Many of us appreciate a juicy pork chop or a slab of brown sugar ham. Pork is the third most consumed meat in the US, with a buzzing industry to meet demand.
But for over three decades, pig farmers have been plagued by a pesky virus that causes porcine reproductive and respiratory syndrome (PRRS). Also known as blue ear—for its most notable symptom—the virus spreads through the air like SARS-CoV-2, the bug behind Covid-19.
Infected young pigs spike a high fever with persistent coughing and are unable to gain weight. In pregnant sows, the virus often causes miscarriage or the birth of dead or stunted piglets.
According to one estimate, blue ear costs pork producers in North America more than $600 million annually. While a vaccine is available, it’s not always effective at stopping viral spread.
What if pigs couldn’t be infected in the first place?
This month, a team at Genus, a British biotechnology company focused on animal genetics, introduced a new generation of CRISPR-edited pigs completely resistant to the PRRS virus. In early embryos, the team destroyed a protein the virus exploits to attack cells. The edited piglets were completely immune to the virus, even when housed with infected peers.
Here’s the kicker. Rather than using lab-bred pigs, the team edited four genetically diverse lines of commercial pigs bred for consumption. This isn’t just a lab experiment. “It’s actually doing it in the real world,” Dr. Rodolphe Barrangou at North Carolina State University, who was not involved in the work, told Science.
With PRRS virus being a massive headache, there’s high incentive for farmers to breed virus-resistant pigs at a commercial scale. Dr. Raymond Rowland at the University of Illinois, who helped establish the first PRRS-resistant pigs in the lab, said gene editing is a way “to create a more perfect life” for animals and farmers—and ultimately, to benefit consumers too.
“The pig never gets the virus. You don’t need vaccines; you don’t need a diagnostic test. It takes everything off the table,” he told MIT Technology Review.
Genus is seeking approval for widespread distribution from the US Food and Drug Administration (FDA), which it hopes will come by the end of the year.
An Achilles Heel
The push towards marketable CRISPR pork builds on pioneering results from almost a decade ago.
The PRRS virus silently emerged in the late 1980s, and its impact was almost immediate. Like Covid-19, the virus was completely new to science and pigs, resulting in massive die-offs and birth defects. Farmers quickly set up protocols to control its spread. These will likely sound familiar: Farmers began disinfecting everything, showering and changing into clean clothes, and quarantining any potentially infected pigs.
But the virus still slipped through these preventative measures and spread like wildfire. The only solution was to cull infected animals, costing their keepers profit and heartache. Scientists eventually developed multiple vaccines and drugs to control the virus, but these are costly and burdensome and none are completely effective.
In 2016, Dr. Randall Prather at the University of Missouri asked: What if we change the pig itself? With some molecular sleuthing, his team found the entryway for the virus—a protein called CD163 that dots the surface of a type of immune cell in the lung.
Using gene editing tool CRISPR-Cas9, the team tried multiple ways to destroy the protein—inserting genetic letters, deleting some, or swapping out chunks of the gene behind CD163. Eventually they discovered a way to disable it without otherwise harming the pigs.
When challenged with a hefty dose of the PRRS virus—roughly 100,000 infectious viral particles—non-edited pigs developed severe diarrhea and their muscles wasted away, even when given extra dietary supplements. In contrast, CRISPRed pigs showed no signs of infection, and their lungs maintained a healthy, normal structure. They also readily fought off the virus when housed in close quarters with infected peers.
While promising, the results were a laboratory proof of concept. Genus has now translated this work into the real world.
Trotting On
The team started with four genetic lines of pigs used in the commercial production of pork. Veterinarians carefully extracted eggs from females under anesthesia and fertilized them in an on-site in vitro fertilization (IVF) lab. They added CRISPR into the mix at the same time, with the goal of precisely snipping out a part of CD163 that directly interacts with the virus.
Two days later, the edited embryos were implanted into surrogates that gave birth to healthy gene-edited offspring. Not all piglets had the edited gene. The team next bred those that did have the edit and eventually established a line of pigs with both copies of the CD163 gene disabled. Although CRISPR-Cas9 can have off-target effects, the piglets seemed normal. They happily chomped away at food and gained weight at a steady pace.
The edited gene persisted through generations, meaning that farmers who breed the pigs can expect it to last. The company’s experimental stations already house 435 edited of PRRS-resistant pigs, a population that could rapidly expand to thousands.
To reach supermarkets, however, Genus has regulatory hoops to jump through.
So far, the FDA has approved two genetically modified meats. One is the AquAdvantage salmon, which has a gene from another fish species to make it grow faster. Another is a GalSafe pig that is less likely to trigger allergic responses.
The agency is also tentatively considering other gene-edited farm animals under investigational food use authorization. In 2022, it declared that CRISPR-edited beef cattle—which have shorter fur coats—don’t pose a risk “to people, animals, the food supply and the environment.” But getting full approval will be a multi-year process with a hefty price tag.
“We have to go through the full, complete review system at FDA. There are no shortcuts for us,” said Clint Nesbitt, who governs regulatory affairs at the company. Meanwhile, they’re also eyeing pork-loving Colombia and China as potential markets.
Once cleared, Genus hopes to widely distribute their pigs to the livestock industry. An easy way is to ship semen from gene-edited males to breed with natural females, which would produce PRRS-resistant piglets after a few generations—basically, selective breeding on the fast track.
In the end, consumers will have the final say. Genetically modified foods have historically been polarizing. But because CRISPRed pork mimics a gene mutation that could potentially occur naturally—even though it hasn’t been documented in the animals—the public may be more open to the new meat.
As the method heads towards approval, the team is considering a similar strategy for tackling other viral diseases in livestock, such as the flu (yes, pigs get it too).
“Applying CRISPR-Cas to eliminate a viral disease represents a major step toward improving animal health,” wrote the team.
Image Credit: Pascal Debrunner / Unsplash
