A CRISPR Disgrace

It’s rather disappointing to hear about this latest controversy, but sadly not that surprising.

For those new to the field, one of the biggest breakthroughs in genomics in the past few years, if not decades, was the development of CRISPR/Cas9 technology. This used a system discovered in bacteria to create breaks in DNA that could be targeted to specific sequences through the use of small guide RNA sequences. Very good reviews on the technology are here and here (behind paywalls), or Wikipedia does a good free description.

It’s pretty clear that this is a really big deal. There’s been some controversy as to which labs discovered and refined the technique first. This really came to a head when different labs applied for patents around the same time, potentially putting millions of dollars on the line.

The main players in this are Jennifer Doudna at the University of Berkeley, Emmanuelle Charpentier at the Max Planck Institute and Umeå University, and Feng Zhang and George Church based at the Broad Institute (joint between MIT and Harvard). While Doudna and Charpentier filed for a patent earlier, Zhang’s patent was approved first sparking off a series of appeals, culminating in Doudna’s request in April of 2015 for the US patent office to determine which team invented the technique first. For an overview of the controversy, look here

Whether or not you think Zhang’s patent deserved to be approved over Doudna’s, (or whether patents should even be awarded for such government-funded work) it seems inarguable that Jennifer Doudna and her lab played an integral role in the development of CRISPR/Cas9.

Apparently it isn’t that clear to Eric Lander.

Lander, who not coincidentally is the director of the Broad Institute (where Zhang and Church are based), recently published a paper entitled “Heroes of CRISPR”  in the journal Cell. Beyond the oddly grandiose title, Lander ostensibly provides a review of the main players in its discovery, from the first work by the Spanish PhD student Francisco Mojica on identifying the CRISPR repeat, to the vast array of researchers now using CRISPR technology to augment their own research.

In theory, this is a pretty laudable idea. This review does the significant service of bringing to the fore the earlier steps of research into CRISPR, like the work done in the early nineties by Mojica, which can often be overshadowed by research giants like Berkeley and the Broad Institute.

But is it really necessary to do so at the expense of a fellow researcher? I have no doubt that the patent controversy played a significant role in the decision to write the review in such a way as to portray the contributions of Doudna’s group as mostly tangential to the progression of CRISPR understanding. Is it just a coincidence that as Doudna is pushing the US patent office to pursue the question of who actually invented the technology, this review appears that seems to sideline her lab’s contributions?

And perhaps I’m just being cynical, but it doesn’t seem like just a coincidence that the group which suffers in all of this is headed by one of the few female Principal Investigators (PIs). It’s quite a jump to compare the discovery of CRISPR/Cas9 with that of the double helix, but wouldn’t it be terrible if we still haven’t learned from Rosalind Franklin? Here’s hoping not…

On the brighter side, Eric Lander is hardly getting away with it (at least as far as online commentators are concerned). Whether being discussed at length on PubPeer, or being chewed out by the Berkeley professor Michael Eisen on Twitter, it’s been hardly a week since the paper was published and already everyone knows that Jennifer Doudna and her group have been treated poorly.

And even if you agree with Lander’s characterization of the events, as many have pointed out, isn’t this the perfect example of an article that needs a conflict of interest statement? Lander might not be a drug company, but as the head of the Broad Institute he surely has a vested interest in supporting the research carried out in his own backyard.

The most telling comment of any of this, though, comes from Doudna herself on PubMed. Perhaps perfecting the art of getting straight to the point, it’s pretty clear that Doudna is neither impressed nor silenced by Lander’s review.

Screen Shot 2016-01-18 at 8.18.16 PM

I hope we have a response from both Eric Lander and the journal itself in the next few days. I, perhaps uncharitably, don’t expect much. But it’s time that all academics realize that it is unacceptable to try to write rival groups out of keystone reviews, and that they won’t get away with it any more.

It’s time to highlight the heroines of CRISPR as well.

Featured Image from Stuart Caie

 

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