--- Log opened Sun Jan 05 00:00:57 2020
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02:01 < adlai> TMA: 'no apologies, no explanations' - hunter s. thompson
02:03 < adlai> there's a reasonably effective parallel to "assume good faith", when dealing with potential trolls, where they are treated as a drunken tourist; you don't need their approval, should probably not take their money, and can be quite certain that they don't know the local meaning of half the idioms they learned yesterday
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08:51 < kanzure> .wik ecdysone receptor
08:51 < EmmyNoether> "The ecdysone receptor is a nuclear receptor found in arthropods, where it controls development and contributes to other processes such as reproduction." - https://en.wikipedia.org/wiki/Ecdysone_receptor
08:52 < kanzure> "The ban on enhancement, moreover, is vulnerable to even small defections because the disadvantages of defecting late will increase the incentives for non-defectors to follow suit, causing defections to cascade."
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09:00 < kanzure> .title https://web.archive.org/web/20070813010925/http://www.germline.ucla.edu/
09:00 < EmmyNoether> Human Germline Engineering - Implications for Science and Society
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09:58 < archels> https://spectrum.ieee.org/energy/environment/us-consumers-might-get-their-first-taste-of-transgenic-salmon-this-year
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11:00 < kanzure> "Tracking the time-dependent role of the hippocampus in memory recall using DREADDs" https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154374 (2016)
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11:56 < kanzure> 2020-01-03 interview with george church https://www.genengnews.com/insights/from-crispr-multiplexing-to-pleistocene-park-2/
11:58 < kanzure> "I would add to your list a fourth issue: CRISPR still does not do its job on target. I think its on-target sins are greater than its off-target sins. The base editors are not perfectly specific for a particularly base, and they're limited to transitions, A's to G's and C's to T's. It's very limiting. They're not the Holy Grail, which is precise editing. I think we should hold ...
11:58 < kanzure> ...that concept as our actual goal."
12:01 < kanzure> "I think the off-target problem has been overstated slightly. I'm partially responsible, because academically, it is a really cool problem that we know how to solve. We and others have published a lot of papers on this. But even in the very first papers, we were getting off-targets that were close to the spontaneous mutation rate. If you're going to worry about CRISPR, you should also ...
12:01 < kanzure> ...worry about the spontaneous mutation rate--which is very, very low."
12:02 < kanzure> "Germline does have three intrinsic advantages. First, it is better than other delivery systems at reaching all cells in the body. Second, after the first generation, it could be free rather than $2 million for somatic gene therapy. (So, like smallpox, an initial investment eventually results in equitable distribution if we work at it.) Third, germline goes through a single cell while most ...
12:02 < kanzure> ...somatic therapies impact millions of cells, any one of which could become cancerous. In a single cell, such an event is, a priori, a million times less likely, and if it is derived from a clonal set of cells, it could be checked by whole-genome sequencing."
12:02 < kanzure> ah so he finally admits that germline is better for delivery
12:02 < kanzure> "This is one of those things where I think it's better to worry too much than too little. . . . Just because it is polygenic doesn't mean it does not have a monogenic solution. For example, there are seven different clinical indications which are treated with somatotropin, human growth hormone--a single-gene product, in the midst of the most complicated genetics of almost any polygenic ...
12:02 < kanzure> ...trait, which is stature...."
12:03 < kanzure> "Finally, with intelligence in particular, there are a number of mouse experiments that show that two or three genes have enormous impact on either specific tasks or general tasks that would be categorized as cognitive enhancement. So, does it help putting blinders on or sticking our head in the sand and saying, "There's no way ...""
12:04 < kanzure> actual interview https://www.liebertpub.com/doi/10.1089/crispr.2019.29074.gch
12:44 < faceface> Thanks for this
12:45 < faceface> Unrealted, I started a nootropics forum.. I know there are probably others....
12:45 < faceface> https://forum.ragerage.life
12:46 < faceface> I'm thinking to start an NMN MLM company, and this is a way to build a community. Please feel free to use it if it's usefull
12:48 < faceface> kanzure: that link links to an article behind a paywall
12:48 < faceface> where is the best place to grab stuff like this these days?
12:48 < faceface> ... (when I'm not at work that is ;-p
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13:00 < faceface> Not sure how to reach out to other life-hacking communities to spam my forum. Any suggestions welcome.
13:08 < LeoTal> faceface: In my experience/literature search, most nootropics are either useless or ridiculously dangerous, and the exceptions are already well-known to the mainstream, like sugar and caffeine. Anyway this is why I refer to a croissant and coffee as "my nootropic stack"
13:13 < kanzure> faceface: http://sci-hub.se/
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16:39 < maaku> LeoTal: eh, caffeine would be a scheduled substance if it wasn't (a) naturally occuring in normal concentrations and (2) so heavily embedded in culture
16:40 < maaku> amphetamine has fewer side effects at comparable dosages than caffine, for example
16:43 < LeoTal> I've observed tolerance building up much faster than for caffeine but that's confounded by people using silly dosages and schedules
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21:31 < nmz787> maaku: eh, caffeine withdrawl doesn't seem to send people to crime
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22:16 < maaku> nmz787: neither does adderall withdrawal in therapudic doses
22:33 < superkuh> The mechanisms of action are somewhat clear and make the current status quo seem sane. Adderall will increase wanting dis-proportionally to liking for cotemporal stimuli. Caffeine doesn't effect reward prediction directly like adderall does and doesn't have this effect.
22:39 < maaku> superkuh: I'm pretty sure the mechanism is similar if not identical and it's just a matter of dosage. but I don't have studies to point to
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23:25 < fenn> i'd like to know what nootropics are "ridiculously dangerous"
--- Log closed Mon Jan 06 00:00:58 2020