I'm a bioengineer. Everyone that gives an answer mostly ignores epigenetics and the fact that RNA can permanently alter the _shape_ (or conformation) of how your DNA is tightly wound up. For example, RNA can direct methylation of DNA and alter histones, which can lead to transgenerational epigenetic effects on gene expression and phenotype [1]. The fact is, molecular cell biology is incredibly complex and the models we have are just that, models. Saying that these mRNA strands don't affect the genome long-term may be correct, but this is an educated guess based on theoretical models. There's a reason why FDA approvals traditionally took 10+ years, we normally verify our educated guesses empirically.

It almost certainly won't have long-term affects, but it may not be trivial to identify if mRNA vaccines have been altering epigenetics.

[1] https://en.wikipedia.org/wiki/RNA-directed_DNA_methylation

> we normally verify our educated guesses empirically

Love that quote! That's going to be my standard comment from now on when I see a pull request that doesn't include any test cases :-)

Wouldn't catching the virus itself also have these epigentic effects?

How would you test the extent of the mRNA's/DNA's impact within the cell?

Is it possible to do something like tagging the molecules with radioisotopes and following their path?

Here's an example: https://www.nejm.org/doi/full/10.1056/NEJM199001253220403

Follow-up question: Do these effects (which are very unlikely) differ between vaccine and the virus itself? Or maybe: Is the epigenetic risk higher/different?

Everything in life has potential epigenetic effects! Not sure what you are trying to communicate with your comment but it sounds like you are saying people should avoid the mRNA vax but then you also say “almost certainly no long term effects.” Your thesis seems to be that 10 years is enough time to know for sure that they are safe. Why is 10 years the right amount of time? Why not 50 years or 5? In other words what’s your model for relative risk/reward and why is it better than what is being done in terms of public health outcomes?

You seem to be putting a lot of words in OPs mouth. I didn't see OP making any sort of suggestion about whether to avoid the vaccine or not. It looked like they were simply explaining some possible outcomes of the vaccine that are unknown.

OP also didn't say 10 years is enough time to know the long-term effects of these vaccines, just that it's traditionally been the minimum amount of time needed for some other drugs.

50 would certainly cover all life stages of humans. I assume you could be sure with shorter.

I have an aviation, biochem, and skydiving background. My rule is for aviation: "if it hasn't been out five years you're a test jumper."

Humans are way more complex than airplanes. I personally wouldn't take the mRNA vaccine because of this rule. Coupled with being unable to sue or get help from the government I think people IN LOW RISK groups have been way too enthusiastic to sign up.

https://www.cnbc.com/2020/12/16/covid-vaccine-side-effects-c...

I'd be happy to take the vaccine if I was in a higher risk group and I'll be happy to take the vaccine in a year or two, but right now I just don't think it's right decision for someone like myself.

Given my risk is very low I'm not too worried about COVID, but I am a little worried (perhaps wrongly) about the risk of finding out about some long-term side effect from these vaccines a few months down the road. I suffer from long-term side effects from another drug I took in the past, and at the time I was told there was no risk of long-term side effects and that it was safe to take. Only recently has the labeling been updated to reflect the discovery that permanent side effects can occur in some cases and for me it's too late, but I learnt my lesson to allow others to be the guinea pig for new drugs wherever possible.

It's really quite alarming how little we know about the body, espically considering the certainty of some "experts" about how extremely low the risk of adverse effects are from newly approved vaccines. I'm aware of a number of drugs which are approved and frequently perscribed which we don't even understand the mechanism of action for -- accutane, for example. Of course in this situation, we do know the mechanism of action, but it would still be wrong to assume we know the full surface area of possible side effects which could occur because our model of the human body is so basic.

I'm happy for someone to explain why I'm wrong on this. I'm obviously not an expert, just an average guy trying to assess the relative risk of two very unlikely events.

There is no reason to expect that side effects from the vaccine are not present or actually dramatically higher from the live virus. An infection by the virus, even if asymptomatic, will likely introduce way more alien genetic material and viral proteins into your body than the non-reproducing vaccine ever would. So one should trust the FDA panel of experts on risk unless there's strong evidence pointing otherwise.

> I think people IN LOW RISK groups have been way too enthusiastic to sign up.

About that...

> In December, we asked, “What percentage of people who have been infected by the coronavirus needed to be hospitalized?”

> The correct answer is not precisely known, but it is highly likely to be between 1% and 5% according to the best available estimates, and it is unlikely to be much higher or lower. We discuss the data and logic behind this conclusion in the appendix.

> Less than one in five U.S. adults (18%) give a correct answer of between 1 and 5%. Many adults (35%) say that at least half of infected people need hospitalization.

https://www.brookings.edu/research/how-misinformation-is-dis...

From what I can deduce using CDC data my chance of hospitalization is 0.5 to 2%. Assuming linear relationship of obesity in the population and assuming the same risk at the top of my cohort to the bottom.

My point was more the last part:

> Many adults (35%) say that at least half of infected people need hospitalization.

This is why so many in low-risk groups have been so enthusiastic - misinformation that has them thinking it really is the Black Death.

Or maybe people are just terrible at judging acute risks? This isn't unique to covid - ask them about flying on an airliner or living next to a nuclear power plant and you would get some equally comical numbers. At any rate risk of hospitalization/death isn't the complete picture since some of those young people are ostensibly doing it to protect the people around them.

So let’s say hypothetically that white people were low risk relative people of color. You would have white people not get vaccinated because the consequences for their group, alone, might be slightly better?

Does that not seem a bit ... immoral?

I assume you eschew all other medical advances that are less than 50 years old? Would you eschew remdesivir? Sorry for the questions but thinking such as yours intrigues me and I want to grasp the logic behind it. Why not avoid all new technology for 50 years? Getting vaccinated seems to me like the logical and moral thing to do, but maybe I’m overlooking something.

Would this be an advantage for the Novavax vaccine as it doesn't do anything to hijack cellular machinery to create the spike protein, it just (as I understand it) has a bunch of pre-made spike proteins.

Thank you for this explanation. I've been wondering this myself especially when it comes to methylation.

Everyone is the world is either going to be exposed to the spike mRNA from the vaccines or the virus.

Pointless FUD to worry about that or even bring it up.

Being in the nucleus and being integrated into your chromosomes so that they are copied during cell division aren't the same thing.

https://www.medpagetoday.com/special-reports/exclusives/9160...

> Adenoviruses -- even as they occur in nature -- just do not have the capacity to alter DNA. Unlike retroviruses such as HIV or lentiviruses, wild-type adenoviruses do not carry the enzymatic machinery necessary for integration into the host cell's DNA. That's exactly what makes them good vaccine platforms for infectious diseases, according to Coughlan.

> And, engineered adenoviruses used in vaccines have been further crippled by deleting chunks of their genome so that they cannot replicate, further increasing their safety.

This sounds a bit like a technicality. The DNA makes it into the cell nucleus and is used by the cell machinery to make proteins. The changes aren't carried over after cell division, but lots of cells in your body last your whole life (nerves, brain cells, eye cells, important stuff).

I was under the impression all cells in the body will be regenerated in 7 years.

Loss of neurons and cardiac muscle cells is permanent. Emergency medical personnel are usually taught "time is brain" and "time is heart" for this reason.

Some body cells can bounce back after serious trauma, liver cells being a prime example: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701258/

I think the argument hinges on the technicality that it's not splicing itself into the host genome, so no chance of it becoming a retrovirus or something like that (in the event that the cell's lineage is not extinguished by the immune system).

I'm not a genetic engineer (what a time to be alive, eh?), but I'm pretty sure an adenovirus that did permanently modify cell DNA would be more like CRISPR, including the risks that entails (such as the risk of incorrectly splicing the host genome and potentially creating a precancerous mutation)

I didn't want to put this into the parent comment because I didn't want to get just shoved into the "vax" vs. "anti-vax" bucket by the replies.

But there's a very well known case where DNA delivered via an adenovirus killed a teenager during a genetic engineering study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/

>> "No one realized that the vector itself might pose a risk"

I'm sure the dosage, type of adenovirus, and modifications to the adenovirus are different. But there are obviously still risks we don't know about.

Don't look at things like that. Shut down your brain and take your pilllls.

I want to be perfectly clear that I didn't bring this up to be alarmist. Jesse Gelsinger's death shed a lot of light on the risks involved with adenoviruses [1]. Those lessons have been carried forward.

>> An autopsy and subsequent studies indicated that his death was caused by a fulminant immune reaction (with high serum levels of the cytokines interleukin-6 and interleukin-10) to the adenoviral vector.

>> The data suggested that the high dose of Ad [adenoviral] vector, delivered by infusion directly to the liver, quickly saturated available receptors ... within that organ and then spilled into the circulatory and other organ systems including the bone marrow, thus inducing the systemic immune response.

He was injected with >3 × 10^13 viruses [2]. The typical J&J dose contain: low-dose (5x10^10 viral particles) or high-dose (1x10^11 viral particles) [3].

[1] https://www.uab.edu/ccts/images/steinbrook_Gelsinger_-_Oxfor...

[2] https://www.cell.com/molecular-therapy-family/molecular-ther...

[3] https://www.jwatch.org/na53085/2021/01/26/adenovirus-vectore...

Whenever you catch a cold or flu those are generally DNA viruses (unless it's a coronavirus cold). Those don't alter your DNA.

Eh, yeah they do. We have tons of base pair sequences in our DNA that we suspect came from viruses.

https://newsroom.uw.edu/news/genes-%E2%80%98fossil%E2%80%99-...

Parent specifically stated DNA viruses. From your article:

> Most of these viral genes come from retroviruses, RNA viruses that insert DNA copies of their own genes into our genomes when they infect cells. HHV-6 is unique because it is the only known human DNA herpesvirus that integrates into the human genome and can be routinely inherited.