Thursday, September 22, 2016

Chain-ring genetics

If you're a bike rider, as I am, you know that there is a huge market out there trying to lure you into a really, really fancy bike.  Bike prices can easily get well into 4 digits, amazingly, and apparently there are enthusiasts who are willing to pay for them--maybe the thrill of the purchase is itself enough!
In a way, fancy bikes serve as an analogy for broader aspects of our society, as I'll try to illustrate.

I live in a pretty hilly area, and even though I just to bike-path or street-and-sidewalk riding, it's a pretty dramatic range of effort one needs in order to navigate the changing ups and downs.  And my bike, shown in this amateur photo, is a Trek Navigator hybrid, with a 3 x 7 gear cog setup: 3 chain rings in the front, and a 7-cog rear gear set.  That's 21 different gears, and I was happy to buy a bike with such a wide range of pedaling-efficiency options.

The next figure shows the gear ratio range schematically.  For each front chainring (Low, Middle, High), the corresponding line shows the relative gear ratio across the 7 rear cogs:So, in the extreme, if you go up a steep hill you want a front-1/rear-1 choice (the easiest combination, with more pedal rotations per rear wheel rotation, making each rotation easier even if you go slower), and downhill you'd want 3-7 for the opposite effects.
High, Mid, Low gear ratio range  for the 3-front, 7-rear cogs (schematic)

This plethora of gears was an attractive selling point when I bought this bike, which is a good one, but now that it's a few years old, I decided to shop around to see what's on offer these days.  I notice some  3 x 8, 3 x 9, and 2 x 9 front/back cog numbers.  The more expensive bikes tend to have more gears, though one had only 2 chainrings in front--and I wondered about that.  If the rear cogs had the right ratios, there is less weight in the front only having two chainrings, and the shifting will be easier and the shifting mechanism may act more quickly.  But the overall range was less, meaning it might not suit all riders as easily. In any case, there's a lot of techie glitter and salesmanship going on to get you to pony up the $K's for the fancier bikes.  They weigh a few pounds less, too, and so on, as the price goes up.

The bike-tech web sites basically warn you to avoid cross-chaining, which is to set the front chainring to a side of the cluster opposite to the cog set in the rear.  Instead, common advice says, shift to front-rear combinations for which the connecting chain is as close to parallel with the frame as possible.
But if you read a bit more carefully, you can see that some of the cross-chaining evidence, for modern bikes, is not very well established: you may not damage the chain, cog teeth, or be detectably less efficient, after all.  And some of the combinations--where the ranges in the above figure overlap--would never really be used.

So I wondered why one would not just stick with the middle front chainring all the time.  If you do that, the full range of rear cogs can be used without cross-chaining issues.  You don't get all of the bike's range, but you do get most of it.  What would the same ride feel like using only the middle chainring?

I've now tried that by taking my ride today without using the high or low chainring (stupidly, I never had tried that before!).  In going up the very steepest hill, I knew I could find it a tad easier to use the easiest front-rear combination.  Going downhill, I could muster up a bit more speed with the opposite extreme front-rear combination. But basically, the ride was the same.  It was also a bit simpler and involved a lot less coordinated shifting.

I decided I don't need a fancy new bike, after all!

So what does this have to do with genetics?
I was led to write this brief reflection when I thought about how many not really avid bikers have been led by cycle makers to get the most extensive, fanciest gearing (among other options), forking over very much more money, for very little gain, in the process.  Yes, performance is a bit better, but it doesn't really match up to the hype, especially not at the cost, unless you are a bike-racer or off-road biker, or have a yen for the latest-and-greatest and lots of 1%er money to invest in ego toys. The marginal gain per unit cost is minimal.

We're getting a lot of similar marketing for gearing up, so to speak, in our biomedical research and its application.  We're being told how marvelous having lots of chainrings and large rear cog-sets will yield miraculously better health than our old-fashioned ways have done so far.  It's called by flashy impressive or intimidating names like 'next-gen sequencing' or 'Big Data' or 'exome profiling', or 'precision genomic medicine', and that's the analog of Big Gearing (though a lot more costly).  Big Data is for the research community as carbon-fiber frames are for the bicycle industry.  Scientist and general public alike are suckers for slogans promising unbelievably more in the health-research industry from gearing up, much as we are for slogans promising unbelievably better biking.

The promotions are always shifting, so to speak, as the science rolls on.

But genetics can be important to our very lives!
The line we are fed by NIH and the research establishment always stresses the vital importance of our Big Data investment.  That is, after all, what 'precision genomic medicine' and wars on cancer and so on suggest they are promising.  It is true that under some circumstances, for some people, large-scale genomic database research may soon, or eventually, lead to more effective treatments of disease. There are already some examples, though how many really required massive genomewide association studies and the like is open to discussion.

As we've noted here many times, there are tons of more clearly genetic, or otherwise-caused, disorders for which the same monetary investment might yield much greater benefit. Most advances still, generally, seem to come from focused research on known, substantial causes.  Lifestyle changes, if our epidemiological data are worth their own huge cost, could much more massively reduce or defer common adult-onset diseases.  And there are a large number of clearly genetic diseases, pediatric and otherwise, for which the actual gene or genes are known.  They often strike at birth or in childhood, and are life-long debilitating,or life-shortening conditions.  They have, in my view, a much stronger and more legitimate claim on research resources.

Nobody wants a disease, genetic or otherwise, not even if it only strikes late in life.  But we should use the gears we have to get up those hills, rather than constantly being promised miracles if we only add another chainring, and then another, and then.....