By Eric S. Lander (Cell) – Three years ago, scientists reported that CRISPR technology can enable precise and efficient genome editing in living eukaryotic cells. Since then, the method has taken the scientific community by storm, with thousands of labs using it for applications from biomedicine to agriculture. Yet, the preceding 20-year journey—the discovery of a strange microbial repeat sequence; its recognition as an adaptive immune system; its biological characterization; and its repurposing for genome engineering— remains little known. This Perspective aims to fill in this backstory—the history of ideas and the stories of pioneers—and draw lessons about the remarkable ecosystem underlying scientific discovery.
It’s hard to recall a revolution that has swept biology more swiftly than CRISPR. Just 3 years ago, scientists reported that the CRISPR system—an adaptive immune system used by microbes to defend themselves against invading viruses by recording and targeting their DNA sequences—could be repurposed into a simple and reliable technique for editing, in living cells, the genomes of mammals and other organisms. CRISPR was soon adapted for a vast range of applications—creating complex animal models of human-inherited diseases and cancers; performing genome-wide screens in human cells to pinpoint the genes underlying biological processes; turning specific genes on or off; and genetically modifying plants—and is being used in thousands of labs worldwide. The prospect that CRISPR might be used to modify the human germline has stimulated international debate.
If there are molecular biologists left who have not heard of CRISPR, I have not met them. Yet, if you ask scientists how this revolution came to pass, they often have no idea. The immunologist Sir Peter Medawar observed, ‘‘The history of science bores most scientists stiff’’ (Medawar, 1968). Indeed, scientists focus relentlessly on the future. Once a fact is firmly established, the circuitous path that led to its discovery is seen as a distraction.
Yet, the human stories behind scientific advances can teach us a lot about the miraculous ecosystem that drives biomedical progress—about the roles of serendipity and planning, of pure curiosity and practical application, of hypothesis-free and hypothesis-driven science, of individuals and teams, and of fresh perspectives and deep expertise. Such understanding is important for government agencies and foundations that together invest, in the U.S. alone, more than $40 billion in biomedical research. It is also important for a general public who often imagines scientists as lone geniuses cloistered in laboratories. And, for trainees, it is especially valuable to have a realistic picture of scientific careers, as both guide and inspiration.
Eric S. Lander1,2,3,*
1 Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3 Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA