Steve Hsu: prediction

Transcript context

…I’m glad you're asking about these questions because these are things that people are very confused about, even in the field. First of all, let me say that when you have a trait that's controlled by 10,000 variants (eg. height is controlled by an order of 10,000 variants and probably cognitive ability a little bit more), the square root of 10,000 is 100. So, if I could come to this little embryo, and I want to give it one extra standard deviation of height, I only need to edit 100. I only need to flip 100 minus variance to plus variance. These are very rough numbers. But, one standard deviation is the square root of “n”. If I flip a coin “n” times, I want a better outcome in terms of the number of ratio heads to tails. I want to increase it by one standard deviation. I only need to flip the square root of “n” heads because if you flip a lot, you will get a narrow distribution that peaks around half and the width of that distribution is the square root of “n”. Once I tell you, “Hey, your height is controlled by 10,000 variants, and I only need to flip 100 genetic variants to make you one standard deviation for a male,” (that would be three inches tall, two and a half or three inches taller), you suddenly realize, “Wait a minute, there are a lot of variants up for grabs there. If I could flip 500 variants in your genome, I would make you five standard deviations taller, you'd be seven feet tall.” I didn't even have to do that much work, and there's a lot more variation where that came from. I could have flipped even more because I only flipped 500 out of 10,000, right? So, there's this quasi-infinite well of variation that evolution or genetic engineers could act on. Again, the early population geneticists who bred corn and animals know this. This is something they explicitly know about because they've done calculations. Interestingly, human geneticists who are mainly concerned with diseases and stuff, are often unfamiliar with the math that the animal breeders already know. You might be interested to know that the milk you drink comes from heavily genetically-optimized cows bred artificially using almost exactly the same technologies that we use for genomic prediction. But they're doing it to optimize milk production and stuff like this. So there is a big well of variance. It's a consequence of the trait's polygenicity. On the longevity side of things, it does look like people could “be engineered” to live much longer by flipping the variants that make the risk for diseases that shorten your life. The question is then, “Why didn't evolution give us life spans of thousands of years?” People in the Bible used to live for thousands of years. Why don't we? I mean, *chuckles* that probably didn’t happen. But the question is, you have this very high dimensional space, and you have a fitness function. How big is the slope in a particular direction of that fitness function? * that probably didn’t happen. But the question is, you have this very high dimensional space, and you have a fitness function. How big is the slope in a particular direction of that fitness function? How much more successful reproductively would Joe caveman have been if he lived to be 150 instead of only 100 or something? There just hasn't been enough time to explore this super high-dimensional space. That's the actual answer. But now, we have the technology, and we're going to fucking explore it fast. That's the point that the big lightbulb should go off. We’re mapping this space out now. Pretty confident in 10 years or so, with the CRISPR gene editing technologies will be ready for massively multiplexed edits. We'll start navigating in this high-dimensional space as much as we like. So that's the more long-term consequence of the scientific insights. Yeah, that's super interesting. What do you think will be the plateau for a trait of how long you’ll live? With the current data and techniques, do you think it could be significantly greater than that?…

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