[ExI] crisper children

Rafal Smigrodzki rafal.smigrodzki at gmail.com
Thu Nov 12 02:05:37 UTC 2015


What do you think, list-friends: When will the first CRISPR children be
born, and where? When will the first child with 100 genetic adjustments be
born? With 100,000 adjustments?

The child with a single adjustment is just a proof of principle. The child
with 100 would be a harbinger of change (assuming the AI singularity is
late). The 100,000-times adjusted ones would be agents of change themselves.

My guess for 1 is around 2020. 100 is 2030. 100,000 is 2035.

With cheap deep sequencing you can verify adjustments in a day. A cycle of
adjustment, verification and preparation for next adjustment might take as
little as a week. At the same you can detect random mutations which are
guaranteed to accumulate during expansion of the cells. These mutations can
be then corrected during the next step of adjustment. If you can achieve
90% success rate on 100 adjustments per cycle of CRISPR->clonal
expansion->deep seq->CRISPR, while removing the new mutations as they show
up, you could accumulate a few thousand adjustments per year.

100 adjustments per cycle is something achievable with current technology.
It is hard to tell if getting 1000 adjustments per cycle is doable, my gut
feeling is yes. The procedure should be highly amenable to automation.
Generating guides, CRISPR reaction itself, clonal expansion, sequencing -
all the wet lab stuff is something that could be done completely without
direct human involvement even today. For a few millions of dollars you
should be able to design an integrated genetic adjustment installation -
with RNA synthesizer feeding directly into a cell culture robot doing the
modification and expansion, feeding into a DNA isolation and sequencing
robot, feeding information back into the RNA synthesizer. This means the
price of adjustments would depend on progress in robotics, which is fast.

This technology would be viable as long as the amount of genetic burden
removed during each cycle sufficiently exceeds the amount of genetic burden
randomly introduced per cycle. We already know it is doable. The genetic
burden increases by about 70 mutations per generation in humans and that
involves tens of years of expansion and maintenance of the germ line - the
increase in genetic burden per cycle of CRISPR should be much less. We can
already introduce 60 adjustments in one cell line. This will work.

The input would be a client's zygote which would be used to make the
working cell line. The end product would be an adjusted, genetically vetted
cell line that could very easily be transformed back into zygotes.

The children of the future will be healthy, smart and beautiful.

Rafał
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