Get ready for the flood of fetal gene screening

21 Feb

In a recent article in Nature, Henry T. Greely, proposes that the time when prenatal genetic screening may be commonplace is closer than, well, I thought.

The world’s news media was buzzing last week after researchers showed that a blood test for mothers could detect Down’s syndrome in their fetuses[1]. Last month, two research groups independently published proof that the fetal genotype — the genetic status at a given locus — can be derived for thousands of sites from samples of fetal DNA with just a 10-millilitre blood draw from a pregnant woman[2, 3].

[1] Chiu, R. W. K. et al. Br. Med. J. doi: 10.1136/bmj.c7401 (2011).

[2] Lo, Y. M. D. et al. Sci. Transl. Med. 2, 61ra91 (2010).

[3] Fan, H. C. & Quake, S. R. Nature Precedings doi:10.1038/npre.2010.5373.1 (2010).

Until now, the main prenatal testing has been for Down Syndrome. It is not common:

Prenatal genetic testing has been clinically available since the late 1960s, but the costs, inconvenience and especially the miscarriage risks have limited its use. Each year, less than 2% of pregnant women in the United States undergo amniocentesis (in which a small amount of amniotic fluid containing fetal cells is taken for analysis) or chorionic villus sampling (CVS — in which fetal tissue is extracted from the placenta). Both procedures increase the risk of miscarriage. Until now, any given sample could be tested for only one or two conditions, typically chromosomal abnormalities such as trisomy 21, the cause of Down’s syndrome.

It is uncommon, but it is offered in high risk situations (older mothers). Since the test has been offered, the prevalence of Down Syndrome has dropped significantly. This in spite of the fact that older mothers are more common now.

Amniocentesis is obviously invasive, resulting in risk to the unborn child. But a blood draw would be a non-invasive prenatal genetic diagnosis (NIPD).

The potential of NIPD goes way beyond Rhesus screening. Two of the leading researchers in cell-free fetal DNA testing — Dennis Lo of the University of Hong Kong and Steve Quake of Stanford University in California — use different methods to analyse fetal cell-free DNA from maternal serum. Each has demonstrated the ability to detect aneuploidies — missing or extra chromosomes, such as in trisomy 21 (refs 5, 6). Last month, both researchers published proof that the fetal genotype could be derived for thousands of sites from cell-free fetal DNA2, 3 — demonstrating the possibility of using maternal blood to test for all fetal genetic traits.

The methods demonstrated are already interesting commercial firms:

Commercial firms are already interested. Sequenom in San Diego, California, is working with Lo; another, Artemis Health of Menlo Park, California, is working with Quake; and still others are also exploring the technology. For-profit development of these methods seems likely within five years, at least for chromosomal abnormalities, such as trisomy 21, and possibly for single-gene traits.

My insurance plan will pay for prenatal genetic testing, but not for genetic testing of a child. I find that thought a bit chilling.

Until now, prenatal genetic testing has been relatively uncommon. The ethics discussions have been largely academic. Important, but academic. The time for academic discussions of the ethics is drawing to a close.

Professional organizations, in medicine and in genetics, need to get involved, both in training their members about these technologies and in beginning to consider guidelines for their use, especially with regard to informed consent. Regulators, companies and consumer advocates need to be talking about pathways for assuring the safety, efficacy and quality of NIPD testing. In the United States, the Food and Drug Administration should start that process immediately. And it is time for ethics commissions, such as the US Presidential Commission for the Study of Bioethical Issues, to report on these issues.

Most importantly, we need to start conversations, between all those concerned, about the limits, if any, to place on this powerful technology. Whether we view NIPD gladly as a way to reduce human suffering, warily as a step towards a eugenic dystopia, or as a mix of both, we should agree that the better we prepare, the more likely we are to avoid the worst misuses of this potentially transformative technology.

What disabilities will eventually have genetic screening possible? How will we as a society take on the ethical challenges? If the drop in Down Syndrome is any indication, I think there is reason to take this discussion very seriously. Now.

11 Responses to “Get ready for the flood of fetal gene screening”

  1. passionlessDrone February 21, 2011 at 14:17 #

    Hi Sullivan –

    Fascinating. IIRC, I ran into something similar on the Interwebs a while ago about the foundation for this, something about the ability to occassionally find a y chromosome in the blood of a woman who had given birth previously as a result of backflow from the fetus. Very neat stuff!

    That being said, there are already people doing something similar; testing for maternal antibodies associated with autism in the mother. There’s a group in California doing it, likely associated with the MIND guys; considering that to my knowledge they haven’t yet released what the antibody looks like in their papers. The literature on it is very specific that pregnant women cannot perform the test. Among the many problems that occur to me is that the test is probably not all that precise, certainly nothing like finding trisomy 21.

    Thanks for posting this, I likely wouldn’t have run into it otherwise.

    – pD

  2. AWOL February 21, 2011 at 19:48 #

    passionless drone

    Great test if it sees light(which i doubt)mothers/autism and so the mother goes selecting a N.T. child to give birth to ,gives it all its shots,and hey presto! at around 2 years they see that the child is starting to be Autistic..
    Would that not prove that the vaccines caused the autism…??

    Would that not just give more power to the anti-vaccine mob like me…

  3. esattezza February 22, 2011 at 01:07 #

    @AWOL: If we knew every gene that contributed to autism, you might have a point.

  4. Julian Frost February 22, 2011 at 06:53 #

    You are assuming that you are correct, and that that would happen.

  5. sharon February 22, 2011 at 10:56 #

    @AWOL, my son was born Autistic. Not all children regress.

  6. Jackie February 23, 2011 at 09:18 #

    There was a sci-fi film in ’97 that had the issues around genetic screening as it’s main plot:

  7. Jackie February 23, 2011 at 09:18 #

    There was a sci-fi film in ’97 called Gattaca that had the issues around genetic screening as it’s main plot:

  8. Julian Frost February 23, 2011 at 10:37 #

    Jackie, I’ve seen Gattaca. Not just genetic screening, but genetic designing of children.

  9. esattezza February 23, 2011 at 15:25 #

    But this actually does raise a lot of the same issues as GATTACA (btw, I spell it with all caps because the name means nothing, it’s just a string of DNA base-pairs).

    ***Minor Spoiler Alert***

    In the end of the movie, the main character overcomes his ‘genetic handicap’ to pursue the profession of his choice (the fact that he games the system not withstanding, he is, in fact, perfectly healthy at the end of the movie). We’re not talking about someone who has overcome an actual disability here, it’s much more subtle. The character simply beat the genetic odds and never developed any of the conditions he was predisposed to.

    Now, relating to the fetal testing: We’re talking sequencing here, not karyotyping, as is currently done to detect Down Syndrome. It’s a much more sensitive technology (it’s also much more expensive, though that cost has been coming down). I would welcome this non-invasive procedure if it was just used for things like Down, where there is a major chromosomal abnormality, which means the child is certainly going to have some disability (By the way, many fetuses in which this scale of genetic abnormality occur end in miscarriage; Down syndrome is the only trisomy in which the child survives to adulthood – in fact, this is one benefit I can see from this new technology, as couples are frequently haunted by miscarriages, and it may help understand what happened). Unfortunately, the technology is sensitive enough, that we could detect much smaller changes that may only predispose to a condition (bringing us back to GATTACA) or may cause a condition, like autism, that can vary in severity. Add to that the potential for false positive results (which is small, .04% according to one paper, but that’s just in testing for one mutation) and we find ourselves in quite the tangled ethical web.

    Other things to consider that you may not have though of: 1) what happens when insurance companies get their hands on the information – does a mutation become a “preexisting condition” for the child? 2) if society chooses to allow abortion decisions to be made based on this type of information, but refuses to pay for it, will it lead to a genetic gap between the rich and poor?

  10. Julian Frost February 24, 2011 at 12:00 #


    1) what happens when insurance companies get their hands on the information – does a mutation become a “preexisting condition” for the child? 2) if society chooses to allow abortion decisions to be made based on this type of information, but refuses to pay for it, will it lead to a genetic gap between the rich and poor?

    This is what worries me. Last year, there was a story in the news. The Managers of a prenatal clinic in Vietnam were prosecuted for telling expectant couples the sex of their babies. This is illegal in Vietnam. My initial reaction was “huh??!”, but then the report mentioned that in Vietnam, 120 boys are born for every 100 girls. Couples were finding out that a foetus was female, then aborting her and trying for a boy. It is not hard to see the same thing happening in the scenarios you mention.


  1. Tweets that mention Autism Blog - Get ready for the flood of fetal gene screening « Left Brain/Right Brain -- - February 21, 2011

    […] This post was mentioned on Twitter by Kev, Wolf Cocklin, D., Robbo, meredith hart and others. meredith hart said: RT @Dianne_: Fetal gene screening becoming commercially available. Time to discuss the ethical implications #LBRB […]

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