Rewriting Life

Gene-Editing Companies Hit Back at Paper That Criticized CRISPR

Report that suggested CRISPR is too dangerous to use as a drug was wrong, say biotech companies.

Two gene-editing companies are hitting back at a scientific publication that caused their stocks to plummet last week, calling it wrong, filled with errors, and saying it shouldn’t have been published.

In separate letters sent to Nature Methods, scientists from Intellia Therapeutics and Editas Medicine criticized a report in the journal that claimed the gene-editing tool CRISPR had caused unexpected mutations in the genomes of mice and which cast a shadow over efforts to initiate human studies using the technique.

Nessan Bermingham, CEO of Intellia, called for the journal to retract the paper, effectively an effort to remove it from the scientific record.

“This publication has garnered a significant level of media and public attention resulting in significant damage,” he said. “Given the issues around the design and interpretation I believe it is appropriate that the Nature Methods editorial board retract this paper.”

A spokesperson at Springer Nature, which publishes Nature Methods, said the organization had received “a number of communications” already about the paper. “We are carefully considering all concerns that have been raised with us and are discussing them with the authors,” the journal said. Vinit Mahajan of Stanford University, who was the paper’s senior author, did not immediately respond to a request for comment. Another author, Alexander Bassuck of the University of Iowa, said he was traveling and unable to respond immediately.

The paper, titled “Unexpected mutations after CRISPR–Cas9 editing in vivo,” triggered a rash of negative headlines after claiming the gene-editing tool caused widespread and unpredictable havoc in the genomes of edited mice, introducing hundreds of unintended errors.

The stock market value of Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics, which together have raised more than $1 billion to pursue CRISPR treatments, all fell sharply on the news.

On Twitter and elsewhere, other scientists quickly pointed out basic mistakes in the paper, including misidentifying genes, the small number of animals involved and, most seriously, that it had mislabeled normal genetic differences between animals as the result of CRISPR editing.

“In our opinion the conclusions drawn from this study are unsubstantiated by the disclosed experiments,” wrote Vic Myer, chief technology officer of Editas, in a letter signed by 11 other company scientists as well as by George Church, a Harvard University professor who is a scientific cofounder and shareholder of Editas. 

Church said the paper should “possibly” be retracted, and at a minimum should be updated to disclose “major missing considerations.”

CRISPR technology is widely touted as a revolutionary new means of easily altering DNA. But its promise is being exaggerated in media reports, including some that claim it will cure all genetic disease and solve the world’s food problems with superplants.

CRISPR can be programmed to cut specific sequences of DNA letters, thereby correcting or changing genes. While this versatility is what makes it powerful, if the same or similar sequence of letters appears elsewhere in the genome, that can result in an unintentional or off-target edit. Concern over the technique’s potential side effects is widely shared, even by some of its inventors.

The fear is that planned medical treatments using CRISPR could prove dangerous. A single erroneous cut could be disastrous for patients if it lands in a vital gene. Fifteen years ago, pioneering experiments in gene therapy were set back when unintentional genetic changes caused cancer in some children. Many scientists believe careful programming can eliminate most of the risk.

The ease of use of CRISPR means nearly any lab can try it. In China, some human experiments have already begun. The rush to use the method is part of what’s creating anxiety, since it makes mistakes more likely. Editas recently postponed its own planned study of CRISPR to correct an eye disease until next year.

According to Intellia, however, the authors showed “disregard” for what’s already known about CRISPR. “It is clear the authors are not experts on the CRISPR Cas9, whole genome sequencing, nor basic genetics. Their claim of ‘unexpected mutations’ clearly demonstrates their lack of scientific acumen around this topic,” the company said.

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