Dairy cows grow horns. But dairy cows in the U.S. rarely have horns because they are seared, cut, or chemically burned off in a process that is as painful as it sounds. When Scott Fahrenkrug, then an animal scientist at the University of Minnesota, learned about dehorning, he decided to apply his genetics expertise to creating a hornless dairy cow. And he left academia job to co-found a company, Recombinetics.
Fahrenkrug and his team ended up using a relatively new gene-editing technique called TALENs. They took a hornless gene from a breed of beef cattle and inserted it into a breed of dairy cattle. The resulting cattle are hornless, good at producing milk, and still genetically 100 percent cattle. In the past, breeders could have crossed dairy cattle and hornless beef cattle to get hornless dairy cattle after many generations. Gene editing is much, much faster, but the end results are genetically almost the same. Does this kind of gene-editing still need to be regulated?
The answer is yes, according to proposed guidelines released by the Food and Drug Administration this week. In an accompanying blog post that cites Recombinetics’s hornless cows, the FDA made clear that it could regulate any “portion of an animal’s genome that has been intentionally altered” as an animal drug. Recombinetics, as far as the FDA is concerned, has essentially been making animal drugs with its hornless cows. This is naturally not the decision the company was hoping for. “We disagree with this guidance and will be doing our best to change this,” Fahrenkrug told me this week. Scientists have also used gene-editing techniques to create pigs resistant to various viruses, though Recombinetics’s cows appear to the closest to commercialization.
If deeming altered DNA in an animal drug sounds kludgy, well yes. But it’s been that way since the beginning. In the early days of genetic engineering in the 1980s, the Reagan administration decided not to pass a new law regulating the technology. Rather, it divvied up regulatory authority among existing agencies under existing laws: The US Department of Agriculture would oversee genetically modified crops under plant pest rules, the Environmental Protection Agency crops engineered to contain insecticides under pesticide rules, the FDA genetically modified animals under animal drug rules. The whole thing is called the Coordinated Framework for Regulation of Biotechnology, and it’s been updated twice, most recently this past month.
This patchwork is massively confusing, but it’s worked okay. New gene-editing technologies, however, have created problems for these old laws. In the past, genetic modification has involved recombinant DNA, which means taking DNA from one species, like bacteria, putting it into a second, like cotton. Recombinant DNA clearly involves adding something new and man-made into an organism. But TALENs, the technique Recombinetics uses, and CRISPR, an even newer and hyped gene-editing technique, allow scientists to make precise edits and deletions to the genome.
The different agencies are now making what seem to be different decisions about how to regulate the products of CRISPR and TALENs. When the comes to plants, the USDA has decided a mushroom with a gene deleted using CRISPR does not fall under its regulatory authority because it contains no new foreign DNA from plant pests. Now, the FDA, has announced it is seeking comment on whether crops that have been edited via techniques like CRISPR pose additional risks compared to traditional breeding. In other words, where the USDA has stepped out, the FDA could now step in.
The FDA’s overall approach is risk based. Even with the proposed gene-edited animal rules, the FDA is still looking for input on which kinds of gene editing might pose little or no risk. That could ultimately mean a range of different requirements, says Jay Cormier, an attorney with Hyman, Phelps, & McNamara who previously worked at the FDA. A full animal drug approval process could require data from multiple generations of animals to prove the genetic alteration is safe and stable. The agency could also exercise regulatory discretion for low-risk situations, requiring a lot fewer safety studies. “The guidance documents are written very broadly,” says Cormier, and it is deliberately vague. “The more details they provide the more they box themselves in.” The proposed FDA guidance is now up for public comment. The final guidance, if and when it comes out, will be likely be during the Trump administration, which has expressed no strong opinions about the FDA’s current handling of genome editing.
The uncertainty doesn’t sit well with Fahrenkrug though. He fears the regulation could stifle his relatively small company. “It will kill the industry. It will restrict the industry to only the most wealthy companies,” he says. Recombinetics is now also looking beyond the U.S.—it has an office in Bangkok—and Fahrenkrug is betting other countries will have more favorable regulations.
In the meantime, don’t hold out for streamlined biotech regulations in the U.S. That would require a law passed in Congress. “It appears that Congress is sufficiently dysfunctional that I’m not confident going back to Congress to seek clear regulatory authority would be a productive use of anyone’s time,” says Cormier. The 1980s patchwork of regulations lives on.