On the limits of PGD

| Comments (4) | Biology
In Slate this week we're treated to William Saletan's usual handwringing about how biotech, though of course inevitable, inevitably cheapens people's attitudes towards reproduction. This time the issue is preimplantation genetic diagnosis (PGD), where you you do in vitro fertilization and biopsy the embryos to decide which, if any to implant. Obviously, this is something you might want to if you know you're a carrier for something nasty (e.g., Tay-Sachs) and want to avoid passing it on. Saletan's objection, predictably, is that people will use it for purposes he doesn't approve of (sex selection, height selection, etc.):
Two months ago, the Fertility Institutes, an assisted reproduction company headquartered in Los Angeles, began advertising the "pending availability" of genetic tests that would offer "a preselected choice of gender, eye color, hair color and complexion" in artificially conceived children. On Thursday, Gautam Naik of the Wall Street Journal reported that "half a dozen" potential clients had contacted the company to request such tests. As of today, the tests still aren't for sale. But several trends are converging to make aesthetic trait selection an impending business.


See how smooth the transition can be? You're already screening for diseases. Why not add one more factor while you're at it? So now you'll know which embryos are male and which are female, just in case two of them turn out to be healthy and you're lucky enough to be able to choose which one to put in the womb. And if you're checking sex, why not throw in eye color and complexion? You don't have to do anything with the information yet. Just run the test and find out what your options are.


This is how revolutions happen: Technology matures, trends converge, and cultural changes pave the way. By the time Steinberg opens his trait-selection business and does for that practice what he's already doing for sex selection, it'll be too late to stop him. In fact, before you know it, we'll be used to it.

Unfortunately (or fortunately, depending on your perspective), the statistics pretty severely limit the use of for trait selection. The problem is that this is a screening procedure: you don't get to make the embryos you want, you just make a bunch of random embryos and then screen out the ones you don't like. And while any given trait may be reasonably probable, they're not that jointly probable.

In case you've forgotten your high school genetics, there are a bunch of common cases with different probabilities of the embryo expressing the trait:

  • Autosomal recessive traits (ones where you need to have two copies of the allele to show the trait) [blue eyes, Tay-Sachs] but both parents are heterozygous (has one copy). In this case, 1/4 of the candidate embryos will express the trait.
  • Autosomal recessive traits where one parent is homozygous and one is heterozygous. In this case, 1/2 of the candidate embryos will express the trait.
  • Autosomal dominant traits [brown eyes, Huntington's] where both parents are heterozygous, in which case 3/4 of the embryos will express the trait.
  • Autosomal dominant traits where one parent is heterozygous, in which case 1/2 of the embryos will express the trait.
  • Sex-linked traits (e.g., hemophilia), where you express the trait if you have two X chromosomes with the allele (i.e., a homozygous female) or be XY with two the X chromosome having the allele. The statistics vary here based on the father's status and whether the mother is homozygous.

Anyway, to a first order you can think of the chances of getting any particular set of alleles as statistically independent. So, if for instance the father is heterozygous for blue eyes and a Tay Sachs carrier, then there's 1/4 chance each of having: blue/Tay-Sachs, brown/Tay-Sachs, blue/normal, and brown/normal. This creates a real problem for a screening procedure: if you want to select for five traits, each of which have a 1/2 chance of being expressed in the embryo, then any individual embryo has only a 2-5 (1/32) chance of exhibiting the trait. A single egg harvesting yields somewhere in the order of 10-30 eggs [*], so even if all of these turn into good quality embryos, you have somewhere between a 30-60% chance of getting even one embryo with the mix of traits you want. Even if you're willing to go with only three traits, your chances of getting one or more matching embryos is only about 70%. And of course if you're doing IVF and PGD (Did I mention it's horrifically expensive?) so you can screen out some trait, you're already down to somewhere between 1/4-3/4 of embryos before you start screening for height, eye color, etc.


So at the end it's only sex that people will be able to select. I don't think there'll be a sufficient market for other traits.

There will still be evolution (that is, a shift in the distribution of genes in the population) with this. It might not work in every circumstance, but it will work in enough for the change to be very noticeable.

If everyone tries to, say, select for blue eyes, having 4 babies and choosing the one that gets to live is a tremendous selection pressure. And of the kind we haven't seen in a while, since these days just about everyone reproduces.

Even with 5 factors that I want that are a coin-flip each way, the expected value with leaving it up to nature is to get 2.5 of them, and only a 19% chance of having a kid with at least 4. If I were to have four kids and smother the three I least like, I'd have a 57% chance of having a kid with at least 4 of the factors I want. (And 11% to get my dream kid.)

This is tremendous pressure selection. Nature can amplify traits that only have a 1% improvement in fitness and make them totally universal in a population. This is major compared to that.

If society keeps a move towards those 5 factors going for a few generations, they'll be at their goal very very quickly. Like compound interest, these effects accumulate rapidly.

Dan, I think you're miscalculating the selection pressure here. You have to factor in the demand curve. How many people will be willing to pay the cost to get the benefit? Multiply that fraction times the efficacy of the procedure and you get a measure of the _total_ selection pressure on the population.

I'd be surprised if demand were even approaching 1% in the developed world. That means we're many generations from fixing any traits in the population. By the time this would have any appreciable affect, we'll either have either killed ourselves off or perfected much more direct techniques of manipulation.

Yeah, I was assuming that everyone was doing it. And also in my last paragraph, assuming that everybody in society is trying to select for the same things. You could have some people deciding that they want blue eyes and others that they want green eyes. Or maybe A-blood-types are in style this decade but B-blood-types are in style the next decade.

But if a fashion hits everyone, it won't take much more than 2 generations to make some genes incredibly rare.

One obstacle is that many traits aren't obvious in 1 gene. Height is probably the mixture of several different genes, and we don't really know which ones. Intelligence is probably a mix of a whole bunch of genes, but maybe getting too many of them leaves you with an autistic kid.

If this article is right, though, we'll probably see people purposefully selecting for wider hips and bigger skulls.

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