Hybridogenesis, Resistance to Disease, Blood Types, Xenotransplantation . . .

[vicky_molokh]

Greetings, all!

TLDR: I'm trying to figure out some biomedical implications for some of the weirder species (and their biological interaction with other species) in a setting I'm currently GMing; requesting help.

Basic setup:
Gross biology in the setting is largely similar to that of our world. However, since DNA hasn't been discovered yet, I have the option of declaring that heredity works by mechanisms different than DNA if I need to. There's some measure of mystical/pseudoscientific stuff that may touch upon biology, but delving into it is not necessary so far.

Species group H0 is for most intents and purposes similar to humans; they have some minor variation in neurology, metabolism and eyelid anatomy, but that's about it.

Species S1 is superficially similar to H0, but has differences on a deeper level. Notably, it reproduces strictly through a variant of hybridogenesis with H0, with the latter carrying the offspring (always). S1 have minor differences in metabolism, and a slightly smarter/tougher immune system (it needs to be smarter so as not to cause clashes with the H0's mother's organism during gestation); some of their tissues have biochemical mimicry capabilities for the same reason. S1 tissues are also somewhat less prone to having problems in cases of chimerism (again, 'smarter' matters of compatibility).

Species S2 is a close relative of S1. They have lots of weirder features (including a much greater phenotypal variation amongst themselves), they can gestate their own young, but they also retain the (now strictly optional) hybridogenetic mechanism. They have usually Unusual Biochemistry by our/H0 standards, Resistant to Metabolic Hazards (including an even stronger immune system, albeit one still capable of adapting to contact with H0 tissues).

Further considerations:
I know about the existence of the placental and blood-brain barrier. I tried reading on things like transplant rejection to better understand tissue [in]compatibility, but apparently my biomedical education is insufficient for fully making sense of it. I know that immune systems can be 'trained' in childhood, and heard that 'mistrained' and 'untrained' immune systems are what can result in autoimmune disorders and allergies.

I think that some sort of internal trigger that switches the immune system into learning/adaptive mode from its usual aggressive mode is the way to go for the implementation of such 'racial' abilities, but maybe I'm wrong.
I saw the xenotransplantation section in GURPS Bio-Tech, but it doesn't seem to go into the issue too deep.

Things I wonder / have questions about:
What factors did I miss / should I be aware of when trying to come up with explanations for how this works?
Is it likely that S1 and S2 should have something resembling a Group O Rh- blood type, or would it be the opposite as some sort of highly aggressive/incompatible type?
Does it make sense that it should be possible to enable safe permanent S1->H0 or perhaps even S2->H0 transplants by triggering the 'adaptation mode' of tissues for a while? I'm assuming that taking tissues and organs from an individual with Unusual Biochemistry is a big no-no, but what about the ones who have only RtMH without the former traits?
Just how possible is it to partially or even fully replace an immune system using xenotransplantational methods (bone marrow etc.)?
What other related matters may be a source of something interesting for a campaign where biotechnology plays a role?

Thanks in advance!

[Varyon]

Is S's immune system really even a consideration during gestation? Isn't it typically the mother's immune system that's potentially problematic? In that case, you probably don't need any special mechanisms at play - this is basically just a hybrid, like a mule or similar.

If S1 isn't really a hybrid between H0 and a theoretical S0, but is doing something funky* to make a new member of its unique species within H0, then there's more of a potential for the mother's immune system to come into play. I imagine, however, that part of what happens is that the right bits of H0's genome are coopted to make the fetus "scan" (to H0's immune system) as being H0. This would make S1 body parts just as compatible (for xenotransplantation) with H0 as another H0's parts would be, although this might not (in fact, probably doesn't with the boosted immune system) necessarily apply for xenotransplantation the other way around. I'd expect S2 to be similar (with the ability to gestate in H0, it should be able to transplant into them as well), but the rejection rate for going the other way would be even higher. However, their unusual biochemistry is going to cause some serious issues here - the organs are likely going to respond incorrectly to various stimuli (like adrenaline and the like), are going to produce the wrong signals, and so forth. In fact, if they're hardy enough to stand up to a rejection response, you might end up with the recipient's immune system significantly overtaxing itself trying in vain to fight off the "invader," which at the very least will make them more susceptible to various metabolic hazards and may well turn into an autoimmune disorder.

Augmenting or replacing an immune system is probably going to need some pretty significant levels of compatibility - otherwise you'll end up giving the recipient an "auto"immune disorder (not really auto, as it's someone else's immune system that's attacking their body). In this case, to give an H0 an S1 immune system, you'll need an H0 and S1 that are so compatible the H0 could provide organs to the S1 without issue (since from the viewpoint of the immune system, this is what you've done). Unusual Biochemistry means you probably can't do anything like this with S2 - even if the transplanted bits are ignored by H0's remaining immune system, S2's immune system is going to be attacking H0.


*For one of my fantasy settings that has a bit of science fiction mixed in, one of the races - succubus - was entirely female and could reproduce with most of the other races, producing a full-blooded succubus. This was accomplished by special Harem Cells, which were covered by receptors corresponding to the sperm cells of all of the various races they were interfertile with. They behave like egg cells (shutting out other sperm once fertilized, etc), but lack nuclei. Once "fertilized," they release RNP's that protect the compatible portions of the genome, then enzymes are released to chew up the rest. The surviving (compatible) bits are arranged into a small number of chromosomes, then the Harem Cells shed most of their mass and grow flagella, competing to fertilize the actual egg. That's the sort of funky mechanism I'm talking about here.
(Succubi were an engineered species - I wouldn't expect something like this to naturally evolve, even with the interference of magic)

[Fred Brackin]

Originally Posted by vicky_molokh

Is it likely that S1 and S2 should have something resembling a Group O Rh- blood type, or would it be the opposite as some sort of highly aggressive/incompatible type?
!

I have never heard of blood type having any functional role. They're just random junk in the genome that sets off rejection is some cases.

Thus if blood type is nonfunctional in your species HO the way it is in humans the relationship of HO blood types to S1 and S2 blood types is probably random also i.e. without any functional weight nothing tips the scales one way or another.

[Flyndaran]

How can a species breed with another producing hybrids and not quickly disappear?
Perhaps when they mate with off species, they don't hybridize but "brood parasitize" via self-cloning. This also explains large variation by way of long lines of such clones diverging slightly from species norm.

Unusual Biochemistry is mainly about drugs, not histocompatibility. Even so, it's only a relatively few genes coding for tissue surface features that matter for transplantation.

Humans have exceedingly invasive fetuses that punch through far deeper into the uterine lining than other primates. It leads to many issues from morning sickness to commonality of spontaneous abortions and some uncommon unique defects, but most likely evolved to allow the mother's immune system to kick out suboptimal offspring.
These aliens not having that would make such matings a bit less problematic, I think.

[Anaraxes]

Originally Posted by Fred Brackin

I have never heard of blood type having any functional role.

There's some evidence that they're a product of evolving to resist diseases. For example, types O and B have survival advantages versus malaria. The antigen acts as a receptor that allows malaria parasites to infect the cell. Lo and behold, type O blood is more common in Africa and other malaria-prone regions.

But the differences aren't fully understood. And some of the correlations (positive and negative) aren't obviously relevant to evolution, as they affect things that tend happen late in life, like stomach cancer. Still, "not understood" isn't the same as "random junk with no significance".

[Flyndaran]

Originally Posted by Fred Brackin

I have never heard of blood type having any functional role. They're just random junk in the genome that sets off rejection is some cases.

Thus if blood type is nonfunctional in your species HO the way it is in humans the relationship of HO blood types to S1 and S2 blood types is probably random also i.e. without any functional weight nothing tips the scales one way or another.

There are correlations between blood type and certain diseases, and the ABO Rh groups aren't the only ones in humans, just the most common and likely to cause lethal clotting. Heck, just yesterday reading up on this, I discovered that there's more than one type of A and B.
Antigens aren't junk.

[Fred Brackin]

Originally Posted by Anaraxes

There's some evidence that they're a product of evolving to resist diseases. For example, types O and B have survival advantages versus malaria. The antigen acts as a receptor that allows malaria parasites to infect the cell. Lo and behold, type O blood is more common in Africa and other malaria-prone regions.

.

That's a rather odd model for causing differential reproduction. Being vulnerable to malaria wouldn't seem to be an advantage. If there was any effect you'd think it'd make vulnerable blood types less successful at reproduction and childrearing.

This actually suggests randomness to me rather than unknown causal relationships i.e. Type O blood spreads in spit of making its' carrier vulnerable to malaria rather than because of it.

[Flyndaran]

Originally Posted by vicky_molokh

...
Just how possible is it to partially or even fully replace an immune system using xenotransplantational methods (bone marrow etc.)?
What other related matters may be a source of something interesting for a campaign where biotechnology plays a role?

Thanks in advance!

The immune system isn't just blood. I believe their are just as important tissue types that matter for transplantation. Though things aren't quite as fussy/lethal now with much more effective anti-rejection drugs.
This is all very setting technologically dependent with a near infinite number of perfectly realistic possibilities other than our present form just for humans let alone aliens.
Xenotransplant technology exists in a rather short time frame all things considered. From experimental surgeries in the 1960s to not that long in the future when possible tech makes growing organs feasible isn't that long really.
Also why would surgeons in setting even try unless one species grossly outnumbers the other(s)? Does one have strong anti-donation religions? I believe Jehovah's Witnesses with their refusal of donated blood fund artificial blood research.

[vicky_molokh]

Originally Posted by Flyndaran

How can a species breed with another producing hybrids and not quickly disappear?

Well, sorta like waterfrogs and other hybridogenetic (hybridogenic?) species. (Somehow I recalled that you were around when the original species idea was discussed, but perhaps I'm misremembering.)

Originally Posted by Flyndaran

Humans have exceedingly invasive fetuses that punch through far deeper into the uterine lining than other primates. It leads to many issues from morning sickness to commonality of spontaneous abortions and some uncommon unique defects, but most likely evolved to allow the mother's immune system to kick out suboptimal offspring.
These aliens not having that would make such matings a bit less problematic, I think.

Hmm. I didn't know this is atypical and that these phenomena are interlinked. Thanks for the idea.

[Flyndaran]

Originally Posted by Fred Brackin

That's a rather odd model for causing differential reproduction. Being vulnerable to malaria wouldn't seem to be an advantage. If there was any effect you'd think it'd make vulnerable blood types less successful at reproduction and childrearing.

This actually suggests randomness to me rather than unknown causal relationships i.e. Type O blood spreads in spit of making its' carrier vulnerable to malaria rather than because of it.

Type O blood lacks the A and B antigens "greasing" the blood, so malaria can't easily grab onto it. Like how that gene for resistance to H.I.V. is really also a "broken" antigen gene.