Thoughts on the Promises of Big Genomics

Last week, David Dobbs wrote a piece about Big Genomics, in which he took a critical look at the Human Genome Project (‘HGP’). Below are some thoughts about his piece and ‘Big Genomics’; this shouldn’t be construed as a ‘response’:

1. The HGP was overhyped. Many biologists, even with our rudimentary late 20th century biological knowledge (heh), realized that a DNA sequence would not be the be all and end all. If memory serves (and at this point, who the hell knows if it does), I thought the claims (“cancer cures in five years”) were absurd (although here’s some ‘countersnark’).

2. The HGP was absolutely necessary. Does anyone think we’re worse off for having done it? Of course we–and the National Institutes of Health–needed a human genome sequence. It’s ludicrous to think otherwise. It was going to be expensive–important data always are, one way or another. It led to significant technological and methodological improvements (one of the key reasons to do ‘Big Science’). Yes, the first genome was largely ‘engineering’, but, after that, we can start ‘doing science.’ For those who think the HGP took all the R01, independent researcher money, that’s not really the case (while $3.8 billion isn’t chump change, it’s a very small percentage of NIH funding over a fifteen year period). And I’ll just lob this grenade out there: as someone who has had salary paid off of R01 grants, most don’t ‘pay off’, especially when sometimes we need to pick an area and ‘go Manhattan Project on its ass‘ (I’m a poet, I really am…).

3. We need to rethink the underlying model for much of human genetic disease. It seems that thinking about this from a genetic load perspective is helpful: most human disease should consist of rare alleles, unless there is some kind of balancing or environment-specific selection. What this means is that a disease like schizophrenia will often be like Tolstoy’s unhappy families–each case (or at least cases in different families) will be schizophrenic in its own unique way, in the same way there isn’t ‘cancer’, but a multitude of different cancers. That we have been as successful as we have been using such primitive approaches with relatively low resolution data (SNPs) is remarkable.

4. We’re missing the short- and medium-term future of genomic technologies. This doesn’t have anything to do with human genetics (so if that bothers you, feel free to ask for your money back). Over the next five to ten years, I think the biggest improvements stemming from genomics won’t be in human disease, but in infectious disease surveillance and diagnosis. It’s already happening, and will continue. Importantly, it doesn’t require that much new basic biological understanding (though more never hurts).

5. Regarding the ‘Big’ part, most U.S. science is bureaucratic in nature, but R01 science is simply uncoordinated and inefficient (which has its advantages). If you don’t believe that, go peruse DrugMonkey’s or Jeremy Berg’s blog, both of whom spend a considerable amount of effort basically telling scientists how to fill out grant application forms more effectively. Pretty much defines bureaucracy. Yes, bold, independent researcher, you are but a small cog in a mighty bureaucratic enterprise. Admittedly, that enterprise is often uncoordinated and somewhat duplicative–which can actually be a good thing (we shouldn’t have only one group doing something). But, as I noted in point #2, sometimes we need to crank up the command-and-control.

6. Behavioral modification, for the most part, has also had limited success. In the piece, Dobbs argues, “Some suggest — and I agree — that we’d do well to take some of the billions spent chasing genes for conditions like Type II diabetes, heart disease, or stroke and spend it instead on finding ways to change risk-elevating behaviors like smoking, overeating, overdrinking, and avoiding exercise.” The problem is that behavioral modification alone hasn’t been successful. Behavioral modification reinforced with government regulation and restriction–smoking costs more and you can’t smoke in certain places–has been successful. But I’m skeptical about our ability to bamboozle people to a low BMI without policy changes, many of which would be very unpopular.


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5 Responses to Thoughts on the Promises of Big Genomics

  1. They didn’t publish my comment over at Dobbs’ piece, so I’ll try a variant of that here.

    I have an automated e-mail that comes to me from OMIM whenever there’s new data on some genetic condition, usually several a week. Sometimes I just scan lightly, other days I’m drawn over for a look. Lately there are so many situations where a gene variant found (by sequencing with new tech) in one family has been tied to a previously undiagnosed condition. I know it’s just one family–but I have exactly the same Tolstoy thing in mind with each of these. And no, they aren’t cures, but at least they are a new direction for someone’s family. And that will drive the research.

    But the other piece completely overlooked is a bit like your comments on infectious disease. The new technology developed associated with this field (although always referred to as “human”) has let the ag genomics folks kick ass on a number of challenges they have. Plant and animal researchers have moved stuff way ahead of the “human” research community for a variety of reasons. There are gene edited plants in the field, and there are edited pigs growing up now. They are moving things to the fields that you can’t get near in human research yet. And that area is almost completely ignored when all you do is gaze at human navels [and I don’t mean to slam the human microbiome here, I’m just talking about the disproportionate focus on human biology.]

    • Chad Niederhuth says:

      Ha! Didn’t see you’re reply when I jumped in…but I prefer how you put it “when all you do is gaze at human navels”….

  2. Chad Niederhuth says:

    David Dobbs…and a lot of people…also completely ignore the impact of genomics and genome projects in plants biology. Since plant breeders actually are able to determine what two individuals get to reproduce and carry on, genomics has had a huge impact on providing markers, QTLs, etc with which the entire industry now depends. It has completely revolutionized the industry.

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