Was this a sports gene? Nay. More like a modest sprinting gene. Did it give a sprinter an advantage? Not really, because about 4 out of 5 people carried at least one clean copy of the gene. So although in theory this gene could help you if you wanted to compete as a sprinter, in practice it probably didn’t help at all, since pretty much every sprinter you ran against probably also carried one or two copies. In other words, ACTN3 didn’t make you fast so much as it made you not slow. A sprinter with this gene was like a basketball player who was 6 feet 4 inches: Being 6 feet 4 inches tall would probably ensure you weren’t the shortest player out there, but to be the tallest, you were going to have to have help from a mess of other genes that no one had yet spotted.
In the end, MacArthur concluded this “sports gene” was no more predictive of athletic performance than, well, athletic performance. Screening for it wouldn’t tell you anything you couldn’t learn from a footrace.
In talking to other geneticists over the past few years, I’ve found many with a similar experience. It’s almost like a rite of passage. A smart young geneticist—sometimes not so young—finds an effect linked to a particular gene, slaps high-fives around the lab, publishes … and then finds the effect turns out to be muddy, faint, and ambiguous.
This is more or less the story of genetics since the human genome was sequenced. As already noted, it’s not the whole story. Geneticists, including MacArthur, are making rare-disease discoveries—more every year—that actually save lives.
Yet the work is proving far harder than hoped. When Watson and Crick cracked the structure of DNA in 1953, it seemed they had found the shape of the key needed to unlock the mystery of life. Half a century later, many thought sequencing the human genome would unlock the door and show us the genome’s machinery, with all the parts and controls and levers and knobs conveniently marked. We’d be able to do almost anything. Instead, it showed us a genome that was mostly unmarked and ludicrously complicated—so complicated that even 13 years later, its workings remain mysterious.
The many geneticists who, like MacArthur, have closely experienced or witnessed disappointment feel keenly their field’s constraints and difficulties. At the same time, many of them are figuring out how at least small systems within this great machine work—a pulley here, a vacuum regulator there. And they rightly find immense satisfaction, not to mention status and opportunity, in identifying faulty parts that can kill.
That day that MacArthur walked me around Cambridge, we finished up with a couple of pints at the Eagle, where Watson and Crick had shouted out their discovery some 60 years before. As we pondered the humility of post-sequence genetics, it struck me that if the field is currently a bit lost in the fog, whoever clears the air could become to Watson and Crick as Watson and Crick were to Darwin. A century passed between Darwin and DNA, and another half-century passed before the human genome sequencing effort promised but failed to explain how DNA worked. There remains the glittering prospect of finding some systemic secret to how the great genomic machine operates.
Does the answer lie, as MacArthur once wondered aloud on Twitter, in some dimension or mode of information exchange we haven’t yet learned to see? Some meta-code we haven’t deciphered? Or will understanding the genome—a patchwork affair by definition—be a matter of finding one unique kludge after another?
History-soaked geneticists like MacArthur are understandably hesitant to shout “Eureka!” They’ve done that once—at least once—and been humbled.
And yet—who can resist reaching for such a prize?
Not to get too fancy, but have you ever seen the actual statue of Michelangelo’s David? Do so and you will of course see the hints of awkward youthfulness familiar from photos—the body’s beauty and promise, but also the oversized hands, the hint of boyhood remaining in his hips.
You’ll also see something I’ve never found perceptible in any photo: David, depending on how you look at him, stands both in contemplative, even humble repose, his weight solidly fixed on his back foot … and, as he moves onto his front, in the moment of initiating action. This effect shifts back and forth depending on your viewing angle and what you look at. From some angles, as with a good visual illusion, you can manage to see only one of these realities. From other angles you can see both at once. It is breathtaking. He is standing inert; he is stepping toward his target. You are watching, for hours if you wish, the flickering microsecond in which a youth becomes an adult.
No model could strike this pose. Yet if you could hold it, what a wonderful stance to take.
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