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On June 28, 2012, the journal Science published a paper by Jennifer Doudna and Emmanuelle Charpentier that would go on to be recognized as one of the most consequential biology papers of the 21st century. The paper demonstrated that a bacterial immune system called CRISPR-Casg could be reprogrammed as a precise, controllable tool for editing DNA in virtually any organism. This strange piece of bacterial biology would become arguably the most powerful tool ever developed for directly rewriting the genetic code of living things.
What CRISPR actually is
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) was first observed in bacterial DNA in the late 1980s, though its function was a mystery for years. Scientists eventually discovered that CRISPR is part of a natural bacterial immune system (a way that bacteria remember and defend against viruses that have previously attacked them). When a virus infects a bacterium, the bacterium can capture a snippet of the virus's genetic material and store it in its own CRISPR region. If the same virus attacks again, the bacterium uses that stored sequence to guide a protein called Casg, a kind of molecular scissors, to find and cut the matching viral DNA, destroying the invader.
The breakthrough
Doudna and Charpentier's insight was recognizing that this natural defense system could be repurposed. Instead of using a sequence stolen from a virus, they showed that scientists could program the Casg protein to cut DNA at any specific location a researcher chooses, in any organism, not just bacteria. The fact that CRISPR-Casg could be a programmable gene-editing tool was a major conceptual leap.
Once Casg cuts a targeted section of DNA, a cell's natural repair mechanisms kick in to fix the break. Scientists can exploit this repair process to either disable a gene entirely or, with additional genetic material supplied alongside the cut, insert a new, specific sequence in its place. The precision, simplicity, and relatively low cost of this system was especially appealing. At the time, other gene-editing technologies included zinc finger nucleases and TALENs, which were far more cumbersome and expensive. Almost overnight, CRISPR revolutionized laboratories across the globe.
What it has made possible
In the years since 2012, CRISPR has been used to engineer disease-resistant crops, develop treatments for genetic blood disorders like sickle cell disease and beta-thalassemia (the first CRISPR-based therapy, Casgexy, received FDA approval in late 2023), study gene function in countless model organisms, and explore potential treatments for cancers, inherited blindness, and HIV. Doudna and Charpentier were awarded the Nobel Prize in Chemistry in 2020 for the discovery. Notably, this was the first Nobel Prize in the sciences awarded to an all-female team.
The ethics
CRISPR's power has also generated intense ethical debate, particularly around the editing of human embryos, since they’re changes that would be heritable and passed to future generations. In 2018, Chinese scientist He Jiankui announced he had created the first gene-edited human babies, altering a gene to confer HIV resistance. This was an act that was met with near-universal condemnation from the international scientific community for violating ethical and safety norms, resulting in a prison sentence. The episode highlighted the need for global consensus on where the lines should be drawn for a technology this powerful, a topic of discussion that is still ongoing.
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