Genetic Future

i-b74df77d0012fa8b429a89248d9839e7-baby_face_3_flickr.jpgI’m slowly catching up on genomics news from the last week – this story in particular has been getting a lot of press.

The executive summary: Jay Flatley, CEO of genomic technology manufacturer Illumina, predicts that whole-genome sequencing of newborns will become routine within a decade.

Flatley has an obvious financial interest in this prediction coming true, since Illumina provides the most commercially successful next-generation sequencing platform currently on the market, the Genome Analyzer, and has recently invested heavily in emerging “third-generation” sequencing technologies (by purchasing Avantome, and signing an $18M deal with Oxford Nanopore). Illumina also apparently plans to launch a commercial whole-genome sequencing service for $10,000-$20,000 within the next two years, going up against newcomer Complete Genomics’ $5000 service. Routine whole-genome sequencing of every baby born in developed nations would provide a massive and secure market for Illumina’s products.

Still, Flatley’s predictions are not mere marketing hype. There’s little doubt – given the impressive rate of advances in the field – that the technology for whole-genome sequencing will be accurate and cheap enough to make this sort of large-scale application feasible in under five years. The major obstacles, as Flatley notes in the article, are not technological:

The limitations are sociological; when and where people think it can be applied, the concerns people have about misinformation and the background
ethics questions.

“I think those are actually going to be the limits that push it out to aten-year timeframe,” [Flatley] added. [my emphasis]

Reading through the public comments on the various online articles reporting Flatley’s comments (for instance here and here), it’s easy to see his point – Gattaca and Hitler are prominent, as is concern about misuse of the data by governments. Widespread concerns about eugenics and genetic discrimination will make it very difficult for any government health service seeking to put make whole-genome sequencing a standard component of their newborn screening procedures.

In order for these sociological barriers to be overcome (and I agree
with Flatley that they should be, almost certainly within the next ten
years) it will need to be very clear to the public that the medical
benefits of whole-genome sequencing outweigh its risks; that will
require both a bigger carrot, and a smaller stick.

Growing the carrot means investing heavily in moving results from basic genetic research into clinical practice.
Regular readers will know that I’m generally an advocate of
direct-to-consumer personal genomics, but I’ll freely admit that the
clinical utility of current genome scans is extremely limited. Right
now, even a complete genome sequence would provide very little value in
terms of individual health prediction for most people (although for some, such as carriers of known severe disease mutations, the value will obviously be much higher).

Those limitations will decrease rapidly over the next decade as we
develop a deeper understanding of the genetic architecture of human
disease. As Anthony Fejes noted in a recent post (and as Steve Murphy
has argued for a long time) the first useful applications will likely
be in the field of pharmacogenomics – using genetic information to
predict individual variation in drug effectiveness and toxicity.

Still, such useful applications won’t exist unless genomic data is actually converted into clinically relevant algorithms, and that isn’t always happening at the pace that it should beo. At the AGBT meeting last week, UNC’s Howard McLeod emphasised that academic researchers often do a poor job of handing their results over to clinical researchers and ensuring that they are ultimately used to develop useful medical products. This really struck a chord with me; it is so easy in academia to stay focused on the metrics of scientific career success (funding and papers), and neglect the development of results into real-world applications. I’ll certainly be thinking harder about how to improve this transfer in my own research.

Shrinking the stick means ensuring that there is a strong regulatory framework in place to prevent the abuse of genetic information, without stifling innovation. To date, governments have generally been excruciatingly slow in preparing for the consequences of the looming explosion of genomic data; that will have to change. However, knee-jerk responses – blanket moratoriums on direct-to-consumer genetic testing, for instance – could do even more damage than inaction.

If researchers and regulators get the balance right, the potential benefits of early whole-genome sequencing are substantial. In terms of individual health, genetic information could be used to target enhanced health screening to individuals at higher risk for severe, preventable diseases, and to minimise the risk of adverse reactions to drugs. From a research point of view, the combination of whole genome sequence data with electronic medical records from millions of individuals – if handled with appropriate care for patient privacy -  would dramatically boost our ability to find new, predictive associations between genetic variants (and gene-environment interactions) and health outcomes.

Concerns about privacy violations, discrimination, or a new era of government-sponsored eugenics are not completely without foundation – but I suspect that the public health benefits of routine whole-genome sequencing will ultimately make its adoption by most governments inevitable. I only hope that in the meantime there is a sufficient investment in translational research, public education and careful regulation to ensure that this adoption is welcomed by the public rather than feared.

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  1. #1 Dave X
    February 12, 2009

    It will soon be cheaper than cord-blood banking, and probably more likely to be helpful.

  2. #2 N/A
    February 12, 2009

    Yes, this is a good thing. We just need to work out the ethics of it. What information should be shared, protecting certain type of information,and so forth. I feel that any information that is not related to a condition that does not impede on the child’s health at the time of testing should not be given unless the parents consent. I don’t see the point in saying to the parents, “your child has a gene mutation that puts your child at an increased risk for this, that, this and that, that and this, and so forth,” because, as we know, having a gene mutation does not mean the person will get the condition. However, it will at least help with trying to prevent the onset of a condition by eating the right type of foods, getting routine tests done, and so forth.

  3. #3 Non-populist
    February 12, 2009

    “ensuring that there is a strong regulatory framework in place to prevent the abuse of genetic information, without stifling innovation. ”

    But what is abuse? The religious right is going to object to any use of genomics that enables embryo selection, as will some of the technophobic left. But embryo selection and successor technologies offer potentially huge benefits, despite claims that they are eugenic (is screening for Down’s syndrome or intelligence really so bad?).

  4. #4 Steven Murphy MD
    February 12, 2009

    Know if we only knew what the other 90% of the genome does we could be off to the races!!!

    Thanks for mentioning me. Obviously the person who wants intelligence selection is a little off base…..And probably still thinks that there is ONE IQ gene out there!

    BTW, has anyone mentioned the 800 lb gorilla of IVF culture media affecting methylation patterns????


  5. #5 N/A
    February 12, 2009


    I think people don’t understand just how complex things really are at the molecular/genomic level. Not only do we have methylation, we also have changes in how tightly packed the genes are and how that changes gene expression and so forth.

    I’ve been reading about genetics since 2002 and in those days we didn’t have genetic testing companies popping up left and right and we now do. Did our understanding of genetics improve enough in only 6-7 years to allow all of these companies to provide consumer genetic testing? If you ask me, NO!!!!!!!!!!!!!!!!!!!!!!!! But we have these genome wide studies showing associations for this and that and we now have all of these companies forming. People are always so quick to make that next million dollars.

  6. #6 Non-populist
    February 12, 2009

    “Obviously the person who wants intelligence selection is a little off base…..And probably still thinks that there is ONE IQ gene out there!”

    Steve, there’s no need to be rude, and as it happens I am very familiar with the genetics of intelligence, and the absence of common variants explaining substantial population variation (I could say similar things about many other highly heritable traits as well, of course).

    Many scientists are on board with the development of drugs for cognitive enhancement:

    Secular bioethicists, like those at Oxford ( who have thought about the issue tend to support PGD for cognitive enhancement, while Catholic and Republican-backed scholars and institutions like Leon Kass and Bush’s bioethics council have led the opposing camp.

  7. #7 Henk Visscher
    February 13, 2009

    In a way we’re already doing the same thing on a smaller scale: the newborn screening for certain diseases (mostly metabolic diseases for which diets can prevent disease progression). Of course, these are inherited in a Mendelian way (afaik).
    Pharmacogenomics could well be one of the first applications of using genetics for personalized medicine. Which parent wouldn’t want to know which drug to give their child and which one not to give. For some drugs, these tests are currently being implemented (i.e. TPMT for azathioprine, CYP2C9 and VKORC1 for Warfarin and others). For these drugs, these gene variants explain a great proportion of drug response/activity. However, just like for disease-causing genes, environmental factors like diet, other drugs etc are important because they can greatly influence drug-metabolism gene expression. So here too it would be to simplistic to think that knowledge of the genetic factor(s) is enough to predict all response and/or toxicity.

  8. #8 Zoe McDougall
    February 13, 2009

    The review by the UK’s House of Lords Science and Technology Committee has discussed the possibility of a body that is similar to NICE but for genetics. Such an organisation might be responsible for reviewing the emerging deluge of information for its clinical applicability although it is not clear where it would sit along the translational medicine pathway.

    For example the recommendations might separate into
    - bad science
    - good science but not cost effective
    - good science, could be cost effective but needs more evidence
    - great evidence, let’s get on with translating this into the clinic
    - and of course ‘refer this one to the ethicists’

    An attractive idea if the organisation is effective, although the task of setting it up would be rather daunting. It will be interesting to see the Committee’s recommendations.

  9. #10 Daniel MacArthur
    February 14, 2009

    what is abuse?

    Well, unfair discrimination for one – using genetic data that is either inaccurate or irrelevant to make decisions about a person’s future. I think most people would agree that this is unacceptable and should be regulated against, although admittedly it’s hard to find much common ground beyond that.

    But I personally have no problem with screening for Down syndrome, or indeed for IQ or other non-disease traits (although like Steve I am skeptical that the genetic architecture of complex traits like IQ will ever be amenable to PGD). As far as I’m concerned, a couple undergoing IVF should be able to choose which of their embryos to implant based on any characteristic they want, except for disease states (IMO selecting a deaf child is morally equivalent to piercing a non-deaf child’s ear-drums; if the latter is illegal, so should be the former).

    Steve – agreed that there are still questions about the long-term consequences of IVF, although for this post (routine post-natal sequencing) this isn’t relevant.

  10. #11 Kristen H
    February 27, 2009

    Hey, anyone out there but me worried about DTC (direct to consumer) testing of children? It seems to me that if adults want to play around with the risks and benefits of genetic susceptibility testing, so be it. The interested parties most likely have the curiosity, intellectual capacity (and funds) to understand the risks (emotional reactions, variants of unknown signficance, potential discrimination or untowards use of results) and benefits of undergoing personal genomic analysis if they so choose to do so.

    But what about children? Most DTC sites require an adult to sign their forms, but many also offer that you can “buy a kit for your kids.” Should parents have the right to send any/all of these tests on their children? If so, does the child need to assent to testing (as currently recommended by the AAP, etc)? And whose responsibility it is to ensure that the risk/benefits/results are expained to children in a developmentally appropriate manner? Should DTC testing of children be regulated/reviewed on a case by case basis? (ie, little harm and forseable benefit in testing children for drug responses, but what about predisposition to mental health disorders?)

    Maybe we will get to whole-genome screening in the next several decades (as a pediatrician this makes me shudder: what the heck would I do with all that information?) but at least the testing would be connected to a somewhat objective profession that is concerned about the child’s well-being, and hopefully, a system designed to follow-up results of testing in a responsible mannner (again, this will be what slows us down, not the technology!)

    But in the meantime..Anyone else concerned about this?


  11. #12 Cully
    June 24, 2010

    Which doctor decides how much collected/discovered genetic information is given to the parents?
    How do the parent(s) decide how much information to pass onto/withhold from the child and which other people they’ll discuss it with meanwhile?
    When a child turns 18 and is legally entitled to withhold health information from his/her parents and parents’ friends, will it be fair that they’ll already know?
    Overall, only the government will have 100% of the test results and no-one or any regulation will be able to stop them or know the full consequences of them having access to the child’s health details.
    I can’t see any benefit to the child. The parents will carry the burden of one day breaking any potentially bad health news to the child. The doctors may benefit slightly from the free research base. The government doesn’t need potential health information to run the country. Or am I missing something?