A discovery made in pieces
CRISPR was not found by one person on one day. It emerged from basic research on bacteria, in which several groups noticed a strange DNA pattern, worked out its purpose, and later realized it could be reused as a tool. The date most people cite is 2012, but that marks the point at which the system was shown to be programmable, not the point at which it was first seen.
Strange repeats in bacterial DNA
In 1987 a Japanese team led by Yoshizumi Ishino, at Osaka University, reported an unusual sequence near a gene in the bacterium Escherichia coli: short repeated segments separated by different short spacers. They did not know what it was for. During the 1990s Francisco Mojica, a microbiologist in Spain, found similar patterns in microbes that live in salty environments and in many other species, which suggested that the repeats were important. By around 2001, researchers had agreed on a name: clustered regularly interspaced short palindromic repeats, abbreviated CRISPR. A set of nearby genes, called cas genes, was also noticed and named.
An immune system for bacteria
Around 2003 to 2005, several researchers, including Mojica, noticed that the spacer sequences matched pieces of DNA from viruses that infect bacteria (called phages). That led to the idea that CRISPR was a kind of adaptive immune system: bacteria store snippets of invaders’ DNA and use them to recognize and cut the same invader later.
Experimental proof came in 2007. Researchers at the food ingredient company Danisco, including Rodolphe Barrangou and Philippe Horvath, were working with the bacteria used to make yogurt and cheese, which are vulnerable to phage attacks. They showed that adding or removing spacers changed whether a culture resisted a particular phage. In the following years, groups including John van der Oost’s and Luciano Marraffini and Erik Sontheimer’s clarified how the system finds and cuts its targets, and showed that in some types the target was DNA.
From natural defense to programmable tool
The key work for gene editing came from studying a simple version of the system in Streptococcus pyogenes, which relies on one protein, Cas9. In 2011 Emmanuelle Charpentier’s group, with Elitza Deltcheva and colleagues, reported an additional small RNA molecule that the system needs. Charpentier then worked with Jennifer Doudna, a structural biologist at the University of California, Berkeley, with Martin Jinek and Krzysztof Chylinski among the authors. Their paper, published in the journal Science in 2012, showed that Cas9 could be directed to cut DNA at a chosen location by supplying a short engineered guide RNA. In effect, changing a short piece of RNA changed where the cut was made.
A group led by Virginijus Šikšnys in Lithuania reported closely related findings in 2012 as well, and their contribution is sometimes overlooked in popular summaries.
Use in human and animal cells
Showing that Cas9 cuts DNA in a test tube is different from editing the genome of a living cell. In early 2013 several teams, including those of Feng Zhang at the Broad Institute and George Church at Harvard, reported that the system worked in human cells; Doudna’s group also published related work. Soon afterward, researchers were using it in plants, mice, zebrafish and many other organisms. Earlier tools for editing genes, such as zinc finger nucleases and TALENs, had existed, but they required designing a new protein for each target, which made CRISPR much cheaper and faster to adapt. The name “gene editing” covers all these approaches, and CRISPR is simply the one that spread most widely.
Who gets the credit
Credit is contested in two ways. The scientific prizes recognized the 2012 work: in 2020 Charpentier and Doudna shared the Nobel Prize in Chemistry. But many scientists point out that the earlier discoveries, from the first repeats to the Danisco experiments, were indispensable, and that Zhang and Church were prominent in extending the tool to human cells.
There has also been a long patent dispute, mainly between the University of California and the Broad Institute, over who first invented CRISPR-Cas9 for use in cells with a nucleus. U.S. patent bodies and courts have issued several rulings, and the situation is complicated by differing rules in other countries. Because decisions have been appealed and revised, it is safest to say that the patent question has been disputed and treat any claim that one side simply won with caution.
Applications and concerns
Researchers use CRISPR to study gene function, to develop crops, and to investigate treatments. In late 2023, regulators in the United Kingdom and the United States approved a CRISPR-based therapy for sickle cell disease, an important milestone, though it is complex and costly. In 2018 a Chinese scientist, He Jiankui, announced that he had edited human embryos that resulted in births, a claim that was widely condemned as premature and unsafe. Editing genes that can be passed to future generations raises ethical questions that societies and scientific bodies are still debating.
CRISPR is also not magic: it can cut in unintended places, and cells repair the cuts in ways that are not always predictable. Newer variants, such as base editing, try to reduce those risks. This article is a history only and not advice about any treatment.