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So to the non-geneticist noobs (like me), is it correct to interpret this finding as suggesting that the promises of CRISPR may be dead in the water? Does this

So to the non-geneticist noobs (like me), is it correct to interpret this finding as suggesting that the promises of CRISPR may be dead in the water? Does this mean all the hype was nothing more than hype? Should anyone with investments in CRISPR be seriously looking at dumping their stock? Should anyone who was holding out on CRISPR to give us super powers / cure disease / etc start drinking copious amounts of alcohol instead? Despite my tone, I seriously am asking what the implications of this are, because it's not my area of expertise.

chongli 8y ago
CRISPR holds way more promise than silly fantasies of human genetic enhancement. The most exciting and practical uses for it apply to challenging everyday problems: food, energy, invasive species, biodiversity. Besides, the ethical problems with experimenting on human beings are extremely intractable.
- nserrino 8y ago
  How is a CRISPR trial on a terminal patient any different than another experimental medical trial on that same terminal patient?
  - whatshisface 8y ago
    Because you don't modify the genetics of terminal, living adults, you want to modify the genetics of single-cell healthy zygotes (who will, you hope, later develop into healthy adults).
    - mbreese 8y ago
      Sure you do. A lot of the promise of CRISPR therapies were for modifying cells in an adult or child. Using CRISPR/cas9 to “fix” a genetic issue in someone who was already born. For example for adding back a good copy of the gene that causes cistic fibrosis or sickle cell anemia. There were also potential cancer therapies based on the technique. In these cases, the presence of cas9 antibodies is a severe limit to many of the techniques that these companies were working towards.
  - SmellyGeekBoy 8y ago
    I agree. My father has terminal cancer and has been practically banging down doors to try to get onto medical trials for new experimental treatments. If other people in his position want to do the same thing then who are we to judge?
- jamesrcole 8y ago
  > CRISPR holds way more promise than silly fantasies of human genetic enhancement I really dislike pandering, dismissive statements like this. What's so inherently wrong with the entire category of genetic "enhancements" (changes for a perceived positive benefit)? You can't respond to this by just pointing out some proposed enhancements or motivations that are silly. I'm asking why you object to the very idea of any enhancements. What about changes to make the following at some point in the future (these are just to give the general idea of positive changes, I'm not saying CRISPR could necessarily be used for them). These are things that in principle could be addressed by genetic "enhancements". - stop people from getting diseases like celiac disease - lessen our evolutionary desire for fatty and sugary foods (that no longer makes sense in the modern world, and which causes great harm) - address some of the more egregious cognitive biases that cause so many problems in the world
  - SmellyGeekBoy 8y ago
    > address some of the more egregious cognitive biases that cause so many problems in the world I'm not sure how to interpret this - are you saying we should use CRISPR to make people think a certain way? If so this seems like a pretty horrific suggestion.
    - jamesrcole 8y ago
      Humans are, for example, very poor at making risk assessments. Evolution has "programmed" our brains to focus too much on certain things and not enough on others. These heuristics might have made sense in ancestral environments bit are quite harmful in today's world. Evolution has already "made us think a certain way". Why would it be so horrific to, for example, lessen certain of those tendancies, if they are harmful?
      - wgjordan 8y ago
        In order to consolidate the consensus needed to genetically alter specific 'cognitive biases' that are 'harmful' to 'humans' in 'today's world', you'll probably first need to establish a global totalitarian dictatorship ('take over the world'). That adds an extra technical challenge beyond CRISPR itself, but you can always shoot for the moon and land among the stars.
acomjean 8y ago
Well CRISPR works in flies as some of the fly stocks have been switched from using RNAi to CRISPR for their gene edits. Fly immune systems obviously are quite different. But the technique still holds a lot of promise. Like any cutting edge technology there are potential problems in developing it into useful therapies, and there is a chance something better will come along and displace it. It is very difficult to edit all the dna of living organism as each cell has a copy. Easier to do as an organism develops.
- meschi 8y ago
  This is how you get Brundlefly :O
mtgx 8y ago
Anything as powerful as CRISPR will most likely be misused and have a very high error rate/unexpected consequences initially anyway: https://labiotech.eu/medical/crispr-therapy-cancer-risk/ https://labiotech.eu/medical/crispr-therapy-cancer-risk/ CRISPR is definitely going to go through the "hype cycle" - as in the hype will die out long before we can prove it can be safely used in humans, and these achievements will likely happen in the background over several decades time span. https://en.wikipedia.org/wiki/Hype_cycle https://en.wikipedia.org/wiki/Hype_cycle
- klmr 8y ago
  The difference between CRISPR and many other overhyped technologies is that CRISPR has already proven its mettle. It’s being used productively daily in labs across the world and has lowered the cost of performing many experiments, or even made new experiments possible in the first place. You’re right that there’s a certain amount of hype surrounding CRISPR, especially when it comes to potential medical application (whether this works remains to be seen, although I and most people in the field remain optimistic). But until something even better comes along I don’t think interest in CRISPR will die down soon.
Camillo 8y ago
It sounds like they can work around this with immunosuppressants. Which may be for the best... you wouldn't want random bacteria to be able to edit your genome at any time, would you?
deleted 8y ago
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- deleted 8y ago
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88e282102ae2e5b 8y ago
No. Working around this takes some effort but is straightforward and uses well-known, existing techniques. There's a lab I know of that considered trying to modify the protein so it could evade the immune system, but they decided against it since they figured the group that published this paper would have too much of a head start and there's no way they'd be able to compete. I'd give it a year or so, and that's assuming none of the other Cas9 or Cas12a variants are already usable.
elocinstr8t 8y ago
I hope not. CRISPR has a lot of potential to change our lives. I thought they're actually a little closer to finding solutions to treatments of incurable diseases and giving us life longevity. Now I'm not so sure.
User23 8y ago
What the layman thinks of genetic engineering magic is going to have to happen in the germline. That means it's not going to help you or me or anyone else already alive.
- klmr 8y ago
  This is true for most genetic engineering applications but not all. Somatic gene therapy has been successfully performed in a few cases. There will almost certainly be more applications in the future, and it’s reasonable to expect that they will be able to handle some prevalent diseases (such as all types of diabetes).
  - refurb 8y ago
    The only approved genetic therapies (Luxturna, Strimvelis, Glybera, others) are all for children or adults. To say you can only use it for germ line modification is just plain wrong.
    - klmr 8y ago
      True but that’s purely for legal/ethical reasons, not (directly) scientific ones. Most scientific uses of CRISPR (and other gene editing techniques) by far happen in the germ line. Germ line research (and, thus, applications) are lacking in humans not because it would be scientifically hard, nor because it won’t eventually happen, but because of hard ethical problems with such research. And the comment that I replied to implies that it is talking about certain applications of genetic engineering which have to happen in the germ line. So I disagree that what it says is “plain wrong”, it’s just incomplete.
      - refurb 8y ago
        I’d say it’s less for ethical reasons (though that’s true) and more because the technology for modifying germ lines is nowhere near as advanced as inserting DNA into non-germ line cells. We have no idea what the impact would be for modifying germ line cells in a developing human being.
justfor1comment 8y ago
Do you think humans would stop at the first hurdle they encounter in their endeavours? How about the 99th hurdle? CRISPR is a naturally occurring gene editing tool. We have only recently started engineering solutions using it. Once this tool meets the full might of human ingenuity and our constant resolve to improve things, it can overcome great biological challenges. Eliminating disease carrying pests, curing genetic defects in children, shortened crop cycles, tastier strawberries these are some amazing possibilities that CRISPR holds. It might take some time but we will get there. So no the game is not over. It won't be over as long as we have a few humans on the case.

chongli 8y ago

CRISPR holds way more promise than silly fantasies of human genetic enhancement. The most exciting and practical uses for it apply to challenging everyday problems: food, energy, invasive species, biodiversity. Besides, the ethical problems with experimenting on human beings are extremely intractable.

nserrino 8y ago
How is a CRISPR trial on a terminal patient any different than another experimental medical trial on that same terminal patient?
- whatshisface 8y ago
  Because you don't modify the genetics of terminal, living adults, you want to modify the genetics of single-cell healthy zygotes (who will, you hope, later develop into healthy adults).
  - mbreese 8y ago
    Sure you do. A lot of the promise of CRISPR therapies were for modifying cells in an adult or child. Using CRISPR/cas9 to “fix” a genetic issue in someone who was already born. For example for adding back a good copy of the gene that causes cistic fibrosis or sickle cell anemia. There were also potential cancer therapies based on the technique. In these cases, the presence of cas9 antibodies is a severe limit to many of the techniques that these companies were working towards.
- SmellyGeekBoy 8y ago
  I agree. My father has terminal cancer and has been practically banging down doors to try to get onto medical trials for new experimental treatments. If other people in his position want to do the same thing then who are we to judge?
jamesrcole 8y ago
> CRISPR holds way more promise than silly fantasies of human genetic enhancement I really dislike pandering, dismissive statements like this. What's so inherently wrong with the entire category of genetic "enhancements" (changes for a perceived positive benefit)? You can't respond to this by just pointing out some proposed enhancements or motivations that are silly. I'm asking why you object to the very idea of any enhancements. What about changes to make the following at some point in the future (these are just to give the general idea of positive changes, I'm not saying CRISPR could necessarily be used for them). These are things that in principle could be addressed by genetic "enhancements". - stop people from getting diseases like celiac disease - lessen our evolutionary desire for fatty and sugary foods (that no longer makes sense in the modern world, and which causes great harm) - address some of the more egregious cognitive biases that cause so many problems in the world
- SmellyGeekBoy 8y ago
  > address some of the more egregious cognitive biases that cause so many problems in the world I'm not sure how to interpret this - are you saying we should use CRISPR to make people think a certain way? If so this seems like a pretty horrific suggestion.
  - jamesrcole 8y ago
    Humans are, for example, very poor at making risk assessments. Evolution has "programmed" our brains to focus too much on certain things and not enough on others. These heuristics might have made sense in ancestral environments bit are quite harmful in today's world. Evolution has already "made us think a certain way". Why would it be so horrific to, for example, lessen certain of those tendancies, if they are harmful?
    - wgjordan 8y ago
      In order to consolidate the consensus needed to genetically alter specific 'cognitive biases' that are 'harmful' to 'humans' in 'today's world', you'll probably first need to establish a global totalitarian dictatorship ('take over the world'). That adds an extra technical challenge beyond CRISPR itself, but you can always shoot for the moon and land among the stars.

acomjean 8y ago

Well CRISPR works in flies as some of the fly stocks have been switched from using RNAi to CRISPR for their gene edits. Fly immune systems obviously are quite different. But the technique still holds a lot of promise. Like any cutting edge technology there are potential problems in developing it into useful therapies, and there is a chance something better will come along and displace it. It is very difficult to edit all the dna of living organism as each cell has a copy. Easier to do as an organism develops.

meschi 8y ago
This is how you get Brundlefly :O

mtgx 8y ago

Anything as powerful as CRISPR will most likely be misused and have a very high error rate/unexpected consequences initially anyway: https://labiotech.eu/medical/crispr-therapy-cancer-risk/ https://labiotech.eu/medical/crispr-therapy-cancer-risk/ CRISPR is definitely going to go through the "hype cycle" - as in the hype will die out long before we can prove it can be safely used in humans, and these achievements will likely happen in the background over several decades time span. https://en.wikipedia.org/wiki/Hype_cycle https://en.wikipedia.org/wiki/Hype_cycle

klmr 8y ago
The difference between CRISPR and many other overhyped technologies is that CRISPR has already proven its mettle. It’s being used productively daily in labs across the world and has lowered the cost of performing many experiments, or even made new experiments possible in the first place. You’re right that there’s a certain amount of hype surrounding CRISPR, especially when it comes to potential medical application (whether this works remains to be seen, although I and most people in the field remain optimistic). But until something even better comes along I don’t think interest in CRISPR will die down soon.

Camillo 8y ago

It sounds like they can work around this with immunosuppressants. Which may be for the best... you wouldn't want random bacteria to be able to edit your genome at any time, would you?

deleted 8y ago

[deleted]

deleted 8y ago
[deleted]

88e282102ae2e5b 8y ago

No. Working around this takes some effort but is straightforward and uses well-known, existing techniques. There's a lab I know of that considered trying to modify the protein so it could evade the immune system, but they decided against it since they figured the group that published this paper would have too much of a head start and there's no way they'd be able to compete. I'd give it a year or so, and that's assuming none of the other Cas9 or Cas12a variants are already usable.

elocinstr8t 8y ago

I hope not. CRISPR has a lot of potential to change our lives. I thought they're actually a little closer to finding solutions to treatments of incurable diseases and giving us life longevity. Now I'm not so sure.

User23 8y ago

What the layman thinks of genetic engineering magic is going to have to happen in the germline. That means it's not going to help you or me or anyone else already alive.

klmr 8y ago
This is true for most genetic engineering applications but not all. Somatic gene therapy has been successfully performed in a few cases. There will almost certainly be more applications in the future, and it’s reasonable to expect that they will be able to handle some prevalent diseases (such as all types of diabetes).
- refurb 8y ago
  The only approved genetic therapies (Luxturna, Strimvelis, Glybera, others) are all for children or adults. To say you can only use it for germ line modification is just plain wrong.
  - klmr 8y ago
    True but that’s purely for legal/ethical reasons, not (directly) scientific ones. Most scientific uses of CRISPR (and other gene editing techniques) by far happen in the germ line. Germ line research (and, thus, applications) are lacking in humans not because it would be scientifically hard, nor because it won’t eventually happen, but because of hard ethical problems with such research. And the comment that I replied to implies that it is talking about certain applications of genetic engineering which have to happen in the germ line. So I disagree that what it says is “plain wrong”, it’s just incomplete.
    - refurb 8y ago
      I’d say it’s less for ethical reasons (though that’s true) and more because the technology for modifying germ lines is nowhere near as advanced as inserting DNA into non-germ line cells. We have no idea what the impact would be for modifying germ line cells in a developing human being.

justfor1comment 8y ago

Do you think humans would stop at the first hurdle they encounter in their endeavours? How about the 99th hurdle? CRISPR is a naturally occurring gene editing tool. We have only recently started engineering solutions using it. Once this tool meets the full might of human ingenuity and our constant resolve to improve things, it can overcome great biological challenges. Eliminating disease carrying pests, curing genetic defects in children, shortened crop cycles, tastier strawberries these are some amazing possibilities that CRISPR holds. It might take some time but we will get there. So no the game is not over. It won't be over as long as we have a few humans on the case.