Discovering CRISPR

Eric Lander tells his version of the story. Here is his take — which might or might not be reasonable — on lessons learned from the story:

The most important [lesson] is that medical breakthroughs often emerge from completely unpredictable origins. The early heroes of CRISPR were not on a quest to edit the human genome—or even to study human disease. Their motivations were a mix of personal curiosity (to understand bizarre repeat sequences in salt-tolerant microbes), military exigency (to defend against biological warfare), and industrial application (to improve yogurt production).

The history also illustrates the growing role in biology of “hypothesis-free” discovery based on big data. The discovery of the CRISPR loci, their biological function, and the tracrRNA all emerged not from wet-bench experiments but from open-ended bioinformatic exploration of large-scale, often public, genomic datasets. “Hypothesis-driven” science of course remains essential, but the 21st century will see an increasing partnership between these two approaches.

It is instructive that so many of the Heroes of CRISPR did their seminal work near the very start of their scientific careers (including Mojica, Horvath, Marraffini, Charpentier, Vogel, and Zhang)—in several cases, before the age of 30. With youth often comes a willingness to take risks—on uncharted directions and seemingly obscure questions—and a drive to succeed. It’s an important reminder at a time that the median age for first grants from the NIH has crept up to 42.

Notably, too, many did their landmark work in places that some might regard as off the beaten path of science (Alicante, Spain; France’s Ministry of Defense; Danisco’s corporate labs; and Vilnius, Lithuania). And, their seminal papers were often rejected by leading journals—appearing only after considerable delay and in less prominent venues. These observations may not be a coincidence: the settings may have afforded greater freedom to pursue less trendy topics but less support about how to overcome skepticism by journals and reviewers.

Finally, the narrative underscores that scientific breakthroughs are rarely eureka moments. They are typically ensemble acts, played out over a decade or more, in which the cast becomes part of something greater than what any one of them could do alone.

Warning: some people on Twitter are saying this article is basically PR for Lander’s Broad Institute, where Feng Zhang did his CRISPR work. Zhang is currently in a patent dispute over CRISPR with Jennifer Doudna.

ETA: Doudna comments on the article. And here is a “Landergate” link list.

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