A war on the ownership of the greatest biological discovery of the decade is quickly exposing the ruthless side of science, which often maintains a veneer of cheerful collaboration. No sooner had we begun to faithfully write six as the last digit in our notebooks, the year itself promised to be an important one for the fate of gene editing. In early January, the United States Patent and Trademark Office granted a motion of interference in a case of the Broad Institute at MIT vs. the University of California, Berkeley, and set up a winner-take-all legal showdown regarding patents for CRISPR, a technology worth billions of dollars, expected to revolutionize science and win a Nobel Prize. All of this is up for grabs, and likely, by the end of the year — intense, right?
So let’s rewind — how did we get here?
The story centers around a technology called CRISPR, short for Clustered Regularly-Interspaced Short Palindromic Repeats, which allows for very specific and efficient binding of bespoke molecular scissors to the genome. This, in turn, allows for precise targeting, cutting, deleting and adding synthetic sequences or proteins to cells on a dish, fish, mice and — eventually, we hope — people! This is a huge leap forward in gene therapy and has significant implications for personalized medicine. Indeed, our imaginations have taken flight, with applications resembling the sci-fi imagined dystopias of designer babies and utopias of absolute freedom from disease. Of course, with great applications, comes great money, and this is where things get cagey.
Here’s a simplified timeline on the discovery of CRISPR: in May 2012 Lithuanian researcher Virginijus Siksnys’s group submits a paper to the journal PNAS characterizing the CRISPR complex in bacteria. The paper, naturally, takes months to be revised and is approved in August 2012. In parallel, Jennifer Doudna’s group from Berkeley, in collaboration with Emmanuelle Charpentier’s group at the University of Vienna, submits a similar paper to Science — a substantially more prominent journal — albeit three weeks after Siksnys’s group. However, editors at Science, recognizing the paper’s potential impact, promptly accept it within two weeks, and Doudna pips Siksnys to publishing. Correspondingly, UC Berkeley files a patent for CRISPR with Doudna as the inventor in May 2012. Two other groups, those of Feng Zhang and George Church from MIT and Harvard, respectively, submit and publish papers in January 2013 in Science demonstrating the use of CRISPR, but in mammalian cells. They, too, file patents, for CRISPR in October 2012. In 2013, Doudna, Zhang and Church proceed to found Editas Medicine — a therapeutic genome editing company based around their patents and expertise, and everyone lives happily ever after.
If only. In April 2014, the USPTO grants the MIT patent, citing Zhang as the sole inventor for broad applications of CRISPR within eukaryotes — essentially all complex living organisms. MIT, it transpires, has paid the USPTO extra to fast-track the patent and has beaten UC Berkeley to the punch. Moreover, the Berkeley patent, which correctly speculates but does not initially demonstrate use in complex organisms, is excluded by MIT’s claim. Doudna promptly leaves Editas to join Intellia, a rival company and Berkeley mounts a legal protest by asking for an interference ruling — seeking review by a tribunal on who was “first to invent” the technology. The “first to invent” rule, incidentally, was revoked in 2013, as the US caught up with the rest of the world in granting patents to those who were “first to file.” However, because the filings were prior to the law change, the interference ruling — one of the last of its kind — was sought.
All of that brings us to this year. The story so far has had science, economics, and law, but 2016 promises to bring theatre. In January, the motion for interference was granted, naming Doudna and Berkeley as senior parties — meaning the burden of proof for invention falls on Zhang. There are a number of nuances at play, but principal among them are: did the groups arrive at the CRISPR results independently? And does Zhang’s finding of CRISPR activity in complex organisms constitute an innovative step, or is it an obvious corollary of Doudna’s finding? An interference tribunal is given a year by statute to complete its decision. Though extensions can be granted, it’s likely that this could be settled before 2017.
Meanwhile, despite its looming legal entanglement, Editas successfully became a publicly traded company in January, and all parties continue to enjoy their well-deserved time in the spotlight. Zhang continues to innovate on CRISPR mechanisms, and has recently discovered an alternate system called Cpf1 that may achieve similar results. Doudna has become a prominent voice for ethical implications of gene editing technology. Labs everywhere continue to use CRISPR, freely available for academic and research purposes, refining uses and expanding contexts. But the calm of academic progress could well be a harbinger of the storm that will be the interference verdict by year’s end.
After all, the science behind CRISPR is only academic in one sense of the word.
Suveg Pandey is a fourth-year PhD candidate at the Weill Graduate School of Medical Sciences in New York City. He may be reached at [email protected]What’s Up Doc? appears alternate Fridays this semester.