Science

The CRISPR controversy: Scientists skeptical over recent critical study

The findings of a recent study on the CRISPR gene editing technique have been called into question
The findings of a recent study on the CRISPR gene editing technique have been called into question

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.

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11 comments
Bob
This should be a lesson to all who think science is pure and noble. Science is mostly funded for profit and war and as such has little tolerance for criticism. In some cases where potential profit is concerned it can be as corrupt as politics. This should have been investigated in greater depth before going to human trials. Hopefully, the problems can be worked out. We are still pretty ignorant about the role of different genes and how they react.
MerlinGuy
Instead of arguing about whether or not the study is valid, I would think it would behoove the 'scientists' from the massive number of colleges and companies to immediately do their own study. If CRISPR is actually causing a large number of unaccounted mutations then the sooner we learn the truth the better. If this is just a quack paper with no substance then this is a great opportunity to prove the safety of CRISPR. This is not a technology that we ignore possible problems with.
Mzungu_Mkubwa
Another example of vested interest having potentially dangerous consequences. The almighty dollar will triumph once again, and those victimized will be shuffled to a 4th page margin paragraph. Haven't we learned our lesson with big pharma already?
CharlieSeattle
The MIC is rushing into this because they really can without caring to ask if they really should.
ljaques
Count me in the skeptical bleachers with regard to the safety of CRISPR. Genetic scientists haven't yet begun to unravel the mysteries of standard genes, let alone recessive genes. With the science still in the "the world is flat" stage, I liken scientific gene editing to a precocious 5 year old boy stumbling into a weapons bunker full of grenades, detonators, C4 charges, and mines thinking "I wonder what this does." and pulling the pin, switching on detonators, and pressing buttons to find out. And that's the _ethical_ scientists. What has Big Pharma flushed down the drain into the waters we humans clean to drink? We can't filter out the pharmacopeia (which flushes out of our systems) at the water plant. And don't get me started on scientists wanting to break the blood-brain barrier. AFAIC, Man isn't mature enough yet to handle this tech.
Tinman_au
I work at a uni, and while I'm not in the field, I know for a fact there are a lot of eye's on this. I'm pretty sure if there is something dodgy about it, it'd be a lot bigger that one outlier study.
christopher
I've had only 1 paper "peer reviewed", but my observation of that process is that it's terrible. The "reviewers" criticize things like spelling and grammar and question irrelevant factors and numerous other things (nb: reviewers are anonymous and we cannot answer their questions!).
In my case, they did not understand my highly-technical work at all, and appeared unwilling to look past a few typos and comprehend the subject matter!
Peer review needs major repair: reviewers should be forced to publish their names and all their opinions, so their reputation is placed on the line, to help them behave appropriately (or at the very least, for observers to point out the duds who can be removed from the process!)
Augure
More and more corrupt science...which is way dangerous than corrupt politics or economics.
Corinne Civish
Seems like the author and editorial board have already made up their minds that the study is invalid, but pretending to take a balanced position. Maybe it just me. I love science. But we've wreaked havoc and irreversible destruction on our planet and it's inhabitants with our "understanding" on nature and it's ways, almost always for profit. While the many benefits of gene editing should be a goal, safety and not proceeding too quickly should be the paramount concern. This to me is akin to tickling the dragon, with potential worldwide horrific repercussions.
RonaldAThomasson
A consensus is being pursued to ensure all skepticism to CRISPR is rebutted and no future studies and/or articles will be funded/published which will impede/damage our CRISPR studies both now and in the future...