By James Evans


DNA sequencing is cheap and getting cheaper. A detailed elucidation of the sequence of one's complete genome will soon be within the reach of all-patient, consumer and genomic thrill-seeker alike. But that doesn't mean it will be useful (or indeed even mildly thrilling) for most of us anytime soon. The idea that your genome is likely to provide you, personally, with information of profound impact on your health is belied by the simple fact that the vast majority of maladies likely to affect you have many causes, of which genetics is almost always a minority component. Therefore, we will need to understand other factors, such as our environment, with far greater precision than we currently do before our genomic sequence provides meaningful health information to most of us. While your genetic code is (literally) a digital code and can thus be parsed and analyzed with ease in this digital age, our environment remains messily analog, imprecise and chaotic. Until we can grasp our (ever-changing) environment with the kind of precision we now apply to our (static) genomes, knowledge of our genomic sequence will remain a dim and imprecise source of useful information. And understanding our environment, I suspect, is the work of more than 20 years. Thus for most of us-the 99%-I doubt that our whole genome sequence will be particularly useful or even interesting anytime soon. Rather, the near to mid-term promise of genomics lies in its application as simply another medical tool; useful to some and meaningless to most. But that should not be depressing (unless your business model hinges on selling everyone their whole genome sequence). After all, magnetic resonance imaging is exceedingly useful and indeed revolutionary-but it doesn't mean that most of us would benefit from a whole body MRI. The trick is to ignore hyperbolic claims about the universal benefits of genomics and think critically about where it is really likely to be of benefit.

While for most of us our genomic sequence will be nothing more than a mild diversion, the situation is different for a small subset of us. For example, about 1/500 individuals in the U.S. carries a highly penetrant mutation in a Lynch Syndrome (LS) gene that confers a greater than 80% chance of colon cancer. Critically, once it is identified, that risk can be radically reduced through preventive measures currently available. While there are not many human genes which, when mutated, lead to a high risk of an eminently preventable disease, there are enough so that about 1% of us carry highly penetrant mutations in one of them and would greatly benefit from knowing it.

My prediction is that in the next 20 years we'll see whole genome sequencing incorporated into medical care as a routine diagnostic tool which will be useful for those relatively unusual individuals who have a major medical condition explained primarily by an underlying genetic lesion. And perhaps most excitingly, we will finally see a productive fusion of genomics with public health. Ubiquitous, population-level sequencing of the handful of genes that actually matter to human health will identify those relatively rare individuals - the roughly 1% - who have mutations that strongly predispose to an eminently preventable disorder (e.g. various cancers or aneurysms). Thus, over the next 20 years, sequencing which is broadly applied to the asymptomatic population but targeted to focus on the handful of genes that really matter for preventing disease, has the potential to save lives and perhaps money (though we should be skeptical of claims that any new technology will actually reduce health care costs; they rarely do). The public health potential for robust sequencing will also likely be realized in the near-term as it is increasingly used to identify the severe recessive diseases for which prospective parents are both carriers.

The application of genomics in public health contexts will inevitably create friction. When couples have ready knowledge of their carrier status for hundreds of severe recessive diseases, the most common use of this knowledge will be, as it is now, abortion of the affected fetus. And as more individuals undergo whole genome sequencing for legitimate healthcare purposes or in the rather silly pursuit of "recreational genomics," some will inevitably find out things that they wish they'd never have discovered (like the fact that they have an exceedingly high risk for a truly awful and untreatable disorder). Such friction, unavoidable with the broad application of any new advance, makes it all the more important that we look with a critical eye upon what genomics really has to offer, apply it with care and don't over-hype the benefits of this amazing new technology.           

James P. Evans, MD, PhD, is Bryson Distinguished Professor of Genetics and Medicine at the University of North Carolina School of Medicine.

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