Harvard and M.I.T. Scientists Win Gene-Editing Patent Fight
nytimes.com
nytimes.com
She worked on this technology for years, developing it from it's infancy to in vitro proof. MIT scientists swooped in and within 2 months applied it in-vivo and patented it.
I guess to be rewarded in science you have to be a master in your field and intensely concerned with IP deadlines.
It's really a shame that Berkeley loses licensing on a tech that was 95% developed at Berkeley.
"Swoop in and patented it" is not exactly how it goes. There is a long back story to this with a lot of people discoing stuff to make this possible.[1]
CRISPR-CAS9 will probably be supplanted by something else. They're already working on it (hopefully with fewer off target effects). http://www.nature.com/news/alternative-crispr-system-could-i...
You can watch a video by Zheng (the patent holder) on how CRISPR works if you are curious[2]
I doubt she's livid, they won a lot of research prize money from their research [2] and she's probably collect money from patents from the company she started with the patent holder "Editas Medicine. Co-founded by the Broad’s Zhang (and also by Doudna, in more collegial days)"[2]
as with most patent disputes the lawyers are the real winners: "The Broad’s legal costs, paid by Editas, topped $15 million last summer. UC’s, paid by Caribou, have passed $5 million. Neither party has said what they have spent since then."[2]
[1]http://www.cell.com/cell/fulltext/S0092-8674(15)01705-5
[2]https://www.statnews.com/2017/02/15/crispr-patent-ruling/
[1] http://genotopia.scienceblog.com/573/a-whig-history-of-crisp...
I don't really have a horse in this race, but I am new to working in the Biology field. I will say that biology seems to depend on the work of many people and is kind of incremental. Its weird that some are getting rich and lots of credit, while a lot of the researchers work in obscurity. That was my take away from the Cell article.
Your first article was a good critique of the Cell article.
The second one was a little hard to take seriously first[1] (plus written by someone from the other side of the dispute), though he does come around to my original point in my original post: "And, as I have long argued, I believe that neither Berkeley nor MIT should have patents on CRISPR, since it is a disservice to science and the public for academic scientists to ever claim intellectual property in their work."
[1]"Lander’s recent essay in Cell entitled “The Heroes of CRISPR” is his masterwork, at once so evil and yet so brilliant that I find it hard not to stand in awe even as I picture him cackling loudly in his Kendall Square lair, giant laser weapon behind him poised to destroy Berkeley if we don’t hand over our patents."
I was reminded of it when Lander's article came out, not just now.
So a $20 million boon for lawyers and who knows how many hours the researchers lost being distracted by legal issues. One wonders how we could rework our legal system so that that kind of funds and that kind of time don't get wasted like this and instead reward both the researchers and the implementers that get it into practically usable form.
Science = standing on the shoulders of others. It is not fair if the one (momentarily) standing on top receives all the benefits.
Yes, one of the two labs discovered CRISPR. OK, now what? It's not a treatment at this point, it's just a technique. So someone has to invest a ton of money to turn the technique into a therapy for humans. And I would bet that investment will absolutely dwarf what's been spent so far.
Instead, we could grant subsidies and have multiple developments working in parallel.
Dr. Zhang and MIT proved that the Crispr technique would work in plant, animal and human cells. The value of the patents is in that research, not Doudna's in vitro proof.
Transferring that body of work over to in-vivo is trivial in comparison to what she did. Transferring genes from one organism to another is run of the mill molecular biology.
Nobody, including Doudna, would agree with this.
This tech has been around for years. Monsanto wouldn't exist without molecular biology. We'd still be extracting insulin out of farm animals if molecular biology hadn't allowed scientists to grow it in yeast.
The tech is really not the same, it's the difference between hand braided core-ram and re programmable memory. It's a huge difference.
The tool is extremely effective, as you say, and was primarily "designed" via natural selection. The researchers (1) discovered it, teased out its mechanism of action, and its programmability, and (2) did standard molecular bio techniques to show that it works across several oragnisms.
This ruling is based on the fact that the original inventors didn't throw the genes into cells, publish, and (most importantly) apply for patents before the Broad group did. Whether it would work in those other cells was a crapshoot and doesn't represent any significant creative work, and a minor work of science. The importance is the result - we know it works in those cells.
Source: I also work in this field. This ruling is absurd.
But what Zhang did was not trivial. He did not just take Doudna's system and threw it into a mammalian system. He modified the system so: 1) codon optimized (not very hard, I know). 2) Added two localization signal sequences so it goes into the nucleus. 3) And most importantly, he modified the system (nuclease to nickase) so mismatch repair (homology based repair) occurs more frequently than non-homologous end joining. These modifications are not trivial and probably took a lot of trial and error.
Just because crispr is so simple to perform now doesn't mean there wasn't a lot of effort on both Doudna and Zhang's part.
Personally, I believe both of them should have been on the patent. For me, Doudna came up with the Ford model T and Zhang iterated and extended it into a Ferrari.
If this was the case then she would have won the patent fight. The Patent Trial and Appeal Board thought otherwise. Did you read their 51-page decision?
This is wrong.
It's really a shame that Berkeley loses licensing on a tech that was 95% developed at Berkeley.
This is very wrong.
However, after an initial period, other companies may apply to license certain CRISPR IP for use against genes of interest not being pursued by Editas. Specifically: (i) a third party interested in an individual gene target would provide a bona fide development plan, (ii) Editas then has a pre-defined period to decide whether it intends to pursue the gene of interest and to commit funding and launch a program, and; (iii) if Editas is not already working on the gene of interest and chooses not to launch a new program of its own within this period, the IP may be available for licensing by Broad, Harvard, and MIT to the third party.
I wouldn't call it "fair reasonable and non-discriminatory", but it's not entirely exclusive.
Is this any different in practice? Don't you have to do a bunch of work before you can provide a bona fide development plan?
Note that they make the tech completely free to the academic community.
Right of first refusal is very different from exclusive licensing. The development plan issue is handled by grownups at companies with hundreds of millions of dollars of funding and they already developed development plans.
One argument is that getting a patent ensures exclusivity to use the technology. In turn, that drastically improves the likelihood of getting a return on any investment dollars. And finally, that attracts a lot more capital than a non-profit or gov't funded agency could typically get.
Like PCR, CRISPR is a relatively simple technology. It doesn't require billions of dollars of R&D to make it useful. Less useful gene editing tech (Zinc fingers, TALENS) have already been used in clinical trials. So just like PCR or that blood Myriad Genetics gene patent on BRCA1, patents hinder progress, make research more expensive, and impair new companies from getting started.
[1] https://www.bloomberg.com/graphics/2016-university-patents/
>Says Doudna, "Our 2012 paper was a big success, but there was a problem. We weren't sure if CRISPR/Cas9 would work in eukaryotes-plant and animal cells." Unlike bacteria, plant and animal cells have a cell nucleus, and inside, DNA is stored in a tightly wound form, bound in a structure called chromatin.
[1] https://berkeley.app.box.com/v/catalyst-9-1 [2] https://twitter.com/antonioregalado/status/83200343447163289...
Most of the time the system works as intended. The researchers do their research on public money, most of what they do becomes public knowledge through papers, if something noteworthy is found, it's patented and licensed and the university gets its cut. The system kind of fails sometimes at giving the researchers (in plural, not just the tenured rockstar) its due, but many times are the scientists the ones that open an enterprise to work it out.
In this case, it's not that system that has failed, it's that different universities are fighting over who has the right to license it. I have no horse in this race, but this it's probably going to become even more common, as improvements on existing technology become smaller and it's harder to tell who deserves the full credit.
MIT is well known for the second form of patient troll where you look for years of very promising research done by someone else, make minimal change using government funds, and then get to lock things up for 20 years.
Worse there is now a huge incentive to find some other trivial change to get around this patent thus costing the field 100's of times more than their initial 'effort'.
Please read the excellent book "Against Intellectual Monopoly" if you haven't already.
http://levine.sscnet.ucla.edu/general/intellectual/againstfi...
I have mixed feeling about biotechnology, though. On one hand I'm a big fan of human genetic engineering for increased IQ which is looking extremely possible in the near future (hopefully something that will be available here in Singapore before I have kids), on the other hand as these techniques get cheaper and easier to use we may get to the point where any madman with an IQ over 145 could kill hundreds of millions. Nick Bostrom asks this question in his book: if building a nuclear bomb turned out to be trivial, like putting sand in a microwave, would human civilization have survived? We will find out if synthetic biology keeps advancing. Or maybe this is my nightmare and the patent system will slow down progress enough to save humanity.
I wouldn't hold your breath. Intelligence is not a single gene you can turn on or off. We don't know enough about what genes to modify (even if we could modify them).
He also said the following:
>I think there is good evidence that existing genetic variants in the human population (i.e., alleles affecting intelligence that are found today in the collective world population, but not necessarily in a single person) can be combined to produce a phenotype which is far beyond anything yet seen in human history. This would not surprise an animal or plant breeder — experiments on corn, cows, chickens, drosophila, etc. have shifted population means by many standard deviations (e.g., +30 SD in the case of corn).
I agree in a way, but every time this comes up I point out that in East Germany they would have pounced on this technique and built a secret base in the wilderness to work on it. I say East Germany because it is a matter of historical record, what they put their athletes through.
So I'm saying that progress on that front is possible but unlikely in this country, where we consider a major ethical breach to be something to be avoided entirely, not just hidden.
So no, I wouldn't be so sure this couldn't in principle happen in the US of A.
The future is the same no matter how long it takes. Advancing slowly doesn't prevent the results of advancement. It just increases the likelihood that something else is advancing faster than you. We should rather humanity destroy itself than lose a fight to a more advanced civilization.
How long is "enough" though, and what stimulus is needed for get that wisdom in place? Probably some form(s) of failure, though I've not thought on it further.
*Edit: I guess time is flying, that was more than a year ago. Previous discussions: https://news.ycombinator.com/item?id=10934149 https://news.ycombinator.com/item?id=10917391
I don't know the whole backstory of Crispr or all the people involved, I just know it sounded amazing when I first heard about it on Radiolab, and then it got mired in this fight over credit and rights. I'm wondering if Lander's piece was influential in this first victory, and whether this outcome was part of his intent in writing it.
TBF we did try this in the US, and this is exactly how things worked for decades. That rule was eventually shot down for a whole host of reasons.
> If you purely take private money you work in some startup you can do stuff like this
How about this scenario:
Person A invents something using public money.
Person B creates a start-up using Person A's invention.
Person C needs said invention, and can only get it from Person B, who charges them for it.
In other words, if the fruits of the labor are going to be extracted by someone, shouldn't that someone be the person who made the actual discovery (assuming they're willing to do the business side as well)?
A lot of this boils down to risk and risk mitigation. Because the monetary outlays and failure risks are so considerable to shepherd a technology through the entire life cycle from conception to commercial availability, big pharma has to be extraordinarily selective about where they place their bets. They generally do not invest in early stage developments. In fact, these days, we have to find partners or spin out startups to help further the research to even get to the point that pharma wants to talk about licensing.
The patent protections allow the time to get to that point and ensure our partners that they will have some protection to assure revenues (assuming the technology even makes it to market) sufficient to offset the costs associated with the various phases of clinical trials.
It's by no means a perfect system, and there are some slightly different models out there. Singapore, for example, requires the research dollars to be reimbursed upon commercialization. That is a fairly small ecosystem to analyze, however, when compared to the scale of US investment via agencies like the NIH and NSF.
Edit to add disclaimer: We have patents licensed to the company referenced in this article (Editas).
That is actually what the article says.
"An appeals board of the patent office ruled that the gene-editing inventions claimed by the two institutions were separate and do not overlap."
"Ultimately, companies wanting to apply Crispr for use in medicine, agriculture or other fields might need licenses from both the Broad Institute and the University of California, a lawyer for the university said. ..."
Or that a foreign nation that didn't accept the patents becomes the only center of innovation and the nation that paid for it becomes a backwater.
One or both of those happened with steam engines, sewing machines, and aeroplanes. Humanity was not better off.
It was narrowly averted in photography, automobiles, and computer software by governments invalidating the pioneer patents in the field for the benefit of mankind.
There seems to be a very sensible, but verboten, middle ground here: government funding of socially beneficial research and, if a significant public benefit can be demonstrated, compulsory state acquisition under the condition that just compensation is given.
The odd part of this case is that it might cause researchers to hold back from publishing their discoveries until they're sure their own institution can 'squeeze out all the juice' and best monetize the novel finding.
On the other hand, perhaps it incentivizes more classical research institutions to employ top teams of researchers who can prototype the 'medicine' part of a biomedicine discovery as quickly as possible. In truth, there are a lot of amazing discoveries at the ground level of molecular biology, which plausibly could revolutionize human health, but are still waiting decades later to be shown to be practical.