Designer babies: selection vs editing

Written by: Stephen Hsu

Primary Source: Information Processing

The discussion in this video is sophisticated enough to make the distinction between embryo selection — the parents get a baby whose DNA originates from them, but the “best baby possible” — and active genetic editing, which can give the child genes that neither parent had.The movie GATTACA focuses on selection — the director made a deliberate decision to eliminate reference to splicing or editing of genes. (Possibly because Ethan Hawke’s character Vincent would have no chance competing against edited people.)At SCI FOO, George Church seemed confident that editing would be an option in the near future. He is convinced that off-target mutations are not a problem for CRISPR. I have not yet seen this demonstrated in the literature, but of course George knows a lot more than what has been published. (Warning: I may have misunderstood his comments as there was a lot of background noise when we were talking.)One interesting genetic variant (Lrp5?) that I learned about at the meeting, of obvious interest to future splicers and editors, apparently conveys an +8 SD increase in bone strength!

My views on all of this:

… given sufficient phenotype|genotype data, genomic prediction of traits such as cognitive ability will be possible. If, for example, 0.6 or 0.7 of total population variance is captured by the predictor, the accuracy will be roughly plus or minus half a standard deviation (e.g., a few cm of height, or 8 IQ points). The required sample size to extract a model of this accuracy is probably on the order of a million individuals. As genotyping costs continue to decline, it seems likely that we will reach this threshold within five years for easily acquired phenotypes like height (self-reported height is reasonably accurate), and perhaps within the next decade for more difficult phenotypes such as cognitive ability. At the time of this writing SNP genotyping costs are below $50 USD per individual, meaning that a single super-wealthy benefactor could independently fund a crash program for less than $100 million.

Once predictive models are available, they can be used in reproductive applications, rang- ing from embryo selection (choosing which IVF zygote to implant) to active genetic editing (e.g., using powerful new CRISPR techniques). In the former case, parents choosing between 10 or so zygotes could improve their expected phenotype value by a population standard de- viation. For typical parents, choosing the best out of 10 might mean the difference between a child who struggles in school, versus one who is able to complete a good college degree. Zygote genotyping from single cell extraction is already technically well developed [25], so the last remaining capability required for embryo selection is complex phenotype prediction. The cost of these procedures would be less than tuition at many private kindergartens, and of course the consequences will extend over a lifetime and beyond.

The corresponding ethical issues are complex and deserve serious attention in what may be a relatively short interval before these capabilities become a reality. Each society will decide for itself where to draw the line on human genetic engineering, but we can expect a diversity of perspectives. Almost certainly, some countries will allow genetic engineering, thereby opening the door for global elites who can afford to travel for access to reproductive technology. As with most technologies, the rich and powerful will be the first beneficiaries. Eventually, though, I believe many countries will not only legalize human genetic engineering, but even make it a (voluntary) part of their national healthcare systems [26]. The alternative would be inequality of a kind never before experienced in human history.

Here is the version of the GATTACA scene that was cut. The parents are offered the choice of edited or spliced genes conferring rare mathematical or musical ability.

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Stephen Hsu
Stephen Hsu is vice president for Research and Graduate Studies at Michigan State University. He also serves as scientific adviser to BGI (formerly Beijing Genomics Institute) and as a member of its Cognitive Genomics Lab. Hsu’s primary work has been in applications of quantum field theory, particularly to problems in quantum chromodynamics, dark energy, black holes, entropy bounds, and particle physics beyond the standard model. He has also made contributions to genomics and bioinformatics, the theory of modern finance, and in encryption and information security. Founder of two Silicon Valley companies—SafeWeb, a pioneer in SSL VPN (Secure Sockets Layer Virtual Private Networks) appliances, which was acquired by Symantec in 2003, and Robot Genius Inc., which developed anti-malware technologies—Hsu has given invited research seminars and colloquia at leading research universities and laboratories around the world.
Stephen Hsu

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