Last week, when a British reporter broke the news that American scientists had used Crispr to edit the first human embryos on US soil, he wasted no time in cutting to the big, juicy, highly controversial chase. “One Giant Step For Designer Babies” ran the headline on Steve Connor’s world exclusive in the i, a London-based online newspaper. A similar report appeared at the same time in MIT Technology Review, though with a far more subdued title. But in both stories, details about the exact experiments were scarce, because the academic paper summarizing the work was still under peer review. Now the study is out, published online Wednesday morning in the journal Nature. And there’s a lot more to talk about.
In the past two years years, boundary-pushing reproductive biologist Shoukhrat Mitalipov led researchers at Oregon Health and Science University, the Salk Institute, and Korea’s Institute for Basic Science through a series of experiments designed to correct a genetic defect in viable embryos. A mutation in MYBPC3 causes a heart condition known as hypertrophic cardiomyopathy that affects one in 500 people—the most common cause of sudden death among young athletes. Using Crispr-Cas9, they successfully replaced the flawed gene with a normal one for 42 out of 58 embryos, the most successful demonstration of the technique’s gene editing prowess in the human germline. And while the mutation-correcting mechanism was highly efficient, it wasn’t the one that Mitalipov, or anyone, was expecting.
Before Mitalipov's team could edit the first embryos in the US, they had to make them. So they took sperm from a guy with a mutation in his MYBPC3 gene and used it to fertilize eggs from 12 healthy females. In addition to the sperm, they also injected each egg with Crispr-Cas9 protein, a guide RNA directing it toward the mutant copy of MYBPC3, and a piece of template DNA, modeled after the normal gene but with a few tags so scientists could find it again later. The idea was for Crispr to cut out the mutant copy and the embryo’s repair machinery to use the supplied template to build a normal gene in its place.
And it worked—surprisingly well. Past Crispr experiments in China have run into issues; sometimes, not every cell in the embryo gets repaired, or Crispr cuts things it shouldn’t. Even earlier attempts by Mitalipov’s team to edit MYBPC3 in stem cells with Crispr ran into similar issues. But when it came to the embryos they injected at the exact time of fertilization, they saw very low rates of either of these failures.