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> 2 - If so, could the use of CRISPR be premature, if not dangerous? This is really an ill-posed question. First off, CRISPR is a tool. Its novelty is the fact

by klmr 8y ago

> 2 - If so, could the use of CRISPR be premature, if not dangerous? This is really an ill-posed question. First off, CRISPR is a tool. Its novelty is the fact that it makes an experiment vastly simpler and more reliable — but, fundamentally, the experiment was already possible beforehand. So CRISPR itself isn’t dangerous. At most, modifying genetic material could be. Secondly, genetic modification — whether by CRISPR or other methods — is an extremely generic process. Sure, it could be dangerous, if you use it to perform dangerous experiments. Can it have unintended side-effects? Sure, we already know about those. In fact, one of the great things about CRISPR is that it drastically decreases side-effects. But is CRISPR dangerous specifically because we underestimate the complexity of DNA? No. Nothing about CRISPR assumes that we know all biological processes that involve DNA. In fact, we know that we don’t know them all. Lastly, somebody with an “alt view on DNA” immediately sounds like a crackpot with a poor handle on modern biology. That may sound harsh but biology is a science, not a pseudoscience or protoscience (or magic): we’re moving within some relatively fixed boundaries imposed by experimentation and evidence. Uncertainty or lack of knowledge isn’t a free-for-all to insert wild speculations that usually amount to “everything we know is wrong”. It’s very rare that “everything we know turns out to be wrong”. In reality, subsequent findings refine existing ones, or disprove specific hypotheses. They don’t disprove an established field. Even something as revolutionary as Einstein’s theory of relativity didn’t do that: gravity continued to function just fine afterwards. Newton continues to be taught in school, because Newton’s laws continue to be relevant.

laythea 8y ago
"...biology is a science, not a pseudoscience or protoscience (or magic)" I agree with your overall point but I take slight issue with this statement. I am not biologically educated, but I am biological. I have no idea what my conscious is or why/how it works, even though I do know that I exist. And neither do you, nor anyone. To me, that is the classic definition of magic. This differs from eg electronics, physics etc, because I am biological. I have a personal perspective on it, in a manner that I could never with electronics, physics etc. Ie. I can readily understand how far away from understanding the biological process humanity is.
- ethelward 8y ago
  With the same idea, you're also made of physical particles, and we don't really understand how they actually work.
  - laythea 8y ago
    Yes I do agree that there is a point we have to stop. However, how would you class yourself: - biological - electrical - chemical - etc It would be biological for me, although I know I am all the above.
    - robbiep 8y ago
      This is a false dichotomy. The layers don’t stop because you choose one: you are biological, because you’re chemical, because you’re physical (which is more like saying you’re electrical). Ie. Laws of physics govern the laws of chemistry and the first couple are chiseled in stone for the most part. Biology, that is to physics what psychology is to surgery (perhaps mathematics is a batter analogy). You can’t choose that you are ‘just’ biological because it is the emergent property of deeper systems of rules. Consciousness, now that is a debate for the philosophers.
- mygo 8y ago
  > This differs from eg electronics, physics etc, because I am biological biology has everything to do with physics and electronics (and chemistry etc). it’s just a frame of reference that decides what you choose to classify as one or the other. But the laws of nature are consistent no matter what you’re choosing to call it or which aspect of it you’re addressing.
Xeoncross 8y ago
> Sure, it could be dangerous, if you use it to perform dangerous experiments. Can it have unintended side-effects? Sure, we already know about those. In my opinion, this is the wrong way to frame this. We know there are unintended side-effects, but you make it sound like we already know what we don't know. Therefore, everything is relatively safe... which can't logically be true. You can't gauge the specific danger or benefit of the unknown.
- klmr 8y ago
  > You can't gauge the specific danger or benefit of the unknown. I’m not claiming to. All I’m saying is that “CRISPR [isn’t] dangerous specifically because we underestimate the complexity of DNA”. In the context of this discussion I can go much further, though: the physiological presence of i-motifs doesn’t change the hazard or risk of CRISPR whatsoever. We know this because our risk assessment of CRISPR never relied on the non-existence of i-motifs.
  - subroutine 8y ago
    Is this necessarily true though? Do you think the situation I illustrate here is not possible (crappy photoshop of cas9 guide RNA matching a DNA sequence across a 'imotif'): https://i.imgur.com/huIKqyD.png https://i.imgur.com/huIKqyD.png
    - ethbro 8y ago
      Parent and microbiologists can correct me if I'm wrong, but the primary drivers of current DNA tampering are correlating different forms of genes with health outcomes. We aren't creating new genetic code ex nihilo (yet). So understanding the nuances of how different forms of genes influence outcomes is less important than knowing that they do. And what the naturally-occurring "correct" form looks like.
      - subroutine 8y ago
        One of the main drivers of CRISPR-Cas9 biotech development is to perform targeted single-nucleotide DNA editing, to cure or significantly reduce the risk of getting a disease. Numerous diseases have a genetic component; some people have a higher risk of getting a disease due to their genetic makeup. Often a significant amount of the risk is attributed to a 'single nucleotide polymorphism' or 'SNP' (this is known to be true for diseases like sickle-cell anemia, cystic fibrosis, Alzheimer's disease, and others). If we could alter this SNP however, from the disease-associated nucleotide to the control nucleotide, theoretically this would substantially reduce the risk of getting that disease. CRISPR-Cas9 allows us to do that. This process relies on fabricating an RNA-guide sequence to match the segment of DNA we want edited; and if we are careful, we make sure this Guide RNA matches ONLY this segment of DNA and nowhere else in the genome. If the Guide RNA matches some other random segment of DNA, it will result in 'off-target' edits. Now, this shouldn't really be an issue if we perform whole-genome sequencing on an individual prior to making the Guide RNA. We can just make sure the Guide RNA doesn't match anywhere else in their genome and all is well, right?! Well... maybe not. Maybe these i-Motifs will fuck us over like in the picture I linked above.
bordercases 8y ago
Are you even a biologist though. Knowing about the existence of unintended side-effects is not the same as predicting their frequency. Ultimately the reduction of risk comes from hedging against an expected frequency of risk, something that we are still learning how to do, or else CRISPR would already be a widespread mode of therapeutic treatment. It seems what you're actually trying to argue against is becoming bearish on new technology due to risk, but you're doing this with posturing that is ungrounded in both the details of the biology and the risk.
- klmr 8y ago
  > Are you even a biologist though. Yes. > or else CRISPR would already be a widespread mode of therapeutic treatment You underestimate how long it takes for anything to get from fundamental research to treatment. Not just because of risk. And CRISPR is already in extremely widespread use as a molecular biology tool.
  - bordercases 8y ago
    In vitro or in vivo?
    - klmr 8y ago
      Both.
- HackerThrow1337 8y ago
  Lol it takes somewhere near an average of 30 years to get a drug/therapy approved.
chiefalchemist 8y ago
> "already possible beforehand" How so? And if so, why is CRISPR such a big deal? Not being a jerk. I'm truly interested in filling the blindspot in my "software." That said, the gist of the guy / article was (and I'm spitballing) CRISPR is an over-simplistic view of DNA. Sure, it might work for a couple of things, but to presume that pov / lens is OSFA is likely not correct. > "Lastly, somebody with an “alt view on DNA” immediately sounds like a crackpot with a poor handle on modern biology." Right. Because the world was and still is flat? SMH If I had $20 for every crackpot in the history of science I'm be FU money wealthy :) __The whole point of my comment_ was to say this new tread/artice, along with the mentioned article in The Atlantic seems to be saying it's __possible__ our understanding of our current understanding of science is off-base. That's not crackpot. That's science.
- okmokmz 8y ago
  >And if so, why is CRISPR such a big deal? My understanding is that CRISPR is popular because it is much simpler and cheaper than other previously available methods "So what makes CRISPR so special? It's much easier to employ than older gene editing technologies, and it also has a very high success rate. Because it is more user-friendly to the average scientist, it has opened the door to all kinds of research that previously would have been too expensive or required too much time to carry out." [1] [1] http://www.latimes.com/science/sciencenow/la-sci-sn-crispr-cas-9-20151218-story.html http://www.latimes.com/science/sciencenow/la-sci-sn-crispr-c...
- klmr 8y ago
  > How so? With other gene editing techniques, such as TALENs (and others before that). > And if so, why is CRISPR such a big deal? CRISPR/Cas9 is a big deal because it makes gene editing a lot easier and less error-prone (and hence cheaper, etc.). But (and not to diminish the tremendous scientific achievement behind the technique) the hype in the press around this technique is only partially warranted, and a lot is getting lost in translation. Part of the reason why CRISPR specifically is a big deal in the popular press is due to the extremely dirty fight for its exclusive patent (and the Nobel prize for its discovery): To gear up support for their side, both institutes involved created substantial media coverage that far exceeds what new discoveries normally get. > CRISPR is an over-simplistic view of DNA I would really like to read that original article because stated like this, the claim is simply incorrect. > Right. Because the world was and still is flat? SMH I honestly don’t know what you mean by the rest of your comment. But it’s worth noting that, in the modern history of science (i.e. since doing something that actually deserves that name), crackpots have virtually never been right. Progress (even paradigm shifts) came always from experts inside the field. The only near-counter-examples I can think of are Semmelweis (but that was before modern biology existed, and even he was an expert in his field), and Wegener (likewise, for continental drift). It’s easy to assert that science doesn’t have all the answers, and that theories are a temporary view of the world that’s going to be proved wrong in the future. But this has never been accomplished by people who doubt the veracity of extremely well established facts. Our knowledge of DNA is far from complete. But the things we know about it today will stick around: they have been tested by millions of experiments, performed around the globe each day. Paradigm shifts will come because we will discover new things about it, not because we’ll disprove established facts.

by klmr 8y ago

laythea 8y ago

"...biology is a science, not a pseudoscience or protoscience (or magic)" I agree with your overall point but I take slight issue with this statement. I am not biologically educated, but I am biological. I have no idea what my conscious is or why/how it works, even though I do know that I exist. And neither do you, nor anyone. To me, that is the classic definition of magic. This differs from eg electronics, physics etc, because I am biological. I have a personal perspective on it, in a manner that I could never with electronics, physics etc. Ie. I can readily understand how far away from understanding the biological process humanity is.

ethelward 8y ago
With the same idea, you're also made of physical particles, and we don't really understand how they actually work.
- laythea 8y ago
  Yes I do agree that there is a point we have to stop. However, how would you class yourself: - biological - electrical - chemical - etc It would be biological for me, although I know I am all the above.
  - robbiep 8y ago
    This is a false dichotomy. The layers don’t stop because you choose one: you are biological, because you’re chemical, because you’re physical (which is more like saying you’re electrical). Ie. Laws of physics govern the laws of chemistry and the first couple are chiseled in stone for the most part. Biology, that is to physics what psychology is to surgery (perhaps mathematics is a batter analogy). You can’t choose that you are ‘just’ biological because it is the emergent property of deeper systems of rules. Consciousness, now that is a debate for the philosophers.
mygo 8y ago
> This differs from eg electronics, physics etc, because I am biological biology has everything to do with physics and electronics (and chemistry etc). it’s just a frame of reference that decides what you choose to classify as one or the other. But the laws of nature are consistent no matter what you’re choosing to call it or which aspect of it you’re addressing.

Xeoncross 8y ago

> Sure, it could be dangerous, if you use it to perform dangerous experiments. Can it have unintended side-effects? Sure, we already know about those. In my opinion, this is the wrong way to frame this. We know there are unintended side-effects, but you make it sound like we already know what we don't know. Therefore, everything is relatively safe... which can't logically be true. You can't gauge the specific danger or benefit of the unknown.

klmr 8y ago
> You can't gauge the specific danger or benefit of the unknown. I’m not claiming to. All I’m saying is that “CRISPR [isn’t] dangerous specifically because we underestimate the complexity of DNA”. In the context of this discussion I can go much further, though: the physiological presence of i-motifs doesn’t change the hazard or risk of CRISPR whatsoever. We know this because our risk assessment of CRISPR never relied on the non-existence of i-motifs.
- subroutine 8y ago
  Is this necessarily true though? Do you think the situation I illustrate here is not possible (crappy photoshop of cas9 guide RNA matching a DNA sequence across a 'imotif'): https://i.imgur.com/huIKqyD.png https://i.imgur.com/huIKqyD.png
  - ethbro 8y ago
    Parent and microbiologists can correct me if I'm wrong, but the primary drivers of current DNA tampering are correlating different forms of genes with health outcomes. We aren't creating new genetic code ex nihilo (yet). So understanding the nuances of how different forms of genes influence outcomes is less important than knowing that they do. And what the naturally-occurring "correct" form looks like.
    - subroutine 8y ago
      One of the main drivers of CRISPR-Cas9 biotech development is to perform targeted single-nucleotide DNA editing, to cure or significantly reduce the risk of getting a disease. Numerous diseases have a genetic component; some people have a higher risk of getting a disease due to their genetic makeup. Often a significant amount of the risk is attributed to a 'single nucleotide polymorphism' or 'SNP' (this is known to be true for diseases like sickle-cell anemia, cystic fibrosis, Alzheimer's disease, and others). If we could alter this SNP however, from the disease-associated nucleotide to the control nucleotide, theoretically this would substantially reduce the risk of getting that disease. CRISPR-Cas9 allows us to do that. This process relies on fabricating an RNA-guide sequence to match the segment of DNA we want edited; and if we are careful, we make sure this Guide RNA matches ONLY this segment of DNA and nowhere else in the genome. If the Guide RNA matches some other random segment of DNA, it will result in 'off-target' edits. Now, this shouldn't really be an issue if we perform whole-genome sequencing on an individual prior to making the Guide RNA. We can just make sure the Guide RNA doesn't match anywhere else in their genome and all is well, right?! Well... maybe not. Maybe these i-Motifs will fuck us over like in the picture I linked above.

bordercases 8y ago

Are you even a biologist though. Knowing about the existence of unintended side-effects is not the same as predicting their frequency. Ultimately the reduction of risk comes from hedging against an expected frequency of risk, something that we are still learning how to do, or else CRISPR would already be a widespread mode of therapeutic treatment. It seems what you're actually trying to argue against is becoming bearish on new technology due to risk, but you're doing this with posturing that is ungrounded in both the details of the biology and the risk.

klmr 8y ago
> Are you even a biologist though. Yes. > or else CRISPR would already be a widespread mode of therapeutic treatment You underestimate how long it takes for anything to get from fundamental research to treatment. Not just because of risk. And CRISPR is already in extremely widespread use as a molecular biology tool.
- bordercases 8y ago
  In vitro or in vivo?
  - klmr 8y ago
    Both.
HackerThrow1337 8y ago
Lol it takes somewhere near an average of 30 years to get a drug/therapy approved.

chiefalchemist 8y ago

> "already possible beforehand" How so? And if so, why is CRISPR such a big deal? Not being a jerk. I'm truly interested in filling the blindspot in my "software." That said, the gist of the guy / article was (and I'm spitballing) CRISPR is an over-simplistic view of DNA. Sure, it might work for a couple of things, but to presume that pov / lens is OSFA is likely not correct. > "Lastly, somebody with an “alt view on DNA” immediately sounds like a crackpot with a poor handle on modern biology." Right. Because the world was and still is flat? SMH If I had $20 for every crackpot in the history of science I'm be FU money wealthy :) __The whole point of my comment_ was to say this new tread/artice, along with the mentioned article in The Atlantic seems to be saying it's __possible__ our understanding of our current understanding of science is off-base. That's not crackpot. That's science.

okmokmz 8y ago
>And if so, why is CRISPR such a big deal? My understanding is that CRISPR is popular because it is much simpler and cheaper than other previously available methods "So what makes CRISPR so special? It's much easier to employ than older gene editing technologies, and it also has a very high success rate. Because it is more user-friendly to the average scientist, it has opened the door to all kinds of research that previously would have been too expensive or required too much time to carry out." [1] [1] http://www.latimes.com/science/sciencenow/la-sci-sn-crispr-cas-9-20151218-story.html http://www.latimes.com/science/sciencenow/la-sci-sn-crispr-c...
klmr 8y ago
> How so? With other gene editing techniques, such as TALENs (and others before that). > And if so, why is CRISPR such a big deal? CRISPR/Cas9 is a big deal because it makes gene editing a lot easier and less error-prone (and hence cheaper, etc.). But (and not to diminish the tremendous scientific achievement behind the technique) the hype in the press around this technique is only partially warranted, and a lot is getting lost in translation. Part of the reason why CRISPR specifically is a big deal in the popular press is due to the extremely dirty fight for its exclusive patent (and the Nobel prize for its discovery): To gear up support for their side, both institutes involved created substantial media coverage that far exceeds what new discoveries normally get. > CRISPR is an over-simplistic view of DNA I would really like to read that original article because stated like this, the claim is simply incorrect. > Right. Because the world was and still is flat? SMH I honestly don’t know what you mean by the rest of your comment. But it’s worth noting that, in the modern history of science (i.e. since doing something that actually deserves that name), crackpots have virtually never been right. Progress (even paradigm shifts) came always from experts inside the field. The only near-counter-examples I can think of are Semmelweis (but that was before modern biology existed, and even he was an expert in his field), and Wegener (likewise, for continental drift). It’s easy to assert that science doesn’t have all the answers, and that theories are a temporary view of the world that’s going to be proved wrong in the future. But this has never been accomplished by people who doubt the veracity of extremely well established facts. Our knowledge of DNA is far from complete. But the things we know about it today will stick around: they have been tested by millions of experiments, performed around the globe each day. Paradigm shifts will come because we will discover new things about it, not because we’ll disprove established facts.