A congressional committee is expected to vote on Tuesday to drop a ban on altering the genomes of human embryos intended for pregnancies, which could open the door to creating babies with genetic material from three people or with genomes that have been modified in a way that would be inherited by their descendants, as China’s “CRISPR babies” were.
The prohibition on modifying the DNA of embryos for reproduction (as opposed to doing so in basic research that stops short of pregnancies) has been attached to bills that fund the Food and Drug Administration since December 2015. But last month, a House appropriations subcommittee approved a version of an FDA spending bill without the amendment, or rider — amid worldwide condemnation of the CRISPR babies experiment last year and calls by leading scientists for a global moratorium on creating gene-edited babies.
“People don’t appreciate that this is the only piece of legislation in the United States that stands between us and genetically engineered children,” said science historian J. Benjamin Hurlbut of Arizona State University, who supports a “global observatory” to track uses of CRISPR, the powerful genome-editing technology.
A number of scientists and legal scholars are nevertheless calling on lawmakers to remove the rider, which prohibits the FDA from considering applications to conduct research “in which a human embryo is intentionally created or modified to include a heritable genetic modification.” They argue that doing so won’t open up some wild west of ethically fraught reproductive medicine experiments, but would simply enable the FDA to review applications to conduct clinical trials of the procedures, just as it does with other innovative technologies.
“What it simply means is that the FDA will be able to accept applications and potentially permit them based on rational reasoning that evaluates risk and benefits,” said Dietrich Egli, an assistant professor of developmental cell biology at Columbia University Medical Center. “It will allow the FDA to do its job, nothing more and nothing less. If the FDA finds it’s ready for going forward, then we can go forward. If the FDA finds that there are risks we don’t understand, then we’ll review them.”
The prospects for the rider are unclear. Even if the FDA spending bill without the rider makes it through the Democrat-controlled House, the Republican-controlled Senate is expected to push to restore it.
When the appropriations subcommittee approved dropping the rider last month, the panel’s ranking Republican, Rep. Jeff Fortenberry of Nebraska, said he had “deep regret” over the decision. “We will of course further deliberate on this at a later date,” he said.
An FDA spokesman said the agency doesn’t comment on pending legislation.
More precisely called mitochondrial replacement therapy, the technology has the potential to prevent severe diseases that result from abnormal mitochondria, energy-producing structures in cells. The therapy transfers the nucleus of an unfertilized egg with defective mitochondria into one with healthy mitochondria and then fertilizing it via IVF. Since mitochondria have a tiny bit of their own DNA, the resulting embryo has nuclear genes from the father, nuclear genes from the mother, and mitochondrial genes from the woman who donated the ovum.
“Mitochondrial replacement therapy became collateral damage in Congress’ effort to prohibit genetically engineered babies,” said bioethicist LeRoy Walters of the Kennedy Institute of Ethics at Georgetown University, who organized the letter. Such “designer babies” had become a hot-button issue in 2015 with the development of CRISPR and its potential for changing the genomes of embryos.
“We don’t think supporters of the rider have any idea of the distinction between mitochondrial DNA,” which affects only how mitochondria function and has nothing to do with any physical, intellectual, or other traits, “and nuclear DNA,” which shapes all of those, Walters said. “We don’t think Congress intended this, so we suggest that Congress stipulate that mitochondrial replacement therapy is not covered by the rider.”
Their goal, Walters said, “is to help families not pass on serious diseases to their children.” About 700 to 1,000 children are born in the U.S. every year with mitochondrial diseases, which cause neuromuscular abnormalities and, often, early, painful death.
The technique is allowed in a number of countries, including Great Britain, where it is being studied as a way to prevent mitochondrial diseases. A New York doctor carried out the procedure in Mexico in 2016, resulting in the birth of a healthy boy. It could also be used as an infertility treatment, something that is being studied in a clinical trial in Greece.
Supporters of the rider argue that allowing mitochondrial replacement therapy would open the door to CRISPR babies, too. “I’m just perplexed why the subcommittee would drop this rider,” said David Prentice of the Charlotte Lozier Institute, a think tank affiliated with the anti-abortion Susan B. Anthony List, who was reportedly instrumental in crafting it in 2015. “It moves us in the opposite direction of the rest of the world and the scientific community, and if it’s passed, the U.S. would have no law to prevent what happened in China.”
As it happens, in the same issue of Nature Medicine, reproductive biologist Shoukhrat Mitalipov of Oregon Health and Science University argues that research on heritable genome editing, or “germline gene therapy,” including for the purpose of establishing pregnancies, should be allowed.
“We are not arguing to use germline gene therapy to change genes to something that is not normal for humans,” Mitalipov told STAT. “Germline gene therapy corrects a mutant gene to bring it back to the wild type,” or the form carried by the vast majority of humankind. In 2017 Mitalipov created the first CRISPR’d human embryos in the U.S., but did not implant them in women.
He was on the verge of requesting FDA approval for a clinical trial of mitochondrial replacement therapy when the rider prohibiting that was enacted. He said he is “ready to submit” the application and to conduct a clinical trial in which 10 to 15 embryos would undergo mitochondrial replacement therapy and be used to create pregnancies.
Among the Democratic lawmakers on the Appropriations Committee who have supported dropping the rider are committee Chairwoman Nita Lowey of New York and Rep. Rosa DeLauro of Connecticut, according to people familiar with the matter. Rep. Sanford Bishop Jr. of Georgia chairs the subcommittee that moved the bill earlier this month. “We believe this provision could limit important scientific research,” a Democratic aide said about the rider.
“We have a really robust oversight system in the United States, and all removal of this rider does is allow that oversight system to work,” said Sean Tipton, chief advocacy and policy officer at the American Society for Reproductive Medicine. “If this policy is adopted, it does not green light anything. It simply allows the FDA to do its work.”