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How genetically different do my human-arthropod hybrid have to be to humans to not be at risk of prion diseases when eating humans? I don't want my monsters to eat a brain for a quick snack and then 10 months later find out he has Kuru...

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  • $\begingroup$ It's difficult to tell, but assume that two creatures' proteins should be as much different from each other as possible. $\endgroup$ – Alexander Mar 22 '18 at 23:48
  • $\begingroup$ If they are arthropods, then they even have brains like humans? $\endgroup$ – Sasha Mar 23 '18 at 3:46
  • $\begingroup$ @Sasha they are part arthropod and aside from some instincts and any other important formations based on the species, they have an average human brain and spinal cord $\endgroup$ – Amoeba Mar 23 '18 at 3:51
  • $\begingroup$ Hi, as long as your creatures don't have the prion gene they will likely be fine. Prion proteins catalyze the formation of the prion fold in native prion protein: no protein, no disease. Mutants with the prion gene deleted do alright except for some minor short-term memory problems $\endgroup$ – SilverCookies Mar 26 '18 at 17:34
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Wait, wait, arthropod-like organisms with human CNS? A mammalian brain and spinal cord aren’t going to come close to functioning with arthropod physiology. For one thing, the human brain and spinal cord require a closed circulatory system for blood supply. A brain with that many condensed folds will not receive sufficient oxygen just by floating in a bath of hemolymph, plus the spinal cord needs a notochord and vertebral column for support or its delicate fibers will collapse under their own weight. The brain itself, one could conceivably shove in an arthropod cephalon of sufficient size for mere physical support, but it would still die from lack of oxygen, fail to connect with any of the radically different sensory/motor nerves of the arthropod head, crowd out the mouthparts, and otherwise fail for a dozen reasons.

Secondly, where will said mammalian CNS originate from, and how, given that arthropods are protostomes and we are deuterostomes? You do know that even in the very beginning of zygote cleavage, let alone germ line formation and invagination of the blastula, the organs and systems of the arthropod form completely backward of how the vertebrate systems do? In other words, their brains form from entirely different tissues, their ganglia and spinal cord are on their ventral (belly) side (usually lining the bottom exoskeleton) instead of on their back, their neural network and their neurons are just so incompatible with anything in the human body that one could not join them up, and...just, everything. Everything here says there is no way you can make such different phyla viably exhibit complete organs and systems of one another. We haven’t shared a common ancestor with arthropods in nearly a billion years. As non-sponge, non-cndiarian metazoans go, vertebrates and arthropods are pretty much maximally different animal taxa.

This is not fixable by genetic engineering on today’s level or even on a level I can reasonably see humans achieving- If only because of the insurmountable amount of time, personnel, and effort it would take per test. See, when we say, cause a goat to secrete spider silk in its milk, or cause a cat to fluoresce under UV light, via genetic modification, we insert a gene that codes for the expression of one protein, and that as a non-essential secreted product. Organs, systems, etc, require millions of interconnected genes expressing god knows how many proteins, many of which are not even structural proteins but signaling molecules or enzymes that have downstream effects. You don’t get to cherry-pick discrete systems from different phyla in biology and just expect it to work when grafted together. And this is ignoring the whole issue of a human-sized (or larger, keep in mind our huge encephalization quotient if you want something with a human-sized brain) arthropod being able to breathe on land (aquatic arthropods can get large), in Earth’s atmosphere and gravity, at all. I ignore this because I see no reason the organism can’t wear an environmental suit, or live in conditions humans can’t survive in but explore regularly (the ocean is likely).

If you want lab-created, insectoid Frankensteinian things that eat brains (what I assume you’re going for, given the use of humanoid organs- a naturally evolved alien species would not be assumed have anything comparable, or so ill-fitted) my advice would be to either A) Have these guys be simply very large, intelligent, genetically-modified (they would still have to be plenty Frankensteinian to get large and individually intelligent) arthropods that are completely aquatic, restricted to cold and oxygen-rich waters, and set the story in the Arctic or Antarctic. Perhaps they are responsible for mass orca die offs, with beached orcas showing up sans brain? Orcas are, after all, a marine animal with a brain almost as big as ours in proportion to its body (much bigger in total mass, of course). Add in some human conservationists or similar checking out the anomaly, and you have a nice horror story. Why they eat brains is probably no mystery- Predators in general love neural tissues for the high fat content. My cats have certainly made it clear which part of the rodent they consider the “best part” (right before they drop the oozing rest of it in my kitchen sink, apparently just to fuck with me). Although, of course, you might invent some other reason- Scientific research? Neurotransmitters for industrial use? Brains are dead useful if you know what to do with them, after all. People used to tan hides with them (still do, some places).

Don’t worry about prions in case A; there’s no way such a thing could pass between phyla (symptomatically, that is- I wouldn’t eat one of these arthropod creatures after it’s been feasting on human or mammalian predator brains for fear it could be a carrier of existing mammalian prions; it’s well known that some prions can be taken up even by plants and go on to infect susceptible herbivores!). How did they get here? Well, maybe the military tried to weaponize lobsters, and it went terribly wrong- They thought they destroyed all the enhanced nymphs/larvae/eggs, but some survived?

Or B} Have the thing look insectoid on some level, but actually be a tetrapod vertebrate that can survive on land, on Earth, in similar conditions to humans. Some sort of heavily armored reptilian creature with organic armor plating, telescoping armored-scute eyelids like an iguana, vibrissiae-ish scales that resemble antennae- Even rudimentary extra eyes that are “upgrades” of the pineal/parietal eye in tuatara lizards. Hell, extended ribs with a membrane for gliding could even give the appearance of insect wings (aka the third set of limbs that a tetrapod doesn’t have). Such a creature could come very close indeed to an insect knockoff, without necessarily sacrificing large size or land dwelling. Still no splicing in the CNS of an ape, of course, but up-regulating intelligence would be, if anything, easier. A reptile would also most likely never symptomatically contract prions that infect mammals, but again it could still carry a mammal-infectious prion to any mammalian predators that eat it, should it routinely ingest their brains.

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    $\begingroup$ Oh boy this is some next level detail, I appreciate the effort you put in but these hybrids aren't half and half or mostly insect, the main reason for the human brain is because of the fact that they are basically humans with arthropod formations, they can be exoskeleton, or sensory, etc... The majority of the physiology is human and they all have endo skeketons(aside from one but he doesn't eat people and us based on celepods so is irrelevant to my question) yes their is some complex factors but all the formations are reconsructed to work for humans. $\endgroup$ – Amoeba Mar 23 '18 at 11:49
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    $\begingroup$ Ok, so these guys are humans/apes/eutherian mammals, but with arthropod-like structures. Well, the “exoskeleton” could be one of many keratinized skin-with-cutaneous ossicles that mammals past and present have used for body armor. Weird in a primate, but not impossible to induce with genetic modification. By “sensory”, do you mean what, antenna analogues? UV/IR vision? You won’t be getting compound eyes in any form, I can tell you that right now. $\endgroup$ – DeathsDentures Mar 23 '18 at 12:00
  • $\begingroup$ Only antenna analogue I can see being possible in a mammal/amniote is whiskers, and those are a very loose analogue. But you could easily have them with very long whiskers in the eyebrow region, which would look like antennae, and would probably enhance their predatory abilities. UV and/or IR vision is easy to do. Pheromone sensing, and balance organs like halteres, are done way differently in vertebrates, but a functional vomeronasal organ and some form of righting reflex aren’t implausible. $\endgroup$ – DeathsDentures Mar 23 '18 at 12:08
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    $\begingroup$ However, if they are fully human/mammalian, I’d do what SudoSedWinifred said and try to “apply phlebotinum” to most of the serious biochemical details re. prion resistance, because yeah, that is some shit that even I wouldn’t touch without some handwave, and I have a degree in zoology. Probably not even my friends with actual biochemistry degrees would touch that, except maybe G who had a CMB-with-genetics emphasis in undergrad and got a masters in biotech. $\endgroup$ – DeathsDentures Mar 23 '18 at 12:14
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The other answers are good, but I'd like to make a shorter one by pointing out the obvious:

  • You don't get that disease if the people you eat are not infected themselves. Many other cultures around the world were and still are cannibalistic. It happens in some prisons in South America. Yet we don't see Kuru outbreaks.
  • Disease resistance through natural selection is a thing. Some people are resistant, maybe even immune to Kuru.

So as long as the hybrids have been eating themselves for a while (decades at the least, according to the wiki), they could be fine.

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    $\begingroup$ Another obvious but important point is that some prion diseases can infect someone other than the usual host species. So, Mad Cow disease might be able to make a human sick if they ate an infected cow. Prion diseases are not always or even necessarily usually single species specific. It is better to think of a prion is just another kind of germ that is extremely hard to sterilize away, than as something primarily associated with cannibalism. $\endgroup$ – ohwilleke Mar 23 '18 at 22:59
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Possibly as little as one gene

This article ( http://www.cell.com/cell/pdf/0092-8674(93)90360-3.pdf ) describes a study in which knockout mice missing a single gene (the one encoding for the protein PRNP, wiki here: https://en.wikipedia.org/wiki/PRNP ) proved resistant to the prion disease Scrapie.

Problem is, PRNP knockout mice have serious issues with long-term memory. This indicates that your hybrids would need alternative cellular machinery that perform the function of the missing protein which is not itself susceptible to the prion protein. There may or may not be such a protein. But there is probably some group of possible proteins which would functionally replace the protein and the surrounding cellular machinery. In writing this story, I would suggest that you hand-wave as much as possible. Going deep into this account would require you to either just be demonstrably wrong, or both become an expert in cell biology AND devise, at the genetic level, an actual prion-resistant neuron whose functionality is not diminished.

Also note that Scrapie doesn't even affect humans, it's a prion disease affecting sheep and goats. It's the same kind of deal, though, a transmissible spongiform encephalopathy (a kind of nervous disease) that appears to be caused by prion proteins, perfectly applicable to this highly generalized account. However, this is a good place to point out that it is unlikely you could engineer a creature with broad-spectrum prion resistance. For example, you might be able to engineer a scrapie-resistant sheep by replacing some sheep genes with human ones, as humans are scrapie resistant. Assuming the human neuron proteins could be made to work with the sheep ones, most likely what you've done is created a sheep that is susceptible to a different set of spongiform encephalopathies than other sheep. So if you don't want your hybrids getting sick, you'll want them to stick to eating things that are not carriers of prion types that could infect them. If they get their Kuru resistance from sheep genes, they'll want to avoid eating sheep.

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Let them get prion disease.

You are asking because some part of you knows it would be cool. It would be cool.

I am inspired by @ErinThursby 's fine answer here How plausible is a parasite that reverts hybrids back to a primal state of mind?

and also the Lovecraft story Shadow over Innsmouth, featuring human / monster hybrids.

You can make a prion disease have an arbitrarily long incubation time and symptoms of your choosing. Symptomatically, kuru is sort of like a miserable cross between Alzheimers and MS but fatal familial insomnia is a prion disease too, with different symptoms. There are others too. Your creatures eat each other from time to time, transmitting it. The incubation is long and onset of symptoms is slow.

The key for your story: symptoms affect only the human parts. The arthropod parts try to heal and replace what is damaged. Like the hybrid fish people in Innsmouth, the hybrids change over time, the human part degenerating and the arthropod part becoming more vital.

There can be one hybrid without this disease - like the good centaur Chiron. He should not show up immediately, but later in the story, to shed light on what is wrong with most of these hybrid creatures.

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  • $\begingroup$ That is actually a perfect idea I could use for this story as that is how a lot of them go insane, but how long would this take exactly for this slow degeneration and replacement and could it happen in the short time of 3 years $\endgroup$ – Amoeba Mar 23 '18 at 19:35
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    $\begingroup$ 3 years is totally possible. The linked source has proven incubations for prion diseases: 18 months to 50+ years. academic.oup.com/bmb/article/66/1/255/284826 $\endgroup$ – Willk Mar 23 '18 at 19:40
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Prion diseases are basically caused by proteins that cannot be digested, that can pass across cellular membrane by transcytosis and that can cause cause huge aggregations with the same form of that protein that naturally exists in cells.

Only some HLA types in humans seem to get disease symptoms with Prions like Mad cow disease; there are many tissue/HLA types so not everyone has the same suspectibility.

Single amino acid changes in the parental protein can prevent some prion diseases if they are located in the zones of the protein associated with aggregation.

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