Whole Genome Sequencing Is the Future of Genetics, BUT the ‘$1000 Genome’ is a Bait and Switch

Let’s STOP talking about the $1000 genome!  Please.

Unless you’ve been living under a rock since 2001, you’ve been hearing about the $1000 genome for years.  The inevitable, the holy grail, the game-changer – the ultimate goal post as proclaimed by an entire chorus of Chicken Little genomicists crying, ‘The cost of sequencing is falling!  The cost of sequencing is falling!’  And it’s true! Not only has the cost of sequencing dropped faster than Facebook stock on IPO day, but the product has improved at the same time, in speed, accuracy and coverage.  Will it be transformational?  It already is. 

The early references to the ‘$1000 genome’ were purely aspirational, tossed out in stark contrast to cost of the newly-completed 2.7 billion dollar genome generated by the Human Genome Project.  But the emergence of the $1000 genome as a meme began in earnest in 2005, when the Craig Venter Foundation offered $500,000 to whoever got there first, an incentive that has since evolved into the $10,000,000 Archon X Prize (100 human genomes/30 days/98% accuracy), to be contested in September, 2013.

But all that money aside (seriously, that’s a lot of zeroes!), the phrase, the ‘$1000 genome’ represents much more than a measure of technological prowess.  As George Church describes it, “The ‘$1,000 genome’ has become shorthand for the promise of DNA-sequencing capability made so affordable that individuals might think the once-in-a-lifetime expenditure to have a full personal genome sequence read to a disk for doctors to reference is worthwhile.”  Which is exactly why, as the technical parameters of the challenge have grown clearer and more explicit, the bandying about of the term has grown more and more misleading.

HERE is what the ‘$1000 genome’ DOES NOT MEAN: that getting your DNA sequenced will cost $1000.  This may be self-evident to all the genomics experts competing to win the Archon X prize, but it is anything but obvious to everyone else.   The $1000 figure covers only renewables – those things like reagents and chips that are consumed in the process of sequencing.  It does not include the cost of the sequencer or the cost of the tech who runs the sequencer.  It does not cover overhead or profits.  And most of all, it does not cover the costs associated with interpretation, without which a DNA sequence is merely an endless stream of A’s, C’s, T’s and G’s. 

Sequencing as a “once-in-a-lifetime expenditure”?  More caveats!  Integrated sequencing and interpretive processes make it difficult to re-examine old data, and with both our knowledge base and our sequence quality improving by leaps and bounds, lab experts have assured me that re-sequencing would make more sense than working with data that is even a few years old.  So the whole sequencing-at-birth idea?  Not so much – at least, not yet.

Finally, while the magic of sequencing may lie in the technology that makes it possible, the value of sequencing lies in our ability to translate that technological virtuosity into improved health.  A number of exciting early reports demonstrate the potential health benefits; unfortunately, most of them fail to acknowledge all the ways in which these early adopters do not represent the general public.  A highly-publicized article in Cell in spring 2012 described the experience of Michael Snyder, a molecular geneticist from Stanford who experimented on himself using genetic sequencing followed by a serially repeated, battery of tests designed to monitor his health and biochemistry.  When his genetic sequence showed a variant associated with an elevated risk for type II diabetes, Dr. Snyder added a close monitoring of his blood glucose and other markers for diabetes — a testing regimen unprecedented for someone without risk factors for the disease.  Lo and behold, following an attack of respiratory virus, Dr. Snyder’s blood glucose levels rose to a level consistent with type II diabetes!  The doctor improved his diet and increased his level of exercise, and six months later his blood glucose levels were normal.

Was this, as suggested, a miracle of preventative medicine?  It’s a little hard to know from a sample of one.  Because aggressive monitoring is not done for individuals with no signs or symptoms of diabetes, we don’t know much about the likelihood of transient high blood glucose.  But one thing is indisputable: like the Personal Genome Project participants and other high profile subjects of whole genome sequencing, Dr. Snyder had available to him levels of expertise and medical care that are not in any way typical.  For much of America, paying for routine medical care is a challenge, and paying for acute or chronic medical care the most likely cause of personal bankruptcy.  And even people with money to spare don’t usually get a sit-down with George Church to discuss their most disturbing sequence variants.

Whoever wins the Archon X Prize next year: I salute you.  The $1000 genome is an enormous technical achievement and you deserve every penny!  But let’s not confuse people about what it means.  Let’s not confuse the $1000 genome with the $10,000 interpretation or the $25,000 follow-up.  The meme that represents the future of genetics should not be a bait-and-switch.