5 ms·

it would appear you are sampling an unknown distribution, finding it mostly to be negligible in its effects, and calling it linear? I’m confused so let me try

by tobmlt 6y ago

it would appear you are sampling an unknown distribution, finding it mostly to be negligible in its effects, and calling it linear? I’m confused so let me try an analogy with DNA: most mutations do nothing. Every now and then, cancer. Sample a large number of mutations for a short duration, and you have proven nothing regarding nonlinearity globally. Roughly speaking. Another example: I can measure a the air near (but not to near) a shockwave, or just under (By human scale) the free surface of the ocean, and find pretty much linear behavior if no other pathologies are present. The underlying physics however, is not linear, it is only my approximation which is. Maybe it’s valid over configurations of interest. But then I better know something about the limits of my approximation.

omegaworks 6y ago
The thing about DNA damage is that it replicates. mRNA is pretty much designed to be degraded almost immediately after it is transcribed. If I understand woofie11 correctly, it means that the probability that an error in a single mRNA corresponds with an error in another mRNA to cause a larger perceivable effect is small. The errors would have to be made in the exact same way.
- tobmlt 6y ago
  Ah okay. Thanks for that insight! That seems key.
  - woofie11 6y ago
    Or alternatively, the odds of a particular mRNA mutation doing something harmful are astronomically low. With 7 billion people being injected with large amounts of mRNA, you have a very small number times a very big number, so I can't estimate how likely something is to happen, but we know it's small since we haven't learned about anything critical with tens (hundreds) of millions of injections so far. If an mRNA mutation were to make a self-replicating virus, or make something which damages DNA leading to cancer, or something wonky like that, I guess that's in abstract possible. It can make abstract proteins, and we don't know what those will do. In that case, if I have twice as much mutated mRNA in my body, the odds of that happening almost exactly double. It's like rolling a 1-trillion sided die twice instead of once and seeing if I roll a 1. With one roll, I have a 1-in-a-trillion chance. With two rolls, I have a 2-in-a-trillion chance (minus 1-in-a-septillion of having the same thing happen twice, which we don't know what it would do, but is a small enough possibility we can ignore). But yeah, unless something really wonky going on, I'm not going to end up with hundreds of strands of mutated mRNA in my body *all doing the same thing*.
    - tobmlt 6y ago
      The large sample size in cross section is not compelling to me - On its on - over a short duration of time. Because I know nothing about long term possibilities from that. The statistics as derived from the dynamics of “how rna works” - yeah that’s compelling. This: “If an mRNA mutation were to make a self-replicating virus, or make something which damages DNA leading to cancer, or something wonky like that, I guess that's in abstract possible. It can make abstract proteins, and we don't know what those will do.” Sounds astronomically I likely, but with unknown error bars. Sounds like our If our cross section test Is large enough going on long enough, we might just get there.
      - omegaworks 6y ago
        Given that the mRNA in the vaccine encodes for just a single protein of a given virus, it seems totally impossible to get an entire virus out of an error. :) A prion (misfolded protein that causes other proteins to misfold) is more likely, but even then prions need to misfold in specific ways that encourage their replication as well. In all likelihood the error is just going to prevent the ribosome from finishing transcription and we'll have just a fragment of whatever protein the RNA initially encoded for.
        tobmlt 6y ago
        Thanks! This is good to know as well. And thanks for pausing to help someone who honestly has no spare time whatsoever to dig in. I know that is probably frustrating for some (not necessarily you, it’s just I’ve been there and it can be exasperating)

by tobmlt 6y ago

omegaworks 6y ago

The thing about DNA damage is that it replicates. mRNA is pretty much designed to be degraded almost immediately after it is transcribed. If I understand woofie11 correctly, it means that the probability that an error in a single mRNA corresponds with an error in another mRNA to cause a larger perceivable effect is small. The errors would have to be made in the exact same way.

tobmlt 6y ago
Ah okay. Thanks for that insight! That seems key.
- woofie11 6y ago
  Or alternatively, the odds of a particular mRNA mutation doing something harmful are astronomically low. With 7 billion people being injected with large amounts of mRNA, you have a very small number times a very big number, so I can't estimate how likely something is to happen, but we know it's small since we haven't learned about anything critical with tens (hundreds) of millions of injections so far. If an mRNA mutation were to make a self-replicating virus, or make something which damages DNA leading to cancer, or something wonky like that, I guess that's in abstract possible. It can make abstract proteins, and we don't know what those will do. In that case, if I have twice as much mutated mRNA in my body, the odds of that happening almost exactly double. It's like rolling a 1-trillion sided die twice instead of once and seeing if I roll a 1. With one roll, I have a 1-in-a-trillion chance. With two rolls, I have a 2-in-a-trillion chance (minus 1-in-a-septillion of having the same thing happen twice, which we don't know what it would do, but is a small enough possibility we can ignore). But yeah, unless something really wonky going on, I'm not going to end up with hundreds of strands of mutated mRNA in my body *all doing the same thing*.
  - tobmlt 6y ago
    The large sample size in cross section is not compelling to me - On its on - over a short duration of time. Because I know nothing about long term possibilities from that. The statistics as derived from the dynamics of “how rna works” - yeah that’s compelling. This: “If an mRNA mutation were to make a self-replicating virus, or make something which damages DNA leading to cancer, or something wonky like that, I guess that's in abstract possible. It can make abstract proteins, and we don't know what those will do.” Sounds astronomically I likely, but with unknown error bars. Sounds like our If our cross section test Is large enough going on long enough, we might just get there.
    - omegaworks 6y ago
      Given that the mRNA in the vaccine encodes for just a single protein of a given virus, it seems totally impossible to get an entire virus out of an error. :) A prion (misfolded protein that causes other proteins to misfold) is more likely, but even then prions need to misfold in specific ways that encourage their replication as well. In all likelihood the error is just going to prevent the ribosome from finishing transcription and we'll have just a fragment of whatever protein the RNA initially encoded for.
      - tobmlt 6y ago
        Thanks! This is good to know as well. And thanks for pausing to help someone who honestly has no spare time whatsoever to dig in. I know that is probably frustrating for some (not necessarily you, it’s just I’ve been there and it can be exasperating)