MPEG LA has very limited market patent positioning in the US.
The Broad Institute is sitting on radically superior IP, including the US patent on CRISPR Cas9 and global control of CRISPR Cpf1, which MPEG LA does not have any access to or control over. MPEG LA also doesn't have any rights to Sherlock.
Nearly all global rights to all forms of CRISPR are controlled by Berkeley, Vienna and the Broad Institute (with some smaller IP held by a few universities, and some corporations like Editas, Intellia, CRISPR Therapeutics, etc). MPEG LA has essentailly zero power over CRISPR, they own zero patents on CRISPR, they're trying to skim money by being a deal connector of the Berkeley & Vienna patents.
I think the biologists need to take a long, hard look at how MPEG-LA has acted and conducted itself in the past. Even if you blame its participants for their collective behavior, it's still pretty damning of this operation and currency of thinking.
Keep CRISPR-Cas9 out of MPEG-LA. Y'all have been warned. Form a pool using defensive patent licenses, do whatever it takes if you really want to reduce "transaction costs", but do it without that community.
No question, both the commercial potential of CRISPR and the humanitarian potential will be served by keeping MPEG LA on the outside. So far that appears to be the case, their dream of acting as the centralized CRISPR patent authority hasn't gotten traction.
I think they probably haven't even sorted out their intentions at this point. But you know, these things just have a way of developing on their own just by tiny nudges at the beginning.
For an overview of the GP-write project, see the following:
Really I'd like to somehow get EFF to ride to my rescue but I've sort of got myself into this mess on my own so it's not really on them. EFF doesn't focus on biological freedom issues like these, anyway. At least not yet.
They don't need to have any control of patents to do this, though, they can simply operate through FUD alone. Even though it's illegal, US IP law is very weak against such fraudulent behaviour and the slap on the wrist they _might_ get if they're caught will be outweighed by the profit they make from those who fall for their racket.
Interesting. From the beginning something has seemed something really, really wrong about CRISPR. The amount of sloppy research, hype, etc has just been well beyond the norm.[1] There is definitely some kind of shady and amoral organization behind it.
[1] For example, in a few years you won't hear anything about the gene editing any longer since that was never going to work (it is too toxic by its very nature of causing DSBs). These other uses may or may not be OK, I haven't looked into it.
So the problem is that there are hundreds or thousands of different types of viral and bacterial infections you can get, many of which probably haven't even been discovered yet, but STD testing only covers the four or five most common things. Even if you can theoretically detect a lot more stuff with CRISPR, it's going to be decades until the technology is anywhere approaching comprehensive.
Not quite true - we're down to around 14 days with the latest generation of tests.
The ideal would be a rapid 'fever' panel that tests for all the viruses we currently pay a ton of money for. This sort of test could pick up early-stage HIV which, if symptomatic, don't feel much different from a cold/flu.
It seems to me that treatment for STDs, and knowing whether someone "might have an STD", are very different problems, that happen to be currently solved by the same solutions.
If you could build a whitelist of known benign strains of bacteria and viruses, and then create a device that tests your urine and dings whenever it detects things that are (positive match) bacterial antibodies or viral capsids, but that aren't (negative match) in its whitelist, that seems like it'd do a lot to help people.
Not really, it's pretty unorthodox to look for genetic sequences as evidence of infection. Typically you look for antibodies, as the virus may not be circulating, or is simply not where you are sampling.
>The prostitution story looks a lot different if every encounter can realistically incorporate a predicated broad-spectrum STD test of both parties.
Disease spread is such a drop-in-the-bucket among the (moral, ethical, personal, societal) issues surrounding prostitution that I have a hard time understanding how this news changes the story.
It's great news; but prostitution is an issue that deserves a lot of time and discussion -- and likely the solutions will be social, not technological.
I think you're underestimating how many men avoid prostitution purely due to fear of contracting disease. Prostitution is legal in Nevada (outside of Reno/Vegas) and the prostitutes operate without pimps. There are far fewer ethical concerns in some places than you imply.
I appreciate your point, but just think of the social changes that came about from birth control and the ability to control when you start a family. This breakthrough might not fix everything but it would be a boon for sexual freedom.
Disease spread is such a drop-in-the-bucket among the (moral, ethical, personal, societal) issues surrounding prostitution
That is simply a matter of perspective and implementation. There are many countries and areas where prostitution is legalised (an sometimes even unionised), and evidence shows that on the whole, the majority of problems associated with prostitution are caused by prohibition.
Given that heterosexual dates are typically paid for by men and husbands typically make a lot more than their wives, it could be argued that the overwhelming majority of heterosexual sex is some form of prostitution. Yet when I criticize dating on that basis, I get called a nutter.
When men and women have some kind of parity where women are not routinely considering their bottom line when deciding how much crap to take in an unhappy relationship, then you can talk to me about the immorality of prostitution. Until then, wow, what a way to put on blinders as to how the vast majority of relationships work.
That's an absurd comparison. Most women have sex with their husbands willingly because they like sex and they like their husband. Prostitution is a quid pro quo business arrangement. Of course, sugar-daddy type relationships
do exist, but they are not the norm. Consider the example of your own parents. Is your mother akin to a prostitute because she had sex with your dad at the same time that he may have been providing for her material needs?
Is your mother akin to a prostitute because she had sex with your dad at the same time that he may have been providing for her material needs?
This is a dirty tactic. It is not good faith engagement.
I'm a woman who has a strict no dating policy, by which I mean that I don't establish romantic relationships based on some man spending money on me. I am entirely satisfied with the positive impact that policy has had on my life.
From what I have read and heard over the years, no, most women don't have sex with their husband because they like him. There are relationships like that, certainly. But the financial factor pretty clearly poisons quite a lot of relationships.
I often think this should be the foundational argument as to why men should be more invested in helping make gender parity happen. If you are a well paid man and tired of feeling like women only date you for your money, fostering a world in which women have money of their own on pat with men is the single best antidote to your dating problem.
As just one supporting citation, this article talks about the fact that pro athletes frequently marry their high school sweetheart because you can't trust that women who met you after you struck it rich really like you. They may just be there for the money. (The article does not use those exact words, but that is the gist of it.)
There are also rap song lyrics about how poor men from the hood can't get a date, but once they strike it rich "it's a puss buffet."
I have read articles where, for example, a guy lost his job and his wife quit having sex with him. He stated that he learned his paycheck was the most attractive thing about him. A friend of a friend lost his well paid job and his wife left him because "it wasn't any fun anymore."
The term gold digging whore is a gendered term. It exists because men typically make a lot more than women and a lot of women are primarily interested in finding someone to pay their bills. This is compounded by the difficulties women face in pursuing serious careers of their own.
While I was homeless, no one wanted to open doors for me career wise. But lots of men wanted to offer me money or a place to stay if I would sleep with them.
In my experience, this problem runs shockingly deep. If your romantic relationships are unaffected by it, count yourself lucky.
> This is a dirty tactic. It is not good faith engagement.
It's not a dirty tactic, it's an analogy meant to snap the reader out of reductive thinking. It's easy to throw out these kind of generalizations when you reduce people to animals, but when you're forced to consider individuals from a human perspective (like in the case of your own mother) suddenly there is a wave of humanizing rationalizations to explain why characterizing marriage as glorified prostitution doesn't really apply in grandma's case.
> most women don't have sex with their husband because they like him
Neither one of us can prove what is in the head of most women when they get into bed with their husbands, but it seems absurd to generally ascribe a financial motivation for married sex-life. Women like sex too, some more than others, it doesn't make a woman a whore if she also enjoys financial support (and you know, all the other qualities that people care about in lasting relationships.
> If you are a well paid man and tired of feeling like women only date you for your money, fostering a world in which women have money of their own on pat with men is the single best antidote to your dating problem
This simply isn't a problem for the vast majority of people. Most eligible bachelors do not make enough money to such an effect where they have to be worried about goldiggers beyond the normal common-sense signs.
> As just one supporting citation, this article talks about the fact that pro athletes frequently marry their high school sweetheart because you can't trust that women who met you after you struck it rich really like you
Individuals with multimillion dollar salaries are clear outliers that have to contend with the impact of their wealth in every personal relationship, trying to generalize that example to the general population doesn't make sense.
> There are also rap song lyrics about how poor men from the hood can't get a date, but once they strike it rich "it's a puss buffet."
Once again, if you become rich and famous you are an outlier that is pointless to apply as a general rule. Also, as someone from the hood, where almost every individual is poor, I promise you that there are LOTS of dates and LOTS of sex, even for broke guys, the most common distinction between guys getting dates and those who are not is confidence, looks, and a sense of humor.
> a guy lost his job and his wife quit having sex with him
Yeah... nobody is saying that doesn't happen, but that is obviously not a common occurrence as any married man who has been unemployed can attest to.
> While I was homeless, no one wanted to open doors for me career wise. But lots of men wanted to offer me money or a place to stay if I would sleep with them.
The fact that men have solicited you has means nothing with regard to the nature of sex within marriage.
Dang, I have the greatest respect for your efforts to improve discourse on the site, but I have to disagree that this is "personally abrasive rhetoric"; the personal aspect is a critical component of the logic within my argument, it is precisely the fact that when we consider our own loved ones in the context of the GP's stated position, it becomes clear that the reasoning is not consistent (because we offer our loved ones a more humanizing outlook when considering the nature of their circumstances rather than describing our mothers and sisters as prostitutes). On a personal note, I am a little surprised that my comment has been flagged as "personally abrasive" but the GP's rhetoric suggesting that married women in general can be likened to prostitutes is not similarly flagged as inflammatory. I am not asking for permission to continue debating this thread, I am only asking that you consider the nuance and context of my reply before judging it as abrasive. Thanks for your hard work.
At least here in NSW Australia, it's a legal and licensed industry. I'm friends with several women who work in the industry, some of which have worked overseas in other brothels. One of the interesting things I've found is how well the regulations, according to them, have worked here in Australia. Due to the protections in place, all of them feel safe in the industry and that it's entirely optional and their own decision. I'm sure this isn't universal, but at least after gleaning this information from them I feel like prostitution can be done right if it's regulated correctly. To ease any thoughts of bias, I've never solicited any of their services - this was told to me strictly as a friend, so there was no need to sugar coat things.
There is no way the majority of the people exchanging sex for money are being accounted for in any reliable fashion. Prostitution is going on all over the place at all times. It's ubiquitous and unless you're participating it's largely kept out of view, being illegal.
This is equivalent to saying we must never legalize alcohol because it will increase the number of people blind from wood alcohol poisoning and increase the amount of money flowing to people like Capone and Nitti.
Also, this:
> with legalization then it only increases the size of the fringe due to the debilitating physical and psychological effects of drug use and promiscuity.
The issue is not just economic, it's spatial and temporal as well. This can provide STD test kits that fit in a pocket, deliver results on-site within minutes, and cost something comparable to an at-home pregnancy test or less.
Just because they have no cost to the end user doesn't mean no one is paying for them. There is a cost associated with producing and distributing those tests.
> Their system uses several CRISPR enzymes, including Cas13 and Csm6, and can be loaded onto a paper strip, making it incredibly easy to use.
Using CRISPR for low cost detection of disease would be a tremendous accomplishment. I wonder if Bill Gates had something like this outcome in mind when he invested into Editas (co-founded by Feng Zhang). It would seem to fit with inexpensive detection approaches he has pursued over the years.
We've been hearing about CRISPR for a couple of years now. Any idea what's the approximate ETA to the market of this kind of technology, and are there any other obstacles except for the human trials? (Don't say "ethical questions" because it's a non-issue, there will be always multiple countries who'd ignore that.)
I hope it won't become another graphene, a discovery with enormous potential that would never leave the lab.
What constitutes "the market" to you? I know someone using CRISPR at work today.
It sounds strange to want it to "leave the lab", since (IANABiologist but) it sounds like a lab-based technology. It'd be like asking when Postgres is going to leave the server. That's where it's used, no?
I think they’re asking when we can expect to see it used clinically. By analogy, vaccines are created in a lab, but they are used outside of one. Clinical CRISPR use would almost certainly require some lab work, but not really much basic science.
>>> graphene, a discovery with enormous potential that would never leave the lab
Just noticed that LL Bean is selling PrimaLoft jackets with Aerogel tech. When mass demand for something like a flexible graphene based display meets economic viability. Then we can expect exponential adoption. But a priori prediction is shrouded in uncertainty.
We've collected a number of the various Cas variants into Pinecone if anyone wants to play around with the proteins [1]. In this article they speak of cheap detection, but in some sense those are the natural technological requirements or outcomes of their much more powerful editors (you have to be able to 'see' the results of what you've edited in order to more efficiently edit). In order to better edit, nice readouts were required to be invented.
The Cas systems are 'pointers' or 'cursors' to locate a specific sequence of DNA or RNA - and once you have a good pointer, you can bring to bear all the rest of biology's tricks at that location. Multi-fluorophore systems are great, and gels are easy. It's a super creative effort to utilize those cheap reagents and assays in the context of a creative 'DNA locator' system in order to amplify a single genomic signal to one that is readable by eye, in the field. And that capability makes the debugging of the editors themselves at the more cheap and easy. Our collective 'toolkit' is now becoming complete enough that the creative and combinatorial usage of existing tools will very quickly explode our capabilities.
(Shame on Science Magazine for publishing a supplemental PDF with Benchling links that you cannot click on and sequences that are not copyable (pg 24). It's 2018!:
http://science.sciencemag.org/content/sci/suppl/2018/02/14/s... (and Benchling, if your target audience is printing out links, you might want to not use both O and 0 in your UIDs))
Pinecone is our public protein design software. Feel free to play around. Feedback is welcomed. We're trying to build an abstraction layer above DNA sequences so you can build genetic tools to fulfill particular capabilities without needing to know how to build DNA.
Or just to help teach what useful designs others have put out there - reveal some of the 'magic' of current gene therapies or genetic editing tools. Some interesting examples: https://serotiny.bio/notes/proteins/
Neat! What sorts of design decisions did you have to confront when designing this language? Have you found it useful as a toy modelling space, i.e. where suitably replicating real-world protein X in “code” reveals interesting things about X?
A bit of a late reply, sorry, but it's a great question.
We found many design decisions we had to confront - more than we expected. The largest two include 1) the decision to use an amino acid sequence as ground truth (and not DNA), and 2) the decision to make the language universally proscriptive (at the cost of being universally descriptive).
Anything you build in the system can be altered, broken apart, and itself be part of a larger whole - all while being manufacturable. But that comes at the cost that there are certain highly complicated overlapping synergistic type designs that just can't be made. Whereas with an entirely descriptive language one can describe the multi-layered fugue that is the HIV genome - but the construction rules become so lax that they lose their instructive capabilities, and can no longer logically guarantee constructibility.
The most interesting (and surprising?) thing we learned is that we now have the only data-structure that can reliable and efficiently answer questions of the sort of, "show me any/all designs that utilize the protein, _GFP_".
These are really great use cases. That said, the article is totally missing the fact that these labs are aggressively developing alternatives to the Cas9 protein to dance around the ongoing CRISPR patent battle...
How do you get information out of a living cell without destroying it?
Right now observing neuron function within our brains is limited to tools such as magnetic resonance imaging. But molecular recorders, such as the Crispr Camera system demonstrated here. Provide a mechanism for cells to log their own history. With storage space extensible to a petri-sized population of bacteria totalling billions of gigabytes!
I think the vision is more than data storage however. Synthetic biological constructs typically involve complex and precise steps. By encoding the recipe in biology. It ushers in the path for automating the laboratory workflow.
Movie Replayed From Living Cells' DNA Debuts "Molecular Recorder"
> How do you get information out of a living cell without destroying it?
Using the existing systems of sensing/data-exfiltration already used by life. Fireflies produce light, jellyfish glow, plants curl up in darkness, fungi bud, flowers blossom, you blush, you sweat, you get hungry, etc.
Couple those outputs to a similar biological input: sensing DNA damage, presence of particular DNA, small molecules, proteins, sugars, etc., sensing of temperature, magnetic field, particular atom/ion, etc.
Couple them: if cold -> glow; if Iron -> blossom, if low blood sugar -> emit light.
The recent "Chimeric Antigen Receptor" approved by the FDA is exactly one such designed way to act on information within a cell; if cancer-like -> kill cell.
These CRISPR tools are similar; if presence of particular DNA -> change DNA, or cut DNA, or activate response.
There is an inherent poetic quality to the inner workings of nature and living beings. Certainly synthetic biology should reflect that ;)
I also think you've hit upon something fundamental. The use of light and photons as the lowest common denominator in biochemical function. Not just in the optogenetic sense. But as the basic building block in biophysics.
And electrons. Amplify an energy difference/transfer to a shift in protein conformation, to the cellular-scale presence/absence of noticable molecules, to actions of cells that are collectively organized to respond, to tissues, to organisms.
Optigenetic tools are just the most clear abstractions from photon->gene, but the same principles apply to thermo-, mechano-, chemo-, etc-, protien sensors (i.e. all of them).
They're all an amplification cascade from photons and electrons upwards. It is elegant in how general that description is (and how it suggests an approach to synthetic designs).
Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6
Jonathan S. Gootenberg1,2,3,4,7,, Omar O. Abudayyeh1,2,3,4,5,, Max J. Kellner1, Julia Joung1,2,3,4, James J. Collins1,4,5,6,8, Feng Zhang1,2,3,4,†
Abstract
Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) that combines isothermal pre-amplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCKv2: 1) 4-channel single reaction multiplexing using orthogonal CRISPR enzymes; 2) quantitative measurement of input down to 2 aM; 3) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxilary CRISPR-associated enzyme; and 4) lateral flow read-out. SHERLOCKv2 can detect Dengue or Zika virus ssRNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.
Abstract
CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing based on its ability to generate targeted, double-stranded DNA (dsDNA) breaks. Here we show that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules. We find that target-activated, non-specific ssDNase cleavage is also a property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase activation with isothermal amplification, we create a method termed DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR), which achieves attomolar sensitivity for DNA detection. DETECTR enables rapid and specific detection of human papillomavirus in patient samples, thereby providing a simple platform for molecular diagnostics.
Wonder where test blood comes from? For the past year or so, whenever I've donated blood, there's an extra page in the donor materials that explains how a sample of each unit goes to research for developing new tests for Zika. (It's a different Zika research project, I'm sure.)
If you want to help researchers developing new blood tests for emergent diseases (or need another reason to donate blood), it's here and it's easy and free. I think that's cooler than anything I'll ever do with technology.
I don't know how significant this [1] is a barrier to such treatments, but it seems likely to be more of a potential problem for cures vs. sensors w/potential false positives.
In theory, yes, but delivery of the CRISPR enzyme to all the infected nuclei is still an unsolved problem. Also, it doesn't cut its target every time it does get in - some of the protein is inactive (probably just broken/malformed/misfolded) - but increasing the dose to compensate leads to more instances where it cuts the wrong target.
Imagine affordable STD test kits adjacent to the pregnancy testers on the shelves of your local store.
The prostitution story looks a lot different if every encounter can realistically incorporate a predicated broad-spectrum STD test of both parties.
Edit: Usual dating would be a lot less risky as well. Has it become standard practice for couples to both get tested before becoming intimate yet?