Prions are a crazy, crazy phenomenon. From wikipedia:
> A protein as a standalone infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both)
In my layman's understanding, they're like this bizarre edge case in the way proteins interact. Of all the myriad way a protien can fold, it happens to find one that induces the same malformation when it interacts with another protein. To me, it almost seems like as much of a mathematical/geometrical problem as a biological one. In any case, very interesting from the perspective of emergent behavior in complex systems.
Right--as I understand it, it's not that different than Google's "Meeting Room Hardware Virus":
"I imagine it started with all of the adapters which were thrown around in every meeting room. Everyone with a Macbook of some flavor needed a DVI to VGA adaptor in order to use the projectors, so they were plentiful. Somehow, someone probably damaged one of them and smooshed a couple of pins into places where they should not have gone.
"Then, someone else forced this into their Mac. Perhaps two pins tried to go into just the one socket. At any rate, it would now break the socket and get it all out of whack. That socket, used with another adapter in another room, would then break that adapter. This new broken adapter would then go on to break even more Macbook DVI connectors.
Also reminiscent of the Zip drive "click of death" problem, in which bad media could damage drives in such a way that the drives could damage media that would further damage other drives:
It sounds very plausible explanation of prion infection. I'm a layman and don't know how far the correspondence go---but if the correspondence holds, is there an agent that complements prions? That is, if prions are damaged receptacle, is there another protein for the damaged plug that propagates damage to other normal proteins?
Similar things happen with PCMCIA cards. The connector design on PCMCIA cards is just awful in that male pins are in the receptacle/PC. If you accidentally clog one of the holes on the PCMCIA cards connector and plug it into a receptacle it will bend the pin over.
Male pins on the card would fail just the same way, plus they'd also get more damage from being exposed. The only upside would be easier repair and, in most cases, cheaper replacement.
The correct fix would be pins with a better length/width ratio.
I was thinking that Prions remind me of biological Ice-nine and sure enough there's a mention of it in the wikipedia article for Ice-nine:
Ice-nine has been used as a model to explain the infective mechanism of mis-folded proteins called prions which are thought to catalyze the mis-folding of the corresponding normal protein leading to a variety of spongiform encephalopathies such as kuru, scrapie and Creutzfeldt–Jakob disease.
Prions remind me of the apocalyptic theory about strangelets and strange matter :
"One speculation that has resulted from the idea is that a strangelet coming into contact with a lump of ordinary matter could convert the ordinary matter to strange matter."
>"Of all the myriad way a protien can fold, it happens to find one that induces the same malformation when it interacts with another protein."
It doesn't really "just happen", amyloids consist of peptides folded into beta-sheets and aggregates of these seem to be the most thermodynamically stable structures it is possible for polypeptide chains (regardless of sequence) to form:
"From a wide range of in vitro experiments on peptides and proteins we now know that the formation of amyloid structures is not a rare phenomenon associated with a small number of diseases but rather that it reflects a well-defined structural form of the protein that is an alternative to the native state — a form that may in principle be adopted by many, if not all, polypeptide sequences
[...]
These observations, therefore, have led to the remarkable conclusion that, at the concentrations present in living systems, the native states may not always represent the absolute free energy minima of the corresponding polypeptide chains — the native form of a protein could in some cases simply be a metastable monomeric (or functionally oligomeric) state that is separated from its polymeric amyloid form by high kinetic barriers"
http://www.ncbi.nlm.nih.gov/pubmed/24854788
Edit:
I realized some people might not be aware of the connection to prions. Here it is from the same wikipedia page as cited by the parent:
"All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets."
https://en.wikipedia.org/wiki/Prion
"Many of the characteristics of proteins that enable the avoidance of aggregation, and amyloid formation in particular, are encoded by their amino acid sequences116. The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules117, 118, 119. Hence, it has been realized that globular proteins fold into structures that sequester aggregation-prone regions in their interior; in addition, typical features of the folding process, such as very high cooperativity, generate considerable kinetic barriers to the conversion of folded proteins into aggregation-prone species50, 120. Furthermore, specific patterns of residues, such as alternating hydrophobic–hydrophilic stretches50, 121, that tend to favour the amyloid state are commonly selected against during evolution119, 121, 122 or are otherwise neutralized by the insertion of highly aggregation-resistant residues, which are known as 'gatekeepers' (Refs 50,123).
Other protective mechanisms against amyloid formation are associated with properties of the cellular environment, including the location of proteins within specific compartments124, 125, and the presence of a multitude of molecular chaperones and degradation processes, such as the ubiquitin–proteasome126, 127, 128 and the autophagy129, 130, 131 systems, which function to prevent the formation and accumulation of misfolded and aggregated polypeptide chains11, 132. Indeed, the major genetic risk factor for late-onset Alzheimer's disease is the presence of an apolipoprotein E variant that reduces the ability of cells to degrade the amyloid-β peptide133."
On topic: I'm not a biologist so here's my layman's TLDR, please tell me if this is close.
1) You can tell whether a protien has this viral property by looking at its amino acid sequence
2) Looking at this seqence has shown several reasons why proteins don't often go viral
- The relevant region ends up on the interior of the structure
- The relevant structure is not mechanically likely
- Evolution has come up with tons of biological tricks to prevent it
Off-topic: That is some of the grossest academese I've seen in a while, and it makes this passage near unreadable. I'm saving this sentence as an example for students of what not to do:
> The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules
I'd have a hard time coming up with a sentence that feels more inside-out than that.
>"2) Looking at this seqence has shown several reasons why proteins don't often go viral"
Yes, but to clarify a bit: It looks like all proteins have this ability, but not all are just as likely to get into that state for the reasons mentioned. IE, it should be possible to find some way to make amyloids/prions out of any protein in the lab. It just requires figuring out the necessary conditions for that protein.
>"The elucidation of this code has enabled the identification of factors that determine the intrinsic aggregation propensity of these molecules"
Translation: Being able to get the amino acid sequence of proteins and predict what type of structures such a sequence leads to has allowed researchers to also predict which are likely to form aggregates.
What's also wild to me is that, conversely, RNA can have enzyme-like behavior [1], including catalyzing their own synthesis [2]. Both types of molecules are amazingly versatile.
There's also a hypothesis, to which I am partial, that RNA was the original self-replicating molecule[1], from which all life evolved, and that DNA was a later development.
DNA gets transcripted into RNA before it codes proteins, so an original RNA moelcule, being both a catalyst and a data store, eventually developed variations that in turn also produced pure catalysts (proteins) and a pure data store (DNA). But it's still the lynchpin of the reproduction process.
Not really. The 3D structure of DNA is also important for its function. The difference is that RNA is more reactive (chemically speaking), else they are pretty much equivalent.
Yes but RNA is much more destructible, whereas DNA is more resilient. RNAses(enzymes that degrade RNA) are everywhere whereas DNA is double stranded and the conditions required for its degradation are harsher. DNA may have 'evolved' as an aberrant form of RNA and because of its durability, it has an increased lifetime. This renders it more apt to serve as an archive that is copied multiple times. An organism relying only on RNA for information storage would have to deal with the shorter lifetime of RNA and that it is more damage prone. That organism would have to spend more energy just propagating its blueprint faithfully and so its population would not grow as fast. Still DNA is not so durable that its sequence is not malleable, like proteins. If I were designing the most robust organism, I would prefer to encode information in amino acids. I would then design a polymerase that would read the protein and copy it. The problem is that proteins are so robust that they are not easily unfolded to be read.
Perhaps a tenuous analogy can be made to information storage in transistors versus magnetic media. Transistors can serve as storage medium as well as logic gates. Yet power fluctuations can corrupt their function. Magnetic storage however can be read many times and is more durable with respect to environmental insults. Of course the most durable form of storage might be laser etching defects in a diamond disc but at the cost of a slow energy intensive process.
How accurate is it to say that life is essentially the result of a biological computing process? That we are quite literally built out of tiny biological machines?
Depends how you define it. A biological system is not deterministic (at least on the scale we typically observe) so from that point no. Else you can see a cell or an organism as one computer but then you can also define the universe one big computer.
I would rather say life is the result of an optimization process.
but the amazing coincidence is that DNA strongly resembles a binary code. There are only two kinds of base pairs- AT and CG - In itself this is a striking similarity to the way we use transistors to define a 0 or a 1.The pairwise complementarity serves as an error correcting algorithm. I am rather surprised though that no one has constructed a biological model of the cyclical redundancy check so common in computer hardware. Error correction in DNA is haphazard in the sense that when DNA polymerase detects a mismatch of a base pair, it really doe not 'know' which one to correct. Errors have a 50% chance of being corrected the 'wrong' way. Still that's better than no correction because broken DNA always fails. A CRC check at every 1000 base pairs would virtually eliminate genetic mutation and all the diseases associated with DNA degradation (cancer, aging, etc)
But that wouldn't necessarily be ideal long term, because there would be near zero adaptability on account of advantageous mutations. Unless the organism could adapt is behavior, it would be really vulnerable to environmental disruption.
In theory, analogous RNA based disease should also be possible, where misshaped RNA molecule interacts with another misshaped RNA molecule and causes the same type of chain reaction as the protein in this case.
You can break it down further into two separate surprises:
1) The normal form (PrPc) is mostly helical, while the diseased form (PrPsc) is mostly beta-sheet.
2) PrPsc catalyses the switch from helix to sheet.
I find the first to be more surprising. After all, chaperones (https://en.wikipedia.org/wiki/Chaperone_(protein)) exist to catalyse folding of proteins - although that is from partly folded to fully folded.
The most terrifying thing about prions is that since they're not reliant on the usual processes for reproduction, they're not susceptible to our usual weapons for dealing with disease (e.g. cooking, antibiotics/antiseptics, vaccines).
"Incineration is possible, but it isn't as easy as burning the carcass in a fire. Temperatures of more than 1,100 degrees Fahrenheit — sometimes up to 1,800 degrees — are required to effectively neutralize prions. Unlike most bacteria, regular cooking won't help at all.
"Disposal issues are tough," says Barbara Powers, director of Colorado State University's Veterinary Diagnostic Laboratory."
No. You have to denature the protein to reduce the infectivity.
You need about 20 minutes, a pressurized autoclave, and some nasty chemicals to do this effectively. There is research into other methods but I really don't know anything about them.
Proteins aren't destroyed by cooking. Otherwise you would not be able to get any proteins from cooked meat or beans.
The only reliable method that I'm aware of to denature proteins without making the whole thing inedible is hydrolysis. Gelatin is made from collagen in the skin, bones, and connective tissues of various animals, but Jell-O is generally considered safe.
> Proteins aren't destroyed by cooking. Otherwise you would not be able to get any proteins from cooked meat or beans.
"Protein" in food really means "amino acids" as far as nutrition is concerned; even if the protein isn't denatured by cooking (and at least some proteins are), it will be broken down to amino acids by your digestive system before being absorbed into your body. Your body uses the amino acids to build its own proteins.
IIRC quite a few animal-source protein strings that are "fully compatible" with our own ('animal') bodies are taken up as-is without breakdown into AA and resynthesis into "human protein". Much more efficient.
"Proteins ingested in the diet are digested into amino acids or small peptides that can be absorbed by the intestine and transported in the blood."
If by "animal-source protein strings" you mean "small peptides", then yes. But in general they still have to be resynthesized into the proteins used by the body. There might be a few useful proteins that are small enough to fall into the "small peptide" range and would therefore be absorbed and used as-is.
Prions have a little over 200 amino acids, so they are on the large side to be considered "small peptides" (which AFAIK are typically a few to a couple of dozen amino acids). They appear to be resistant to the enzymes that normally digest proteins, and it doesn't appear to be clearly understood how they get from the digestive tract into the bloodstream. See, for example, here:
"Denaturing" means to make the protein take on a different shape, which is all that is necessary (since a prion is the correct amino acids arranged in a pathological arrangement). You can denature proteins with heat or very high or low pH, depending on which protein that it is.
But the dangerous part of a prion is the way it's folded, right? All you have to do is denature it to render it harmless. It's just harder to do for some proteins than others.
plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with Chronic wasting disease (CWD) were buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment
It makes sense that we find this on occasion (once you accept that there exists some combination of folding that produces this). Once one protein folds in a way that can induce the same modification, it will replicate rather quickly.
Are there proteins that cause looping multiple-step reactions as well? Maybe that's what this is and I need to read more :p.
Well, I don't know of any protein folding examples, but it seems a lot like an "autocatalytic cycle" which is an interesting part of origin-of-life theories.
Stuart Kauffman wrote some things about this, but here is a counterpoint from Leslie E Orgel:
Makes logical sense that it would be a part of life (once you can synthesize a few things from a given one thing you can build all sorts of logical structures...), but I see there are tons of biological probabilities at play that I don't understand.
How did school manage to make biology so boring? They did it with math too, so I shouldn't be surprised, but damn.
Would love resources on an intro to bio for the CS folk. I'm sure there are some good ones out there.
The most recent Radiolab was about an idea that the existence of cellular organelles are the product of an extremely unlikely merging of two cells that didn't immediately die afterwards.
Stemming from the observation that we had an extremely long period of simple life, coupled with a sudden explosion where life rapidly increased in size and complexity.
A 0.0...01% likelihood event will still happen, given an entire planet of simple cells and hundreds of millions of years.
The most terrifying thing about prions is that they are infectious but not alive: they can't be "killed" in the normal sense by sterilization. The proteins must literally be dissolved to neutralize them.
When I was a teen I was so freaked out by this fact during the mad cow episode in England that I never ate beef since. I would not for a few years even eat anything prepared in close proximity to where beef was being prepared.
I lived in the Caribbean at the time...
The risk with beef was always pretty low. Actually not eating beef and eating an alternative meat is probably riskier given the prevelance of salmonella and other nasty bacteria in chicken.
If you are specifically (and erroneously) terrified of catching a prion disease, chicken is still better. You're much more likely to get sick but much less likely to catch a prion disease.
Which has to be the leading contender for our civilization's equivalent to "those Roman Empire folks were so dumb for using lead, ha ha". Though it is highly doubtful that lead poisoning caused the downfall of the Roman Empire, one to two order of magnitude elevated levels of exposures compared to normal background levels were no picnic the bodies of for those exposed.
Another example of distributed costs, concentrated benefits really screwing us over in the long-run.
I thought that the spooky thing about prion-based diseases like CJD is that symptoms can take a long time to appear after exposure. (Although, on reflection, I can't justify this, and quick googling does not turn anything up.) The onset of death after first symptoms is relatively quick (a few months to a year).
The point being, that we may not be able to measure risk at this time, because the prions may be latent in people. (Cue spooky music.)
I lived in Germany in the 80's when my dad was stationed there as part of the military. I am barred from giving blood in the United States, as are many military men and women who served during that time, because of this [1]. This is especially sad because many active and former military personnel, and their families, take blood donation very seriously.
I was raised to do it, but I am now barred due to the note on the eligibility sheets. I talked to a Red Cross area administrator about it and he said that, even though it has been over 20 years, they are unlikely to lift the ban until effective testing and treatments are found. Since there are no tests, they can't risk the blood supply.
Back when the UK banned butchers from selling beef on the bone, my mother was still buying it "under the counter". Her argument was always- if it's here then we've already got it.
And it makes them incredibly hard to fight. We basically have two ways of dealing with them:
• Use vaccination to train the host's immune system deal with it, should it ever encounter the full version.
• Use special drugs to slow down their replication to let the host's immune system deal with the rest.
Prions have no special, prion-only replication strategy we can target, and I'm not sure whether the immune system can be trained to attack only prions and not their regular protein equivalents.
I think you underestimate the immune system. We automatically remoce thousands of misfolded proteins every second in our cells. Its just those few the cellular defence has not yet adapted to too much that we notice. Some kinds of vaccination might work (like expressing part of the misfolded protein to make it an antigen) etc. The reason why we do not have any medication against prions is because they have never been a big thread to us. Pretty much like asteroids, if they fell on us regulary, we would build a planetary defense. But for now, that not up on the agenda
>and I'm not sure whether the immune system can be trained to attack only prions and not their regular protein equivalents.
A prion tends to be vastly different than the original protein. I thought the bigger problem was that prions are the metaphorical tanks of the protein world. Just look at what it takes to denature a prion compared to other proteins.
Of the 6 or 7 criteria biologists usually use to define life, viruses often fall short. E.g. viruses do not have their own metabolism.
Everyone has their own definition though. I remember reading a novel where life was defined simply as heredity, mutation, and adaptation. The second definition makes more sense to me, and implicitly includes viruses.
Spores formed by bacteria like C. botulinum or B. anthracis are also very difficult to neutralize. The key is knowing if there is an exposure risk and taking added precautions.
The good news is that some people are "immune" to developing an infectious prion disease. Turns out that certain mutations prevent normal proteins from interacting with a complementary prion in a way that would cause them to become misfolded.
So for people with Alzheimer's disease, is that plaque always associated with prions/protein mis-folding? (and if so, is it worthless to do things like "Learn a second language," "Learn to play more instruments," etc because our brain usage doesn't really play into the development of Alzheimer's? It's mostly a genetic thing?
It's an unsatisfying answer, but Alzheimer's (and most disease for that matter) is a combination of genetic risk and what you do with your life. It is hard to know exactly how much genes or the environment contribute. There are subsets of neurodegenerative diseases that are almost entirely genetic (Huntington's, some forms of Parkinson's, etc.) and some that are almost 100% environmental (there's an interesting story about a group of IV drug users in San Francisco who developed Parkinson's after taking something laced with MPTP). Most cases are somewhere in the middle though.
Learning other languages or instruments is probably useful from a brain health standpoint regardless of your genetics (even if you already have early-stage AD you can slow progression), but they are just proxies for activity. I would guess that learning something that interests you is more important than what that thing actually is.
I guess it's more complicated than that. Brain usage affects its chemistry - how much of what is available where - which, in turn, may have an effect on how misfolded proteins interact with normal ones.
Keep in mind I'm no expert, but this seems to be a reasonable assumption.
Yes, it can not be "killed" but, as other dangerous/infectious particles (like viruses), it can be destroyed. The immune system is able to naturally develop defenses against both live and inert foreign bodies, but only if the given body is over a certain size. The small objects (relative to cell size) do not trigger antibody creation and that is why this abnormally folded protein is so dangerous. There are, however, methods in which the organism is trained to recognize and develop natural defenses against bodies as small as a molecule, say, to prevent relapse in drug addicts:
This method may be a little bit costly (relative to promised returns of solving a problem that does not directly affect humans) and with limited effect, but still, it may be a way worth investigating.
Viruses have two main components. The first is the delivery package. This is the element that is capable of delivering a payload into the interior of a cell. The second is the genetic code that hijacks a cell's normal functioning to produce more viruses. Viruses have a genetic component, either RNA or DNA, which contain instructions for building their viral envelopes. The genetic material is as vulnerable to damage as cellular DNA.
Prions are a single component. They are proteins with the same amino acid sequence as a protein normally produced by an organism. Except they have been misfolded. The geometry of the misfolded protein is such that it becomes a catalyst to reproduce the same misfolding error. There are no "brains" in them. They can arise entirely accidentally. They're a bit like the ice-nine from Vonnegut's _Cat's Cradle_, in which a crystal of a novel form of solid water that melts at a higher temperature can recruit liquid water to grow the crystal without limit. Each individual prion can misfold any number of same-sequenced amino acid chains.
And like the ice-nine, which melted at a temperature above human body temperature, the prion may be able to survive through more extreme conditions than other forms of the protein.
In the best case scenario, the prion does little more than cause a deficiency of the normally-folded protein forms in the body. In the worst-case scenario, it poisons some other process within the body in its misfolded form.
Pet peeve of mine, but it looks like you slept through English class as well. The plural of "virus" in English is "viruses". "virus" in latin is a mass word and has no plural, like "sugar" and "air".
Your perscriptivism here seems misguided then, because if virus is a mass word we shouldn't be saying viruses either: just "virus". And anyway, if we absolutely had to express a plurality of virus, it would be "vira".
Anyway, this is hackernews.
For those of us who grew up in internet hacking communities of the early 90's "virii" was the plural form in the lingua franca. As a descriptivist of great habit, I will continue to use that form.
I am actually a descriptivist myself, but the prescriptive approach usually works best when trying to convince people how to write. Apparently not so in this case.
How about this argument then: "virii" is f*ckin ugly? No? Darn. :-)
Just because a noun is a mass word in one language, it doesn't mean it has to be in other languages that have borrowed the word.
For example, in my language, "lego" is a mass word, and to make a plural you would have to say something like "pieces of lego", but in English, the plural of "lego" is "legos".
My understanding is that the fact that viruses are not alive is more of a convention, similar to Pluto not being a planet. This is more of a question than a statement, I would love it if somebody with some knowledge on the matter could chime in.
life, species, organism.... all are leaky abstractions.
[There's a "species" that spread around the Andes and eventually reached itself on the other side---and could no longer breeed with "itself". Genes could still in theory travel all the way around and back to the discontinuous point, however.]
Having thought about this a lot, the best definition of life I've been able to come up with is as follows:
An object is considered to be alive if it consumes energy to create or maintain its own order (in opposition to the general effect of the second law of thermodynamics in the wider system in which it finds itself).
Bacteria can do things on their own (say, swim in water). Viruses can't do anything without a host's reproduction engine (like a program which can't do anything without a computer to run on). Prions are misshapen proteins which tend to damage other proteins such that the result is the same misshapen, and thus duplicating, form.
I think what was meant is that on the grand scale of "aliveness" viruses are more alive than prions. Viruses have DNA, they actively seek out host cells to hijack so they can reproduce, etc. Prions are much simpler and aren't alive at all. They're just accidentally self-reproducing patterns, basically. They don't have DNA, they don't make any specific effort to reproduce, they just "happen" from weirdly broken matter bumping together.
"You Can't Kill What's Not Alive: Prions cannot be destroyed by boiling, alcohol, acid, standard autoclaving methods, or radiation. In fact, infected brains that have been sitting in formaldehyde for decades can still transmit spongiform disease. Cooking your burger until it is well done will not destroy the prions!"
http://learn.genetics.utah.edu/content/molecules/prions/
So there's no cure, no vaccine, and you can't kill them. Terrifying. An outbreak of this thing would have free pass to eradicate entire species, including us.
Oh, and the incubation time can be extremely long. A burger you ate 5 years ago could've been infected but it could still be years before you begin showing signs. I remember reading a bit about some connection between prions and dementia in elderly individuals but I don't remember any of the details.
One sci-fi horror series had an episode where the plot was that some mass produced chickens were getting ill because the feed was made from other chickens and they eventually discovered that it involved a prion that was dangerous to humans as well. This was discovered after massive numbers of those chickens had been consumed in large quantities by society.
No. It is just that we do not have a cure or vaccine because it does not appear that often. And no, prions will not eradicate entire species because they not living under any definition. Therefore there is no direct evolution, if you are resistant against an outbreak, your are resistant against it. The prion cannot develop to overcome this resistance. Essentially, a prion disease is very like the computer virusses we have today: They do not change their source code, so fixing the issue in your code will disable them.
>>Although the disease is not known to be transmissible to humans
This is not quite correct, the disease is believed to be transmittable to humans, but we're not in the practice of eating deer brains, so there are no confirmed cases. All of the states with CWD have advisories on reducing the risk with consumption. Eg: http://www.dgif.virginia.gov/wildlife/diseases/cwd/deer-carc...
Given that we don't really know how CWD is transmitted among animals it is still pretty worrying.
Prions are both beautiful and terrifying. One of my favorite science fiction stories is Kim Stanley Robinson's "Aurora". He makes great use of the prion concept, and its consequences for human life, in relation to space exploration. Fascinating read if you're interested in the topic.
CWD was just found this past deer season in my county, in the Arkansas Ozarks.
They did a harvest of deer in a small area near where CWD had been found (in an Elk, actually) and found a staggering number of the deer were infect, I think it was 36%.
There's virtually no way to get rid of it, apparently.
The method of CWD transmission is unknown, however there is strong evidence to suggest that abnormally-shaped proteins called "prions" are responsible. The agent responsible for this disease may spread directly through animal to animal contact or indirectly through soil or other surface to animal contact. It is thought that the most common mode of transmission from an infected animal is via saliva and feces. A recent study confirms that CWD prions can be shed into the enviroment in feces from animals showing no clinical signs of the disease and can contaminate the soil, leading to infection in other animals. CWD can be spread from region to region by the movement of captive deer or through the improper disposal of a harvested deer transported from a CWD infected area.
Prions are fucking scary. They survive all regular decontamination procedures - alcohol, boiling, even autoclave. Patients had been infected through the sterilized scalpels and endoscopes.
Could a prion have been the precursor to life? Seems simpler for a protien to accidentally come into existence and start replicating than a string of rna?
Possibly, but the modern age has considerably more vectors for exposure to these misfolded proteins, and the last statement of what logfromblammo said[0], these misfolding proteins don't always affect core processes of the body.
To be fair, this doesn't have to have originated via animal-to-animal infection, but could be an example of sporadic CWD.
As far as I know, sporadic CWD is relatively uncommon, but given CWD is caused by the PrP protein, and there are a number of known mutations in PrP which can increase its likelihood of undergoing prion-conversion, I'd hope they're going to sequence this animal's PrP gene to see it it shed's some light on the etiology.
Irrespective, this could still mean that CWD is now endemic in Europe.
>>>
Updated for clarity and extra info/context (thanks pbhjpbhj!)
>>>
CWD: Chronic Wasting Disease (deer-based prion disease - main topic of article)
PrP: The specific prion protein involved here. Note that (confusingly!) prions are both a 'class' of proteins but also refers to a specific protein (PrP).
Prions (class) are proteins which can exist in one of two states. In their soluble form they're happy-go-lucky proteins that are monomeric (i.e. exist as a single unit). However, these soluble-form prions can undergo a conformational change (re-arrange their shape) into a different conformation (the infectious form). The infectious form of the prion can do two specific things: 1) Aggregate (so all the previous soluble prion proteins get stuck into a big wad of protein) 2): Catalyze the conversion of soluble-form prion into the infectious form. Herein lies their infectivity - you get an exponential growth in the number of proteins in the infectious state.
Prions (PrP) is a specific protein found in many higher-order multicellular organisms that is the SPECIFIC protein that causes a range of prion diseases (Creutzfeldt-Jakob Disease (CJD), BSE [mad cow], CWD, Scrapie etc). There are species barriers to these diseases, even though the proteins are pretty similar (i.e. humans cannot catch CWD from deer, even though the PrP protein misfolds in CWD and the same human version misfolds in CJD). These species barriers are convenient (!!) but very poorly understood, which is somewhat concerning.
Finally - it's worth point out prions aren't always bad. Fungi use them as a mechanism to facilitate non-genetic heritability/diversity [1], and we're increasingly finding examples of prion-like mechanisms that facilitate fast and irreversible signalling in cells (e.g. in the inflammation response [2])
[1] True, H. L. & Lindquist, S. L. A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407, 477–483 (2000).
[2] Cai, X. et al. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell 156, 1207–1222 (2014).
Too bad DNA doesn't stick around more than a few million years [1]. It'd be interesting to research the possibility of prions wiping out the dinosaurs from Mad Herbivore Disease.
Off topic, kinda: is anyone else having problems with nature.com not resolving? Firefox and Safari both fail to load it, but for some reason Chrome manages to find the server. OSX, latest.
A prion that infected people rapidly, through saliva-to-blood contact, and had similar symptoms to rabies without the rapid death would be very similar to traditional zombie lore.
The protein would probably also have to effect the olfactory glands, creating an attraction to uninfected humans.
It's hard to tell if you've been sincerely misled or if this is just a joke. Either way, though, it's not really plausible. The closest thing to a "zombie" that we get in nature are ants that are infected by Ophiocordyceps unilateralis. This fungus causes the infected ants to crawl to a fungus-friendly location on a leaf and remain there until the fungus kills it and produces more spores.
In the I Am Legend novella (a big contributor to modern zombie), the infected are more like vampires and retain their intelligence. The book is notable for the primary theme it introduces, the otherness of the zombies (in earlier depictions they are largely undead plot devices)
Romero's Night of the Living Dead also plays with the otherness theme, but the dead are numb and more ghoulish than vampiric.
28 Days Later finally has something I would agree is rabies inspired. It probably contributed to the frantic behavior of zombies in several recent movies.
"The roots of the vampire myth stretch back nearly as far. Tales of vampire-like creatures, formerly dead humans who return to suck the blood of the living, date to at least the Greeks, before rumors of their profusion in Eastern Europe drifted westward to capture the popular imagination during the 1700s.
In its original imagining, though, the premodern vampire differed from today's in one crucial respect: His condition wasn't contagious. Vampires were the dead, returned to life; they could kill and did so with abandon. But their nocturnal depredations seldom served to create more of themselves.
All that changed in mid-19th century England—at the very moment when contagion was first becoming understood and when public alarm about rabies was at its historical apex. Despite the fact that Britons were far more likely to die from murder (let alone cholera) than from rabies, tales of fatal cases filled the newspapers during the 1830s. This, too, was when the lurid sexual dimension of rabies infection came to the fore, as medical reports began to stress the hypersexual behavior of some end-stage rabies patients. Dubious veterinary thinkers spread a theory that dogs could acquire rabies spontaneously as a result of forced celibacy.
Thus did rabies embody the two dark themes—fatal disease and carnal abandon—that underlay the burgeoning tradition of English horror tales. Britain's first popular vampire story was published in 1819 by John Polidori, formerly Lord Byron's personal physician. The sensation it caused was due largely to the fact that its vampire, a self-involved, aristocratic Lothario, distinctly resembled the author's erstwhile employer."
> A protein as a standalone infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both)
In my layman's understanding, they're like this bizarre edge case in the way proteins interact. Of all the myriad way a protien can fold, it happens to find one that induces the same malformation when it interacts with another protein. To me, it almost seems like as much of a mathematical/geometrical problem as a biological one. In any case, very interesting from the perspective of emergent behavior in complex systems.