Wednesday, August 13, 2014

Designer babies: selection vs editing



The discussion in this video is sophisticated enough to make the distinction between embryo selection -- the parents get a baby whose DNA originates from them, but the "best baby possible" -- and active genetic editing, which can give the child genes that neither parent had.

The movie GATTACA focuses on selection -- the director made a deliberate decision to eliminate reference to splicing or editing of genes. (Possibly because Ethan Hawke's character Vincent would have no chance competing against edited people.)

At SCI FOO, George Church seemed confident that editing would be an option in the near future. He is convinced that off-target mutations are not a problem for CRISPR. I have not yet seen this demonstrated in the literature, but of course George knows a lot more than what has been published. (Warning: I may have misunderstood his comments as there was a lot of background noise when we were talking.)

One interesting genetic variant (Lrp5?) that I learned about at the meeting, of obvious interest to future splicers and editors, apparently conveys an +8 SD increase in bone strength!

My views on all of this:
... given sufficient phenotype|genotype data, genomic prediction of traits such as cognitive ability will be possible. If, for example, 0.6 or 0.7 of total population variance is captured by the predictor, the accuracy will be roughly plus or minus half a standard deviation (e.g., a few cm of height, or 8 IQ points). The required sample size to extract a model of this accuracy is probably on the order of a million individuals. As genotyping costs continue to decline, it seems likely that we will reach this threshold within five years for easily acquired phenotypes like height (self-reported height is reasonably accurate), and perhaps within the next decade for more difficult phenotypes such as cognitive ability. At the time of this writing SNP genotyping costs are below $50 USD per individual, meaning that a single super-wealthy benefactor could independently fund a crash program for less than $100 million.

Once predictive models are available, they can be used in reproductive applications, rang- ing from embryo selection (choosing which IVF zygote to implant) to active genetic editing (e.g., using powerful new CRISPR techniques). In the former case, parents choosing between 10 or so zygotes could improve their expected phenotype value by a population standard de- viation. For typical parents, choosing the best out of 10 might mean the difference between a child who struggles in school, versus one who is able to complete a good college degree. Zygote genotyping from single cell extraction is already technically well developed [25], so the last remaining capability required for embryo selection is complex phenotype prediction. The cost of these procedures would be less than tuition at many private kindergartens, and of course the consequences will extend over a lifetime and beyond.

The corresponding ethical issues are complex and deserve serious attention in what may be a relatively short interval before these capabilities become a reality. Each society will decide for itself where to draw the line on human genetic engineering, but we can expect a diversity of perspectives. Almost certainly, some countries will allow genetic engineering, thereby opening the door for global elites who can afford to travel for access to reproductive technology. As with most technologies, the rich and powerful will be the first beneficiaries. Eventually, though, I believe many countries will not only legalize human genetic engineering, but even make it a (voluntary) part of their national healthcare systems [26]. The alternative would be inequality of a kind never before experienced in human history.

Here is the version of the GATTACA scene that was cut. The parents are offered the choice of edited or spliced genes conferring rare mathematical or musical ability.

27 comments:

weiner_dawg said...

I like this future, but I have a few concerns...

1. Will this lead to dangerous homogenization of human DNA over time? Supposedly Amerindian homogeneity contributed to their mass die-offs from disease.

2. When we begin splicing, at what point will people become unmotivated to reproduce? When the child is less than 50% of its parents' DNA?

3. If future children are mostly non-parental spliced DNA (and everyone is highly similar due to generations of homogenization) who will bother to have children?


Dystopian potential: Governments growing children in vats and raising them without the need for family.

steve hsu said...

Alpha children wear grey. They work much harder than we do, because they’re so
frightfully clever. I’m really awfully glad I’m a Beta, because I don’t work so hard.
And then we are much better than the Gammas and Deltas. Gammas are stupid.
– Brave New World, Aldous Huxley

Ricky said...

I don't want to live in a future where babies are treated as products that you want to configure, as if you were ordering a Lenovo or Apple computer. What happens when people design their babies to have certain genes, and then the kids grow up not living up to their parents' expectations? When you treat something as a product, they stop being the gift that they really are. When you save enough money to buy the computer of your dreams, it's not a gift. And what happens when something goes wrong and the baby doesn't have the genes they were supposed to have, and you're already pregnant. Just abort, of course. After all, the baby is just a product. You can cancel the order and order another one.

Shawn said...

So with splicing or gene editing, how can inbreeding be avoided for future generations if those future generations decide not to undergo editing? This of course assumes that certain gene varients are especially popular with parents. Maybe there will be some sort of massive computer database to prevent this?

Shawn said...

So in GATTACA there's a scene where there's an amazing piano player with 6 fingers. I suppose it will be possible to create all sorts of weird mutations. Perhaps future MMA fighters will have 4 arms like Goro http://en.wikipedia.org/wiki/Goro_(Mortal_Kombat)

5371 said...

Just the idiotic name CRISPR is a strong hint that this enterprise has closer links to "tech startups" (i.e. the advertising industry) than to scientific research.

Matt Perry said...

I hope this isn't a very dumb question. But I'd think with selection very few parents would choose for just one trait. What if, say, I wanted to choose for height, IQ and conscientiousness? Is it likely that any one of the 10 zygotes would be the best for all three traits? And what if it was but it was also the one with the greatest risk of some form of mental illness? How would parents navigate those sorts of tradeoffs?

steve hsu said...

The IVF counselor could turn over all the information about each zygote to the parents and let them choose.

You could also imagine that the parents fill out a survey about their preferences. This defines a kind of utility function (e.g., linear combination of traits with certain weights) which is then used to score the zygotes from best to worst.

In any case, on average the parents won't do worse than they would without any predictive information.

dxie48 said...

http://en.wikipedia.org/wiki/Multi-objective_optimization
"Multi-objective optimization methods can be divided into four classes.[2]
In so-called no preference methods, no DM (human decision maker) is expected to be available,
but a neutral compromise solution is identified without preference
information.[1]
The other classes are so-called a priori, a posteriori and interactive
methods and they all involve preference information from the DM in
different ways."

dxie48 said...

These is at least already one such db,
http://www.wired.co.uk/news/archive/2013-04/18/iceland-incest-app
"App to prevent 'accidental incest' proves a hit with Icelanders"

dxie48 said...

1. Diseases already lead to homogenization of human DNA, e.g. Europeans have higher frequency of blood type A probably due to history of small pox and black death.
2. Without gene splicing, the fertility rates of developed countries are already declining.
3. The governments will have to secure their future tax incomes e.g. by offering baby bonus.
Or this guy, http://www.mirror.co.uk/news/uk-news/sperm-donor-may-have-fathered-1000-babies-784615
"Grand daddy: Sperm donor scientist may have fathered 1,000 babies at clinic he ran"

jeffhsu3 said...

George Chruch is amazing. Did he give a talk and do you know if it will be available online?

reservoir_dogs said...

I think you got the idea all wrong. The reason inbreeding cause problems, is because the imperfections in the genes, which we all have are at the same locations. So it is probable that at one of these locations, two copies of the defective genes(one from each parent, but both carry one good and one bad copy) are inherited, thus causing problems. The similarities that people will all have are going to be in the functional genes in that they all have the same alleles. This may mean that they have similar capabilities and dispositions, but would not increase the birth defects.

Erik Sieven said...

Fascinating. Science Fiction in real life.
Please excuse my bad understanding, maybe someone can help me with one question I have.
If a person has the gene variant for bigger bone density because his/her parents did editing/splicing would this gene variant get passed on the children? Would it get passed with a certain probability? I suppose this is the case for editing, but it is also the case for splicing?
If this is true the genetic set-up of all future generations could be changed by one effort for editing/splicing in ONE generation. For example the CP China could decide to raise bone density for every child born between say 2025 and 2035 in China and all future generations of Chine would had a higher probability of having higher bone mass.

weiner_dawg said...

Agree the rates are already declining, but how low will they go where there isn't even an intellectual reason to reproduce?

But yeah, baby bonuses sounds like the solution. And the psychological benefits of having a family are also there for the intellectual reasoning.

Far-future concern: non-human DNA!!!

Anonymous_IV said...

The 6-finger mutation already exists, and is genetically dominant and more common than you'd think (Wikipedia says about 0.7% of African or AA births, and 1/10 this frequent in Caucasians) because the sixth fingers and/or toes are often surgically removed soon after birth even if they're fully functional. http://en.wikipedia.org/wiki/Polydactyly#Ulnar_or_postaxial_polydactyly A fully functional second pair of arms must take a lot more work to arrange...

steve hsu said...

I don't know the details. It has been investigated in mouse models already (see link), but it was described to me at the meeting as originally discovered in humans in an African village. Locals hit by cars simply got up and walked away! I don't know whether the general health or development of these villagers is affected by the mutation.

Karch_Buttreau said...

Having greater bone density would probably be terrible for active tasks like running (it'd be like wearing ankle weights), swimming (sink to the bottom), climbing (too much weight)...

jeffhsu3 said...

Babies/children will never be thought of as products simply because you can nudge them towards desired outcomes. Lots of children fail to meet their parents expectations. That has been a trope since biblical times and likely way before that, but the parents still bear responsibility towards their children. Parental love is a love that love is unconditional no matter how they are brought into this world. You also have to remember that parents are already 'designing their children' by choosing who they mate with. Polling of young people without children consistently finds that as their top priority. The difference now, is that the parents have more freedom and are no longer constrained by some arbitrary history.

In regards to abortion, designer babies can be made without having to waste a single embryo and with technical advances fall way below the natural abortion rate.

5371 said...

You actually believe stories like this?

LaurentMelchiorTellier said...

The car accident which led to the discovery of the variant:
http://www.the-scientist.com/?articles.view/articleNo/24344/title/The-world-s-densest-bones/

5371 said...

So the African village was bullshit. Ten to one the rest is, at best, wildly exaggerated.

steve hsu said...

A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait

AMERICAN JOURNAL OF HUMAN GENETICS
DOI: 10.1086/338450

... In an effort to identify genetic factors influencing bone density, we characterized a family that includes individuals who possess exceptionally dense bones but are otherwise phenotypically normal. This high-bone-mass trait (HBM) was originally localized by linkage analysis to chromosome 11q12-13. We refined the interval by extending the pedigree and genotyping additional markers. A systematic search for mutations that segregated with the HBM phenotype uncovered an amino acid change, in a predicted beta -propeller module of the low-density lipoprotein receptor-related protein 5 (LRP5), that results in the HBM phenotype. During analysis of > 1,000 individuals, this mutation was observed only in affected individuals from the HBM kindred.

This paper has ~1000 citations.

Peter Connor said...

For the .1% of the world population that will be able to afford either of these techniques, they would provide a useful method of reversing the ongoing dysgenic decline in intelligence and fitness worldwide. On the other hand, I don't think the remaining 99.9% are going to be very happy about it.....

David Coughlin said...

This is a statement rich with implications: In any case, on average the parents won't do worse than they would without any predictive information.

John Fuerst said...

"Eventually, though, I believe many countries will not only legalize human genetic engineering, but even make it a (voluntary) part of their national healthcare systems...

If it's voluntary and some choose otherwise, how would "we" avoid "inequality of a kind never before experienced in human history"? Either coercive international eugenics or vaster inequality.

Cornelius said...

"...the consequences will extend over a lifetime and beyond."

My money says homo sapiens sapiens will speciate in less than 1,000 years. Our great-great-grandchildren will be as different from us as we are from erectus.

Blog Archive

Labels