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

https://bessstillman.substack.com/p/mrna-vaccines-lets-be-sick-a-whole

by LaurenSerino • 2 years ago

112 58 2 years ago

bessstillman.substack.com

cgh• 2 years ago

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."

kingkawn2• 2 years ago

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

DiscourseFan• 2 years ago

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.

CJefferson• 2 years ago

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

stolen_biscuit• 2 years ago

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.

tjpnz• 2 years ago

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

mateo1• 2 years ago

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.

epistasis3• 2 years ago

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.

ljsprague2• 2 years ago

the creation of foreign proteins

Those proteins are already there though, right?

azangru3• 2 years ago

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?

virgildotcodes2• 2 years ago

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

azangru3• 2 years ago

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.

s0rce• 2 years ago

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.

dapf• 2 years ago

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.

ImPleadThe5th• 2 years ago

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?

HPsquared• 2 years ago

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.

tux3• 2 years ago

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.

JPLeRouzic• 2 years ago

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.

hitpointdrew• 2 years ago

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.

epistasis3• 2 years ago

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.

azangru3• 2 years ago

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?

imtringued• 2 years ago

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.

georgeplusplus2• 2 years ago

>> 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.

ljsprague2• 2 years ago

You didn't answer his/her questions.

thehappypm4• 2 years ago

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

maxerickson• 2 years ago

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

Izkata2• 2 years ago

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.

1vuio0pswjnm7• 2 years ago

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

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

sandspar• 2 years ago

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.

amluto3• 2 years ago

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?

thehappypm4• 2 years ago

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

amluto3• 2 years ago

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.

lamontcg2• 2 years ago

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.

whiterknight2• 2 years ago

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

cbeach4• 2 years ago

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.

Cornbilly• 2 years ago

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

0dayz• 2 years ago

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.

cbeach4• 2 years ago

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.

pcthrowaway• 2 years ago

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

cbeach4• 2 years ago

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."

tptacek• 2 years ago

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

kqr2• 2 years ago

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.

someotherperson• 2 years ago

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.

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

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