3 ms·

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 confi

by 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.
- ak217 7y ago
  I don't follow. Gametes are isolated from many viral infections, but even assuming that a gamete undergoes viral mutagenesis, that's not evolutionarily novel (viruses follow relatively predictable insertion patterns, and transposons are basically degenerate/grounded viruses that are almost certain to generate mutation events in any given zygote, unlike viral mutagenesis). It's also outside our control, unlike germline editing, which is not random in completely novel ways. It is precisely because the stakes are so much higher that the calculus changes. We have to be reasonably certain that we can safely edit germline by experimenting with somatic editing and germline in lab animals before we can do something as consequential as deploying it clinically.
  - wahern 7y ago
    Sure, they are more isolated. And in some ways they are more fragile. But my point is that they're not nearly as fragile as we believed. And more importantly a faulty premise--that they're extremely fragile--gave way to a faulty scientific conclusion--that gametes were impervious to common environmental stressors like the many infections that ravage our bodies. We can't draw simple, categorical conclusions about gene editing, nor even germline editing in particular, because there are no simple, categorical distinctions. Suffice it to say, it's complex. Whenever we try to be reductivist about such things we end up drawing erroneous and even dangerous conclusions; e.g. gamete fragility -> viral imperviousness as solution to observed lack of harm -> underestimation of viral stressors and risks, and overestimation of gene editing risks. Regarding stakes, what I had in mind was classic economic behavioral experiments where they show that a change in the magnitude of a bet changes choices in an irrational manner even though the expected payoff is exactly the same; even when you take into account marginal utility effects. Yes, germline edits don't just effect one person, they theoretically could infect all of humanity. But so what? Remember when they were firing up the LHC and people were freaking out at the possible creation of blackholes. Given the error bars in known physics, there was a non-zero chance running the experiments could have destroyed the world.[1] Because nothing we could possibly learn would compensate for losing everything, does that mean we should never have turned it on? No. The calculus didn't change. That germline edits propagate doesn't mean our harm+benefit calculus changes; it's just that one of the risk factors in the equation changes from a 1 to something larger. Other factors, like confidence, may or may not need to be changed. Regarding the argument that by intervening scientifically we're categorically more culpable than if we didn't do anything, that touches upon the is/ought and naturalistic fallacies. From a utilitarian perspective intervention vs non-intervention is irrelevant. I'm not a Utilitarian (capital U), but I don't see how we can have a constructive, scientific debate outside a utilitarian framework. Such lines of reasoning are more relevant to political and religious contexts. [1] Well, maybe. Actually, perhaps many physicists would have said that the consensus science would have put the chance at 0. But the best argument was made by people pointing out that the Earth's atmosphere was constantly bombarded by particles far more energetic than what the LHC would create. Which is exactly analogous to germline editing. The fact is, the germline undergoes far more genetic stressors than we once believed. It must follow that it's more resilient than we believed, genetically, developmentally, and from an evolutionary perspective.

by ak217 7y ago

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.
ak217 7y ago
I don't follow. Gametes are isolated from many viral infections, but even assuming that a gamete undergoes viral mutagenesis, that's not evolutionarily novel (viruses follow relatively predictable insertion patterns, and transposons are basically degenerate/grounded viruses that are almost certain to generate mutation events in any given zygote, unlike viral mutagenesis). It's also outside our control, unlike germline editing, which is not random in completely novel ways. It is precisely because the stakes are so much higher that the calculus changes. We have to be reasonably certain that we can safely edit germline by experimenting with somatic editing and germline in lab animals before we can do something as consequential as deploying it clinically.
- wahern 7y ago
  Sure, they are more isolated. And in some ways they are more fragile. But my point is that they're not nearly as fragile as we believed. And more importantly a faulty premise--that they're extremely fragile--gave way to a faulty scientific conclusion--that gametes were impervious to common environmental stressors like the many infections that ravage our bodies. We can't draw simple, categorical conclusions about gene editing, nor even germline editing in particular, because there are no simple, categorical distinctions. Suffice it to say, it's complex. Whenever we try to be reductivist about such things we end up drawing erroneous and even dangerous conclusions; e.g. gamete fragility -> viral imperviousness as solution to observed lack of harm -> underestimation of viral stressors and risks, and overestimation of gene editing risks. Regarding stakes, what I had in mind was classic economic behavioral experiments where they show that a change in the magnitude of a bet changes choices in an irrational manner even though the expected payoff is exactly the same; even when you take into account marginal utility effects. Yes, germline edits don't just effect one person, they theoretically could infect all of humanity. But so what? Remember when they were firing up the LHC and people were freaking out at the possible creation of blackholes. Given the error bars in known physics, there was a non-zero chance running the experiments could have destroyed the world.[1] Because nothing we could possibly learn would compensate for losing everything, does that mean we should never have turned it on? No. The calculus didn't change. That germline edits propagate doesn't mean our harm+benefit calculus changes; it's just that one of the risk factors in the equation changes from a 1 to something larger. Other factors, like confidence, may or may not need to be changed. Regarding the argument that by intervening scientifically we're categorically more culpable than if we didn't do anything, that touches upon the is/ought and naturalistic fallacies. From a utilitarian perspective intervention vs non-intervention is irrelevant. I'm not a Utilitarian (capital U), but I don't see how we can have a constructive, scientific debate outside a utilitarian framework. Such lines of reasoning are more relevant to political and religious contexts. [1] Well, maybe. Actually, perhaps many physicists would have said that the consensus science would have put the chance at 0. But the best argument was made by people pointing out that the Earth's atmosphere was constantly bombarded by particles far more energetic than what the LHC would create. Which is exactly analogous to germline editing. The fact is, the germline undergoes far more genetic stressors than we once believed. It must follow that it's more resilient than we believed, genetically, developmentally, and from an evolutionary perspective.