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Expert offers insight into new swine genetics research

by Wyoming Livestock Roundup

During Kansas State University’s Agriculture Today podcast, aired on Jan. 31, Host Samantha Bennett sat down with Dr. Randall Prather, University of Missouri curators’ distinguished professor in the Animal Sciences Research Center, to discuss new genetic engineering projects in the swine industry. 

“In our conversation, Prather will share examples of how advanced technology could benefit the ag industry and explain outside-of-the-box thinking, which has led to numerous medical advancements in human medicine,” says Bennett. 

Ag industry application

To begin, Prather shares he likes to think of cells as a factory with the ability to do a number of different things. He notes these “factories” have “blueprints,” which can be used to make new “factories.” 

Through genetic modification, Prather explains pages of the blueprints – or a specific protein on a string of amino acids – can be taken out, added or switched with pages from blueprints of other factories – or species. 

The act of adding, deleting and changing the blueprints of these factories has led to several real life applications in the agriculture industry. 

“An estimate from a decade ago shows losses of $660 million a year in North America and 1.5 billion euros in Europe – the equivalent of $6 million a day between the two countries – from porcine reproductive and respiratory syndrome (PRRS),” Prather explains. 

Because PRRS infects white blood cells through antibody-enhanced infection, vaccines do not work for the virus.

“If antibodies recognize the PRRS virus, where do they take it? Right to the white blood cells, which get infected. So, antibiotics don’t work,” he says. “There isn’t a good solution to this problem.” 

“However, there is a molecule that sticks up on the cell surface called CD163, and it has a bunch of repeat domains,” Prather explains. “What we can do is change the letters of a three-billion letter genome and get rid of the mutation so it never gets made. It is kind of like ripping a page out of the blueprint and throwing it away.” 

Prather notes since the virus uses this mutation to infect a cell, pigs become resistant to the virus without it. 

He also shares, through the same technology, researchers have been able to knock out receptors for Senecavirus A, which presents itself as blisters on the coronary bands and snout. 

“If an operation gets this, it will shut them down until they can prove it isn’t foot and mouth disease,” he states. “Historically, there hasn’t been any solutions to a lot of these viruses, so it has been exciting to see what we can do through genetic engineering.” 

Other projects Prather shares include a solution for mastitis in cattle and heart-healthy pigs, which can convert omega-six fatty acids to omega-three fatty acids. 

Use in human medicine 

In addition to the many applications in agriculture, swine research has also been integral in the advancement of human medicine. 

“Swine are the optimal species for a lot of medical conditions where research on other species just won’t work,” Prather states. “A lot of research has been done on mice, but unfortunately they are not able to answer some important questions.” 

He says one example of this shows up in cystic fibrosis research. 

“Cystic fibrosis is caused by a mutation in the CFTR gene, and it pulls out a single amino acid in a long string. The chloride ion transport can be knocked out in mice, but we still get all of the symptoms of cystic fibrosis,” he explains. 

“For example, 15 percent of people with cystic fibrosis have mucoviscidosis, which is a mucus plug in the intestine. This makes it so they can’t defecate, and the intestine has to be opened up for the patient to survive,” he adds. “There is also blockage of the gallbladder, bile duct and pancreatic duct, they have liver lesions, and males may have blocked vas deferens. On top of all of this, they usually get lung disease.”

Prather notes when this mutation occurs in pigs, 100 percent of them have the same symptoms as people. 

“Now, physicians can go in invasively and monitor progression and development of disease in a way that just wasn’t possible prior to this,” he says. 

Another example where swine research has benefitted human medicine is through the use of green pigs, according to Prather. 

He explains green pigs have been genetically modified by adding genes from jellyfish to make them self-fluoresce, which makes them useful for tracking studies.

He gives the example of Baby Owen, a newborn from North Carolina who needed a valve replaced in his heart. 

“A colleague from the Medical University of South Carolina came to us and said there is a problem when a baby is born and they need a new heart valve, because although they can transplant a heart valve for the baby, the valve doesn’t grow as the baby grows,” Prather shares. “So, babies with this issue have to have life-long repetitive surgeries.”

Prather continues, “They had this idea that if they took a bigger piece of the heart – a partial heart transplant, in other words – with more tissue around the valve, the valves would grow with the baby. They used some of our green pigs so they could track which cells grew.” 

Prather notes the research was successful, and Baby Owen was the first human in history to undergo this new partial heart transplant. The valve grew with him, and he never had to have another surgery. 

“I got an e-mail right before Christmas from Baby Owenʼs family. He got to celebrate his first Christmas this past year because of the work all of us had done,” Prather states. “It’s really exciting because we are impacting lives and improving quality of life.” 

Hurdles and roadblocks

Although the same could be true for livestock through agriculture application, Prather says projects which have found solutions to many costly and animal-welfare related issues, like mastitis and PRRS, have been hung up in hurdles and roadblocks in the way of regulatory approval.

“The Food and Drug Administration regulates intentionally changing the letter of a genome in a pig, or any mammal, as they would a new drug. It costs an awful lot of money to get approved, which is the hold up for some of our projects,” he explains. 

“It’s interesting when we put things into erspective, because at every fertilization there is one to 200 random mutations occurring in the genome, and nobody regulates that. Nobody perceives these mutations as a health risk,” he notes. 

Prather further notes there is no regulation for mutagenesis of pigs through radiation or changing letters in the genome of mushrooms to increase their shelf life. 

“We have a solution to a lot of the problems we see in agriculture, but when trying to get it through regulatory approval, there are a lot of hurdles to jump over,” he says. 

Hannah Bugas is the managing editor for the Wyoming Livestock Roundup. Send comments on this article to roundup@wylr.net.

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