It seems like with the flurry of support behind mRNA tech, right now is quite an exciting time to be in biotech. It's early days, but from what (little, admittedly) I've read there seems to be a lot of promise behind it. If it lives up to even 10% of its theorised promise, we're potentially going to see a lot of amazing treatments in the coming couple of decades.
Bio tech is fascinating those days. The anti-aging community, the athletes and the nutrition crowd are so enthusiastic it created a wave of funding and activity. Of course, quantity doesn't mean quality, but you can find some real gems. And now with covid, it's exploding in popularity.
This is a pretty exciting part of the mRNA field. There are some mutations that cause cancer (like G12D, G12V, G13D or G12C in KRAS) which allows you to make a single vaccine that can be used by anyone with those mutations. There is also a push to do personalized cancer vaccines where you sequence a single person's cancer and find the top 30 or so mutations in any gene that are different from their normal cells.
The biggest issues IMHO with cancer vaccines in the past has been your bodies natural ability to prevent your immune system from attacking itself. With the discovery/invention of checkpoint inhibitors like Keytruda, we may finally have a way to allow your immune system to attack yourself by co-administering Keytruda with the vaccine against your cancer cells [1].
Another reason cancer vaccines may finally show promise is mRNA inherently has the ability to drive an immune response (see BNT162b2/Comirnaty) that elicits T-cell specific to the protein you're coding for. It is believed that cancer-epitope CD8 T-cells specifically are critical for anticancer vaccines, but even if you get good CD8 cells, the second it binds the cancer cell it gets shutdown by the checkpoint proteins on the surface of the cancer cell. If you add a CPI, boom, you don't prevent the CD8 from shutting down and you get cell killing!
If I recall correctly one hurdle for customized medications is the licensing process. Licensing and FDA approving a new medicine is costly. That's one of the reasons bacteriophages are not used nowadays, besides a few exclusions. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521264/)
Thank you for sharing that link. I always wondered why phage therapy isn't more widely developed. This feels like an example of an exponential tech improvement that our linear democratic institutions are having trouble adapting to. I wonder what the answer will be.
The important bit: "The researchers injected the mRNA mixture into colon and melanoma tumors in 20 mice. The treatment halted tumor growth, and caused a complete regression of the cancer in 17 of the animals, they reported."
most cancers induced in mice are artificially managed so its hardly telling in terms of human efficacy. And in any case toxicity profile is another hurdle to cross in Phase 1 trials.
Moderna seems to be also developing an Epstein-Barr virus (EBV) vaccine [1]. It might not only prevent from some lymphomas and other oncologal diseases, but might also help the people who suffer from the EBV subset of the chronic fatigue syndrome (CFS/ME) or similar post-viral disorder.
It is very exciting, yet it will probably take a decade until these inventions will become available in the market. Medicine is painfully slow.
According to the article, the treatment needs to be injected directly into the tumour (although this may change in the future) so the focus of these trials is melanomas. They tested on mice with both melanomas and lung tumours, and found that it reduced the size of the lung tumours even though it wasn't directly injected into them. Seriously exciting!
Today, tumor removal means cutting a big hole in the skull, digging and scraping and trying to remove all of the tumor, then closing it all up and hoping you didn't cause any serious brain damage while you did all this. I mean, we use the term 'brain surgery' to mean something overly complex, detailed, and confusing.
My father had it done in March and we were warned ahead of time that he may go blind, or may have unexpected personality changes. It was all very frightening though he came out just fine, except for a wicked scar.
But imagine if instead, doctors could drill a tiny hole just large enough for a needle, inject some mRNA into the tumor and release the patient the same day.
Proton therapy is another relatively recent development (recent as in "becoming more widely available"). Unlike photons (gamma/x-ray), protons are charged particles, so they follow a Bragg curve - releasing most of their energy in a narrow range before being fully stopped by the material. This can give very accurate control over where dose is delivered, and also leads to the somewhat paradoxical-seeming situation that the tissue "in front" of the cancer actually receives less dose than the cancer covered by it.
Wonder if Covid, in terms of deaths, ends up being seen as a significant moment in history as it moved the needle on different kinds of vaccines/treatments and they, in turn, saved more lives than Covid could claim...
This pandemic is also significant a moment in history when antivacc views gained wide social acceptance. This will hinder future vaccination efforts. I agree with you otherwise.
1. "mRNA" is still new tech in the public eyes, so it'll take some time to familiarize people with it and not see it as "scary new tech".
2. Covid is (fortunately) less deadly than initially feared, which lead to people not being very worried about it at a personal risk level. If mRNA therapy start rolling out for cancer, you bet people will take it.
The non-mRNA alternatives are also pretty experimental, still take the new approach of having your own cells manufacture the protein for your immune system to train against, and have been subjected to numerous safety pauses. I'm staunchly opposed to taking either kind of vaccine but if I had a gun to my head (and hey, given the rate things are going maybe I soon will!) I would probably pick mRNA, and specifically Pfizer since its dose is less than half of Moderna's.
Why don't we have an inactivated virus or subunit (i.e. Novavax) vaccine as an option?
I know several people who have been hospitalized immediately after getting the Pfizer shot. I know one woman, whose daughter is a nurse, who died immediately after getting the shot. This daughter told me that in the hospital she works, all doctors publicly recommend the shot, and most doctors are privately pro the shot, but by no means all.
She said that the doctors discuss this among themselves professionally, and there are legit doubts and fears.
Despite having waded through many technical articles and endless discussion threads on mRNA, autoimmune responses to mRNA, yadda yadda, I consider myself not knowledgeable enough to have a "legitimate" opinion. Even so, I would think anyone above 50 should get the shot, and anyone who is young and healthy should talk with their doctor.
But plenty of responsible people are learned enough to be anti, and even more have seen the vaccine send themselves or their neighbors to the hospital. They are not "emotional people who will parrot whatever piece of misinformation supports their worldview"
> I know several people who have been hospitalized immediately after getting the Pfizer shot.
The first or second shot? Can you elaborate on what the complication was? Did you know them directly or know of them (like via someone else telling you about them)
1. My next door neighbor, a healthy 80 year old and good friend, took the first shot as soon as he was able to. Within hours he had to be rushed to the hospital where he was in ER for five days.
He returned home and called it a fluke. A month later he got the second shot, but stayed at the medical center for watching. Good thing too, since he soon passed out and was in the hospital for a week (though not ER).
He has decided to skip the third shot. He never had Corona.
2. Four buildings away, a story with a thirty-something year old man. Someone I have met but do not know him well.
Took the first shot and was immediately hospitalized.
3. The father of a friend who lives on the other side of town. Never met the father, but am friends with his son and believe he did not make up the story.
4. The aforementioned nurse's mother - I know her family very well, and have met the mother at least once a few years ago.
Real people. I know that I am just a person on the internet and there is no way I can prove it without giving actual names (and even that might not help). But try looking for a community that has close connections with their parents (NY or Miami) and I am sure you will find plenty of similar cases.
I have extended family, my girlfriend has extended family (we would have to make 250 person wedding to invite them all, but my mother has contacts with even more people) and no one we know had any complications apart from a mild two-day fever. Some of them had covid and some were hospitalized, but no one after vaccine. Also we don't know of anyone who had any covid symptoms after vaccine.
That's just anecdotal. (My grand-parents, parents, friends took Pfizer/Moderna and there was nothing beyond the regular symptoms; and my grand-parents are in a bad shape).
There are stats about the side-effects of the vaccine, I think we better stick to those.
In Germany the PEI reported ~two cases where they consider it likely or very likely that Comirnaty caused death (out of ~100 million doses). Obviously, this is extremely rare (~10 ppb), but saying that the notion is "ridiculous" is... ridiculous. Overall these are very safe as far as we can tell, but as with everything in life, this does not mean zero risk (the obverse risk of not being vaccinated is how many orders of magnitude higher? Five. Five orders of magnitude.)
> Im Rahmen einer Obduktion wurden ein Fall eines akuten Rechtsherzversagens bei fulminanter Thrombosierung der Lungenarterie nach Comirnaty sowie drei Fälle eines akuten Linksherzversagens mit myokardialen, lymphozytären Infiltrationen im Sinne einer möglichen Myokarditis nach Comirnaty (n=1), Spikevax (n=1), Vaxzevria (n=1) als wahrscheinlich oder gesichert im Zusammenhang mit der Impfung beschrieben.
I too don't consider myself knowledgeable enough, even though I've tried to learn as much about how both covid and the vaccines work as possible. And I was wiped out for a full 36 hours (all the nasty flu symptoms except respiratory: cytokine storm!) and the worst reaction I know of first-degree was someone with the same who had to take a full week off.
But ultimately it all boils down to trading-off risks.
So many of the anti-vaccine arguments only look at absolute risk, instead of the risk compared to getting covid itself, or even just everyday risks that we shrug off. (At one point in the AZ discussion, I worked out that the risk of a blood clot was around the same as getting killed on your commute... every week).
I'm sure this is what the doctors do as well. Unless they're immunologists etc, it's quite easy as a layman (at least if you're on HN) to bring yourself up to the level of understanding of your average general practitioner, so there's probably the exact same conversations happening. I browse the published medical studies, same as they do.
Was it the vaccine or just two independent events close in time. Because when you give anything, even water to 160M people and then record adverse events afterwards you're going to get a lot of them and some will die. The question is are they happening at a higher rate than normal and could they be attributed to the vaccine (is there a pattern.)
There are some patterns. Blood clots for one. Inflammation of the heart.
But both of those are also caused by covid at several orders of magnitude higher rates. Not a good reason to avoid the vaccines. Covid is here to stay, most of us will get it. The only question is do you want to be vaccinated when it happens? Any logical person who honestly did the research should answer this with a clear yes by now. We have so much data. Yes we don't know what we don't know, but that's also true for Covid.
Yeah exactly. I think the risk/reward ratio for many people is still not skewed enough in vaccine's favor compared to COVID. If COVID had been as bad as originally feared, I don't think we'd see as much hesitancy. But if somebody told an anti-vax person "you'll be dead in 3 months if you don't take this mRNA treatment", they'll take it for sure.
Taking one person's opinion and projecting it to millions is not part of the scientific method. It is like being angry to one jew and killing 6 million (see Hitler's life).
Yes, but my post an example of possible arguments. Conspiracy theorists are not a part of scientific method too. They don't care about live-streaming and they will spread another nonsense. We should take care of underlying problem of anti-vaxxers (pro-pandemics) doing anti-health propaganda, but I don't know how.
That would be a good idea, it's hard to get a proper breakdown of the demographics involved because of the way it's reported. Why make people bury their head in stats when they can get an idea of their personal risk with a quick scan of a few ICUs?
Right. I think the concerns actually played out exactly as feared. Hospitals filled up with people sick with Covid, health care system got overwhelmed, everyone is at heightened risk due to the difficulty in getting treated for anything.
The point of getting vaccinated is not to protect yourself, as much as to protect your community. I view people who won't take the vaccine because they perceive their personal risk as low to be selfish. Additionally, anyone who won't get vaccinated because they don't want anyone else to tell them what to do is childish.
> The point of getting vaccinated is not to protect yourself, as much as to protect your community.
The point is first and foremost, and by a long way, to protect yourself. Herd immunity is a by-product of mass immunisation programmes, not the main goal.
> I view people who won't take the vaccine because they perceive their personal risk as low to be selfish
If their personal risk is low (as opposed to perceived low), which it is for the vast majority, then they're not having a selfish effect on others as they won't be taking up medical resources they shouldn't. If there's any "selfish" people - according to this strange standard you've built - it's those with high risk due to comorbidities they could've done something about, like their weight, and I wouldn't for one second paint them as some kind of moral deviants, they're people who need help in the short term and long.
> Additionally, anyone who won't get vaccinated because they don't want anyone else to tell them what to do is childish.
To make your own decisions and take your own risks is the mark of an adult because adulthood is about taking responsibility on, not abrogating it. Whether they are good decisions is a different discussion.
Honestly, if the decision to not get a vaccine because you are young and healthy only affected you then your argument would make sense. Why are there laws against drunk driving? It isn't to solely protect the driver from injuring themselves correct?
Edit: BTW I do not support mandated COVID vaccination. I just wish more people would think of the societal good instead of "muh freedoms" when making choices. Especially when certain side effects of vaccines actually happen at a higher incidence rate from getting COVID then from the vaccine (I.E. myocarditis).
Freedom is harder to find than health, and the lack of it and the fight for it has certainly cost far more lives than this pandemic could, even without a vaccine. Additionally, places with greater freedom correspond to places with greater wealth and hence, greater health. There is more societal good in freedom than a vaccine. It’s possible to stand up for the good of both without denigrating one or the other, because they’re not really relevant to each other... until mandates and vaccine passports come in.
However, I agree that many people refusing the vaccine aren’t doing it based on sound reasoning (beyond the freedom argument) or are well informed on the matter. Again, however, the government and media have the lion’s share of responsibility here, they haven’t been honest nor transparent, and they’ve politicised things that should never be political - just think “Trump”, “hydroxychloroquine”, and “the Lancet” and you’ll get an immediate insight into where the lack of trust comes from, and those no shortage of examples (this week’s is “Joe Rogan” and “ivermectin”, can we just wait for a larger scale study to come in before rubbishing this stuff?)
Eh, we’ll just see a split in the population between the vaccinated and disease riddled. The Amish similarly split in the industrial revolution and they’re, for the most part, doing fine and not ruining it for the rest of us.
Given the current research paths and traction, that future list of preventable diseases looks likely to include most STIs. That will motivate young people such that it cleaves off the current voluntarily unvaccinated generation.
Long story short, this is likely to be a temporary phenomenon. That, or a hard split for a self-selecting minority. (We’re already seeing economic effects in skilled labor hiring.)
I disagree, it's all a perception issue.
The authoritarian part of population (including the government, obviously, and mainstream media) conflate people who don't want to take vaccines for various reasons with people who believe conspiracy theories about vaccines. I talked at length with these people and it's almost comical how wrong and ignorant they are. They are also very few an apart, some were homeless, other were xanax and wine soccer moms.
The rest of people who don't want to take the vaccine recognise the goods the vaccine can do but:
- They don't care about avoiding mild covid effects if they think they're healthy enough
- They don't know which long term effects mRNA vaccines will have, if any (10+ years)
- They oppose compulsory or practically compulsory (if I can't travel or visit a bar, it's practically compulsory) vaccines for a disease with a sub 1% mortality rate, which keeps having different variants which drop vaccine efficacy, which still requires you to wear a mask not to transmit it.
As it is right now, the only reason to take the vaccine is not to feel covid symptoms / reduce the damage to your organs by covid, which is a decent reason.
I got covid towards the beginning of the "two weeks lockdown to flatten the curve turned in 1.5 years", I felt flu-like bad but barely had any issues. Yet last summer I was forced to vaccinate because proof of recovery older than 6 months is worthless to travel and to spend hundreds in useless covid tests. I also had zero symptoms after both vaccinations, probably because my body already knew how to fight it.
Sure, the government really makes it harder and harder to believe in anything they say, but the number of conspiracy nuts remained constant. It's just that society started calling people who care about individual freedom, conspiracy nuts (on top of nazi and white supremacists).
> As it is right now, the only reason to take the vaccine is not to feel covid symptoms / reduce the damage to your organs by covid, which is a decent reason.
This is obviously false antivax nonsense. The COVID vaccine, by and large, prevents you from dying or ending up in the ICU.
> It's just that society started calling people who care about individual freedom, conspiracy nuts (on top of nazi and white supremacists).
Or we're just tired of people buying into antivax propaganda and dying and wasting hospital resources?
Well then let’s bring out the big guns. HIV/AIDS patients. How do we keep those people from transmitting their disease? Should we force them to isolate and potentially even form their own cities?
Again, it's not THAT contagious. Aids doesn't spread through air or simple touch. And those with aids still can use condoms (for sex) or handlers can use gloves (when hiv patient has wounds).
The main problem with covid is the tempo it spreads. Covid symptoms are not that bad, most of victims survive, but because it spreads so fast, that ~5 percent of hard cases can overwhelm a country. THAT is the problem, but almost no one adresses it in comments on forums, instead they give comparisons to other diseases which have completely other problems.
It's very contagious if you come in contact with certain bodily fluids. ORs, and traditional rooms in hospitals are sterilized with bleach after a stay from an HIV positive patient. There's even plenty of stories of Dr's and surgeons contracting it when they've slipped with a scalpel or needle.
Further are you 100% confident people are not bleeding on shared surfaces and that other people do not come in contact with this? In SF I once saw a woman slip in a homeless person's urine, with her hitting the sidewalk and breaking skin with her arm in the urine. Wanna play guess the disease there?
> The main problem with covid is the tempo it spreads.
Great so self isolate since you're scared. In fact I see most of the problem being with the vaccinated thinking they're totally safe, and not using a mask. They still get the virus, still spread it, and yet they think they're not the problem.
> It's very contagious if you come in contact with certain bodily fluids
Yeah, IF you come in contact with certain bodily fluids. We don't do that everyday, but we do it everyday with airborne diseases when breathing. So, it's not THAT contagious. I've heard stories of doctors being infected when trying to help some junkie who started being aggressive.
> Further are you 100% confident people are not bleeding on shared surfaces and that other people do not come in contact with this?
I've seen such occurence maybe once every several years where I live. Typically it's because of some acident and it's cleaned in reasonable time.
> In SF I once saw a woman slip in a homeless person's urine
We don't shit on sidewalks, homeless here are a very rare sight, I don't remember seeing one since at least a month.
> Great so self isolate since you're scared.
I'm not scared, I'm vaccinated and still use mask. I'm currently self-isolating because I've got some mild cough and don't want to spread whatever I have, I've cancelled todays dinner with remote (other country) coworker who I would see live first time since a year, but that could mean spreading some flu to him and others in restaurant.
> In fact I see most of the problem being with the vaccinated thinking they're totally safe, and not using a mask.
I'm 100% with you about this. They should isolate more. Now, what was your argument again?
> Yeah, IF you come in contact with certain bodily fluids. We don't do that everyday
Did I not just give an example of this? Maybe not for you, but for some people it is very much possible to come into contact with these body fluids on a daily basis, if not multiple times a day.
> I've seen such occurence maybe once every several years where I live.
You can see droplets of blood? What's your vision like? Are you also aware blood can be in coughs?
> We don't shit on sidewalks, homeless here are a very rare sight, I don't remember seeing one since at least a month.
Again, just your location.
> I'm not scared
If you're not scared you wouldn't be here arguing anything about COVID atm.
> How do we keep those people from transmitting their disease?
PrEP exists. But it’s costly and tedious. When we have an HIV vaccine that’s free and two shots, yes, it would make sense to restrict those who choose to be infected.
> Using this logic, why did we isolate prior to having a vaccine?
To prevent hospitals overrun by sick people.
If more people get vaccine, I'm for ending with isolation or other pandemic safety measures. Those who didn't want to vaccinate can die if they want to. The problem AT THIS MOMENT is that there is too many unvaccinated people, so when covid spreads, hospitals will be overflowed and other people will die from other preventable diseases from lack of care.
> As it is right now, the only reason to take the vaccine is not to feel covid symptoms / reduce the damage to your organs by covid, which is a decent reason.
Well, no
It reduces severity and incidence of disease. Yes, you can still get covid if you encounter SARS-Cov-2. But you are less likely to. And if you are less likely to get the disease, you reduce the risk of infection to others.
They had wide social acceptance each time there was a new vaccine, going back to the first vaccines (which, btw had not-insignificant mortality rate). In five years when there are no long-term side-effects the antivaxxers will die down again.
> In five years when there are no long-term side-effects the antivaxxers will die down again.
You seem very certain. I'm not convinced. Some of them are simply making things up. I had one of my coaches try to show me a video of a guy sticking spoons to his body trying to tell me it was the vaccine making him magnetic.
How do you reconcile "hey, once we can show that long term side effects are non-existent" with "because there aren't enough side effects right now, they're just inventing completely crazy nonsense that defies all logic"?
The person in question isn't even a fringe conspiracy theorist, she just browsed Facebook a little too much, this is just mainstream stuff...
Most anti-vaxxers are not that crazy though. Most will be convinced by a few years of nothing bad happening. It's an easy mistake to make to focus on the most extreme people when they just aren't representative.
I would argue that a critical view of vaccinations has always been widely present. We see this now as gaining traction only because they speak up as mandatory vaccines are becoming a real possibility. (otherwise: lose job, can't travel, etc) Maybe it's time to actually have a conversation with them, instead of labelling them and regard them as idiots.
You should go try to have a conversation with those people and you will understand why we stopped. My wife had this conversation with her grandfather and just got disowned.
Maybe 50% of the people I know haven’t gotten the vaccine. They are generally reasonable, and I’ve had healthy back and forth with many of them. Many of them are highly educated.
None has disowned me.
My point is, it’s not fair to lump them into one big Idiocracy category.
>mandatory vaccines are becoming a real possibility
Becoming? Becoming!?
Vaccines for many infectious diseases are mandatory (with some exceptions) to enter for public schools in all 50 states, DC, and Puerto Rico. They are also mandatory to immigrant to the United States. The supreme court first upheld mandatory vaccinations as constitutional in 1905, more than a century ago (Jacobson v. Massachusetts).
Mandatory vaccinations have been a thing since we've had vaccinations.
What's your point? I wasn't claiming that the supreme court is infallible, or even giving any opinion about mandatory vaccinations, just pointing out the concept is not new.
But this is pretty clearly not the same thing as is currently being talked about. No one expects to have a right to travel to another country, it's well understood they can create whatever rules they want.
What the vaccine passport debate centers around is whether it is fair to require vaccines for entry into events and businesses.
The hassle / reward for most people is much higher for those many other infectious diseases than covid.
By all means, now that the government paid for it with our tax money I'll take it and skip the mild covid side effects for my age range.
If I had to pay, unless I was 40+, I wouldn't have bothered for something with such a low mortality rate.
I thought you were going to mention the ridiculous state powers raised against individuals in otherwise relatively free countries for an illness that mostly affects people with multiple comorbidities. Thats a lot more scary than a few antivaxers.
That's a great conspiracy theory! Hear me out before you downvote:
This could be the reason the WHO has been scaring everyone for the last two years for something with such a low mortality rate. Or maybe even why American tax dollars were spent on gain-of-function research in a laboratory in China!
Maybe this was all a tax payers funded friendly fundraiser to beat cancer with mRNA!
I'm sure tons of smart educated authoritarian people wouldn't refrain from manipulating entire populations for such a noble goal.
Here's a summary from Lowe on mRNA for an effective cancer vaccine
> And those issues, among others, are what has kept the cancer vaccine field from taking off, mRNA-powered or not. Pre-pandemic, Moderna was working on these, and no doubt they still are. But whereas we could go from "new pathogen" to "new vaccine" in about a year (an amazing feat, to be sure), developing any similarly effective cancer vaccine is already in the "decades and counting" category. There's a huge amount of promise in this area, but don't expect it to zip along like a viral vaccine might be able to.
Apple News has the complete article at https://apple.news/ANRRWdjsrPEW3QIouD9dSnw. (I subscribe to Apple News+ through Apple One. Not certain if it's free for everyone or just for subscribers like me.)
This article only talks about colon cancer in mice. BioNTech has multiple mRNA based cancer treatment projects and some of them, such as a melanoma treatment, are already in phase 2 trials [1] on humans. Moderna has similar candidates in the pipeline. It looks like it's time to hold our breaths this time.
As someone who has already had a severely atypical mole removed before the age of 23, and who has a family history of melanoma on both sides of my family, man do I hope their mRNA cancer treatment works well.
Though luckily, melanoma seems to be waaaay more treatable now than it was even 15 years ago, but hopefully in another 10-15 years, Stage III or IV melanoma isn’t much more serious than a basal cell carcinoma.
When my music teacher had melanoma, they tried so many things. Some of them were so new that when she was first diagnosed they didn't exist outside a research lab. The progression of cancer treatment has been amazing, but with its ultimate spectre of being a disease that could start with any cell division, any time, anywhere in your body it's so good to see more research paying off. I think most people are scared of it, since we know it's going to get us all eventually (if we don't die of something else first).
Sadly my teacher ultimately didn't survive - but without new developments she would probably have died a good five or six years earlier, and her quality of life was really only bad for the last three months or so. She lived to see her children become adults, and she was so grateful for that. But we can dream of a world where nobody in their fifties succumbs to something like this.
