“Heroes of CRISPR” Disputed

Critics have harsh words for the Broad Institute’s Eric Lander and Cell over a recent perspective piece describing the history of CRISPR.

By | January 19, 2016

In a perspective piece published in Cell this week (January 14), Eric Lander, president and director of the Broad Institute of MIT and Harvard, outlined the history of achievements behind the precision gene-editing technique known as CRISPR. The problem is, the Broad is a copatentee embroiled in an intellectual property battle being investigated by the US Patent and Trademark Office (USPTO). And Lander’s Cell paper does not disclose the potential conflict of interest.

Furthermore, Jennifer Doudna of the University of California, Berkeley—who, along with Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Germany, is currently locked in the patent dispute with the Broad’s Feng Zhang and colleagues—called Lander’s account “factually incorrect” in a January 17 PubMed Commons comment. Doudna wrote that Lander’s description of her lab “and our interactions with other investigators . . . was not checked by the author and was not agreed to by me prior to publication.”

In a statement emailed to The Scientist, Lander said he did disclose “both real and perceived conflicts to the journal,” including that his institution has CRISPR patents and patent applications. Lander also said he emailed Doudna in mid-December, requesting that she fact-check material to be published in his perspective.

“She confirmed the information about her personal background, but said she did not wish to comment in any way on historical statements about the development of CRISPR technology,” Lander wrote. “In writing the article, I received input about the development of CRISPR from more than a dozen scientists around the world. Dr. Doudna was the only one who declined, which is unfortunate. Nonetheless, I fully respect her decision not to share her perspective. I also understand that there will be varying perspectives.”

Doudna told The Scientist that Lander did contact her on December 18, but said that he only shared an excerpt of the article. “He refused to share with me many sections concerning my lab’s research,” Doudna wrote in an email. “I never saw the entire piece until publication, and have the email correspondence to prove it. Dr. Lander should name the other scientists he received input from.”

One of those scientists was George Church, who has appointments at Harvard and the Broad and has collaborated with Zhang and others on CRISPR research. “Eric [Lander] asked me some very specific questions on 14-Dec and I offered to fact check (as I generally do),” Church wrote in an email to The Scientist. “He sent me a preprint on 13-Jan (just hours before it came out in Cell).  I immediately sent him a list of factual errors, none of which have been corrected.”

PubPeer lit up with anonymous comments on the article shortly after it was published. “This is extraordinarily suspect,” one user wrote. “We are in the middle of a CRISPR patent fight, a patent fight frequently referred to as the biggest in biotech history. In the midst of this fight, Cell allows Eric Lander, who is leading an institute embroiled in said patent, decide who to highlight as a hero in these discoveries. At best, untimely, and at worst, propaganda.” Another wrote: “The paper is a bald-faced effort to stake a claim for Zhang, and the Broad stands to profit royally.”

On Twitter, Michael Eisen of the University of California, Berkeley, who on his website discloses his potential conflict when discussing CRISPR and the associated patent dispute, voiced several objections to the piece. Among other things, he wrote, the “most damaging Lander distortion is that all his 'Heroes of #CRISPR' are PIs—what happened to students & postdocs?”

The Scientist reached out to Cell Press but did not receive a response by press time.

Update 1 (January 19): After publication of this article, Church told The Scientist in an email that “as with Jennifer [Doudna], the fact-checking with me was (unnecessarily) very limited. I sent Eric [Lander] corrections early morning on Jan 14, and these have not (yet) been included in the online paper. Basic full fact-checking (as I offered in December) would have caught these earlier and with much less drama. Even at this point, these are not hard to fix, and would make a big difference.”

Among the facts Church is disputing is that he was “aware of Zhang’s efforts” when his team “set out to test crRNA-tracrRNA fusions in mammalian cells,” as Lander wrote.  Furthermore, Church noted, “Prashant Mali and Luhan Yang did the testing”—not he.

Overall, Church told The Scientist,“Eric’s Cell paper systematically misses the important role of many younger researchers (heroes).”

In an email to The Scientist, Lander confirmed that Church responded to the initial fact-check correspondence. Later, “when the review appeared, he [Church] sent me some factual questions that we agreed to discuss,” Lander added. “I am glad to do so.”

Cell Press has not yet responded to questions from The Scientist about the editorial handling of the article.

Update 2 (January 19): In a statement sent to The Scientist, Cell Press spokesperson Joseph Caputo reiterated that Lander provided a conflict-of-interest (COI) statement and that, while Lander had institutional conflicts to declare, he did not have any personal financial conflicts. The publisher’s COI policy does not apply to institutional conflicts, Caputo said, so Cell did not publish a statement. “We are currently evaluating our COI policy to determine if we should extend it to include institutional COIs going forward,” Caputo wrote in an email. “I can’t comment on whether there will or won’t be changes to Dr. Lander’s piece.”

Update 3 (January 20): In a comment posted to PubMed Commons, Charpentier said she was not contacted prior to the paper’s publication. “I did not see any part of this paper prior to its submission by the author. And the journal did not involve me in the review process,” Charpentier wrote. “I regret that the description of my and collaborators’ contributions is incomplete and inaccurate.”

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Comments

Avatar of: dumbdumb

dumbdumb

Posts: 48

January 19, 2016

I would say, shame on Cell for publishing such article. What was possibly the last truly high qualty scientifc publication appears to have given up.

It would be interesting to compare the CRISPR saga with what happened with the PCR technology. Probably, there are many analogies.

January 19, 2016

The sad story about this paper is that not many are talking about the early and real pioneers of the CRISPR field and everyone is obsessed about Doudna vs. Zhang. If you read this and other CRISPR papers, neither Doudna nor Zhang contributed to the identification of the three essential components of the CRISPR-Cas9 system.

Doudna even went on to claim that she invented CRISPR-Cas9 in her TED talk even though her contribution is to convert a 3-component system to a 2-component system—an engineering feat at best. Doudna & Zhang are more like Steve Jobs while the early pioneers are more like Wozniak and others.

I really hope the Nobel committee recognizes the early contributors–these scientists were given a hard time by the scientific community (their papers were rejected!) and the scientist are again doing a disservice by willfully ignoring early pioneers and obsessing about the engineering feats of Doudna and Zhang.

January 19, 2016

I noted that George is throwing Eric under the bus...  I have the beginning of a joke, and need help finishing it:

"George Church, Craig Venter, and Eric Lander walk into a bar...."

I'm thinking in terms of an explosion caused by too much ego in one place...

Avatar of: Kathy Barker

Kathy Barker

Posts: 32

Replied to a comment from Stem Cell Scientist made on January 19, 2016

January 19, 2016

It is all quite funny and sad, just a few weeks after the Scientist article about Church in which he puts foward as important in CRISPR- Church.

Avatar of: Prakasha

Prakasha

Posts: 3

January 20, 2016

"The Scientist reached out to Cell Press but did not received a response by press time." - this needs correction, i guess. i am not a native speaker...

Avatar of: tvence

tvence

Posts: 879

Replied to a comment from Prakasha made on January 20, 2016

January 20, 2016

Thanks for catching our typo, Prakasha. It's fixed.

All the best,

Tracy Vence

News Editor, The Scientist

Avatar of: xtsam

xtsam

Posts: 2

January 20, 2016

From when adapation and application equal to invention?

Avatar of: zackcc1

zackcc1

Posts: 2

January 20, 2016

 

 

With CRISPR, it is better for it not be patented but remain open source.  We should learn the lessons of other technologies that were patented "too early" and this resulted in poor development until the patents ran out.   The original patent on the car is one example.  Similarly, when CT/MRI imaging technology was developed, it was hailed as major technology which could allow the cure for cancer.  This has not been realized, but ironically it is not entirely a false statement.  The majority of solid cancers CAN be cured if they could be identified when they are small and growing (1-2 cm).  MRI is perfectly capable of picking up such small nodules if it was cost-effective to use frequently enough.  Unfortunately, decades after its development, MRI are bulky unecessarily expensive machines with poor development, although there are many possible improvements and miniaturizations which have yet to be explored (SQUID, etc).  One wonders whether it would almost be better when there is a very promising new technology not to rush to patent it, but rather allow the government to buy off the patent from these various "claimers of rights" and make it open source for rapid low cost development.  If the "internet" had been similarly patented during its inception by ATT or some other big corporation, we most assuredly would have been offered a watered down, poorly developed, and overly monetized system that would probably have ultimately failed and then been shelved...and no one to take up the torch under the fear of patent infringement.  Its just not right to patent CRISPR or many other such promising technologies, particularly when the lionshare of effort that went into their development was taxpayer funded.

 

 

 

 

 

Avatar of: MRDG

MRDG

Posts: 1

January 22, 2016

Readers should take a look at two accounts of the history of CRISPR
that have appeared in Journal of Biosciences. The first 
dates from a while ago. They are by the historian of science Michel Morange. 
They offer a different perspective to that of Lander.  

The pieces can be found at 
http://www.ias.ac.in/public/Downloads/jbsc_040_02_0221-0223.pdf and
http://www.ias.ac.in/public/Downloads/jbsc_040_05_0829-0832.pdf.
Avatar of: MainQuestion

MainQuestion

Posts: 1

January 31, 2016

The main question I have is why everyone diminishes contribution of Siksnys? Is it because he is not from famous institution? Is it possible that his paper was intenionally delayed by PNAS, so that Berkely group publishes there's paper in Science (in 20 days !!!). 

Just wondering what others think? 

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