Wednesday, April 23, 2014

Genomics in microbiomic clothing: The next 'hula hoop'?

So we've just been through 20 years of genomics, GWAS based on genetic markers tested in samples such as ever-growing huge numbers of cases compared to hordes of controls.  We know that mapping even in simple organisms including flies, yeast, and bacteria, show genomic causal complexity.  We know that whole population genome sequencing is the next way the marketeers will promise immortality.  We know this teaches us lessons for biology that we don't want to listen to.

We know that even without the exotic technology that makes all this possible, there are relatively strong, simple genetic causes of traits--this goes back in a formal sense to Mendel, and even GWAS, though often thought-free, can find these strong effects and will continue to find them here and there.  This, even though after all the effort of 20 years or more we still don't really understand the traits for which the mirage of an oasis of solutions has failed us (obesity, diabetes, schizophrenia, asthma, autism,.....).

So this is not no-yield science even if it is science of diminishing returns.  And it's our current way of doing business (and, perhaps, 'business' is the right word for it?).  It's our 'anthropology', how our culture works.  Big Ag is doing it, the military is doing it, NASA is doing it.   Big Data and other Big Projects are the order of the day and, to be blunt, the way to secure large long-term funds in a fickle market.

But as at least some are tiring of the over-marketing of all of this, the next genomic hula-hoop fad down this particular technology's line looks like it's the microbiome.  DNA sequencer makers can sell machines for this type of study, if the GWAS market shrinks.

But isn't it basically just the same?

We will find that the community of bugs in this or that part of your body will differ over time, will differ among sampling sites (this or that part of the skin, gut, or wherever).  It is even more complex than genomes because not only will we have the DNA sequences of large numbers of recognized microbes, but the microbial species will vary within their population and we'll have their relative frequencies in our samples.  In other words, from each person we get one genotype, alleles present or absent (or present in one or two copies), but for microbes we'll have their relative frequency in the sample (how many times their sequence was identified in the sample).  So there will be another very major variable added to the mix.

Everyone will differ in these regards, within and between populations, with age, sex, all sorts of environmental variables, and over time.  And while these variables may be enumerated one by one, in fact their dynamics involve interactions among them (often, probably, more than just two-species interactions in complex microbiome ecologies).  And there will be interactions with the host's genome as well.   If interaction among genomic sequence elements has proven largely intractable, wait til you see what the Wizards of Microbiomics turn up and start touting to the media.  This if anything bodes to make genomic variation rather simple!

Of course, we will learn a lot in this endeavor.  And, as with genetics, there will be strong and important signals related to human, animal, and plant well-being.  Some of these we know of already (e.g., some nasty strains of infectious bugs, E. coli, and so on).  Many would not require expensive exhaustive enumeration studies to find.  Just as with genetics, there will be successes.  But, we think, just as with genomics, we can already see the over-selling and the faddishness and band-wagoneering of microbiomics (and, similarly, of epigenetics).  Can basically the same knowledge come with fewer, more focused and disciplined microbiomic studies?

Perhaps we are over-reacting here, or perhaps this is just how humans, individually pursuing careers behave.  To get the minority of brilliant discoveries, perhaps the price to pay is of the sea of not-so-brilliant incremental work.  Only history will filter through the din of self-promotion to show what was actually important and in itself actually worth paying for.

If this is just how we are, in science, the arts, business, then progress is expensive, a fact we have to live with.  Of course, if resources were not captured by this academic welfare system, many other people could actually live, literally, or have better health and living standards.  Priorities on what to do with resources are societal, and we acknowledge that the sentiments we express presents a political view that.

But in terms of science itself, one could discuss whether there might be a better, more focused and modest, and less costly way to enhance creativity per dollar invested.  We and others have been writing with occasional suggestions about how funding could be less institutionalized, and we recently asked whether all of those ideas are rather irrelevant to the societal processes that will actually make change, when and where it happens.  Repetition and persuasion are perhaps essential parts of the jockeying 'game' of resource distribution.

Meanwhile, we'll be treated to the predictable years of breathless fantastic unprecedented paradigm-shifting discoveries in microbiomics.  Eventually, its dust will settle.

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