Nearly all organic material (like bacteria and viruses) is destroyed at temperatures above 60° Celsius. Some temperature resistant pathogens can survive slightly higher temperatures than this, but even the most hardy will be destroyed at temperatures above 150° Celsius.
But for prions these temperatures are hardly sufficient. They can survive being frozen, cooked, steamed, and even chemically treated with substances like formaldehyde and alcohol. Temperatures as high as 600° Celsius will not reliably kill them, and only in the 1000° Celsius range are they destroyed. At this temperatures, most *metals* will melt.
Why are prions so hard to destroy if they are chemically identical to the organic material inside our body already?
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The only thing you need to do to a living thing to “destroy” it is to kill it. Even viruses, which are debatably alive, have mechanisms in them which, when put out of order, make the whole not work. Because you’re dealing with complex mechanisms, something like 60C is enough to knock it out of order.
Prions are organic, but they aren’t alive. You can’t “kill” it any more than you can kill a rock. The only way to render it unable to infect is to physically break its shape, which is difficult.
As per [this manual](https://www.fao.org/3/a1001e/a1001e00.pdf), they really don’t routinely survive extreme heat, since it reports only “trace amounts of infectivity” and then speculates that it’s due to the inorganic skeleton of the prion surviving the process. Which makes sense, since if the shape remains, it might be able to still cause the same effect as an untreated prion.
Also, that paper goes on the detail that if moisture is added to the process, prions can be reliably destroyed at temperatures as “low” as 130C
Any organic organism dies when it gets hot enough for the lowest temperature resistant protein that makes up that organism changes shape. In humans this is a protein in the nerve cells. So the rest of the body can be fine but the nerves dies taking the rest of the body with it. Viruses and bacteria have fewer proteins and therefore are unlikely to have proteins that can not withstand heat. Prions however is just a single protein. And it is destroyed at its own temperature no matter what the other proteins around it does.
>Nearly all organic material (like bacteria and viruses) is destroyed at temperatures above 60° Celsius.
It is not destroyed. A dead bacterium is still a bunch of organic material. Most of its components are just fine. That’s why other things can eat dead bacteria.
A bacterium is a complex system that requires many components to be in a specific configuration – or within a relatively small “acceptable window” of that configuration – to function. Further, a bacterium has constantly ongoing processes – and if those processes are disrupted, it is likely to also stop the whole system from functioning as “a bacterium” (and turn into “a pile of organic matter”).
By comparison, a prion is essentially just a single component. It isn’t interacting with anything. It has no internal processes (on this scale). It’s just sitting there.
So, a bacterium is comparable to a car; you can make the car stop working in a bunch of ways. Some of them are very low-effort. Cut some ignition wires, toss some sugar in the gas tank, overheat the engine, etc.
If a bacterium is a car, a prion is a bar of metal. Making a bar of metal stop being a bar of metal takes a *lot* of effort. You have to melt it or apply significant force.
So “killing” a bar of metal is harder than “killing” a car – even though a typical car has many “bars of metal” inside of it!
This actually sent me into a heavy deep dive, and so I’ll drag you in. We’re going to jump around a bit, but we’ll come back to prions toward the end. Chemistry happens first.
Prions are, quite simply, a protein that has misfolded. They’re typically isomers of a regular protein.
Isomers, put plainly, are differing molecules with the same chemical composition, but different structures. Chirality is a type of isometry where a molecule ends up mirrored but is otherwise chemically identical. An example of this is L-methamphetamine, which is literally methamphetamine but mirrored. It doesn’t have the same biological effect because the different geometry doesn’t let it bond to cell chemoreceptors.
If you’re having a hard time picturing this, imagine a North American wall outlet. Two parallel prongs with a centered bottom ground prong, but the prong on the right is smaller than that on the left, so you wouldn’t be able to plug in a mirrored (chiral isomer) plug.
Similarly, if you bent the prongs on a normal plug, it might be chemically identical with the same makeup as the undamaged plug, but it’s not going to fit. You’ve made a nonchiral isomer.
Pivoting back to proteins, they interact with each other and with cells by **nature** of their shape. The placement of certain atoms in a protein molecule is what allows it to bond with cells, with other molecules, and so on. That’s actually how a lot of medications work. The drug has a small area that is shaped the same as the area that a natural protein bonds with, and it can interface with those receptors.
And proteins themselves are just singular molecules. *Huge* molecules, very long and string-like, and the actual folding is caused by some areas of the molecule having a net positive or negative charge and attracting other areas of the molecule. Still following along?
“Denaturing” is what we tend to refer to as proteins “breaking down” but it’s more accurate to say that it’s the process of a protein losing its shape. Increasing temperature means that electrons can get excited and bump up to different orbitals of their atom, which means those local charges that keep areas close together move around and you lose that bond. When the molecule cools back down, it can form different shapes as different areas bleed off energy and have their electrons drop into lower orbitals, causing different local charges. The protein “misfolds” and since it can no longer interface with receptors in the same way, it’s effectively dead. Denatured. (Acids and bases can technically denature proteins, as does ethanol, but in those cases it’s not that different a process. Strong ions in the solvent have a stronger attraction to those charged areas of the molecule than the internal charge bonds, and then the protein misfolds when the solvent is removed.)
Prions are bad proteins. Misfolded for whatever reason, they can interface with cell receptors. That said, they don’t interface in the right ways. Either they interface incorrectly, or they interface with the wrong kind of cell. And by doing so, they can cause other proteins to be misfolded or mismanufactured by cells.
And that might tip you off to the problem.
The reason heat or acid or base or alcohol or bleach kills cells is that it causes the proteins to denature. That’s why it’s relatively easy to kill cells and viruses. They fall apart.
But prions? They’re already the result of denaturing. You can do it again, but it will still be a misshapen protein at the end.
A bit more specifics on prions.
Proteins, which they are made of, tend to denature at higher temperatures. They are folded in a specific way, and if you imagine temperature as other atoms bumping into the protein, the hotter it is the faster the bump meaning at some point it overcomes the folds and forces it into positions it doesn’t naturally fold into which is essential for its operation.
Cooling it down doesn’t necessarily mean it will fold the right way, it may actually misfold and be rendered inoperable and this is probably what happens most of the time. But some of the prions will refold back into their prion shape. And that will be enough to infect someone.
You can’t destroy a crappy blueprint (misfolded protein). Bacteria, yes. Viruses, yes. They just don’t register on our defenses.
Bacteria:
White Blood Cell: Nope.
Misfolded Protein:
White Blood Cell: ……
I heard there was a santization step for prion infected ones but it’s pretty long.
There’s a great episode of “this podcast will kill you” about prions. It’s the only disease that is actually 100% fatal, from what I understand.
Because covalent bonds take way more energy to break than; polar, hydrophilic, hydrogen, and ionic bonds.
For a true ELI5 answer, proteins aren’t destroyed when heated or treated chemically. They’re still there, they just aren’t in the right shape to do what they need to do for life/infectivity.
Imagine a normal protein as a ball of string or twine, thar you get from the store. It’s pretty easy to mess up by unwinding or cutting, and you’re unlikely to get it back exactly as it was. A prion is a ball of string where it’s all tangled up and knotted, and very very difficult to unwind, even cutting strands doesn’t unwind the thing.
The secondary structure of PrPc (the normal prion protein) is made up of three alpha helices and two beta sheets. When a prion attaches to a PrPc, a notable part of the conversion to PrPsc (the infectious prion) involves the decrease into alpha helix structures and the increase in beta sheet structures.
A high content of beta sheets in a protein makes it prone to aggregation. Beta sheets occur from the overlap of two or more linear polymers of amino acids, held by hydrogen bonds. Beta sheets are stacked on top of one another, and these strands can be parallel or antiparallel. This means that any beta sheet polymer may stack on another beta sheet, giving them a high predisposition to forming hydrogen bonds with the beta sheet structures of other proteins. It is likely this process that gives prions the ability to induce a change in conformation of adjacent PrPc proteins.
This high beta sheet content gives prions the predisposition to aggregate together and form giant structures called amyloid fibrils. Since beta sheets tend to attach to each other, the hydrophobic side chains of these amino acids will come into contact as they are trying to move inwards, away from the water. As such, the hydrophobic side chains of beta sheets will be the key in creating the hydrophobic core when stacked on to other beta sheets.
In amyloid fibrils, beta sheets of different prions are tightly stacked by various nonpolar covalent bonds, creating a strong hydrophobic core. These bonds contribute to the tightening of the beta sheet packing through the quaternary structure interactions between the elements of the amino acid side chains, which are caused by their proximity in the hydrophobic core of the amyloid structure. Among the many quaternary interactions identified, one is the formation of disulfide bridges, which have one of the highest dissociation energies among naturally occurring bonds, meaning it requires an incredibly high amount of energy to overcome these binding forces. Other such bonds work to increase the stability of amyloid fibrils by significantly lowering the energy state of this conformation (meaning it is incredibly stable). In other words, once prions form a giant polymer, it takes an incredibly high amount of energy to solubilize the fibrils. An amount of energy so high that its pretty much impossible for your body to break it down on its own and we haven’t evolved to produce enzymes that would break down the freaks of nature that are prions.
Hope this helps. I did a 4,000 word research paper on prions last year, so I’m pretty knowledgeable when it comes to prions, but I am in no way an expert.
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