The Pfizer and Moderna vaccines are mRNA vaccines. mRNA does not enter the cell nucleus--it remains in the cytoplasm. There is a paper that studied how mRNA synthesized in the nucleus diffuses into the cytoplasm (after transcription) which may be worth reading. mRNA is used by ribosomes in the cytoplasm to synthesize proteins, enzymes, and other bits--it's how the virus produces more virions with the exception that the mRNA fragments used by both of these vaccines are the sequences that produce the surface receptors.
You cannot modify DNA from mRNA.
What's making people sick in these vaccines is the polyethylene glycol used to stabilize the lipid nanoparticles that encapsulate the mRNA as its delivery system, and PEG are known to cause anaphylaxis. PEG as a component of vaccines is not well-studied and should be viewed with caution, because it certainly does provoke an immune response that can be dangerous if not outright lethal.
If you wanted to go down the rabbit hole of a vaccine that could feasibly modify the patient's DNA, then I'd suggest looking into the AstraZeneca vaccine which uses a modified adenovirus (DNA virus) to inject DNA into the nucleus where the cell transcribes mRNA from the DNA. There's a YouTuber who used a similar adenovirus to "cure" his lactose intolerance for a couple of years by modifying his own DNA in intestinal tissue responsible for producing lactase. Except that the effect wasn't permanent because the modifications could not be transcribed to the daughter cells.
So just have blind faith in the government and big pharma that the mRNA sole purpose is to translate spike proteins and nothing more. Sounds smart to trust the government with this.
I'm not saying to trust them; I'm saying that's how biology works. mRNA cannot modify genes and the only thing it does is produce proteins. That's it.
Where I would direct my concern with these vaccines is toward the PEG-stabilized lipid nanoparticles, because PEG absolutely can kill people if they have a reaction to it. Based on the data that's currently available, it appears that there are a growing number of patients exhibiting anaphylaxis post-vaccination.
Honestly, the problem with this sort of thing is it something that CAN NEVER HAPPEN until it does happen and we realize we missed something important. It happened several times in history of technological development.
Except that in the case of mRNA, it cannot enter the nucleus of the cell where the DNA is located. This actually is impossible. I've linked research related to the chemical gates that are used for mRNA egress.
Regardless, assuming that it could enter the nucleus, mRNA has no function inside there that the cell would use, because the nucleus is where mRNA is manufactured--not read.
That's the point I'm trying to get across.
Just to be clear, I am not saying that something bad WILL happen, I am saying there is a RISK something bad will happen and we should be more conscious of that
There's no risk with mRNA once you understand the processes at play.
The risk with these vaccinations is in the polyethylene glycol used to stabilize the lipid nanoparticles. That is what people are reacting to, and that appears to be the dangerous aspect of this vaccine that is absolutely causing adverse reactions.
People shouting about the mRNA have absolutely no clue what mRNA is or what its function is inside the cell, which is stupid because it's easy enough to research. What's worse is that it's distracting from the actual dangers that are present in these vaccines that is not well understood, and that's the use of PEG.
Most people seem to tolerate PEG just fine. The people who don't may experience anaphylaxis. As far as long term effects, we have no idea what the long term effects of PEGylated lipids will do to the body.
mRNA has a very short half-life and breaks down pretty rapidly. That's why I don't find it concerning at all. Within a few days, the mRNA of the vaccine won't be present. The PEGylated stuff? Who knows how long that will persist.
Direct your attention there. That's where the interesting effects will begin.
My fixation on PEG is mostly with regards to the reality that the side effects people are witnessing are exclusively from its use, as you noted. Of course, I may be grossly exaggerating it in effort to direct people's attention away from their absurd obsession with mRNA (somehow being stupid enough to think that it will modify their genome).
You're right, of course. My opinion is that the risk of adverse reactions from PEGylated nanoparticles is so comparatively minor that if you do the math, you're probably something like 50 times more likely to die from COVID-19 even with the exaggerated figures than you are to have an adverse reaction.
But, I think part of my whinging is due in part to frustration. I do greatly appreciate your clarifications and defense of this strategy. Thank you so much.
My opinion is also that I sincerely hope the Pfizer and Moderna vaccines demonstrate a safe delivery of mRNA for the reasons that I understand these were originally thought up in the late 1980s as a treatment for cancer (e.g. cancer vaccinations). If this is successful, then it means that the delivery mechanism works, and we might see the COVID-19 fallout lead toward workable vaccinations for common cancers.
FWIW, I don't have any idea what I'm talking about, because I'm a programmer. I have nothing to do with the medical industry. I do, however, happily read whatever research is available at any given time because I'm a bit touched in the head and maybe borderline crazy. But what frustrates me is that this information is freely available, the research is quite sound, and there's no reason for idiots to start spreading completely false information that isn't supported by biochemistry.
I really hate conspiracies. Doubly so when it's completely fallacious, such as the absolutely asinine claims that mRNA is going to modify our DNA and make us slaves to the Bill Gates mastermind or some such nonsense. If some dumbass programmer like myself can figure out what mRNA does, I don't understand why so many people eat up the conspiracy that it does something impossible.
Thank you again for stepping in and bringing real experience to this conversation. It's sorely needed. There's only so much an amateur such as myself can argue without requiring authoritative assistance.
The thing is that 99.9% of the population is what I would posit are "headline-educated." They're unwilling to read beyond headlines, and in most cases are consumed by a fascination with conspiracy that has no basis on reality. It's unfortunate, but it's the reality that we have to face. Those of us who do try to educate ourselves--even if we often fail--do so for a variety of reasons. I can't speak to the others here who follow suit, but my line of work requires a degree of analytical thinking (systems design, development, debugging, etc); consequently, I'm not entirely fond of taking rumors at face value. It does a disservice to humanity to ignore the plethora of information available on the Internet at our fingertips. Yet here we are.
I'm grateful there are people like you posting on TDW to help keep those few of us who actually do read honest. My understanding on this matter is exceedingly limited, but I know enough to debate the conspiracists on the grounds that I have at least some idea how this technology functions (even at my most basic level of understanding, it's not hard to see how even if there's a TON of research and effort that goes into the what and the why).
I am a bit disappointed that someone downvoted you, but it doesn't really surprise me: No one likes to be told their conspiratorial line of thinking is wrong. Not when it's a strongly held conviction.
Once again, I find myself thanking you for sharing your knowledge. I've never been hugely interested in biology, but your "niche" industry is awfully fascinating, even to laypersons such as myself. Know that there are at least some of us who are cheering you on from the sidelines, because your efforts aren't in vain. We know that one day, you'll develop therapeutics for all manner of diseases. This is really just the beginning of a long and fruitful journey.
I would say the very small chance of treatable anaphylaxis is worth ending a pandemic and getting back to normal life. I’d also argue that mRNA nanoparticles offer better protection against mutated strains than live attenuated viruses.
Oh, and I meant to address this too. You're absolutely right. We need to do something, even if it gives some percentage of the population the confidence to open everything back up. The economic disaster unfolding in every state (especially mine) because of these draconian lockdown measures will almost certainly kill more people than the pandemic ever could.
I do have a question for you. Moderna claimed that their tooling is such that once the Chinese released the sequence genome of the virus, they were able to a) pinpoint the receptor sites to target for a vaccine and b) manufactured it in about 2 days since they're able to chemically synthesize the mRNA. Their explanation for it taking so many months since January to release the vaccine is due to federal regulations and the required trials.
Is this true? It seems to me that if that's the case and we can demonstrate that lipid nanoparticles are a comparatively safe delivery system, almost anything could effectively be vaccinated against in short order provided it has structures the immune system can recognize that are also possible to generate from within infected cells via mRNA.
That seems... groundbreaking, to be completely honest, and may be one of the most important breakthroughs in medical history.
Likewise, I agree 100%. Live attenuated vaccines and inactivated vaccines seem grossly inefficient compared to mRNA vaccinations, which in my understanding appear to be highly targeted with the advantage of a very short time to manufacture!
Do you have any concerns at all about this new mRNA method of vaccinating a population? This is the last article I found on JAMA, the news seems good but the caveat is always that this is new and untested on humans for a long enough period of time:
Not over the use of mRNA. My primary concerns are with the PEGylated lipid nanoparticles. These seem to be the source of adverse reactions, sometimes serious, and are the reason why this untested vaccine is somewhat concerning.
The science behind mRNA vaccination is fairly sound and has been considered since circa 1989 for cancer treatment. As far as I understand, there have been attempts since 2005 to manufacture it, but all of them were hampered by the inability to consistently devise a delivery mechanism to get the mRNA into the cytoplasm of the cells.
The idea of encapsulating mRNA inside lipid nanoparticles is fairly new. That's the part that's untested, and unfortunately seems to be the most dangerous aspect.
I call bullshit on the Lactose Intolerance part. :)
Being intolerant of Lactose is a natural process, not an illness ? The body will stop producing Lactase that prevents a reaction to Lactose if the subject is not exposed to Lactose for a period of time, like say, coming away from being breast fed. Its why societies that dont use dairy as part of their normal diet, East Asians for example, are predominantly Lactose Intolerant.
I call bullshit on the Lactose Intolerance part. :)
It's not. Your bullshit detector needs recalibration.
He used an engineered adenovirus that attacked the cells responsible for transcribing lactase, which would insert the appropriate sequence into the cells genome which would then manufacture mRNA required to... generate the lactase.
He released all of the files related to the design of the viral genome on GitHub here.
Being intolerant of Lactose is a natural process, not an illness ?
I guess it depends on how you look at it, but it's technically a genetic disorder. Exposure has very little to do with it, because some people lose the ability to produce it at a very early age--regardless of whether they've been exposed to it or not.
Historically, humans from cultures that have long used milk for a variety of foodstuffs are the least likely to become lactose intolerant as they age regardless of exposure. Those whose heritage is from cultures that do not are more likely to become intolerant regardless of exposure.
This is probably an area that warrants further study, but the answer appears to be largely genetic as the production of lactase is "turned off" because of gene expression that tells it to turn off. Reworking the genome of the appropriate intestinal cells to reactivate lactase production will work, and if it could be done on a basis that allowed the daughter cells to retain this gene expression, it could be permanent.
Both videos are linked from the GitHub repo. I'd highly recommend watching them as he explains the thought processes that went into this as well as the genetic background how and why.
The Pfizer and Moderna vaccines are mRNA vaccines. mRNA does not enter the cell nucleus--it remains in the cytoplasm. There is a paper that studied how mRNA synthesized in the nucleus diffuses into the cytoplasm (after transcription) which may be worth reading. mRNA is used by ribosomes in the cytoplasm to synthesize proteins, enzymes, and other bits--it's how the virus produces more virions with the exception that the mRNA fragments used by both of these vaccines are the sequences that produce the surface receptors.
You cannot modify DNA from mRNA.
What's making people sick in these vaccines is the polyethylene glycol used to stabilize the lipid nanoparticles that encapsulate the mRNA as its delivery system, and PEG are known to cause anaphylaxis. PEG as a component of vaccines is not well-studied and should be viewed with caution, because it certainly does provoke an immune response that can be dangerous if not outright lethal.
If you wanted to go down the rabbit hole of a vaccine that could feasibly modify the patient's DNA, then I'd suggest looking into the AstraZeneca vaccine which uses a modified adenovirus (DNA virus) to inject DNA into the nucleus where the cell transcribes mRNA from the DNA. There's a YouTuber who used a similar adenovirus to "cure" his lactose intolerance for a couple of years by modifying his own DNA in intestinal tissue responsible for producing lactase. Except that the effect wasn't permanent because the modifications could not be transcribed to the daughter cells.
So just have blind faith in the government and big pharma that the mRNA sole purpose is to translate spike proteins and nothing more. Sounds smart to trust the government with this.
I'm not saying to trust them; I'm saying that's how biology works. mRNA cannot modify genes and the only thing it does is produce proteins. That's it.
Where I would direct my concern with these vaccines is toward the PEG-stabilized lipid nanoparticles, because PEG absolutely can kill people if they have a reaction to it. Based on the data that's currently available, it appears that there are a growing number of patients exhibiting anaphylaxis post-vaccination.
Except that in the case of mRNA, it cannot enter the nucleus of the cell where the DNA is located. This actually is impossible. I've linked research related to the chemical gates that are used for mRNA egress.
Regardless, assuming that it could enter the nucleus, mRNA has no function inside there that the cell would use, because the nucleus is where mRNA is manufactured--not read.
That's the point I'm trying to get across.
There's no risk with mRNA once you understand the processes at play.
The risk with these vaccinations is in the polyethylene glycol used to stabilize the lipid nanoparticles. That is what people are reacting to, and that appears to be the dangerous aspect of this vaccine that is absolutely causing adverse reactions.
People shouting about the mRNA have absolutely no clue what mRNA is or what its function is inside the cell, which is stupid because it's easy enough to research. What's worse is that it's distracting from the actual dangers that are present in these vaccines that is not well understood, and that's the use of PEG.
Most people seem to tolerate PEG just fine. The people who don't may experience anaphylaxis. As far as long term effects, we have no idea what the long term effects of PEGylated lipids will do to the body.
mRNA has a very short half-life and breaks down pretty rapidly. That's why I don't find it concerning at all. Within a few days, the mRNA of the vaccine won't be present. The PEGylated stuff? Who knows how long that will persist.
Direct your attention there. That's where the interesting effects will begin.
The govt always loves us and takes care of us. They always care about us.
My fixation on PEG is mostly with regards to the reality that the side effects people are witnessing are exclusively from its use, as you noted. Of course, I may be grossly exaggerating it in effort to direct people's attention away from their absurd obsession with mRNA (somehow being stupid enough to think that it will modify their genome).
You're right, of course. My opinion is that the risk of adverse reactions from PEGylated nanoparticles is so comparatively minor that if you do the math, you're probably something like 50 times more likely to die from COVID-19 even with the exaggerated figures than you are to have an adverse reaction.
But, I think part of my whinging is due in part to frustration. I do greatly appreciate your clarifications and defense of this strategy. Thank you so much.
My opinion is also that I sincerely hope the Pfizer and Moderna vaccines demonstrate a safe delivery of mRNA for the reasons that I understand these were originally thought up in the late 1980s as a treatment for cancer (e.g. cancer vaccinations). If this is successful, then it means that the delivery mechanism works, and we might see the COVID-19 fallout lead toward workable vaccinations for common cancers.
FWIW, I don't have any idea what I'm talking about, because I'm a programmer. I have nothing to do with the medical industry. I do, however, happily read whatever research is available at any given time because I'm a bit touched in the head and maybe borderline crazy. But what frustrates me is that this information is freely available, the research is quite sound, and there's no reason for idiots to start spreading completely false information that isn't supported by biochemistry.
I really hate conspiracies. Doubly so when it's completely fallacious, such as the absolutely asinine claims that mRNA is going to modify our DNA and make us slaves to the Bill Gates mastermind or some such nonsense. If some dumbass programmer like myself can figure out what mRNA does, I don't understand why so many people eat up the conspiracy that it does something impossible.
Thank you again for stepping in and bringing real experience to this conversation. It's sorely needed. There's only so much an amateur such as myself can argue without requiring authoritative assistance.
The thing is that 99.9% of the population is what I would posit are "headline-educated." They're unwilling to read beyond headlines, and in most cases are consumed by a fascination with conspiracy that has no basis on reality. It's unfortunate, but it's the reality that we have to face. Those of us who do try to educate ourselves--even if we often fail--do so for a variety of reasons. I can't speak to the others here who follow suit, but my line of work requires a degree of analytical thinking (systems design, development, debugging, etc); consequently, I'm not entirely fond of taking rumors at face value. It does a disservice to humanity to ignore the plethora of information available on the Internet at our fingertips. Yet here we are.
I'm grateful there are people like you posting on TDW to help keep those few of us who actually do read honest. My understanding on this matter is exceedingly limited, but I know enough to debate the conspiracists on the grounds that I have at least some idea how this technology functions (even at my most basic level of understanding, it's not hard to see how even if there's a TON of research and effort that goes into the what and the why).
I am a bit disappointed that someone downvoted you, but it doesn't really surprise me: No one likes to be told their conspiratorial line of thinking is wrong. Not when it's a strongly held conviction.
Once again, I find myself thanking you for sharing your knowledge. I've never been hugely interested in biology, but your "niche" industry is awfully fascinating, even to laypersons such as myself. Know that there are at least some of us who are cheering you on from the sidelines, because your efforts aren't in vain. We know that one day, you'll develop therapeutics for all manner of diseases. This is really just the beginning of a long and fruitful journey.
Oh, and I meant to address this too. You're absolutely right. We need to do something, even if it gives some percentage of the population the confidence to open everything back up. The economic disaster unfolding in every state (especially mine) because of these draconian lockdown measures will almost certainly kill more people than the pandemic ever could.
I do have a question for you. Moderna claimed that their tooling is such that once the Chinese released the sequence genome of the virus, they were able to a) pinpoint the receptor sites to target for a vaccine and b) manufactured it in about 2 days since they're able to chemically synthesize the mRNA. Their explanation for it taking so many months since January to release the vaccine is due to federal regulations and the required trials.
Is this true? It seems to me that if that's the case and we can demonstrate that lipid nanoparticles are a comparatively safe delivery system, almost anything could effectively be vaccinated against in short order provided it has structures the immune system can recognize that are also possible to generate from within infected cells via mRNA.
That seems... groundbreaking, to be completely honest, and may be one of the most important breakthroughs in medical history.
Likewise, I agree 100%. Live attenuated vaccines and inactivated vaccines seem grossly inefficient compared to mRNA vaccinations, which in my understanding appear to be highly targeted with the advantage of a very short time to manufacture!
Will do! And thank you for sharing your expertise! I'm indebted to your willingness to take the time to reply!
Do you have any concerns at all about this new mRNA method of vaccinating a population? This is the last article I found on JAMA, the news seems good but the caveat is always that this is new and untested on humans for a long enough period of time:
https://jamanetwork.com/journals/jama/fullarticle/2770485
Not over the use of mRNA. My primary concerns are with the PEGylated lipid nanoparticles. These seem to be the source of adverse reactions, sometimes serious, and are the reason why this untested vaccine is somewhat concerning.
The science behind mRNA vaccination is fairly sound and has been considered since circa 1989 for cancer treatment. As far as I understand, there have been attempts since 2005 to manufacture it, but all of them were hampered by the inability to consistently devise a delivery mechanism to get the mRNA into the cytoplasm of the cells.
The idea of encapsulating mRNA inside lipid nanoparticles is fairly new. That's the part that's untested, and unfortunately seems to be the most dangerous aspect.
Thanks so much for such a comprehensive answer, I appreciate it!
I call bullshit on the Lactose Intolerance part. :)
Being intolerant of Lactose is a natural process, not an illness ? The body will stop producing Lactase that prevents a reaction to Lactose if the subject is not exposed to Lactose for a period of time, like say, coming away from being breast fed. Its why societies that dont use dairy as part of their normal diet, East Asians for example, are predominantly Lactose Intolerant.
It's not. Your bullshit detector needs recalibration.
He used an engineered adenovirus that attacked the cells responsible for transcribing lactase, which would insert the appropriate sequence into the cells genome which would then manufacture mRNA required to... generate the lactase.
He released all of the files related to the design of the viral genome on GitHub here.
I guess it depends on how you look at it, but it's technically a genetic disorder. Exposure has very little to do with it, because some people lose the ability to produce it at a very early age--regardless of whether they've been exposed to it or not.
Historically, humans from cultures that have long used milk for a variety of foodstuffs are the least likely to become lactose intolerant as they age regardless of exposure. Those whose heritage is from cultures that do not are more likely to become intolerant regardless of exposure.
This is probably an area that warrants further study, but the answer appears to be largely genetic as the production of lactase is "turned off" because of gene expression that tells it to turn off. Reworking the genome of the appropriate intestinal cells to reactivate lactase production will work, and if it could be done on a basis that allowed the daughter cells to retain this gene expression, it could be permanent.
Both videos are linked from the GitHub repo. I'd highly recommend watching them as he explains the thought processes that went into this as well as the genetic background how and why.