8 ms·

I would love to know (to assuage any family members' doubts) -- Are there any possible long term side effects of using such an mRNA drug that are yet unanticip

I would love to know (to assuage any family members' doubts) -- Are there any possible long term side effects of using such an mRNA drug that are yet unanticipated? All the short term side effects are known / will soon be. Anything beyond that, we haven't had enough experience to know?

ch4s3 6y ago
Probably not. There was about 20yrs of research on using mRNA for gene therapy before the CRISPR/Cas9 discovery. It was abandoned as a route for gene therapy specifically because it wasn't long lasting. The mRNA isn't incorporated into the DNA, so it isn't reproduced by the cells and eventually breaks down. Things inside of cells are flying around at high speeds and constantly colliding, so it's not a very stable environment. There are people that this was tested on still hanging around with no lasting negative effects (to my knowledge).
- marvin 6y ago
  My partner, a biochemist, has mentioned the potential possibility of RNA viruses causing the RNA of the vaccine to stabilize as some sort of DNA structure. Normally RNA is quickly broken down by RNase, but apparently RNA viruses have a mechanism to defend against this, that it's possible to imagine having an interaction with an RNA vaccine. I don't know anything about biochemistry, and I'm aware that the above is just remote speculation. It is meant as an example of food for thought. But I do wonder when a whole field of scientists state "there is no possibility of unexpected long-term side effects" to a therapeutic tool that has never been used at anything resembling this scale. Would love to hear more experts discuss why this is considered sufficiently long-term safe to make the decision of vaccinating a billion people after nine months of testing. Am I missing something, or is it just a question of the precautionary principle in this case being considered too costly?
  - jgable 6y ago
    Given that this pandemic has killed millions, shut down the world economy, and caused untold long term damage to children due to lack of stable schooling: yes, it’s because the precautionary principle is too costly. Edit: sorry, my comment may have sounded snarky, which was not my intention. World-wide vaccinations do carry a risk. It’s just that such a risk clearly pales in comparison to the very known downsides of the current situation. I am in no way a vaccine expert and cannot comment intelligently on why long-term risks are considered to be low.
    - chrisco255 6y ago
      It killed a million because it's novel. The flu also has killed millions, but because it's been around a while there's a lot of herd immunity to the flu. As time goes on, Covid's severity naturally decreases. Same as it has always been. And kids being kept out of schools despite being 99.999% immune is ridiculous.
      - amanaplanacanal 6y ago
        Kids are being kept out of school so they don’t get the virus and spread it to somebody else. They aren’t immune, as far as I know. Just less likely to die from it.
    - perf1 6y ago
      You mean million that died, had a positive PCR test at some time. There are still less people dying in 2020 than in 2018 in most countries even though population gets older and therefore more people are dying every year on average anyway.
      - amznthrwaway 6y ago
        It fucking sucks that dang allows perpetually dishonest assholes like you in here, just because he and Paul love your far right agenda.
  - darkerside 6y ago
    There could certainly be a logical error in play here, but considering this is mRNA, and not DNA, it seems like it would be fairly amazing for it to spontaneously form into DNA. Similar to a load of parts spontaneously forming into a bicycle. That's not to say it isn't possible, but many things are possible but sufficiently unlikely that we take those risks. We eat, drink, and breathe many things every day that we don't fully understand the ingredients or impacts of.
    - dragonwriter 6y ago
      > Similar to a load of parts spontaneously forming into a bicycle. For the analogy to be more accurate, the parts should explicitly not be bicycle parts.
    - deleted 6y ago
      [deleted]
    - hybrid_cluster 6y ago
      Spontaneously, yes - fairly amazing. But what if the person treated with the mRNA vaccine happens to be infected with another RNA virus that is producing reverse transcriptase enzymes to convert its own RNA into DNA?
      - tylerhou 6y ago
        To prevent an immune response and degradation, the mRNA vaccine nucleosides are modified from normal human mRNA. It's possible that RNA virus reverse transcriptase may not be able to work on these modified nucleosides. https://www.nature.com/articles/nrd.2017.243 https://www.nature.com/articles/nrd.2017.243
    - deleted 6y ago
      [deleted]
    - globular-toast 6y ago
      Retroviruses carry reverse transcriptase which does exactly that: turns RNA into DNA.
  - greedo 6y ago
    Just a slight correction; as I understand it, these vaccines are prophylactic, not therapeutic.
  - akiselev 6y ago
    > Would love to hear more experts discuss why this is considered sufficiently long-term safe to make the decision of vaccinating a billion people after nine months of testing. Am I missing something, or is it just a question of the precautionary principle in this case being considered too costly? FDA approvals aren't a black and white affair. Some drugs are approved as orphan drugs through trials designed to be much cheaper than Phase 1-3 trials when they treat diseases that wouldn't be profitable for pharma, for example, and there is a path for preliminary compassionate use approvals and accelerated development for stuff like chemo where the disease is terminal anyway. The FDA works with each company to tailor the process to their needs (although, obviously, they stick to a strict standard unless there's good justification). Likewise, the vaccine rollout won't be all or nothing. We won't even have a billion doses for a long while and the focus will (likely) be on vaccinating those for whom the benefits outweigh the extra risk like front line medical staff and the immunocompromised or elderly. I don't expect the world to get vaccinated at gun point, although the rules for schools and other institutions will quickly accumulate to cover most of the population. Personally, I'm not going to be taking the vaccine for a while since no one in my family is at risk and we're (mentally) preparing for several years of varying levels of isolation and other precautions. I have faith in the system for the most part since I've worked on an FDA application before (clinical diagnostics, not therapeutics), but the kind of geopolitical and economic pressure its under right now is unprecedented and should keep epidemiologists up at night (hell, it probably does). It's going to be up to each individual to balance their risks and obligations at least until we get more data.
    - marvin 6y ago
      That's the most level-headed response I've heard yet. Most people just equate my worries to those of an antivaxxer and move on. These new vaccines have a 90% efficacy. It's probably a no-brainer to give them to someone in their 70s or 80s with a high likelihood of having an adverse covid case. But a 20-year-old? Out of a purely selfish wish of having a more normal world, part of me wants to suppress these thoughts and think "I'm probably excessively cautious, it's a good thing that the economic pressures will probably ensure that most are vaccinated in a year or two". But I do worry that many healthy people don't have a complete view of the potential for unknown unknowns when they decide to take it. The selfish part of me is thankful that someone else does the dirty job for ensuring that those thoughts aren's spread wider. I'm really hoping that the authorities know what they're doing, and I'd definitely be lying awake at night if I was in that role. I probably won't take it myself - there, I said it - but rather wait and get more data, or maybe go as far as seeing when one of the protein-based vaccines are ready.
  - BurningFrog 6y ago
    > is it just a question of the precautionary principle in this case being considered too costly? People only use the precautionary principle for things they don't want to do. It's very good for that, since it always results in recommending not to do things.
  - brendoelfrendo 6y ago
    > Would love to hear more experts discuss why this is considered sufficiently long-term safe to make the decision of vaccinating a billion people after nine months of testing. Am I missing something, or is it just a question of the precautionary principle in this case being considered too costly? I think, generally, it has been discussed. There's lots of research on mRNA vaccines going back decades at this point, though they haven't made it to market until now. I see people saying "it's not being discussed" often on this site, but really, anyone saying "no, this is safe" has the implicit support of all that research behind them.
    - chrisco255 6y ago
      It's not really that many decades of research. This tech is from the 90s. This is the very first mRNA vaccine to be deployed on a mass scale. Does it cause cancer 10, 20 years from now? Does anyone know that for sure? It's not like we have a perfect scientific statistical sampling of people who received mRNA vaccines 30 years ago and we can evaluate those long term effects.
  - nocturnial 6y ago
    This was one of the questions someone posed during the FDA approval of the pfizer vaccine. I'm paraphrasing here, but you can look up the exact question on one of the youtube videos or read the transcription: "Suppose someone was infected with a retrovirus, could reverse transcriptase embed that rna into the dna? This could be especially worrisome if we're talking about a pregnant woman and fetus undergoes rapid cell division... etc.." I would be surprised if I did not mangle up some terms & concepts in the paraphrasing above. Someone who knows more can correct me or just watch/read the fda hearing. Another thing that was mentioned in the FDA hearing was that pfizer also tested it on HIV positive people. HIV is a retrovirus which also carries the reverse transcriptase enzyme. I don't want to draw any conclusions from this because I don't have any medical knowledge. Maybe someone here with more insight could comment.
- MrBuddyCasino 6y ago
  Has there ever been an instance of genetic transformation as a consequence of a mRNA vaccine? Saw this listed as a potential risk in a paper[0], but I have no expertise at all to judge if this a possibility or not. [0] https://www.mdpi.com/2076-393X/8/2/212/pdf https://www.mdpi.com/2076-393X/8/2/212/pdf
  - blackbear_ 6y ago
    If you are referring to the following sentence in the introduction, I understood it to mean the opposite: > Moreover, mRNA vaccines induce transient antigen expression, while DNA vaccines provide a long-lasting expression, thus mimicking an acute viral infection. Although a transitory gene expression might be desirable as it minimizes potential risks of genetic transformation, this inevitably affects mRNA potency, thus necessitating a dose increase. This means that mRNA reduce the risk of genetic transformation compared to DNA vaccines, but it comes as a price because you have to deliver a larger dose of mRNA.
    - MrBuddyCasino 6y ago
      Yes that was the sentence. The expression "minimizes potential risks of genetic transformation" implies that there is a non-zero risk, and I'm curious how minimal it is.
      - rolph 6y ago
        Biology is about finding a productive exception to the rules. This means that when circumstances say no you cant, biological entities find a work around. as a cover your ass practice, even the smallest chance of occurence means non zero chance. in this case an mRNA would have to be captured by a reverse transcription system most likely due to co-infection with a retro virus, that complex would have to be functional and would have to be transported into the nucleus. this is a very remote chance but non zero, thus : "minimizes potential risks of genetic transformation"
        MrBuddyCasino 6y ago
- anonymouse008 6y ago
  You’re going to tell me building random proteins in a persons body is not a Faustian Bargain?
  - m3kw9 6y ago
    Prob a safety req foe most work or travel. You gonna need one or another.
    - chrisco255 6y ago
      Sorry. No that's a violation of HIPAA and basic human rights.
      - vkou 6y ago
        Being a vector of a deadly infectious disease, and not taking basic precautions infringes on the human rights of people around you. Anti-vaxxers are generally tolerated until there's a critical mass of them, which start causing problems for everyone else.
        chrisco255 6y ago
        No it doesn't. Viruses have been around longer than humans have, so NOTHING HAS CHANGED. We have been through SMALLPOX, TUBERCULOSIS, SPANISH FLU, PLAGUE, AIDS, and many, many other pandemics and NEVER, EVER has anyone been insidious enough to suggest a vaccine as a prerequisite for human rights. You need to reevaluate your logic and life choices. This disease already has a 99.9% survival rate for the general population and much higher in certain demographics. At any rate, government tyranny has killed millions and millions more than viruses have. And I won't stand for it. Medical tyranny will never be tolerated. If YOU want the vaccine, you get it. That's how liberty works.
        anonymouse008 6y ago
        It feels like screaming into the void
- an_opabinia 6y ago
  Moderna’s one other trial in the last 10 years failed due to toxicity. Their filing cabinet is full of deadly mRNA therapies.
  - astronautjones 6y ago
    that is absolutely false
- perf1 6y ago
  What do you think about one of the Australian Vaccine that got everybody in the study to test HIV positive. I don't think researches know enough to claim it save without long term tests. I also heard that HIV can hide in mRNA from your Immune system. I would call that long lasting. https://www.youtube.com/watch?v=v4C9huNGdSw https://www.youtube.com/watch?v=v4C9huNGdSw
  - AareyBaba 6y ago
    Rubbish. It did not cause HIV. The reason they cancelled the project was that uninformed people would go around claiming that it caused HIV. Also, other vaccines are now available. https://www.reuters.com/article/uk-factcheck-hiv/fact-check-an-australian-vaccine-trial-did-not-give-trial-participants-hiv-idUSKBN28R2WT https://www.reuters.com/article/uk-factcheck-hiv/fact-check-... "This is a reference to trials of a vaccine being developed by the biotech company CSL and The University of Queensland which used a fragment of a HIV virus protein as a component to stabilise the vaccine (here). Production was halted after trials showed that antibodies generated in response to the protein fragment could lead to false positives on some HIV tests (here)."
AntiImperialist 6y ago
>Are there any possible long term side effects of using such an mRNA drug that are yet unanticipated? I'm not sure but I strongly assume yes. The MAIN reason for this skepticism is that if it was just possible to introduce RNA such that we could have a net positive benefit against coronavirus, a virus that has existed for almost as long as mammals have, we'd have naturally evolved this ability. The reason we haven't is because it will introduce more problems than it solves down the line. It could very well be that with a limited understanding of human immune system, we have stumbled upon a solution to a problem that has affected us for millions of years. So, I think some people should try it. But forcing it on the masses is a terrible idea.
- reissbaker 6y ago
  This take implies that no medicine for deadly diseases can work because otherwise we would have evolved the medicines ourselves. Also, COVID-19 has not been around "for millions of years." Other coronaviruses, such as the common cold, have. The evolutionary benefits of defense against the common cold are fairly different than benefits against COVID-19. And immunity against one coronavirus doesn't grant immunity against all other coronaviruses.
  - throwaway316943 6y ago
    Two points, the most effective treatments we have for deadly diseases are vaccines which are effective precisely because they rely on our naturally evolved defences. Antibiotics are a runner up but are eventually rendered ineffective by evolution of bacteria they target. Second, Covid-19 is only new to humans, given time it will adapt to us and will likely attenuate.
  - AntiImperialist 6y ago
    >This take implies that no medicine for deadly diseases can work because otherwise we would have evolved the medicines ourselves. That is true. Most of them don't work, not without creating worse problems down the line. Specially, if it's something as simple as creating some proteins that the body can already produce (which is what happens when mRNA vaccine is given). If the solution was as simple, evolution would have found ways to do that. Currently, some deadly diseases do have some treatments that work... but that comes at HUGE expense i.e. a LOT of energy has to be spent for little gain. It is only possible because there is huge inequality among people and the rich class can afford to spend enormous energy and manpower to treat those diseases. If and when the world becomes more equal, this will no longer be possible (you'd think that "robot slaves" working off of "free energy" would solve that... I don't think that's going to happen but that's a different discussion). >Also, COVID-19 has not been "around for millions of years." We can't know that. It could very well be that COVID-19 had infected mammals before and we naturally god rid of it in a few generations. When infections come about, "weaker" individuals die and those with stronger immunity survive and reproduce and the species of COVID-19 might have died out. Some coronaviruses continue to live with us because they don't cause major problems... but there must have been many more which caused major problems and we had had to deal with them differently... and one of them could have been very similar to COVID-19. But yeah, it could also be that this is the first time we're encountering it. So, let's go with that. My argument doesn't change. >immunity against one coronavirus doesn't grant immunity against all other coronaviruses True. However, in millions of years, our immune system has encountered many species and strains of coroviruses, and trained on that data and come up with a much more generalized and long term solution. I'd rather trust that than some random know it all people who think that have a better solution with very limited knowledge of what is going on. Having said that, I'm not against testing new solutions. It's the scale that bothers me.
biophysboy 6y ago
I work with RNA, but not in medicine. mRNA is not a long-term molecule in the body, so its difficult to imagine direct long-term effects. Of course, immune responses can cause long-term damage. So the question is: should we wait to find out? The doses have 30-100 ug. Assume 1)this is pure RNA, and 2)the molecules are about the same size as the spike protein sequence. With these assumptions, a dose gives you 10^10 RNA molecules. Average sputum samples show about 10^6 molecules/mL; max samples show 10^9/mL. I don't know how vaccines dilute when you inject it into somebody's shoulder, but it doesn't seem unreasonable to say the final conc will be between 10^6 and 10^9 RNA/mL. So RNA is going to be in us, whether we want it or not. The question is, do you want the whole genome, or part of the genome. I'm picking the one that doesn't make more virus.
- contravariant 6y ago
  Would you perhaps be able to answer a question I've been wondering about? Is this way of injecting mRNA really any different from just injecting someone with a virus? Not in the sense that it makes you ill but in the sense that a virus would do the same thing just with more harmful mRNA.
  - jartelt 6y ago
    In this case, the mRNA just gets your body to produce a part of the spike protein that is on the virus. Once the spike protein is floating around in your body, your immune system recognizes the spike protein and starts an immune response. The spike proteins themselves cannot actually replicate and attack the body. They are just a small part of the virus structure. If you inject with virus, presumably the virus would begin to replicate and attack your body.
  - mancerayder 6y ago
    It's RNA to make the spike protein, so your immune system becomes infuriated and produces a reaction to kill cells that turned into factories for that protein. You don't want the virus RNA, that would be presumably all that plus more! The answer to your question is, it's a subset of the virus.
IfOnlyYouKnew 6y ago
The difference to "traditional" vaccines is really not significant with regards to risk. The mRNA is translated to a protein, which is the actual target your immune system then recognises as foreign, attacks, and remembers. In a sense, it's a lot like a prodrug, which is a "traditional" small-molecule that is turned into the actual drug by some interaction with your body–your stomach acid, for example. "mRNA" might sound scary. But it isn't going to change your genome or anything like that; it's strictly downstream from DNA. Any virus, bacteria, or salad you eat contains far more mRNA in addition to DNA or RNA, and the first of those really does come with mechanisms to insert itself into your cells' DNA and has evolved to defend itself against your defences, and to slowly take over your body in some way or other. There are some short-term risks on the order of, say, eating lobster for the first time. Allergies, for example, which can be quite severe and even deadly. But those are exactly the risks the trials would have uncovered, and the people possibly at risks of such things would already know they are susceptible. There is no known mechanism for any risk that would not manifest within the first day or two.
- anonymouse008 6y ago
  For some reason I worry about proteins made by fallible humans freely roaming the halls of my veins. You have heard of mad cow disease? Also how misshaped proteins are pretty much impossible to destroy eh?
  - vkou 6y ago
    Then you should be truly horrified about all the proteins from the hundreds of billions of bacteria and viruses, and of course, cancer cells, that are currently roaming your veins, because said bacteria or viruses did not even try to make them safe for their hosts.
    - anonymouse008 6y ago
      *if I viewed all proteins as equal... I take solace knowing that if said virus creates something truly catastrophic to the human race - its way beyond the realm of caring for we shall be dead soon. However, its evolutionary time scale factored by its probability of being that horrible means I’m better off waiting to win the lottery. HOWEVER, knowing we as humans tried to replicate the exact “key card” into our cells that makes this virus so potent (aka the spikey bits with the ACE receptor end) worries me greatly. That’s not on evolutionary time scales or mutations... that sounds like IVF and diabetes.
aazaa 6y ago
Some clinical work has been done with mRNA vaccines as treatments for other diseases, including cancer. Nothing has made it to Phase 3 yet (other than for Covid-19), but on this page you'll find links to a slew of clinical trials over the years. https://www.modernatx.com/pipeline/modernas-mrna-clinical-trials-cmv-mma-zika-several-types-cancer-and-other-diseases https://www.modernatx.com/pipeline/modernas-mrna-clinical-tr... A handful of studies are currently recruiting for Phase 2, so that means there was a successful Phase 1 some years ago. So those people would, I believe, be the longest-surviving patients to have received an mRNA vaccine.
- Scoundreller 6y ago
  The Phase 1 study might just mean it didn’t immediately harm the people that got it. They might be followed closely for a long time; but it may only be a handful of people too.
- divbzero 6y ago
  Yes, and also a number of non-Moderna clinical trials dating back to 2008. [1] The largest of those trials enrolled around 200 participants — not Phase 3 sized but still significant. [1]: https://www.nature.com/articles/nrd.2017.243/tables/2 https://www.nature.com/articles/nrd.2017.243/tables/2
- dharma1 6y ago
  Which companies besides Moderna are at/near phase 2 for vaccines against other diseases now?
deleted 6y ago
[deleted]

ch4s3 6y ago

Probably not. There was about 20yrs of research on using mRNA for gene therapy before the CRISPR/Cas9 discovery. It was abandoned as a route for gene therapy specifically because it wasn't long lasting. The mRNA isn't incorporated into the DNA, so it isn't reproduced by the cells and eventually breaks down. Things inside of cells are flying around at high speeds and constantly colliding, so it's not a very stable environment. There are people that this was tested on still hanging around with no lasting negative effects (to my knowledge).

marvin 6y ago
My partner, a biochemist, has mentioned the potential possibility of RNA viruses causing the RNA of the vaccine to stabilize as some sort of DNA structure. Normally RNA is quickly broken down by RNase, but apparently RNA viruses have a mechanism to defend against this, that it's possible to imagine having an interaction with an RNA vaccine. I don't know anything about biochemistry, and I'm aware that the above is just remote speculation. It is meant as an example of food for thought. But I do wonder when a whole field of scientists state "there is no possibility of unexpected long-term side effects" to a therapeutic tool that has never been used at anything resembling this scale. Would love to hear more experts discuss why this is considered sufficiently long-term safe to make the decision of vaccinating a billion people after nine months of testing. Am I missing something, or is it just a question of the precautionary principle in this case being considered too costly?
- jgable 6y ago
  Given that this pandemic has killed millions, shut down the world economy, and caused untold long term damage to children due to lack of stable schooling: yes, it’s because the precautionary principle is too costly. Edit: sorry, my comment may have sounded snarky, which was not my intention. World-wide vaccinations do carry a risk. It’s just that such a risk clearly pales in comparison to the very known downsides of the current situation. I am in no way a vaccine expert and cannot comment intelligently on why long-term risks are considered to be low.
  - chrisco255 6y ago
    It killed a million because it's novel. The flu also has killed millions, but because it's been around a while there's a lot of herd immunity to the flu. As time goes on, Covid's severity naturally decreases. Same as it has always been. And kids being kept out of schools despite being 99.999% immune is ridiculous.
    - amanaplanacanal 6y ago
      Kids are being kept out of school so they don’t get the virus and spread it to somebody else. They aren’t immune, as far as I know. Just less likely to die from it.
  - perf1 6y ago
    You mean million that died, had a positive PCR test at some time. There are still less people dying in 2020 than in 2018 in most countries even though population gets older and therefore more people are dying every year on average anyway.
    - amznthrwaway 6y ago
      It fucking sucks that dang allows perpetually dishonest assholes like you in here, just because he and Paul love your far right agenda.
- darkerside 6y ago
  There could certainly be a logical error in play here, but considering this is mRNA, and not DNA, it seems like it would be fairly amazing for it to spontaneously form into DNA. Similar to a load of parts spontaneously forming into a bicycle. That's not to say it isn't possible, but many things are possible but sufficiently unlikely that we take those risks. We eat, drink, and breathe many things every day that we don't fully understand the ingredients or impacts of.
  - dragonwriter 6y ago
    > Similar to a load of parts spontaneously forming into a bicycle. For the analogy to be more accurate, the parts should explicitly not be bicycle parts.
  - deleted 6y ago
    [deleted]
  - hybrid_cluster 6y ago
    Spontaneously, yes - fairly amazing. But what if the person treated with the mRNA vaccine happens to be infected with another RNA virus that is producing reverse transcriptase enzymes to convert its own RNA into DNA?
    - tylerhou 6y ago
      To prevent an immune response and degradation, the mRNA vaccine nucleosides are modified from normal human mRNA. It's possible that RNA virus reverse transcriptase may not be able to work on these modified nucleosides. https://www.nature.com/articles/nrd.2017.243 https://www.nature.com/articles/nrd.2017.243
  - deleted 6y ago
    [deleted]
  - globular-toast 6y ago
    Retroviruses carry reverse transcriptase which does exactly that: turns RNA into DNA.
- greedo 6y ago
  Just a slight correction; as I understand it, these vaccines are prophylactic, not therapeutic.
- akiselev 6y ago
  > Would love to hear more experts discuss why this is considered sufficiently long-term safe to make the decision of vaccinating a billion people after nine months of testing. Am I missing something, or is it just a question of the precautionary principle in this case being considered too costly? FDA approvals aren't a black and white affair. Some drugs are approved as orphan drugs through trials designed to be much cheaper than Phase 1-3 trials when they treat diseases that wouldn't be profitable for pharma, for example, and there is a path for preliminary compassionate use approvals and accelerated development for stuff like chemo where the disease is terminal anyway. The FDA works with each company to tailor the process to their needs (although, obviously, they stick to a strict standard unless there's good justification). Likewise, the vaccine rollout won't be all or nothing. We won't even have a billion doses for a long while and the focus will (likely) be on vaccinating those for whom the benefits outweigh the extra risk like front line medical staff and the immunocompromised or elderly. I don't expect the world to get vaccinated at gun point, although the rules for schools and other institutions will quickly accumulate to cover most of the population. Personally, I'm not going to be taking the vaccine for a while since no one in my family is at risk and we're (mentally) preparing for several years of varying levels of isolation and other precautions. I have faith in the system for the most part since I've worked on an FDA application before (clinical diagnostics, not therapeutics), but the kind of geopolitical and economic pressure its under right now is unprecedented and should keep epidemiologists up at night (hell, it probably does). It's going to be up to each individual to balance their risks and obligations at least until we get more data.
  - marvin 6y ago
    That's the most level-headed response I've heard yet. Most people just equate my worries to those of an antivaxxer and move on. These new vaccines have a 90% efficacy. It's probably a no-brainer to give them to someone in their 70s or 80s with a high likelihood of having an adverse covid case. But a 20-year-old? Out of a purely selfish wish of having a more normal world, part of me wants to suppress these thoughts and think "I'm probably excessively cautious, it's a good thing that the economic pressures will probably ensure that most are vaccinated in a year or two". But I do worry that many healthy people don't have a complete view of the potential for unknown unknowns when they decide to take it. The selfish part of me is thankful that someone else does the dirty job for ensuring that those thoughts aren's spread wider. I'm really hoping that the authorities know what they're doing, and I'd definitely be lying awake at night if I was in that role. I probably won't take it myself - there, I said it - but rather wait and get more data, or maybe go as far as seeing when one of the protein-based vaccines are ready.
- BurningFrog 6y ago
  > is it just a question of the precautionary principle in this case being considered too costly? People only use the precautionary principle for things they don't want to do. It's very good for that, since it always results in recommending not to do things.
- brendoelfrendo 6y ago
  > Would love to hear more experts discuss why this is considered sufficiently long-term safe to make the decision of vaccinating a billion people after nine months of testing. Am I missing something, or is it just a question of the precautionary principle in this case being considered too costly? I think, generally, it has been discussed. There's lots of research on mRNA vaccines going back decades at this point, though they haven't made it to market until now. I see people saying "it's not being discussed" often on this site, but really, anyone saying "no, this is safe" has the implicit support of all that research behind them.
  - chrisco255 6y ago
    It's not really that many decades of research. This tech is from the 90s. This is the very first mRNA vaccine to be deployed on a mass scale. Does it cause cancer 10, 20 years from now? Does anyone know that for sure? It's not like we have a perfect scientific statistical sampling of people who received mRNA vaccines 30 years ago and we can evaluate those long term effects.
- nocturnial 6y ago
  This was one of the questions someone posed during the FDA approval of the pfizer vaccine. I'm paraphrasing here, but you can look up the exact question on one of the youtube videos or read the transcription: "Suppose someone was infected with a retrovirus, could reverse transcriptase embed that rna into the dna? This could be especially worrisome if we're talking about a pregnant woman and fetus undergoes rapid cell division... etc.." I would be surprised if I did not mangle up some terms & concepts in the paraphrasing above. Someone who knows more can correct me or just watch/read the fda hearing. Another thing that was mentioned in the FDA hearing was that pfizer also tested it on HIV positive people. HIV is a retrovirus which also carries the reverse transcriptase enzyme. I don't want to draw any conclusions from this because I don't have any medical knowledge. Maybe someone here with more insight could comment.
MrBuddyCasino 6y ago
Has there ever been an instance of genetic transformation as a consequence of a mRNA vaccine? Saw this listed as a potential risk in a paper[0], but I have no expertise at all to judge if this a possibility or not. [0] https://www.mdpi.com/2076-393X/8/2/212/pdf https://www.mdpi.com/2076-393X/8/2/212/pdf
- blackbear_ 6y ago
  If you are referring to the following sentence in the introduction, I understood it to mean the opposite: > Moreover, mRNA vaccines induce transient antigen expression, while DNA vaccines provide a long-lasting expression, thus mimicking an acute viral infection. Although a transitory gene expression might be desirable as it minimizes potential risks of genetic transformation, this inevitably affects mRNA potency, thus necessitating a dose increase. This means that mRNA reduce the risk of genetic transformation compared to DNA vaccines, but it comes as a price because you have to deliver a larger dose of mRNA.
  - MrBuddyCasino 6y ago
    Yes that was the sentence. The expression "minimizes potential risks of genetic transformation" implies that there is a non-zero risk, and I'm curious how minimal it is.
    - rolph 6y ago
      Biology is about finding a productive exception to the rules. This means that when circumstances say no you cant, biological entities find a work around. as a cover your ass practice, even the smallest chance of occurence means non zero chance. in this case an mRNA would have to be captured by a reverse transcription system most likely due to co-infection with a retro virus, that complex would have to be functional and would have to be transported into the nucleus. this is a very remote chance but non zero, thus : "minimizes potential risks of genetic transformation"
      - MrBuddyCasino 6y ago
anonymouse008 6y ago
You’re going to tell me building random proteins in a persons body is not a Faustian Bargain?
- m3kw9 6y ago
  Prob a safety req foe most work or travel. You gonna need one or another.
  - chrisco255 6y ago
    Sorry. No that's a violation of HIPAA and basic human rights.
    - vkou 6y ago
      Being a vector of a deadly infectious disease, and not taking basic precautions infringes on the human rights of people around you. Anti-vaxxers are generally tolerated until there's a critical mass of them, which start causing problems for everyone else.
      - chrisco255 6y ago
        No it doesn't. Viruses have been around longer than humans have, so NOTHING HAS CHANGED. We have been through SMALLPOX, TUBERCULOSIS, SPANISH FLU, PLAGUE, AIDS, and many, many other pandemics and NEVER, EVER has anyone been insidious enough to suggest a vaccine as a prerequisite for human rights. You need to reevaluate your logic and life choices. This disease already has a 99.9% survival rate for the general population and much higher in certain demographics. At any rate, government tyranny has killed millions and millions more than viruses have. And I won't stand for it. Medical tyranny will never be tolerated. If YOU want the vaccine, you get it. That's how liberty works.
        anonymouse008 6y ago
        It feels like screaming into the void
an_opabinia 6y ago
Moderna’s one other trial in the last 10 years failed due to toxicity. Their filing cabinet is full of deadly mRNA therapies.
- astronautjones 6y ago
  that is absolutely false
perf1 6y ago
What do you think about one of the Australian Vaccine that got everybody in the study to test HIV positive. I don't think researches know enough to claim it save without long term tests. I also heard that HIV can hide in mRNA from your Immune system. I would call that long lasting. https://www.youtube.com/watch?v=v4C9huNGdSw https://www.youtube.com/watch?v=v4C9huNGdSw
- AareyBaba 6y ago
  Rubbish. It did not cause HIV. The reason they cancelled the project was that uninformed people would go around claiming that it caused HIV. Also, other vaccines are now available. https://www.reuters.com/article/uk-factcheck-hiv/fact-check-an-australian-vaccine-trial-did-not-give-trial-participants-hiv-idUSKBN28R2WT https://www.reuters.com/article/uk-factcheck-hiv/fact-check-... "This is a reference to trials of a vaccine being developed by the biotech company CSL and The University of Queensland which used a fragment of a HIV virus protein as a component to stabilise the vaccine (here). Production was halted after trials showed that antibodies generated in response to the protein fragment could lead to false positives on some HIV tests (here)."

AntiImperialist 6y ago

>Are there any possible long term side effects of using such an mRNA drug that are yet unanticipated? I'm not sure but I strongly assume yes. The MAIN reason for this skepticism is that if it was just possible to introduce RNA such that we could have a net positive benefit against coronavirus, a virus that has existed for almost as long as mammals have, we'd have naturally evolved this ability. The reason we haven't is because it will introduce more problems than it solves down the line. It could very well be that with a limited understanding of human immune system, we have stumbled upon a solution to a problem that has affected us for millions of years. So, I think some people should try it. But forcing it on the masses is a terrible idea.

reissbaker 6y ago
This take implies that no medicine for deadly diseases can work because otherwise we would have evolved the medicines ourselves. Also, COVID-19 has not been around "for millions of years." Other coronaviruses, such as the common cold, have. The evolutionary benefits of defense against the common cold are fairly different than benefits against COVID-19. And immunity against one coronavirus doesn't grant immunity against all other coronaviruses.
- throwaway316943 6y ago
  Two points, the most effective treatments we have for deadly diseases are vaccines which are effective precisely because they rely on our naturally evolved defences. Antibiotics are a runner up but are eventually rendered ineffective by evolution of bacteria they target. Second, Covid-19 is only new to humans, given time it will adapt to us and will likely attenuate.
- AntiImperialist 6y ago
  >This take implies that no medicine for deadly diseases can work because otherwise we would have evolved the medicines ourselves. That is true. Most of them don't work, not without creating worse problems down the line. Specially, if it's something as simple as creating some proteins that the body can already produce (which is what happens when mRNA vaccine is given). If the solution was as simple, evolution would have found ways to do that. Currently, some deadly diseases do have some treatments that work... but that comes at HUGE expense i.e. a LOT of energy has to be spent for little gain. It is only possible because there is huge inequality among people and the rich class can afford to spend enormous energy and manpower to treat those diseases. If and when the world becomes more equal, this will no longer be possible (you'd think that "robot slaves" working off of "free energy" would solve that... I don't think that's going to happen but that's a different discussion). >Also, COVID-19 has not been "around for millions of years." We can't know that. It could very well be that COVID-19 had infected mammals before and we naturally god rid of it in a few generations. When infections come about, "weaker" individuals die and those with stronger immunity survive and reproduce and the species of COVID-19 might have died out. Some coronaviruses continue to live with us because they don't cause major problems... but there must have been many more which caused major problems and we had had to deal with them differently... and one of them could have been very similar to COVID-19. But yeah, it could also be that this is the first time we're encountering it. So, let's go with that. My argument doesn't change. >immunity against one coronavirus doesn't grant immunity against all other coronaviruses True. However, in millions of years, our immune system has encountered many species and strains of coroviruses, and trained on that data and come up with a much more generalized and long term solution. I'd rather trust that than some random know it all people who think that have a better solution with very limited knowledge of what is going on. Having said that, I'm not against testing new solutions. It's the scale that bothers me.

biophysboy 6y ago

I work with RNA, but not in medicine. mRNA is not a long-term molecule in the body, so its difficult to imagine direct long-term effects. Of course, immune responses can cause long-term damage. So the question is: should we wait to find out? The doses have 30-100 ug. Assume 1)this is pure RNA, and 2)the molecules are about the same size as the spike protein sequence. With these assumptions, a dose gives you 10^10 RNA molecules. Average sputum samples show about 10^6 molecules/mL; max samples show 10^9/mL. I don't know how vaccines dilute when you inject it into somebody's shoulder, but it doesn't seem unreasonable to say the final conc will be between 10^6 and 10^9 RNA/mL. So RNA is going to be in us, whether we want it or not. The question is, do you want the whole genome, or part of the genome. I'm picking the one that doesn't make more virus.

contravariant 6y ago
Would you perhaps be able to answer a question I've been wondering about? Is this way of injecting mRNA really any different from just injecting someone with a virus? Not in the sense that it makes you ill but in the sense that a virus would do the same thing just with more harmful mRNA.
- jartelt 6y ago
  In this case, the mRNA just gets your body to produce a part of the spike protein that is on the virus. Once the spike protein is floating around in your body, your immune system recognizes the spike protein and starts an immune response. The spike proteins themselves cannot actually replicate and attack the body. They are just a small part of the virus structure. If you inject with virus, presumably the virus would begin to replicate and attack your body.
- mancerayder 6y ago
  It's RNA to make the spike protein, so your immune system becomes infuriated and produces a reaction to kill cells that turned into factories for that protein. You don't want the virus RNA, that would be presumably all that plus more! The answer to your question is, it's a subset of the virus.

IfOnlyYouKnew 6y ago

The difference to "traditional" vaccines is really not significant with regards to risk. The mRNA is translated to a protein, which is the actual target your immune system then recognises as foreign, attacks, and remembers. In a sense, it's a lot like a prodrug, which is a "traditional" small-molecule that is turned into the actual drug by some interaction with your body–your stomach acid, for example. "mRNA" might sound scary. But it isn't going to change your genome or anything like that; it's strictly downstream from DNA. Any virus, bacteria, or salad you eat contains far more mRNA in addition to DNA or RNA, and the first of those really does come with mechanisms to insert itself into your cells' DNA and has evolved to defend itself against your defences, and to slowly take over your body in some way or other. There are some short-term risks on the order of, say, eating lobster for the first time. Allergies, for example, which can be quite severe and even deadly. But those are exactly the risks the trials would have uncovered, and the people possibly at risks of such things would already know they are susceptible. There is no known mechanism for any risk that would not manifest within the first day or two.

anonymouse008 6y ago
For some reason I worry about proteins made by fallible humans freely roaming the halls of my veins. You have heard of mad cow disease? Also how misshaped proteins are pretty much impossible to destroy eh?
- vkou 6y ago
  Then you should be truly horrified about all the proteins from the hundreds of billions of bacteria and viruses, and of course, cancer cells, that are currently roaming your veins, because said bacteria or viruses did not even try to make them safe for their hosts.
  - anonymouse008 6y ago
    *if I viewed all proteins as equal... I take solace knowing that if said virus creates something truly catastrophic to the human race - its way beyond the realm of caring for we shall be dead soon. However, its evolutionary time scale factored by its probability of being that horrible means I’m better off waiting to win the lottery. HOWEVER, knowing we as humans tried to replicate the exact “key card” into our cells that makes this virus so potent (aka the spikey bits with the ACE receptor end) worries me greatly. That’s not on evolutionary time scales or mutations... that sounds like IVF and diabetes.

aazaa 6y ago

Some clinical work has been done with mRNA vaccines as treatments for other diseases, including cancer. Nothing has made it to Phase 3 yet (other than for Covid-19), but on this page you'll find links to a slew of clinical trials over the years. https://www.modernatx.com/pipeline/modernas-mrna-clinical-trials-cmv-mma-zika-several-types-cancer-and-other-diseases https://www.modernatx.com/pipeline/modernas-mrna-clinical-tr... A handful of studies are currently recruiting for Phase 2, so that means there was a successful Phase 1 some years ago. So those people would, I believe, be the longest-surviving patients to have received an mRNA vaccine.

Scoundreller 6y ago
The Phase 1 study might just mean it didn’t immediately harm the people that got it. They might be followed closely for a long time; but it may only be a handful of people too.
divbzero 6y ago
Yes, and also a number of non-Moderna clinical trials dating back to 2008. [1] The largest of those trials enrolled around 200 participants — not Phase 3 sized but still significant. [1]: https://www.nature.com/articles/nrd.2017.243/tables/2 https://www.nature.com/articles/nrd.2017.243/tables/2
dharma1 6y ago
Which companies besides Moderna are at/near phase 2 for vaccines against other diseases now?

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