Re: Guest Post - Asilomar, zinc-fingers, etc

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Related, no Science subscription needed. The technology is very impressive.


Posted by: ydnew | Link to this comment | 03-30-15 6:31 AM
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If everybody can not have cystic fibrosis, I won't feel special anymore.


Posted by: Moby Hick | Link to this comment | 03-30-15 6:32 AM
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It was a big week for science news last week. Between RoundUp's listing as a likely carcinogen, approval of GM potatoes and apples, Biogen's (fingers-crossed) promising Alzheimer's drug candidate, and the ability to genetically engineer primates, I've been struggling to keep up.


Posted by: ydnew | Link to this comment | 03-30-15 6:37 AM
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This relates to my one decent scholarly publication, so I will promote it a little.


Posted by: rob helpy-chalk | Link to this comment | 03-30-15 6:42 AM
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Moby Hick invited you to join their network on ResearchGate and confirm authorship of your publications.

Germ-line enhancement of humans and nonhumans


Posted by: Moby Hick | Link to this comment | 03-30-15 6:53 AM
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The In the Pipeline comments to this are frightening. The chemistry blog's normally staid comments section of people whining about drug company management has been taken over by techno-futurists.

We have taken a look at a family member's exome and it was terrifying. There were hundreds of serious mutations (including stop loss, stop gain, frameshift), thousands of missense mutations, and many very rare disease hits.
When mainstream society appreciates the extraordinary level of genetic errors in typical people, there will be no longer be any argument about the necessity of genetic engineering.
It is unlikely that many would agree to marry if they carefully analyzed their partner's genome.

Posted by: Cryptic ned | Link to this comment | 03-30-15 6:56 AM
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I wish people would hurry the fuck up and engineer a transgenic green-flourescing human.


Posted by: Sifu Tweety | Link to this comment | 03-30-15 6:58 AM
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If everybody can not have cystic fibrosis, I won't feel special anymore.

I'm surely not the only person who first turns to the "Losses in the DHC/your-college-here Family" section of the alumni magazine in order to be sure to come across someone who I feel I am doing better than.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 6:59 AM
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I initially read this as "German editing of the genome in human embryos" and thought, at it again, are they?


Posted by: Jesus McQueen | Link to this comment | 03-30-15 6:59 AM
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6: I read In The Pipeline regularly, and while I appreciate the posts, the comment section is frequented by libertarians. The prevailing tenor comments on the gene editing post doesn't surprise me at all.


Posted by: AcademicLurker | Link to this comment | 03-30-15 7:00 AM
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There's an editing/"murder your darlings" jole in here somewhere.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:01 AM
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The good news is that we have invested wisely in the institutions necessary for the kind of highly functional national political dialogue a subject like this requires.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:03 AM
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11: - l +k

I blame my exome.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:05 AM
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"Jole" is itself an editing jole.


Posted by: essear | Link to this comment | 03-30-15 7:06 AM
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10, I don't think they're libertarians so much as your average UMC white male. Someone has shown up recently pushing the Howard Roark philosophy, and the general response is "If you think big businessmen are all smart you've either never met one or you're lucky enough to be one, so fuck off".


Posted by: Cryptic ned | Link to this comment | 03-30-15 7:06 AM
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I don't think they're libertarians so much as your average UMC white male.

You're likely right. Although it's depressing how much overlap there is.

As for gene editing, on the one hand the tendency of engineered higher organisms to have weird unexpected health problems aught to do a good job of discouraging people from trying it on their own kids anytime soon. On the other hand, there are enough sketchy people in the world that I suppose someone is bound to try it.


Posted by: AcademicLurker | Link to this comment | 03-30-15 7:16 AM
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They'll try it on other peoples' kids first.


Posted by: Moby Hick | Link to this comment | 03-30-15 7:17 AM
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Is the machine that you use to edit the human genome* in embryos really called the CRISPR? Like what keeps kale fresh? "Put your fetus in the CRISPR, he'll find girlriends on the TINDR"

*n.b. -- I have no idea what this means.


Posted by: T"R"O | Link to this comment | 03-30-15 7:25 AM
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Yes, if you think that acronym is bad you should meet fly geneticists and NMR scientists.
I don't know how much I should comment on this since I personsly know and work with several of the players.


Posted by: SP | Link to this comment | 03-30-15 7:27 AM
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I'm going to assume that 6 is a joke, because the alternative is too terrifying.


Posted by: Walt Someguy | Link to this comment | 03-30-15 7:27 AM
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15/6: No, I think it's a little more libertarian than the UMC white male chemists I know in real life. Also, chemists generally really, really suck at understanding nuances of biology, so it doesn't surprise me that this topic would lead to weirder than normal discussion.


Posted by: ydnew | Link to this comment | 03-30-15 7:30 AM
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CRISPRs are repeating DNA sequences that were discovered in bacteria. Later it was found that they are incorporated into enzymes (e.g. "Cas9") for the purpose of cutting similar DNA sequences out of the genomes of viruses that infect bacteria.

It stands for "clustered regularly interspaced short palindromic repeats".


Posted by: Cryptic ned | Link to this comment | 03-30-15 7:31 AM
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19: Or people who name clinical trials.


Posted by: ydnew | Link to this comment | 03-30-15 7:31 AM
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palindromic repeats

A man, a plan, A CAnal. Panama.


Posted by: Moby Hick | Link to this comment | 03-30-15 7:35 AM
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A GATTACA, TGTAATC T.
Damn four letter alphabets.


Posted by: SP | Link to this comment | 03-30-15 7:38 AM
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A man, a plan, AC, anal. Panama!


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:39 AM
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from the link in 6

I'm pretty sure if we don't use it, it's going to be done in China and South Korea (and elsewhere).

I hate the way this argument combines "Everybody's doing it" with xenophobia and nationalism.

On the other hand, I like the idea that Cold War rhetoric would transfer over into a race for beauty. "The South Koreans have a modification that makes your ass 50% firmer. Mr President, we must not allow a sexy-booty gap!"


Posted by: rob helpy-chalk | Link to this comment | 03-30-15 7:42 AM
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Doh! I never made that connection. Not that I'd ever spent more than 2 seconds thinking about that move.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:43 AM
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The South Koreans are way ahead of everyone on large-scale modification of the population's appearance by surgery.


Posted by: essear | Link to this comment | 03-30-15 7:45 AM
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Kurt Vonnegut on to that kind of thing in his (not very good at all) Slapstick (summary from Wikipedia):

In the meantime, Western civilization is nearing collapse as oil runs out, and the Chinese are making vast leaps forward by miniaturizing themselves and training groups of hundreds to think as one. Eventually, the miniaturization proceeds to the point that they become so small that they cause a plague among those who accidentally inhale them, ultimately destroying Western civilization beyond repair.
Lonesome No More!


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:46 AM
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30: Written in 1976 I meant to add.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 7:46 AM
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29: Plus, most of them have the same name.


Posted by: Moby Hick | Link to this comment | 03-30-15 7:48 AM
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3,4. I'm hoping for better plants sooner as a consequence. The eventual eugenics experiments (which I think yes likely will be in China or South Korea) will I think be pretty pointless-- most of the phenotypes people care about tuning are pretty complex. Increased height is a pretty popular choice though, maybe that will be commercially available.

Jennifer Doudna, who discovered/created the protein/RNA complex that does this, is a great speaker. The technologically relevant system differs from the bacterial defense Ned describes, in being able to cut and modify at a location defined by a selected synthetic RNA rather than just at the evolved targets present in the bacterial systems.


Posted by: lw | Link to this comment | 03-30-15 8:33 AM
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Increased height is a pretty popular choice though, maybe that will be commercially available

Based on the experience of a friend who many, many years ago worked in a lab where they were testing human growth hormone, I would say it would be very popular. Probably too popular.


Posted by: JP Stormcrow | Link to this comment | 03-30-15 8:58 AM
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34: A height arms race would be pretty amusing.


Posted by: AcademicLurker | Link to this comment | 03-30-15 9:11 AM
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Or an arms arms race.


Posted by: heebie-geebie | Link to this comment | 03-30-15 9:13 AM
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35: Making it even more difficult for some of us to find comfortable chairs and clothes that fit. Real fucking amusing. At least we can count on the airline industry to fight it.


Posted by: Jesus McQueen | Link to this comment | 03-30-15 9:15 AM
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Can you imagine the lobbying as different kinds of companies make their case that people should be engineered in their favor?


Posted by: heebie-geebie | Link to this comment | 03-30-15 9:18 AM
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Think of 38 as a prompt.


Posted by: heebie-geebie | Link to this comment | 03-30-15 9:18 AM
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Without going into too much detail, let me just say that the IP arms race around the patents for this is going to be awesome- some expert witnesses are going to get very rich @ $500/hour.
One technical issue here is that knockout is pretty easy, homologous recombination ("knock-in") of a desired gene is currently pretty poor, I think 1-5% efficiency. So if you have a disease allele that can be destroyed as a cure with no other loss of function (e.g. certain blood cancers) great. If you want to repair a misfunctioning gene by replacing it with a good sequence, tougher. If you want to alter a bunch of genes for a polygeneic train, no, not going to happen with current capabilities. OTOH there are interesting physical things you can do e.g. taking off the brakes of certain traits like with myostain (google for images of very buff bulls.)


Posted by: SP | Link to this comment | 03-30-15 9:19 AM
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The six million dollar man is only 3x the replacement value of a human life per govt cost/benefit analysis (govt sets alue of humnan life at roughly $2 million per life). So if we eliminated 2/3 of the population and made the rest bionic, we solve the overpopulation crisis, and create fewer, but more awesome (because bionic) humans, for no net additional cost other than the transition costs of murder and making the human remnant bionic. Maybe we should kill 3/4 of the population so it nets out.


Posted by: TRO | Link to this comment | 03-30-15 9:20 AM
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That should be myostatin, not myostain.


Posted by: SP | Link to this comment | 03-30-15 9:21 AM
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What's a good concise way to indicate that a statement is opinion rather than certainty?

pretty pretty pretty in 33. Writing without the qualifiers sounds apodictal, pushy. "Quite" or "rather" both sound stuffy. Maybe kind of, or using an alternative verb - lean or incline.

An opportunity for new punctuation, or possibly like the 18th century thing where italics indicate emphasis. Possibly an emoticon to indicate hand waggling.


Posted by: lw | Link to this comment | 03-30-15 9:21 AM
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$32M man after inflation from when the show started in 1973.


Posted by: SP | Link to this comment | 03-30-15 9:22 AM
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Yes but technology costs have also come down since 1970s, plus economies of scale.


Posted by: TRO | Link to this comment | 03-30-15 9:25 AM
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No one's going to buy it then, why get an implant when you can wait 18 months and get one twice as good.


Posted by: SP | Link to this comment | 03-30-15 9:27 AM
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"Will want to" misses a core element of the eliminate 3/4 of the population, make the remaining 1/4 bionic plan.


Posted by: TRO | Link to this comment | 03-30-15 9:38 AM
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Oh hey someone important is getting lunch down the street- speculation is POTUS or Badass Biden.


Posted by: SP | Link to this comment | 03-30-15 9:39 AM
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If Biden gets extensive lifespan-extension genetic modification, that should put him ahead of Hillary in the 2016 race.


Posted by: Cryptic ned | Link to this comment | 03-30-15 9:46 AM
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On the other hand, there are enough sketchy people in the world that I suppose someone is bound to try it.

Or people who have a 1 in 4 chance of losing every baby they conceive.

My partner and I still don't know which gene we both carry a recessive mutation for that gives our children hydrocephalus. But if we knew and could change it in our embryos? We would.

The other choice, if you know the problem is to make a lot of embryos and only put back the ones without the double mutation. Or test the fetus and end the pregnancy, 25% chance each time. The cell-free DNA tests are starting to test for single gene disorders, which is really helpful. But we're talking tons of tech and sorrowful choices no matter what option we pursue.


Posted by: Megan | Link to this comment | 03-30-15 9:53 AM
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I am pretty sure the situation you are in Megan is the same for friends of mine who haven't yet managed a healthy pregnancy and it is indescribably heartbreaking. So so so happy you have a healthy young one!


Posted by: dairy queen | Link to this comment | 03-30-15 10:44 AM
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Heh. I killed the blog. Brave work, dairy queen.

Yeah, having the healthy one is as great as I expected.


Posted by: Megan | Link to this comment | 03-30-15 10:53 AM
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Congratulations on a healthy kid, and sympathies on the difficult position.

The only other things I can think of writing are basically advice on finding the relevant gene, but I'm not an MD and don't see clear candidate genes in the literature, so this won't be great reading.

It's pretty clear there's no strongly associated SNP, which is the kind of variation that the 23-and-me style assays can detect. Consequently, whole genome sequencing (more expensive and difficult to interpret than SNP calls, unfortunately) might be something to discuss with a good genetic counselor or your doctor. Looking for a deletion or CNV that you both share is similar to assessments of individual variation that are increasingly being done for some cancer patients. I can send more info if you're interested in thinking about this line of tech and don't have anyone already discussing this option with you.



Posted by: lw | Link to this comment | 03-30-15 11:19 AM
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Oh, we've had the four of us sequenced (exome only) already. That was a year ago, at Yale. But after hearing that the sequencing was done, the analysis must have stalled because they haven't told us anything in a year. We sent Yale our fifth sample (healthy!) in November, so maybe that'll be the key? But Yale doesn't appear to be in any hurry to get news to us. I have started the relentless friendly phone calls.


Posted by: Megan | Link to this comment | 03-30-15 11:33 AM
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Yeah, having the healthy one is as great as I expected.

Not to (badly) VTSOOBC, but that's a good looking baby.


Posted by: Turgid Jacobian | Link to this comment | 03-30-15 11:47 AM
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Re the OP, unlike the lede, "Asilomar" conjured up "asilon" for me. An Unfogged-centric view of the world.


Posted by: bill | Link to this comment | 03-30-15 12:26 PM
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I'm touched! I definitely stumbled over reading it.


Posted by: asilon | Link to this comment | 03-30-15 9:57 PM
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