6 ms·

Intactness of 55% vs 75% should make no real difference to your view either of efficacy or of danger. Because: Efficacy: the mRNA vaccines have a large margin

Intactness of 55% vs 75% should make no real difference to your view either of efficacy or of danger. Because: Efficacy: the mRNA vaccines have a large margin for error with respect to dose. 55% of several times more than enough is still more than enough. Danger: suppose the danger of broken-up mRNA to increase linearly with the amount given. Then the increase of danger would be by a factor of (100-55)/(100-78) ~= 2. The substantiated near-term danger of Pfizer is very low. We're at 5.2 million people vaxxed in Israel now… Twice of very low is very low. In order to argue for "too much" danger you have to argue either for non-linearity or for long-term high danger. If you argue for the latter then you already think the danger to be high, so there's no real difference between your view now and your view before. If you want to argue non-linearity of danger then you are arguing for a very remarkable biological coincidence. You also have to explain why the occasional 5x overdoses, which happen when a someone is given a whole vial by mistake, don't seem to be doing any harm. Never mind that it would have come out in the animal trials.

ppf 6y ago
It's not the percentage of intact mRNA that's the problem, it's what the other bits of mRNA happen to do.
- et2o 6y ago
  Encode smaller bits of the same protein? Who cares. Otherwise, the mRNAs aren’t present in high enough quantities to do significant signaling or silencing things, and it’s going in the deltoid... not really a medically interesting place. You could inject 1mL of dilute HCl there and it wouldn’t be a big problem.
  - ppf 6y ago
    I'd rather not be injected with bits of mRNA that encode random bits of proteins, thanks. The deltoid is "medically interesting" enough to produce Covid spike proteins.
    - timy2shoes 6y ago
      Won't non-intact mRNA without a stop codon get degraded by Non-stop decay?
      - rolph 6y ago
        you have the idea right , but it isnt a stop codon its a signal sequence on the mRNA that would give it a hall pass. no cytoplasmic nucleotide transport signal and it gets degraded quickly.
    - et2o 6y ago
      Don’t get the vaccine then, because you are getting small pieces of mRNA.
  - Tossitto 6y ago
    Proteopathy is a real thing. Prion dysfunctions can cause self-replication, not that the makeup is necessarily there for that in these vaccines. Interesting starting point for consideration nonetheless.
- cfu28 6y ago
  Anything particular reason you're worried about extra mRNA fragments? mRNA needs a initiation sequence in order to be translated into a protein, which only exists at the front. It also needs a polyA tail to maintain stability or it would just degrade. Random fragments don't do anything on their own
- rolph 6y ago
  these fragments of mRNA will be recognized as antigens, until the point that the folded structure of the epitopes is destroyed, these smaller fragments are still recognized as viral PAMPs and evoke innate immune responses.
- topynate 6y ago
  Didn't I cover that in "danger"? The leaks are talking about maybe twice as much broken bits of mRNA in early batches. That's assuming all the not-intact stuff is broken mRNA rather than simple amino acids or something else just as boring. That shouldn't make much difference to anyone's view. If you think it's "doing" stuff that makes you not want to get vaccinated, well you probably thought that before you read this report, too.
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.
jberryman 6y ago
Your efficacy point should be obvious from just realizing that a 300lb man gets the same dose as a 80lb child.

ppf 6y ago

It's not the percentage of intact mRNA that's the problem, it's what the other bits of mRNA happen to do.

et2o 6y ago
Encode smaller bits of the same protein? Who cares. Otherwise, the mRNAs aren’t present in high enough quantities to do significant signaling or silencing things, and it’s going in the deltoid... not really a medically interesting place. You could inject 1mL of dilute HCl there and it wouldn’t be a big problem.
- ppf 6y ago
  I'd rather not be injected with bits of mRNA that encode random bits of proteins, thanks. The deltoid is "medically interesting" enough to produce Covid spike proteins.
  - timy2shoes 6y ago
    Won't non-intact mRNA without a stop codon get degraded by Non-stop decay?
    - rolph 6y ago
      you have the idea right , but it isnt a stop codon its a signal sequence on the mRNA that would give it a hall pass. no cytoplasmic nucleotide transport signal and it gets degraded quickly.
  - et2o 6y ago
    Don’t get the vaccine then, because you are getting small pieces of mRNA.
- Tossitto 6y ago
  Proteopathy is a real thing. Prion dysfunctions can cause self-replication, not that the makeup is necessarily there for that in these vaccines. Interesting starting point for consideration nonetheless.
cfu28 6y ago
Anything particular reason you're worried about extra mRNA fragments? mRNA needs a initiation sequence in order to be translated into a protein, which only exists at the front. It also needs a polyA tail to maintain stability or it would just degrade. Random fragments don't do anything on their own
rolph 6y ago
these fragments of mRNA will be recognized as antigens, until the point that the folded structure of the epitopes is destroyed, these smaller fragments are still recognized as viral PAMPs and evoke innate immune responses.
topynate 6y ago
Didn't I cover that in "danger"? The leaks are talking about maybe twice as much broken bits of mRNA in early batches. That's assuming all the not-intact stuff is broken mRNA rather than simple amino acids or something else just as boring. That shouldn't make much difference to anyone's view. If you think it's "doing" stuff that makes you not want to get vaccinated, well you probably thought that before you read this report, too.

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.

jberryman 6y ago

Your efficacy point should be obvious from just realizing that a 300lb man gets the same dose as a 80lb child.