little secrets, tremors, turn to quakes

My favorite kind of stories are these. Over 25 years ago, scientists were fiddling with the genetics of fruit fly development. There were two organisms scientists toyed with most in those days: fruit flies and worms. Also known as Drosophila Melanogaster and C. Elegans, respectively (like you cared). Both were chosen because they are easy to work with- they are easy to manipulate and they reproduce quickly. Researchers could mess and mutate the genes of fruit flies, and within a few days, they would discover they had found a way to get the fly to grow an extra set of wings, or a leg where its antenna should be, etc. etc. In the course of messing around in this manner, they found this mutation:You can't see it so well from this picture (which was taken in 1980, before we had all the nifty camera technology that still doesn't help me take a worthwhile picture), but this fly wound up a spikey ball with no wings. So, they called the gene that had been mutated Hedgehog. And back then, most people rolled their eyes, and shrugged, thinking nice work, fruit fly dudes, but I really wonder if we should be funding you crazy scientists for this random work that has no applicable value. A classic issue that comes with working in basic research.

As it turns out, all of this work in fruit fly and worm development wound up being immensely important. It turns out fruit flies and worms are not that different from you and me, especially in terms of how we decide what we want to be when we grow up. As embryos, our cells figure out what they want to be by listening carefully to what is going on around them, reacting to small changes. It turns out what keeps a normal fruit fly from looking like a hedgehog also helps human embryos figure out how they should be growing. The researcher that found this structurally similar gene in humans wanted to piggyback on the original name, and also was something of a videogame buff, so guess what he came up with?
You can't say these dudes didn't have a sense of humor. At this point, people became a little more interested. Hmmm, cool, we've got this same development pattern as flies, but... so what? Well, have I got a story for you. It turns out that Sonic Hedgehog is activated in embryonic cells that are figuring out what they want to be. Then they get shut down for the most part, because we're all grown up- our fate has been decided to a large extent. But, there's still a small part of us that's constantly renewing, certain things in our body have to be recycled. In those instances, Sonic Hedgehog is still doing its thing, telling cells these are not the droids you're looking for and sending them to become what Sonic Hedgehog wants them to be.

Here's the thing. If Sonic Hedgehog goes haywire and doesn't behave as it's supposed to, it goes to the dark side of the force. It programs cells improperly, and the next thing you know, the dreaded big C looms on the horizon. In fact, researchers have found that almost all basal cell carcinomas, a type of skin cancer, have defects in Sonic Hedgehog signaling. Dig that.

In an even crazier, parallel development, some sheep farmers found that ewes eating corn lilies were giving birth to mutant lambs with only one eye! Be glad I didn't dig up a picture of that. Some scientists got on the case, and discovered that there's actually a substance in corn lilies called cyclopamine. And guess what cyclopamine inhibits? The Sonic Hedgehog pathway. Now, even though that was bad news for those poor lambs, cyclopamine turns out to be very good news in fighting cancer. It basically tells Sonic Hedgehog to STFU, so that adult cells remain behaved.

I could never do the work of those fruit fly researchers, because I am short-sighted and impatient. But I am a big advocate of funding those mad scientists doing their seemingly fringe research. Sometimes, you have to take it on faith that a small discovery that might seem irrelevant will eventually serve to sharpen the big picture in important, unforeseeable ways.