Tuesday, November 13, 2012

Go west, young man...thar's gold in them thar hills!

I was sitting in the lobby of the Moscone Center in San Francisco last week, at the American Society of Human Genetics meetings when amid the stir and din I heard bits of a conversation nearby, just as one person was saying, "Genome sequencing has been a huge disappointment," and the other answered, "Huge." I didn't see them, and have no idea who they were (and wouldn't say if I did!), but I was rather surprised to hear this at these meetings, where so many of the sessions and educational workshops were about how to analyze the huge amounts of data being generated by sequencers all over the world.

Even the more conciliatory presentations were acknowledging that we're just finding the 'low hanging fruit', a confession that most of the genetic causal factors we believe, or profess to believe are there to be plucked, are not being found by current methods. This is a big problem given the funding flow that promises to the contrary have engendered for a number of years.

 Indeed, it was appropriate that the meetings were in San Francisco, not only because it's a great city but because of all the 'gold' that is currently to be found in human genetics: gold in the form of investigators and their grant funding, equipment and supply makers, science journalists, myth-makers and hero groupies, and the like.

This largess seemed appropriate a decade or two ago, when ordinary epidemiology was flopping (environments caused our common disease burdens but we couldn't identify the factors, the associated risk, or the causal mechanism very well), and the genetic theory (or ideology) that genes were our inherent determinants and there was gold in them thar hills.

As the wells run dry...
Those days have passed, though nobody wants to acknowledge it openly.  Some clearly still believe.  Others know we are in a holding action.  We need to let the next Big Technique ('next-generation sequencing') have its day, along with some others (other types of whole-throughput 'omics detection).  But sooner or later the ore will play out unless we find a better way--genetic fracking!

Since outcomes must have causes, and since preachers have competition from scientists for the ear of the fearful, there must come some really next-generation ideas about disease cause and prevention.  This is too big a topic for now, and we've opined about it many times past and will doubtlessly do so in the future.  But the promise of the ASHG's rhetoric, masquerading in relentless thousands (yes, literally) of posters and presentations buried in minute technical detail, will provide some leads and a lot more obscuring smoke screen for the time being.

Once upon a time the ASHG meetings were a more or less modest scientific affairs, not so huge as to require basically a football field-size arena.   The founders and leaders were trying to work out what genes were and how they worked, and their relevance to human traits and human origins.  It was, literally, a new science with new methods and routine discoveries.  There was hype and salesmanship, of course, but much less than now.  Those were days when some of the fundamentals of genetics were yet to be discovered much less understood in relation to humans.

But that changed over the years, and for a long time now this has been a huge meeting.  For decades we have been collecting tomes of data, most of it trivial but much of it important and even fundamental to a general understanding of genetics.  The flood of funds led to a flood of students and faculty delving into this subject.  In many ways, especially 20 years or so ago, this was important and progress in understanding was accelerating.  That led to some really important disease discoveries, mainly in terms of identifying cause of large numbers of traits that really are genetic.  The record of major advances in treatment has been very far less successful, despite rhetoric.  Most chronic diseases are at least as prevalent as they were then.  Many single-gene, truly genetic diseases are better understood in terms of the genes involved, but treatment mainly remains empirical rather than based on specific genetic knowledge.

When causation really is genetic, one can hope that human ingenuity and engineering can solve those problems.  But most traits that are common and the main targets of this research are complex, and there is no sign yet that they will yield to personalized genome-based risk prediction nor gene-based therapy or prevention.  The meetings did not provide much that seriously suggests the contrary, and informally of course most of us know that regardless of what is said in public, or in the news media stories.

We're sure we'll see lots of research result 'announcements' made, and hopefully among the hubris will be some major discoveries of importance. But mainly this is still an expensive, market-driven, boast-laden holding action.

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