mRNA vaccines: let's eradicate herpes, cure cancer, and be sick a whole lot less | Hacker News Reader

mRNA vaccines: let's eradicate herpes, cure cancer, and be sick a whole lot less

bessstillman.substack.com

112 pointsLaurenSerino76 comments

> RNA is fragile. So, like in the COVID mRNA vaccines, these instructions can be delivered in a protective fatty bubble called a “lipid nanoparticle.” Think of it like a balloon made of fatty acids, with the instructions nestled inside. Once injected, these lipid nanoparticles take the mRNA instructions into cells, where the fatty bubble degrades, mRNA instructions are released, and the cell’s machinery start to produce whatever protein the mRNA tells it to.

I still don't understand how writers about mRNA vaccines gloss over the numerous details that should be important. The picture that she paints lacks a targeting mechanism. Which cells will these lipid nanoparticles enter? She does not say. How much protein from the mRNA will those cells produce? It can't be predictable, right? Will there be significant differences in the dose of the final product between individuals? Is this important? She does not say. Will the cells that engulf those lipid nanoparticles be destined to die, in case the protein they produce is a foreign one, like the spike protein of Covid? They must be, right? After all, that's how immunity works. Is this important, given that there is no targeting mechanism? She does not say. And so on...

What makes an mRNA vaccine more appealing than a protein-based one?

Isn’t this also basically what happens to countless of our cells every day through natural exposure to viruses?

Maybe? Although viruses that we are naturally exposed to on a daily basis don't routinely bypass the mucous membrane barrier, and do not roam freely throughout our bodies. And they normally do have a targeting mechanism that allows them to selectively infect certain types of cells. And in any case, viruses are supposed to be bad for the organism; so I am not sure how this consideration helps.

I mean viruses target everything and nothing, and mutate insanely rapidly. I imagine the majority that enter our bodies aren’t able to perform any function, and then the ones that can will opportunistically infect anything without regard for the consequences.

As for whether or not viruses are bad for us, I mean I don’t think we have any choice in the matter anyway, they’re even more numerous than bacteria, and absolutely everywhere.

I wonder how many viruses infect our cells every day vs how many “lipid viruses” are in a standard Moderna Covid shot.

Everything you said sounds interesting, but my experience, as a scientist in a different field, is that media focused for regular non-expert people simply isn't going to capture those kinds of things. You need to find recent papers, review articles or maybe textbooks to get that kind of information, basically its going to be in documents targeted at experts in this field not lay people.

You are correct, and the problem with these articles is that they sound too much like a sales pitch and less like a responsible general-public divulgation article.

She may not go in detail about the items aforementioned, but she doesn't even mention once that the technology might have have possible dangers, and that one must exercise caution in its evaluation. The article its all about the potential benefits of the technology, without warning the public about its potential dangers.

She even mentions that "the FDA is so painfully slow, and so indifferent to human suffering. It takes, on average, eight years to get a new drug through clinical trials."

Yeah, those pesky thorough clinical trials, they are a hurdle on the return on investment.

Similarly, my question is if we trick random cells around the body into producing these spike proteins, and they presumably don't stop for a while (no idea on how long), does this not also create an undo burdon on the immune system until the cells artificially producing the protein die? And if there's loose RNA floating around, after these cells die can another cell _also_ start reproducing the protein?

I think the idea is that the RNA doesn't last long. It's quite fragile. You might get fragments of it though, but not enough to print out the whole protein.

The mRNA vaccine mostly stays near the site of injection: your arm. This is why your arm mostly aches, and the rest of your body not so much. A bunch of cells there will die, because your immune system much prefers an innocent cell dead than a infected cell continuing to multiply. But you have plenty of cells. Really quite a lot. So it is entirely worth it.

We can try to optimize how much protein cells will make from the mRNA. The goal is "as much as possible, for as long as possible", but mRNA is not meant to be long lived. And foreign mRNA trying to make its way into cells would be destroyed very quickly without trickery (like the nanoparticle and the pseudouridine).

But either way, medicine works just the same (a surprising amount of the time!) in the cases where the precise details and mechanisms haven't been elucidated yet. If it works empirically, the details are just details.

> But you have plenty of cells. Really quite a lot.

We have also a lot of cells that do not divide such as neurons, or some cardiac cells.

> The mRNA vaccine mostly stays near the site of injection: your arm.

This patently false, and medical disinformation. It is proven with the Covid vaccines that it spreads to the entire body.

> What makes an mRNA vaccine more appealing than a protein-based one?

Having worked on the same targeting mechanisms for protein based vaccines meant to be personalized cancer therapies, and having followed the mRNA vaccines with envy, the benefits are absolutely massive. But there's not a single alternative. In comparison to each type:

Short peptides injection are worse because: minimal immune stimulation, less of a mechanism to train the immune system on the peptide targets, have not been effective.

Viral delivery of mRNA, that makes proteins, or more exotic methods like yeast with modified genomes: this is a traditional vaccine with a custom viral genome with the peptides of interest added as part of the viral genome. This is not directly a protein virus, but it does make the cells it infects produce the peptides. This requires cell culture to grow the virus, which requires a unique clean room per vaccine, which can be impractical and expensive for a custom virus. It's also very very slow to produce, QC, and make sure it's safe. mRNA production is faster, cleaner, safer, just all around better in every possible way.

As for your other questions, sure they are interesting, but get ready to gear up and read tooooons of literature. Most people don't have any of these questions unless they have a deep distrust of the technology, and don't trust that others have bothered to investigate.

Skepticism is good, and if you are truly curious I really applaud you and encourage you to pick up an immunology text book so that you can also read and understand the papers. But mRNA vaccine skepticism has to be the stupidest "skepticism" and falsehoods I have ever seen of a new technology. As the competitor to what I was working on, I must concede that it's better on all metrics, and I am kind of saddened for humanity that all these lies about mRNA seem to dominate over the true and huge technological advancement that has occurred.

> Short peptides injection are worse because: minimal immune stimulation, less of a mechanism to train the immune system on the peptide targets, have not been effective.

If the problem of peptide vaccines is weak immune stimulation, then wouldn't the problem of mRNA vaccines be autoimmunity?

No, why would that be? Auto-immunity comes from immune cells targeting healthy cells, and the mRNA peptide translations do not correspond to healthy cells.

Don't feel sad. There are many people in your situation, who wonder why there is so much backlash to their ideas even though you have done due diligence and are working in good faith and genuinely think that your approach/idea/invention is a boon to humanity.

>>> But mRNA vaccine skepticism has to be the stupidest "skepticism" and falsehoods I have ever seen of a new technology.

To be fair the media and government are more to blame. By attacking and trying to silence the skeptics during COVID only proved to make what you said worse.

You wont make a very attractive product by shaming, deriding, or forcing someone into taking said product that deals with their health.

I don't see how you can convince a skeptic who doesn't have the same knowledge as say a educated professional working on vaccines.

Either the skeptic needs the same level of education or an explanation from someone they trust with the level of education needed. You can't convince the skeptics with a sound byte. If they truly believe the government has it out for the entire country. I don't know where you would even begin.

I think the flaw here is you don't form your success or failure of adoption based on if you can convince the skeptics.

Thinking everyone can be brought to your side with reason is not a logical assumption. Some people no matter how strong an argument will not want to do something no matter the level of evidence or reasoning. Be it their faith or stubbornness and we need to be ok with that.

jailing them, excluding them from society, or forcing them from their jobs to provide to their famalies is how you get people to side with skeptics and does the opposite effect

You didn't answer his/her questions.

What makes it more appealing is that you can change the mRNA sequence and change the proteins that are created, meaning you can make arbitrary proteins. Traditional vaccines are far less flexible like that since the process to create proteins has more steps

One of the big breakthroughs was techniques to modify the mRNA to increase stability and resulting protein production. So it is somewhat predictable.

Don't forget reverse transcription into free-floating DNA. That's much more stable and can last a long time, and it was confirmed in a lab back in 2021 or 2022 that our liver cells are capable of doing it with the Pfizer mRNA covid vaccine.

There was another study last year on long covid that found some vaccine-specific spike proteins persisting weeks or months after they should have degraded/been removed by the immune system, but IIRC they didn't find a reason why.

"What makes an mRNA vaccine more appealing than a protein-based one?"

For one, mRNA is easier to produce/manufacture than protein.

It seems like our hot pace of trendy advances has let non-fiction writers flirt with writing in the science fiction genre. If you see some articles as hard science fiction with a "this is a true story" framing device then they make more sense.

> Why are mRNA vaccines the future?

This may well be true, but I’ll be far more likely to believe it when there’s an mRNA vaccine that’s anywhere near as effective as the best old boring vaccines.

(I admit that my personal favorite, not-mRNA, HSV vaccine candidate is from a company, X-vax, that appears to have forgotten to renew its domain.)

I’m also not entirely clear about the path by which mRNA technology might eliminate persistent infections. Maybe by preventing them in the first place? Maybe via CRISPR?

The covid mRNA vaccines were wildly effective at the original covid strain—95%. But respiratory viruses mutate like crazy.

They were wildly effective for a few months after being given. We don’t know how well they would continue to work in the absence of mutation.

But it’s worse than that: the revised vaccines appear to be nowhere near as effective even against strains closely related to those which they target. As a somewhat plausible mechanism, repeated doses have been shown to induce IgG4 production, which non-mRNA vaccines don’t seem to do.

Measles and Chickenpox are both airborne, although they’re not respiratory the way Covid is. But their respective vaccines are vastly more effective.

I’m not saying that I know, or have strong evidence, that mRNA vaccines are weak. But I do think it’s fair to say that we have no evidence that they can be comparably effective to earlier vaccine technologies.

Measles and chickenpox are both respiratory and airborne. The serial interval is longer though, gives the vaccines more time to work to prevent transmission. Though, the chickenpox vaccine is more of a "parental time off work harm reduction" thing, however the newer shingles vaccines make that somewhat less so, as the combined vaccines do probably have a RRR on getting symptoms for your whole life.

Edit: not to say there's no "positive" effect on the total death rate (i.e. the vaccine causes there to be less deaths overall), it's just not a cost effective positive effect considered in isolation.

Coronavirus were thought to be non-vaccinable, even worse than the flu. They are behind a lot of winter colds, and they are a great pain in veterinary. Veterinaries are the ones that were pessimistic before mRna vaccines, because they were trying vaccines for decades to no avail.

Measless and chickenpox are very stable, and even the body gains inmunity for life just being exposed to it in the childhood.

All of them are virus the same way an ant and a elephant are animals. You might kill the ant with a magnifying glass, but good luck trying with th elephant.

> Coronavirus were thought to be non-vaccinable, even worse than the flu.

Citation needed. I think the biggest reason there’s no common cold vaccine is that there are too many common cold varieties, often not even related to each other.

Dengue was thought to be a difficult target, and are some non-mRNA vaccines looking pretty good in trials right now.

You require citations, and start your assertions with "I think". Seems unfair. In fact, we have some vaccines for some "common colds" (https://en.wikipedia.org/wiki/Respiratory_syncytial_virus_va...), but none for coronavirus common colds.

I refered to veterinary as a source of pesimism. There are a number of veterinary serious problems related to coronavirus. I'm going to just refer to https://en.wikipedia.org/wiki/Coronavirus#Infection_in_anima.... Labs are trying to get vaccinations for those infections for years if not decades, to no avail. We are talking of millions, if not billions, in farm loses, so not a minor issue.

When all the SARS-CoV-2 event was raging, people from veterinary were very pesimistic, because they knew coronaviruses change so rapidly that no (traditional) vaccine holds for long enough. Luckily, mRNA vaccines shorten the window between variant detection and roll-out. They are trying genetically altered viruses that include multiple versions of the S protein, to induce the immunity, so it's not like they are working with ancient technology or no resources.

You also recognize that "dengue was thought to be a difficult target", and indeed it was. You don't need [citation] to assert that. The fact that we were trying to vaccinate against Dengue for almost a century is [citation] enough. The same holds true for coronavirus, specially in veterinary.

> repeated doses have been shown to induce IgG4 production

I have a strong suspicion that this finding explains some if not all of the weird results with these vaccines.

* The 95% effective was a measurement solely of sickness, not infection. At the time this was reported, we had no idea if this meant it prevented infection/improved the immune response (good) or suppressed the immune response so we didn't develop symptoms (bad).

* Tons of countries had huge infection spikes just a couple months after reaching high vaccination rates.

* "Long Covid" seems to have become far more prevalent after the vaccines than before.

Here's what I think is happening: The IgG4 finding is key in explaining all of these. It suppresses the immune response, which would allow the virus to run wild without any immediate symptoms (95% initial efficacy). This could cause small amounts of damage that accumulate into Long Covid (why it's associated with infection but seems more prevalent in vaccinated people), as well as turn the vaccinated into asymptomatic spreaders (the high infection spikes).

Personally, I think mRNA vaccines were a complete failure.

Is it possible that long Covid developed in people who prior to vaccination, would have simply died of Covid?

The larger point is that there are many many confounding factors including Survivor bias

The new vaccines are always outdated by the time they get to market, it just mutates too fast. For example Omicron emerged in November 2022, and booster shots for Omicron weren’t available until far later. And now the disease is much more diverse.

No vaccine technology will be able to solve that on its own. There would need to be a significant change in risk tolerance of approving and manufacturing vaccines and deploying them on a rapid timescale.

> Measles and Chickenpox are both airborne, although they’re not respiratory the way Covid is. But their respective vaccines are vastly more effective.

Natural infection with Measles and Chickenpox are also vastly more effective at preventing reinfection than natural infection with SARS-CoV-2. It is a property of the virus, not the vaccine.

> This may well be true, but I’ll be far more likely to believe it when there’s an mRNA vaccine that’s anywhere near as effective as the best old boring vaccines.

You mean like the influenza vaccine that is only about 50% effective and you have to get a shot every year because the virus eventually achieves immune escape? You mean like the old boring human coronavirus vaccines against things like HCoV-229E or HCoV-OC43... that just don't exist?

If you're thinking of something like measles where the vaccine confers lifelong protection, that has nothing to do with the vaccine. The virus just can't mutate to escape the immune system response to it without negatively affecting replication and transmission.

And you can see that with the immune effects of the virus itself. Get actually infected with measles and recover and you'll be protected for life against getting measles again. Get influenza and you won't have lifelong protection. Get COVID or any other human coronavirus and you won't have lifelong protection. Go get into an argument with your own T-Cells about they're so shit against respiratory viruses, they're the ones at fault.

Although with mRNA vaccines we actually might be able to generate vaccines that target more conserved sequences the stalk of influenza's hemagglutinin surface protein and get the immune system to recognize a much broader spectrum of influenza viruses and possibly give lifelong protection. You'll never get that with inactivated or attenuated virus vaccines since you can't target that specifically.

This is Jake Seliger ('jseliger)'s partner, if you're wondering.

https://substack.com/@bessstillman

  I'm an ER doctor, writer, and wife to Jake Seliger (JakeSeliger.com)
  who is dying of squamous cell carcinoma of the tongue

It's very sad that Jake has terminal cancer.

Very excited to look forward to a future where the entire Herpesviridae family is wiped out (whether it's Epstein-Barr, HSV-1/2, whatever). HPV too. Really exciting time. I tend to visit /r/HerpesCureResearch every now and then to see the progress. I imagine something like this would be a gamechanger on so many levels.

One day I hope that HIV is also finally vaccinated for.

This is about as succinct a summary as it gets re mRNA's potential:

"To create an mRNA cancer vaccine, a patient’s tumor is biopsied to identify unique target mutations —> mRNA correlating to mutations is synthesized and injected into the patient —> the patient’s cells create the targeted protein —> the creation of foreign proteins stimulates the immune system and teaches it how to recognize the target protein —> The immune system (especially T cells) search for this target protein and destroy the cancer cells to which it’s attached."

Making the immune system target tissue produced by the body, even a cancerous growth, is risky business.

I've said above, if there aren't other treatment options available, it makes sense, but even then I don't know why one wouldn't use standard immunotherapies instead, which are less risky.

I think Moderna and Pfizer generated a lot of profit from the vaccines, and now they need a way of turning that over into capital, and they are still trying to find ways to have widespread adoption of regular mRNA treatments. But even millions or billions of dollars of capital investment will not yield a profit if its a bad investment.

Of course, but so are almost all cancer treatments, and many cancers are still a death sentence.

The immune system does this all the time. They're called natural killer cells (NK Cells) and they regularly target cells that have become cancerous or infected.

Well yes, NK cells do that when we're infected with a malignant infection.

For the last hundred years, or so, vaccines have been non-malignant, so we've never had to question such things.

However, mRNA vaccines are an entirely novel class of technology, so it's appropriate for us question:

a) how long mRNA vaccines persist in the body? b) how discriminating are mRNA vaccines in which cells they impact? c) if any testing was done on the side effects of accidental intravenuous injection of mRNA vaccines? (given that there are plenty of blood vessels in muscle tissue) d) if any longitudinal studies have been done on mRNA vaccination of humans? e) if any comprehensive studies have been done on pregnant or nursing women injected with mRNA vaccines, and the impact on their infants?

Even if that statement were correct what difference does it make if you're going to be in the ground in six months?

The difference between those 6 months being a slow grind that gives you the chance to say goodbye to the world vs. sudden onset death from overwhelming immune malfunction. Quality of life is not an afterthought, even with the end in sight.

This has a precondition: the existence of targets unique to the cancer cell. That's not necessarily true. In theory you can have cancerous cells that are (at least in the epitope-space) indistinguishable from normal cells. I'm not a doctor, and I guess (and hope) this is an usual case, but finding a truly unique and dissimilar mutation sounds pretty hard, training the immune system to detect it correctly without generalizing sounds even harder. Potential, sure, and I hope this proceeds and yields some therapies that are safer than chemotherapy, but we need to be realistic with what we'll probably get.

It's not that hard, in patients with cancer, it's very common for the immune system to go after the cancer specific mutations, until the cancer learns to express the cell-surface checkpoints that deactivate the immune system.

Its extremely rare (or at least I have not heard of it) to develop auto-immune activity during the course of cancer.

T-cell receptors that recogize HLA-bound epitopes tend to be extremely specific, and rarely go after other parts of the body. There's nothing special about cancer in this regard.

>the creation of foreign proteins

Those proteins are already there though, right?

It's a shame mRNA vaccines don't work like traditional vaccines. The problem with mRNA vaccines is that they cause the immune system to attack healthy cells throughout the body, when the injected mRNA causes those cells to emit foreign proteins. For most parts of the body, that's fine, because it's okay to gain some muscle scar tissue in the arm. But muscle scar tissue in the heart will measurably shorten one's life expectancy.

mRNA injections are meant to be intramuscular, but some will become accidentally intravenous if the needle accidently enters (or nicks) a blood vessel. And then the substance will enter the heart and lungs where healthy heart and lung cells will begin expressing the Covid spike protein, causing those heart and lung cells to be killed by cytotoxic T cells and NK (natural killer) cells.

We used to protect against accidental intravenous injection by a technique called "aspiration", where the plunger of the syringe is withdrawn slightly prior to injection, to check for blood. However, aspiration was stopped around 2010 as it was feared the slight increase in injection pain might put people off getting routine vaccinations.

This is fascinating. Where can I learn more about this?

Doctor John Campbell is a good place to start:

This video focusses on the aspiration technique, and the consequences of inadvertantly giving an mRNA injection intravenously: https://www.youtube.com/watch?v=nBaIRm4610o&t=13s&ab_channel...

His bio:

"My name is John Campbell and I am a retired Nurse Teacher and A and E nurse based in England. I also do some teaching in Asia and Africa when time permits. These videos are to help students to learn the background to all forms of health care. My PhD focused on the development of open learning resources for nurses nationally and internationally."

This comment section is being heavily censored even for very mild criticisms.

Scary to see this censorship still goes on, even now, at this latter stage, where the studies on myocarditis are numerous and no longer debunked.

The censorship was even worse during the initial rollout of mRNA technology, blocking fair scrutiny of a widespread rollout.

Proper scientific scrutiny and debate is vital around novel technologies. Particularly novel MEDICAL technologies. And particularly where governments are mandating that the technology is administered to whole populations.

I think the world will be just fine if a few mediocre coders have their medical hot takes downvoted on an online forum.

If it doesn’t matter then it also doesn’t hurt to leave the posts up. Thanks.

Unfortunately you can’t see how mild these “hot takes” are.

I've yet to find a single dead comment that isn't just trying to troll, insult or peddle the whole "it's a hoax" meme.

In fact one of the top rated comments with child comments is specifically as you claim is bring censored mild but fair criticism of mRNA vaccine and it's effectiveness.

Reply on news.ycombinator.com