It is hard to overstate how much the CRISPR world exploded following Zhang’s breakthrough paper in January 2013. Before then, a few dozen CRISPR-related papers were published each year. In the three years following that report, the number rocketed to 3,000. As researchers worldwide gleefully embraced the technology, the competition for prizes and patents intensified.
In January 2016, Cell published an extraordinary perspective by Lander. Titled “The Heroes of CRISPR,” Lander framed this lengthy article as an educational essay paying tribute to the dedicated unsung heroes who had paved the way for the CRISPR gene-editing revolution.3 He wrote eloquently, more in the style of a New Yorker piece than a typically turgid scientific review.
But some suspected that Lander was using this platform to spin the accomplishments of his protégé. The cues were apparent from the opening line of the abstract: “Three years ago [in 2013], scientists reported that CRISPR technology can enable precise and efficient genome editing in living eukaryotic cells.” From the outset, Lander was charting the birth of the CRISPR revolution as Zhang’s landmark paper. Lander appropriately paid tribute to many figures but downplayed the contributions of Charpentier and Doudna, devoting just a few paragraphs to their work compared to a page-and-a-half extolling the life and work of Zhang.
The article also included a map of the world, with the locations of the CRISPR pioneers marked in colored dots, from Japan to Lithuania, Germany to Spain, Boston to Berkeley. But there was something askew. On a closer look, the Atlantic Ocean had been magically compressed, while Greenland and Iceland had been erased completely.II As a result, the map conveniently centered on Cambridge, Massachusetts, home of the Broad.
Readers also objected to the fact that Lander declared no conflicts of interest: he had no direct financial stake in Zhang’s work but the Broad was embroiled in a fierce patent dispute with Doudna and Charpentier’s respective institutions (see chapter 13). Cell Press, the publisher, said it did not require authors of commentaries to declare any conflicts of interest, although in the circumstances, it wouldn’t have hurt either the editor or author to have included such a note.
The critics pounced. Michael Eisen, an outspoken geneticist and a friend of Doudna’s, posted a scathing rebuttal, branding Lander “The Villain of CRISPR.” “There is something mesmerizing about an evil genius at the height of their craft,” Eisen wrote.4 Lander’s masterwork was “so evil and yet so brilliant that I find it hard not to stand in awe even as I picture him cackling loudly in his Kendall Square lair, giant laser weapon behind him poised to destroy Berkeley if we don’t hand over our patents.” He accused “the most powerful scientist on Earth” of scheming to help Zhang win a Nobel Prize and give the Broad Institute the inside track on “an insanely lucrative patent.”
Such a clapback among prominent scientists is both rare and fascinating. Eisen’s objection to Lander’s history lesson was nothing personal against Zhang but a judgement of what he considered the most crucial discovery in the CRISPR timeline. If there was a pivotal step in bringing CRISPR to the genome editing party, Eisen said, it was Doudna and Charpentier’s 2012 demonstration that CRISPR could be adapted into a molecular scissors following a decade of heroic foundational work. “Once you have that, the application to human cells, while not trivial, is obvious and straightforward,” Eisen declared.
Piling on was science historian Nathaniel Comfort, who labeled Lander’s essay a “Whig history” of the CRISPR saga—an effort to rationalize the status quo and spin the establishment’s point of view. Comfort was pleased to see Mojica and others receive some overdue credit. “Too often the early players and the scientists at lesser-known universities become lost to history altogether. But we should also recognize how Lander uses those actors to create a crowd in which to bury Doudna and Charpentier.”5
Not surprisingly, neither Doudna nor Charpentier were too thrilled with Lander’s account. “The description of my lab’s research and interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication,” Doudna said.6 Charpentier added that the description of her group’s contributions was “incomplete and inaccurate.”III By this time, however, the two women were receiving ample opportunities to give their own accounts of the story.
George Church wasn’t thrilled with the media narrative, either. After all, his paper appeared in the same issue of Science as Zhang’s, but as the Nobel Prize is awarded to a maximum of three recipients, there is a tendency during prize season to search for the holy trinity. In CRISPR circles, that trio was usually Charpentier, Doudna and Zhang. Church aired his frustration a couple of years later to The Scientist. He wasn’t trying to take anything away from Doudna and Charpentier, pioneers who deserved credit for getting gene-cutting to work. “The spark that [they] had was that CRISPR would be a programmable cutting device.” But getting it to do precision editing was another matter. Indeed, Church argued that his human cells were a more accurate system than the aberrant culture cells that Zhang’s group had used.IV In terms of credit, Church said, “you could say two and two. But to oversimplify that back down to three is like consciously omitting one.”7
Church later told me it wasn’t so much to cement his own place in history, whatever that matters, but the “egregious omission” of the postdocs who did the work—his and others. “I felt that Martin Jínek had been left out of the story, and Prashant Mali, and Luhan Yang, and Le Cong. You just never heard of them.”8
Doudna did not make a habit of putting on her “out of office” email message but her travel schedule soon became packed with prize ceremonies, media interviews, and keynote lecture invitations. Her talks were polished and accessible, generously crediting Charpentier and her colleagues. Despite her rapidly growing profile, she wasn’t thinking about writing a book until she received a surprise invitation from Max Brockman, the son of a leading New York literary agent, John Brockman. Doudna’s initial proposal, co-written with graduate student Samuel Sternberg, was a little dry, with references to Thomas Kuhn’s The Structure of Scientific Revolutions. As Sternberg admitted later: “What kind of person on the street was going to read that?”9
But public interest was intensifying. That was driven home when Sternberg accepted an invitation to breakfast at a Mexican restaurant in Berkeley from a woman who asked if he would be interested in starting a company to deliver CRISPR gene editing to future parents. Sternberg had no interest in that particular venture, but it supported giving the proposal another shot. The result was A Crack in Creation, published in spring 2017, which tells Doudna’s personal story, although she deftly sidestepped any commentary or controversy on the patent dispute.10