The Enzyme is NOT the Protein

In my previous post I emphasized that the map is not the territory. I took String Theory off the shelf, dusted it off a little, and then mercilessly beat it up for no good reason. That was all well and good, but I want to address a point about biology that I think we sometimes loose site of.

The enzyme is not the protein. More precisely, the enzymatic activity is not the protein. Really said most completely, the function is not the protein.

Really, I am attacking a map. It's a map many have seen. It looks something like this. Or even like this.

As biologists, we often want to identify a protein's function. We're sort of obsessed with it, I guess. If a protein is necessary to survive, presumably it does something in the cell that allows life to happen. Maybe it helps break down bad stuff, or build up good stuff. Maybe it replicates DNA. Maybe it guards against invaders somehow. Perhaps it's a messenger of some kind, 'transducing' signals through the cytoplasmic ether.

We're helped along by the fact that a lot of genes really do seem to have a particular task to which they are assigned. Hexokinase has a very specific enzymatic reaction that it appears to be dedicated to catalyzing. It lives for the service of catalysis. Our very understanding of genes is driven largely by the observation of mendelian inheritance of genes that break these rigidly defined and clearly necessary functions. Animals with defects in these sorts of genes often suffer most obviously from some metabolic dysfunction, and we assign the gene to the metabolic disfunction.

Now that we have moved past simple metabolism to much more murky phenotypes, we seem to still be tied to the idea of proteins as acting to fulfill a certain function. It's as though they are machines designed to act as some cog that a watchmaker planned to use. Some examples: p53 protects against tumors. It's a tumor suppressor. Hif is a hypoxia sensor. VEGF is an angiogenesis factor.

Why can't these proteins have hobbies? Let's remember that evolution pressures a cell to survive, not to be elegant. In as much as survival is elegant, I guess that gets the cell there. But in the end the thing we're talking about is the most complicated gamish of protein you could think of, and it will do just about anything to get by. Whose to say that VEGF, in its off hours, doesn't swing by the glycolytic cycle for a little regulatory interlude. Perhaps Hif, during lunch hours, cruises by the spliceosome for a little slice and dice. Even the 'housekeeping gene' and paragon enzyme GAPDH appears to spend lazy sundays in the nucleus, a horrifying prediction for the one protein one function minded.

Let us remember that's what really happens in the cell is a very very complicated mess of reactions. Once a day in some cell in the human body I'd guess that every possible protein interaction pairing can and does occur. There's no reason that the cell hasn't evolved to use some of those strange pairings to give it a little more juice towards the end of its endless quest for self replication.


Which is all just to say that a protein doesn't need an easy to pin down function to be very important for the cell. Nor does a transcript with a well defined function necessarily not have other very important roles.


Here is the question we should be most concerned with. In all the cartographic glory of drawing out these maps, have we missed something essential? I've argued above that we've probably missed the fact that some proteins act in different places, and again missed that some places might occasionally be occupied by different proteins. I would argue that this is more than a frivolous attack, it explains why our experiments are so difficult to replicate and real advances are only rarely driven by deduction alone. We've only just scratched the surface of the combinatorial possibilities.

The Map is NOT the Territory

I know very little about Alfred Korzybski, and even less about general semantics for which he is famous. I do, however, know his most famous quote: "The map is not the territory". So it is with complete academic ignorance that I co-opt the term for use in the world of biology. You've been warned.

Here's the idea, as I conceive it. You have a map. You have a model. You have a theory. Your theory is awesome, beautiful, exciting and entrancing. Let's say it's string-theory. Let's say it's relativity. Let's say it's evolution. Whatever.

This thing you have, this idea, it's a map. It's a guide to something. It's a flat piece of paper that represents and distills something about reality. It is not its own reality. It is not its own truth. It's serenity is not the same as the actual cold hard truth of the thing that it describes.

In the case of a map, like the kind you hang on your wall, this is obvious. No one is lining up troops to defend the borders on the map in the atlas on your coffee table. They are lining up to defend the real borders of the real states on the real rivers of the real earth.

But in the ivory tower there is a proneness to confusion. String theory, perhaps the best example I can think of, is lauded for its elegance and seeming brilliance. Few people could imagine an explanation for the complexity of quantum physics and relativity in a set of dimensions coiled down so small that they cannot be perceived at our scale of life. It is an impressive theory.

Where is the territory to go with it? String theory has yet to make a single testable prediction. Its details are so arcane that those who study it seem to inevitably be lost in its folded dimensions, content to treat the theory a platonic ideal to which the universe we live in might aspire to reach.



The map exists in service of those who live in the territory. Our theories exist in service of our abilities to make predictions and interact with our world. We draw Australia into our map because it helps us to make predictions about the consequences of certain actions (e.g. hey, I wonder what will happen if I sail South from Indonesia).

In Biology we are plagued by pseudo-predictive models. We spend a lot of time flailing around trying to come up with "mechanism" to explain our observations. We often find that we can come up with two or three. Sometimes we bother to test the predictions that our hypothetical mechanism would imply. Too much of the time the data show muddled and confusing support. We often pick and choose the experiments we want to perform that seem to bolster our point, and dig in for the academic fight over the arcana we've brought into the world.

In the end, the mechanism doesn't mater. The elegance of our theory doesn't matter. We can fight over the lines on the map until Armageddon, but what matters is whether we've done something positive in the real world. This should be completely obvious, but I am shocked at how quickly I am loosing touch with that simple fact. Keep your wits about you, and tuck Korzybski's saying in the back of your mind.