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Physicist, Startup Founder, Blogger, Dad

Sunday, November 17, 2013

CRISPR

This looks like a huge development. Video. See also here, and this talk (audio) by Harvard graduate student Patrick Hsu (no relation; recent paper in Cell; genome-engineering.org).


Independent (UK): Scientists are calling for a wider public debate on a new development in genetics that could allow the simple and accurate manipulation of the human genome, as revealed yesterday by The Independent.

The technique, known as CRISPR, could revolutionise human gene therapy and genetic engineering because it allows scientists for the first time to make the finest changes to the DNA of the chromosomes with relative ease.

One Nobel scientist, Craig Mello of the University of Massachusetts, said that the “jaw dropping” technique has the potential to transform the study and manipulation of genes and “lowers the barrier” to genetic engineering of human IVF embryos – something he would oppose.

Professor George Church of Harvard University, who was the first scientist to get the process working in human cells and mouse embryos, said that it was important to air the social and ethical implications of the technique to the wider public.

“Talking about the future is better than letting it sneak up on us. We need to do more of this or we will be left with very limited vocabulary in the space between positive and negative hype,” Professor Church said. ...

The CRISPR technique has developed rapidly since last year when Jennifer Doudna and her colleagues at the University of California, Berkeley, first demonstrated how it can be used in genetic engineering.

Scientists have since shown that it works well on human cells and mouse embryos and are talking about the possibility of refining it for gene therapy trials on patients with HIV and inherited disorders such as sickle-cell anaemia and Huntington’s disease.

Professor Dagan Wells, an IVF researcher at Oxford University, said that although there is still a long way to go before CRISPR could even be considered for use on IVF embryos, the technique could overcome many of the objections to permanently altering the germline of families affected by inherited disorders

“If the new method is as precise as has been suggested then concerns about inducing inadvertent, detrimental changes to the genome might start to subside. In that case, permanently fixing a lethal genetic defect might not seem so controversial,” Professor Wells said.

“However, I'm sure there will be some concern about the possibility that the technology could be used for 'enhancement' rather than repair, veering from medicine towards eugenics,” he warned. ...

41 comments:

Kudzu_Bob said...

I have a bad feeling about this. I also have a good feeling about this.

twoL said...

So the obvious implication here is that once we have the data on the genetic architecture of intelligence, we will also have a reliable way of manipulating specific parts of the genome. How long till we get a baby designed to be +4 SDs in IQ, blue eyed, and with no significant genetic health risks?

LondonYoung said...

Our generation is the last that will get to hide hypocrisy about what we value. Everyone will be asked about their children, and they will answer. The games of liberals talking about public education while sending their kids to private schools will seem a child's game.

oregonlocal said...

I for one welcome the rule of our new genetically engineered ubermenschen.

Diogenes said...

i would welcome it too. BUT "it's not gonna happen." if you've been reading this blog long you'd know why. why? because the number of genes which affect iq and other desirable traits is of the same order of magnitude as the TOTAL number of genes. are these manipulations capable of changing 10,000 genes in one genome? and god knows the probability that such a manipulation, were it possible, would result in non-viable embryos is so close to 100%, it's not worth trying.


ONLY embryo selection will do the job. that is, eugenics at the embryo stage. BUT even here the results will depend on the number of embryos one can select from. LIKELY that at first it will just assure smart parents that all of their children will be smart rather than some.


genes for iq are like genes for physical beauty. iq and beauty are an orchestra and a symphony not a piano concerto.

Diogenes said...

way too optimistic LY.


my own family is an example of pure breeding for blue/green eyes. no known brown eyed direct relatives. why not the same for iq or physical beauty? because the number of genes is far greater for these.



BUT still, even my benighted alcoholic brother has a masters in civil engineering and is one of the world's best video game players (is that g-loaded?). just as iq is LESS heritable for children with high iq, there is considerable variability in the degree of regression to the mean.

Diogenes said...

gordon gecko (oliver stone) said, "lunch is for whimps." i say, "feeling is for whimps."


the ONLY reason why there is worry about this is the experience of national socialism and its identification with absolute evil by mass media (for obvious reasons---wink, wink). BUT hitler was also an animal lover, a tree hugger, etc. (in his "myth of the 20th c", alfred rosenberg even came up with the absurd excuse for german peoples' retarded development (compared to romans and greeks) that germans loved nature more.)

Shawn said...

"People say it would be terrible if we made all girls pretty. I think it would be great." - James Watson.

I agree wholeheartedly.

5371 said...

It's clear you don't recognise the overwhelming majority of humans - who will never produce genetically modified offspring - as belonging to the same species as you. They should draw the appropriate conclusions.
Breathless excitement like this erupts twice a year, if not more frequently. I expect nothing to come of it.

Diogenes said...

ly was born with low empathy, quite unlike buffet (whom ly resents as a cheat). buffet has expressed the view NO ONE else in the public eye has ever expressed to my knowledge. despite his "folksiness" it shows the man is a genius, as celebrities go anyway. that view: that talent should not be regarded any differently from inherited wealth or privilege.



conservatives explain differences in outcomes by differences in virtue. the liberal straw man for conservatives denies differences in virtues innate or otherwise and makes excuses for everyone. HA! (clinton has said he had brains and his brother didn't. obama is hbd aware as exemplified by this quote, " "). the real difference isn't a cognitive one or a matter of interpretation or matter of how knowledgeable one is. the real difference is empathy.

Hacienda said...

I don't want a 4 sigma retard. I want a baby with 10 sigma with 10 arms in perfect coordination and able to f+ck with
at 20 in dick while traveling in a FTL ship. Then I want this baby to give me the same powers.

steve hsu said...

To get an SD change in g you only need to alter of order sqrt(10k) alleles. Actually the number is even less than that because the minor allele frequency p of causal alleles could be much smaller than 0.5 on average -- 1 SD ~ sqrt(p 10k).

oregonlocal said...

With fewer alleles of high effect to manipulate would it not be more efficient to modify germ line cells rather that embryos? Then fertilize these and gestate them in the proverbial "test tubes" of Brave New World.

oregonlocal said...

Dog and cattle breeders are always talking about certain traits that "breed true" so I assume that some traits are more inclined to show up in subsequent generations than others.

Richard Seiter said...

Depending on exactly what can be done with CRISPR why not do both? Take a selection of germ line cells (both sperm and egg) and modify them for selected attributes. Then combine and take resultant embryos and select for other traits (e.g. make sure no nasty homozygous disease mutations).


One thing nobody seems to talk about is selecting for different HLA variants. Given how much variability there is here and how highly selected for this area seems to be I would think it a logical candidate. This is actually one I worry about. A monoculture could be disastrous.

Bobdisqus said...

Diogenes,

This is so seldom acknowledged by the right hand tail of the curve by either left or right on the political spectrum.

Thank you

AG said...

Wow, gene therapy is reality now. Just imagining all potentials including IQ, athletic ability, even height.
Then no body will argue against IQ with genetic base any more since low IQ people have chance what nature give to them.

Aaron Sheldon said...

REGEX for DNA?


But before we start talking LALR parser generators for DNA mark-up the whole process still begs the question:


How do you safely transfect embryos with the CAS92 protien and RNA package? Let alone transfecting a whole human.

dxie48 said...

"In vitro REGEX for DNA?"

http://www.washington.edu/news/2013/09/30/uw-engineers-invent-programming-language-to-build-synthetic-dna/
"UW engineers invent programming language to build synthetic DNA"

Underachiever said...

It would be even easier if Cochran is right and that the dominant variant of the gene which sometimes causes torsion dystonia also boosts intelligence. One gene change leads to a 10 IQ point increase over their siblings (plus a chance of having a debilitating disease). Unfortunately this disease is dominant.

One of the recessive diseases which probably boost IQ among Ashkenazi Jews (Gaucher's, Tay-Sachs, etc.) could give us all of the benefits of improved IQ with little or no downside. Also with this method, very few genes would have to be altered.

Diogenes said...

and what part of the high correlation between twins is due to sharing the same womb and the same genes x womb environment effect? that is, whatever the womb the high correlation might still obtain, but the difference between smart and dumb might not be genes per se but the right and wrong wombs for those genes.

Diogenes said...

steve has the mathematical talent and sophistication to answer this. perhaps it's obvious, but my guess is, without thinking about it, that the more genes are involved in determining a trait the less likely there will be pure breeders, the greater the tendency to "regression", to use it in two senses.

one sad story:

one of the findings of terman was that those of his subjects (childhood iq > 140) who came from humble backgrounds tended to have relatively stupid siblings. so conservatives might conclude that these were "sports" http://www.thefreedictionary.com/Sport+%28biology%29 whereas the higher class children were true breeders.

my dad had a friend at the da's office who later became da. his wife was an md. but their son was "not so bright", and he explained this as not so surprising, as regression to the mean.

and ol, you're half right. my parents' marriage was a bit of a mesalliance. (my dad was hypogamous.) my mother's father was a moonshiner (or rather a transporter/distributor of moonshine) in his youth (the 20s), and he spent a year in prison for bookmaking. but then again two of her cousins on her father's side became profs. one in romance languages, the other in fluid dynamics. that one is in who's who and turned down an offer from stanford because it had rejected his daughter.

Diogenes said...

right. there will be some alleles with more effect than others, but studies to date have found no "super" genes? perhaps they missed these purported ashkenzai super genes.

Diogenes said...

but, as lenin said, "to each according to his ability, from each according to his need" is wrong too. but it seems in reading the bios of the very rich and self-made that as that rare gentile media mogul kluge said, "work really isn't work for me. i've never like the weekend in my life." or, there is a limit on how far one can go doing things one hates to do. as buffet has said, "the greatest luxury is to be paid for what you would pay to do." buffet knows he's been lucky, in that, the one thing he most likes to do is rewarded like nothing else.

Diogenes said...

but, as lenin said, "to each according to his ability, from each according to his need" is wrong too. but it seems in reading the bios of the very rich and self-made that as that rare gentile media mogul kluge said, "work really isn't work for me. i've never like the weekend in my life." or, there is a limit on how far one can go doing things one hates to do. as buffet has said, "the greatest luxury is to be paid for what you would pay to do." buffet knows he's been lucky, in that, the one thing he most likes to do, and has a talent for, is rewarded like nothing else.


speaking (somewhat) figuratively: predestination and justification by works are an antinomy. a few centuries ago it was theological. now it's political.

Diogenes said...

and if there are any human pure-breds, the british aristocracy would be it, because it was smaller than other aristocracies. the common wisdom is that this group is inbred and shared with other inbred groups madness, imbecility, ugliness, etc. but there might also be wisdom in what one duke said:


"when you're a duke everyone assumes you're an idiot, but when they discover that you're not they give you credit for being much more intelligent that you are."


or maybe if you're a british peer and not an idiot maybe you ARE pretty smart.

steve hsu said...

Heritability can be studied now in populations of unrelated individuals (regress phenotype similarity in pairs against genetic similarity as measured by SNPs). The results are consistent with the much earlier estimates from twins studies. So it doesn't seem that the shared womb is a big effect.

5371 said...

Might still be a huge effect from individual to individual, even if it levels out over populations.

AG said...

Also personality defect, psychopath, criminal behavior might have genetic basis. Then this breakthrough will take care of them.

Underachiever said...

If these studies were done on representative western populations, these genes would have been missed because many of these variants are rare even among Jews who are themselves a small fraction of western populations. Even among studies with only Jewish subjects, it would be difficult to find these effects unless the study was designed to look for them in particular (e.g. compare heterozygotes with homozygote siblings).

We do have this information however:

"Professor Ari Zimran, who heads the Gaucher Clinic at the Shaare Zedek Medical Centre in Jerusalem, furnished us a list of occupations of 302 Gaucher patients. Because of the Israeli medical care system, these are essentially all the Gaucher patients in the country. Of the 255 patients who are not retired and not students, 81 are in occupations that ordinarily average IQ’s greater than 120. There are 13 academics, 23 engineers, 14 scientists, and 31 in other high IQ occupations like accountants, physicians, or lawyers. The government of Israel states that 1.35% of Israeli’s working age population are engineers or scientists, while in the Gaucher patient sample 37/255 or 15% are engineers or scientists. Since Ashkenazim make up 60% of the workforce in Israel, a conservative base rate for engineers and scientists among Ashkenazim is 2.25% assuming that all engineers and scientists are Ashkenazim." From: http://web.mit.edu/fustflum/documents/papers/kim-beder.pdf

Unfortunately, the Gaucher's patients are the homozygotes. Colchran cites a study in the linked paper where patients with Torsion Dystonia were smarter than their siblings; however, the sample size was quite small which is not surprising given the rarity of the disease.


I encourage everyone to read the Cochran paper as I think the evidence is pretty clear cut. Given the fact that medical, military, and educational records are all presumably known to the Israeli government, I wouldn't be surprised if such a study had already been done surreptitiously.

Kudzu_Bob said...

Unless it is the psychopathic criminal defectives who end up in possession of this technology.

Riordan said...

Can anyone pinpoint the original "paper 0" (aka the one where the light bulb first went off about connecting the dots between a random bacterial protein and genome editing)? My head is still spinning trying to go through all those exhaustive links.

Emil Kirkegaard said...

Why do critics focus on MZT-DZT studies? ALL the pedigree studies give similar results. For the non-genetic hypothesis to be true, every single pedigree method that has been tried so far has to be wrong due to some other influence. It's not going to happen and as Steve points about as well, modern methods don't need pedigree study assumptions. See:

http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.0020041

Cornelius said...

Just to play Devil's advocate..what of the benefits we get from individuals who are only part of the way down the psychopath or criminal spectrum?

Richard Seiter said...

To me this illustrates the scary side of (potential) genetic engineering. Who decides what constitutes a defect? Will they demonstrate judgment as good as those who dictate federal dietary recommendations? ;-/ I lean towards the let the individuals decide view, but what if someone wants to strive for a psychopathic (destructively so, not borderline) genius.

Diogenes said...

and the % variance explained = rho is a bit misleading. if one imagines his own iq is drawn from a population of clones, then with rho = 69%, if one scores 2 sds above the mean the likelihood his twin will score > 133 is only 2.5%. high iq people, your own high iq is not so much due to your genes.

Diogenes said...

wrong d. that should have been the chance your twin has an iq > 138 is only 5%. but the point is the same. the models which speak of heritability as if it were meaningful, require that the very smart (many of whom belong to the elite)have been lucky.

Diogenes said...

and the chance your twin has an iq < 103 is also 5%.

ben_g said...

Won't genetic similarity also covary with maternal behaviors that effect the womb?

ben_g said...

Not to mention that some of the assumptions favor the environmental side (e.g. MZ twins having identical genes)

Alex said...

This may seem like a dumb question but I'm not a scientist. Gene therapy changes the genes of an embryo without killing it, right? If that's the case then it's going to be revolutionary: it would make humans evolve in a somewhat Lamarckian way.

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