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Back in my genetics class in Uni, unitended mutations from gene editing struck me as a concern almost immediately. and its scary to think about. these unknown

Back in my genetics class in Uni, unitended mutations from gene editing struck me as a concern almost immediately. and its scary to think about. these unknown mutations could be benign, harmful, or even helpful, but if they entered the population through procreation... i mean i had an anxiety that the whole human genome could be damaged at a fundamental level. the complexity of the biological machinery that occurs during gene transcription and replication and translation is maddening. yes, its sort of like a zipper in some ways, but remember that the geometry of a zipper is 2 dimensional, teeth and grooves. DNA is "zipped" by a protein that will fit with the geometry of hundreds or thousands of nucleotide pairs, and even that is a really basic way of putting it. and that natural system of transcription, translation, and protein synthesis at the core of DNA still makes mistakes. You think index mismatch by 1 in an array can be a bit tricky, imagine how with DNA you have a long array, sort of, with millions of discrete parts that have start and end segments sort like how memory is managed in ram. CRISPR is in some ways, like trying to write perfect memory safe code in a non mem-managed language. crude metaphor but it was how i thought about it during university learning about both compsci and genetics.

markdown 7y ago
If you want to play god, you have to take it all the way ie. be prepared to sterilize or kill your creations.
- holler 7y ago
  Or you know, set them free...
jandrese 7y ago
For the most part mutations like that simply reduce the reproductive viability of the offspring. We can't really poison the entire human genome worldwide without going to absolute extremes. Could we engineer a human so irresistibly sexually desirable and voracious that they could spread their genetic material with a subtle recessive defect across the globe in the span of a generation so that it could take effect before people realized what was going on?
- deusofnull 7y ago
  Dunno, but all kinds of things could happen with novel co-dependent alleles with devistating effects when the express. Imagine theres a cool gene edit in 100 years that lets you live to 200 easy and it becomes normal for most people to get it. But, it just so happens that thers an early gene edit that was available 20 years from now, less ethically created and expensive. but hundreds of thousands of people get that first life extender. Then, turns out the better / safer one 70 years from now has a co-expression with the decendents of the people who got it 20 years from now that makes you infertile, senile, or whatever. thats the danger. If these edits become available broadly, youre not only worrying about co-expressions of edit genes developed at the same time, but edit genes developed at any time in the past (oh and also the rest of the human genome, which we still dont understand fully, and is a base concern for any gene editing whatsoever)
  - bsder 7y ago
    > thats the danger. If these edits become available broadly, youre not only worrying about co-expressions of edit genes developed at the same time, but edit genes developed at any time in the past (oh and also the rest of the human genome, which we still dont understand fully, and is a base concern for any gene editing whatsoever) <shrug> Then people who chose that mating pair will get weeded out. It sucks to be the individual victims of that, but that's not a big deal for the species. In addition, biological systems almost always have variation. Even Ebola isn't 100% fatal. So, even if you have an interaction, some people will have another mutation that deactivates the interaction.
  - imtringued 7y ago
    I'm now wondering what measures scientists use to prevent genes that reduce child mortality but also decrease life expectancy. It's unlikely that the company that designed your genes will stay in business for 70 years so that it can update its gene designs to fix this fatal flaw.
- omegaworks 7y ago
  You don't need to. Read up on gene drive. Just need to engineer the next generation to only produce males.
wahern 7y ago
> natural system of transcription, translation, and protein synthesis at the core of DNA still makes mistakes. Exactly, which means the system is resilient, which means it's more forgiving of random mutations introduced by gene editing, which is perhaps why most scientists are less concerned than you think they ought to be. Imagine if we took the same approach to surgery--overly worried that scar tissue of any kind at any point would completely disrupt the functioning of an organ. We'd be a hundred years or more behind where we are now. Scientists and doctors understand that the body is both much more complex than a simple machine, but also much more resilient. Such criticism cuts both ways. Likewise for GMOs. Demanding perfection is unreasonable and unnecessary.
- pythonaut_16 7y ago
  To play devil's advocate: Scar tissue doesn't get passed to offspring or propagated throughout the population though.
  - TeMPOraL 7y ago
    To play the angel's advocate (or whatever is the next-step reverse of devil's advocate): natural selection helps eliminate problematic genes in populations. A good chunk of harmful mutations will prevent people from procreating, either by killing them first, or making it unlikely for them to find a mate.
    - sudosysgen 7y ago
      Not nearly as much in 2019's modern societies.
      - mattkrause 7y ago
        Less now, for sure, but you're overlooking a major category. Many of the really bad mutations are embryonic-lethal, which is why a surprisingly high proportion of pregnancies "don't take" or end in miscarriage.
willis936 7y ago
From conversations with a biochemist, I gained an appreciation for the complexity of genetics. It’s like a computer reading byte code to boot, except the computer makes the hardware that executes the code. That’s the simplest layer of it. I only know a scratch On the surface of how interconnected it all is. If you have an error in a gene that will likely cause an incorrectly generated protein. Proteins and protein synthesis must be relatively resilient to this kind of common error. If that system isn’t resilient then other systems prevent the error from propagating. These solutions must exist or else life wouldn’t work. And this is all in a single cell. Cells coexisting is such a strange thing.

markdown 7y ago

If you want to play god, you have to take it all the way ie. be prepared to sterilize or kill your creations.

holler 7y ago
Or you know, set them free...

jandrese 7y ago

For the most part mutations like that simply reduce the reproductive viability of the offspring. We can't really poison the entire human genome worldwide without going to absolute extremes. Could we engineer a human so irresistibly sexually desirable and voracious that they could spread their genetic material with a subtle recessive defect across the globe in the span of a generation so that it could take effect before people realized what was going on?

deusofnull 7y ago
Dunno, but all kinds of things could happen with novel co-dependent alleles with devistating effects when the express. Imagine theres a cool gene edit in 100 years that lets you live to 200 easy and it becomes normal for most people to get it. But, it just so happens that thers an early gene edit that was available 20 years from now, less ethically created and expensive. but hundreds of thousands of people get that first life extender. Then, turns out the better / safer one 70 years from now has a co-expression with the decendents of the people who got it 20 years from now that makes you infertile, senile, or whatever. thats the danger. If these edits become available broadly, youre not only worrying about co-expressions of edit genes developed at the same time, but edit genes developed at any time in the past (oh and also the rest of the human genome, which we still dont understand fully, and is a base concern for any gene editing whatsoever)
- bsder 7y ago
  > thats the danger. If these edits become available broadly, youre not only worrying about co-expressions of edit genes developed at the same time, but edit genes developed at any time in the past (oh and also the rest of the human genome, which we still dont understand fully, and is a base concern for any gene editing whatsoever) <shrug> Then people who chose that mating pair will get weeded out. It sucks to be the individual victims of that, but that's not a big deal for the species. In addition, biological systems almost always have variation. Even Ebola isn't 100% fatal. So, even if you have an interaction, some people will have another mutation that deactivates the interaction.
- imtringued 7y ago
  I'm now wondering what measures scientists use to prevent genes that reduce child mortality but also decrease life expectancy. It's unlikely that the company that designed your genes will stay in business for 70 years so that it can update its gene designs to fix this fatal flaw.
omegaworks 7y ago
You don't need to. Read up on gene drive. Just need to engineer the next generation to only produce males.

wahern 7y ago

> natural system of transcription, translation, and protein synthesis at the core of DNA still makes mistakes. Exactly, which means the system is resilient, which means it's more forgiving of random mutations introduced by gene editing, which is perhaps why most scientists are less concerned than you think they ought to be. Imagine if we took the same approach to surgery--overly worried that scar tissue of any kind at any point would completely disrupt the functioning of an organ. We'd be a hundred years or more behind where we are now. Scientists and doctors understand that the body is both much more complex than a simple machine, but also much more resilient. Such criticism cuts both ways. Likewise for GMOs. Demanding perfection is unreasonable and unnecessary.

pythonaut_16 7y ago
To play devil's advocate: Scar tissue doesn't get passed to offspring or propagated throughout the population though.
- TeMPOraL 7y ago
  To play the angel's advocate (or whatever is the next-step reverse of devil's advocate): natural selection helps eliminate problematic genes in populations. A good chunk of harmful mutations will prevent people from procreating, either by killing them first, or making it unlikely for them to find a mate.
  - sudosysgen 7y ago
    Not nearly as much in 2019's modern societies.
    - mattkrause 7y ago
      Less now, for sure, but you're overlooking a major category. Many of the really bad mutations are embryonic-lethal, which is why a surprisingly high proportion of pregnancies "don't take" or end in miscarriage.

willis936 7y ago

From conversations with a biochemist, I gained an appreciation for the complexity of genetics. It’s like a computer reading byte code to boot, except the computer makes the hardware that executes the code. That’s the simplest layer of it. I only know a scratch On the surface of how interconnected it all is. If you have an error in a gene that will likely cause an incorrectly generated protein. Proteins and protein synthesis must be relatively resilient to this kind of common error. If that system isn’t resilient then other systems prevent the error from propagating. These solutions must exist or else life wouldn’t work. And this is all in a single cell. Cells coexisting is such a strange thing.