5 ms·

Apologies, but I must have missed it when you said: “If you want to argue non-linearity of danger then you are arguing for a very remarkable biological coincid

by tobmlt 6y ago

Apologies, but I must have missed it when you said: “If you want to argue non-linearity of danger then you are arguing for a very remarkable biological coincidence.“ What do you mean here? Can you give a bit more info? Note, I am pretty well versed on nonlinearities from a mathematical-engineering point of view, but know very very little about biology. (If that’s of any use to know)

topynate 6y ago
Just that increases in risk are usually approximated pretty well by a linear change with dose. Radiation, poison, allergens, etc. Drugs too – the ones where the toxic dose is close to the therapeutic dose are generally pretty nasty even when used as intended. It's possible for there to be a transition between "very safe" and "noticably unsafe" as the quantity of something increases twofold, but a priori unlikely. For this to happen not only in vaccines, but through an unknown mechanism that operates precisely in this particular range, would be truly rotten luck. It's also contradicted (a posteriori) by the evidence I referred to (overdoses and animal models).
- woofie11 6y ago
  This isn't right. Risk from overdoses of drugs, poison, and allergens is *highly* nonlinear. It'd be exceptionally unlikely in the case of mRNA vaccine, but that's the case the majority of the time. There's a specific minimum dosage most people have of allergen before they hit on a life-threatening reaction. You might be okay with trace amount of peanuts, swell up with one peanut, and die with five. It's pretty consistent, and very nonlinear. That's why you can build up a tolerance to iocane powder too; small doses won't do anything, while large ones are guaranteed to kill. If it was linear, a 1/10th lethal dose would have a 10% chance of killing you.
  - topynate 6y ago
    I mean, they're all nonlinear at some point in the range of possible doses. Radiation too. I should have specified I was focusing on the "very low" bit of the curves. Chest X-ray vs two chest X-rays, rather than Louis Slotin vs the guy at the back of the room.
    - deleted 6y ago
      [deleted]
    - woofie11 6y ago
      Nope. Most medicines are totally nonlinear. Almost any function is affine if you look close enough, but that's different from linear. If you half the dosage of ibuprofen, your odds of complications rarely fall by 50%. Chest x-ray is pretty linear within reasonable dosage ranges, for much the same reason I'd expect mRNA damage to be.
woofie11 6y ago
Let's say a piece of mRNA has a 1E-12 chance of causing you to grow a third arm by virtue of a defect. Two pieces of mRNA would have very close to a 2E-12 chance of causing you to grow a third arm. That's linearity. If you've doubled the defect rate, you've doubled the risk. This contrast with e.g. sports brain trauma, where one sports brain trauma might be relatively moderate risk, but two might be very high risk (much more than double). Or risk from ibuprofen, where 600mg is has close to zero risk, but an overdose of 60,000mg poses a significant risk of death (much more than 100x the risk of death of a 600mg dose). That's nonlinear. I'm not sure how risk from mRNA defects would be anything but linear. It would take an extraordinary set of coincidences.
- 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.

by tobmlt 6y ago

topynate 6y ago

Just that increases in risk are usually approximated pretty well by a linear change with dose. Radiation, poison, allergens, etc. Drugs too – the ones where the toxic dose is close to the therapeutic dose are generally pretty nasty even when used as intended. It's possible for there to be a transition between "very safe" and "noticably unsafe" as the quantity of something increases twofold, but a priori unlikely. For this to happen not only in vaccines, but through an unknown mechanism that operates precisely in this particular range, would be truly rotten luck. It's also contradicted (a posteriori) by the evidence I referred to (overdoses and animal models).

woofie11 6y ago
This isn't right. Risk from overdoses of drugs, poison, and allergens is *highly* nonlinear. It'd be exceptionally unlikely in the case of mRNA vaccine, but that's the case the majority of the time. There's a specific minimum dosage most people have of allergen before they hit on a life-threatening reaction. You might be okay with trace amount of peanuts, swell up with one peanut, and die with five. It's pretty consistent, and very nonlinear. That's why you can build up a tolerance to iocane powder too; small doses won't do anything, while large ones are guaranteed to kill. If it was linear, a 1/10th lethal dose would have a 10% chance of killing you.
- topynate 6y ago
  I mean, they're all nonlinear at some point in the range of possible doses. Radiation too. I should have specified I was focusing on the "very low" bit of the curves. Chest X-ray vs two chest X-rays, rather than Louis Slotin vs the guy at the back of the room.
  - deleted 6y ago
    [deleted]
  - woofie11 6y ago
    Nope. Most medicines are totally nonlinear. Almost any function is affine if you look close enough, but that's different from linear. If you half the dosage of ibuprofen, your odds of complications rarely fall by 50%. Chest x-ray is pretty linear within reasonable dosage ranges, for much the same reason I'd expect mRNA damage to be.

woofie11 6y ago

Let's say a piece of mRNA has a 1E-12 chance of causing you to grow a third arm by virtue of a defect. Two pieces of mRNA would have very close to a 2E-12 chance of causing you to grow a third arm. That's linearity. If you've doubled the defect rate, you've doubled the risk. This contrast with e.g. sports brain trauma, where one sports brain trauma might be relatively moderate risk, but two might be very high risk (much more than double). Or risk from ibuprofen, where 600mg is has close to zero risk, but an overdose of 60,000mg poses a significant risk of death (much more than 100x the risk of death of a 600mg dose). That's nonlinear. I'm not sure how risk from mRNA defects would be anything but linear. It would take an extraordinary set of coincidences.

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.