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Moving Away from Antibiotics in Animal Agriculture

Bacteria-killing viruses could protect livestock without the risk of creating resistant microbes

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This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American


The farming of livestock is facing major challenges in the 21st century. The United Nations predicts that global population will reach approximately 10 billion people by 2050. Combined with increased economic prosperity in emerging economies, this means the demand for meat and dairy food products will rapidly increase. Such an insatiable demand for animal food products simply cannot be met by traditional farming methods, and in the 20th and 21stcenturies there has been a significant transition toward intensive farming practices—a shift that is especially pronounced in industrialized countries such as the U.S., where of the 121 million pigs slaughtered annually 75 million are now reared in an industrial farm.

Honed by industrialized countries such as the U.S. and the U.K., industrialized farming combines the principles of mass production with technological innovations in animal nutrition and automation, allowing animals to be reared in greater numbers and for lower costs. Yet although the economies of scale practiced by factory farms have allowed supply to increase and prices to fall, the practice of holding large populations of animals at high densities has led to a number of serious problems.

As in human populations, the practice of housing livestock animals such as poultry, pigs and cattle at high densities allows for disease to spread more rapidly. Indeed, the very conditions that make factory farming so profitable provide a perfect environment for disease spread. Large populations of animals produce—unsurprisingly—large volumes of waste which if improperly sanitized provides an ideal habitat for infectious agents. Housing animals in close proximity also increase the likelihood of exposure to an infected animal or infected feces. Furthermore, living space restrictions cause stress in animals. Chronic stress may supress the immune system and reduces resilience to infection, and may also increase instances of fighting and wounding, providing a point of entry for pathogens. To mitigate this, debeaking of chickens, while unpopular, is still routinely conducted.


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Common livestock pathogens include strains of E. coli, Salmonella and Campylobacter all of which may infect humans and cause sickness. The risk is therefore not only loss of animals and profit to disease, but also transmission of infections to humans, either through contact with animals (alive or post-slaughter) or through contaminated meat and milk. Antibiotics have been key in the battle to prevent disease at factory farms. Often, these are the same medications as those used to treat humans; they are administered to livestock pre-emptively and are supplied at low doses throughout life in the animal's feed to prevent infection and promote growth. In the U.S. the practice was so widespread that prior to a 2017 FDA guideline attempting to restrict it, 80 percent of the sales of some antibiotics was for use in animals.

This strategy, however, was never going to work forever; the classic evolutionary principle of survival of the fittest, when applied to an environment of constant antibiotic exposure, is driving antibiotic resistance in pathogenic bacteria. In recent years the prevalence of MRSA (Staphylococcus aureus strains resistant to the antibiotic methicillin) has greatly increased. A sampling of retail meats including turkey, pork, beef and chicken conducted by the Translational Genomic Research Institute revealed 47 percent of samples were contaminated and of those, 52 percent were with bacteria resitant to at least three classes of antibiotics.

Given these pathogens' ability to infect humans and that antibiotics supplied to animals are also used to treat people, there is the very real prospect of disease outbreaks we are powerless to treat. As the Centers for Disease Control and Prevention warns: "If we are not careful, we will soon be in a post-antibiotic era," a time in which formally routine infections will prove fatal, especially for the young and elderly. As such, there is a tremendous demand for new antimicrobials.

It is possible to glimpse what the future might hold for antimicrobials by searching patent filings. The cost of research and development for any new medicine is extremely high, with an estimated average cost of U.S. $2.6 billion to bring just a single drug to market. As such, any medicinal product represents a significant investment.

Unsurprisingly, with such a tremendous outlay, it is essential for commercial organizations to maximize profits from a given invention, and to reduce the competition for their product in the market. Patents are often considered the gold standard for protecting an invention, preventing others from making, using or selling a given invention over a limited time period, in exchange for publication. The granting of patents is integral to the pharmaceutical business model; preventing competition during the patent's life allows for discretionary pricing and the confidence that initial investment will be recouped. Patent applications can, therefore, be used as indicators of emergent technologies in a given field, indicating which areas of fundamental research show commercial potential.

An exciting area of growth is a technology known as phage therapy. Phage therapy involves using viruses known as bacteriophages to kill pathogenic bacteria. Bacteriophages target bacterial cells as part of their life cycle, by inserting their DNA or RNA into their target on binding. They can use their genetic material to hijack the host cell, using its machinery to produce multiple copies of the virus. Ultimately resulting in the death of the cell when it bursts, releasing the bacteriophage copies, which can go on to infect further cells.

Bacteriophages have several properties that make them a desirable tool; they are highly specific with each one only infecting its target bacterial cell. As such, phage therapies won't kill the so-called "good bacteria" that inhabit an animal's gut, unlike some currently available antibiotics. Phages are also highly diverse, capable of recognising the same bacteria in different ways. Additionally, they are living organisms and so evolve over time, representing a "moving target" for bacteria to evolve resistance to. It is therefore thought that it is highly improbable for bacteria to evolve resistance against a phage "cocktail" of multiple strains. Finally, phages have low toxicity compared with antibiotics, which is a key advantage for the treatment of animals reared for food.

U.S. patent 9,433,653 B2 is one of a group of granted patents for a bacteriophage product. The patent claims protection for a composition of bacteriophages for the treatment of E. coli infection in pigs. E. coli infection may cause diarrhoea in newborn piglets, which can slow growth and often proves fatal. The disease represents a significant threat to the global swine industry, afflicting up to half of all piglets. The current treatment strategy involves the use of Colistin, an antibiotic which is key for the treatment of multi-antibiotic-resistant bacteria in humans.

Recently, a Colistin-resistance gene was identified in an E. coli plasmid, one of the tools bacteria use to transfer resistance genes between species, raising the alarming prospect of reduced effectiveness of this vital antibiotic in human medicine. In response, European regulatory agencies have branded Colistin a "last resort" treatment for animals and in India the drug has recently been banned for animal use altogether.

In light of this, a patent for an alternative treatment to post-weaning diarrhea could be a valuable piece of intellectual property should the invention be brought into widespread usage. Commercial application of just one bacteriophage product could provide the spark for a highly lucrative industry. In the U.S., however, there is a challenge to the bacteriophage industry posed by the 2013 Association of Molecular Pathology vs. Myriad Genetics Supreme Court ruling. In the U.S., an exemption states that inventions relating to laws of nature or natural phenomena may not be granted a patent.

The Myriad ruling has raised questions about the ability to patent bacteriophages. Put simply, prior to the case the company had patented two gene sequences, the mutations of which are commonly associated with cancer. The court concluded that since these genes exist in nature, the company "did not create anything new" by identifying and isolating the gene sequences. The invention was found to be unpatentable.

This ruling has potentially tremendous implications for bacteriophage therapies, as Duke University's law journal noted in light of this decision. Bacteriophages, which are naturally occurring organisms, would not be eligible for a patent. The inability to patent such inventions could represent a major blow to investment as companies may be reluctant to invest large sums if there is no confidence they can protect their invention from competition to recoup costs.

The ruling did, however, leave some room for maneuver: while the court decided that the DNA sequences were not eligible for a patent, they did conclude that cDNA, an artificial form of DNA made by scientists, would be eligible as it represents "something new" they had created and does not occur in nature. It may, therefore, be possible to argue that if a naturally occurring phage were modified, perhaps using some gene-editing technology such as CRISPR/Cas9 to express genes it would otherwise not possess this would result in a "novel" phage that does not exist in nature. At present, there are relatively few inventions relating to phage therapies, as more companies enter the field, a legal challenge could provide the opportunity for clarification on the patentability of this type of invention.