6 ms·

Gene Editing Tool Hailed as a Breakthrough, and It Really Is One

84 points by evo_9 11y ago

reasonattlm 11y ago
Something to consider: it is now technically possible and within the grasp of hundreds of clinics worldwide to run gene therapy. The only reason they aren't yet doing this is that it takes some increment of time to get things lined up; funding, customers, propagation of knowledge, etc. But all the pieces are in place. Myostatin or follistatin gene therapy is about as proven as these things get. It exists in heavily muscled natural mutants, including humans (look up brute whippets). Antibody myostatin blockade has just completed phase 2 clinical trials, adding muscle mass to 75 year olds. Chinese labs are turning out myostatin-free dogs. The BioViva CEO organized her own follistatin gene therapy earlier this year in an overseas lab. Five years from now it won't take starting a company level of networking to fly somewhere and do this. But myostatin for muscle mass is just the best risk/benefit/knowledge picture out of hundreds of alterations that could in theory now be run up in humans, many of which are high risk in the sense that they've only been tried a few times in mice and not followed for a long time. For example adding additional lysosomal receptors to mice restores liver function in old mice to be the same as in young mice. Increased GDF-11 sends stem cells back to work and improves health in old mice. And so on and so forth. The eager early adopter with a hundred thousand dollars to spend ten years from now could spend the time between now and then mining the research literature and organizing collaborators, making connections with labs overseas and setting up for multiple gene therapies down the line, many of which are associated with interventions shown to delay or turn back specific measures of aging in mice. This isn't SENS, it isn't repair of underlying damage, but it is a step ahead of what is currently possible.
- jforman 11y ago
  The greatest barrier here is the FDA. They don't let you perform medical interventions (even breakthroughs like this) without going through a rigorous process. Companies like Editas ($43M Series A) are going through those motions right now.
  - mkempe 11y ago
    The inevitable consequence will be either the abolition of the FDA; or a chasm between advanced medical therapy readily available in some places outside of the US and sclerotic, bureaucratic "healthcare" in the US. Long-term, where I live will depend on the above outcome.
    - deleted 11y ago
      [deleted]
    - jforman 11y ago
      CRISPR is far from being the first technology to be held up in the United States while being available elsewhere. There is very little chance the FDA will materially budge on their standards, and even less chance the FDA will be abolished. Most people have a high degree of trust in the FDA (they have a 65% favorability rating according to Pew). Note that the FDA does allow some compassionate use of experimental medications and technologies in extreme cases. I'm not familiar with Editas's regulatory strategy but it wouldn't be crazy for them to pursue that avenue for, say, a child cancer patient as an early step. But even they will be cautious, as any misstep (i.e., harm to a patient) will have major negative consequences for the technology as a whole.
- dekhn 11y ago
  I'm not denying running these experiments is becoming much more feasible for small institutions but you have a pretty naive understanding on how to turn these kinds of experiments into successful therapies. There is often a huge disconnect between what we can reliably and reproducibly show in a lab, and what can be turned into therapy. And that's not just as simple as mining the literature and running more trials.
  - reasonattlm 11y ago
    One of my points is that adoption is going to precede the current consensus definition of "successful therapy" by a decade, in much the same way as happened for stem cell therapies following the turn of the century.
kauffj 11y ago
In the debate over the continued utility of human labor in the face of automation, I suspect gene editing (and/or embryo selection) is the most ignored countervailing factor.
- circlecrimson 11y ago
  So all these truckdrivers that are being replaced with self driving rigs are going to get into biotech now?
  - valarauca1 11y ago
    Nope. Self driving cars are gonna be a huge problem. I don't think many people realize that nearly 9% of the US Employed workforce has no skill other then driving a vehicle.
    - livingparadox 11y ago
      What exactly is to stop them from learning a new trade?
      - pc86 11y ago
        Nothing except time and money, but that's a lot of people. Even occurring over a decade or more it's going to cause the wages of a lot of those trades to plummet.
        livingparadox 11y ago
        The specific instance here was drivers, who in this hypothetical, will be outcompeted by self driving cars, and and naturally find themselves with more time on their hands whether they want it or not. As to money, there are a number of trades you can learn without spending money. And there are also jobs where you get on-the-job training. I'm not saying it won't be a problem for these people, but eventually, most if not all will adjust to the new situation and find themselves in a new job.
dekhn 11y ago
The application of CRISPR/Cas to gene editing, while a breakthrough, is more about technology than science. It just makes things easier- similar to the way compilers make it easier to program computers than assembly language. I also find it interesting that we consider this tool a breakthrough when nearly all our tools for gene editing are just copped off bacteria that have been using them for billions of years.
- zzalpha 11y ago
  Yeah! Like, antibiotics, man. It was basically mold that invented that! Totally not a medical breakthrough at all... no idea why so many people were impressed by it.
  - bostonpete 11y ago
    Fusion was invented by the sun (at least in this solar system -- there are theories that it was independently invented elsewhere too)!
    - zzalpha 11y ago
      Pfft, the sun just cribbed that idea from the big bang. Typical, unoriginal sun...
  - dekhn 11y ago
    The difference is that antibiotics weren't a tool to make more discoveries. They were an immediately applicable medical breakthrough (which also happens to be a useful tool, for example as a genetic marker). CRISPR/Cas9 is just a tool, not an immediately applicable therapy.
leeoniya 11y ago
From what I understand (from a PhD in biotech), the price for utilizing CRISPR/Cas9 is extraordinary. So much so that only multi-million dollar labs can afford to use it in any meaningful quantity. The price "per reaction" is in the thousands.
- zzalpha 11y ago
  Any insight into the source of those costs?
  - leeoniya 11y ago
    licensing the tech, plus no competition = charge what the market will bear http://labiotech.eu/crispr-patent-war-end-discovery-new-editing-protein-cas9/ http://labiotech.eu/crispr-patent-war-end-discovery-new-edit...
    - zzalpha 11y ago
      So patents. That was going to be my guess. So in 20 years it'll be pretty cheap. Meanwhile, China and other parts of the world that happily ignore patents will use the technology without restriction.
      - mentat 11y ago
        There's a common sci-fi theme about China being way ahead in the future. I've never heard a plausible explanation in book but ignoring patents is a really interesting angle.
        CamperBob2 11y ago
        That's how it always works. Early American industrialists weren't exactly diligent at paying royalties to British and continental European patent holders... and now it's China's turn to prosper by doing the same thing to us. More power to them. Patents are a racket that governments run against their own people, exclusively for the benefit of a very few inventors and a whole lot of lawyers.
MathsOX 11y ago
A quote that stuck with me from a molecular biology class taken a year ago, "It's not who wins a Nobel Prize off of CRISPR work, it's how many there will end up being".
smoyer 11y ago
It's funny that this should appear on HN ... Sunday I just completed a bit of software that looks for candidate CRISPR sites in a particular mouse genome for my daughter. In our case, the real trick is to find repeats in the section of the chromosome she wants to manipulate that don't also exist in the rest of the chromosome - or any of the other chromosomes. Like any "big data" project, the trick is representing your data in a way that makes searching it trivial as well as parallelizable.
- junto 11y ago
  That sounds like a very interesting and I'm assuming, a sad story. Do you mind if I ask if you are sharing it publicly?
  - smoyer 11y ago
    It took me a few rereads of my original post to realize what might be sad about it ... then I got it. It's actually a happy story (for me). My daughter is a PhD candidate at the Johns Hopkins school of medicine and is working towards becoming a researcher (molecular genetics). I'm not sure I should comment on which lab she's working in or what they're trying to accomplish. It might not be fun for the mouse but I'm thankful for projects like this because we get to work on something together. It's almost like going back to when she was a girl doing a science project in elementary school.
miiiiiike 11y ago
Radiolab had a great episode about CRISPR earlier this year: http://www.radiolab.org/story/antibodies-part-1-crispr/ http://www.radiolab.org/story/antibodies-part-1-crispr/
fasteo 11y ago
Although not usually mentioned, it is important to note that CRISPR is a natural process that bacteria use as part of their immune system. For what is worth, the mechanistic process and a specific functional result - defend against viruses - have stood the proof of time. "bacteria use Cas enzymes to grab fragments of viral DNA. They then insert the virus fragments into their own CRISPR sequences. Later, when another virus comes along, the bacteria can use the CRISPR sequence as a cheat sheet to recognize the invader." [1] [1] https://www.quantamagazine.org/20150206-crispr-dna-editor-bacteria/ https://www.quantamagazine.org/20150206-crispr-dna-editor-ba...
thecosas 11y ago
I am excited and worried about what CRISPR will bring about.
entee 11y ago
I've often wondered how CRISPR is actually useful, because at its core it's just a nuclease. It allows to you precisely cut DNA where you want to cut it. But for that to be useful you still have to put the DNA back together afterwards. I found this article useful for understanding the different ways that happens in practice: https://www.addgene.org/CRISPR/guide/ https://www.addgene.org/CRISPR/guide/ Turns out you get some small mutations in the most common mechanism (non-homologous end joining or NHEJ). This could be a problem for use in therapies, but definitely not a huge issue for most research-based applications where you can control which mutants you allow to proceed to the next experiment.
- 88e282102ae2e5b 11y ago
  This is one reason why Cpf1 could be interesting, since it leaves sticky ends when it cuts: http://www.cell.com/cell/abstract/S0092-8674%2815%2901200-3 http://www.cell.com/cell/abstract/S0092-8674%2815%2901200-3

84 points by evo_9 11y ago

Something to consider: it is now technically possible and within the grasp of hundreds of clinics worldwide to run gene therapy. The only reason they aren't yet doing this is that it takes some increment of time to get things lined up; funding, customers, propagation of knowledge, etc. But all the pieces are in place. Myostatin or follistatin gene therapy is about as proven as these things get. It exists in heavily muscled natural mutants, including humans (look up brute whippets). Antibody myostatin blockade has just completed phase 2 clinical trials, adding muscle mass to 75 year olds. Chinese labs are turning out myostatin-free dogs. The BioViva CEO organized her own follistatin gene therapy earlier this year in an overseas lab. Five years from now it won't take starting a company level of networking to fly somewhere and do this. But myostatin for muscle mass is just the best risk/benefit/knowledge picture out of hundreds of alterations that could in theory now be run up in humans, many of which are high risk in the sense that they've only been tried a few times in mice and not followed for a long time. For example adding additional lysosomal receptors to mice restores liver function in old mice to be the same as in young mice. Increased GDF-11 sends stem cells back to work and improves health in old mice. And so on and so forth. The eager early adopter with a hundred thousand dollars to spend ten years from now could spend the time between now and then mining the research literature and organizing collaborators, making connections with labs overseas and setting up for multiple gene therapies down the line, many of which are associated with interventions shown to delay or turn back specific measures of aging in mice. This isn't SENS, it isn't repair of underlying damage, but it is a step ahead of what is currently possible.

jforman 11y ago
The greatest barrier here is the FDA. They don't let you perform medical interventions (even breakthroughs like this) without going through a rigorous process. Companies like Editas ($43M Series A) are going through those motions right now.
- mkempe 11y ago
  The inevitable consequence will be either the abolition of the FDA; or a chasm between advanced medical therapy readily available in some places outside of the US and sclerotic, bureaucratic "healthcare" in the US. Long-term, where I live will depend on the above outcome.
  - deleted 11y ago
    [deleted]
  - jforman 11y ago
    CRISPR is far from being the first technology to be held up in the United States while being available elsewhere. There is very little chance the FDA will materially budge on their standards, and even less chance the FDA will be abolished. Most people have a high degree of trust in the FDA (they have a 65% favorability rating according to Pew). Note that the FDA does allow some compassionate use of experimental medications and technologies in extreme cases. I'm not familiar with Editas's regulatory strategy but it wouldn't be crazy for them to pursue that avenue for, say, a child cancer patient as an early step. But even they will be cautious, as any misstep (i.e., harm to a patient) will have major negative consequences for the technology as a whole.
dekhn 11y ago
I'm not denying running these experiments is becoming much more feasible for small institutions but you have a pretty naive understanding on how to turn these kinds of experiments into successful therapies. There is often a huge disconnect between what we can reliably and reproducibly show in a lab, and what can be turned into therapy. And that's not just as simple as mining the literature and running more trials.
- reasonattlm 11y ago
  One of my points is that adoption is going to precede the current consensus definition of "successful therapy" by a decade, in much the same way as happened for stem cell therapies following the turn of the century.

kauffj 11y ago

In the debate over the continued utility of human labor in the face of automation, I suspect gene editing (and/or embryo selection) is the most ignored countervailing factor.

circlecrimson 11y ago
So all these truckdrivers that are being replaced with self driving rigs are going to get into biotech now?
- valarauca1 11y ago
  Nope. Self driving cars are gonna be a huge problem. I don't think many people realize that nearly 9% of the US Employed workforce has no skill other then driving a vehicle.
  - livingparadox 11y ago
    What exactly is to stop them from learning a new trade?
    - pc86 11y ago
      Nothing except time and money, but that's a lot of people. Even occurring over a decade or more it's going to cause the wages of a lot of those trades to plummet.
      - livingparadox 11y ago
        The specific instance here was drivers, who in this hypothetical, will be outcompeted by self driving cars, and and naturally find themselves with more time on their hands whether they want it or not. As to money, there are a number of trades you can learn without spending money. And there are also jobs where you get on-the-job training. I'm not saying it won't be a problem for these people, but eventually, most if not all will adjust to the new situation and find themselves in a new job.

dekhn 11y ago

The application of CRISPR/Cas to gene editing, while a breakthrough, is more about technology than science. It just makes things easier- similar to the way compilers make it easier to program computers than assembly language. I also find it interesting that we consider this tool a breakthrough when nearly all our tools for gene editing are just copped off bacteria that have been using them for billions of years.

zzalpha 11y ago
Yeah! Like, antibiotics, man. It was basically mold that invented that! Totally not a medical breakthrough at all... no idea why so many people were impressed by it.
- bostonpete 11y ago
  Fusion was invented by the sun (at least in this solar system -- there are theories that it was independently invented elsewhere too)!
  - zzalpha 11y ago
    Pfft, the sun just cribbed that idea from the big bang. Typical, unoriginal sun...
- dekhn 11y ago
  The difference is that antibiotics weren't a tool to make more discoveries. They were an immediately applicable medical breakthrough (which also happens to be a useful tool, for example as a genetic marker). CRISPR/Cas9 is just a tool, not an immediately applicable therapy.

leeoniya 11y ago

From what I understand (from a PhD in biotech), the price for utilizing CRISPR/Cas9 is extraordinary. So much so that only multi-million dollar labs can afford to use it in any meaningful quantity. The price "per reaction" is in the thousands.

zzalpha 11y ago
Any insight into the source of those costs?
- leeoniya 11y ago
  licensing the tech, plus no competition = charge what the market will bear http://labiotech.eu/crispr-patent-war-end-discovery-new-editing-protein-cas9/ http://labiotech.eu/crispr-patent-war-end-discovery-new-edit...
  - zzalpha 11y ago
    So patents. That was going to be my guess. So in 20 years it'll be pretty cheap. Meanwhile, China and other parts of the world that happily ignore patents will use the technology without restriction.
    - mentat 11y ago
      There's a common sci-fi theme about China being way ahead in the future. I've never heard a plausible explanation in book but ignoring patents is a really interesting angle.
      - CamperBob2 11y ago
        That's how it always works. Early American industrialists weren't exactly diligent at paying royalties to British and continental European patent holders... and now it's China's turn to prosper by doing the same thing to us. More power to them. Patents are a racket that governments run against their own people, exclusively for the benefit of a very few inventors and a whole lot of lawyers.

MathsOX 11y ago

A quote that stuck with me from a molecular biology class taken a year ago, "It's not who wins a Nobel Prize off of CRISPR work, it's how many there will end up being".

smoyer 11y ago

It's funny that this should appear on HN ... Sunday I just completed a bit of software that looks for candidate CRISPR sites in a particular mouse genome for my daughter. In our case, the real trick is to find repeats in the section of the chromosome she wants to manipulate that don't also exist in the rest of the chromosome - or any of the other chromosomes. Like any "big data" project, the trick is representing your data in a way that makes searching it trivial as well as parallelizable.

junto 11y ago
That sounds like a very interesting and I'm assuming, a sad story. Do you mind if I ask if you are sharing it publicly?
- smoyer 11y ago
  It took me a few rereads of my original post to realize what might be sad about it ... then I got it. It's actually a happy story (for me). My daughter is a PhD candidate at the Johns Hopkins school of medicine and is working towards becoming a researcher (molecular genetics). I'm not sure I should comment on which lab she's working in or what they're trying to accomplish. It might not be fun for the mouse but I'm thankful for projects like this because we get to work on something together. It's almost like going back to when she was a girl doing a science project in elementary school.

miiiiiike 11y ago

Radiolab had a great episode about CRISPR earlier this year: http://www.radiolab.org/story/antibodies-part-1-crispr/ http://www.radiolab.org/story/antibodies-part-1-crispr/

fasteo 11y ago

Although not usually mentioned, it is important to note that CRISPR is a natural process that bacteria use as part of their immune system. For what is worth, the mechanistic process and a specific functional result - defend against viruses - have stood the proof of time. "bacteria use Cas enzymes to grab fragments of viral DNA. They then insert the virus fragments into their own CRISPR sequences. Later, when another virus comes along, the bacteria can use the CRISPR sequence as a cheat sheet to recognize the invader." [1] [1] https://www.quantamagazine.org/20150206-crispr-dna-editor-bacteria/ https://www.quantamagazine.org/20150206-crispr-dna-editor-ba...

thecosas 11y ago

I am excited and worried about what CRISPR will bring about.

entee 11y ago

I've often wondered how CRISPR is actually useful, because at its core it's just a nuclease. It allows to you precisely cut DNA where you want to cut it. But for that to be useful you still have to put the DNA back together afterwards. I found this article useful for understanding the different ways that happens in practice: https://www.addgene.org/CRISPR/guide/ https://www.addgene.org/CRISPR/guide/ Turns out you get some small mutations in the most common mechanism (non-homologous end joining or NHEJ). This could be a problem for use in therapies, but definitely not a huge issue for most research-based applications where you can control which mutants you allow to proceed to the next experiment.

88e282102ae2e5b 11y ago
This is one reason why Cpf1 could be interesting, since it leaves sticky ends when it cuts: http://www.cell.com/cell/abstract/S0092-8674%2815%2901200-3 http://www.cell.com/cell/abstract/S0092-8674%2815%2901200-3