Twiblings, four-parent babies and other reproductive technology

post by GeneSmith · 2023-05-20T17:11:23.726Z · LW · GW · 33 comments

Contents

  What are Twiblings?
  Twins of different ages
  Four-parent babies (or 6-parent babies, or 8-parent babies, or…)
  A weird and wonderful future?
None
33 comments

Two weeks ago I finally published my year-long research project into how to have polygenically screened children [LW · GW]. In that post, I explained all the practicalities of embryo screening and how parents can use it right now to make their children smarter, happier, and less prone to disease.

This week I'm going to talk about some of the more off-the-wall methods that have been proposed for increasing genetic gain across a variety of traits, along with their implications for family structure, society, and the human experience.

What are Twiblings?

A twibling is somewhere between a sibling and a twin. If identical twins share 100% of their DNA and siblings share about 50%, twiblings share 75%.

To the best of my knowledge, twiblings don’t exist in nature. EDIT: This process is rare, but we have documented cases of it happening in humans. The proper scientific term is "Sesquizygotic Twins". See ScottNYX's comment for more [LW(p) · GW(p)]. To get one, you’d need two different genetically identical eggs to be fertilized by different sperm. But why would we create twiblings?

Anyone who has gone through IVF knows that the main limiting factor in all cycles is the number of eggs the female partner can produce. In an average menstrual cycle, a woman will produce exactly one egg. In an average ejaculation, a man produces about 100 million sperm. Using a specialized set of medications, we can increase the number of eggs harvested per menstrual cycle to between 5 and 100 (there's a lot of variance depending on maternal age and other factors). But even 100 is a lot less than 100 million.

Older women in particular have a very hard time producing eggs. Women over the age of 42 often produce 5 or fewer per retrieval, and many of those have chromosomal issues that prevent them from turning into a baby. So the few eggs without such issues are very precious.

It sure would be nice if there was a way to duplicate the few viable eggs these women can produce…

As it turns out, this is possible! And we’ve already done it in the lab. You can make a haploid stem cell line by tricking an egg into thinking it’s an embryo; you let a sperm fertilize it, then you pull out the sperm’s pronucleus before it fuses with that of the egg. 

Success! The egg now thinks it’s an embryo and will start dividing. 
 

So now you have a bunch of haploid embryonic stem cells, each of which is fairly epigenetically similar to an egg.

But there’s still one tricky step left; how do you derive an egg from these haploid embryonic stem cells such that it can be fertilized again?

The most obvious answer is to use nuclear transfer; pull the haploid nucleus out of these embryonic stem cells and stick it in another egg. So you do this for a bunch of the haploid embryonic stem cells using a bunch of other eggs and now you have many eggs from the same mother!

Of course this necessitates HAVING other eggs, which we already established are in short supply. But thankfully, those other eggs don't need to come from the same woman. You can get donor eggs without too much trouble. And if you don’t care much about the donors' DNA you can get them for quite a bit less money.

But if you can clear that hurdle you now have a very interesting situation: you’ll have multiple genetically identical eggs, each of which can be fertilized by a different sperm. 

If the mother decides to have multiple children, they will be more genetically similar than any siblings, but less similar than identical twins. Twiblings!

Twins of different ages

At the 2, 4 or 8 cell stage, the cells in an embryo can turn into any tissue in the body or placenta. This leads to a natural question: if we split the embryo in half at that stage, will it form two embryos?

It would! Or at least it did in other mammals we’ve studied. For some reason, no one seems to have tried this in humans yet. I don’t fully understand why other than to gesture at the general hand-wringing that happens any time someone proposes doing something new in human reproduction. 

However, if the ART establishment ever decides that maybe those parents that desperately want two kids should be able to have them, maybe they will try out embryo splitting and see if it works.

If they do it would lead to quite an interesting possibility; you could have two children that are identical twins, but different ages! Sometimes when I was younger I wished an older wiser version of myself would help me out. With embryo splitting, it could happen!

This could also lead to some very interesting studies on birth order effects and all kinds of other research on temporal effects that would benefit from controlling for genetic influences. Plus it would be neat to have an older or younger version of yourself!

Four-parent babies (or 6-parent babies, or 8-parent babies, or…)

Imagine you’re really into the idea of improving the genetic lot of your future children. Wouldn’t it be great if your kids had all the best traits of you and the best traits of your spouse?

One way to do that is with regular old embryo selection; you grow a bunch of genetically distinct embryos in a dish using regular IVF, sequence the genome of each, then select the best couple according to which traits you think are important.

But this has problems; most traits are normally distributed. And although there’s a slight correlation across traits, you just can’t produce very large gains by selecting from a normal distribution.

One way around this is to select chromosomes instead of embryos. You and your spouse can produce a bunch of embryos, sequence them using normal PGT techniques, then look at all of their chromosomes. Instead of picking an entire embryo, you pick the best chromosomes among all the embryos. Then you assemble all the best chromosomes together into one cell using some complicated techniques which I won’t get into here and (probably) transfer the resulting nucleus into an egg cell.

But wait! Why stop with two parents? Couldn’t we get chromosomes from the embryos of more than one couple?

And the answer of course is yes. You could get embryos from any number of couples and pick the best chromosomes from all of them, and assemble the best into one single nucleus.

The level of gains you could get through this technique is quite impressive; on a single trait you could expect up to maybe 12 standard deviations of gain. Of course it would be quite insane to select so strongly for a single trait so in reality it would probably be closer to 4 or 5 standard deviations across a broad panel of traits.

Still, 4 or 5 standard deviations is a lot. That’s enough to take an average IQ person to the level of Judit Polgar or Andrew Wiles, or a person of average height to the level of Kevin Durant or Anthony Davis.

The benefits of having children in this manner would be so extreme that if we ever get chromosome selection working I suspect the manner in which we choose our pool of co-parents to become very important.

In a strictly genetic sense, every contributor to the pool has a smaller vested stake in each child because they share less genetic material with the child and many other children raised by different parents will have that same level of genetic similarity. With 8 parents, you’ll share the same amount of genetic material with your child as a great-grandparent.

Would this make parents care less about their kids? Maybe a little? But I suspect not much. Parents that adopt seem about as committed to their kids as those that have kids biologically related to them, although there are likely strong selection effects going on; those that wouldn’t care about their adoptive kids will not adopt.

It also brings up some interesting questions about contact between the “parents” of the children. Would each set of parents raise the kids separately like we do today? Would they all live in one big group house? Would we see couples dating services spring up where couples would try to meet other couples to join their chromosome selection pool?

And how many genetically distinct children would be produced from each pool anyways? Would each group of parents get genetically different kids according to their preferences, or would the cost of assembling genetically distinct genomes be prohibitive enough that only a few different genetic identities be created from each pool?

You could see some very interesting situations where some children differ from others by only a couple of chromosomes, making them almost but not quite twins.

A weird and wonderful future?

I’m probably a little unusual in this respect, but I find something oddly charming and hopeful about the idea of going on double dates with your fellow co-parents down the street who are raising your quarter-son and daughter. You take your prodigious kids over for playdates with their prodigious kids and get a chance to see what the future of the human race is going to look like. They grow up so fast; at 7 years old they are already eclipsing your abilities in mathematics and reading comprehension. But they’re so kind and emotionally mature that you feel alright about being obsolete. You’ve done your part. In another ten years, the world will be in some very good hands.

And who knows; maybe one of them will figure out how to reverse aging and enhance adult intelligence and you’ll be able to catch up to them.

Thank god we paused AI development in the 2020s so these kids would have time to grow up. Can you imagine how bad things would have ended if your generation was the one that had to solve alignment?

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