Backwards-compatible Transhumanism: Is this feasible?

Question

Let's say that we have a human society somewhere away from Earth which is psychologically ready for genetic transhumanism... perhaps humans just aren't coping with the environment, perhaps the local religion supports it, perhaps the local wildlife are a bit much to handle, or perhaps people just want their kids to have better bodies than theirs.

So, the geneticists whip up the DNA to insert into an embryo so that the baby will be born with the desired alterations. It's tested and approved for general release.

Now, the thing is, the parents paying for their child to receive this upgrade want their grandchildren and their descendants to inherit the augmentation... regardless of whether their child is male or female, and regardless of whether their child's reproductive partner is enhanced... without their grandchild having to be modified at the embryonic stage.

Conversely, those commissioning certain enhancements may not want the enhancements propagated to the next generation, except under specific circumstances... perhaps only if the reproductive partner also has the enhancement, or perhaps only if a particular environmental factor is present or absent.

So, the geneticists add an extra chromosome pair to the zygote, containing all the necessary genes for the enhancement. The added chromosomes are replicated along with the others as usual during mitosis (normal cell division), and have the desired effect upon the individual carrying them.

Now, the difference that allows both backwards-compatibility and selective non-transmission is only noticeable during meiosis (the cell divisions that produce haploid gametes).

Normally, before mitosis or meiosis occurs, a cell's DNA is replicated once. To prevent the creation of too many copies during mitosis or meiosis, a protein that binds to a start sequence on the chromosome is produced, and replication starts from there. The copies do not have the starter protein bound to them, and so are not themselves copied.

The difference is that the backwards-compatible chromosomes have an extra start-sequence that is different to the natural one. During mitosis, this is of no consequence. However, during meiosis, during DNA replication, another, different starter protein is produced that only binds to the extra different start sequence. This results in the two cells that result from the first meiotic division having four copies of the extra chromosomes rather than two. Then, during the second meiotic division, the paired chromosomes are split between the resultant cells. This results in the gametes being haploid with respect to the original chromosomes, but being diploid with respect to the new chromosomes.

So, whether the enhanced person's gamete is an egg or a sperm, on fertilisation with the gamete of an unenhanced person, the resultant zygote is fully diploid and enhanced, gaining both copies of the enhancement chromosome from their enhanced parent.

Now the trick is to not end up with extra copies of the enhancement chromosome when both parents are enhanced. This may be achieved by signal proteins on the surface of the gametes. When fertilisation occurs, if both egg and sperm are carrying the enhancement chromosome, they each have a male or female specific marker protein on their surface. If the sperm detects the female marker or the egg detects the male marker, a process similar to X-inactivation occurs to one of the enhancement chromosomes within that gamete, rendering that chromosome inactive. However, unlike X-inactivation, the inactivated enhancement chromosomes are destroyed shortly after fertilisation.

In order to transmit an enhancement chromosome only when reproducing with a similarly enhanced partner, meiosis is left unchanged, so that the resultant gametes are fully haploid. If the other gamete does not have the requisite marker, the enhancement chromosome is inactivated and destroyed. When both gametes have the enhancement chromosomes, the zygote should be properly diploid for all chromosomes.

When the enhancement chromosome must be transmitted only in the presence or absence of a particular environmental marker, that chromosome has only an alternate start sequence, and during meiosis, the alternate starter protein is produced only in the presence or absence of the marker, and the enhancement chromosome is destroyed in the absence of the alternate starter protein, resulting in unenhanced gametes. The alternate starter protein is always produced during mitosis.

So... is this feasible or would it have problems? Could it be improved?

Answer 1

Why put the enhancements into the base human genome itself?  Why not put them in their own artificially engineered organelles? 

Like mitochondria, these "metachondria" would be genetically isolated.  The traits encoded in them don't participate in the chromosomal square-dance of meiosis.  Unlike mitochondria, metachondria would be inheritable from either or both of the parents.  Whatever mechanism destroys paternal mitochondria simply need not affect these artificial organelles. 

Having your enhancements locked inside metachondrial bodies gives you more flexibility in your engineering.  You can have traits that are only carried through paternal lines, if p-metachondria self-destruct during egg formation.  Likewise, m-metachondria that self-destruct during sperm formation only pass through maternal lines, just like the mitochondria that inspired them.  You can have u-metachondria that pass universally, regardless of which parental line. 

Do you want traits that pass paternally, but only express when the maternal line is also properly enhanced?  Then you make p-metachondria that lie dormant except when the matching m-metachondria are present.  That way, if Daddy marries the wrong girl, but Junior marries the right girl, the grand-kids still get to be part of the enhanced extended family.  Do you want more flexibility than that?  Ok, how about p-metachondria that lie dormant unless Mommie has been taking the right supplements since before conception? 

The best thing is the option of a fail-safe kill-switch.  Engineer things such that the right drug purges any metachondria from the reproductive system. You're back to baseline humanity in a single generation, if you need to be.  If there's an undesirable metachondrial mutation, it can be not merely treated but outright eradicated. 

Don't patch the human genome itself.  Leave all that code intact.  Instead, write an overlay.  Write a plug-in.  Write something that's easier to roll back, easier to upgrade, easier to debug in isolation. 

An entire and separate artificial organelle body earns you a wider range of solutions than just a few strands of customized DNA could every buy.  It's not just new code; it's a new sub-processor handling the new code. 

Answer 2

Well, as long as the enhanced humans don't have any changes to the core structure of their genes (no extra chromosomes and such), they are automatically backwards compatible with normal humans since they are still human.

Then the inheritance issue could be solved by being able to decide if a gene is recessive or dominant. That way if they want their child to be able to spread, they can force the gene to be dominant or maybe even super dominant so that it also overrules normal dominant genes.

Now this would still create an issue when both partners have a dominant enhancement, since that is just a limitation of biology, but that could be an interesting part of the story. They might be forced to seek the assistance of a geneticist to make a custom combination of their genes.

Answer 3

It should work, but...

• It would be simpler to rearrange the genes on the chromosomes so that the transhumans would be incapable of mating with non-transhumans since the genes wouldn't line up. Or if you add a 24th pair of chromosomes, then the resulting children with a normal will have mismatched chromosomes like a trisomy (resulting in an infertile mule?) Thus preventing uncontrolled gene transfer. The transhumans would be a new species.
• But maybe you don't want to start a new species altogether. An insertable copy of the gene with built-in CRISPR could excise the gene in the absence of a suppressor, also added, which needs to be homozygous to function. All transhumans would be homozygous positive for the suppressor, all normals would be homozygous negative.Two transhuman parents have homozygous suppressor kids who become transhumans. A transhuman and a normal have heterozygous kids who delete the genes (including the suppressor) and are normals.
• A fun alternative would be to have normals all have a built-in anti-CRISPR defense gene engineered in so they're protected from people misusing CRISPR. All inserted genes from transhuman people would be excised as pro-CRISPR, and would result in a normal, whereas all transhumans wouldn't have the anti-CRIPSR gene. The anti-CRISPR would (ironically) CRISPR itself into the chromosome copies from the transhuman parent so the anti-CRISPR gene would always be homozygous. Again, two transhumans will have transhuman kids, but a transhuman and a normal will have the anti-CRISPR and give birth to normal kids. Just a thought.
• This should give you two additional alternatives that allow interbreeding. Your idea should still work, but messing with chromosome migration seems like dangerous territory. (I know, wild gene rearrangements like I'm suggesting sound PERFECTLY safe, right?) The last option (CRISPR defense) allows for a society that was abused by uncontrolled gene manipulation but doesn't want it any more, and doesn't rely on "good" actors who design their kids to only pass on genes to other transhumans. It does require everyone but transhumans to accept gene alteration (even if just for defense.)