The CRISPR controversy: Scientists skeptical over recent critical study

Last month, a study was published claiming that the groundbreaking CRISPR-Cas9 gene-editing technique could potentially introduce hundreds of unintended mutations into an animal's genome. Unsurprisingly, this study sent shockwaves through the scientific community, with the stock prices from several gene-editing companies falling. Critics are now calling into question the veracity of the study, claiming it is filled with flawed assumptions.

Published in the journal Nature Methods, the research from a team of scientists from Stanford, the University of Iowa and Columbia University examined the entire genome of mice that had undergone CRISPR gene-editing. The study claimed to find over 100 unintended large deletions or insertions in each of the two mice examined, and attributed these alterations to the CRISPR gene-editing process.

Within 24 hours of the research being published, stocks in several major biotech companies fell up to 14 percent. Two of these companies have since published open letters to the journal Nature Methods, criticizing the veracity of the study.

Editas Medicine, in a letter co-signed by 13 of the company's scientists, claimed the conclusions drawn from the study could not be ascribed to CRISPR and any observed mutations were likely present prior to the genome-editing procedure.

A letter from Intellia Therapeutics made similar claims, questioning the study's conclusions and pointing out flaws in the study design. Nessan Bermingham, CEO of Intellia, has even called for Nature Methods to retract the study.

While it is not unexpected to see these letters criticizing the study coming from companies with a financial interest in CRISPR, several independent scientists have also voiced concerns over the findings of the study.

Gaetan Burgio, a geneticist from Australia National University, has been working with CRISPR for several years and was vocal in his skeptical response to the study. He published a comprehensive essay detailing several misgivings around the study. He noted numerous factors as to why the mutations found in the research should not be necessarily attributed to CRISPR.

From an unusual delivery mechanism to a low sample size, Burgio explained the abnormal number of mutations are unlikely to be CRISPR related. He also wrote a scathing critique of the journal itself for publishing what he felt to be dubious research.

"I find absolutely astonishing this paper got published in Nature Methods," Burgio writes. "This is a terrible paper and as a reviewer I would have dissmiss (sic) it from the first round of review. This is a worrying trend from 'high impact' journals to promote the hype over good science. The publication of this paper is clearly a failure in the peer review process."

Other CRISPR specialists including Dr Lluis Montoliu, from the Spanish National Centre for Biotechnology, and Matthew Taliaferro, from MIT, backed up Burgio's concerns, tweeting doubts about the study's conclusions.

With such a public, and vociferous backlash, focus has now turned to the journal Nature Methods. If the original study's findings are so easily called into question then, as Gaetan Burgio noted, the question over how this article was published in the first place needs to be answered.

A spokesperson from the publishing company behind Nature Methods commented to MIT Technology Review, "We are carefully considering all concerns that have been raised with us and are discussing them with the authors."

With human trials involving CRISPR already underway, it is no surprise that a study like this has kicked up such a controversy. There has already been plenty of time and money invested in CRISPR, so it's not unexpected to see such vociferous criticisms of a study claiming flaws in the technology.

What is surprising is the broad spectrum of critics pointing out such a volume of flaws in the study. Only time will tell whether it is ultimately discredited or vindicated.