Explosive disagreements over the origins of CRISPR, the leading methodology for editing genes, were inevitable. CRISPR has given scientists (and journalists) dizzying dreams of a near-unlimited ability to manipulate the genomes of animals and plants, to change (improve?) existing organisms in almost any way imaginable, and perhaps to invent new ones. Its impact on the life sciences is likely to be immense.
Not to mention that the origins story will be critical in bestowing the Nobel Prize that is pretty much a sure bet for CRISPR. Not to mention that the origins story will be critical for bestowing the immense amounts of money–billions, perhaps–that will flow to whoever has the legal right to license other scientists to use CRISPR. This has turned into an epic patent battle.
But there’s an additional twist to the disputes about CRISPR origins–especially now that we know how sexist acts large and small have systematically downgraded and ignored the contributions of women scientists. Are Emmanuelle Charpentier (now at the Max Planck Institute for Infection Biology in Berlin) and Jennifer Doudna (UC-Berkeley), who were indisputably present at the beginning, being written out of CRISPR history?
That’s what Joanna Rothkopf argues at Jezebel in a post headed “How One Man Tried to Write Women Out of CRISPR, the Biggest Biotech Innovation in Decades.” She is talking about Eric Lander’s Jan. 15 paper in Cell (not open-access, of course.) It is headed “The Heroes[sic] of CRISPR.”
Rothkopf’s summation: “What Lander failed to recognize in his article—and what many of his colleagues and commenters on the piece have recently condemned him for—is that his institute is currently involved in a billion-dollar patent dispute with the University of California’s Jennifer Doudna and Emmanuelle Charpentier of the Helmholtz Center for Infection Research in Germany, which played a vital role in developing CRISPR-Cas9. Not only did the Cell paper fail to disclose the potential conflict of interest, it significantly minimized the role of Doudna’s lab in advancing the technology.”
THE HEROES (AND VILLAIN) OF CRISPR
Lander, the hugely influential mathematician-turned-biologist, has been a top dog in genetics forever. His most recent admirable accomplishment is to have built the former startup Broad Institute, the Harvard- and MIT-affiliated research institution he heads, into a research powerhouse in just a decade.
The highest-profile blast against Lander’s Cell paper came in a post from Michael Eisen at his blog It is NOT junk. Eisen’s was also the most eloquently indignant critique, even though he lapsed occasionally into simple name-calling. (In one of a barrage of tweets, Eisen called Lander a scum-sucking POS. I am cravenly abbreviating the commonplace barnyard epithet, which Eisen did not, because I fear the displeasure of my masters. Michael’s brother Jonathan Eisen has Storified a selection of tweets, not including that one.)
Unfortunately, as Eisen himself explained, he has a potential conflict of interest too. His lab is at Berkeley and stands to benefit from CRISPR money if Berkeley wins the patent fight. He would not personally benefit, and in fact argues against a patent to anybody for CRISPR because “it is a disservice to science and the public for academic scientists to ever claim intellectual property in their work.”
Calling Lander “at once so evil and yet so brilliant,” Eisen details some anti-Lander beefs of long standing in addition to savaging the Cell paper. He concludes that the paper not only subtly elevates the contributions of Broad’s Feng Zhang to foundational CRISPR research, it also tears down the contributions of Doudna and Charpentier by portraying them only as two among many researchers doing early CRISPR work.
The facts of the matter: Doudna and Charpentier and their colleagues were first to publish (in June 2012) how to use CRISPR to cut DNA easily at specific points, while Zhang and his colleagues showed (in January 2013) how to adapt CRISPR for use in human cells.
At The Niche, Paul Knoepfler goes for data to show how Lander slanted the evidence. The paper’s word cloud reveals that “Zhang” is larger than “Charpentier” and larger still than “Doudna.” Knoepfler also just adds up the number of mentions. “Zhang” appeared nearly twice as often (15 times) as “Doudna”(8) and significantly more often than “Charpentier” (11).
At Technology Review, Antonio Regalado has written something of a plague-on-both-your-houses piece. He says, “to anyone who has delved into thousands of pages of patent office documents, Lander’s CRISPR tale is clearly an attempt to back up Broad’s patents, granted based on the surprise claim that Zhang hit on the technology in 2011 on his own, unbeknownst to anyone outside the institute, and before Doudna’s work was ever published.” If so, Zhang did not publish at the time.
Regalado calls Lander “a little Machiavellian,” but notes that Doudna is no shy violet either. In a TED talk “she said she and a colleague ‘invented a new technology for editing genomes called CRISPR-Cas9’—a claim of cartoon simplicity that makes even those in her camp cringe.”
Historian of science Nathaniel Comfort charges at Genotopia that Lander’s paper is an example of “whig history,” the use of history as a political tool. Comfort details how Lander uses writing techniques to seem generous and all-inclusive while actually downplaying the work of Doudna and Charpentier.
Sharon Begley’s piece “Why Eric Lander morphed from science god to punching bag” at Stat struck me as being, tonally at least, a little more friendly to Lander than absolutely necessary. (Also the many flattering photos of the subject, which were way more, and way larger, than necessary. But I doubt that was Begley’s doing.) I much enjoyed her background tales of how anger at Lander’s high-handedness has been building over the years. Very annoying when someone so irritating is undeniably brilliant, talented, successful, etc.
FOLLOW THE MONEY TO THE PATENT OFFICE
At Fortune, Laura Lorenzetti explains details of the patent dispute, incuding why the US Patent Office did something it hardly ever does: launch an official “interference” proceeding. Which means that “a panel of three patent judges will determine whether Zhang should hold onto the rights to the foundational CRISPR patent, as well as other patents related to the technology.”
This being a patent war, details are brain-numbingly intricate. But On Science Blogs aims to serve all science nerds, so here’s Jacob Sherkow to explain it all at the Stanford Law School Law and Biosciences Blog.
To get an idea of the financial stakes, read Farai Chideya’s post at FiveThirtyEight. The target sum for the coming initial public offering of Editas Medicine, which Zhang co-founded, is $100 million. This on top of the $160 million investors have already given Editas.
The stakes go way beyond the patent fight and commercial ventures that involve Charpentier, Zhang, and Doudna. Katrina Megget describes how pharma giants like AstraZeneca, other pharmas, and several startups have plunged into CRISPR. Her post appeared in Chemistry World and was reprinted by Scientific American.
Chideya points out a factor that financial pieces about CRISPR often fail to mention. CRISPR applications, especially potential direct applications to the human genome, are rife with ethical and policy issues such as the morality of editing human embryos. Policy decisions by governments will determine what researchers can do with gene editing techniques, and may impose limits on them. Although, given the potential rewards of CRISPR research, some of which may accrue to governments as well as citizens, maybe not.
CONFLICTS OF INTEREST LEAD TO WHIG HISTORY
A final point especially salient for those of us professionally concerned with the conduct of science. The Lander paper brouhaha is a high-profile illustration of a topic considered here at On Science Blogs just last week: how badly science in general, and scientific journals in particular, handle conflict-of-interest issues.
The issue here last week was a paper published last fall by the British Medical Journal. The topic was the new US Dietary Guidelines, in particular their stand against saturated fat. The paper’s author is Nina Teicholz, author of The Big Fat Surprise: Why Butter, Meat, & Cheese Belong in a Healthy Diet.
The BMJ didn’t mention the book in promotional material it sent to the media. Teicholz says that’s the BMJ’s policy. Why is a mystery to me, and I hope complaints about a topic so obviously relevant to conflict-of-interest will cure the journal’s cluelessness. But this not-very-worldshaking issue occasioned an extended dispute, carried out most recently in the comments to my post, with comments by nutrition researcher Yoni Freedhoff and responses by Teicholz.
Retraction Watch’s Adam Marcus and Ivan Oransky explored journal conflict-of-interest cluelessness about the Lander paper at Stat. Cell’s COI rules cover only personal COI issues, not institutional ones. So the journal included no COI statement even though Lander had told journal editors that Broad was a principal in the CRISPR patent dispute. Marcus and Oransky propose that journals should publish author COI statements in full and let readers decide whether the author’s affiliations matter.
I’m all for full disclosure of COI statements, although it seems to me the issue with the Lander paper goes way beyond simple disclosure of his institution’s stake in the CRISPR origin story. Why do you suppose Cell’s editors convinced themselves that it was a good idea to publish CRISPR history as written by one of the principals?
Hard to avoid the suspicion that they were drawn to an author so illustrious and clickworthy. Also, in terms of promotion of the journal, Lander’s paper has been a huge success.
But this is, as Comfort points out, inevitable whig history. It’s bound to be biased. A completely even-handed account of CRISPR’s early days from someone heavily invested in it would be a miracle of superhuman objectivity. Beyond, I suspect, even Lander’s obvious talents.