In Embryos, Crispr Can Cut Out Whole Chromosomes—That's Bad

In 2017, researchers at Oregon Health and Science University came out with some big (if true) news . Led by a reproductive biologist named Shoukhrat Mitalipov, the scientists had used the Nobel Prize–winning molecular tool known as Crispr to fix a heart-condition-causing mutation in human embryos—a first in the US. A week later, the journal Nature published details of these boundary-pushing experiments. Up until that point, viable embryos had only been Crispr’d once before, in China. As WIRED reported at the time , Mitalipov’s team’s editing appeared to work surprisingly well. But one thing didn’t go as expected.Crispr works by cleaving DNA apart at a specific location in the genome . Then it’s the cell’s job to repair the resulting double-stranded break. One way to make sure it does it right is to supply a bit of corrective DNA along with the Crispr components. But Mitalipov’s group reported that their embryos didn’t use the template they provided. The embryos had been created by fusing a healthy donor’s egg with a sperm that carried the mutation. But it turned out that the newly fertilized embryos borrowed the egg donor’s healthy copy to rebuild the gene, rather than the string of DNA the scientists had supplied it.

This was weird, but potentially really cool. It meant that early-stage embryos might have unique repair mechanisms other cells don’t that could be harnessed for gene editing. And that might make it easier to correct life-threatening mutations in embryos for which only one parent carries the genetic glitch. (The template-feeding technique is notoriously inefficient; cells don’t like being told what to do.)

Not every scientist bought this explanation, though. It kicked off a dispute within the Crispr community about what else might be going on, although only a few of the skeptics had the expertise and resources to investigate. One of them was Dieter Egli, a stem cell biologist at Columbia University. Editing viable human embryos isn’t illegal in the US. But it is controversial, and Congress won’t foot the bill for any such research. So scientists who want to pursue human embryo editing have to find private philanthropies to fund the work. Egli had backing from the New York Stem Cell Foundation and the Russell Berrie Foundation. His team started work almost immediately. Now, nearly three years later, he thinks they finally have a more plausible answer to what happens when you edit a human embryo. More often than not, Crispr doesn’t spur some novel repair mechanism. It makes the whole gene—sometimes the whole chromosome—disappear.
“Our results point to the extraordinary caution necessary before progressing this kind of research to the clinic,” says Egli, whose study was published Thursday in the journal Cell. He believes that had such data existed two years earlier it would have discouraged anyone from attempting to use Crispr to edit human embryos with the intention of starting a pregnancy. But in 2018, a Chinese scientist named He Jiankui did just that, claiming to have created the world’s first Crispr’d children and bestowing upon them a mutation that’s protective against HIV infection. The experiment was a catastrophic scandal —a failure of science , ethics , and regulation . He Jiankui is now serving a three-year prison sentence, but his work opened the door for others eager to advance the technology. Last year, a Russian scientist made public his plans to use Crispr to help deaf parents have children who won’t inherit a gene mutation that causes hearing impairment.