Of all the big, world-remaking bets on the genome-editing tool known as Crispr, perhaps none is more tantalizing than its potential to edit some of humanity’s worst diseases right out of the history books. Just this week, Crispr Therapeutics announced it had begun treating patients with an inherited blood disorder called beta thalassemia, in the Western drug industry’s first test of the technology for genetic disease. But despite the progress, there remain a host of unknowns standing in the way of Crispr-based medicines going mainstream, chief among them safety.

That’s because the classic, most widely used version of Crispr works by slicing open a strand of DNA in a specific spot in the genome and letting the cell stitch it back together. The major concern is that an army of DNA-breaking enzymes might sometimes wander astray and cause unintended mutations in places it shouldn’t. When a more precise technique, called base editing—which swaps individual letters of DNA without severing the strand—arrived in 2017, it promised a safer way forward. The technique had specific potential for the two-thirds of the 50,000-plus human genetic diseases caused by a single-letter screwup, and investors wasted no time licensing the technology. Researchers in China immediately began testing one such base editor in viable human embryos.

It now appears that may have been premature. Using a new method for measuring unplanned edits, a team of American, Chinese, and European scientists has found that the same base editor, widely in use by researchers today, actually messes up the genome at an eyebrow-raising rate.

Their report, published today in Science, claims a 20-fold increase in mutations over what would be expected in the normal course of cell division and repair in mouse embryos. “That number will vary depending on a lot of factors, but the major takeaway is that if you want to move this particular base editor to a clinical setting, you should probably be concerned,” says Stanford biochemist Lars Steinmetz, a co-author on the paper. That advice goes out especially, he says, to scientists who might be tempted to skirt rules and regulations to rush base editing into humans, a concern that’s been on his mind since the Crispr baby scandal broke in November.

LEARN MORE The WIRED Guide to Crispr

David Liu, the biochemist whose lab at Harvard and the Broad Institute developed the base editor in question, isn’t so sure of the clinical impact. Steinmetz’s group found almost 300 more mutations in edited cells as opposed to un-edited cells. Three hundred errors across the whole six billion bases in the mouse genome yields a mutation rate of one in 20 million. Liu points out that number is within the range of errors your cells spontaneously make on their own—more than neurons, but fewer than skin cells. Even so, he says the Science paper is an important advance in a field that is still figuring out its safety standards. “It’s a clever, elegant method designed to boost the signal so that we can now detect and understand these rarer types of guide-independent, off-target events.”

A little bit of backstory: In 2017, Nature Methods published a one-page letter claiming that a Crispr treatment that cured two mice of blindness also caused a massive number of unintended mutations. Crispr stocks plummeted and scientists threw shade at the dramatic results, which relied on sequencing each of the mice and comparing their DNA to unedited siblings. The paper was eventually retracted, and the changes determined to be just the natural genetic variation between different individuals of the same lab strain. But the episode pointed out an important blind spot in these error-detection technologies. Virtually all of them use some sort of algorithm to pick places in the genome where Crispr is likely to accidentally go to work, and observe what happened there. “This is a field where you only see what you look for,” says David Jay Segal, a molecular geneticist who studies these effects at the Genome Center at UC Davis, and who was not involved in either study. Scanning the entire genome for changes would be ideal, he says. But no one had figured out a good way to do that in living animals with the proper controls until Steinmetz’s group came along.