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Genetic Load

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PAPER REVIEW

Tang, Lichun et al. 2017
CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein


Abstract:

Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.

Gwern Branwen’s comments:

Even nicer: another human-embryo CRISPR paper. Some old 2015 work – results: no off-target mutations and efficiencies of 20/50/100% for various edits. (As I predicted, the older papers, Liang et al 2015 / Kang et al 2016 / Komor et al 2016, were not state of the art and would be improved on considerably.)

Back in February 2015, qualia researcher Mike Johnson predicted that dedicated billionaire with scant regard for legalistic regulations could start genetically “spellchecking” their offspring within 5-7 years.

But if anything, he might have overestimated the timeframe.

tang-2017-crispr-cas9

 
• Category: Science • Tags: Crispr, Genetic Load, Paper Review, Transhumanism 
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mike-johnson-iq-talk

Founded by eight NASA scientists, the Rainbow Mansion is a kind of academic coop, where you have to demonstrate you’re working on something interesting to get a rental agreement. The building itself is true to its name, a mansion spacious within, and surrounded by lush gardens without. Every week they host a group dinner, followed by a speech from an invited guest. This week’s guest was Mike Johnson, a philosopher and transhumanist who is currently working on a treatise that could lay the groundwork for a mathematical model of pain/pleasure.

His talk, however, wasn’t about that, but about another topic and interest of his – genetic typos, the possibility of “correcting” them, and the profound effects that might have on human intelligence and capability if widely implemented.

Genetic editing tools are already coming online that would work for already existing organisms: CRISPR, whole-chromosome DNA synthesis, viral vectors (adenoviri), etc. What can we edit? We could try to maximize for some trait using the GWAS approach (e.g. as BGI is trying to do with IQ). We could go for transgenic bioengineering, you know, the Spiderman/Resident Evil-type stuff. But that’s pretty hard. Just fixing our own broken genes is much easier and could potentially generate tremendous payoffs in increased health, intelligence, and longevity.

We all have varying amounts of “broken genes,” the genetic equivalent of spelling errors. Of those errors that have an effect, the vast majority are bad; as Mike pointed out, if you were to open up a computer program and edit code at random, you are far more likely to ruin or degrade the program than improve it. There are several different definitions and estimates of the numbers of these errors: 100 semi-unique Loss of Function mutations (MacArthur 2012), 1,000 minor IQ-decreasing variants (Hsu 2014), 300 health-decreasing mutations (Leroi 2005).

Broken genes have a broadly linear additive effect on general fitness, which is well approximate by IQ. Stephen Hsu’s research indicates that people have an average of 1000 broken genes, with 30-40 mutations contributing to a stunning -1SD drop in intelligence. In essence, it’s not so much that there are genes for intelligence, as there are genes for stupidity. Fix all of them, and theoretically, you might get IQs never before observed on this planet. As Greg Cochran memorably put it:

What would a spelling-checked person, one with no genetic typos, be like? Since no such person has ever existed, we have to speculate. I figure that kind of guy would win the decathlon, steal your shirt and your girl – and you still couldn’t help liking him.

Here is a list of (optimistic) estimates for other traits that Mike collated from various sources.

genetic-spell-checking-benefits

While Mike, understandably, did not go into this in his talk, one more important point has to be mentioned: There is also an explicit HBD angle to the theory of genetic load.

Studies show significantly more Loss of Function mutations amongst Africans than Europeans or East Asians, which would tie in not only to well-known psychometric data but Satoshi Kanazawa’s theories on the relatively low atttractiveness of Black women (specifically female beauty, like g, appears to be a good proxy for overall fitness). Cochran ascribes it to heat. I am not so sure. Peak wet bulb temperatures are actually higher today in the Ganges delta and interior China than most of Africa, which has some really cool (temperature-wise) places like the Ethiopians highlands and the Great Rift region. This might not have been quite the case during the Ice Age, of course, but still, 10,000 years is a long time to adjust to a new equilibrium.

Another possible determinant of genetic load is male parental age. Offspring genetic load and paternal (though not maternal) age are positively correlated. Paternal age in traditional societies can differ substantially according to their particular family system. For instance, within the Hajnal Line encompassing most of Western Europe, characterized by nuclear families, average paternal age was considerably higher than amongst say the neighboring Poles and Russians. What specific family system is highly prevalent in the traditional global South, especially in Africa? Polygamy. This implies one dude monopolizing a lot of the chicks. What would he be like? Big, bad, bold – naturally. But he’d also have a reputation, and he’d probably be someone who can spit smooth game. Both the latter require some time to build up. So he would probably be considerably older than fathers elsewhere in the world who entered into monogamous marriages. But this is just a theory, it would be great to actually get concrete anthropological data on average paternal age in traditional Africa.

Though I’m taking steps to remedy this, I am not sufficiently well versed in genetics as to offer a valid judgment on the plausibility of Cochran’s and Hsu’s mutational load theory of IQ. Still, it does appear to have a great deal of face validity to it, though I remain skeptical of whether spellchecking can truly create “superhumans,” as opposed to just some very healthy and athletic 145-175 IQ types with a life expectancy of maybe 105 years. Surely at some point basic biological limits will be hit, and there will be diminishing returns?

Still, the potential for improvement are immense, and eventually, it will be possible to apply them to grown adults as opposed to just embryos. Even raising the global IQ by one SD will basically solve India’s and Africa’s development problems, while making the two odd billions of Europeans, Americans, and Chinese as innovative per capita as the world’s 20 million Ashkenazi Jews. Near instant technological singularity! When asked to give an estimate, Mike Johnson said that this “spellchecking” technology will become available in 5-7 years for billionaires who wish to have a designer baby and are unconstrained by any regulatory restrictions.

There’ll inevitably be a lot of hand-wringing about this, lots of soul searching and moral queasiness, and no doubt some attempts at restriction, but it’s hard to stop a moving train. As Mike said, the Chinese and East Asians in general don’t share these concerns; if they can safely have a more intelligent child, well, why on earth not? It is telling that the global focal point for research on the genetics of IQ, which Steve Hsu is incidentally heavily involved with, is the Beijing Genomics Institute. Regardless of their reasons or justifications, those who refuse to get on this train will simply be left behind.

 
• Category: Science • Tags: Crispr, Family, Genetic Load, Transhumanism 
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Anatoly Karlin
About Anatoly Karlin

I am a blogger, thinker, and businessman in the SF Bay Area. I’m originally from Russia, spent many years in Britain, and studied at U.C. Berkeley.

One of my tenets is that ideologies tend to suck. As such, I hesitate about attaching labels to myself. That said, if it’s really necessary, I suppose “liberal-conservative neoreactionary” would be close enough.

Though I consider myself part of the Orthodox Church, my philosophy and spiritual views are more influenced by digital physics, Gnosticism, and Russian cosmism than anything specifically Judeo-Christian.