Zompist Bboard Again

i promise this is for conworlding purposes lol

working on a conworld and i want the people to be mostly the same as humans, but with a couple physiological differences. one is handedness—there's no such thing as being left- or right-handed, you just use whichever is most convenient for the task in question—but i also wanted to have a situation where they're immune to something that is harmful or poisonous to us, and they're also harmed by something that's totally innocuous to us. still thinking about the second one, but for the first one i'm thinking i'd like them to be basically immune to heavy metal poisoning

why are heavy metals poisonous? what is the mechanism by which they interact with our bodies in harmful ways? and what would need to be different about our bodies to make heavy metals relatively harmless to us? (i wouldn't be surprised if different ones work in different ways, so if this is too broad a question then let's start with lead and mercury)

Emily wrote: ↑Mon May 24, 2021 6:45 pm i also wanted to have a situation where they're immune to something that is harmful or poisonous to us, and they're also harmed by something that's totally innocuous to us. still thinking about the second one, but for the first one i'm thinking i'd like them to be basically immune to heavy metal poisoning

why are heavy metals poisonous? what is the mechanism by which they interact with our bodies in harmful ways? and what would need to be different about our bodies to make heavy metals relatively harmless to us? (i wouldn't be surprised if different ones work in different ways, so if this is too broad a question then let's start with lead and mercury)

Organic compounds would be easier. Koalas have specialized gut microbes for digesting eucalyptus leaves, which are poisonous to most mammals; deer (and some humans!) are immune to urushiol, the toxin in poison ivy leaves that causes contact dermatitis (actually an allergic reaction!); American deer are additionally immune to yew-derived taxines and can eat the leaves of yew trees (eating two ounces of yew needles will kill a human); and there are a lot of things that are poisonous to cats but not humans, because cats are adapted for a primarily carnivorous diet and can outsource toxin processing to their prey.

Wikipedia has a decent-looking overview on the chemical causes of lead poisoning, but I think ~every animal is immune to lead. A conspecies that's relatively resistant to lead poisoning would probably need high natural or environmental production of some chelating agent, I guess? But chelating agents aren't that discriminating, so they'd probably need high essential metal intake in general. Maybe there's another way to do it?

Mercury might be easier. AIUI there's a site in certain proteins that's "supposed to" have a selenium atom but can take a mercury one instead, and if it has a mercury atom it doesn't do the thing it's supposed to do - mercury irreversibly inhibits thioredoxin reductase and some other enzymes that I can't remember. Fish generally have higher selenium requirements than humans; can they get mercury poisoning?

Emily wrote: ↑Mon May 24, 2021 6:45 pm i promise this is for conworlding purposes lol

working on a conworld and i want the people to be mostly the same as humans, but with a couple physiological differences. one is handedness—there's no such thing as being left- or right-handed, you just use whichever is most convenient for the task in question—but i also wanted to have a situation where they're immune to something that is harmful or poisonous to us, and they're also harmed by something that's totally innocuous to us. still thinking about the second one, but for the first one i'm thinking i'd like them to be basically immune to heavy metal poisoning

why are heavy metals poisonous? what is the mechanism by which they interact with our bodies in harmful ways? and what would need to be different about our bodies to make heavy metals relatively harmless to us? (i wouldn't be surprised if different ones work in different ways, so if this is too broad a question then let's start with lead and mercury)

I’m taking medicinal chemistry at the moment, so this is a conworlding question I can answer. (Finally!) Unfortunately we haven’t covered metal poisoning specifically, so I’m just going on what I can read online here.

So, just looking at lead poisoning for now, it looks like there’s quite a few different ways in which lead can mess things up. For one thing, lead ions are pretty similar to calcium ions, but bind more strongly to the same areas. Thus lead can pass through the blood-brain barrier via Ca channels, where it affects numerous neurotransmitters. Additionally lead can be stored in the bones, where it replaces calcium; once stored, it only slowly diffuses out, meaning that lead is present for a long time after initial exposure. Lead also affects the blood by interfering with haem synthesis, causing affected haemoglobin molecules to bind zinc rather than iron; long enough exposure can cause anaemia. It also has various renal and cardiovascular effects which I don’t really understand. Lead poisoning treatment is through chelation therapy, involving administration of a specific molecule which binds to lead making it unreactive.

Thus, in order to prevent lead poisoning, you will either have to (a) change biology, such that every single Ca channel no longer admits lead, every protein which previously could bind to lead now cannot, etc.; or (b) change quantum mechanics such that lead somehow differs in its properties from calcium. Moreover, you must do either in such a way that their behaviour changes only for lead while maintaining exactly the same behaviour otherwise, because otherwise humans will simply stop working (see Universal Fire for a detailed explanation). The alternative is somehow producing some sort of chelating agent naturally, and I don’t see how that would evolve in the absence of natural lead. Or you can simply increase calcium intake, which to some extent provides some limited protection against lead poisoning.

(The same of course applies to mercury — you have to figure out how to stop mercury binding to things which selenium normally binds to.)

I agree with Nort that organic molecules would be easier, if only because they’re more commonly present in the environment and so you have a chance to evolve resistance naturally. Small molecules are probably more difficult than larger ones: I wouldn’t like to design an animal resistant to methanol poisoning, since I’m sure methanol gets into about as many places as lead does (and then gets metabolised to formaldehyde for good measure), but larger molecules can be fairly picky about where they bind to. And the very largest molecules (like RNA) get handled by the immune system, which is very complicated and specifically designed to keep some molecules out and some molecules in, so as far as I’m aware, it’s totally fine to say that such-and-such an animal doesn’t have an immune reaction to such-and-such a molecule.

hmm. well if it's unlikely, it's unlikely

i'm not really sold on having the differences be based on organic compounds, because wouldn't these be different on a planet with different plant and animal species? unless i'm completely misunderstanding

Emily wrote: ↑Mon Jun 28, 2021 4:35 pm hmm. well if it's unlikely, it's unlikely

i'm not really sold on having the differences be based on organic compounds, because wouldn't these be different on a planet with different plant and animal species? unless i'm completely misunderstanding

Organic compounds are compounds with carbon-hydrogen bonds. Unless you're doing alternate biochemistries (silicon instead of carbon, ammonia instead of water, etc.), your planet will have organic compounds. What those organic compounds do will be different, though.

bradrn wrote: ↑Mon May 24, 2021 9:08 pm Small molecules are probably more difficult than larger ones: I wouldn’t like to design an animal resistant to methanol poisoning, since I’m sure methanol gets into about as many places as lead does (and then gets metabolised to formaldehyde for good measure), but larger molecules can be fairly picky about where they bind to.

Would methanol be that hard? If your con-biochem handles formaldehyde differently, it probably doesn't evolve alcohol dehydrogenase in the first place. Which would have other implications.

Nortaneous wrote: ↑Mon Jun 28, 2021 6:58 pm

bradrn wrote: ↑Mon May 24, 2021 9:08 pm Small molecules are probably more difficult than larger ones: I wouldn’t like to design an animal resistant to methanol poisoning, since I’m sure methanol gets into about as many places as lead does (and then gets metabolised to formaldehyde for good measure), but larger molecules can be fairly picky about where they bind to.

Would methanol be that hard? If your con-biochem handles formaldehyde differently, it probably doesn't evolve alcohol dehydrogenase in the first place. Which would have other implications.

Oh, I dunno, I’m not particularly good with med-chem. (And now that my exams are finished, I’m getting worse by the day!) But that’s basically my point: to handle one thing differently — especially if it’s a small molecule — would need a redesign of the whole system. To prevent methanol from working properly, you’ll need to remove alcohol dehydrogenases. To make formaldehyde non-toxic, you’ll need to redesign cytochrome c oxidase. And to prevent intoxication, you’ll need to change GABA_A. And doing any of those will probably require huge differences in nearly every other biochemical process. (I really like Eliezer Yudkowsky’s essay on this topic; I already linked it once in this thread.) Of course, there’s nothing to stop you handwaving the problems away, but I’m assuming maximum realism and rigour here.