Monday, February 14, 2011

Omics and the atomic bomb

As we noted last week, Nature and Science, and surely many others involved in the 'genomics revolution', are feting the 10th anniversary of the human genome sequence, Nature in its Feb 10 issue, and Science all month.  It's petty at this juncture to point out that 'the' human genome sequence is still not complete, and that the anniversary being celebrated was a date on which it was politically expedient for all those involved in the rancorous sequencing race to declare victory....and go back to work.

But we point these things out anyway, as a reminder of just how much hype the human genome sequencing project has been from the start.  The hype ain't going away anytime soon. In fact, it is leading to an epidemic medical condition, of geneticists needing expensive physical therapy to repair their shoulders that have been dislocated in the latest round of exuberant patting themselves on the back.

DNA sequence,
Wikimedia Commons
This is not at all to say that nothing good (in addition to business for the physical therapists) has come of this whole endeavor.  We know a lot more about gene structure and function and so on than we used to, and indeed genetic technology as represented symbolically by the human genome sequencing has led to many new discoveries across the spectrum of the life sciences.

But when even the best believers in the project say, when confronted with more biological data than ever before amassed in the history of science, that what we need is ..... more data, or that the promised immortality due to genome-based cures will be decades in the future, one has to wonder what we're dealing with.

In fact, the completion of the human genome was quickly followed by the birth of a whole new -omics infrastructure; proteomics, biomics, nutrigenomics, cistronomics, epigenomics, microbiomics, metabolomics, connectomics and on and on, a recognition, tacit or otherwise, that genomics just wasn't going to be enough.  Surprise surprise.  And to some extent we owe it all to the atomic bomb.

The Manhattan project showed that mega-science with huge, long-term funding would be an employment boon unlike anything since the gold rush.  After the catastrophic end to WWII, a foundation was set up in Hiroshima to study the effects of radiation exposures to survivors.  That was about 65 years ago, and the Radiation Effects Research Foundation is still going strong.  Mega-science became the strategy du jour and that view has been growing ever since.

It's a little known fact that the origin of the term Omics is from the Greek, meaning either "Too-Big-to-Kill" or "No-Need-to-Think."  That's because once you start down the 'omics' pathway, that is, of using technology to document absolutely everything in everybody, rather than to think about what you're doing carefully and justify doing something selectively--that is, once you become an omicist, you'll never think again.  The project will involve so much investment that your Senator will not allow NIH to cancel the project--a good deal if ever there was one!  Or, if you're doing science but want to keep up with the Joneses, once you see the guy in the next department doing it, you have to have your own omics project, too.  After all, fair's fair!

We've written numerous times before about the exaggerated (some would make strong arguments for 'knowingly false') promises of the human genome project, and it's true that this is not being entirely overlooked in this celebratory time.  But feting this overwhelming mass of data, that we've just barely begun to make sense of, by calling for more data, to be collected at huge expense even as the cost of sequencing single genomes has plummeted, before we work out what we can do with the data we now have, is a cynical abuse of public trust.  The last set of promises is far from being filled, and we're now supposed to trust researchers with more money to answer the same questions they couldn't answer last time?

We have, say, 10 good candidate genes for effects on some disease, be it psoriasis or diabetes, and yet we continue to map, map, map to find even more genes--hundreds of them--that make ever more trivial contributions.  Why not stop spending on these larger-scale studies, and figure out what the reliably known genes, that may really do something, are doing and how to develop therapies and the like?  Of course some investigators are doing that, but more funds could be diverted to real problems if we but had the will....and hadn't set up so many Too-Big-to-Kill omics endeavors.

At least as serious is that scaling up means more money and longer-term research comfort, which is always easier than trying to think out serious problems to find more creative ways to understand them.  That is the situation we're in now.  New ideas come from the combination of data, genius, luck--and the struggle against a conceptually challenging problem.   Megafunding and megaprojects undermine the last, and most important of these, because they institutionalize science.  Many, including Darwin and Einstein and others of their stature, remarked that they couldn't have done what they did in the stultifying environment of universities, for example, and that was long before universities became the way they are today. 

The challenging problem is not a secret, and yet too many geneticists continue to dance around it -- complex traits are complex.  This is the single most consistent finding to come out of the last several decades of genetic research, including as we've also noted numerous times, from genomewide association studies (GWAS).  It's not a surprise, it's not a secret, and it's actually a positive finding, though too often ignored.  It is not that business as usual has brought no new findings, but the miniaturization of findings, the loss of focus on the really general, central issues we think is the problem.

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