Why would two scientists who were awarded the Nobel Prize in Chemistry in 2020 for developing the revolutionary genome editing tool, CRISPR, withdraw their patents on this breakthrough? A startling news report at the end of September says that the much awarded and feted scientists, Emmanuelle Charpentier and Jennifer Doudna, have asked for their patents to be retracted, marking the most dramatic turn in a decade-long fight to the control what is routinely described as “the biggest biotech discovery of the century”.
Did Charpentier and Doudna suddenly decide, like some illustrious scientists of an earlier era, that their discovery should not be controlled and be given for free to all of humanity? Or was the duo tired of the long chase for intellectual property rights on their breakthrough, which is embroiled in disputes in Europe and the US? It is neither. According to MIT Technology Review the duo decided to withdraw their patents after a technical appeals board of the European Patent Office (EPO), which has been examining several opposition appeals against the 2017 patents, came to the conclusion that earliest patent filing failed to explain CRISPR clearly so that others could make use of it. As a result, it does not qualify as a proper invention.
To understand why this is such a damaging observation for the Nobel laureates, we need to understand the four basic criteria that must be fulfilled in order to get a patent. First, it has to be something novel, meaning the product or process has to be new, a first of its kind. Then,
it must not be “obvious”, that is, a person skilled in the art should not be able to replicate it. The invention claim must meet two other important conditions: it can be used and is not just an abstract theory; and must include a clear description of how to make and use the invention.
The review board says that since a key detail was omitted from its first patent application, even a person skilled in the art would not be able to carry out the claimed method. In other words, the invention was not fully described or enabled. How did this happen? Was EPO in too much of a rush to grant the patents, or was it trying to set a precedent? In essence, the technical review board is that the two patent claims awarded in 2017 on Charpentier-Doudna’s basic CRISPR discovery are not valid because these are too sweeping. These patents covered the use of the single-guide CRISPR-Cas9 technology in cells of all types and included applications for treatment of various human diseases as well as veterinary, agricultural and other biotech applications. The claims were opposed by several, including TestBiotech, a German non-profit institute that makes an independent risk impact of biotechnology, especially genetic engineering.
The Nobel awardees, who hold another patent in Europe and also have a thicket of other pending claims, have, surprisingly, decided to withdraw their patents instead of battling it out at EPO. This marks a rare occurrence in the annals of patent litigation. In the US, where the big fight over patents is taking place, there is elation in the rival camp over the news from Europe because it would have a significant fallout on the outcome of a protracted and bitter struggle to control the technology, the core of it being the CRISPR-Cas9 DNA-targeting technology.
Involved in this contest are the top universities in the US and Europe where other scientists who also have claims on the technology have worked. Apart from the University of California, Berkeley, where the pioneers worked, there is also the University of Zurich and the University of Vienna involved, the latter two being the centres from where Martin Jinek and Krzysztof Chylinski listed as co-inventors are drawn. These scientists, known as the CVC group—the initials are taken from the names of the universities—are pitted against Feng Zhang, a researcher at the Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, who claims to have discovered CRISPR first. Ten years ago, Zhang and the Broad Institute won the controlling US patent on CRISPR’s main uses. There is patent litigation over most of the 15 patents granted so far.
All this raises questions about scientific discoveries and the puzzle of who gets to be named as the real inventor. Can scientists in this day and age claim to be true pioneers or inventors when they rely so much on the work done over the decades? The idea that scientists are lone geniuses working in secluded laboratories is no longer tenable although it is embedded in the popular imagination. Without collaborations, significant breakthroughs are not possible; nor are they possible without a sizable body of research work in related fields. And very rarely do fellow researchers, such as post-doctoral students of the laboratory heads, get to share the limelight even if they have done the laborious work. Take Martin Jinek, for instance. He was lead co-author of a ground-breaking research paper that came up with the revolutionary discovery that the enzyme Cas9 can be retooled to target specific sequences of DNA using only a short strand of RNA. He might be named in the patent, but no honours or awards have been bestowed on him. That is how the system is.
There are others, completely unknown in the CRISPR story. Like Prashant Mali, a post-doctoral researcher who played a key role in launching the CRISPR project in the laboratory of George Church, a geneticist at Harvard Medical School in Boston who was one of the pioneers of the CRISPR technology. Mali was first author in the laboratory's 2013 paper which established that CRISPR-Cas9 could be used to edit the genome in human-induced pluripotent stem cells.
But the saddest story is that of the group of scientists headed by Virginijus Šikšnys from Lithuania, who discovered the ability of CRISPR-Cas9 to cut DNA at the same time as the Nobel scientists. Šikšnys had been focused on CRISPR-Cas research since 2007 and was among the first to demonstrate programmable DNA cleavage by the Cas9 protein. But he lost out again because of a system that ignores landmark research unless it comes from the known hubs in the West. In 2012, that Šikšnys sent a paper to Cell, where it was rejected in just five days—without review and without being assigned any reason. After all, it was a paper from Lithuania, completely off the beaten track of scientific research! Šikšnys and lead author Giedrius Gasiunas then submitted the paper to the Proceedings of the National Academy of Sciences, but while it was being reviewed, the Jinek paper appeared in Science.
Šikšnys has patents on the technology that have been licensed to DuPont, but no honours and recognition have come his way except for the tacit admission among scientists that he was probably first to discover the CRISPR tool. There is proof in his US patent application filed in March 2012.