I'm curious, if it's a "misfolding protein" (my knowledge of biology is not sufficient to know what "misfolding" means here, I understand that proteins fold, but "misfolding" is a mystery to me), then what is the reproducing mechanism?
My understanding is that viruses reproduce themselves by hijacking the DNA (or RNA?) in cells. DNA being a cell reproduction mechanism that copies protein structures. But what is it about a particular protein that can make itself reproduce and infect the body?
Proteins are produced as a string (either literally as a chain molecule, or in the computer science sense of a string of characters/amino acids).
Once a protein is formed in the body, it naturally folds into its useful, functional shape with the purpose it was designed for.
A 'misfolding protein' is then a folding into a stable shape which is not desired.
A 'prion' is a misfolding protein that encourages other proteins of the same type to misfold in the same way - maybe by acting as an incorrect template for folding. When this is folded in a way that is difficult for the body to break down, and somehow enabling its sibling proteins to do the same, you start to have problems.
So, a prion is a protein structure able to reproduce itself, in some way. Prions are not 'viruses', where viruses have their own DNA (or RNA) for making their own proteins.
There's an argument about whether viruses are 'alive', since they depend on others' cells to make their proteins. Prions are even less considered 'alive' - they are just inert single protein molecules folded in a particular way. But, they have the ability to reproduce, in some sense.
In terms of folding, you can imagine a protein as balls on a string, where each ball has some extra stuff on its surface. One may have a bit of velcro hooks here and a small magnet there (N outwards). Another one may have some surface adhesive and a S-outwards magnet. Another one, velcro loops and a blob of adhesive. Etc. You put such a string of balls in a box and shake it for a while. After you're done, you'll have a somewhat stable structure made of various balls connected by their relevant attachment mechanisms. If you were clever at designing the original string of balls, you could make it highly probable that any such string would reach the same connected structure after being tumbled a bit.
Proteins are like that. The connections are chemical bonds; velcro, magnets and glue represent different structures on protein pieces that allow some kids of bonds to form with given strengths, and disallow others. The tumbling/shaking part is matter and temperature - in a living organism, everything mostly keeps bumping into everything else at random, and in particular, there's plenty of water molecules to push things around randomly. Pieces of protein thus keep connecting and disconnecting with other pieces, until the whole molecule reaches a stable state where the constant bumping isn't enough to break any of the bonds. That's how proteins fold.
Somehow, it turns out that any given protein tends to almost always fold into a very specific shape (which is currently impossible for us to compute a-priori, given just an ordered list of amino acid residues). But there are other possible shapes that a protein can sometimes reach, which are also stable but do not let it perform the functions the body needs it to. That's bad - such a protein is at best useless, at worst disruptive, and stability makes it hard for the body to get rid of it. Then there sometimes are stable shapes whose presence cause other similar proteins to fold to that same shape, instead of the one they'd ordinarily do - that's prions. That's very bad news. They reproduce through catalyzing creation of more of them, and their stability means they can just linger around after the host organism has died, and it's not easy to destroy them through boiling or denaturing agents.
I’m not clear on the mechanism by which the prion encourages other proteins to fold the same way. Is the protein interacting with the other protein directly like an Ice IX situation? Is it an interaction between the body and the prion, like the prion causing the body to create an enzyme which interacts which then folds the next protein? Something else?
From what I've read, it seems accepted that the mechanism is closer to Ice-nine - a bad protein shows up next to a good one, and causes the latter to re-fold into a copy of the bad one. The exact mechanism of this is not known.
Many things. In CS, gossip-protocol based DB systems. In chemistry and physics, phase transitions. Many processes like nucleation/crystallization during freezing are very similar.
When simulated, the code generally resembles cellular automata. Look up Ising model simulation if you want a better understanding.
Yes! In this case the contagion is the alternate metastable state of the protein that is passed from one to the other on contact. After which, the previously healthy protein quits its job, leaves its family and starts hunting for fresh victims.
"There's an argument about whether viruses are 'alive', since they depend on others' cells to make their proteins. Prions are even less considered 'alive' ..."
I have read several proposals for a "viral LUCA" in the past ... does anyone ever suggest a prion LUCA[1] ?
Yes, it totally makes sense to talk about a common ancestor!
There's one known prion-disease-causing protein in humans, the "major prion protein".
You can see the gene containing the code for this protein in human DNA, and any mammal DNA has a similar gene that is still very closely related. This suggests that the protein has some important function(s) in mammals, and has a common ancestor before these species existed.
Genes that have a shared history but are less closely related (and don't appear to cause disease) can be found for example also in zebrafish ('Shadoo' gene) and in humans ('Doppel' gene).
Could you develop a bit the last part please? How does it go from "you have accumulating useless proteins in your body" to "you die"?
Is it because too many "good" proteins are turned into "bad" proteins and thus you don't have enough anymore to function properly? Is it because the "bad" proteins somehow "clog" the system? Something else?
Either of these theories [not enough good protein/too much bad protein] could contribute to disease, yes.
The correct function of the disease-causing 'major prion protein' in humans is not known, so I think the answer is "we don't quite know which of these factors is more important".
We observe that diseased brains have 'plaques' where they have been turned into sponge, so-called "spongiform encephalopathy". The brain's neurons have simply died, one way or another.
I'm sure the latter is possible in some way but the common prion-based diseases kill by misfolding functional proteins in the body (or in this case the brain). As the misfolding spreads, the cells in the immediate vicinity are destroyed and ultimately the surrounding tissue.
You can google it if you want, but the end result is a brain that is essentially turned into a sponge with voids throughout.
I've always understood that viruses are not alive but does the statement "since they cannot reproduce without depending on others' cells..." Not also cover plants that require insects for pollination?
OP's argument is a little bit unorthodox. Generally maintaining homeostasis is seen as a threshold for life and that's why viruses are often excluded, they cannot really maintain internal state.
There's no clearly agreed definition of 'life', and in my opinion, scientists are moving gradually towards an idea that viruses should count as life. Hank Green recently posted that he finds it obvious that viruses are alive.
The argument that viruses are not life has become a bit circular - viruses are not life, therefore, we have to come up with awkward definitions of life that exclude viruses.
You've posited a different definition, which I'd suggest is very close to mine - 'maintaining homeostasis' is meant to express the idea that a cell is able to produce its own proteins in order to control its own environment to its own benefit.
[When a virus changes that environment to suit its own needs, we don't want viruses to be considered life, so we don't call that 'homeostasis' any more - at least, we don't when we're talking about the context of what 'life' is. There are plenty of academic papers that do call this homeostasis, considering homeostasis as an interplay between cells and its viral infections.]
a reasonable definition for alive is that they carry their own energy production mechanism to reproduce. They can intake materials, produce energy, and reproduce.
If we created robots that could harvest their own raw materials to produce energy and reproduce, then they would be alive too.
It’s not just a misfolded protein, it’s a misfolded protein that catalyzes other proteins (with the same chemical structure) to misfold. So proximity of a “good” protein to a “bad” protein is sufficient to turn the “good” protein “bad”.
It’s an interesting hypothesis to consider that there could be other prion variations out there that misfold other types of proteins, but they don’t misfold the “good” versions of themselves, so they don’t self-replicate and instead just create one-off instances of a broken protein.
Huh, that's very interesting. I certainly didn't know that protein folding could be influenced by other proteins around them; I guess I sort of thought that proteins and their structure were fully defined by DNA. But it makes sense.. if a particular folding has an unstable point (ie., could go one way or another), it would naturally be influenced by the forces around it in addition to its "code". Thanks for the insight!
My (admittedly, very layman) understanding is that prions are proteins that are misfolded in such a way that when in proximity or contact with their 'correctly folded' version can induce them to change shape to the misfolded version. Prions are below the level of things like viruses or bacteria -- they are a result of the underlying chemistry of making proteins. Proteins and their folding is arranging atoms into energetically favorable states. A prion is then a different arrangement of the atoms that is somewhat more energetically favorable, one that can induce other proteins to transition to this different state. It is this last property that makes them infectious.
Any chance we've got time for the meta question.. Does anyone have a clue why prion diseases are so popular on HN at the moment? AFAIK it's not something that often turns up in mainstream media? Not even as something they keep in the 'slow news day' draw..
Are we genuinely scared by the idea of getting a prion disease? Is there an actual risk of a prion epidemic? ..or putting my Freud hat on, does everyone on HN share a weird masochistic fetish about 'the next big pandemic'?
For my part I don't really get it, but then maybe it's because I'm british and for us prion diseases have been boring (or rather the news isn't interested in prion diseases) since mad cow disease stopped being a thing 20 years ago.
I'm not so sure it is that popular on HN. I don't remember seeing any articles all that often before recently with the outbreak in Canada. I'll see the topic pop up far more often on Reddit, but it's still fairly rare. I think people are interested because it is such a terrifying thing that we don't have any good solutions for. So it inspires discussions whenever somebody reminds everybody else "so, hey, this is still a thing" and it makes its rounds.
Someone posted an article recently. Morbidly fascinated people dig out more and post that, too. It all performs moderately well so karma hunters start doing it for the points. Eventually, the audience is saturated with prion content and the fad dies down.
the 'at the moment' probably explains it - a lot of online fora have, for want of a better word, fads where there is a lot of discussion of a particular topic for a brief while, then it fades and sooner or later a new topic comes along. I quite like the phenomenon personally.
Prions have been posted a lot about before Corona. If I had to hazard a guess, it's because they're even more of a curio than viruses, bacteria or fungi.
> But it wasn't a virus — or a bacterium, fungus, or parasite. It was an entirely new infectious agent, one that had no genetic material, could survive being boiled, and wasn't even alive.
Well because it's "just" a protein which by itself isn't alive. It's like how heavy water(water where the hydrogen atom is replaced by a deuterium atom) will eventually kill you if ingested in large quantities, because your body just doesn't recognize it as any different from normal water - it takes the molecules and builds stuff with it, but because it's not quite the same, things start breaking down eventually.
This is roughly the same - body takes this protein in, "thinks" it's a different type of protein, the resulting cell is "broken" diseases follow.
You'd literally need to break that protein down so that it's completely destroyed, either with extremely high temperatures(not boiling) or with acids. People think of it like bacteria and then are surprised it can't be "killed" - well it can't be killed because it's just a basic building block, it just happens to be defective.
My expectation is that most proteins would be broken down into their amino acids before being absorbed. Maybe it's just the law of large numbers that lets some through? It seems like a pretty spectacular feat to be cooked, digested, and enter the brain intact.
Sounds very like Creutzfeldt-Jakob Disease[0] which can result from the bovine equivalent[1]. There was a major outbreak of ‘mad cow disease’ in the UK and elsewhere and was related to cows being fed feedstuff made from offal.
Thank you. That is actually well-covered in the article.
The article states this:
"The epidemic likely started when one person in a Fore village developed sporadic Creutzfeldt-Jakob Disease, a degenerative neurological disorder similar to kuru."
And this:
"People have developed variant CJD after eating the meat of cattle infected with mad cow disease. Dr. Ermias Belay, a prion disease researcher with the Centers for Disease Control and Prevention, says that's the only scenario in which there is "definitive evidence" that humans can develop a prion disease after eating the infected meat of another species."
Whatever they were, Lysenko had nothing to do with it.
His argument with Vavilov was a purely scientific one - Lysenko campaigned for epigentic heredity, while Vavilov was a reductionist geneticist who was against epigentics on principle. (Modern science vidicated Lysenko, by the way.)
Their argument was very dirty - "administrative resource" was mobilised and political sides were picked, but there is no way Lysenko had enough clout to be anywhere near setting government policy.
This is not really hard to explain. In both the USSR and in China you had massive famines in the countryside during the initial periods of rapid industrialization. Why? Well, put yourself in the shoes of the party officials:
1. They wanted to rapidly convert the society from one that was based on subsistence farming with very few factories (read, steel production) to a modern industrial society in which a small group of farmers produced large amounts of surplus food that can support a growing urban population of factory workers (and thus produce lots of steel. Never underestimate the fetish for steel production in early communist economic planning).
But how to reach that point when most people were peasant farmers growing just enough for themselves and there was no surplus for all the planned factories?
2. All communist (and indeed, left-wing) movements in Europe originated among urban intellectuals that viewed the poor serfs/farmers as dangerous political enemies (although sometimes there was a romanticism involved). This was because actual farmers tended to be very conservative, devoutly religious, and not really interested in building utopian societies. The hotbed of "class consciousness" was always the factory (in the city) and sometimes the mine, but never the poor rural farm. This divide between the higher income urban left and the lower income conservative/religious rural areas continues to the present, and from the slaughter of the farmers in the Vendee during the French revolution to the slaughter of farmers by Mao, it's usually the rural population that gets hammered in the wake of a successful left-wing revolution.
So there is an obvious opportunity to kill two birds with one stone: confiscate food from the farmers, take it to the cities to feed the new urban workforce, and in the process you eliminate a lot of people who were never really part of the revolutionary team.
Now in both China and Russia, this was not advertised as a program to kill farmers. It was advertised as bold new agricultural reform program that would unlock massive productivity gains via collectivization, and wouldn't loyal workers in the countryside want to send some of their extra food to the city? The party will be sending someone by to collect.
And this is the good-enough first order explanation of why we had all these famines, rather than specific scientific theories about agriculture.
You see to be asserting that the scientific theories (which led to executions, don't forget) were never instituted, but there's a lot of evidence that digging deeper was used in China before their famine, and planting seeds closer together, resulting in stunted crops, also played a part.
Where are on earth did I say that "scientific theories were never instituted"? I have no idea how could be parsing my comment, so I can't point out where your parser went off the rails.
And the original true story that Moby Dick was based on. Quite gruesome. Lesson learned, don't wait until your ship mates have no body fat to eat them, or the protein won't be absorbed.
It comes up a lot, especially in areas that lack a natural protein source (eg Papua New Guinea or parts of Africa). People aren't really short of calories but they lack other nutrients so...
Eating your own kind should definitely expose you to pathogens, infections and parasites that are directly compatible with you.
I think in nature it would tend to be a bad strategy due to this, even though in cases it would make a lot of sense otherwise.
IIRC the SF novel 'The Legacy of Heorot' had an alien life cycle/population dynamic based on this idea of using cannibalism coupled with a staged life-cycle to allow the creature to exploit a wider ecological niche. The juveniles were herbivores and the adult forms then ate the juveniles, forming a joined niche.
"A 'prion' is a misfolding protein that encourages other proteins of the same type to misfold in the same way - maybe by acting as an incorrect template for folding."
So, if you introduce a human prion - here by eating a human and perhaps brain in particular - it will potentially start this process by acting as a first template.
(Other animal prions are typically less likely to start this process, since animal proteins will likely be too different)
Maybe a lot of humans have prions, and the ones who survive until birth are just lucky enough to be genetically immune to their own. Cannibalism copies the protein to someone without that immunity.
And maybe the proteins of different species are usually too incompatible to be dangerous.
I once heard a story of how a report by historian turned into cannibalism report after bad translation. Apparently he quoted the phrase "they eat each other alive for food", while the true story was that farmers kill each other fighting for land and water.
Weirdly the name of this tribe happens to be an exact match for the name of an android library that I publish - needless to say it didn't come up when I googled potential names :)
Revulsion is a "seriously, this is a bad idea" signal from evolution.
Do a quick inventory and see just how many psychological barriers there are to cannibalism. Considering how important calories have been for most of history and what a 'traditional' diet looks ... it must be really be a mistake to eat people.
That's a postdoc rationalization based on your western perspectives
There are more than a few cultures which disprove your general angle, on South East Asia there are still a couple cannibal groups, which base their cannibalism on eating perceived witches and did it on a semiritualistic fashion to ensure that the witches spirits could not come back and haunt them/put a spell on them
There are many, many, many references of through the discovery of SEA islets of colonizers finding Cannibal tribes and groups whom would instead eat them to (is through) acquiring "their power" which is a strong motif that's replicated on West and Central African animistic groups and tribes
Do remember reading of more than a couple times several years ago of reading East European cannibal tribes through the 700s, and this was beyond the post Roman vilification of "barbarians"
Anyhow my core is that, this is quite, quite common throughout human history, same with human sacrifice
Apologies for lack of references I am on my phone, I'll add them later
wow, one wonders what the spike protein made by the covid-19 vaccines could do...the narrative appears presenting just a protein for the immune system to tackle instead of the whole virus is without risk.
>presenting just a protein for the immune system to tackle instead of the whole virus is without risk.
The level of S protein produced from a vaccine is substantially less than someone infected with SARS-CoV-2. Covid-19 is not a prion disease, the protein doesn't cause any kind of catalytic misfolding of other proteins. No one said new vaccines are without risk, that's why even a one-in-a-million reaction causing blood clots was enough to halt the administration of the J&J vaccine until it could be studied further. These vaccines have been studied for over a year on a massive chunk of the world population, any kind of adverse reaction that hasn't already been caught would have to be so rare that no matter what demographic we're talking about you're at substantially greater risk of harm from Covid-19 than from any as of yet unknown side effect of any of the mainstream vaccines.
> [I]t was just a twisted protein, capable of performing the microscopic equivalent of a Jedi mind trick, compelling normal proteins on the surface of nerve cells in the brain to contort just like them. The so-called "prions," or "proteinaceous infectious particles," would eventually misfold enough proteins to kill pockets of nerve cells in the brain […]
Disclaimer: Somebody stop me if I'm spreading misinformation, because I am way out of my wheelhouse. Honestly, I would like to be disabused of this suspicion if it's entirely fanciful. So, if someone knows something about what I'm about to discuss, please weigh in. The subject is genetically modified organisms.
My understanding is that at least some (if not all) GMO's are produced by bombarding an organism's genetic material with radiation and then separating out modified organisms that seem to be useful. This process, however, does result in misfolded proteins. Often, scientists judge that these misfolded proteins are of no harm, and so some GMO's (if not all) make it to market with misfolded proteins. That's my understanding.
I'm wondering two things. First, is my above account (over-simplified in any case) basically right or way off base? Second, if it's basically right, aren't we playing a very dangerous game with things we don't understand well enough?
GMO's are not produced by targeted radiation in the way you have described, at least not as common practice (i.e. the GMO food you buy isn't created this way). GMO crops are generated in two ways: targeted gene modification (with deliberate modifications being made in contrast to the randomness of the radiation method you described) and crossbreeding (which has a more randomized effect but does not involve radiation).
You're right, it is done. I worded my comment carefully to leave room for this because it's hard to prove a negative, but I stand by my statement, specificay in refuting the implication from the original comment: we aren't haphazardly blasting plant genome with radiation, at scalr, and guessing it's safe enough to feed to the world. I don't have numbers but GMO crops today are by and large the result of non-radiation genetic engineering.
Radiation methods for mutating species are 'traditional' methods that have been employed for decades and aren't considered GMO. A lot of the standard crops have been developed this way.
> My understanding is that at least some (if not all) GMO's are produced by bombarding an organism's genetic material with radiation and then separating out modified organisms that seem to be useful.
GMOs usually refer to a more targeted approach to gene introduction. In the US, a food can be labeled organic and GMO-free even if it was developed with chemical or radiation mutation breeding.
My understanding is that viruses reproduce themselves by hijacking the DNA (or RNA?) in cells. DNA being a cell reproduction mechanism that copies protein structures. But what is it about a particular protein that can make itself reproduce and infect the body?