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Genome editing has created cows that grow no horns, the better to avoid painful dehorning.

Genome editing has created cows that grow no horns, the better to avoid painful dehorning.

Cornell Alliance for Science

NAS panel tackles—and is tackled by—genome editing in animals

WASHINGTON, D.C.—A 2-day National Academy of Sciences (NAS) workshop here last week exposed just how far scientists, ethicists, and regulators are from agreeing on the best way to move forward with genome editing in animals. Following on the heels of this month’s NAS summit on genome editing in humans, the workshop attracted much less attention, even though the work has more immediate regulatory and scientific implications. It also has the potential to shape how these technologies may one day be used in humans.

In one sense, gene editing has been going on for nearly 10,000 years. The selective breeding of livestock leads to changes in a breed’s genetic makeup similar to what can be done with modern techniques. The big difference, say genome-editing advocates, is that these new molecular tools make the process much more efficient, with precise ways of deleting, inserting, or regulating genes. One approach, called CRISPR, has made gene editing so easy that in little more than 2 years, researchers have used it to change the genomes of more than a dozen plants and animals. With CRISPR, researchers have modified or disabled multiple genes at once, in some cases leaving no trace of the foreign DNA that makes it possible.

Such ease of use will likely encourage  the use of more animal models in the study of human diseases, says Rhonda Wiler, a geneticist at biotech giant Genentech in San Francisco, California, who co-chairs the Roundtable on Science and Welfare in Laboratory Animal Use (which organized the workshop). For example, model mice, which were once modified by a laborious process that required multiple generations of breeding, can now be modified in just one generation. In theory, this approach means that all researchers have to do is simply isolate and modify an unfertilized egg in order to modify a genome. “This will have a massive impact on the use of animals in sciences,” says Peter Hohenstein, a development biologist at the Roslin Institute at the University of Edinburgh, Easter Bush in the United Kingdom. Not only is genetic modification easier in mice, but it is likely to become much more feasible in a wide range of other species, including pigs, fish, monkeys, and even humans.

In addition, researchers may be able to make more use of less complex, so-called “lower” organisms -- say fish instead of mice -- in their work, an important goal for animal welfare enthusiasts. And because CRISPR works so well in cells growing in a lab dish, some tests can forgo using animals altogether.

Such efforts can also improve conditions for farm animals. In the works is an oinker that will be resistant to swine flu. A company called Recombinetics, based in St. Paul has produced calves that won’t grow horns, so they won’t have to undergo the painful process of being dehorned. It’s taken just a few years to do what breeders would need 50 to 100 years to do, notes Recombinetics’s Scott Fahrenkrug, whose company is working on pigs that will never have to be castrated.

However, some worry it’s becoming too easy to make animals “just because,” says Hohenstein, who adds that people may pay less mind to minimizing the use of animals in research. Ethicists cite similar concerns. Researchers in China have created a CRISPR-generated line of micropigs as pets, for example.

Still, Angelika Schnieke from the Technical University of Munich, Freising-Weihenstephan, in Germany says that she and her colleagues are trying to ensure they follow the animal welfare principle of minimizing animal use through a European program to coordinate the development of large animal models. She and others are making pigs that get cancer, polycystic kidneys, heart disease, and other conditions.

Still up in the air is the role of federal regulation. The U.S. Department of Agriculture (USDA), the Food and Drug Administration, and the Environmental Protection Agency are all “wanting a little piece of the pie,” says David Kurtz from the National Institute of Environmental Health Sciences in Raleigh. In the 1980s, these agencies came up with the Coordinated Framework for the Regulation of Biotechnology, last updated in 1992 and now under review. “Many provisions for the regulation of conventional transgenic animals may not apply to genome editing,” says Susan Harper from the Agricultural Research Service, part of USDA, in Beltsville, Maryland.   

But so far no one has been able to reach a consensus. Some of the meeting attendees favored increased or different regulations, some argued that genome editing should be less strictly controlled, and some wanted to maintain the status quo. Among supporters of fewer regulations,  Alison Van Eenennaam, an animal breeder at the University of California, Davis, says that some editing is “just a way to enable base pair changes” that doesn’t actually add new DNA to an organism. She says she is particularly concerned about the cost of complying with regulations, which may be so high that universities and other institutions can’t afford to follow up on good ideas. But others are okay with adding regulatory brakes to genome editing. “That’s the government’s job,” Hohenstein says. “We spend a lot of time and effort in making sure we comply or the public wouldn’t accept what we are doing.”