TBT: Of monsters and developmental mysteries

Once upon a time, I applied for an internship at my local public radio station. While I didn’t end up getting it, I sent them this writing sample that gives an informal explanation of developmental biology, which I stumbled across today. Since I am a freshly-minted PhD as of this month (yay!), and still love development after devoting most of the last 10 years to studying it, I feel that my thoughts on development from several years ago still apply. So, TBT, here’s my waxing poetic on the underpinnings of all multicellular organisms:

Few things are as fascinating as creatures mistakenly born with a single central eye, or those with too few or too many fingers on each hand. How did they get to be that way? When things go so drastically wrong, what is the culprit, and should we care? It would be easy to dismiss such anomalies as freaks of nature. After all, they are exceedingly rare. But in the study of developmental biology these monsters are the key to understanding why most living things aren’t that way, and how they form correctly. The mistakes show us not only who we are, but why we are.

Every living thing, whether it’s plant, animal or fungus, has an instruction manual that tells how to make more of it. This manual, known as the genome, contains the code for every building material, every map of where things go, and every step needed to make and maintain a creature. The manual has a section (called a gene) on how to make a molecule named Sonic Hedgehog, which looks nothing like the video game character. However, this molecule and the instructions telling where to make it are crucially responsible for ensuring that a creature has two eyes on its face and five digits on its hand. Without Sonic Hedgehog, creatures are born cyclopic, with a single central eye, or with only one digit on each limb. Change the instruction manual and you’ll change how or what gets made. These changes, called mutations, are often disastrous. But every so often a creature is born with a mutation that helps it, gives it a little superpower over its peers, so that it’s a little more successful at reproducing. When this happens the mutation is passed along to the progeny of the original mutant, and those progeny are more successful than their peers, and so on until the mutation becomes present in every member of the species, or until a new species entirely breaks off on its own. Mutation, the anarchy of the genome, is responsible for the incredible diversity among living things.

Developmental biologists love firstly to break things, and secondly to hijack them. We use mutation, nature’s own act of rebellion and innovation, to control development so that we can study it in animals like mice and chickens. Remember how the instruction manual includes a map for where things go? This applies to Sonic Hedgehog. By destroying, via mutation, the part of the manual that says where to put Sonic Hedgehog in the growing limb, we can block the growth of digits there. On the other hand (no pun intended), if we duplicate the map for where to put Sonic Hedgehog and put the copy on the other side of the limb, we can cause extra digits to sprout in mirror image to the original ones. By creating this controlled disorder developmental biologists may be making monsters, but the monsters let us answer the deepest questions about ourselves.

By looking for the misfits, by breaking the system in myriad ways, developmental biologists seek to understand. We study chaos so that we can see what order is supposed to look like, and so that we can recognize and fight chaos effectively when it knocks on our doors in the form of diseases like cancer. And sometimes we study chaos simply because we’re drawn to it, because it’s a fascinating corruption of ourselves. We study mutants because that’s what we are.

 

Featured image: my favorite model organism.

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