If gene editing could create domestic pigs resistant to the African Swine Fever (ASF) virus, what value would that have to the swine industry worldwide?
With a devastating ASF outbreak in at least 10 provinces right now, China is probably too busy cleaning up farms to calculate. In Scotland, animal biotechnology professor Bruce Whitelaw, chair of genomics at the Roslin Institute in Edinburgh, is working on this very research. Details of the ASF studies are top secret, but Whitelaw will say that the research is ongoing and the ASF virus challenge on the pigs “will happen later this year.” The world is waiting.
In the U.S., it’s full speed ahead for gene editing in animal agriculture. In August, the biotech company Recombinetics, based in St. Paul, Minnesota, received $34 million in new funding to speed up research and development of its gene-editing products. The company’s main focus is to improve livestock health and welfare and to grow human organs in pigs.
Will gene editing be accepted by the public? “I’m cautiously optimistic that we can move this technology forward without reliving the GMO experience,” says John Johnson, chief operating officer for the National Pork Board. “There is a commitment by industries involved, as well as academics, to have transparent conversations about this. They are not trying to hide anything. The approach is very different than it was with GMOs 30 years ago. The transparency, dialogue, and conversation may lead us down a path where we can achieve consumer acceptance more readily and with more confidence.”
When asked what gene- editing research could produce down the road, University of CaliforniaDavis geneticist Alison Van Eenennaam and Mitch Abrahamsen, chief commercial and scientific officer for Recombinetics, gave these 10 predictions for the next decade.
More products will be on the market for farmers.
Recombinetics already has commercial deals with Hendrix Genetics, DNA Swine
Genetics, and Semex, a Canadian dairy AI cooperative. Abrahamsen can’t publicly talk about all the partners they are negotiating with, but it is a growing list. “We expect additional acknowledgements with commercial partners – both in North America and Europe – within the next year,” he says. “Health and welfare traits will be deployed and available to the entire industry through our commercial partnerships.”
There is currently one product going through the FDA regulatory process – a gene-edited pig resistant to the PRRS
(porcine reproductive and respiratory syndrome) virus. That was developed by the University of Missouri and is being licensed by Genus.
The work Recombinetics is doing with Semex to introduce the polled (hornless) trait into their elite dairy sire lines, is encouraging, says Van Eenennaam. Other animal welfare applications like pigs that do not require castration and
further disease-resistance traits are in the pipeline. “Whether these come to market will depend upon the regulatory requirements and whether they are compatible with animalbreeding program design,” she says.
Animal welfare will be improved.
• Hornless cattle are
here. Semex is partnering with Recombinetics to commercialize the polled trait. “It won’t be the only genetics company offering our solution for the dehorning process,” says Abrahamsen.
• Swine will be naturally castrated.
“Today in the marketplace, we have a castration-free swine project,” he says.
• Cattle will be naturally heat-tolerant.
A program at Recombinetics focuses on improving the heat tolerance in both beef and dairy cattle. This will allow improved efficiency of production in the tropical regions. “If dairy cows in the tropical environments are heat adapted, we’d see a sevenfold decrease in the number of animals required to produce the milk we do today in those regions,” says Abrahamsen.
• Cattle and swine will be healthier.
Cattle will be free of bovine tuberculosis, says Abrahamsen. Recombinetics is working with a collaboration in Europe. Other programs focus on foot-and-mouth disease, as well as the PRRS virus. “Right now those are the two big ones we can talk about publicly,” he says. “There are clearly other diseases that have impact around the world that would be very amenable to a research effort to identify the genetic variation that provides that resistance.” ASF is one of those diseases.
Livestock genetic quality and production could soar.
“I’m interested in using editing to knock out the germ cell, or testes, of a bull and replace it with the testes of a much better genetic animal,” says Van Eenennaam. “You could have a bull that is well suited to your environment but is carrying the genetics – or just the testes – of the very best bull in the breed. That has a lot of potential in developing countries like Africa, where facilities aren’t there for reproductive technologies. I call it the surrogate sire idea. In New Zealand, they are working on it in sheep.”
Traits will be stacked.
“Our goal is to put multiple edits in an animal,” says Abrahamsen. Think of it as stacking traits. “We would have animals that are hornless, diseaseresistant, heat-tolerant, and produce less methane and less waste compared with animals today in our production systems.”
Consumers will better understand that gene editing is distinct from GMO transgenic technology.
How well consumers understand gene editing “probably depends on who is disseminating the message,” says Van Eenennaam. Gene editing can actually be used to introduce DNA from a different species, so it is not necessarily distinct from transgenic technology, she explains. At the same time, it can also be used to make alterations that exactly mimic existing genetic variants within a species or spontaneous genomic alterations.
“None of these is uniquely risky, as demonstrated by decades of GMO safety studies and conventional breeding,” she says. “However, some groups have successfully spread fear around GMOs, resulting in a lucrative non-GMO labeled market. They may also find it to their advantage to conflate gene editing with GMO technology and continue to monetize that fear-based messaging around gene editing.”
Regulatory agencies will continue to regulate the safety of gene-edited products.
Hopefully, they don’t continue to regulate the process itself if the resulting product is indistinguishable from a natural product, says Abrahamsen. “The focus is on accelerating the natural breeding process. We identify the genetic variation that controls welfare and health traits, and then we increase the frequency of that variation within our elite, efficient animals.”
The USDA regulates gene-edited plants with the approach that if the plant contains no novel DNA and could have been produced using conventional breeding, then it is not subject to additional regulation. In the case of edited animals, the FDA is in charge. It is asking for a premarket “new animal drug” approval
application for all intentional edits in food animals, says Van Eenennaam. “It is difficult to understand what potential risks from editing animal genomes might warrant such a high regulatory bar, considering alterations that could have been obtained using conventional breeding – such as polled dairy cattle.”
International acceptance to gene editing will grow.
In August, Japan announced that it considers a geneedited animal no different than a normal animal in the food chain, says Abrahamsen. South America has approved geneedited animals. Canada regulates the process based on whether the product is novel or not. “These countries are regulating the product – not the process,” he says.
Whether other countries accept gene editing is complicated, says Van Eenennaam. “There is no consistency or even sciencebased rationale to trigger regulation. It appears almost arbitrary. Given the lack of regulatory harmony among countries, it is almost impossible to predict international acceptance. Rather, it is likely there may be trade disruptions and fraud, because many edits cannot be detected.”
Farmers will continue to support the technology.
Farmers are on board, says Abrahamsen. “When Semex announced its deal with us, it received positive feedback from co-op members.” Ten years from now, farmers will accept the innovations even more than they do today, he predicts.
“Farmers are very pragmatic and businessminded,” says Van Eenennaam. “If a technology helps address a problem in a cost-effective way, they will adopt it.”
Government funding for research may be dicey.
Recombinetics gets some funding from the USDA and FFAR (Foundation of Food and Agriculture Research), which funded the company’s castration-free program, but the conflict between USDA and FDA regulations has hurt the industry, says Abrahamsen.
If regulations involve a “new animal drug” approval for every edit, this will confine commercial developments to large companies, says Van Eenennaam, effectively shutting out the public sector and small companies. “This happened with genetic engineering. It makes little sense to develop applications that cannot ever be commercialized.”
Biomedicine solutions for human health will boom due to gene-edited livestock.
Recombinetics has two business units outside agriculture. One is focused on using pigs as models for human disease research. The physiology and metabolism of a pig (vs. a mouse) is more similar to a human, says Abrahamsen. “Our animal models will allow us to predict and identify those changes that happen before the disease appears. We’ll understand which animals will get the disease and which animals won’t.”
For example, the company has developed pigs with high blood pressure. “We should be able to identify biomarkers that indicate before the high blood pressure increases, that these animals are the ones that will need therapy,” he explains. “We can develop preventive medicine vs. treatment medicine.”
The second biomedical unit is focused on regenerative medicine. “We use pigs as ‘oinkubators’ to produce human cells, tissues, and organs,” says Abrahamsen. Within six years, he predicts, the company will produce human cells and tissues that will address issues with blood shortages, storage of blood products, diabetes, and liver disease.
“Ultimately, in the next 10 years, we will develop human organs for transplant, specifically with a focus on cornea, heart, kidney, and liver,” he says.
Elsewhere, Harvard University geneticist George Church is using gene-editing technology to create pigs that are free of harmful viruses, an important step toward transplanting pig organs into humans.
Even the world’s largest pork producer, Smithfield Foods, has established a bioscience unit in the hopes of growing pig organs that could one day be transplanted into humans.
The world is waiting.
Farmers are very pragmatic and business-minded. If a technology helps address a problem in a costeffective way, they will adopt it.
Alison Van Eenennaam