4 ms·

> natural system of transcription, translation, and protein synthesis at the core of DNA still makes mistakes. Exactly, which means the system is resilient, w

by 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.
      - ak217 7y ago
        Yes, and many more cause carrier mutations that won't surface until the next generation, or late-onset metabolic or neural disorders that will cripple the individual later in life, or increase mutational load resulting in much higher chance of cancer. The fact that some mutations are benign and others fatal really doesn't change the issue that we don't yet know how to safely edit the human germline.
        mattkrause 7y ago
        Totally agreed--I think this was a horrific and stupid thing to do. I just wanted to push back a bit on the idea that medicine is badly "breaking" evolution by keeping people alive.
  - deusofnull 7y ago
    >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. well, what about a recessive allele that doesnt cause problems in the first generation but does in subsequent? What about co-dependent deadly / devastating gene expressions between newly added genes that pop up after 2 people with these co-active genes expressing like a hundred years from now? look, given what i studied and why, i would never say we should forever abstain from gene editing technology. BUT, we have to hold those who conduct genetic modification experiments to the absolute highest ethical and engineering standards. It is akin to the level of power given by atomic science, maybe even more. one can be sure that the powers of a God would include the power of the atom and the power of the gene near the top of the list.
ak217 7y ago
There's a huge difference between somatic and germline editing. Surgery is like somatic editing. It's elective, based on medical need, and its effects are confined to one individual. Germline editing is more like forcing an entire population to undergo surgery that is claimed to enhance their bodies. Nobody is particularly concerned about somatic editing where a medical need exists. Everybody is rightly freaking out about germline editing because it's non-elective for the babies, its consequences are permanent and can be severe, and we aren't good enough at it yet (not even the somatic variety) to claim anything about its safety.
- wahern 7y ago
  IIRC, when I studied biology in secondary school and as a freshman in college, it was believed that gametes were completely isolated and untouchable by viral infections. Turns out this is not true. But if you believe that gametes are incredibly fragile, I can see how it would be easy to believe this as otherwise you'd expect to see mutants everywhere. I realize the stakes are higher for germline editing, but rationally speaking higher stakes alone don't change the calculus.
  - coolguy132435 7y ago
    Is what you describe the basis of Human Endogenous Retroviruses?
    - wahern 7y ago
      I've assumed so, but I'm not a scientist by trade and never looked deeply into it. I just know that over the years I've crossed paths with several papers that showed infection of gametes (usually sperm) by common viruses and often gave them a cursory look. These papers always catch my attention because what I was taught in school never made sense to me. I mean, I know gametes are in some ways more fragile than most cells, and they are clearly isolated to an extent (for obvious reasons), but the imperviousness I was taught seemed unlikely and unsupportable. And because of that I've always been especially skeptical of arguments premised, directly or indirectly, on the extreme mutagenic fragility of gametes and germlines.
deusofnull 7y ago
I agree it is resilient, but that resilience has been tested by a slow, small increment evolution over millions of years. And even given that, genetic disorders with novel expressions exist that confound modern science. if we start making very fast changes, the resilience of the genetic system shouldn't be expected to hold up against a far faster change rate. And more to my point about the complexity of it all, there are huge regions of our genome that we thought were "unrelated" to human phenotypes (physical expression of genetic code) until very recently when we discovered some of this "junk" DNA actually is critical for certain types of RNA transcription / repair. GMOs are a different issue. My underlying concern about the influx of new genes introduce to the wild quickly being potentially dangerous aside, the genetic modification have mostly been to make plants resilient to various herbicides/fungicides/pesticides to allow large scale monoculture farming. That's one solution, but not the only. And we have seen invasive forms of GMO crops spread out of containment, thus entering the wild population, and we wont know the consequence of that for a long time, if any. takeaway being, its probably worth being conservative about even moderate scale genetic manipulation of any species we rely on, and especially our own genome. Not saying dont do any genetic modification, just that it really has to be air tight, you might say NASA level standards of engineering. Now, you tell me if you think Monsanto's engineering standards are at NASA level, or that the Chinese Governments ethical standards are without problems.
VectorLock 7y ago
The human body, incredibly robust and frustratingly fragile at the same time.
imtringued 7y ago
>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. The argument should go the other way. Because these DNA mistakes are predictable our genes have designed safeguards against them. If you now randomly introduce a "mistake" that is beyond the capability of the system then it won't help you.

by wahern 7y ago

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.
    - ak217 7y ago
      Yes, and many more cause carrier mutations that won't surface until the next generation, or late-onset metabolic or neural disorders that will cripple the individual later in life, or increase mutational load resulting in much higher chance of cancer. The fact that some mutations are benign and others fatal really doesn't change the issue that we don't yet know how to safely edit the human germline.
      - mattkrause 7y ago
        Totally agreed--I think this was a horrific and stupid thing to do. I just wanted to push back a bit on the idea that medicine is badly "breaking" evolution by keeping people alive.
- deusofnull 7y ago
  >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. well, what about a recessive allele that doesnt cause problems in the first generation but does in subsequent? What about co-dependent deadly / devastating gene expressions between newly added genes that pop up after 2 people with these co-active genes expressing like a hundred years from now? look, given what i studied and why, i would never say we should forever abstain from gene editing technology. BUT, we have to hold those who conduct genetic modification experiments to the absolute highest ethical and engineering standards. It is akin to the level of power given by atomic science, maybe even more. one can be sure that the powers of a God would include the power of the atom and the power of the gene near the top of the list.

ak217 7y ago

There's a huge difference between somatic and germline editing. Surgery is like somatic editing. It's elective, based on medical need, and its effects are confined to one individual. Germline editing is more like forcing an entire population to undergo surgery that is claimed to enhance their bodies. Nobody is particularly concerned about somatic editing where a medical need exists. Everybody is rightly freaking out about germline editing because it's non-elective for the babies, its consequences are permanent and can be severe, and we aren't good enough at it yet (not even the somatic variety) to claim anything about its safety.

wahern 7y ago
IIRC, when I studied biology in secondary school and as a freshman in college, it was believed that gametes were completely isolated and untouchable by viral infections. Turns out this is not true. But if you believe that gametes are incredibly fragile, I can see how it would be easy to believe this as otherwise you'd expect to see mutants everywhere. I realize the stakes are higher for germline editing, but rationally speaking higher stakes alone don't change the calculus.
- coolguy132435 7y ago
  Is what you describe the basis of Human Endogenous Retroviruses?
  - wahern 7y ago
    I've assumed so, but I'm not a scientist by trade and never looked deeply into it. I just know that over the years I've crossed paths with several papers that showed infection of gametes (usually sperm) by common viruses and often gave them a cursory look. These papers always catch my attention because what I was taught in school never made sense to me. I mean, I know gametes are in some ways more fragile than most cells, and they are clearly isolated to an extent (for obvious reasons), but the imperviousness I was taught seemed unlikely and unsupportable. And because of that I've always been especially skeptical of arguments premised, directly or indirectly, on the extreme mutagenic fragility of gametes and germlines.

deusofnull 7y ago

I agree it is resilient, but that resilience has been tested by a slow, small increment evolution over millions of years. And even given that, genetic disorders with novel expressions exist that confound modern science. if we start making very fast changes, the resilience of the genetic system shouldn't be expected to hold up against a far faster change rate. And more to my point about the complexity of it all, there are huge regions of our genome that we thought were "unrelated" to human phenotypes (physical expression of genetic code) until very recently when we discovered some of this "junk" DNA actually is critical for certain types of RNA transcription / repair. GMOs are a different issue. My underlying concern about the influx of new genes introduce to the wild quickly being potentially dangerous aside, the genetic modification have mostly been to make plants resilient to various herbicides/fungicides/pesticides to allow large scale monoculture farming. That's one solution, but not the only. And we have seen invasive forms of GMO crops spread out of containment, thus entering the wild population, and we wont know the consequence of that for a long time, if any. takeaway being, its probably worth being conservative about even moderate scale genetic manipulation of any species we rely on, and especially our own genome. Not saying dont do any genetic modification, just that it really has to be air tight, you might say NASA level standards of engineering. Now, you tell me if you think Monsanto's engineering standards are at NASA level, or that the Chinese Governments ethical standards are without problems.

VectorLock 7y ago

The human body, incredibly robust and frustratingly fragile at the same time.

imtringued 7y ago

>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. The argument should go the other way. Because these DNA mistakes are predictable our genes have designed safeguards against them. If you now randomly introduce a "mistake" that is beyond the capability of the system then it won't help you.