<html><head><meta http-equiv="Content-Type" content="text/html charset=utf-8"></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space;" class=""><div class="">Can you explain the technology to me—I’m not sure I understand.</div><div class=""><br class=""></div><div class="">Are these adjustments done at the stage of sperm/egg, at zygote, and then no further changes until the next generation; or are you talking about changes to each successive flux of cells within a growing person, throughout a single lifetime? </div><br class=""><div apple-content-edited="true" class="">
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<br class=""><div><blockquote type="cite" class=""><div class="">On Nov 11, 2015, at 6:05 PM, Rafal Smigrodzki <<a href="mailto:rafal.smigrodzki@gmail.com" class="">rafal.smigrodzki@gmail.com</a>> wrote:</div><br class="Apple-interchange-newline"><div class=""><div dir="ltr" class=""><div class="gmail_signature">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?</div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">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.</div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">My guess for 1 is around 2020. 100 is 2030. 100,000 is 2035.</div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">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. </div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">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. </div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">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.</div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">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.</div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">The children of the future will be healthy, smart and beautiful.</div><div class="gmail_signature"><br class=""></div><div class="gmail_signature">Rafał</div>
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