First they came for the trisomies….

By Razib Khan | July 18, 2013 5:52 am

At 9 weeks
Credit: Ed Uthman

A new opinion piece in The New England Journal of Medicine is titled A New Era in Noninvasive Prenatal Testing. It is free, so I commend you to read the whole thing. But this is the key section, “A new, noninvasive prenatal test is poised to change the standard of care for genetic screening. Cell-free fetal DNA (cfDNA) testing requires only a maternal blood sample, can be performed as early as 9 weeks of gestation, and outperforms standard screening tests for trisomies 21, 18, and 13 in high-risk populations.” Nine weeks is of course still in the 1st trimester.

While 60 percent of Americans support the legality of 1st trimester abortions, only 30 percent support the legality of those in the 2nd, and it is in that trimester that the abortion of a fetus with a trisomy abnormality now occurs because the various prenatal tests are at this stage. Mind you, I understand that despite what the public says a larger share of parents who receive “positive” results in that trimester abort the pregnancy than might be expected based on surveys about the legality of the practice. But, there is probably considerable room on the margin for the class of those who would opt for this if the results arrived in the 1st trimester.

And of course trisomy tests are just the beginning. Whole genome sequencing of 2nd trimester fetuses is now possible, and it seems very likely that in the next few years they’ll move all the way to the 1st trimester. At that point the genetic analysis of 1st trimester fetuses will be routinized and be a simple consumption good. The ultimate question is what are we going to do with all that information? This is not hypothetical, speculative, or blue sky. It’s almost a reality.

MORE ABOUT: Prenatal Screening
  • Dmitry Pruss

    The key point of the article is statistical in nature. Even tests with seemingly very sensitivity and specificity numbers may have inappropriately low predictive value if the condition is very rare. This has a very strong relevance for the headline: for the tests to expand from the common triploidies to other, far less common grave congenital conditions, the techniques must be proven to be much more specific. Sequencing has a potential to get there, but depth of coverage / avl copy number / fluctuating sequence-specific error rates are an issue.

    • razibkhan

      re: last sentence, any reason that these are not all likely to be overcome as problems within the next decade?

      • Dmitry Pruss

        It is quite probable, but it will require one more technological revolution in sequencing. A large fraction of severely penetrant mutations, especially de novo mutations, involve genomic rearrangements over repetitive sequences. Today’s “next-gen” (now-gen) is likely to improve beyond substitution detection and into small indel and unique-sequence fusions and rearrangements. But to resolve repeats, that would require a different technology, like single-molecule nanopore long-read for example. It’s been promised for some time, but the promises sort of fizzled?

        Then the number of available molecules of fetal DNA may still be a problem?

        I’m afraid that the imminent solution will be legal or ethical rather than technical. Either people will learn to leave with insufficiently reliable tests, or the societies will frown on them (insurers won’t cover, obgyns won’t accept, ethicists won’t allow…)

        • razibkhan

          yeah, aware of the pacbio fiasco. but i’m hopeful that 10 years is enough time that someone will come up with something that produces very long reads (relatively).

  • Louis

    Malorye Allison’s written a review about this in the latest Nature Biotechnology too

  • Robert Ford

    I’ll bet xtians are *really* gonna start attacking genetics and science in general if they find out this is leading to more abortions.

  • toto

    Sorry for stating the obvious: this “reality” is already very evident right now, in some parts of the globe, with sex-based abortion.

    Indian experience with selective abortion of girl foetuses constitutes a good test of what happens when you have a non-invasive test for an “undesirable” characteristic. And in the case of sex ratios, the social cost is pretty obvious. So for characteristics with no obvious conflict between individual and social benefit, the effect will presumably be even larger.

    My guess is that the coming wave of selective abortion will provide interesting sociological data: what is it that people find “undesirable”, to the extend that they would go through abortion and/or IVF to avoid it? Given the cost, this “natural experiment” will presumably be much more reliable than any interview-based data.

  • Gene Partlow

    Your piece on “…trisomies” reminded me of a new paper on the possibility of eventually inactivating an entire extra chromosome in the same manner as the normal inactivation of one of the X chromosomes of a pair in female embryogenesis (Barr Bodies); i.e.: leading toward “…successful trisomy silencing in
    vitro.” As you suggest, both technical and moral issues seem to be accelerating toward us. I hope their complexities can be laid out clearly for discussion and sympathetic understanding in an
    increasingly frightened world.

    More on the site:

    and at

  • kurt9

    The ultimate question is what are we going to do with all that information?

    It should be obvious that the more intelligent, thoughtful, career-oriented people (e.g. “yuppie” types) are going to use this technology to have better kids and those that tend to pop out kids without thinking about it (e.g. underclass) will not. The result, at least in this country, will be an increasing bifurcation in the population.

    It will be different in other countries. East Asian countries, for example, will see this kind of technology universally used throughout the population. I don’t know about Europe or the “southern” world (e.g. Latin America, South Asia, etc.). The overseas Chinese of S.E. Asia will certainly use this technology

  • skadhithjassisdottir

    I think everyone can agree its better if severely dysgenic traits disappear even though we may disagree about the ethics of abortions. Nonetheless, only an unwarranted faith in human nature would make anyone think a combination of reproductive choice and advanced genetic screenings will in fact be beneficial over the long term.

    We all know what ‘orchid children’ are – gifted children may be exceptionally difficult to raise and present the parents with behavioural problems.

    We all know most Down’s Syndrome aborters are motivated by the extra effort needed to raise such children, not by a belief in some kind of eugenics.

    We also know the cultural ideal is of an airhead with good looks, not necessarily someone intelligent (to the degree smartness enters into it, parents misconceive of intelligence as simply passing tests by rote to get through the school system, rather than in terms of innovation or critical thinking – passing degrees by rote is what brings social prestige to the parents). And we know society doesn’t like smart people questioning authority.

    Ultimately attempts at negative eugenics must be strictly state controlled else not practiced at all lest people make short-sighted decisions. Reproduction must be divorced from individual, parental choice lest screenings backfire.

  • skadhithjassisdottir

    Also most people know little about embryology. If they say they approve of abortion in the first trimester but not the second, then reading between the lines they’re really saying they’re against abortion the more ‘human’ the foetus gets.

    At 9 weeks the foetus already has tissues like a head and embryonic limbs as you can see in the picture provided. So that will affect people’s decisions more than the actual trimester IMO.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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