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Comment by hashtagmarkup | Hacker News Reader

No one seems concerned that this is the first "Genetic Vaccine". It doesn't just contain proteins to train your immune system... it rewrites your own cells to produce those proteins. There is no off switch.

The only approved vaccine like this (that I know of) is to protect horses from west nile virus.

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That is not true, there is an inherent off-switch in this method. Messenger RNA is not stable in cells and is actively degraded. A typical mRNA has a half-life of a few hours in a cell. After the mRNA is degraded, no more viral protein will be produced.

This has nothing to do with gene therapy or anything that would permanently modify your genome.

I'm so glad you pointed this out. A horse in search of a mule and et cetera.

> Messenger RNA is not stable in cells and is actively degraded. A typical mRNA has a half-life of a few hours in a cell.

Can anyone speak to the confidence we have in these claims? That is, are we virtually 100% sure that these mRNA have no mechanism to stick around for longer than intended?

GP's point is valid - that this is the first mRNA vaccine that would be widely used.

Let's say our assumption is wrong - these mRNA have a way to stick around forever. Is there an off switch?

These things have been in development for over a decade. There's mountains of in vivo data on mRNA vaccines.

They have never been approved for human use, so you might want to check sources on that data.

One question I got in an organic chemistry exam many years ago was why RNA is not as suitable as DNA for storing genetic information. Essentially why it is inherently less stable than DNA.

With a bit of organic chemistry knowledge you can determine how the additional OH in RNA allows for water to attack there and cleave the RNA strand. This is very dependent on pH, but RNA is inherently less stable than DNA.

But that's not actually the most important mechnanism here, but it is one that is inherent in the chemistry of the molecule, there is no way around it.

Cells need to regulate protein production up and down. If mRNA were to live eternally, there would be no way to reduce protein production. So cells obviously have a way to remove mRNA. What actually happens is that mRNA is permanently degraded by RNAses, so any mRNA that isn't replenished will be gone after a while and protein production will stop. This is a fundamental part of regulation of protein biosynthesis, and you can find that in every textbook.

In addition to the the additional hydroxyl group and cellular RNAses, mRNA is predominantly single stranded while DNA is double stranded, which provides additional stability and protects the nucleotide.

In addition to that being a fact, synthetic mRNA can predominantly reprogram cells to create arbitrary proteins, which provides additional stability and protects the programmer.

One conclusion I got in a mathematical logic exam so many many moons ago was how something being "not as X" still implied that something was "somewhat X".... so just because "RNA is not as suitable as DNA for storing genetic information", essentially it still is somewhat suitable, and perhaps suitable enough.

What about reverse transcription? For example let's imagine you use this vaccine on someone with HIV or another retrovirus.

I haven't looked at the sequence of the vaccine, I assume it is not public. But for the HIV reverse transcriptase to bind the sequence would need to have the proper binding site, and there is no reason to put that in there. Those enzymes are specific, they don't just transcribe anything they come across.

Just because a light-bulb will more than likely burn out eventually doesn't mean there is an inherent off switch.

I can't think of a single existing drug with an off switch. Food doesn't have an off switch. Everything in your body goes in, and then goes out according to the pharmacokinetics that your liver, kidneys, and other parts impose.

This isn't like the first person biting into a new apple variety for the first time... this is like the first person growing an apple from scratch in their stomach, using techniques that have never before been approved for human use.

I can't think of a single existing drug that works like that, because there hasn't been one. Food doesn't reprogram my cells before it "goes out".

The first vaccine was a live virus (cowpox), and it reprogrammed your cells in a way stronger sense than an mRNA injection does.

Yeah... and that's why cowpox was bad.

If your immune system realizes the source of the spike proteins is your own reprogrammed cells, and then attacks them, it will lead to cascade autoimmune disorders mimicking the symptoms of AIDS.

I don't know where you're getting this information from, AIDS isn't an autoimmune disorder. HIV destroys immune cells directly. The symptoms are mainly from secondary infections. Also, if your immune system realizes that your own cells are making virus particles, it will destroy them... and every other cell will survive. That's what happens when you catch a cold - every virus works that way. mRNA is even better because it probably won't cause any of your cells to get targeted for destruction. The failure mechanism you're proposing would at worst make it as bad as some other vaccines.

I don't know why you don't see the difference between similar symptoms and similar mechanisms.

A compromised immune system spiraling out of control attacking itself looks the same from the outside.

I do know where you're not getting information from, as there isn't any... because it's never been approved for human testing.

>it's never been approved for human testing.

That's not accurate, there have been several studies where mRNA vaccines have been tested. They were previously being developed for cancer treatment.

It's never been approved for human testing *until now under the administration of a lame duck lunatic begging for a reason to take credit for a solution.

How did those cancer treatments pan out? Why weren't they FDA approved?

Maybe you could have started your thinking with the #1 abused drug in the world, heroin; and the nearly instant off switch drug, narcan, that is carried by everyone in emergency medical services.

How much is pfizer paying you? or are you just a r/wsb autist? #YOLO

I was thinking of drugs like penicillin when I said that. I guess you could count the chelating agents they give to people with heavy metal poisoning in that, too. But by and large, drugs do not come with off switches.

Oh... so you only thought of 1 fungus, and then concluded that there couldn't be any drug at all... by and large.

I guess you never learned 1 =/= ∞.

Your off switch is probably stuck.

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