Would you like a glass of hornless cow milk with your influenza-immune chicken divan?
For millennia, the quest to raise domestic livestock with desirable traits came down to good old selective breeding: take an animal that has the traits you want and breed it. Do it enough, and you get the desired result, or at least a reasonable facsimile.
Today, CRISPR does the hard work of selective breeding for us.
Previously, geneticists dabbling in gene-edited livestock used viruses and bacteria to shuffle DNA, but that process proved expensive and time consuming. CRISPR introduced the ability to create bigger, better, tastier domestic animals more easily—but success in this burgeoning field has also been tempered by setbacks.
In the beef industry, the push has been toward creating more males, which gain weight more efficiently than females. The effort is advancing, though in fits. This spring, scientists at the University of California, Davis successfully CRISPR-edited a gene called SRY, which instructs mammalian embryos to develop male traits, into a bovine embryo, the result of which produced a phenotypic male with plasmid in its DNA, improperly oriented DNA, and multiple copies of SRY.
The success and failures of the UC Davis experiment showed that issues will arise—and there are ways to overcome them once you know they have appeared. Future experiments building on the one from Davis will dictate if dreams of an all-male herd ever become a reality, but meanwhile, other research is ongoing.
In Australia, for example, research is underway to determine the sex of a chick before it hatches. Why? Since male chicks don’t lay eggs or put on the bulk required to be sold for meat, they are culled almost the moment they peck their way out of their eggs. The federal Commonwealth of Scientific and Industrial Research Organisation is in the midst of a proof-of-concept project that places a biological marker, courtesy of a sea anemone, on the chicken’s sex-determining chromosome to make the egg glow under a special light.
In Germany, researchers are using CRISPR to edit pig sperm so that all their offspring are female. Males grow up to produce an appetite-ruining chemical cocktail called “boar taint” in their meat, and as of now, the only way to get around that is castration. The change would improve animal welfare, but it must first get beyond regulatory hurdles, particularly in Europe. There are also widespread public concerns about possible unintended downstream consequences, although it’s important to note that such possible unintended downstream consequences have not been proven.
In the UK, CRISPR technology is used to delete a section of chicken DNA to make the animals immune to avian influenza.
And in the US, researchers at the University of Missouri are gene editing pigs to make them resistant to porcine reproductive and respiratory syndrome.
“The challenge is no longer technical,” declare the Uruguayan authors of an overview in the journal Theriogenology. “Controversies and consensus, opportunities and threats, benefits and risks, ethics and science should be reconsidered to enter into the CRISPR era.”
The world of CRISPR-edited livestock is not uniformly rosy. A host of potential drawbacks and complications is present.
Perhaps the biggest of those complications is simply the amount of time and money needed to complete experiments successfully. The production of the male calf by the team from UC Davis took five years and ran a tab of at least a half-million dollars, with setbacks including dozens of failed pregnancies and countless scientific challenges. And for what, exactly? As Wired stated, the male calf is “just pure research … Neither he nor his progeny will ever enter the food supply. Their story is likely to end in a UC Davis incinerator.”
“The breeding cycle is long,” stated a 2017 article in Transgenic Research. “Molecular marker selection can help to speed up the breeding process by eliminating the need of effects from environmental conditions and developmental stages. However, the predicament of a long breeding cycle still exists.”
Off-target editing is another concern, the Transgenic Research paper said, with all the current genome editing techniques carrying the potential to include off-target mutations: “Although these mutations may not have any impact on the health of the individual animals, they still carry a potential risk and can create obstacles for the future promotion of genome editing.”
One of the more notable setbacks was another effort borne from the need to reduce animal suffering: the quest to grow dairy cows that don’t need to go through the painful process of dehorning. Led by a Minnesota company called Recombinetics, a bull in the experiment wound up with a genome housing a stretch of bacterial DNA, including a gene conferring antibiotic resistance—the sort of resistance you don’t want in your herd.
Recombinetics has also been at work creating heat-resistant cattle and pigs that never hit puberty. The setback was just one of many as CRISPR editing technology advances, though this case was stickier as the company had recently lobbied the federal government for relaxed regulatory oversight.
And then there are the bioethical issues. As noted in a 2019 article in Molecular Therapy: Nucleic Acids, in the wrong hands, CRISPR editing technology can be abused, with risks including manipulating germline genetics, clones, and more.
“While time will be the actual judge of these technologies as boon or bane, still the methods can impact the human race probably in the most (fundamental) ways, and our incoming human race may be victimized in ways we do not yet understand,” the authors stated.
Another drawback is a lack of regulatory clarity. As Robbie Barbero, who helped modernize biotech regulations for the Obama administration, told Wired, “In the absence of a regulatory path that’s rational and easy to understand, it will be almost impossible for any animals to make it to market. When you’re talking about regulating changes to the genome that could’ve happened naturally, you’re asking to stretch the imagination.”
Still, other drawbacks to gene editing livestock are the same sorts of drawbacks present in any agricultural gene-editing scenario—pathogens may adapt to new genetic profiles, for example, and any patented tech will be expensive to use.
The lists of both drawbacks and advantages are long—and growing—but as this technology is still young, it’s important to note that many issues seen as potential drawbacks may not turn out to be real drawbacks, and potential negative facets could be partially or completely overcome by future scientific discoveries. As technologies are refined, processes are streamlined, and costs fall, we should get used to seeing more CRISPR editing in livestock. And why not? The science is producing more of what people need and doing so as growers face both economic and environmental hardships. If ethical, scientific, financial, and regulatory hurdles can continue to fall, the science will progress.
“Genome editing offers a new opportunity to further accelerate the rate of genetic gain in livestock,” noted an article in the Journal of Experimental Biology. “Genome editing offers an opportunity for the targeted modification of existing genes and regulatory elements, without necessarily introducing foreign DNA.”