The fight for ownership of the powerful gene-editing technique known as CRISPR-Cas9 is over, at least for now. A panel of judges at the U.S. Patent and Trademark Office ruled Feb. 15 in favor of the Broad Institute of the Massachusetts Institute of Technology and Harvard, despite the fact that the University of California, Berkeley, had pioneered the technique using less complex bacterial systems.
The CRISPR-Cas9 system is a versatile and affordable gene-editing technique that has a much broader range of applications than its predecessors. It exploits a cell's own repair mechanism, acting as a metaphorical pair of scissors to cut DNA sequences and create openings in which to splice new ones. The technique can be used to insert other genes or simply delete portions of genomes, thereby altering phenotypes (the physical properties resulting from a specific genetic code as it relates to organisms, from bacteria and plants to humans).
Though the laboratory at U.C. Berkeley filed for the patent first, scientists at the Broad Institute fast-tracked their application. And despite the California school's claims to have invented the technique, the Broad Institute argued that U.C. Berkeley focused on proof of concept by showing that the technique worked outside its natural environment. By contrast, the Broad Institute said it had advanced the technique, using it on eukaryotic (specifically, mammalian) cells instead. (Eukaryotic cells have a membrane-enclosed nucleus and make up advanced organisms, including humans.) The extended intellectual property battle ultimately hinged on whether the use of the technique in the different types of cells constituted an obvious next step in U.C. Berkeley's research. The California university argued that the leap from one to the other was completely logical and thus should be covered in its original patent. The Broad Institute convinced the panel that there was no interference, meaning that there was no conflict in the two organizations' patents.
The ruling is at odds with the opinions of most of the scientific community, which views the discoveries of Jennifer Doudna at U.C. Berkeley and Emmanuelle Charpentier at the University of Vienna and Umea University as the seminal work. The two researchers used the technique first on simpler organisms, but the jump to eukaryotes was considered a natural step by many of their scientific peers. This is evidenced, in part, by the numerous awards that have been lauded on them in recent years.
Beyond the scientific ramifications of the ruling, there are obvious financial incentives for biotechnology companies able to license CRISPR. Not only could the decision influence the success or failure of individual companies, but it also brings to light a broader issue: In an age of rapidly advancing technology, patent holders of disruptive or geopolitically significant technologies have the ability to wield disproportionate influence as government policy catches up with scientific advances.
Policy on the Heels of Technology
From a financial perspective, the Broad Institute — and the associated Zhang lab at MIT that performed the research — is the one that can now benefit from licensing its patent. Editas Medicine, a biotech startup closely associated with the Broad Institute, saw its shares jump by 20 percent after the ruling was announced. (Editas holds exclusive licenses for CRISPR-related disease applications.) Other companies with non-exclusive licenses from the Broad Institute include GE Healthcare, Monsanto and German drug developer Evotec. By comparison, companies associated with U.C. Berkeley — including Caribou Biosciences and CRISPR Therapeutics — have been left scrambling.
Until there is a more specific policy governing new technologies, patent holders have greater influence over who uses them, and to what end.
The impact of the ruling goes beyond just making money, though. Gene-editing technology could have a global impact across many different sectors. Yet public policy is still catching up with scientific progress. So far only piecemeal decisions or advice by countries and experts have been applied to the emergent technology. Most recently, the U.S. National Academy of Sciences released a recommendation that said CRISPR should be used to modify human DNA to treat diseases but warned against the enhancement of the human genome — a polite way of coming down against designer babies. When it comes to agriculture, there are often general policies regarding biological research or the genetic modification of crops. But it is becoming increasingly clear that gene-editing technology could avoid some of those regulations. For example, in farming, gene-editing technologies such as CRISPR or TALEN are not always held to the same standards as more traditional genetic modification techniques.
As far as human applications go, the global scientific community and governments alike are still determining just where and how gene-altering techniques can and should be used. Until there is a more specific policy governing new technologies, patent holders have greater influence over who uses them, and to what end. They also hold the power to issue licenses and stand to reap the financial rewards. When it comes to the CRISPR-Cas9 system itself, the Broad Institute has already issued licenses to several companies in a number of sectors. It has also indicated that it will not charge research universities to use its technology, maintaining open access for academic and scientific purposes. But as gene-editing technology continues to improve and new systems not covered by the debated patent develop, the situation will naturally evolve.
Groundbreaking technologies afford patent holders clout far beyond what most people perceive. Who could have imagined the impact of global, digital communications in the latter half of the 20th century and the companies that profited from them? CRISPR is a geopolitically critical technology that is likely to affect agricultural output, industrial biotechnology and human health care. It will therefore be important to watch how the CRISPR technique is disseminated in the future. In the realm of geopolitics, it doesn't necessarily matter which institute won the patent case. It does, however, highlight a pattern that is becoming more important and that will continue to impact disruptive technologies like CRISPR in the future. As policymakers struggle to keep up with rapidly evolving technologies, patent holders will continue to wield disproportionate influence until slow-moving bureaucracies draw even, at which point the next globe-changing innovation may already be on the horizon.