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Gene-Editing Research Could End Pig Castration

Castrating pigs is not a favorite chore for pork producers, but it’s necessary for meat quality and barn management. Now, scientists at the gene-editing company, Recombinetics, have developed a precision breeding method resulting in male piglets that remain in a prepubertal state, thus, ending the need for castration. Recombinetics has partnered with Nebraska-based swine genetics supplier DNA Genetics to evaluate, develop, and commercialize the castration-free (CF) swine trait. Research is being led by Tad Sonstegard. 

SF: What is the time line for this project? 

TS: The basis of the knowledge for the castration-free trait came from research in human infertility and mouse physiology. Now work is progressing to develop castration-free pigs. We optimize everything in the lab first before we make the initial animals to ensure we can safely bring this to the marketplace. Within a year, we will move from development into breeding animals for evaluation of health and safety. We anticipate that the development and evaluation period will be completed within the next two to three years.

SF: What are the regulations on gene editing of livestock?

TS: There are currently no U.S. regulations in place to govern the use of advanced reproductive methods in animal agriculture. The FDA believes it has jurisdiction and authority because of guidelines it issued in early 2017, but those guidelines have not been accepted as law. Gene editing and advanced reproduction techniques are not covered under previous guidelines for transgenics because gene editing does not result in transgenic animals.

We will continue to work closely with the appropriate regulatory agencies and participate in the discussion of how gene editing can address many animal health and welfare concerns in agriculture. 

SF: These pigs never go through puberty?

TS: That is true for pigs intended for food production. However, we have to provide the ability to breed animals as part of the commercial genetics program. We have to restore fertility in a way that is commercially feasible while ensuring the pigs are taint-free and have improved health and welfare.

Additionally, the castration-free pigs need to perform effectively in production systems in order to gain wide acceptance in the swine industry.

SF: What role will DNA Genetics play? 

TS: It’s important to have a commercial partner for a number of reasons. Our company doesn’t own commercial swine genetics that deliver high-quality pork products. We also don’t have the distribution network or expertise to manage, improve, and multiply these elite genetics.

We can do the gene editing to make castration-free pigs, but the DNA Genetics team has the experience to implement these improvements into commercial genetic systems. 

Also, if we are doing experiments in commercially relevant pigs, then we can definitively prove whether or not it’s better. I’ve visited the DNA Genetics facility. It’s impressive the system they have for collecting data to do improvements.

SF: What other projects are you working on? 

TS: We have two other divisions in our company. One (Surrogen) works on biomedical swine models. Our scientists introduce human genetic maladies into the swine genome and then create pigs that provide better models for human diseases. Those pigs can go to the pharmaceutical companies to improve drug testing or be used to test biomedical devices that would help against certain diseases.

Another division (Regenevida) uses pigs to grow human cells, tissues, and organs using a patient’s own DNA. It’s what we call oincubators. This ability will provide significant opportunities to support efforts to improve human health and begin to address the critical shortage of human organs for transplantation programs that are saving human lives every day. There is still a lot to be worked out, but the impact could be tremendous.

 SF: What other research at Recombinetics could have implications for commercial livestock?

TS: We can genetically dehorn animals, so farmers don’t have to go through the process of dehorning. Other research programs are focused on thermal tolerance in cattle. Just by removing one base in a gene, we can adapt an animal to a tropical environment. We are working on Angus that are thermal-tolerant. They would be like Senepol, except they would have Angus genetics instead of Senepol genetics. People cross-breed Senepol and Angus to make crossbred cattle with higher meat quality and thermal tolerance. In this case, we are taking one specific base deletion from Senepol and moving it into Angus. There are other gene variants that enable this same thermal tolerance, which means we have multiple ways to naturally make these animals thermal-tolerant.

SF: What does your family think about what you’re working on?

TS: They are interested, but until the technology is proven to deliver economic value, curiosity remains relatively high. Genetic providers realize it is of enormous strategic importance to implement gene editing into genetic improvement programs for all food animals all the way down to aquaculture. We can solve many practical problems with management and animal well-being. It makes production more sustainable. If you do that by conventional breeding, it takes a lot longer.

SF: Are we at the very beginning of gene-editing technology? 

TS: Yes. If you think back to the beginning of storing data and writing code for computing, that is where we’re at in this genetic revolution. These gene editors provide us the ability to write back to the genome. We’re still in the early days, and I’m sure the technology is going to get much more elegant. For producers and consumers to fear this technology is ridiculous considering that global expenditures on understanding DNA exceed $300 billion.

SF: Will farmers accept and use this technology? 

TS: Oh, absolutely. If it makes life easier, why not? In one recent survey of farmers, they were asked if they would support research to replace the horned gene with the polled gene using precision breeding technology. Four out of five farmers said yes.

SF: What livestock would you like to have in commercial production in 10 years?

TS: I would like to have a thermal-tolerant, tick-resistant Bos Taurus breed of cattle in Brazil and in the southern U.S. Everywhere there is subtropical production, those sorts of cattle are needed.

They would also be applicable in Africa, where the demand for animal protein is going to increase sharply. Africa is way behind in animal productivity, and it’s really hard for the country to get around diseases and tropical adaptation problems. Africa is at the point where we were in the 1800s before we started farming with improved breeds. This technology can help get Africa there faster. It won’t completely solve everything, because the country still needs to do other important management practices to support production.

SF: Will we get to the point where we can use pig livers in human transplants? 

TS: The pig liver in a human is step one. Researchers have successfully resolved key incompatibility genes in the pig genome and developed pigs that cannot transmit pig retroviruses. The next phase is testing these organs.

Step two is using human livers that are grown in pigs. That is one of the reasons why I joined this company. Can we successfully grow human livers in a pig for transplant back to humans? That’s where our company is putting at least a third of its effort.

Bio for Tad Sonstegard

Title: Chief scientific officer of Acceligen, the agriculture division of Recombinetics, St. Paul, Minnesota

Hometown: Montivideo, Minnesota

Background: Sonstegard grew up on a fourth-generation crop and livestock farm. He bought his first cows when he was 12 and was active in 4-H, FFA, and the Red Angus Junior Association. His brothers are still on the farm selling purebred Red Angus seed stock. 

Education: Sonstegard graduated from Iowa State University in ag biochemistry and got a doctorate in molecular genetics at the University of Minnesota. He spent 20 years with the USDA before joining Recombinetics.

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