Researchers Are Divided as FDA Moves to Regulate Gene Editing

As U.S. regulators threaten broad new limits on the use of gene-editing technology, a Utah State University researcher now engineering goats to produce spider silk in their milk isn’t particularly worried.

“They’re just trying to modernize” rules to keep up with technology, the Utah professor, Randolph V. Lewis, said of the changes proposed by the U.S. Food and Drug Administration.

But over in Minnesota, a researcher working to create cows without horns — as a way of keeping the animals safe from one another — has a far different take.

“It’s a huge overreach” by the FDA that could stifle innovation, said Scott C. Fahrenkrug, an adjunct professor of functional genomics at the University of Minnesota at Twin Cities.

The FDA is responsible for ensuring the safety of food and drugs sold to Americans, and for years it has defined that oversight to require its approval when genes are added to animals whose products might be consumed. The change it proposed last month would expand that authority to cover new technologies such as CRISPR that enable gene-specific editing, potentially enabling changes not found in any known species.

To supporters, the FDA is simply trying to keep up with the science. To detractors, it’s a reach for authority so broad as to go beyond any reasonable definition of the FDA’s mandate.

The outcome, to be decided in the next few months, is a matter of great concern for companies that work with such animals. And that concern is shared by many university researchers, as the need for their scientific services could be dramatically shaped by how readily such genetic changes lead to marketable products.

“There’s a lot of money at stake here,” said Robert Klitzman, a bioethics expert at Columbia University.

Those high stakes are reflected in two other developments in the past week concerning Crispr, a technique that lets scientists activate or silence specific genes in an organism. One is the continuing battle between the University of California and the Broad Institute of Harvard and MIT over Crispr patent rights. (The U.S. patent office reiterated its awards to the Broad Institute, though more legal challenges may be coming.) The other was a report by an advisory group formed by the National Academies of Sciences, Engineering, and Medicine giving its cautious approval to the use of such gene-editing methods in humans to help cure or prevent diseases.

For the FDA and animals, gene editing poses — at most — indirect effects for humans. Some researchers point out that there’s never been any evidence of a genetic mutation in a plant or animal leading to a genetic change in a human. Others say that the possibility can’t be ruled out, and that regardless there are a host of other ways in which a genetic change in an animal could have harmful repercussions for humans.

One high-profile example is the question of whether and how to handle mosquitos. Mosquitos are responsible for more than 800,000 deaths a year, and the Bill & Melinda Gates Foundation has devoted $75 million to using Crispr technology to kill them off.

But some fear unanticipated consequences for the overall food chain, given that mosquitoes are eaten by bats and other predators. “There is a lot what we don’t know” about unintended side effects from actions such as the genetic manipulation of mosquitos, Mr. Klitzman said.

Some government authority needs to consider all the factors associated with making genetic changes in animals, beyond the question of any direct genetic effects on humans, said George M. Church, a professor of genetics at Harvard University. “If anything the FDA is underregulating,” Mr. Church said.

Process vs. Outcome

Mr. Fahrenkrug certainly doesn’t feel that way. Some types of livestock have long lacked horns, but farmers and scientists have had trouble breeding that trait into some of the most productive types of beef cattle and milk-producing cows. The result is a costly and bloody practice of dehorning animals to keep them safe from one another on farms. Crispr offers a solution that could shortcut what the industry anticipates would be another 20 years and $1 billion spent on conventional breeding research.

But the proposed new FDA rules threaten that use of Crispr, said Mr. Fahrenkrug, the founder and chief scientific officer of Recombinetics, a company working to create the hornless cows. For Mr. Fahrenkrug and other critics, the danger of FDA regulation is demonstrated by the two decades and $60 million that developers of a fast-growing transgenic salmon have spent so far trying to win market approval for their product.

The underlying problem, Mr. Fahrenkrug and other critics contend, is that the FDA and other government regulators have been basing their approvals on the process of making a genetic change rather than focusing on the change itself. In cases such as hornless cows, he explained, there should be no regulatory approval necessary if the genetic change — even if accomplished by Crispr — is no different than a change that does or could occur naturally.

Farmers simply want to make a “correction” that already exists in nature, one “that we’ve been eating for 1,000 years,” Mr. Fahrenkrug said. Regulating genetic changes that are indistinguishable from natural mutations “makes not a lot of sense,” said James M. Reecy, a professor of animal science at Iowa State University.

Under the federal rule-making process, the FDA is taking public comments for a 90-day period ending April 19 before deciding its next steps. In a written explanation of the proposed policy changes, the agency said it had the right and responsibility to treat a change made by genome editing as drug requiring regulation “because it is intended to alter the structure or function of the animal.”

The statement, by the FDA’s commissioner at the time, Robert M. Califf, and a senior policy adviser, Ritu Nalubola, also noted that genome editing risks mistakes and unintended effects, and that the technology “has raised fundamental ethical questions about human and animal life.”

Yet Dr. Califf and Ms. Nalubola acknowledged the need for American research to remain internationally competitive, and promised that the FDA would work closely with experts inside and outside the government to keep apprised of scientific developments.

The FDA’s proposed changes look less threatening to a researcher such as Mr. Lewis because his goats are not intended to be eaten. Spider silk is valuable in a wide range of applications, such as flexible adhesives, films and gels used in drug delivery, and coatings for catheters and medical implants, he said. The FDA is happy just to see protective steps such as double walls of fencing around their pens and microchip identification systems to ensure that the goats do not escape and somehow mix with other animals, he said.

“I have not had any particularly unpleasant interactions with the FDA,” Mr. Lewis said.

And there are other examples where the FDA has moved quickly, Mr. Church said, including its approvals of a pill containing a radio transmitter that responded to stomach acid, and a treatment for cystic fibrosis. The salmon industry may be having a less-urgent experience, Mr. Church said, because it’s largely a pursuit of economic gain. “I’m not saying it would be harmful,” he said of genetically engineered fish, “but the benefit is not high.”

But too much regulation, even in the case of genetic changes that promise only economic gain, could hurt university researchers, Mr. Fahrenkrug said. Investments in research will eventually go elsewhere, including overseas, he said.

The effects can already be seen in endeavors such as the pursuit of disease-resistant pigs or extra-beefy cattle, said Alison L. Van Eenennaam, a cooperative extension specialist in the department of animal science at the University of California at Davis. Regulatory requirements to kill and incinerate all test animals have “crippled” such research in the United States for decades, Ms. Van Eenennaam said.

One hopeful sign for such researchers, Mr. Klitzman said, is the fact that the FDA is under political pressure to be more accommodating to industry. The proposed new limits on gene-editing technology were initiated by the Obama administration and now depend on the Trump administration, which has promised a broad crackdown on the growth of government regulations. And just a couple of months ago, Congress passed the 21st Century Cures Act, which pushed the FDA to speed the approval of drugs and medical devices involving patients with dire prognoses and poor treatment options.

“There are people,” Mr. Klitzman said, referring to the current political climate in Washington, “who would love to get rid of the FDA altogether.”

Paul Basken covers university research and its intersection with government policy. He can be found on Twitter @pbasken, or reached by email at paul.basken@chronicle.com.