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So, having rejected mind uploading in their quest for immortality, the people of my worldbuilding project now seek to develop brain transplanting. The main problem is immunorejection; if you simply chucked a brain into an donated body, then said body’s immune system will attack it and the brain will die, if Robert J. White’s attempts are anything to go by, within ten days.

So, then I considered having the body be instead cloned from the stem cells of the original, (with some genetic modifications to prevent it growing it’s own brain). Since the brain and the body will therefore be genetically identical, will this prevent the body’s immune system rejecting it?

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    $\begingroup$ I think the bigger problem is that the brain, as a physical organ, is subject to the same effects of aging as the rest of the body. If you can overcome that, why not simply use the same technique on the rest of your parts? $\endgroup$
    – Michael Hall
    Jan 20 at 16:47
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    $\begingroup$ @stix The problem with the OP's approach is that neurons have a finite lifespan. While it's not known just how long a neuron can live for, more neurons are generated only in the hippocampus and olfactory bulb in humans, so one would also need to devise a therapy to make more neurons in other parts of the brain to replace ones that are lost either to aging or brain damage. $\endgroup$
    – user73910
    Jan 20 at 17:56
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    $\begingroup$ "with some genetic modifications to prevent it growing it’s own brain" why? probably easier just to nip out the small bud of cells in the developing foetus that are going to be the brain. $\endgroup$
    – Pelinore
    Jan 20 at 18:08
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    $\begingroup$ @MichaelHall Heinlein addressed this (To Sail Beyond the Sunset)--the clone is kept unconscious, the mind never develops. $\endgroup$
    – Loren Pechtel
    Jan 21 at 1:14
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    $\begingroup$ @MichaelHall If you can transplant the brain you can probably provide direct neural stimulation for exercise. We can already do that to a limited degree externally. $\endgroup$
    – Loren Pechtel
    Jan 21 at 3:12

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No, not if the body was cloned.

The white blood cells/lymphocytes in the body would find the proteins in the brain to be histocompatible.

The lymphocytes work by detecting proteins, and proteins are made by the DNA. "Clone" means "identical DNA" which means "identical/compatible proteins".

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"Would a brain transplant suffer immunorejection if the new body was cloned from the original?"

No, thrice no, definitely no and indubitably no.

"The main problem is immunorejection"

Nope, there's not even the smidgen of a hint of a faint suggestion of a problem of that if you're using a cloned body.

..

And as it happens theres not as much of a problem with a brain transplant into any old random non-cloned body as you might think as practically all of the immune system avoids going in there .. it's a no go zone for much if not most of our bodies defense systems against foreign objects which is why so many viruses hide in nerve tissues to avoid our bodies defenses .. so if there's anything you can transplant and expect a relatively minimal immune reaction from the body then that's it.

Sure the immune system can attack the brain .. encephalitis is a thing .. but not all of it can effect the brain which will reduce the types of immune suppressant treatments you might need and also allow some elements of the immune system to safely remain active to protect you from infection.

..

But that aside allow me to suggest a small additional procedure, inject a very small number of pig stem cells into the sole of one foot of the developing embryo of your people, done correctly at the right stage of development it will have no effect on the developing baby except allowing it to accept any and all transplants from a clone of that pig with no immune reaction at any later point in life .. it essentially tricks the developing immune system as it calibrates itself into recognising the pig DNA as its own .. keep your original body healthy longer with any repairs or spare parts it might need.

Which unless you have a way to fast track your clones or you start one for everyone as soon as they're born and everyone always has a spare adult clone on hand is something you may need to keep you going while you wait for your clone to grow enough for your brain to fit in its cranium.

Incidentally, a useful little trick to use if you want to be someone else in your next body that, you can use it to 'inoculate' a new clone of anyone you like against rejecting your tissues, man, woman, even reasonably compatible animals (that provide your brain's nutrient requirements in their blood, who's bodies operate at an appropriate temperature, etc), you can be them all if you want.

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    $\begingroup$ Not all white blood cells can pass the blood brain barrier, but the T Cells responsible for identifying foreign cells can; so, a foreign brain can still be rejected. $\endgroup$
    – Nosajimiki
    Jan 20 at 17:15
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    $\begingroup$ ”Practically all of the immune system avoids going in there?” What are microglial cells if not immune cells in the central nervous system?? The only workaround I can see here is if the microglia are from the original brain owner. But if that’s the case, they’d attack the host. $\endgroup$
    – Theresa Kay
    Jan 20 at 17:25
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    $\begingroup$ Also, no. The endothelium cells of the blood-brain barrier that lines the capillaries in the brain would also be detected by the host immune system. $\endgroup$
    – Corey
    Jan 23 at 6:31
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Rejection may be a problem

The issue lies in this statement:

with some genetic modifications to prevent it growing it’s own brain

We don't understand everything there is to know about how the immune system works, but we do know that mammal immune systems starts off in early life more or less dormant as it uses the mother's immune system to keep it safe as it "learns" to defend your body from infections based on the anti-bodies the mother gives it. This means that it is possible that you are not born with an immune system that understands what your body looks like, but instead figures out what normal looks like during this early "safe mode" stage of development.

So, if you were to clone a body that never had a brain in it, then it is possible that the brain, once introduced, would be identified as a foreign object.

But more importantly, your clone body NEEDS a brain. Holoprosencephaly(HPE) is a developmental defect in which the brain fails to fully form. While a fetus can survive until birth from mild forms of HPE where only the frontal parts of the brain fail to develop, in more severe cases where lower brain function fails to develop properly, the fetus dies in utero despite the body getting all the nutrients it needs from the mother. This is because your brain does more than just conscious thinking, it is responsible for regulating your other vital organs. If a fetus does not have a working brain, then it does not have a working heart, lungs, etc. and it will spontaneously die when those organs start to try to form.

Instead, it might be preferable to make a perfect clone of the host (brain and all), and to simply put the body into a forced comma at as young of a stage as possible. Then you simply remove the un-needed bits when the time comes.

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  • $\begingroup$ Rather than "gene engineer" a clone you'd probably just physically nip out the little bud of cells in the early stage embryo that's going to develop into the brain, done at the right stage it won't replace itself and you get a brainless clone .. no alteration to any DNA is actually required. $\endgroup$
    – Pelinore
    Jan 20 at 17:45
  • $\begingroup$ That preferable option makes the whole plot way more creepy $\endgroup$
    – Nikita Bosik
    Jan 22 at 21:16
  • $\begingroup$ @NikitaBosik Creepy yes, but also something we know that humans are perfectly capable of coming to terms with. About 60% the human population world wide believes it is okay to suck the brain out of a living fetus for the mother's convenience, and the most common justification is that it does not count as human because it has no experience of life. If your clones are measured by the same values that we measure abortions, then it seems not only believable, but inevitable. $\endgroup$
    – Nosajimiki
    Jan 23 at 15:24
  • $\begingroup$ It could also become a point for some very interesting plot hooks since we know that some people will consider this practice deeply immoral regardless of if they are created with brains or not. Some people will call it murder, some will call it an affront against God, and some will hate it just because It increases the socioeconomic gap by letting the rich live much longer lives than the poor. These cloning sites, and people who use them should develop a stigma no matter how you approach it. Actually addressing how creepy it is could add a lot of depth to the story. $\endgroup$
    – Nosajimiki
    Jan 23 at 15:37
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There are two possible though extremely unlike opportunities for rejection.

First:

There are some things that can modify genetics. Radiation. Some chemicals. Some viruses.

If the subject had been exposed to these at a very young age, his brain might have a significant portion of its mass of a different genetics to the remainder of his body. His immune system grew used to it slowly as he grew up. A fresh new immune system cloned from his original DNA would not have had time to get used to the "foreign" DNA.

This is unlikely at multiple-stupidly-unlikely level. First the DNA modifying event had to occur and not kill the subject. That's unlikely on its own. Second, the immune system has to not tag the new material as foreign and kill it. Third, the modified material has to be in the brain only. And fourth, it has to be such that it does not turn into cancer and kill the subject outright.

So, to summarize, this one is daytime-TV-soap-opera unlikely.

Second:

The subject is a chimera. This happens very rarely indeed among humans that survive to adulthood. As explained on the TV series House, it can happen when fraternal twins "snuggle up" shortly after fertilization. It means one individual can have two sets of DNA. The immune system of the individual develops with both sets present so it is possible for an individual with this situation to grow to adulthood.

However, a cloned body be from one cell and so would not have this double DNA to practice its immune system on. So if the brain was from one set of DNA, and the portion cloned for the fresh body was from the other, then the brain could be rejected.

This is also multiply-stupidly-unlikely. The condition is fairly rare. The brain being one DNA and the cloned cell the other is 50-50. And getting rejection from a sibling is not automatic.

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Wildly unclear, but you can probably safely decide either way.

If "clone" is shorthand for "exact copy," then almost certainly not.

If "clone" means identical DNA, then it's likely okay, but not at all guaranteed.

The issue is that you have a whole bunch of stuff in your body that isn't strictly based on DNA. The obvious example is immunities: you developed an immunity to chicken pox (or whatever) by exposure to it. There are genetic factors that make you more or less fit to survive chicken pox (or bubonic plague, or whatever), but the actual environment you've lived through has a strong effect on your immune system.

So: will the clone body reject a genetically identical brain? Probably not. It avoids most of the largest pitfalls. But at the same time, if your original body was bitten by a tick and had a meat allergy (or whatever) your new body might be shocked enough at this to give your brain a bad time (and your brain is not a good place to have immune/allergy reactions going on!).

Ultimately, your probably fine fudging it whichever way make sense for your world. Rejections might be rare or common, but it's probably not an all-or-nothing proposition regardless.

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