The Villain of CRISPR (opens in new tab)

Jonah Salk, the guy who developed the polio vaccine

"When asked who owned the patent to it, Salk said, 'There is no patent. Could you patent the sun?'"

There's a big difference between exclusive licensing and non-exclusive licensing. New drugs (like penicillin) tend to be exclusively licensed because of the costs involved in regulatory approval, and that can slow down technology diffusion - the wrong licensee can sink the technology.

But enabling technologies (like CRSPR) get licensed non-exclusively, particularly when the patent holder is an academic institution. If the patents around CRSPR are licensed non-exclusively, at reasonably prices, and with appropriate treatment for academic researchers, these patents aren't going to slow science down.

A good example is the original polymerase chain reaction patents, which were held by Cetus. Despite lots of legal arguments, PCR was always widely available.

Here's a nice analysis of the PCR patent situation and its effects on technology diffusion: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523369/

If CRISPR gets/stays patented, the part of the world that respects patent law is going to get left out of whatever innovations it yields. Or maybe not completely left behind, but the groups that will be able to license it will number few.

I generally agree that discoveries like this should go in the public domain as quickly as possible.

The pissing contest about "who invented what, when" is fine and good, to a point; nobody cares if "Cancer Immunity 1.0" drug has a tagline "brought to you by Lander's Finest". To the extent that success and notoriety determine careers, and so we should "get it right" so that the "right" people get credit... I think most researchers will persevere and continue to do science (for the benefit of humanity or for personal glory, or whatever) even if they get shafted for credit.

But the technology itself.. get it into everybody's hands and let the thousand flowers bloom already.

I think the notion that one can own facts will one day be viewed as archaic as the notion that one can own people.

The inventions of scientists in academia, like employees in the private sector, are owned by their employers. Universities and research institutes typically have a policy to profit from these inventions via patents in order to fund more research.

The people that need to change this are at the administrative level: laws via congress, and then chancellors of universities.

Also Banting, the discoverer of insulin (or at least its potential to treat diabetes).

It will take millions of dollars of research to turn this basic bioengineering technique into an approved (safe and effective) human therapy. How do you motivate investors to fund this research without the safety net of a patent to protect that investment from free-loaders?

I think that means you hate breakthroughs.

While there’s a patent issue, this is an issue of attribution (i.e. ego). I know most would prefer either a non-profit (The Broad Institute of MIT and Harvard) or a public institution (University of California, Berkley) than some commercial entity.

This article has a little more background: http://www.statnews.com/2016/01/25/why-eric-lander-morphed/

My experience with software patents makes me believe that Lander and Zhang, being part of the group that most aggressively pursued patents, are scam artists that should be drummed out of science forever. I actually have to remind myself not to feel hostility toward them.

I know it's not valid reasoning but it would be almost certainly right in software. I'm pretty sure software patents are poisoning the whole patent system both from the inside and in public opinion.

After reading the article, it appears that the author shares your position that both groups should share the credit, FWIW

He is also a firebrand who does not care who he upsets, which works for both good and ill. (I have worked with Mike before, although in a distant capacity.) This explains why he can sometimes appear highly quixotic.

> Michael Eisen is a professor at Berkeley

and friend and colleague of Jennifer Doudna.

What’s the path forward? Is labeling Lander a “villain” useful?

> Lifespan, disease and the human race is at stake.

CRISPR is just one tiny replaceable part of any therapy-driving genome editing technique. The frenzy around it overstates its importance.

Cas9 is significant as the first RNA-guided nuclease that we learned how to manipulate, but there are probably many more in nature. Hopefully we will be able to construct our own in short order.

We have had very high quality programmable nucleases for a long time. Nucleases are not the principal expense in genome engineering. Further, if you want to be sure that the cuts you make are correct and on-target you might want to take the time to use another system than Cas9/tracRNA.

However, dCas9 (disabled Cas'es) and friends are amazingly novel, in that they allow us to make huge libraries of targeted DNA binding complexes that don't cut DNA, but let us pull particular things to particular places in the genome. This is an incredible boon to certain research threads. For example, see http://www.sciencedirect.com/science/article/pii/S0092867413...

A lot of breakthroughs in science have a similar fate. One example was finding that DNA was a double helix with Watson, Crick, and Rosalind Franklin. Watson and Crick got all the credit but Franklin definitely played a major role in that discovery and was mostly written out.

From what I broadly understand from CRISPR, the Nobel is almost a footnote in history, the real prize seems to be the patent.

Of the many examples of science getting nasty in the past, one could hardly do better than to revisit the "invention" of calculus. One which raged for at least two decades, and involved names now rightfully known to nearly the entire human race[1]. Then there's the still unresolved mess of who discovered the structure of DNA and the question of whether the Nobel prize partly went to someone who 'stole' the data 'over the shoulder' of someone who should have received far more credit[2]. So over its long history I think we've been very consistent in our discreditable behavior of granting scientific credit; and notice that the business notions of IP are a very recent addition to this struggle. When the treasure is seen as vast, and there's clearly enough for all, that's exactly when sharing is likely to be at a nadir; such is lamentable human nature -sigh-

[1] https://en.wikipedia.org/wiki/Leibniz%E2%80%93Newton_calculu...

[2] https://en.wikipedia.org/wiki/Rosalind_Franklin#Contribution...

Science has always been a human endeavor. The politics around mid-20th century physics is a similar minefield.

However, it's far more pure, than, say, typical SV venture capital.

Lander is widely known for being both a scientific and political heavyweight. He knows how to gain power, knows how to wield it, and uses it both to serve scientific goals and his own.

Such use of power has pushed forward science to some degree by allowing considerable economic resources to be applied in a focused manner. But it gets used for other purposes too, because Lander is still a human, and still makes mistakes.

I'm pretty confident that all the people here have human good and knowledge as their highest priority. They just differ on how to achieve it.

If you are Eric Lander, you've already tuned the Broad Institute towards what you expect to be the most fruitful paths of research to improve humankind, and the best way to have it improve humankind is more funding. Michael Eisen might have different opinions on the best paths of research, and you probably have some things you think will pay off that he doesn't, or he thinks will pay off that you don't. It is entirely rational to look at the amount of money available to fund research from public sources and the amount available from private industry, and determine that the best way to save the world is to get that patent and license it aggressively.

And, if you're Michael Eisen, you know that your colleagues are doing excellent work and only one person can own the patent, and that patent going to the Broad represents a significant loss to your colleagues' potential funding, so it's entirely rational to decide the best way to save the world is to contest the patent aggressively.

If we, the onlookers, want to fix this, we need to fix the funding problem. I rather doubt that either Lander or Eisen were driven by desires of patent ownership or denying other people patent ownership when they originally entered the field.

This is about right, but I think you're not properly weighting the rising role of institutional corporatism at research universities. The push for "translational" research was not driven by scientists. Scientists are not idiots, of course. They know when they have something useful. But the institutions built enormous offices filled with lawyers and finance types to promote and manage their "IP portfolios," as if schools suddenly became VCs. The proceeds from this portfolio feeds back only fractionally into research and education, but primarily it funds a vicious circle of administrative executives and contractors who are the main beneficiaries.

IP is just another form of applause, and with it or without it wouldn't matter or change the behavior. People who want the prestige will rise to the occasion and treat the world as a zero sum game.

It's not clear to me what you are saying. Cas9/CRISPR unambiguously cuts the genome at a target site determined by the guide RNA sequence. In the presence of a DNA oligo with partial complementarity to the cut site, the DNA repair mechanism will sometimes incorporate the "payload" oligo, causing the genetic locus to be engineered from one sequence to another, predetermined sequence.

My sister was sent by Brazil's government to MIT so she can bring back CRISPR technology to Brazil public universities to speed a research here about using gene editing to control stem cell expression.

I've seen plenty of people and papers where dna was edited in across entirely different organism realms, bacteria dna in animals, animal dna in plants, and so on...

I honestly don't understand how the technique ins't about editing, the only use I saw for it is editing.

EDIT: I asked my sister to give me links to some papers, I will post them after she replies.

But there are plenty of knock-in experiments where foreign DNA was put into the cut site. Are you saying a pre-existing mutant with the foreign DNA was used in those cases too?

The papers I've looked at sequence and measure the on-target mutation rate, and don't have any steps in them that would select for mutants (because that would ruin the measurement). Where do you propose the selection for mutants would be happening?

Unless I'm misunderstanding something about how the experiments are done, your theory would require many groups to be independently committing scientific fraud, which is very implausible.

Lol, what, just what... the biophysics of the Cas9 system are understood pretty well. We literally get as close as you can get to observing the accepted mechanism of action. How would you explain the consistency of site specific gene integration? You can't be selecting from existing mutants and "just happen" to get your transgenic product inserted at the exact site you specified. Your comment is just absurd. You also don't seem to realize that CRISPR is used at pretty much every university in dozens of different systems by thousands of different scientists. What a bizarre comment. Edit: uh, if you actually need a "source" for this:

http://m.pnas.org/content/109/39/E2579.full

This is a baseless critique.

No one has to address alternative hypotheses that don't make any sense. Are you unaware that Sanger Sequencing exists, and the actual lesions can be read? Or that heterologous genes are being introduced with CRISPR methods? Neither of these common results can be explained by the spontaneous insertion of hundreds of nucleotides that happen to precisely match the sequence of the construct being inserted.

Again, this is utter nonsense and demonstrates a complete absence of basic understanding in molecular biology.

CRISPR is a mechanism by which some species of bacteria and archea can edit a virus out of their genome -- it's essentially a small immune system. CRISPR is "hot" right now because of the potential to use it to edit arbitrary genomes. Bear in mind that the technique has a long way to go. It's more or less impossible to do it right now without causing a lot of side effects elsewhere in the genome.

As with most science, this has taken a long time and been the result of work by many, many scientists. Some scientists have big egos and are fighting about who the "real genius" is. Furthermore, it's widely thought that there's going to be a lot of money in this technique, if you can get a patent on it.

TL;DR; cool and potentially very useful science happened, now big egos, big greed, and people who would rather get rich and win a Nobel prize than share the discovery and its benefits with the world are having a fight about it.

Lander wrote an article in "Cell" about the history as he saw it of the invention of the Crispr technique. It covered the bases but was flawed, but it did include a lot of scientists that weren't included before. The article basically tries to discredit it. It wasn't a great argument and frankly the authors not a impartial (Friends with one of the scientist, and works at one of the universities) I'm surprised it made it this far on Hacker News.

There is a patent dispute about who owns the patent on this technique. Lots of money is potentially at stake. This article was written from one of the parties (Broad institute and UC Berkely) being one of them. Oddly the Lander article supports the notion that this invention is evolution not revolutionary.

Broad has been working to move from from CRISPR/CAS9 to CRISPR/Something else better). The UC Berkley seems to have come up with it first, but is it obvious or obvious to use in editing is the question. The UC [2]team has pulled all there patent claims and resubmitted them twice, presumably to broaden the scope and cover any use. Add some east coast/west coast rivalry and some other biases and you have a powder keg of science.

Anyway lots of blame to go around.

siyer posted this in a previous article which puts the patent dispute in context and if the patent is only cas9:

[1]http://www.ipscell.com/2016/01/patent-expert-weighs-in-on-cr...

and the strange patent application by UC and :

[2]https://law.stanford.edu/2015/12/29/the-crispr-patent-interf...

Egos are colliding over attribution. Go figure!

There’s a patent issue too, but it’s difficult to evaluate since the issue is between a non-profit (The Broad Institute of MIT and Harvard) and a public institution (University of California, Berkley) and most people acknowledge that either would be better for progress than any commercial entity.