“IT HAS not escaped our notice”, wrote James Watson and Francis Crick in 1953, “that the specific pairing we have postulated immediately suggests a possible copying mechanism.” What they had discovered was the structure of DNA and the way its halves matched up. It was a classic of understatement, for what they had noticed would revolutionise biology.
With similar self-restraint, results published in Science, in 2012, noted “considerable potential for gene-targeting and genome-editing applications”. In fact, the study revealed a simple method allowing scientists to tinker, at will, with the genomes of animals and plants. It threw open the doors to a new and egalitarian era of genetic engineering—a way to tackle problems ranging from pest control to drug design to the undoing, with military precision, of harmful mutations. What remains to be determined, however, is who can claim to have discovered it.

The CRISPR-Cas9 approach, as it is known, consists of a protein that can cut DNA and a short string of RNA that identifies where to do the cutting. It won two of the authors of the Science paper—Jennifer Doudna, of the University of California, Berkeley, and Emmanuelle Charpentier, of the Helmholtz Centre for Infection Research, in Germany—a $3m Breakthrough Prize in 2014. This week, Dr Doudna told a packed house at the AAAS meeting how it worked. She recounted how a serendipitous discovery about a bit of biochemistry, borrowed from a bacterium, led her team to a transformative technique that is already being put to use.
In parallel, however, a nasty patent dispute has been unfolding. Although Dr Doudna and her colleagues were the first to file a patent on CRISPR-Cas9, they were not awarded the rights to exploit it commercially. That privilege was granted in 2014 to Feng Zhang, of the Broad Institute and the Massachusetts Institute of Technology (MIT), both in Cambridge, who also claim to have discovered the technique. This decision has been challenged, and in January the United States Patent and Trademark Office (USPTO) said it would begin a process to decide which side could claim ownership.
Cutting questions
The nub of the Broad’s argument is that what Team Doudna did is not gene-editing but rather little more than a study of the properties of a purified protein in a test tube. Robert Desimone, head of the McGovern Institute for Brain Research at MIT, has written that their work “involved no cells, no genomes and no editing”. Team Zhang, by this account, really put CRISPR-Cas9 to work by showing it functioned in mammalian cells. This view was reflected in a hackle-raising paper in January in Cell, by Eric Lander, head of the Broad, outlining a history of gene-editing that elevated the work of Team Zhang while marginalising that of Team Doudna.
Supporters of Dr Doudna and her colleagues argue differently. Although CRISPR-Cas9 is by far the simplest gene-editing technique, it is not the first; others that rely on different nucleases, which do the DNA snipping, have been in use for a number of years. There is a pattern in the development of these other, trickier techniques: the substantive innovation, the one that ultimately leads to a functioning gene-editor, has been the ability to cut DNA at specific locations, something Dr Doudna did in fact show—in a test tube.
The forthcoming USPTO proceedings must therefore determine who knew what and when. Although these days patents are granted on a simpler “first to file” basis, the dispute will be settled under the older, “first to invent” standard, which was in place when both applications were made. The question for the USPTO in its hearings, which start on March 9th, is which party made the discovery in the lab first—something that is as yet not clear.
Team Zhang will be the “junior party” in the dispute, so the burden of proof lies with them. To win, Dr Zhang will need to show that he discovered CRISPR-Cas9 editing long before Dr Doudna’s paper in 2012. The Broad may even use as evidence work that was carried out in test tubes.
None of this seems to have slowed commercial activity surrounding the technique. Editas, a company that currently holds the disputed patent, has said it will go public this year. Firms such as Caribou Biosciences, CRISPR Therapeutics and Intellia Therapeutics are also pursuing commercial applications of the approach; these either hold or license a patent filed by Dr Doudna that is pending. Whoever ultimately lays claim to the power over genomes that CRISPR-Cas9 represents, its “considerable potential” will be realised.
But some things—including more prizes, and possibly a Nobel—do hang in the balance. When Dr Doudna took questions from the press at the AAAS meeting, there was more interest in legal, rather than scientific, issues. Asked how she was dealing with the furore, Dr Doudna said: “Fortunately there are people who are way above my pay grade dealing with that.”