In 1974, a former Nature editor named Benjamin Lewin launched a journal called Cell, devoted to “the molecular biology of cells and their viruses.” Whereas Nature and Science printed on gossamer-thin paper the consistency of a toilet roll, Cell looked and felt like a fashion magazine for science, with a thick cover, sensual glossy paper, and a heretical Helvetica logo and typeface. Whereas Nature editors would typically squeeze authors down to fewer than 1,000 words for their reports, Lewin gave scientists free rein to lay out and discuss their results without arbitrary page limits. And Lewin, who authored a string of successful textbooks on genetics, knew the science and befriended the scientists. He set up shop in Harvard Square, where top scientists from Harvard and MIT would often hand deliver their latest manuscripts. And although Cell was a biweekly publication, in the ultracompetitive world of molecular biology, Lewin routinely scooped his rivals. In 1990, someone composed a Cell parody15 and distributed it by fax. It was called Cool.I Lewin sold his company Cell Press to the Dutch publishing giant Elsevier in 1999 for more than $100 million.
Šikšnys was proud of his Cas9 results, which he concluded “pave the way for the development of unique molecular tools for RNA-directed DNA surgery.” He submitted the paper, with Barrangou and Horvath as co-authors, to Cell in March 2012, but soon regretted the decision. Within a week, the editor had rejected the paper without consulting any outside experts, doubtful that the story was of “sufficient general interest.” Šikšnys was upset. “We thought that it was a big thing because we showed in this paper that in principle you can reprogram this Cas9 to [cut] any sequence.” He resubmitted to Cell’s sister journal, Cell Reports—a notch lower on the prestige pole—but Cell’s song remained the same. The clock was ticking.16
By now it was May: Šikšnys resubmitted to the Proceedings of the National Academy of Sciences—a famous journal but lacking the wow factor of the CNS glamour journals. He addressed the cover letter to a member of the editorial board whom he felt would have the most expertise to appraise his manuscript: one Jennifer Doudna. But by the time his revised paper was finally published17 in September 2012, Šikšnys was yesterday’s news. It was an important paper in its own right, but didn’t have the single-guide RNA that Jínek had developed. His results were a day late and a dollar short, and while the experiments were conducted around the same time as (if not before) Jínek, the belated publication date made the study look merely like a confirmation of the Doudna-Charpentier breakthrough.
“These two papers, if you look side by side, look nearly identical,” Šikšnys told me. “The only thing I think that they showed [beyond our paper] is that they can use this single-guide RNA.” Unfortunately, PNAS took more than three months to review and publish the report. The rejection by Cell in itself was not a problem, says Horvath. “The problem appeared when we saw the [Jínek et al.] Science paper!” Would history have been different if his paper had been published in Cell? Horvath shrugged: “Nobody knows,” he said. “Nobody will ever know.”
Over the past few years, the CRISPR narrative has been shaped around the dream team partnership between Charpentier and Doudna. As the profile and fame of the two women grew, Šikšnys was, except for CRISPR insiders, the forgotten man. That began to change following an insightful article in WIRED by Sarah Zhang, who spotlighted the Lithuanian’s lament.18 Šikšnys earned some belated international recognition when he shared the 2018 Kavli Prize with his two illustrious peers.
After their “immortal” 2012 study, the transatlantic collaboration between Charpentier and Doudna devolved naturally. Jínek was busy juggling his research with job interviews. Charpentier was relocating from Sweden to Berlin. Chyliński was writing up his PhD thesis. Charpentier joined the Berkeley team on a follow-up report in 2014, but all good things come to an end. “We didn’t decide to end the collaboration,” Jínek recalls. “I’d enjoyed it immensely. We made a really good team.”
After almost six years with Doudna, Jínek took a faculty position in Zurich in early 2013, where he continues to study the finer details of Cas9 and other DNA-cutting enzymes. In 2016, he won a prestigious Swiss prize for young biochemists, named after the physician Friedrich Miescher, the father of DNA. In 1868, Miescher set up a lab in Tübingen Castle, where he studied white blood cells in pus isolated from surgical bandages collected from a nearby clinic. Miescher extracted a substance from the cell nuclei that he first described in a letter in February 1869. He dubbed the substance, which “[does] not belong to any known type of protein,” nuclein.19 Almost 150 years later, Jínek won the Miescher Prize for his seminal role in laying the groundwork for editing nuclein.
And yet, Jínek’s vital contribution to the CRISPR story remains underappreciated. Jínek is humble to a fault, not one to draw attention to himself. When he was asked after a lecture in Germany what he considered the keys to his breakthrough, he offered three reasons. First was the old “we stand on the shoulders of giants” quote.II Nobody does science in a vacuum, he said. Second was stressing the value of curiosity, the fundamental importance of basic research, and the freedom to pursue the unexpected. Jínek’s goal with Doudna was simply to understand how RNA-targeting enzymes work. “I trained as a structural biologist. I think very deeply about how molecules work,” he said. “I get very excited when I see molecules like this!” he said, gesturing to a cartoon of Cas9 and drawing laughter.
Some politicians take pleasure in cherry-picking federal research grants (“sexual preferences in fruit flies,” etc.) as evidence of wasteful government spending. But the CRISPR gene-editing discovery and the scientific, medical, and economic bounty it has delivered, would not have happened but for public funding of unfashionable research conducted by diehard microbiologists, evolutionary biologists, biochemists, and structural biologists studying CRISPR purely for the thrill of discovery, not the lure of money or prizes. Fundamental and applied research are not “two spigots that can be operated independently,” says Stuart Firestein, a professor at Columbia University. “They are one pipeline, and our job is to keep it flowing.”20
Jínek’s third key to success was serendipity—being in the right place at the right time. “I was very privileged to be in a great academic environment, where we were encouraged to think about our projects, to ask the right questions, to think outside the box, where we had the freedom to explore ideas, to work with other people, exchange ideas, and be quite pragmatic about the way we worked.” The rest, he said, was just hard work: 10 percent inspiration, 90 percent perspiration.
In December 2018, Jínek was invited back to his hometown to give a TED-style talk in his native language.21 He spoke about the rapid progress in DNA sequencing, the $1,000 genome (a shout-out would have been nice!) and the diagnosis of genetic diseases. Now, thanks in part to his work, we have the ability to rewrite genes and transform medicine. To illustrate gene editing, he used a famous Czech nursery rhyme, Skakal pes pres oves (“the dog was hopping over the wheat”). To explain how bacteria capture the signatures of viruses in the CRISPR array, he showed a photo of an ockovaci prukaz—an international vaccination booklet containing stamps for various immunizations. As for germline editing, regulation had to be a global decision, not nations or researchers alone but the entire human race.