Well, the key time to implement an increase in brain size is when the neuron-precursors which are still capable of mitosis (unlike mature neurons) are growing. This is during fetal development, when there isn’t a skull in the way, but vaginal birth has been a limiting factor for evolution in the past.
Experiments have been done on increasing neuron count at birth in mammals via genetic engineering. I was researching this when I was actively looking for a way to increase human intelligence, before I decided that genetically engineering infants was infeasible [edit: within the timeframe of preparing for the need for AI alignment]. One example of a dramatic failure was increasing Wnt (a primary gene involved in fetal brain neuron-precursor growth) in mice. The resulting mice did successfully have larger brains, but they had a disordered macroscale connectome, so their brains functioned much worse.
it’s probably possible to get neurons back into mitosis-ready mode via some sort of crazy levin bioelectric cocktail, not that this helps us since that’s probably 3 to 30 years of research away, depending on amount of iteration needed and funding and etc etc.
Fleshing this out a bit more: insofar as development is synchronized in an organism, there usually has to be some high-level signal to trigger the synchronized transitions. Given the scale over which the signal needs to apply (i.e. across the whole brain in this case), it probably has to be one or a few small molecules which diffuse in the extracellular space. As I’m looking into possibilities here, one of my main threads is to look into both general and brain-specific developmental signal molecules in human childhood, to find candidates for the relevant molecular signals.
(One major alternative model I’m currently tracking is that the brain grows to fill the brain vault, and then stops growing. That could in-principle mechanistically work via cells picking up on local physical forces, rather than a small molecule signal. Though I don’t think that’s the most likely possibility, it would be convenient, since it would mean that just expanding the skull could induce basically-normal new brain growth by itself.)
I hope by now you’re already familiar with michael levin & his lab’s work on the subject of morphogenesis signals? Pretty much everything I’m thinking here is based on that.
Yes, it’s absolutely a combination of chemical signals and physical pressure. An interesting specific example of these two signals working together during fetal development when the pre-neurons are growing their axons. There is both chemotaxis which steers the ameoba-like tip of the growing axon, and at the same time a substantial stretching force along the length of the axon. The stretching happens because the cells in-between the origin and current location of the axon tip are dividing and expanding. The long distance axons in the brain start their growth relatively early on in fetal development when the brain is quite small, and have gotten stretched quite a lot by the time the brain is near to birth size.
Neurons are really really hard to reverse. You are much better off using existing neural stem cells (adults retain a population in the hippocampus which spawn new neurons throughout life just specifically in the memory formation area.)
So actually it’s pretty straightforward to get new immature neurons for an adult. The hard part is inserting them without doing damage to existing neurons, and then getting them to connect in helpful rather than harmful ways. The developmental chemotaxis signals are no longer present, and the existing neurons are now embedded in a physically hardened extracellular matrix made of protein that locks axons and dendrites in place. So you have to (carefully!) partially dissolve this extracellular protein matrix (think firm jello) enough to the the new cells grow azons through it. Plus, you don’t have the stretching forces, so new long distance axons are just definitely not going to be achievable. But for something like improving a specific ability, like mathematical reasoning, you would only need additional local axons in that part of the cortex.
The developmental chemotaxis signals are no longer present,
Right. what I’m imagining is designing a new chemotaxis signal.
So you have to (carefully!) partially dissolve this extracellular protein matrix (think firm jello) enough to the the new cells grow azons through it
That certainly does sound like a very hard part yup.
Plus, you don’t have the stretching forces, so new long distance axons are just definitely not going to be achievable.
Roll to disbelieve in full generality, sounds like a perfectly reasonable claim for any sort of sane research timeframe.
But for something like improving a specific ability, like mathematical reasoning, you would only need additional local axons in that part of the cortex.
Maybe. I think you might run out of room pretty quick if you haven’t reintroduced enough plasticity to grow new neurons. Seems like you’re gonna need a lot of new neurons, not just a few, in order to get a significant change in capability. Might be wrong about that, but it’s my current hunch.
Yes, ok. Not in full generality. It’s not prohibited by physics, just like 2 OOMs more difficult. So yeah, in a future with ASI, could certainly be done.
My hope here would be that a few upstream developmental signals can trigger the matrix softening, re-formation of the chemotactic signal gradient, and whatever other unknown factors are needed, all at once.
15 years ago when I was studying this actively I could have sent you my top 20 favorite academic papers on the subject, or recommended a particular chapter of a particular textbook. I no longer remember these specifics. Now I can only gesture vaguely at Google scholar and search terms like “fetal neurogenesis” or “fetal prefrontal cortex development”. I did this, and browsed through a hundred or so paper titles, and then a dozen or so abstracts, and then skimmed three or four of the most promising papers, and then selected this one for you. https://www.nature.com/articles/s41386-021-01137-9
Seems like a pretty comprehensive overview which doesn’t get too lost in minor technical detail.
More importantly, I can give you my takeaway from years of reading many many papers on the subject.
If you want to make a genius baby, there are lots more factors involved than simply neuron count. Messing about with generic changes is hard, and you need to test your ideas in animal models first, and the whole process can take years even ignoring ethical considerations or budget.
There is an easier and more effective way to get super genius babies, and that method should be exhausted before resorting to genetic engineering.
The easy way: find a really smart woman, ideally young. Surgically remove one of her ovaries. Collect sperm from a bunch of very smart men (ideally with diverse genetic backgrounds). Have a team of hundreds of scientists carefully fertilize many thousands of eggs from the ovary.
Grow them all into blastocysts, and run a high fidelity genetic sequencing on all of them. Using what we know about the genes associated with intelligence, pick the top 20 who seem likely to be the smartest. Implant those in surrogate mothers. Take good care of the mothers.
This is likely to get you multiple nobel level geniuses, and possibly a human smarter than has ever been born before.
Raise the children in a special accelerated education environment.
I think this would work, and it doesn’t require any novel technology.
But it would take a while to raise the children… (Credit to Stephen Hsu for the idea)
Well, the key time to implement an increase in brain size is when the neuron-precursors which are still capable of mitosis (unlike mature neurons) are growing. This is during fetal development, when there isn’t a skull in the way, but vaginal birth has been a limiting factor for evolution in the past. Experiments have been done on increasing neuron count at birth in mammals via genetic engineering. I was researching this when I was actively looking for a way to increase human intelligence, before I decided that genetically engineering infants was infeasible [edit: within the timeframe of preparing for the need for AI alignment]. One example of a dramatic failure was increasing Wnt (a primary gene involved in fetal brain neuron-precursor growth) in mice. The resulting mice did successfully have larger brains, but they had a disordered macroscale connectome, so their brains functioned much worse.
it’s probably possible to get neurons back into mitosis-ready mode via some sort of crazy levin bioelectric cocktail, not that this helps us since that’s probably 3 to 30 years of research away, depending on amount of iteration needed and funding and etc etc.
Fleshing this out a bit more: insofar as development is synchronized in an organism, there usually has to be some high-level signal to trigger the synchronized transitions. Given the scale over which the signal needs to apply (i.e. across the whole brain in this case), it probably has to be one or a few small molecules which diffuse in the extracellular space. As I’m looking into possibilities here, one of my main threads is to look into both general and brain-specific developmental signal molecules in human childhood, to find candidates for the relevant molecular signals.
(One major alternative model I’m currently tracking is that the brain grows to fill the brain vault, and then stops growing. That could in-principle mechanistically work via cells picking up on local physical forces, rather than a small molecule signal. Though I don’t think that’s the most likely possibility, it would be convenient, since it would mean that just expanding the skull could induce basically-normal new brain growth by itself.)
I hope by now you’re already familiar with michael levin & his lab’s work on the subject of morphogenesis signals? Pretty much everything I’m thinking here is based on that.
Yes, I am familiar with Levin’s work.
Yes, it’s absolutely a combination of chemical signals and physical pressure. An interesting specific example of these two signals working together during fetal development when the pre-neurons are growing their axons. There is both chemotaxis which steers the ameoba-like tip of the growing axon, and at the same time a substantial stretching force along the length of the axon. The stretching happens because the cells in-between the origin and current location of the axon tip are dividing and expanding. The long distance axons in the brain start their growth relatively early on in fetal development when the brain is quite small, and have gotten stretched quite a lot by the time the brain is near to birth size.
Neurons are really really hard to reverse. You are much better off using existing neural stem cells (adults retain a population in the hippocampus which spawn new neurons throughout life just specifically in the memory formation area.) So actually it’s pretty straightforward to get new immature neurons for an adult. The hard part is inserting them without doing damage to existing neurons, and then getting them to connect in helpful rather than harmful ways. The developmental chemotaxis signals are no longer present, and the existing neurons are now embedded in a physically hardened extracellular matrix made of protein that locks axons and dendrites in place. So you have to (carefully!) partially dissolve this extracellular protein matrix (think firm jello) enough to the the new cells grow azons through it. Plus, you don’t have the stretching forces, so new long distance axons are just definitely not going to be achievable. But for something like improving a specific ability, like mathematical reasoning, you would only need additional local axons in that part of the cortex.
Right. what I’m imagining is designing a new chemotaxis signal.
That certainly does sound like a very hard part yup.
Roll to disbelieve in full generality, sounds like a perfectly reasonable claim for any sort of sane research timeframe.
Maybe. I think you might run out of room pretty quick if you haven’t reintroduced enough plasticity to grow new neurons. Seems like you’re gonna need a lot of new neurons, not just a few, in order to get a significant change in capability. Might be wrong about that, but it’s my current hunch.
Yes, ok. Not in full generality. It’s not prohibited by physics, just like 2 OOMs more difficult. So yeah, in a future with ASI, could certainly be done.
My hope here would be that a few upstream developmental signals can trigger the matrix softening, re-formation of the chemotactic signal gradient, and whatever other unknown factors are needed, all at once.
Any particular readings you’d recommend?
15 years ago when I was studying this actively I could have sent you my top 20 favorite academic papers on the subject, or recommended a particular chapter of a particular textbook. I no longer remember these specifics. Now I can only gesture vaguely at Google scholar and search terms like “fetal neurogenesis” or “fetal prefrontal cortex development”. I did this, and browsed through a hundred or so paper titles, and then a dozen or so abstracts, and then skimmed three or four of the most promising papers, and then selected this one for you. https://www.nature.com/articles/s41386-021-01137-9 Seems like a pretty comprehensive overview which doesn’t get too lost in minor technical detail.
More importantly, I can give you my takeaway from years of reading many many papers on the subject. If you want to make a genius baby, there are lots more factors involved than simply neuron count. Messing about with generic changes is hard, and you need to test your ideas in animal models first, and the whole process can take years even ignoring ethical considerations or budget.
There is an easier and more effective way to get super genius babies, and that method should be exhausted before resorting to genetic engineering.
The easy way: find a really smart woman, ideally young. Surgically remove one of her ovaries. Collect sperm from a bunch of very smart men (ideally with diverse genetic backgrounds). Have a team of hundreds of scientists carefully fertilize many thousands of eggs from the ovary. Grow them all into blastocysts, and run a high fidelity genetic sequencing on all of them. Using what we know about the genes associated with intelligence, pick the top 20 who seem likely to be the smartest. Implant those in surrogate mothers. Take good care of the mothers. This is likely to get you multiple nobel level geniuses, and possibly a human smarter than has ever been born before. Raise the children in a special accelerated education environment. I think this would work, and it doesn’t require any novel technology. But it would take a while to raise the children… (Credit to Stephen Hsu for the idea)