June 2012 · Berkeley, California, USA (and Umeå, Sweden)
CRISPR-Cas9: the age of writing the script of life
A paper in Science by Jennifer Doudna and Emmanuelle Charpentier turned a bacterial antiviral system into a "programmable" DNA cutter: a guide RNA plus the Cas9 nuclease. Ten to a hundred times cheaper and faster than earlier tools, it turned genome editing into a weekly bench routine. Nobel Prize in Chemistry 2020; first clinical approval in 2023.
In the 1980s, biologists noticed strange repeating sequences in bacterial genomes: short palindromes interrupted by other DNA fragments of similar length. In 2005 the Spanish researcher Francisco Mojica showed that these "spacers" came from viral DNA — they were a form of bacterial immune memory. In 2007 Danish dairy-industry researchers demonstrated experimentally that this CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) system really did protect a bacterium against viral attack. For years the mechanism remained a quiet curiosity — until someone realised the same system could be redirected, in the lab, to cut wherever a researcher wanted.
That moment began with Emmanuelle Charpentier (first in Vienna, then Umeå) and her discovery of a small RNA molecule called tracrRNA in the CRISPR system of Streptococcus pyogenes; this RNA linked the guide RNA to the Cas9 protein, and Cas9 then sliced the DNA sequence the guide pointed to like a knife. In 2011 Charpentier met Jennifer Doudna of Berkeley in a hallway at a conference; by the spring of 2012 the joint teams had simplified the system so far that the tracrRNA and the guide RNA fused into a single 'single-guide RNA' molecule. The paper, submitted to Science on 28 June 2012, said this: design a 20-nucleotide RNA, deliver it with Cas9 into a cell, and you can cut any single site in the genome you choose. Earlier gene-editing tools (zinc-finger nucleases, TALENs) required months of protein engineering per target; CRISPR-Cas9 reduced this to a few days of RNA design. Costs fell by 10 to 100 times.
The revolution then accelerated. In January 2013, Feng Zhang's group at the Broad Institute and George Church's at Harvard independently showed the system worked in human cells; a patent war broke out (the Broad-Berkeley case is still not fully settled). Over the following decade CRISPR spread from crop breeding to mosquito control, from cancer therapy to projects to restore endangered species. The 2020 Nobel Prize in Chemistry went to Doudna and Charpentier — the first time the same Nobel had ever been awarded to two women alone.
But in 2018 a global ethical crisis erupted: the Chinese biophysicist He Jiankui announced that he had used CRISPR to edit twin baby embryos so they were born HIV-resistant. A germline edit had been performed — meaning those children's altered DNA was permanently introduced into the human gene pool. The world's scientific community condemned it sharply and He went to prison, but Pandora's box was now visibly ajar. Regulation debates aside, on the therapeutic front the first CRISPR medicine — Casgevy, for sickle cell disease — was approved in the US and UK in 2023; rewriting somatic (non-heritable) cells to erase a lifelong disease is now an FDA-listed treatment option. The double-helix structure of DNA was solved in 1953; 59 years later, humanity moved from being able to read that script to being able to edit and rewrite it.
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Location
Berkeley, California, USA (and Umeå, Sweden) · OpenStreetMap →
Sources
- A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity — Jinek, Chylinski, Fonfara, Hauer, Doudna, Charpentier (Science 2012) — Science (AAAS)
- The Nobel Prize in Chemistry 2020 — Emmanuelle Charpentier, Jennifer A. Doudna — The Nobel Foundation
- CRISPR — Britannica — Encyclopædia Britannica