Hacker News Reader

Comment by ch4s3 | Hacker News Reader

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).

View on HN

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?

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.

> 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.

Retroviruses carry reverse transcriptase which does exactly that: turns RNA into DNA.

Yep. That was her point.

From the responses you’d think I was talking about brain chips injected by Bill Gates, but I suppose this is the result when a layman attempts to explain something unfamiliar to other laymen.

The thing that all biologists fundamentally understand is that none of this stuff has been designed. Every process in the body happens due to chemical reactions that do happen spontaneously. The replies above don't seem to get this and instead consider a human body to be the product of design like a car or something. You can't just throw metal at a car and hope to invent a new type of gearbox. But throwing stuff at living things is exactly how change is driven. If we were immutable we wouldn't be here.

The part about parts spontaneously forming a bicycle is a nice soundbite, but reverse transcriptase (an enzyme) is used by RNA viruses to do just that.

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?

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

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.

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.

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.

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.

> 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.

> 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.

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.

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.

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.

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.

Just a slight correction; as I understand it, these vaccines are prophylactic, not therapeutic.

You’re going to tell me building random proteins in a persons body is not a Faustian Bargain?

Your body constructs "wrong" proteins all the time due to translation or folding errors.

It depends on the function of the protein if this leads to a bad outcome.

Exactly — and I rely upon the many hundreds of thousands of years of experience and direct “winning” to beat adversaries.

This statement cuts both ways — if this recent pandemic was human made we need human solutions... only IF the virus is insurmountable.

As someone with direct experience with a large N, this virus is nothing to exponentially increase long term and second order risk with human “solutions” ... UNLESS the long term effects for asymptomatic cases are severe and under reported.

Again... too many variables outstanding to be certain, but highly cautious

Viruses do it all the time. It can indeed cause trouble, but a random mutated rhinovirus is more likely to do so (allergies, typically) than a vaccine which was developed specifically to not cause any damage.

This xkcd from last week is about precisely this issue! https://xkcd.com/2397/

We think way too highly of ourselves as a species

I’ll fight natural selection any day... crispr, no way.

We are not gods. At least with previous vaccines we just killed off the active parts and said “hey, go bull fight this” to our immune system.

Last bit: Leverage works in both ways

Organism evolves the capabilities to understands diseases and develops ways to fight them, if that isn’t natural selection what is?

This idea that "We are not gods." Such a peculiar argument. If something is capable by a mortal man what makes you think it has god-like qualities? To me it is the opposite. Also since you're using the word "gods" are you referring to polytheism? Where did you decide you were capable of determining a "god-like" thing? You. Are. Confusing. Me.

Prob a safety req foe most work or travel. You gonna need one or another.

Sorry. No that's a violation of HIPAA and basic human rights.

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.

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.

Uhm, the Spanish flu infected 500 million people (6.5 times more than covid19) and killed about 50 million (33 times more than covid19). And if you consider that the world at that time had just about 2 billion people, a modern Spanish flu would have killed 175 million people (100 times more than covid19), and probably more since denser population makes it easier for viruses to spread.

Now, we have the (repeatedly) proven ability to avoid such a disaster, and you argue we should not? You really think protection from disease is not a basic human right?

It feels like screaming into the void

I've mostly given up on HN as a forum for free discussion, because the mods' endorsement of downvote-for-disagreement results in comments like yours (reasonable, historically informed, advocating liberty and actual human rights) being downvoted to obscurity, while the comments full of manipulative, Orwellian word games ("You don't want to take a vaccine? You're refusing basic precautions and infringing upon my human rights!") are prized.

So, while I used to write comments like yours, myself, I don't bother anymore. I'd have to spend years toeing the line to build up enough karma to not get shadowbanned for it.

Anyway, I sign in here to say that I'm with you. I think it's important to show that this point of view is not the minority view in this country, and maybe even the world, despite all the media does to make it look like it is.

It looks like China's already started World War 3 in terms of "Unrestricted Warfare" (China's term, not mine): financial, biological, psychological, political. Just regarding COVID, they told the world COVID wasn't infectious between people, they held a 40,000-person potluck dinner in Wuhan while the virus was spreading and then let people travel out of the city, they threatened to turn ships around and withhold masks and medicine produced in China...how can anyone look at what China's done and not recognize their malicious intent? At the same time, they're building up their military around the world, indebting poor African nations, pushing their troops into Nepal and India (and actually killing Indian soldiers)...the list goes on and on. We have to wake up before it's too late.

[Of course, the 50 Cent Army is active on HN. Watch my comment fade away...]

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

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.

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.

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"

Would this be an accurate summary: „There is a slim chance the mRNA is incorporated into the DNA if there is an ongoing infection with a retro-virus during vaccination“?

somewhat less than slim.

the RNA must interact with retroviral reverse transcriptase in a manner that makes a functional complex or it will just be snipped apart and decycled like garbage.

RNA will fold and produce 2' structure this has interesting consequence. catalytic RNA, structural RNA, stabilizing or protective RNA..

[0] https://www.youtube.com/watch?v=RYwVnzYf4V8

[1] https://pubmed.ncbi.nlm.nih.gov/20358252/

[2] https://sci-hub.st/https://doi.org/10.1007/s00018-010-0346-2 [PDF]

[3] https://www.researchgate.net/profile/Tania_Matamoros2/public... [PDF]

from the paper [3] above: "Reverse transcription initiates after binding of a cellular tRNA primer (in HIV-1, tRNA Lys,3 ), to the primer binding site (PBS). The PBS is a sequence of 18 nucleotides, located downstream of the 5’-end of the genomic RNA. The viral RNA that serves as template for reverse transcription is flanked by repeat (R) sequences at its 5 ́ and 3 ́ termini."

the vaccine mRNA does not meet these requirements.

retroviral RNA is configured to function with the reverse transcriptase. Promiscuity to include other RNA is exceptional not common.

virally infected cells also undergo changes that exclude further infection so they have the cell to themselves.

i would like to say zero chance, but life is in the business of sidestepping the rules to its advantage, however you have a much greater chance of being attacked by a shark while hiking the sahara dunes.

Interestingly, it seems this has already happened with the virus being integrated into human DNA in rare cases, though apparently to no ill effect: https://www.sciencemag.org/news/2020/12/coronavirus-may-some...

this is a preview paper.

the situation was artificially created.

the retroviral Reverse Transcriptase must be present in the individual cells also infected with the covid virus.

Thanks, appreciated.

you have a non zero chance of changing your DNA every time you do something.

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

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-...

"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)."

Reply on news.ycombinator.com