Turned up to eleven: Fair and Balanced

Wednesday, March 22, 2006

Challenges in Microbiology
Here's a little thought experiment for you. You've set yourself up a nice little system for examining the genome of an environmental isolate for genes involved in some important phenotype. Now, there are lots of ways to do such a thing, but lets keep it simple. You use a mutagenic technique (and there are many) to introduce random changes in the genome. You then use your powers of observation to identify colonies (or growth in some other form) that is unusual. When you find a wierd colony, you isolate it for further study.

Is this science?

It is a real question. Many rigorous science theorists (Kuhn, I'm looking at you) would say "no". After all, at this point, you don't have a "falsifiable hypothesis", unless you would suppose "Mutagenesis causes changes in phenotypes" is a falsifiable hypothesis, but that's a bit trivial. However, I'd say "bollocks!" to that (or at least, if I was English I'd say that).

This is the start of science. It's not a full experiment, but rather a way to build hypotheses. And, if you want my opinion, this is the most underappreciated part of the scientific method. After all, hypotheses don't fall out of the sky like apples. We don't just wake up in the middle of the night thinking "maybe Scar-2 is encodes a phospholipase C like protein" or something like that. A huge part of the process is recognizing something interesting when you see it, and then following it up with efforts to gather supporting evidence.

Why am I belaboring this? Well, I think it's worth thinking about generally, first of all, but also because it gets at something I've been thinking about a lot lately, which is "how do you know when you've found something?"

This is particularly important when studying previously uncharacterized bacteria. If you go out to a patch of uncultivated land, and dig in the dirt, you will find countless bacteria. Simple technques can allow you to culture many of them (not percentage-wise, but numerically, thousands of unique strains); alternatively, you can use molecular methods to catalogue all the different types of organisms in that sample. However, when we look in the literature, we find people don't explore all this diversity. Rather, they pick things of well understood importance, and probe them deeper. So, instead of finding a brand new never cultured previously organism from the soil, they find a new nuance to the pathogenesis of E. coli gastroenteritis. One reason for this is obviously that it is much easier to figure out what's important with E. coli (or some other well known pathogen) because the parameters have already been hashed out historically. Another reason is funding (there's much more money in studying disease).

Here's an underappreciated reason. It's tough to study previously unstudied bugs. How do you know that you've identified a mutant, and not a variable phenotype. If it has a complex lifestyle, how many person-years can you devote to figuring it out? How do you attack the basic questions of function without clear guideposts. How many things can you assume are the same as the ones known in E. coli (depends!). Will you be able to use genetic tools? How hard are you willing to try to find out? Finally, how will you know when to publish it? (that's a big one!) And how will you persuade the editors to accept it? (another big one!)

Comments? Thoughts? It's not quite the usual animalcules fare, but it explains a lot about why we know so much about so few organisms, and so little about the vast, vast majority.