Tuesday, April 17, 2012

A bit of a storm

Our post yesterday asking whether support for whole genome sequencing was fading seems to have triggered a bit of a storm.  We know this because our hit count for the day was astronomical (well, for us).  We noticed that a bunch of tweets were sending readers our way, so, naturally enough we thought we'd check out what people were saying about the post on Twitter.  And it was interesting.

Most people, though not all, who made an editorial comment disagreed with us.  And, ok, it's hard to go into detail in 140 characters, but the comments were pretty uninspired, shall we say (along the lines of "Is whole genome sequencing fading? The answer is No!"), but even so, to us, an indication that we'd hit a nerve.  As far as we can tell, the argument is that because sequencing is still being done, it should continue to be. 

This looks to us basically like some serious circling the wagons going on.  People with vested interest in the status quo protecting their interests.  Ok, fair enough, and understandable.  But, this does the science a disservice.  There are serious issues here -- tweeting about how sequencing has to happen because it's happening just doesn't do them justice.

As Ken posted yesterday, writing about why whole genome sequencing hasn't met the promises made about it:
There are too many variants to sort through, the individual signal is too weak, and too many parts of the genome contribute to many if not most traits, for genomes to be all that important--whether for predicting future disease, normal phenotypes like behaviors, or fitness in the face of natural selection.
As he also wrote, there are some traits for which one or a few genes are important, and working those out is where the genetics money should be spent.  Doing whole genome sequencing because we'll surely learn something even if we don't yet know what, or because personalized medicine is just over the horizon, or just because we can, are not good reasons to keep spending the kinds of money on this that we're spending.  We know enough now to know that genomic contributions to most traits are multiple, varied and complex.

This is not an admission of defeat.  This is an acknowledgement that we've learned a lot of genetics in the last century, reinforced clearly by the new sequencing technology; and what we've learned is that most traits are multifactorial, due to gene by gene and/or gene by environment interactions, there are most often many pathways to the same phenotype, and so on.  We should give up the conceit that we're going to be able ubiquitously to predict and prevent diseases based on genomes, and get on with solving problems.  Those that are genetic need genetic approaches.  But there are other issues, and other ways, to learn about evolution, disease, and the basic nature of life.


James Goetz said...

If Ken's anecdotes turn into an undeniable trend, then that would be great and worthy of celebration. Perhaps some of Ken's critics failed to see that he encourages a shift of focus to the hard work of taking care of easily discoverable genetic diseases, which is sadly underfunded compared to the over-funding of GWAS.

Now off the topic,

Happy Birthday Anne : -)

Anne Buchanan said...

Thanks, Jim! And, good to see that what's being overlooked by some readers is clear to others! We were also interested to see Ken's anecdotes anecdote confirmed by at least one commenter. The beginnings of a groundswell? Time will tell.

Ken Weiss said...

Amen to your message(s).
We have been very casual about the lack of progress in tackling the truly genetic disorders. And what about rare ones...no market for the Pharmas?

Well, if people can avoid serious common chronic diseases by behavioral changes (as, it seems, is certainly possible), then why shouldn't a population with a conscience be willing to invest in whatever it takes to attack the devastating major-gene diseases?

The current effort, by whatever fancy names people want to give it, is basically like what Congress does: instant gratification by spending up front, and kick the real problem down the road.

Prediction is the up-front way of making quick harvest in genomics, leaving treatment for somebody else to deal with at some vague point in the future. And even the up-front genomically based prediction is falling far short of its promised efficacy.

I didn't make the promises, but those who have done that seem to be the ones most likely to complain if the level of results is taken to task.

It's a complex mix of issues, no matter how one views it.

Anne Buchanan said...

Something we haven't talked much about, too, is how many GWAS results implicate immune function. How many of these chronic diseases being treated as genetic would be better thought of as infectious?