--- Log opened Fri Nov 30 00:00:38 2018
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07:54 < kanzure> i think the ethical standard is something like "if we can imagine additional ethical steps then you have not behaved ethically" in this area, which is obviously bullshit
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08:28 < kanzure> https://tree.sci-hub.tw/ another server
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08:47 < kanzure> https://www.technologyreview.com/s/612494/despite-crispr-baby-controversy-harvard-university-will-begin-gene-editing-sperm/
08:47 < kanzure> RaisdbyRobots: be greeted
08:53 < kanzure> ".. research to improve the next generation of humans is happening in the US, too. In fact, it’s about to happen at Harvard University. At the school’s Stem Cell Institute, IVF doctor and scientist Werner Neuhausser says he plans to begin using CRISPR, the gene-editing tool, to change the DNA code inside sperm cells. The objective: to show whether it is possible to create IVF babies with ...
08:53 < kanzure> ...a greatly reduced risk of Alzheimer’s disease later in life."
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09:53 < kanzure> .tw https://twitter.com/pgmid/status/1065668735367671808
09:53 < yoleaux> So fun to learn about the potential of neuromorphic chips to make neural networks energy efficient and, you know, save the planet. This week I talk with @julie_grollier about her spin-torque nano-oscillator neural nets. Thanks Julie! https://braininspired.co/podcast/19/ (@pgmid)
09:55 < kanzure> "Neural-symbol VQA: Disentangling reasoning from vision and language understanding" https://arxiv.org/abs/1810.02338 https://twitter.com/SciFi/status/1048025603046170626
09:58 < kanzure> .tw https://twitter.com/zz_zhaozhang/status/1068159445908291587
09:58 < yoleaux> Voice from the couple dropped out from #CRISPRbabies: 1. They were never explained and told this technique is unethical. 2. When the husband pressured “what if the baby is unhealthy”. Response from the He team: “we can help to GET RID OF it” He Jiankui should be sentenced! https://pbs.twimg.com/media/DtLdWWZU4AANP97.jpg (@zz_zhaozhang)
10:00 < kanzure> .tw https://twitter.com/ColinVParker/status/1068541620285517824
10:00 < yoleaux> @4LOVofScience Could you, theoretically, CRISPR a human without opioid receptors, or is that way harder than what was allegedly done to make these babies HIV-resistant? (@ColinVParker, in reply to tw:1068540352234053632)
10:04 < kanzure> .tw https://twitter.com/starstrickenSF/status/1068251671610834945
10:04 < yoleaux> do you guys realize there’s a planet in our solar system entirely inhabited by robots (@starstrickenSF)
10:09 < kanzure> "Base editing generates substantial off-target single nucleotide variants" https://www.biorxiv.org/content/early/2018/11/27/480145
10:11 < kanzure> jiankui he was also doing pcsk9 editing https://twitter.com/antonioregalado/status/1068495711556259841
10:13 < kanzure> .tw https://twitter.com/antonioregalado/status/1068562037322715136
10:13 < yoleaux> Here’s my idea of fun: stay up late inputting @geochurch list of rare protective alleles (aka “Space Genes”) into the Chinese clinical trial database. https://pbs.twimg.com/media/DtRLgnBX4AEwRY9.jpg (@antonioregalado)
10:14 < kanzure> hmph he posted a photograph of his monitor displaying my webpage instead of a screenshot? wat
10:25 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=57c6af62 Bryan Bishop: add protective alleles for myocardial infarctions >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
10:25 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=8d5adc2c Bryan Bishop: add space genetics to same document >> http://diyhpl.us/diyhpluswiki/transcripts/2017-01-26-george-church/
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10:35 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=ae0c9938 Bryan Bishop: disable germline transmission, it was only there because of low mosaicism goal, not for inheritance >> http://diyhpl.us/diyhpluswiki/genetic-modifications/
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11:19 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=704e0f9c Bryan Bishop: forgot to save a few igem 2018 projects >> http://diyhpl.us/diyhpluswiki/dna/projects/
11:23 < kanzure> https://quillette.com/2018/11/29/academias-case-of-stockholm-syndrome/
11:23 < kanzure> "Science thrives by fostering what Feynman called a culture of doubt, not of consensus or signaling."
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12:04 < kanzure> ethics should be reformed into something like, allowing people to actually do things, and then having ethical norms about what to do when problems occur (unethical to freakout, support should be provided in some cases, etc).
12:04 < fenn> did you have a specific way of disabling germline transmission, or is it just a statement of wanting to have an option
12:05 < kanzure> well i was thinking gene drives
12:05 < fenn> i can never remember how that works
12:06 < fenn> something on one chromosome attacks the other chromosome?
12:06 < kanzure> another way (or same way?) is insert recombinant protein expression that will cut out the modifications if the cell detects that it happens to be a germline cell niche type..... but the downside is that the effectiveness of these techniques may be low and cause other genomic damage.
12:07 < fenn> hm ok
12:07 < kanzure> another way would be to disable fertility completely, in a way that is simple to rescue by IVF or whatever; which sounds a lot like involuntary sterilization but if you commit money to a medical fund for the child then maybe you can argue this is harmless.
12:08 < fenn> you could just not activate the editing system until a certain point in development, and wait for an external factor to be present. or instead of an external factor, try to sense the type of cell you're in
12:08 < fenn> they will hate you for diabling fertility for sure
12:08 < kanzure> ah, sure. tetracycline activation of genomic modifications. same concern about genomic damage. if you do everything upfront then you can assess the quality of the genome before implanting an embryo...
12:09 < fenn> the concern is that CRISPR doesn't work right and has off-target mutations?
12:09 < kanzure> well there's a few different problems to debug here
12:09 < kanzure> one is that the default use of CRISPR-Cas9 is double strand breaks.... it's up to the host cell to repair the break, which can happen minutes or hours later after cas9 has done its magic.
12:10 < kanzure> in addition to that, cas9 with its little sgRNA could conceivably select other (wrong) locations with some probability, which can be partly mitigated by checking the genome upfront beforehand, and partly mitigated by checking the results of any modification by checking in vitro with sequencing before implantation or whatever
12:11 < kanzure> if you are clever enough during the design phase then you can select a region for genomic insertion or modification (or whatever) that is less likely to cause cas9 to edit other areas of the genome
12:11 < fenn> yes but that shouldn't be an additional concern, because the genotype is the same
12:11 < fenn> you'd have to do it anyway
12:12 < fenn> the double strand break is a problem though
12:12 < fenn> did "Base Editor" have that problem?
12:12 < kanzure> dCas9 doesn't cause a double strand break, and it's useful for localizing a cytidine deaminase to that location on the dna molecule to edit the base pair or whatever.. but still same concerns about regexp fuzzy matching.
12:13 < kanzure> i pasted a link to a paper on that just earlier today,
12:13 < kanzure> 10:09 < kanzure> "Base editing generates substantial off-target single nucleotide variants" https://www.biorxiv.org/content/early/2018/11/27/480145
12:13 < kanzure> i'm really not seeing a future here for anything without gobs and gobs of sequencing before and after each edit attempt
12:14 < kanzure> maybe that will drive better synthesis tech.
12:18 < kanzure> .wik gene drive
12:18 < yoleaux> "A gene drive is a genetic engineering technology that can propagate a particular suite of genes throughout a population. Gene drives can arise through a variety of mechanisms. They have been proposed to provide an effective means of genetically modifying specific populations and entire species." — https://en.wikipedia.org/wiki/Gene_drive
12:19 < kanzure> "At the molecular level, an endonuclease gene drive works by cutting a chromosome at a specific site that does not encode the drive, inducing the cell to repair the damage by copying the drive sequence onto the damaged chromosome. The cell then has two copies of the drive sequence. ... the gene drive insertion in the genome will re-occur in each organism that inherits one copy of the ...
12:19 < kanzure> ...modification and one copy of the wild-type gene. If the gene drive is already present in the egg cell (e.g. when received from one parent), all the gametes of the individual will carry the gene drive (instead of 50% in the case of a normal gene)."
12:20 < kanzure> you could do crazy stuff like auto-apoptosis if the cell detects that it's a germline cell and that the modification is still present in the dna.....  during early development this should allow for correctly self-edited germline cells to outcompete the modified germline cells..... or it may kill the fetus who knows.
12:29 < fenn> it seems like it could work, but... i doubt the ethics people will have any of it, because there's still a small chance that you'd end up modifying the germline cell, if the self-censoring mechanism doesn't work
12:32 < fenn> say you have 1 out of 100 eggs with a faulty censorship gene, that will get passed down to the next generation with 1% probability, and then those people will pass the whole package to their kids, faulty censoring mechanism and all
12:32 < fenn> anyway i don't think it's worth making too many logical debates about all this stuff
12:32 < kanzure> also anything like this will get abused by companies that are trying to do stupid DRM shit
12:32 < fenn> the opponents of gene editing are not going to listen to a well constructed argument
12:33 < kanzure> agree, although if their concern is really about germline then technically there's very little about modifying *germline* cells that we actually care about-- other than the fact that it's the perfect full-body delivery vehicle.
12:33 < fenn> that gene encryption thing seemed even worse than DRM
12:33 < fenn> "happy 18th birthday, SURPRISE SMALLPOX!"
12:35 < kanzure> genecryption isn't worth it compared to advantages of ultra-safe cell line magic http://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/ultra-safe-cell-line/
12:36 < fenn> of course they don't really care about germline engineering, it's all a front for stopping human genetic engineering in general
12:36 < fenn> i mean, it's not the heritability that's what has them worried
12:36 < fenn> it's the fact that anyone can be anything
12:37 < fenn> "how will i be racist now?!"
12:37 < kanzure> some of them expressed concern about heritability- one of the questions in the jiankui he Q&A was from someone worrying that one of the girls might get married off to a wealthy family that wants HIV protection in their bloodline.  i think that's fine but apparently everyone gets upset by literally anything.
12:37 < fenn> oh noes, they might get married to someone wealthy
12:38 < fenn> we must save them!
12:38 < kanzure> out of all the concern trolling i didn't see anyone offering to fund the medical expenses of the twins... they expressed so much concern about their health but not any financial support. riiight.
12:38 < fenn> what medical expenses
12:38 < kanzure> i mean, i don't think it should be society's job to fund this guy's edited kids, but if they want to do something positive about it then they should pony up
12:39 < kanzure> well they are concerned about hypothetical medical problems and also ongoing testing and monitoring through childhood and into adulthood
12:39 < fenn> they're normal baseline humans, except for CCR5 knockout, which apparently does nothing important (as far as we know)
12:39 < fenn> the testing and monitoring was supposed to be paid for by the clinical trial
12:40 < fenn> to have been* (before all the drama)
12:41 < fenn> biorxiv always gives me a 404 when using dillo
12:42 < kanzure> the plos.org opinion article mentioned the idea of something like gp-write for embryo editing... sort of a universal project.... i'm not sure these anti-editors would find that appealing. haven't played with the idea enough.
12:42 < kanzure> fenn they are probably just assholes try modifying the user agent
12:42 < fenn> why would anyone scrape biorxiv with dillo as the user agent? it doesn't make sense
12:43 < fenn> anyway i didn't like the future world that plos.org article by mehta was trying to construct
12:44 < fenn> a whitelist of alleles you're allowed to edit, enforced by legal and professional penalties, with support of all countries in the UN
12:44 < fenn> and no incentive to make sure that this is the right whitelist, or any process to change it in the future
12:47 < kanzure> anyway the urls are easy to guess it's just wget https://www.biorxiv.org/content/early/2018/11/27/480145.full.pdf
12:48 < fenn> thanks lazyweb
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12:54 < fenn> hank greely is doing an acceptable job at being a professional ethics person
12:57 < kanzure> any ideas for something to put in the media to unite the pro-editing people together? maybe just announce an organization or something.
12:57 < kanzure> the anti-editing advocates are very well organized already
12:58 < fenn> i have no idea how these things actually get started
13:02 < kanzure> probably write a book, plan a conference, announce an advocacy organization. etc.
13:38 < kanzure> (warning: harry potter fan fiction) "Origins of magic: review of genetic and epigenetic effects" https://www.bmj.com/content/335/7633/1299
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14:11 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=4caebfa1 Bryan Bishop: transcript: junjiu huang (beta thalassemia embryo editing) >> http://diyhpl.us/diyhpluswiki/transcripts/human-genome-editing-summit/2018-hong-kong/junjiu-huang-beta-thalassemia-embryo-editing/
14:13 < gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=aec03bf3 Bryan Bishop: add tweeter link >> http://diyhpl.us/diyhpluswiki/transcripts/human-genome-editing-summit/2018-hong-kong/junjiu-huang-beta-thalassemia-embryo-editing/
14:18 < kanzure> a review of genome editing before crispr http://diyhpl.us/~bryan/papers2/bio/Genome%20editing%20BC%20(before%20CRISPR):%20Lasting%20lessons%20from%20the%20old%20testament%20-%202018.pdf
14:20 < kanzure> "Optimized base editors enable efficient editing in cells, organoids and mice" https://static1.squarespace.com/static/54d26ad7e4b0ea0c54e892ee/t/5ba998137817f72d16484111/1537841177912/nbt.4194.pdf
14:34 < kanzure> "SCN9A channelopathy associated autosomal recessive congenital indifference to pain: A case report" https://www.ncbi.nlm.nih.gov/pubmed/28494607 (scn9a knockout)
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15:43 < Jay_Dugger> "out of all the concern trolling i didn't see anyone offering to fund the medical expenses of the twins... they expressed so much concern about their health but not any financial support. riiight."
15:43 < Jay_Dugger> Best laugh I've had today. Good point.
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16:27 < kanzure> .tw https://twitter.com/james_ough/status/1068657489732882433
16:27 < yoleaux> @kanzure I also like the idea of setting up ionizers in the desert to increase rainfall (cheaper than desalination) +grow phytoplankton ... but ground-truth data seems kinda scarce, so it's hard to know how far you could scale it... http://carbon.ycombinator.com/desert-flooding/ http://newsfeed.time.com/2011/01/03/scientists-create-52-artificial-rain-storms-in-abu-dhabi-desert/ (@james_ough, in reply to tw:1068162710184038400)
16:28 < kanzure> (he is replying to the self-deployed kilometer-wide bubble disc concept for geoengineering earth temperatures)
16:31 < kanzure> for double strand break repair what you would really want is a cas9 protein that has the nuclease cutting activity but also captures both strands it just cut, and then later expose both strands to ligation once an insert is performed or whatever. unfortunately nobody is any good at novel protein engineering to this extent.
16:31 < kanzure> instead of just letting the strands float around aimlessly
16:34 < kanzure> he jiankui lab youku account https://i.youku.com/i/UMTQ0NTAyNjkyOA==?spm=a2h1n.8251843.0.0
16:34 < kanzure> list of followers https://i.youku.com/i/UMTQ0NTAyNjkyOA==/followers?spm=a2hzp.8244740.0.0
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16:57 < kanzure> i think "Dan 4973848482" goes to the same university https://i.youku.com/i/UNjEyNjIzNzAzNg==?spm=a2hzp.8253898.0.0
17:30 < kanzure> "The couple who quit told the Beijing-based LifeWeek magazine that He’s assistants promised “a high success rate proven in animal tests”, as well as the chance to “select the best from a number of genetically edited zygotes and embryos to have a healthier and smarter baby”."
17:30 < kanzure> "The Beijing News has reported that couples who agreed to participate were paid 280,000 yuan (US$40,000), on condition that they did not seek further compensation should the experiments go wrong."
17:37 < kanzure> "天行健，君子以自强不息"
17:38 < kanzure> from one of he's followers https://baike.baidu.com/item/%E5%A4%A9%E8%A1%8C%E5%81%A5%EF%BC%8C%E5%90%9B%E5%AD%90%E4%BB%A5%E8%87%AA%E5%BC%BA%E4%B8%8D%E6%81%AF
17:49 < kanzure> https://blog.ap.org/behind-the-news/aggressive-but-delicate-reporting-produces-gene-editing-scoop
17:53 < kanzure> .tw https://twitter.com/DocDellaire/status/1068670832732499968
17:53 < yoleaux> @antonioregalado @techreview Here is a handy list of US States with outright bans (or restrictions on state funding) of human fetal research for the budding gene-editing mavericks to avoid: @LandonGetz @FrancoiseBaylis http://www.ncsl.org/research/health/embryonic-and-fetal-research-laws.aspx https://pbs.twimg.com/media/DtSuRl5XoAIuGwv.jpg (@DocDellaire, in reply to tw:1068669803152461824)
17:57 < kanzure> clonaid/raelian stuff from 2002 https://www.wsj.com/articles/SB1041200630722499673
18:06 < kanzure> "P53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells" https://www.nature.com/articles/s41591-018-0050-6
18:10 < fenn> the list of states seems to be primarily related to the use of aborted fetuses, not byproducts of IVF
18:11 < fenn> this is leftovers from the embryonic stem cell research ban
18:12 < kanzure> "祝贺中国科学家贺建奎！ 明天我就开始对日本人胚胎的lysine methyltransferase 2A（KMT2A）基因的改造实验，希望制造出可以混用所有血型、并且自然免疫所有血液疾病的新人种——名字还没想好。"
18:12 < fenn> .tr
18:12 < yoleaux> Translate some text between languages
18:13 < kanzure> universal blood donor stuff
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--- Log closed Sat Dec 01 00:00:39 2018