Controversial CRISPR history sets off an online firestorm
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It isn’t often that biology finds itself in the same galaxy of the Twitterverse as, say, “The Bachelor,” but on Tuesday morning CRISPR did. The trending topic was sparked by a recent “Perspective” in Cell limning the history of the gene-editing technique.

But this history was loaded, as history often is. CRISPR’s history could determine the outcome of a bitter patent fight worth many millions of dollars, and this version was written by the director of the institute that stands to reap some of those millions.

The essay has triggered a deep controversy over disclosing conflicts of interest and the close ties between journals and certain research groups.

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The Perspective’s author, Eric Lander, is president of the Broad Institute, the home institution of biologist Feng Zhang. Zhang won key CRISPR patents in 2014. But the University of California has challenged those patents, arguing that research led by UC Berkeley biochemist Jennifer Doudna preceded Zhang’s. The US Patent and Trademark Office agreed last week to hear those “interference” claims, setting up a winner-take-all intellectual property brawl that will begin in March.

Despite the Broad’s involvement in the patent fight, however, Lander’s Perspective includes no “conflict of interest” statement. That prompted one Toronto-based biochemist to ask on Twitter, “No conflict of interest declared? Broad can potentially gain billions from patent.”

In a statement emailed to STAT, Lander said, “As Cell has stated, I disclosed both real and perceived conflicts to the journal,” including that he has “no personal financial interest (which is the subject of Cell’s COI statements) in CRISPR technology” and that “Broad, MIT and Harvard have patents and patent applications.”

Dom Smith/STAT CRISPR is a tool that acts as a microscopic pair of scissors with the ability to slice DNA.

A problematic history

More substantively, Doudna and others disputed key parts of Lander’s history of CRISPR, which he said began in 1989 “in the Mediterranean port of Santa Pola on Spain’s Costa Blanca, where the beautiful coast and vast salt marshes have for centuries attracted vacationers, flamingoes, and commercial salt producers.”

Although scientists in Spain, Lithuania, and elsewhere made important contributions to the development of CRISPR, the key dispute is between Doudna and her collaborator Emmanuelle Charpentier, now at the Helmholtz Centre for Infection Research in Germany, on one side, and Zhang on the other. Over the weekend, in a comment posted to PubMed on Sunday night, Doudna said that although a Cell editor had claimed that Lander had “engaged in substantial fact checking directly with the relevant individuals,” in fact “the description of my lab’s research and our interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication.”

Lander said he was “disappointed to read Dr. Doudna’s comment,” and that he had emailed her in mid-December “specifically asking her to fact-check material to correct or improve it,” but that she said she “did not wish to comment in any way on historical statements about the development of CRISPR technology.”

Doudna, who is on a panel with Vice President Joe Biden at the World Economic Forum in Davos Tuesday, told the industry publication The Scientist that although Lander did contact her last month, “he refused to share with me many sections concerning my lab’s research.”

Details disputed

Doudna wasn’t the only scientist critical of Lander’s account. Harvard biologist George Church, who also has an appointment at the Broad, told STAT that he, too, disputes some important details. He received a draft of the paper last Wednesday and sent corrections early the next morning, before the paper was posted on Cell’s website, “but those have not (yet) been included in the online paper.”

Church takes issue with Lander’s failure to mention junior scientists who contributed to the development of CRISPR, and disputes that Zhang’s team made a key technical breakthrough that “solved the problem” that had hampered the use of CRISPR to edit genomes. In fact, the Church lab’s own CRISPR paper, published in the same 2013 issue of Science as Zhang’s, “did mention this [solution],” he told STAT. Nor was Church aware, he said, that Zhang was testing particular genome-editing molecules in mammalian cells, as Lander asserted; instead, Church’s lab did this without knowing that a competing lab was pursuing the same goal, he said.

Lander told STAT he “had a long conversation with Dr. Church” while writing his account “and later called him to check facts. When the review appeared, he sent me some factual questions that we agreed to discuss.”

An online firestorm

Until a few years ago, reactions to scientific publications had to wait weeks if not months to be published in a journal, but thanks to websites like PubPeer, responses to this paper appeared nearly instantly.

Because of the Broad’s involvement in the CRISPR patent fight, one PubPeer contributor said, “Lander and Cell should have disclosed the clear conflicts that Lander has on this topic which would have allowed people not in the loop to better assess the objectivity, or lack of it, in this piece.”

It was “at best, untimely, and at worst, propaganda,” and “a bald-faced effort to stake a claim for Zhang, and the Broad stands to profit royally,” according to other commenters. There were digs at Cell’s ties to Harvard and MIT, with another person saying, “it does not surprise me at all that Cell volunteers as a MIT community propaganda journal.” For instance, one former editor at a Cell Press journal now holds a position as “scientific advisor” at the Broad.

In a statement, Cell spokesman Joseph Caputo said that “attention to balance, fairness and accuracy were front and center for both the editors and the author throughout the consideration process. The peer reviewers were specifically asked to comment on balance and fairness and any comments they provided back were addressed in revision. In addition, the author engaged in substantial fact checking directly with the relevant individuals.”

On Twitter, biologist Michael Eisen of the UC Berkeley, who always discloses that his institutional affiliation can give the appearance of a conflict of interest on CRISPR, called Lander’s article “science propaganda at its most repellant.” He, too, questioned the absence of a conflict-of-interest disclosure.

Lander co-chairs President Barack Obama’s panel of science advisors, which makes him “the most powerful person in science,” Eisen said on Twitter. That made it all the worse that his version of CRISPR history is “manifestly self-serving” and “horrible for science.”

In a statement on Tuesday, Lander said that he recognizes “that opinions — including of those involved [in CRISPR] — will sometimes differ.”

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