Gene editing holds promise as animal disease prevention of the future

 

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Researchers at the University of Missouri have genetically modified pigs to be immune to a common swine disease. Photo courtesy of the MU News Bureau.

The disease first appeared in Brent Sandidge’s farm in 1992, back when it was still called “mystery swine disease.” Sandidge wasn’t fully aware yet of how this disease would plague him over the next two decades, how he would watch countless pigs succumb, becoming feverish, refusing food and failing to reproduce. He vaccinated his pigs, but it had limited effect. He finally eliminated the disease in 2005, but it returned just five years later. This time, he knew what was coming, and after trying some less dramatic methods, he sold off all his pigs to farms already operating with the disease. And then he started cleaning.

“I didn’t sleep well for probably a month,” he said of the early days after the discovery of the disease on his farm near Marshall, Missouri. “We had a horrible experience with it.”

He repopulated his farm soon afterward, but the disease — porcine reproductive and respiratory syndrome, or PRRS — had cost his farm around $3 million in total, he estimates, killing off about 20 percent of the herd.

In January, he discovered the disease again.

“When you’re having to go through something like this, it takes its toll on you,” he said. “It’s a pretty devastating disease.”

Enter Randall Prather and his team of researchers at the University of Missouri. Prather, an animal sciences researcher, decided to take on the disease in a way that would not just rout the disease but protect the pig at its most fundamental level — in its genes. To defeat the disease, Prather changed the pigs themselves.

Prather’s research, which began over 10 years ago, became truly feasible with the recent development of a revolutionary gene-editing tool. The tool, known as CRISPR-Cas9, has opened a new world of gene editing potential, as work that previously would have taken years or even decades can be done in a matter of months. CRISPR technologies are allowing more studies like Prather’s to take off, holding the promise of eliminating more livestock diseases and saving billions in veterinary costs and animal losses. But in agriculture, genetic modification has always been a controversial notion. The new animals are years away from appearing on dinner tables, and in the meantime they could spark another round of public debate over food and the place of genetic engineering in modern society.

The CRISPR technology is only a few years old, and while it has exploded in popularity, the field of agriculture remains hesitant to use it with animals. But PRRS is such a devastating disease, people were willing to go for it.

Pronounced “purrs,” PRRS spreads quickly and proves frustratingly resistant to vaccines, mutating and slipping around the host’s immune system. According to Kristin Whitworth, a research specialist in Prather’s lab, PRRS called for more dramatic solutions because it so easily eludes the vaccine.

“I don’t want to knock vaccines; they’re really very important,” she said.  “They should be the first option.”

PRRS also gives the industry a strong financial incentive to look for more effective solutions. The disease costs an estimated $664 million in the U.S. every year, according to the Global PRRS Solutions website. Farmers have to shell out for vaccinations and special biosecurity protocols that try to ward off the disease or fight its spread once it arrives. Oftentimes, when farmers find the disease, they, like Sandidge, have to rid themselves of their entire herd and start fresh — or, sometimes, shut down. Dr. R.C. Ebert, a veterinarian from Pleasant Hill, Missouri, said the virus can blow in on the wind. It’s even been found in the wheel well of a delivery van, packed in the snow under the fender, he said.

Ebert agreed that the disease calls for more than just a vaccine. Genetic engineering could be part of the solution, he said.

“I think it’s a very long-term solution,” Ebert said. “Hopefully it’s the wave of the future.”

Prather, Whitworth and Kevin Wells, another researcher, began working with traditional, pre-CRISPR methods when they started the project in the early 2000s but quickly switched over to the CRISPR-Cas9 system in 2013 when it became available. The system can sound complicated, but for disease prevention, the concept behind the gene editing is simple — knock out the gene that produces the molecule where the virus latches on to enter the pigs’ cells, and you’ll eliminate the entire pathway for the virus. Whereas vaccines protect the door that allows viruses in, gene editing removes the door altogether.

Kristin Whitworth demonstrates the preparation of a gel used to separate DNA amplified through a process called polymerase chain reaction. Photo by Molly Olmstead.

Kristin Whitworth demonstrates the preparation of a gel used to separate DNA amplified through a process called polymerase chain reaction. Photo by Molly Olmstead.

In 2015, the researchers sent their pigs off to Kansas State, where a researcher exposed the pigs to PRRS and found them to be completely resistant to the disease. Not long after, a large company that specializes in biotechnology for cattle and pig farmers snapped up the technology to produce the pigs.

Researchers are beginning to tackle other major hog diseases, but little has been done. Today, Prather is collaborating with another researcher at Kansas State in an attempt to develop pigs resistant to swine flu — a development that could have implications for human health. They’ve developed a small number of the altered pigs, and they are waiting to breed more before they send them off to be exposed to the disease and monitored, Whitworth said.

And a scientist at the Roslin Institute, an animal sciences research institute attached to the University of Edinburgh in Scotland, is currently working on developing pigs with a genetic resistance to African Swine Fever, considered to be one of the worst swine diseases globally.

There are other diseases that haven’t yet been the subject of genetic modification research but may yet attract it. The second-worst porcine disease in Missouri after PRRS, according to Ebert, is Porcine Epidemic Diarrhea, which appeared in the U.S. in 2013 and swept the Midwest. While little data exists about the effect PED has had on the industry, a report by the US Department of Agriculture says that the disease usually kills all piglets it infects. There is no effective vaccination for the disease, according to the report.

And diseases in other animals are also prompting similar research, according to the FDA. Cows are under development that could be resistant to udder infections and “mad cow” disease.

The CRISPR gene editing technology has the potential to rewrite the rules of agriculture, according to Tim Safranski, an associate professor of animal science at MU and a state swine breeding specialist who focuses on genetics and reproductive management. While he said the PRRS-resistant pigs likely won’t hit markets for at least another five years after further breeding and testing, he believes that once they do, farms all over the country will have to invest. They will become the industry standard, he said.

“If there’s some technology that comes along that makes a quantum leap in the economics, eventually everyone’s going to use it,” Safranksi said. “Or they’re not going to be able to compete.”

According to the FDA, all genetically engineered animals will go through a process of regulation under the “new animal drug” provisions of the Federal Food, Drug and Cosmetic Act.

The producers of the genetically modified animals will need to submit to a review process that examines the nature of the engineering, the health of the animal and proof the modification won’t change. The regulators will also look at the environmental impacts of the animals and the safety of the food produced from the animals. The process will likely take years.

As each case of a new genetically modified animal will involve different factors and serve a different purpose, the FDA has loose guidelines rather than a strict process for the approval process.

The FDA has approved only one genetically modified animal, the AquAdvantage salmon, a fish able to grow-year round and therefore much more rapidly than other salmon. Even with the FDA’s approval, the fish is caught in a political purgatory. Congress passed a bill that required the FDA to finalize its labeling rules for the fish before it can be imported and sold.  But this rapidly growing salmon differs from Prather’s pigs in an important way — it contains genetic material from a different species.

Specifically, a growth hormone from another salmon species was spliced into its DNA, along with a strand of DNA from another species of fish that helps activate that growth hormone. It has, essentially, foreign DNA. Prather’s pigs merely lack a gene they originally had — the gene that allowed the virus to copy itself and spread. They have no foreign genetic material.

“It’s just a pig,” Safranski said.

Some believe that because no foreign DNA is introduced, consumers will be more comfortable with this type of engineering. Will Buschert, a lecturer at the University of Saskatchewan in Canada who studies ethics and technology, said that because these pigs were developed without a transgene — genetic material transferred from one organism to another — the modification can sound safer and less unnatural. Adding material from another species can sound to opponents of GMOs like playing God.

“CRISPR-like techniques, because they don’t include a transgene, don’t seem to push the same buttons about violating the species,” he said.

Others are not so sure. Andreas Boecker, a professor at the University of Guelph in Canada who researches food-related risk perception, believes anti-GMO campaigners would want to label genetic modification in a broad way that would likely include the deletion and not just the addition of genetic material.

“Consumers won’t understand the difference,” he said. “Explaining this to them is going to be a challenge.”

Another possible difference between the salmon and the pigs for consumers is the purpose of the engineering. Preventing animal suffering could be defended as a more justifiable reason for tampering with genetics than making animals that grow faster to fatten farm profits, for example.

One common argument against genetic modification has been based on animal welfare, according to Buschert. He cites the Beltsville pig, an early attempt at genetically modified pigs that grew faster but suffered from arthritis and other medical issues. This argument could be flipped around to support genetic engineering if it decreases animal suffering, Buschert said.

Both he and Boecker believe there is a good chance the consumers wouldn’t notice the pigs at all. Up to 70 percent of the food supply in the U.S. has been genetically modified, according to Buschert.

“North American consumers don’t seem aware,” he said. “Or, if they are, they don’t seem particularly worried.”

If Prather’s pigs are shown to have no health issues for the pigs or for the humans who eat them, Buschert believes there is enough financial incentive for the large agricultural companies to go forward.

“I see no reason it wouldn’t be widely adopted,” he said.

Prather’s PRRS-resistant pigs have all been healthy, but it’s too soon to have tested for all unknowns, according to Prather. The pigs will have to be bred for a large enough pool of animals to test, and they’ll have to be monitored to see if they grow and reproduce normally. 

The unknowns are what cause many opponents to hesitate. No evidence points to any health risks posed by FDA-approved genetically modified organisms, but opponents can always argue the possibility of unpredictable effects.

Others, though, think popular opinion about genetic engineering in agriculture is destined to change. Safranski argued that people are starting to talk more about food scarcity — a talking point that could favor genetic modification. Pigs could be designed to gain more nutrients from their feed, for example, or even to live longer — though both possibilities still exist only in the realm of speculation. Those who do speculate can imagine countless spectacular and horrifying outcomes that can stray into the arena of science fiction.

For Sandidge and other farmers, genetic engineering for disease-prevention provides a hope for more successful farming. He said he would love to see PRRS-resistant pigs on the market, even though he knows they are still years away.

Sandidge recently moved all his pigs off the farm to be cleaned and disinfected, and he is working now to repopulate the farm. He keeps his employees busy repairing things around the farm. He stays vigilant, disinfecting everything he can and isolating his pigs from all other animals. He knows the disease could come back, carried by a breeze from a passing livestock truck. But for now, he’s doing all he can do.

“We need to figure out better ways to deal with this disease,” he said. “This is the first real breakthrough we think we’ve had.”

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One thought on “Gene editing holds promise as animal disease prevention of the future

  1. Such a fantastic story! Really captures the issue and the anecdote at the beginning draws you into the piece well. Great research!

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