1980 by John D. Dingell Dingell, John D. and Henry Waxman Waxman, Henry , but the bill died in committee.

Eleven years after its original proposal to restrict the use of penicillin and tetracycline in animal feeds, the FDA proposed allowing new animal feed uses of penicillin and tetracycline, though it also acknowledged that there was strong evidence of a connection between use of antibiotics in feed and antibiotic resistance. The Natural Resources Defense Council Natural Resources Defense Council (NRDC), a nonprofit, environmental law firm, drafted a petition in 1983 signed by approximately three hundred scientists, which urged President Ronald Reagan and the secretary of health and human services Department of Health and Human Services, U.S. to ban the subtherapeutic use of penicillin and tetracycline in livestock feed. Al Gore Gore, Al , then a congressman, held more hearings on the topic in 1984. That same year, the NRDC filed a petition of “imminent hazard” with the FDA, and again hearings were held, but the petition was rejected in 1985 by Secretary of Health and Human Services Margaret Heckler Heckler, Margaret , upon recommendation of FDA Commissioner Frank E. Young Young, Frank E. .

Among the studies of possible links between antibiotic residues in meat and public health risks was one by a team of scientists from the Centers for Disease Control Centers for Disease Control in Atlanta headed by Scott D. Holmberg, which studied outbreaks of salmonellosis caused by antibiotic-resistant salmonellae bacteria in the United States between 1971 and 1983. The study showed that animal-to-human transmission of resistant bacteria occurred in a significant portion of the cases and that the fatality rate was higher in infections with resistant bacteria than in those with antibiotic-sensitive salmonellae. In another study, Thomas O’Brien, director of the microbiology laboratory at Brigham and Women’s Hospital in Boston, compared the DNA fingerprint from resistance plasmids suspected of having been transmitted from animals to humans. By using enzymes that split DNA only at certain of its building-block sequences, scientists could produce patterns, or fingerprints, unique to it. O’Brien found that the resistance plasmids from salmonellae bacteria taken from animals and people throughout the United States often had nearly identical fingerprints. Using the same technique, Richard Novick and his associates at the Public Health Research Institute in New York and the College of Veterinary Medicine at Cornell University found that DNA sequences on resistance plasmids from staphylococcus and streptococcus bacteria in pigs and pig handlers were nearly identical. Studies such as these suggested that transmission from animals to humans was occurring frequently and easily.

The use of antibiotics in feed continued to be controversial, particularly as the situation was further complicated by factors such as the overprescription of antibiotics in the treatment of human diseases, the extent to which bacteria obtained through food become resident in humans, and the effects of using the same antibiotics both in feed and in the treatment of livestock diseases. It remained unclear whether discontinuing the use of low doses of antibiotics in livestock feed would affect the numbers of antibiotic-resistant bacteria circulating in the human population. Antibiotics
Animal feed
Bacteria, drug-resistant[Bacteria, drug resistant]

• “Breeding an Epidemic: Antibiotics and Meat.” Mother Earth News, September/October, 1985, 130-131. Brief overview of the controversy on antibiotics and discussion of the lack of government regulation in response to experimental findings.
• Gustafson, Richard H. “Symposium: Antibiotic Residues in Meat and Milk: Use of Antibiotics in Livestock and Human Health Concerns.” Journal of Dairy Science 74 (April, 1991): 1428-1432. Concise history of the controversy, committee reviews, government action, and research concerning use of antibiotics and public health risks. Includes a comprehensive list of references.
• Holmberg, Scott D., Joy G. Wells, and Mitchell L. Cohen. “Animal-to-Man Transmissions of Antimicrobial-Resistant Salmonella: Investigations of U.S. Outbreaks, 1971-1983.” Science 225 (August 24, 1984): 833-835. One of the first important studies linking human disease and antibiotic-resistant bacteria in food animals. Suitable for general readers. Includes references and notes.
• Interagency Task Force on Antimicrobial Resistance. A Public Health Action Plan to Combat Antimicrobial Resistance. Washington, D.C.: U.S. Department of Health and Human Services, 2001. Available at http://www.cdc.gov/drugresistance/actionplan/araction plan.pdf. A government report on the resistance of microorganisms to antibiotics.
• Levy, Stuart B. The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers. Cambridge, Mass.: Perseus, 2001. A leading researcher in molecular biology explores a modern-day evolutionary change in bacteria because of misuse of antibiotics.
• Nicolaou, K. C., and Christopher N. C. Boddy. “Behind Enemy Lines.” Scientific American, May 21, 2001, 54-60. Examines in nontechnical language how microbes are fast becoming resistant to antibiotics. Discusses the history of antibiotics and provides a breakdown of how microbes resist antibiotics.
• Schell, Orville. Modern Meat. New York: Random House, 1984. A detailed account of the meat industry and the controversy surrounding the use of low-dose antibiotics as livestock feed additives. Includes information on the biological basis of antibiotic resistance and resistance transfer among bacteria.
• Wirth, David A. “FDA Flip-Flops on Antibiotic Hazard.” Environment 25 (June, 1983): 4-5. Gives a brief history of the controversy concerning whether antibiotics in food pose a significant public health risk and of the actions of governmental advisory groups. Indicates additional sources in the Federal Register and congressional committee reports.
• World Health Organization. Food Safety. Antimicrobial Resistance. The World Health Organization’s Food Safety program offers many resources on antibiotics and antibiotic-resistant diseases and illnesses. Highly recommended. http://www.who.int/foodsafety/micro/en/.

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