(1) there are only so many resources to go around. Should we be devoting them to vanishingly rare things rather than things that might actually affect you?
(2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein. One step up from that - encoding the protein for space constraints and encapsulating it - is called a virus.
> In a particularly vexing twist, prions are also nearly impervious to destruction, even when attacked using a strenuous combination of disinfectants, heat, and pressure.
Not really. The point your parent is making is that prions themselves don't reproduce like viruses and bacteria. Its basically impossible for a large scale breakout to occur and spread.
They can't reproduce outside of the body, but neither can viruses.
It’s orders of magnitude less reproduction.
From my (ignorant, despite being interested in prions for decades now) perspective, you have something that (1) can replicate, (2) is durable (3) is harmful, and only the relative rarity of prions in general (because 1 and 3 are physically unusual to combine) have kept them from being a general problem. As we tinker with DNA and thus look into creating new proteins and factors that would influence protein-folding, I'd think it's worth taking the matter seriously (though not fear-mongering), certainly as part of our need to understand proteins better anyway.
What are my faulty assumptions?
A virus can overtake a cell and mobilize its resources to create a bajillion copies of that virus. A prion can transform only as much copies of that protein as that cell has made in its normal processes.
A virus requires a cell to replicate, bacteria require a much more limited range of hospitable environments.
Both bacteria and viruses "attempt" to create exact copies, just as a prion does. Admittedly prion replication probably has more accuracy, but that prions occur at all indicates the process allows for natural selection.
These don't seem to put prions outside of the "replication" category - they replicate by encountering other proteins, so they are in a body. Their rate of replication is limited (or boosted) by the rate of encountering these proteins. They attempt to create copies of themselves with the chance of failure or different end result.
>"combining autoclaving (even at 121 degrees C) with a sodium hydroxide treatment is extremely effective." https://www.ncbi.nlm.nih.gov/pubmed/10658760
Usually there is some sodium hydroxide in standard sodium hypochlorite bleach solution as well though, perhaps that explains why they reported it is the most effective of the chlorine bleaches.
One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denature, or modify proteins do have activity against prions [7]. The PrP purified from the brains of scrapie-infected animals (PrPSc) can be inactivated by prolonged autoclaving (at 121ºC and 15 psi for 4.5 hours), or immersion in 1N NaOH (for 30 minutes, repeat three times), or immersion in concentrated (>3 M) solutions of guanidine thiocyanate [10]. However, certain cautions prevail; it appears that inadequate autoclaving can establish heat-resistant subpopulations that fail to diminish with a further cycle of autoclaving [11]. Stainless steel instruments also may retain infectivity even after treatment with 10 percent formaldehyde [12,13].
Newer decontamination techniques are being investigated. There has been some success in sterilization using a combination of sodium dodecyl sulfate (SDS), proteinase K, and pronase [14]. A radio-frequency gas-plasma treatment has been shown to effectively decontaminate surgical instruments [15]. Another group has tested a decontamination formula combining copper metal ions with hydrogen peroxide [16].
As it is, very few proteins in humans have alternate favorable form (by luck or selection?). The exception appears to be the extremely complex and relatively new nervous system of mammals. I'd guess that our immune systems might be another place to look, but that is very highly tested.
Frankly, this seems like a susceptibility that is rare because it is chemically odd not that there is a lack of potential exploitation. Luckily, the range of creatures that share our respiration system far exceeds the range of creatures which share our recently evolved nervous system.
https://www.theguardian.com/society/2018/dec/10/mysterious-p...
Chronic wasting disease (CWD) (affects deer) can be transmitted by infected saliva. One of the symptoms of symptoms of CWD is excessive saliva production. It is very transmissible, and is devastating captive populations of deer, although it is relatively rare in the wild.
I think if a similar TSE affected humans, spreadable by infected saliva, it would absolutely be a wildfire plague.
At first I assumed that 'prions' came in many flavors, like virus. However from my brief lit search, it seems like people are talking about (p)rion proteins as if they were't all (P)rion proteins (PRNP). If all mammalian 'prion' disease can be traced to a single conserved gene, I think the risk of another 'prion-like' disease cropping up is pretty low.
But then again, who knows? Prion disease still seems shrouded mystery, which I find odd given (1) how inherently interesting this topic seems, and (2) we've gotten really, really good at molecular biology.
I feel like we are missing a key piece of the puzzle when it comes to understanding prion disease. The literature seems to want people to conceptualize the disease etiology as such: an alternately folded (disease causing) variant of PRNP protein (PrPs) bumps into a normal version of PRNP (PrPc), causing a normal copy of PrPc to also misfold into PrPs. Rinse, repeat. So you can basically think of it like an enzyme that catalyzes a conformational change on versions of itself, in a feed-forward cascade. I feel like an alternative hypothesis however, could be one of an autoimmune response. The mammalian immune system, particularly the antibody system, is mind blowing. This system can recognize virtually any foreign protein -- it can even recognize specific sub-moieties and conformations of proteins (antigens). It must, do this while never mistaking an endogenous protein to be foreign; if it does, you get an autoimmune disease. My idea is basically that PrPs is just slightly different enough from PrPc to get tagged as foreign by the antibody system (which it absolutely can do, given that we can perform western blots to detect the PrPs variant), but also just similar enough for the antibody system to mistake some endogenous PRNP for the foreign version.
What if this were suddenly transmissible to humans?
https://en.wikipedia.org/wiki/Scrapie
"In the United Kingdom, the government has put in place a National Scrapie Plan, which encourages breeding from sheep that are genetically more resistant to scrapie. This is intended to eventually reduce the incidence of the disease in the UK sheep population."
Mad Cow Disease was caused by a prion[0].
[0]:https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...
> In a particularly vexing twist, prions are also nearly impervious to destruction, even when attacked using a strenuous combination of disinfectants, heat, and pressure.
I'm not sure there will ever be a prion that hasn't already existed, whereas I am sure there will be new viruses and bacteria.
A prion only makes itself. Even if it replicated imperfectly, the odds of a slightly different misfolded protein becoming another prion are vanishingly small (otherwise we'd all be dead) because there probably just are very, very few configurations possible. The vast majority of misfolded proteins just do nothing.
There are several billion humans who are each replicating millions of copies of each of the 20,000 or so proteins during their lifetimes. It seems pretty unlikely that there are many misfolds that haven't occurred. It's just that only a handful become prions. And even if they do, prions are thankfully very hard to communicate (again, we'd all be dead if they weren't).
Well now I have new nightmares... :)
But in seriousness, I don't know much, but I believe that protein-folding is a hugely complicated problem that still lies at the edge of our understanding, therefore I conclude that we can't really conclude that the options for a replicating, harmful prion are basically harmless.
I mean...we don't even really know how common prions are, right? We only have noticed a handful because they have dramatically bad symptoms. A large number of replicating but harmless prions could exist (right?).
Obviously there's no reason to panic, but considered caution and study seems a better reaction than overconfident dismissal.
Whether that replication can be incorrect and produce a different kind of prion, I don't know. If it can, evolution will do its work.
Given that each human replicates each protein many millions of times over the course of their life, and that there have been several billion humans alive, if that were possible we'd probably have experienced it by now and again all be dead.
The phrase is actually “deep seated.”
Merriam-Webster at least (the only one I've checked) says that "deep-seated" is the only correct version:
Definition of deep-seated
1 : situated far below the surface
2 : firmly established
https://www.merriam-webster.com/dictionary/deep-seated
“deep-seeded”
The word you've entered isn't in the dictionary.
https://www.merriam-webster.com/dictionary/deep-seededP.S. Inconsistency: I assumed that whiddershins was complaining about the hyphen, rather than correcting ‘seeded’, which had been changed to ‘seated’ by the time I first saw it.