8 ms·

Umm maybe because the blood clot issue is being underreported because no one is looking for it? We’re essentially doing mass experimentation with gene-based vac

Umm maybe because the blood clot issue is being underreported because no one is looking for it? We’re essentially doing mass experimentation with gene-based vaccines on the US population, all the vaccines use either mRNA or DNA insertion. Caution here is the logical and ethical thing. Also: the side effect profile for the moderna and pfizer vaccines in the clinical trials was far WORSE than the jnj vaccine. Edit: gene-based not gene-therapy

simple_phrases 6y ago
Gene therapy and mRNA vaccines are two very different things.
- kaczordon 6y ago
  True corrected it to “gene-based”, both jnj and astra use DNA encoding btw.
  - tylerhou 6y ago
    But neither have the ability to alter your DNA, so they are unlikely to be able to cause long-term symptoms though a gene-expression mechanism.
    - kaczordon 6y ago
      Right but they are still gene-based. No gene-based vaccine has ever received approval for human use, and the present coronavirus vaccines have not undergone preclinical testing as normally required by international regulations. A potential danger of DNA-based vaccines is the integration of plasmid DNA into the cell genome (1). Insertional mutagenesis occurs rarely but can become a realistic danger when the number of events is very large, i.e. as in mass vaccination of a population. (1) https://www.nature.com/articles/3302213 https://www.nature.com/articles/3302213
      - tylerhou 6y ago
        I'm not a biologist, so I could be completely wrong here, but I disagree with you. First of all, plasmid != viral vector. That's why the Nature paper you cited had to use electroporation to introduce the payload. As J&J is a viral vector vaccine, I would not be confident in using this paper to make the argument that an adenovirus-based vaccine could modify a host's DNA. Second, your article does not make the claim you think it does. Specifically, the discussion says: > Using simple intramuscular injection, the vast majority of plasmid DNA that persists is extrachromosomal, and the frequency of integration, if it occurs at all, is negligible. > However, even if the residual plasmid in the gel-purified genomic DNA did represent integrated plasmid, one copy... would be at least three orders of magnitude below the frequency of spontaneous gene-inactivating mutations... That is, the delivered gene does not integrate directly into the genome itself, but rather stays in the cell. To detect whether the gene stays in the host cell, the article compares molecular weight and uses a PCR test. Both methods do not tell us whether the gene inserts itself into the host DNA; one way to detect that would be to sequence the subsequent DNA, which would be monstrously expensive (because the modification incidence is extremely low). The only way that a gene might integrate itself into the chromosome is if during DNA transcription, an error occurs and the foreign DNA is merged onto the host DNA. But this would be incredibly rare because it would require most base pairs to match up between the host & foreign DNA; otherwise, the cell would attempt to repair itself or induce apoptosis. And even if the resulting base pairs match up, the resulting DNA might not have any behavioral differences because it's (approximately) the same sequence of characters. (And you would need another transcription error later on that happens to reduce the non-modified strand by approximately the same length. That's also extremely unlikely.) Fourth, the Pfizer and Moderna vaccines use a mRNA-based vector, which (in my limited knowledge) is very difficult to integrate into the genome. The most plausible mechanism I could imagine would be: 1. (Optional) an enzyme which converts a modified nucleoside mRNA strand into one that mimics the mRNA chemical structure that is compatible with a reverse transcription enzyme [1]. 2. A reverse transcriptase to convert the mRNA strand into a (foreign) DNA strand. 3. A restriction enzyme that cleaves the host DNA suitably so that the foreign DNA can be inserted. 4. A matching ligation enzyme which actually inserts the foreign DNA into the the host DNA. All these above enzymes do not naturally occur in humans, so DNA modification through this mechanism would be incredibly rare. [1] https://link.springer.com/protocol/10.1007/978-1-4939-6481-9_6 https://link.springer.com/protocol/10.1007/978-1-4939-6481-9...
- amalcon 6y ago
  This is the J&J vaccine, which is not mRNA-based. It's an adenovirus vector vaccine, which is also not gene therapy but is a (tiny) bit closer than an mRNA vaccine.
serial_dev 6y ago
Yes, as a non medical/statistician person, I'd be really surprised if we had the same quality and quantity of data on the birth pills and this new vaccination. The risks could be higher, but maybe our data is not yet there. Just as a side note, the risks (and gains) are different, maybe I really don't want a child accidentally, but I don't consider the coronavirus too dangerous to me (it's just a hypothetical, this hypothetical person could be wrong, but in the end we all operate on incomplete data)
ABeeSea 6y ago
This is sensationalism and fear mongering. The type of blood clots (low platelet) the J&J causes gets worse with the standard treatment of blood thinners. This was on the CDC call this morning.
- fastball 6y ago
  I don't think causality has been demonstrated, no?
loeg 6y ago
Definitely not under reported. I've heard about it, despite an incidence rate of ~10^-6.
- kaczordon 6y ago
  Underreported means how many cases of this have been caught. Not how much news agencies report on this.
theptip 6y ago
> Caution here is the logical and ethical thing. In this pandemic, inaction costs lives. The logical and ethical thing to do is evaluate the cost/benefit and choose the path that kills fewer people. You wouldn't say "we should exit the burning house one at a time in case we get hit by a meteor outside, caution here is the logical and ethical thing"; you're making the same kind of logical error, just with a less-absurd difference between the risk of the two options we need to choose between.
- electrondood 6y ago
  > You wouldn't say "we should exit the burning house one at a time in case we get hit by a meteor outside, caution here is the logical and ethical thing" I always appreciate an apt analogy.

simple_phrases 6y ago

Gene therapy and mRNA vaccines are two very different things.

kaczordon 6y ago
True corrected it to “gene-based”, both jnj and astra use DNA encoding btw.
- tylerhou 6y ago
  But neither have the ability to alter your DNA, so they are unlikely to be able to cause long-term symptoms though a gene-expression mechanism.
  - kaczordon 6y ago
    Right but they are still gene-based. No gene-based vaccine has ever received approval for human use, and the present coronavirus vaccines have not undergone preclinical testing as normally required by international regulations. A potential danger of DNA-based vaccines is the integration of plasmid DNA into the cell genome (1). Insertional mutagenesis occurs rarely but can become a realistic danger when the number of events is very large, i.e. as in mass vaccination of a population. (1) https://www.nature.com/articles/3302213 https://www.nature.com/articles/3302213
    - tylerhou 6y ago
      I'm not a biologist, so I could be completely wrong here, but I disagree with you. First of all, plasmid != viral vector. That's why the Nature paper you cited had to use electroporation to introduce the payload. As J&J is a viral vector vaccine, I would not be confident in using this paper to make the argument that an adenovirus-based vaccine could modify a host's DNA. Second, your article does not make the claim you think it does. Specifically, the discussion says: > Using simple intramuscular injection, the vast majority of plasmid DNA that persists is extrachromosomal, and the frequency of integration, if it occurs at all, is negligible. > However, even if the residual plasmid in the gel-purified genomic DNA did represent integrated plasmid, one copy... would be at least three orders of magnitude below the frequency of spontaneous gene-inactivating mutations... That is, the delivered gene does not integrate directly into the genome itself, but rather stays in the cell. To detect whether the gene stays in the host cell, the article compares molecular weight and uses a PCR test. Both methods do not tell us whether the gene inserts itself into the host DNA; one way to detect that would be to sequence the subsequent DNA, which would be monstrously expensive (because the modification incidence is extremely low). The only way that a gene might integrate itself into the chromosome is if during DNA transcription, an error occurs and the foreign DNA is merged onto the host DNA. But this would be incredibly rare because it would require most base pairs to match up between the host & foreign DNA; otherwise, the cell would attempt to repair itself or induce apoptosis. And even if the resulting base pairs match up, the resulting DNA might not have any behavioral differences because it's (approximately) the same sequence of characters. (And you would need another transcription error later on that happens to reduce the non-modified strand by approximately the same length. That's also extremely unlikely.) Fourth, the Pfizer and Moderna vaccines use a mRNA-based vector, which (in my limited knowledge) is very difficult to integrate into the genome. The most plausible mechanism I could imagine would be: 1. (Optional) an enzyme which converts a modified nucleoside mRNA strand into one that mimics the mRNA chemical structure that is compatible with a reverse transcription enzyme [1]. 2. A reverse transcriptase to convert the mRNA strand into a (foreign) DNA strand. 3. A restriction enzyme that cleaves the host DNA suitably so that the foreign DNA can be inserted. 4. A matching ligation enzyme which actually inserts the foreign DNA into the the host DNA. All these above enzymes do not naturally occur in humans, so DNA modification through this mechanism would be incredibly rare. [1] https://link.springer.com/protocol/10.1007/978-1-4939-6481-9_6 https://link.springer.com/protocol/10.1007/978-1-4939-6481-9...
amalcon 6y ago
This is the J&J vaccine, which is not mRNA-based. It's an adenovirus vector vaccine, which is also not gene therapy but is a (tiny) bit closer than an mRNA vaccine.

serial_dev 6y ago

Yes, as a non medical/statistician person, I'd be really surprised if we had the same quality and quantity of data on the birth pills and this new vaccination. The risks could be higher, but maybe our data is not yet there. Just as a side note, the risks (and gains) are different, maybe I really don't want a child accidentally, but I don't consider the coronavirus too dangerous to me (it's just a hypothetical, this hypothetical person could be wrong, but in the end we all operate on incomplete data)

ABeeSea 6y ago

This is sensationalism and fear mongering. The type of blood clots (low platelet) the J&J causes gets worse with the standard treatment of blood thinners. This was on the CDC call this morning.

fastball 6y ago
I don't think causality has been demonstrated, no?

loeg 6y ago

Definitely not under reported. I've heard about it, despite an incidence rate of ~10^-6.

kaczordon 6y ago
Underreported means how many cases of this have been caught. Not how much news agencies report on this.

theptip 6y ago

> Caution here is the logical and ethical thing. In this pandemic, inaction costs lives. The logical and ethical thing to do is evaluate the cost/benefit and choose the path that kills fewer people. You wouldn't say "we should exit the burning house one at a time in case we get hit by a meteor outside, caution here is the logical and ethical thing"; you're making the same kind of logical error, just with a less-absurd difference between the risk of the two options we need to choose between.

electrondood 6y ago
> You wouldn't say "we should exit the burning house one at a time in case we get hit by a meteor outside, caution here is the logical and ethical thing" I always appreciate an apt analogy.