Several years ago, at a lab near a massive experimental farm in Guangdong Province in China, scientists prepped a whopping 4,008 genetically modified pig embryos for implantation into just 16 sows. It’s a numbers game these livestock engineers are familiar with; knowing that many embryos will not survive the procedure—and those that do may not make it through gestation or life beyond the womb—the researchers overproduce embryos and hope for the best.
Normally, a sow will have a litter of 10 piglets from 15–20 fertilized eggs, says Jinzeng Yang of the University of Hawai‘i at Manoa. “When we do transgenic nuclear transfer, you need to do 200 eggs. You don’t know how many are alive, how many are dead. If you are lucky...
As a member of the team developing these pigs, Yang kept his fingers crossed. About seven years ago, he had traveled to the lab in China to help set up the micromanipulator the researchers used for somatic cell nuclear transfer—the insertion of a genetically manipulated nucleus into an enucleated egg. Producing so many transgenic embryos is a labor-intensive process, but China has made considerable investments in livestock technology, and now the country has some of the largest and most advanced facilities in the world, says Yang. Whereas a transgenic livestock facility in the US might have around 20–50 sows, the experimental farm in China has hundreds.
And for good reason. For this project, Yang’s colleagues were trying something scientifically ambitious: introducing genes for three microbial enzymes into the pigs’ genomes that were intended to help the animals metabolize their feed more efficiently, while producing less nitrogen and phosphorus waste. Those enzymes, β-glucanase, xylanase, and phytase, break down matter that pigs don’t otherwise digest; the researchers engineered them to be produced in the modified pigs’ salivary glands.
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The endeavor was a success. Months after the embryos’ implantations, 33 live piglets were born, eight of which survived to sexual maturity. In a paper published in eLife a few months ago, the scientists report that the transgenic pigs indeed produced less nitrogen and phosphorus in their feces, had a faster growth rate, and boosted their feed conversion—the proportion of food that turns into meat.
Most impressive among the genetically engineered improvements, according to Christine Tait-Burkard of the University of Edinburgh, was the reduction in pollutants in the pigs’ poop. “Waste is starting to pose a real problem,” she says. “If we can tackle things like that through breeding or editing, it would have very good environmental benefits.”
But perhaps an even more pressing problem in the swine industry is one that Tait-Burkard is working on: porcine reproductive and respiratory syndrome virus (PRRSV). It’s a nasty infection that causes huge economic losses across Europe, Asia, and North America. “It can kill basically all the suckling pigs on a farm in a week,” she says. Her group and others have homed in on a particular receptor, CD163, on macrophages in the pigs’ immune system that the virus grabs hold of and uses to infect the cells. One team from Kansas State University reported this year that disabling the CD163 gene via CRISPR-Cas9 in sows could protect developing fetuses, which have a functioning CD163, from a viral infection in utero.
In a study published in 2017, Tait-Burkard and collaborators used CRISPR-Cas9 to clip out a section of CD163 that codes for a single protein domain. The receptor, they observed, seemed unperturbed, while both of the two problematic PRRSV species were still blocked from entry into pig cells in vitro. What’s more, the same team reported this year that gene-edited pigs don’t become infected when exposed to the virus. “It is a complete resistance,” Tait-Burkard says. “It truly is a dead end for the virus.”
The savings in terms of cost and lost animal lives could be tremendous were genetically resistant pigs to become available to the livestock industry. And biotech firms have started work to commercialize them. But will this little piggy go to market? That’s far from certain.
“It’s a quagmire of crap,” says Charles Long, who studies livestock diseases at Texas A&M University, when asked about genetically engineered animals getting regulatory approval in the US. Long, too, is using transgenic technologies to create solutions to farm animal diseases. None of his projects have been commercialized to date. So far, three genetically modified (GM) animals have been approved by the US Food and Drug Administration (FDA). Two are engineered to produce medications for human use: a goat that produces an anticoagulant drug called ATryn in its milk and a chicken whose eggs contain a recombinant enzyme that’s missing or depleted in people with a rare genetic disease.
The only GM food that the FDA has given the green light to is a fast-growing salmon, which earned approval in 2015 after years of consideration and public debate. And still, you won’t find it in grocery stores. That’s because the company that owns it got tied up in red tape regarding the importation of the genetically engineered fish eggs from Canada.
As far as considering GM livestock for approval goes, the FDA says it’s game. “We want to facilitate innovative products getting to market,” while also making sure they’re safe, durable, and do what they claim to do, says Laura Epstein, a senior policy advisor at the FDA’s Center for Veterinary Medicine.
But there are forces outside the FDA’s purview that can hold up GM animals from making it to market, such as Congressional food-labeling mandates and the public’s distaste for laboratory-conceived enhancements to food. Yang and his colleagues aren’t the first to have developed a pig with a transgene in its salivary gland that reduces phosphorus production, after all. The so-called Enviropig, a trademarked line of swine developed by researchers at the University of Guelph in Canada, was submitted for FDA consideration more than a decade ago, but funders backed out, presumably not foreseeing much in the way of commercial returns.
Long says it’s more likely that the livestock he and others engineer will have appeal in countries that don’t have the luxury of spurning GM swine and cattle. “There’s a lot of countries where just producing enough food is a serious problem,” he says. “Anything we can do here in the US and other developed countries to give them the technological advances they need is the right thing to do.”