Gattaca will never be

Yesterday CBS had a segment on hyperbolically titled Breeding out Disease. First, we will never “breed out” disease. Part of the reason is that a large fraction of disease is due to non-genetic factors. Perhaps in the future with nanotech we might get at all the biological misfires due to developmental problems which emerge out of the “environmental” (a word for stuff we basically can’t understand in any causal sense) effects. But genes aren’t everything.

Second, the CBS piece had two segments, which differ a lot in terms of their implications. The first involves preimplantation genetic diagnosis (PGD). This is already happening, so what you will see in the future is a matter of scale or magnitude, not a paradigm shift. I do think it is possible that in the next generation we will see the diminishing of recessive diseases due to highly penetrant deleterious alleles. Every birth of a child who is diagnosed with such a disease will allow us to predict future births, because presumably their parents will have rare variants which can then be put in the database. I don’t think this is controversial or scary in any way. It’s classic “science makes the world better.” Your child having a recessive disease or a karyotype abnormality is not part of some grand plan.

But the next element of the segment dealt with the firm GenePeeks. I saw the founder speak at the Consumer Genetics Conference in 2013, and it seemed to be a reasonable idea. Basically right now the play is to simulate the outcome of genotypes for combinations of sperm (donors) and eggs (the founder herself has a child with a recessive disease due to herself and her sperm donor being carriers for a rare disease). Enter Lee Silver, a famous geneticist before genetics was even quite so big. He makes many claims, some entirely reasonable, and some which I view to be a stretch. It seems that in concert with PGD simulating genotypes and looking to avoid highly penetrant alleles is very smart. In fact this is just carrier screening on steroids. But then Silver begins to imply that genetic methods are going allow to predict complex traits. On the face of it this seems likely to be true. The work on height is just a trial run for all sorts of complex traits, in particular diseases. In the next 10 years it is entirely likely that genomic techniques will allow us to capture most of the heritable variation which we now classify as “missing heritability”. Making a prediction which is actionable is a different thing altogether.

If you have a trait whose genetics is distributed across thousands of loci then simulating the gentoypes is going to be a brute force affair. I trust computation to catch up to this problem, but then it is making predictions on the individual level. It is one thing to capture the heritable variation on the population scale, but predicting in an individual case is going to be harder. Then, once you have the prediction you have to screen an enormous number of genetic combinations. If you want more than one complex trait, and they are independent, then the problem becomes exponentially more difficult.

There are two things which I think can get around this. One, which I’ve already mentioned, is to skew the embryos which are enriched for a grandparent whose quantitative trait you value (intelligence, height, or agreeability). Second, as I have said, the 2010s are the decade of reading the genome. The 2020s are going to be the decade of writing the genome. That seems a more viable and probable solution than screening for variants which are “in house.”

Finally, there is the standard question about selecting for non-disease traits like eye color. Silver doesn’t blink, and admits that this might happen. Norah O’Donnell is unsurprisingly concerned. I would reassure that we already select for non-disease traits in our children by selecting our spouses. It’s not that big of a deal. I’m rather sure that O’Donnell’s husband didn’t marry just because she’s a great journalist.

In the end Gattaca is a great movie with contemporary relevance. And thanks to the statistical shenanigans which went on in fMRI research it seems that genetics is unchallenged today as the queen of the biological sciences in our age.* But a movie is not reality, and geneticists have not bit into the apple of knowledge and are not as the gods. Relax, though expect a better future.

* Neuroscience made a play, but I think that’s done.

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