Michael Eisen is a known shit-stirrer, but he's often (and in this case definitely) right. This is getting vicious now though. Thankfully Zhang, Doudna, & co have the sense not to take the argument to social media. To academic labs, it matters little. Cas9 has and will continue to be free for non-commercial use. To industry licenses, Zhang's lab has Cpf1 nailed down, so there's that as a fallback if Cas9's patent goes to Berkeley. However I wouldn't be surprised if there just turns out to be a lot of heterogeneity in gene editing implementations, as there are already therapies using ZFNs and TALENs in the clinic, and it may turn out that different proteins work better in different parts of the genome / age of patient. That said, a few of my friends at the Broad have been discussing this (I was chatting with a friend in Zhang's lab just two days ago about it). They've been saying that the institute would stand to make hundreds of millions if not billions of dollars if they win the Cas9 patent (Also with all of the derivative patents they've published since 2012). But they also think it might be a toss-up who gets it. It as before the recent change in patent law from first-to-invent to first-to-file. And Doudna was the first to publish in a scientific journal, but Zhang was the first to file a grant application with the idea. So it really is a situation where lab notebooks are out and whoever has the earlier scrawled notes and wherever that grey definition of "invented" is drawn will decide which university gets a whole lot of money.Woah. I knew about Sayre's law, but this is pitched battle. Granted, a Nobel and lots of prestige is on the line, but this is some vicious shit.
Thundara, how big of a deal is this dispute from where you're standing, work-wise? Like is this stuff everyone you work with is talking about right now?
Is there not any precedent as to what happens in cases like these? I feel like I've been hearing about patents on gene mapping, gene editing, even genes themselves, for a while now. And an aside: how ground breaking is CRISPR? I've read a little bit about it, and listened to a Radiolab episode where a science writer answers questions that the hosts put to him, but I don't quite understand its scope. CRISPR is a gene editor. Had there been no editor before?So it really is a situation where lab notebooks are out and whoever has the earlier scrawled notes and wherever that grey definition of "invented" is drawn will decide which university gets a whole lot of money.
I'm not sure. The sequence of the original Cas9 gene found in S. pyogenes cannot be patented, as it is a naturally occurring DNA sequence. However, in this case, I believe the many modifications people have made to Cas9, as well as methods that use it to edit genes, constitute as patentable inventions. As far as "who gets the patent", by law it's whoever was the "first to invent" this use of Cas9, but I'm not sure the exact details of how that will be argued in this case. Commenting to your friend that X could be used to do Y might be considered the first novel description of a process, but I don't think that's enough to hold water. But IANAPL. At its heart, Cas9 it a DNA nuclease. It cuts DNA. Plenty of enzymes cut DNA, but what makes it unique is that where it cuts is controllable. Again, other the cut sites of other enzymes are controllable, but what makes Cas9 particularly unique is that that control is specified by an RNA sequence. TALENs and ZFNs are two other controllable-DNA-cutting-enzymes, but they both are targeted by the sequence of the protein. It's hard to predict in advance how different protein sequences will interact with DNA, so for ever new site you want to target, you must mutant, screen, and evolve a new protein. That can take months to years of work and is a barrier to use by most researchers. In contrast, if you want to target a new sequence of DNA with Cas9/CRISPR, you simply find a sequence that is complementary to that sequence. In practice, there are still some caveats, but as a starting point, that gives you a lot more speed and power to new sequences or large sets of sequences. ---- The "editing" part of the equation comes from the fact that when DNA is cut, the cell has a number of repair pathways to reseal that break. The one of the major ones is Non-Homologous End Joining (NHEJ), which just glues either end back together (sometimes inserting an extra bit of DNA in between). The other is Homology Directed Repair (HDR), which looks for DNA that is similar to the sequences around the cut site and copies that sequence over while sealing the break. So in that latter case of HDR, if you also provide a short, similar sequence with the modification you want, the cell can repair that site, copying the new DNA, achieving that final goal of an "edit". It's not perfect, often the efficiency is rather low, but it's still proven to be a robust enough tool that people have rolled with it.Is there not any precedent as to what happens in cases like these? I feel like I've been hearing about patents on gene mapping, gene editing, even genes themselves, for a while now.
And an aside: how ground breaking is CRISPR? I've read a little bit about it, and listened to a Radiolab episode where a science writer answers questions that the hosts put to him, but I don't quite understand its scope. CRISPR is a gene editor. Had there been no editor before?