19 ms·

It is now easy to edit the genomes of plants, animals and humans

92 points by thomasrossi 11y ago

mirimir 11y ago
The article links to another on "gene drives" that use CRISPR to spread genes far more quickly through populations.[0] Cities of the Red Night? >ANIMALS typically have two versions of any given gene stored on two different chomosomes—basically large DNA molecules—and the two versions can have important differences. Offspring normally inherit only one of each pair of chromosomes from each parent, and thus each version of the gene typically gets into only half of them. Technologies like CRISPR make it possible to break this rule with something called a gene drive—a gene that uses gene-editing techniques to copy itself from one chromosome to the other, so that whichever chromosome the offspring inherit they get the same version. The same will then apply to their offspring, too (see diagram). [0] http://www.economist.com/news/briefing/21661801-giving-bits-dna-power-edit-themselves-intriguing-and-worrying-possibility http://www.economist.com/news/briefing/21661801-giving-bits-...
- thomasrossi 11y ago
  nice, thanks. I think the most important step we are still missing are: 1) the reverse drive, so say that some edit is spreading, you must have a way to stop it eventually; 2) telomere-elongating or other DNA repairing goodies (maybe copying from water bears).
  - eggie 11y ago
    The most important step we are missing is the first one, where we "easily" edit the genomes of humans. It is not yet easy, despite the enormous hype surrounding CRISPR-based approaches. Edit: and I understand that gene drive could make it easier to introduce biallelic changes, but this isn't really easy because the drive systems themselves are not even 10% efficient at introducing the exact modification which is desired.
nsns 11y ago
I would say these so-called "ethical questions" are always a red herring (not because they're unimportant, but rather because we don't have a reliable authority to handle them); the real problems that should really be explored beforehand are matters of jurisprudence (e.g. commercial control vs. state control and its implications) and potential weaponization.
- realusername 11y ago
  And also to define guidelines on what to do if shit hits the fan. As an example (nothing related to DNA modification but anyway), I have a few neighbours who planted balsamine plants (I guess it's this one: https://en.wikipedia.org/wiki/Impatiens_glandulifera https://en.wikipedia.org/wiki/Impatiens_glandulifera) because it's a bee friendly plant. The problem is it's an invasive plant, it's now absolutely everywhere and spread kilometres away from the original point. I don't mind because it's harmless and the pink flowers are quite beautiful but it's an example of the kind of unforeseen consequences that can happen.
  - hga 11y ago
    When you're making just a few changes to an organism it's a lot easier to predict and test the outcome, vs. inserting a complete batch of genes in the form of a new to the ecosystem plant like the balsamine you mention. That Wikipedia article details a bunch of ways in which balsamine can out compete local plants and do other undesirable things like encourage erosion by dying each season. In either case a degree of caution is warranted. Which scientists did for genetic engineering, during a period when I was preparing to join them (actually did some E. Coli genetic work in the summer of 1977 in a NSF Summer Science Training Program between my high school sophomore and junior years): https://en.wikipedia.org/wiki/Asilomar_Conference_on_Recombinant_DNA https://en.wikipedia.org/wiki/Asilomar_Conference_on_Recombi... The restrictions resulting from the conference were relaxed over time as appropriate as we gained the relevant knowledge, especially the way in which genes naturally jump around all the time between species. I.e. nature has already tried out a lot of stuff we might want to try, given zillions of organisms and years.
marktangotango 11y ago
The difficulty in realizing the promise of genetic engineering to treat disease, or even do the more esoteric things like enhance abilities or create new species has not been altering genomes. The difficulty has been and continues to be the tremendous difficulty in understanding how proteins fold, given a DNA sequence, and on top of that understanding the biochemical reaction pathways and feedback loops. In the 90's early work showed that sime changes could profound and often detrimental effects.
- ejstronge 11y ago
  Perhaps this is what you mean but I'd add an additional difficulty - we can't predict the organismal impact of many of the genetic manipulations we make. As a result of this, we must perform time-intensive experiments using model organisms like bacteria, flies, mice, etc.
  - marktangotango 11y ago
    Yes that's what I was attempting to illustrate, thank you!
datashovel 11y ago
My only hope, with regard to genetic engineering, is that the people who are actually discovering this stuff are strong enough to prevent large corps from patenting all of the most important intellectual property that will empower future generations. My active imagination hypothesizes that the people who go to work every day to invent / discover this stuff go to work only with the meager hope of collecting on their 6-figure salaries to provide for their families and pay their children through higher education. Perhaps even a stint at an Ivy League school. Meanwhile empowering large multinational corporations / conglomerates with the enormous wealth of intellectual property that their grandparents would be ashamed of.
- onewaystreet 11y ago
  > My only hope, with regard to genetic engineering, is that the people who are actually discovering this stuff are strong enough to prevent large corps from patenting all of the most important intellectual property that will empower future generations. Why? If you ever want this technology to be accessible to the public then someone somewhere is going to have to be making money on it. Drug manufacturing isn't done by colleges or governments.
- melling 11y ago
  I thought patents only lasted 17 years. Having said that, would it be possible to publicly fund more open research? The ALS Ice Bucket Challenge raised $100m, for example. http://www.washingtonpost.com/news/to-your-health/wp/2015/08/19/scientists-are-crediting-the-ice-bucket-challenge-for-breakthroughs-in-research/ http://www.washingtonpost.com/news/to-your-health/wp/2015/08...
- ci5er 11y ago
  I don't know. In the US you get 20 years of protection from a patent from time of filing. If somebody beats you to it, you don't. This means that a lot of tech filings are going to be pre-commercial. This means that once on the market, it will need to be tested by the market. Once the market decides that it is a better/faster/cheaper tool than the competitive product/process/genome, you've got, what, 7~10 years? Maybe? So, during this window, if you over price it, it isn't better/faster/cheaper. If it is priced competively, people benefit. The only "losers" are those that have to wait 10 years to rip off your research and clone your product and undersell you. What's the problem here?
obel1x 11y ago
There was a great talk on the topic of CRISPR-Cas9 at the Hacker News London meet up this month by Edward Perello. Video is here: https://vimeo.com/137001197 https://vimeo.com/137001197. It's a good introduction to the topic from a hacker's perspective.
arvinjoar 11y ago
Here's a Radiolab segment about it (CRISPR) if anyone is interested: http://www.radiolab.org/story/antibodies-part-1-crispr/ http://www.radiolab.org/story/antibodies-part-1-crispr/ I highly recommend listening to it
- belltyler 11y ago
  I came here to post the same thing - an awesome listen.
astazangasta 11y ago
Having worked with this technology, there is a ton of hype. This is NOT easy. First of all you cannot target any sequence; it must match a certain consensus pattern. Second, while cutting is easy (to delete or knock out a gene), introducing a substitution is hard and requires a lot of chance. Third, the process is extremely noisy. You cannot guarantee your edit will occur. Usually you must verify by resequencing, which is actually worse than shRNA. Finally we are far away from full body gene therapy this way, which would involve delivering a CRISPR kit to every cell. In short this is a powerful experimental tool but it is extremely far from freely editing the genome.
- untilHellbanned 11y ago
  Agreed. Biologist here who uses CRISPR too. Gene therapy is limited by getting the DNA into the right cell and having it only do the genome manipulation you want and nothing more. This was hard before and will continue to be hard. That said, it is an amazing advance. There is good reason for excitement.
- deleted 11y ago
  [deleted]
- defen 11y ago
  > Finally we are far away from full body gene therapy this way, which would involve delivering a CRISPR kit to every cell. My layman's understanding of the situation is that the most likely first use of this in humans will be for personal eugenics of one's offspring. Meaning, removing deleterious genes from, or adding beneficial ones to, your sperm or egg cells in a lab and then implanting an embryo.
  - OopsCriticality 11y ago
    > My layman's understanding of the situation is that the most likely first use of this in humans will be for personal eugenics of one's offspring. Meaning, removing deleterious genes from, or adding beneficial ones to, your sperm or egg cells in a lab and then implanting an embryo. My non-layman's prediction is that you are quite incorrect. As others are pointing out, successfully using CRISPER/Cas is hardly as trivial or as easy as the media's hype machine (or university PR offices) would like us to believe. Blatantly obvious ethical issues aside, embryos are hard to tamper with, and the odds of successfully achieving multiple edits to the genome are miniscule. I think the most likely first application of the CRISPER/Cas system in human medicine will be in an autologous bone marrow transplant to correct a genetic disorder of the blood, likely sickle-cell anemia.
dekhn 11y ago
It's more accurate to say, CRISPR represents a technology which makes it easier to change genes in living organisms, possibly in a heritable way. It makes no changes to the delivery mechanism, that is, you still have to make the genomic changes in the cells that matter. I'm greatly appreciative of CRISPR because it elegantly solves the "specific template problem": by providing a generalized sequence non-specific mechanism, any target sequence can be addressed using DNA synthesis. previously, you would have to engineer a unique protein to locate a specific sequence, and because peoples genomes differ, you'd have to reengineer the protein for individuals.
TylerH 11y ago
"easy"
ccvannorman 11y ago
Where would I go to get a job as a software engineer working on CRISPR simulations?
- ejlperello 11y ago
  Hi there, this is Edward (I spoke at the HN London event a few weeks ago on CRISPR - https://vimeo.com/137001197 https://vimeo.com/137001197). I'd encourage you to get in touch with us at Desktop Genetics. We are always on the lookout for talented developers with an interest in biology!
hadeharian 11y ago
Nice paywall you have there.

92 points by thomasrossi 11y ago

The article links to another on "gene drives" that use CRISPR to spread genes far more quickly through populations.[0] Cities of the Red Night? >ANIMALS typically have two versions of any given gene stored on two different chomosomes—basically large DNA molecules—and the two versions can have important differences. Offspring normally inherit only one of each pair of chromosomes from each parent, and thus each version of the gene typically gets into only half of them. Technologies like CRISPR make it possible to break this rule with something called a gene drive—a gene that uses gene-editing techniques to copy itself from one chromosome to the other, so that whichever chromosome the offspring inherit they get the same version. The same will then apply to their offspring, too (see diagram). [0] http://www.economist.com/news/briefing/21661801-giving-bits-dna-power-edit-themselves-intriguing-and-worrying-possibility http://www.economist.com/news/briefing/21661801-giving-bits-...

thomasrossi 11y ago
nice, thanks. I think the most important step we are still missing are: 1) the reverse drive, so say that some edit is spreading, you must have a way to stop it eventually; 2) telomere-elongating or other DNA repairing goodies (maybe copying from water bears).
- eggie 11y ago
  The most important step we are missing is the first one, where we "easily" edit the genomes of humans. It is not yet easy, despite the enormous hype surrounding CRISPR-based approaches. Edit: and I understand that gene drive could make it easier to introduce biallelic changes, but this isn't really easy because the drive systems themselves are not even 10% efficient at introducing the exact modification which is desired.

nsns 11y ago

I would say these so-called "ethical questions" are always a red herring (not because they're unimportant, but rather because we don't have a reliable authority to handle them); the real problems that should really be explored beforehand are matters of jurisprudence (e.g. commercial control vs. state control and its implications) and potential weaponization.

realusername 11y ago
And also to define guidelines on what to do if shit hits the fan. As an example (nothing related to DNA modification but anyway), I have a few neighbours who planted balsamine plants (I guess it's this one: https://en.wikipedia.org/wiki/Impatiens_glandulifera https://en.wikipedia.org/wiki/Impatiens_glandulifera) because it's a bee friendly plant. The problem is it's an invasive plant, it's now absolutely everywhere and spread kilometres away from the original point. I don't mind because it's harmless and the pink flowers are quite beautiful but it's an example of the kind of unforeseen consequences that can happen.
- hga 11y ago
  When you're making just a few changes to an organism it's a lot easier to predict and test the outcome, vs. inserting a complete batch of genes in the form of a new to the ecosystem plant like the balsamine you mention. That Wikipedia article details a bunch of ways in which balsamine can out compete local plants and do other undesirable things like encourage erosion by dying each season. In either case a degree of caution is warranted. Which scientists did for genetic engineering, during a period when I was preparing to join them (actually did some E. Coli genetic work in the summer of 1977 in a NSF Summer Science Training Program between my high school sophomore and junior years): https://en.wikipedia.org/wiki/Asilomar_Conference_on_Recombinant_DNA https://en.wikipedia.org/wiki/Asilomar_Conference_on_Recombi... The restrictions resulting from the conference were relaxed over time as appropriate as we gained the relevant knowledge, especially the way in which genes naturally jump around all the time between species. I.e. nature has already tried out a lot of stuff we might want to try, given zillions of organisms and years.

marktangotango 11y ago

The difficulty in realizing the promise of genetic engineering to treat disease, or even do the more esoteric things like enhance abilities or create new species has not been altering genomes. The difficulty has been and continues to be the tremendous difficulty in understanding how proteins fold, given a DNA sequence, and on top of that understanding the biochemical reaction pathways and feedback loops. In the 90's early work showed that sime changes could profound and often detrimental effects.

ejstronge 11y ago
Perhaps this is what you mean but I'd add an additional difficulty - we can't predict the organismal impact of many of the genetic manipulations we make. As a result of this, we must perform time-intensive experiments using model organisms like bacteria, flies, mice, etc.
- marktangotango 11y ago
  Yes that's what I was attempting to illustrate, thank you!

datashovel 11y ago

My only hope, with regard to genetic engineering, is that the people who are actually discovering this stuff are strong enough to prevent large corps from patenting all of the most important intellectual property that will empower future generations. My active imagination hypothesizes that the people who go to work every day to invent / discover this stuff go to work only with the meager hope of collecting on their 6-figure salaries to provide for their families and pay their children through higher education. Perhaps even a stint at an Ivy League school. Meanwhile empowering large multinational corporations / conglomerates with the enormous wealth of intellectual property that their grandparents would be ashamed of.

onewaystreet 11y ago
> My only hope, with regard to genetic engineering, is that the people who are actually discovering this stuff are strong enough to prevent large corps from patenting all of the most important intellectual property that will empower future generations. Why? If you ever want this technology to be accessible to the public then someone somewhere is going to have to be making money on it. Drug manufacturing isn't done by colleges or governments.
melling 11y ago
I thought patents only lasted 17 years. Having said that, would it be possible to publicly fund more open research? The ALS Ice Bucket Challenge raised $100m, for example. http://www.washingtonpost.com/news/to-your-health/wp/2015/08/19/scientists-are-crediting-the-ice-bucket-challenge-for-breakthroughs-in-research/ http://www.washingtonpost.com/news/to-your-health/wp/2015/08...
ci5er 11y ago
I don't know. In the US you get 20 years of protection from a patent from time of filing. If somebody beats you to it, you don't. This means that a lot of tech filings are going to be pre-commercial. This means that once on the market, it will need to be tested by the market. Once the market decides that it is a better/faster/cheaper tool than the competitive product/process/genome, you've got, what, 7~10 years? Maybe? So, during this window, if you over price it, it isn't better/faster/cheaper. If it is priced competively, people benefit. The only "losers" are those that have to wait 10 years to rip off your research and clone your product and undersell you. What's the problem here?

obel1x 11y ago

There was a great talk on the topic of CRISPR-Cas9 at the Hacker News London meet up this month by Edward Perello. Video is here: https://vimeo.com/137001197 https://vimeo.com/137001197. It's a good introduction to the topic from a hacker's perspective.

arvinjoar 11y ago

Here's a Radiolab segment about it (CRISPR) if anyone is interested: http://www.radiolab.org/story/antibodies-part-1-crispr/ http://www.radiolab.org/story/antibodies-part-1-crispr/ I highly recommend listening to it

belltyler 11y ago
I came here to post the same thing - an awesome listen.

astazangasta 11y ago

Having worked with this technology, there is a ton of hype. This is NOT easy. First of all you cannot target any sequence; it must match a certain consensus pattern. Second, while cutting is easy (to delete or knock out a gene), introducing a substitution is hard and requires a lot of chance. Third, the process is extremely noisy. You cannot guarantee your edit will occur. Usually you must verify by resequencing, which is actually worse than shRNA. Finally we are far away from full body gene therapy this way, which would involve delivering a CRISPR kit to every cell. In short this is a powerful experimental tool but it is extremely far from freely editing the genome.

untilHellbanned 11y ago
Agreed. Biologist here who uses CRISPR too. Gene therapy is limited by getting the DNA into the right cell and having it only do the genome manipulation you want and nothing more. This was hard before and will continue to be hard. That said, it is an amazing advance. There is good reason for excitement.
deleted 11y ago
[deleted]
defen 11y ago
> Finally we are far away from full body gene therapy this way, which would involve delivering a CRISPR kit to every cell. My layman's understanding of the situation is that the most likely first use of this in humans will be for personal eugenics of one's offspring. Meaning, removing deleterious genes from, or adding beneficial ones to, your sperm or egg cells in a lab and then implanting an embryo.
- OopsCriticality 11y ago
  > My layman's understanding of the situation is that the most likely first use of this in humans will be for personal eugenics of one's offspring. Meaning, removing deleterious genes from, or adding beneficial ones to, your sperm or egg cells in a lab and then implanting an embryo. My non-layman's prediction is that you are quite incorrect. As others are pointing out, successfully using CRISPER/Cas is hardly as trivial or as easy as the media's hype machine (or university PR offices) would like us to believe. Blatantly obvious ethical issues aside, embryos are hard to tamper with, and the odds of successfully achieving multiple edits to the genome are miniscule. I think the most likely first application of the CRISPER/Cas system in human medicine will be in an autologous bone marrow transplant to correct a genetic disorder of the blood, likely sickle-cell anemia.

dekhn 11y ago

It's more accurate to say, CRISPR represents a technology which makes it easier to change genes in living organisms, possibly in a heritable way. It makes no changes to the delivery mechanism, that is, you still have to make the genomic changes in the cells that matter. I'm greatly appreciative of CRISPR because it elegantly solves the "specific template problem": by providing a generalized sequence non-specific mechanism, any target sequence can be addressed using DNA synthesis. previously, you would have to engineer a unique protein to locate a specific sequence, and because peoples genomes differ, you'd have to reengineer the protein for individuals.

TylerH 11y ago

"easy"

ccvannorman 11y ago

Where would I go to get a job as a software engineer working on CRISPR simulations?

ejlperello 11y ago
Hi there, this is Edward (I spoke at the HN London event a few weeks ago on CRISPR - https://vimeo.com/137001197 https://vimeo.com/137001197). I'd encourage you to get in touch with us at Desktop Genetics. We are always on the lookout for talented developers with an interest in biology!

hadeharian 11y ago

Nice paywall you have there.