Sigh. Ontogeny is NOT evolution. It is not the same thing as having a low MHC diversity due to a genetic bottleneck as well as lacking tens of thousands of years of evolution to a pathogen. Not the same at all. It's silly to even suggest that. Epigenetic shifts in an individual do not create new HLA genes.

Consider COVID. Novel bat coronavirus, nobody had preexisting immunity. Did everybody die? No. Because we had high HLA/MHC diversity, making it easier to target SARS-COV-2 epitopes. Native Americans lacked this diversity. It left them ill prepared for novel pathogens.

Also, you seem to believe that any disease you've never encountered before is fundamentally dangerous to an adult. That's simply not the case. Rhinovirus is intrinsically mild. It's an upper respiratory infection; it's not adapted to lower respiratory or systemic infection. It's not ebola. It's not going to become like ebola just because you've never caught it before. If a rhinovirus strain was reintroduced after 200 years after having been eradicated, we'd all get a cold, but by and large, we'd be fine.

And what would happen if Yamagata reappeared? We'd just add it back to our flu vaccines. Furthermore, the reintroduction of Yamagata wouldn't be catastrophic without that. You do not have to catch every Influenza B lineage at all, let alone every year. If you had been infected with B/Victoria and you were exposed to B/Yamagata, you'd have little sterilizing immunity against it - you'd very likely catch it. But your past exposure to B/Victoria is still greatly protective against hospitalization and death; B and T immunity against NA and the HA stem and stalk are conserved.

And this is about whether or not to catch every lineage. Well guess what, even with air filtration, that's still going to happen. Air filtration only has a meaningful impact for people at a distance, not people close together. It's about protecting the person across the room, not the person you're standing 50 centimetres away from. What it does change is how often you catch them. And if lineages or whole viruses go extinct, that's great. Worrying about some sort of reintroduction 200 years later is just inventing your own unrealistic misery when we have actual pandemic threats to worry about.

I guess I should be more obvious with the sarcasm in the future ;)

On the 5 year post. Don't want to think about how much time I've spent commenting here since then. Damn, I've been here almost 30 years. Still spending my work day in Linux.

Who's this old guy in the mirror?

Fact check / Analyze (post is in response to an article about a new program to install better air purification systems):

Sigh, need an edit button. :P (But yes, it would be nice if more people actually cared about ensuring the accuracy of what they write and would do that before spouting off scientifically ignorant statements. I rather wish browsers had a "fact check" text box would flag in red any factually questionable statements the poster is making, with a mouseover note explaining what's wrong, with references)

"âoe" - what are you pasting from? Google Search AI? ;)

Naive vaccine approaches do struggle with long-term sterilizing immunity against fast-mutating viruses like influenza, COVID, rhinoviruses, etc (but non-sterilizing immunity from vaccines is actually quite effective at preventing the worst consequences!). Which is why new techniques are being developed to cause the body to target evolutionary-conserved regions of the pathogens rather than the "immunologically easy" (immunodominant) epitopes like COVID's RBM, influenza's hemagglutinin's globular head, and such. These regions are easy for the immune system to "see" and target, but at the same time, the virus is also evolved to be able to shuffle them easily, so you need vaccines designed to train the immune system to attack the parts that the virus can't readily change without breaking things. Some include things like having the vaccine present a large number of very different RBDs at once (making it easier to develop immunity by attacking the evolutionary-conserved regions instead), glycan masking the variable regions, and so forth.

True. But we were never "meant" to be locked inside with lots of other people, continuously breathing recycled, stale air over and over and over again.

Nonsense - Upper Paleolithic excavations of early-modern human villages show that rather than being nomadic hunter-gatherers in loose tribal bands as previously believed, they instead lived densely packed high-rise apartment buildings built of sinew-bound mammoth bone trusses and clad in hides.

In fact, a recent dig in southern France unearthed what researchers believe was a "co-living" mammoth-bone complex, where millennial Cro-Magnons paid a monthly subscription of two reindeer carcasses for a micro-alcove. The site contained numerous preserved slate tablets detailing how the "open-concept communal hearth" was always occupied, the resident shaman's smoke-signal network was frustratingly slow, and the neighbors upstairs kept pacing around in uninsulated, heavy-soled mammoth-skin boots at three in the morning.

The pressures facing the human body in modern society have not changed at all, so we should change nothing in response!

Look at how many Native Americans died from their first exposure to various European diseases.

Yes, they had genetic disadvantages in dealing with European diseases, having had a low MHC diversity due to the Beringian Bottleneck (particularly HLA genes), combined with no evolutionary pressures from European diseases. Is your belief that children evolve in the process of becoming adults?

To be clear, this isn't the only problem that they had. It is also true that many diseases are more severe if first contracted as an adult instead of as a child, Europeans had contracted many of these diseases as children, while the native populations were encountering them at a broad range of ages. But there's a massive difference between "being exposed less often" and "not being exposed at all", as if you're living in a hermetic bubble. We all saw during COVID how hard it is even with extreme precautions to stop airborne virus propagation from person to person. Even if you significantly clean the air, people are still going to get infected with them as children. What you change is how frequently people get reinfected. And it's a myth that you need to keep catching the same disease every time it comes around to maintain immunity. T and B cell immunity against severe outcomes is far more durable than that.

There's also some nice side effects from reducing the rate of infection. During COVID, we literally drove one of the major influenza lineages extinct with our infection control measures. Now flu vaccine makers don't need to try to target it anymore - it simplifies the job of making effective flu vaccines. Having consistently good infection control measures (without inconveniencing people!) will likely heavily genetically bottleneck many airborne diseases, and may outright drive some extinct - which makes the work of targeting the remainder easier.

Air cleaning doesn't stop you from infecting the person you're talking to. What it does do is stop you from infecting a person across the room. And that's a good thing.

Seriously. It will raise a generation who will drop down dead if they catch a cold.

That's not how this works. Common misunderstanding.

yet we're supposed to believe that our immune system is a piece of junk which can't deal with a few viruses by itself.

It's great that you're so proud of your immune system - and you should be, it's amazing! Now, if I handed you a vial of serum from an ebola patient, would you rub it all over yourself, because "You Have An Immune System!"?

Do you understand that the way that the innate immune system attacks pathogens is by attacking / disregulating your body, and that this is harmful? You know how much everyone (rightly) hates "inflammation" and the harm it does? That's what inflammation is, it's the activity of the innate immune system.

Do you understand that viruses have evolved specifically to disregulate the body in order to avoid the immune system, that this disregulation is commonly scattershot rather than focused, and its impacts may or may not go away immediately - or in some cases, even ever - after infection? And that some viruses undergo long-term persistent states in the body?

Do you understand how associated viruses are with sequelae (do you understand what sequelae are)? As a random example, read the second paragraph of this article. And that's just the start.

Do you understand how common autoimmune disease is, and that it most commonly develops as a result to antigen exposure, such as during infection? That frequent and severe inflammation encourages autoimmune disease, and can even cause cancer (repairing inflammatory and viral damage requires cell replication, and the replications that occur as part of the immune response itself can specifically lead to lymphoma)?

No, getting sick is not harmless just because you "got better". Sorry.

TL/DR: don't live in a bubble, but do avoid needless infection. So long as you have some exposure - and it's extremely hard to prevent any exposure unless you're a hermit living in a cave, as we all saw during COVID - you're fine.

Fact check / Analyze (post is in response to an article about a new program to install better air purification systems):

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This will just weaken immune systems since people will not be exposed to viruses.

That's not how this works, and is a misunderstanding of the Hygeine Hypothesis. Viruses are not Pokémon - you don't need to catch them all. T and B cell immunity is generally long-lived - many decades, and tolerant of viral evolution in the interim (it varies from pathogen to pathogen, and for some you lose that first-line humoral immunity with time, e.g. you will get infected if exposed, but T and B cell immunity generally remains highly effective at preventing the worst outcomes). There is no need to, say, catch influenza every winter. All you're doing is increasing the risk of sequelae (there are a vast number, and they can be miserable. I had a cold virus progress to pneumonia to pleurisy early this year, spent a month feeling like I was being stabbed every time I coughed, laughed, sneezed, or drove over a bump. My father recently developed Guillain-Barré after a nasal infection and became paralyzed - was doing an 8km walk to prepare for hiking to Everest Base Camp during the day, and by the evening was in the hospital losing control of his body. Sequelae suck, man.

(That's one thing we increasingly learned during COVID. Huge numbers of people were developing COVID sequelae - the rates of bloody everything rise after infection, from heart attack to stroke to kidney disease and on and on - but largely because everyone was getting infected, not necessarily/not exclusively because of unique properties of the virus. Influenza, RSV, colds, etc all cause broad rises in a vast range of conditions post-infection, we've just neglected them. Turns out that having your body attack itself (systemic inflammation and a prothrombotic state) to fight off a virus is inherently actually as bad for you as it sounds, that viral actions taken to deregulate the body are indeed as bad as that sounds, and that some common viruses (Epstein-Barr being a classic example) can cause a staggering number of terrible sequelae)

That's not to say that you should never get infected. First off, children lack most humoral and cell-mediated immunity to common pathogens; to get it they either need vaccination and/or infection (ideally the former if available, and in the latter case, ideally after the former), for the whole range of commonly circulating pathogens. Since children tolerate most infections better than adults, it is best to get them for the first time as a child. And while T and B cell responses are long lived, they do slowly weaken with time. If you're 86 and you haven't caught a certain disease since you were 5 years old, that's probably not good. It probably would have been best if you had caught it again when you were, say, in your 40s or 50s (or better, where available, restored immunity by vaccination instead). But you don't need to catch every variant that goes around every year. All you're doing with that is feeling miserable and accumulating damage / risk of sequelae.

If you feel the need to eat an unidentified mushroom, though, boletes (pore mushrooms) are what you want to pick. Leave anything with gills alone. The family lacks the deadly amatoxins and orellanine. They only have gastrointestinal irritants and potential allergens (and, apparently, novel psychedelics!), and even then, it's only like a dozen species that have them, and nearly all, if not all, are either red and/or stain blue, with the biggest culprits doing both. There's only been one confirmed death from a bolete that I'm aware of (from the red-+pored bolete (red pores, stains blue), an elderly man, and it seems to have been linked to (at least in part) severe dehydration from the mushroom's gastrointestinal effects (dehydration, vomiting). This despite the fact that boletes are among the most popular mushrooms globally to collect.

Don't get me wrong, if you eat the wrong bolete, you're going to have a really miserable time of it. If you're really unlucky you'll need to go to the hospital (among other things, to get an IV to keep you hydrated). But it's exceedingly unlikely that one will kill you. And it's quite unlikely that anything bad at all will happen.

Still, yeah, not worth it for a fancy meal!

Random agarics (gilled mushrooms), though, that can readily kill you. There are certain *subcategories* of agarics with very distinct characteristics that are safe, but if you just go out there and pick some random white mushroom or some LBM (Little Brown Mushroom), well, roll the dice ;)

... two warning signs are red colour and bluing when cut, and this has them both.

So, "People With Disabilities Don't Exist" then?

My father was recently paralyzed by Guillain-Barré, so I'll let him know, thanks.

Oh god. If I spent enough time digging through my ancient Slashdot posts, somewhere back there there are posts of me going, "While I loved the strategy behind Falcon 9, I'm really not keen on this plan to make Starship out of huge carbon fibre tanks, that sounds like a really failure-prone solution..." I'm glad they only spent like a year on that idea before deciding it was dumb; somewhere back there there's also a bunch of posts of me cheering their switch to steel ;) . SpaceX still keep having random COPV problems (most of which they don't even make themselves). Not too encouraging for the notion of the cold gas thruster add-on to the Roadster, where the plan is to replace the back seat with COPVs, so you have a COPV right behind your head.

Electron has been getting by on CF, and honestly I'm impressed, but they've also been only working with very small launch vehicles thusfar. We'll see how neutron goes...

Risk without labour is just jumping off cliffs.

But hey, let's talk about risk. Most of these ultra-wealthy people don't know what risk is. Some of them really did come up from nothing, sure, but Musk had millions of dollars backing him in the form of his wealthy father. Trump, famously, would have made more money investing the money his father gave him in a stock ETF than going into real estate.

And further, I think it's reasonable to make a profit on some risk. I'm sure that the folks that own my favourite local coffee shop took on some risk to do it. You can't be sure a shop is going to succeed. I'm glad they have, and I wish them every success.

Of course, they've also worked VERY hard at making it a success. For those people that do take risks, it's their own LABOUR that makes these businesses work (that, and a bit of luck--opening up a month before COVID would have been bad luck, and nothing to do with risk OR labour).

But once you get in to the many hundreds of millions of dollars, I think we should be able to agree that there's never anything risky in their lives ever again. I'll keep repeating this every time I get a chance, but you can't make a billion dollars on a salary. $5000/day for 500 years is still not a billion dollars. It's a level of wealth that is impossible to accrue by any work of your own. It takes the work of other people.

As I said in another comment, if you have Jeff Bezos and no workers, Amazon is nothing. If you have all of Amazon, but no CEO, you can probably make a lot of money. The labour of the people at Amazon is what made it huge, and what made him rich. It is necessarily the case that those people produce more value than they are remunerated for--that's what a profit is. But when you have such a huge profit value, it tells you that the gap is *enormous*. Why is that okay? Why don't we think that those people that actually made the software and delivered the packages--the things that define Amazon as a company--don't deserve the value that they created?

It used to be that a CEO would only make 20x what their workers did, and they would be paid a real salary, one that could be taxed. Now they get paid hundreds or thousands of times what their workers do, just in stocks so it can't be taxed. They have an endless army of lawyers and accountants. They'll pay $80 million to avoid a $10 million tax, just to show you that they actually HAVE the money, they just refuse to give it back to the governments and people that provided the conditions to make them so fabulously wealthy. The roads, the education system, the laws, the safe borders--all these things went into the building of these hoards.

Work is how you make value. You have to plant crops and harvest them; or drill into the ground and extract and refine the petroleum; or write the software and fulfill the orders. All of that is labour. I have plenty of ideas and if I never execute on any of them, the idea is worth zero. That's why I'm banging on about wealth.

It's not impossible to tax; that's loser talk for defeatists. We made these laws, we've created these monetary fictions, we can write new laws and come up with more equitable systems. Stocks and bonds don't HAVE to exist, but given that they do, I think we can figure out a way to make sure that people don't become extremely wealthy and leave the rest of the country fighting for scraps, living paycheque to paycheque, hoping that their insurance premiums don't bankrupt them before the medical expenses do.

And hey, it doesn't have to be a wealth tax the way I define it--I think the things you suggested are de facto wealth taxes. But based on what you're saying, it sounds like you also believe in the necessity and the moral correctness of taxing them, especially when you and I are paying much higher proportions of our comparatively meagre holdings.

It's small segment of the population, the 0.1% and the 0.01%. They can be taxed. They are not special.