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A Note about Biology
Dec 25, 2009, 3:11a - Science

(This is the first in a 3-post series on biology. I begin with some background, mostly to provide context for the second post, which is about a behavior in bacteria called chemotaxis. The third post will introduce a web app that simulates bacterial chemotaxis, and will be explained in gratuitous detail. I made it over a year ago, and it's about time that it saw the light of day. And yes Sundar, I know you don't find biology interesting, but maybe one day you'll agree with me that it's the most interesting thing in the world, far more interesting than business or technology. Also, don't forget the bonus video post.)

A biologist's task is to understand how those objects that we think of as "alive" work. Just as a curious engineer might ask, "How does a car work?", a biologist might ask, "How does a bacterium work?". But biology is actually very different from engineering. In the first case, an engineer deconstructs a human-made device, while in the second, a biologist dissects an organism of unknown origin following unknown rules. Biologists often revert to using engineering-style language (e.g. calling an organism a "system") as a linguistic shortcut, but this is more metaphor than actual truth. Biological organisms seem to be fundamentally different than devices that we've engineered so far, and part of the reason I find biology so intriguing is because I'm curious about the nature of this difference. Is it just that biological organisms are grounded in messy biochemistry, while most devices we create are built on far "cleaner" substrates? Or is there a basic biological principle that is currently missing in our engineered constructions?

In trying to understand how an organism works, biologists tend to work at 3 different levels. Ordered from the macroscopic to the microscopic, these levels are 1) the behavioral level, 2) the physiological level, and 3) the molecular level.

When biologists study behavior, they study the whole organism in its environment, including how it moves through the world, how it interacts with other organisms, how it eats, how it reproduces, how it poops, etc. They're looking for macroscopic events that can be observed just by looking at the organism usually without the aid of any additional tools (except, say, a microscope in the case of really small creatures). In the case of bacteria, the behavior under study could be the bacterium's ability to navigate through a gradient of sugar concentrations until it reaches the area of highest concentration. This behavior is called "chemotaxis".

When biologists study physiology, they're looking one level deeper into the organism. Take the example of bacterial chemotaxis. Rather than just observing that bacteria move to the peak of a sugar gradient, a physiologist will be interested in whether the electrical activity or calcium concentration within a bacterium changes as a function of where the bacterium is in the gradient. They'll be curious about whether this lower-level activity might actually be part of the physical mechanism that senses the sugar and determines how the bacterium moves through it. To start all the physiologist has is a correlation, but by mucking with the signal of interest (by, say, injecting electrical current), they can provide evidence for a causal role as well. Physiologists want to peer beyond behavioral observation into the mechanisms that might underlie a phenomenon. The physiological level is intermediate between the behavioral and molecular levels.

The lowest level that biologists tend to study is the molecular level. In the example of bacterial chemotaxis, the molecular biologist might try to remove molecules and see if the bacterium can still chemotax. For example, they might mutate the DNA of a bacterium, turning off different genes until they find a mutant bacterium that can no longer chemotax. Then they know that the normal functioning of that specific gene is required for chemotaxis, and have added a new molecule to the grab-bag of molecules that are believed to be important for chemotaxis.

The line between molecular biology and physiology can blur. In the example above, I mentioned calcium concentration as a signal that physiologists look at. But of course calcium is also a molecule, so in that case it can be thought of as a molecular analysis as well.

So who really cares about all this stuff? In my opinion, all levels matter if you want to answer the question of "how does a bacterium work?" What's funny is that in my experience, biologists tend to pigeon-hole themselves into looking at one level of analysis exclusively. For example, the researchers in my lab often focus on the molecular level, finding genes that may affect other molecular or cellular phenomenon (but not behavior). I always wonder whether that's really useful. I mean, who's to say that if gene A changes the concentration of molecule B, that it means anything to the functioning of the organism itself? It might just be the way it is, for no real rhyme or reason, with no real function or purpose. So while you've made a valid observation, I'm not sure why I should find it interesting...

For me, biology is all about behavior, or other macroscopic effects (such as disease and death) that really affect the survival of the organism. If you believe that evolution by natural selection contributed to how organisms came to be the way they are, then whatever it is that contributes to reproductive success is what really matters to the functioning of an organism. Whether molecule A is required for the survival of cell B may be of no consequence to the organism as a whole, so figuring out what molecule A is isn't really very interesting to me.

I am really curious about how an organism can do a behavior, and when I study behaviors I want to understand them all the way down to the molecular level.

Within biology, an organism's behavior is notoriously difficult to study, because it depends on so many variables; it's hard to know which ones matter and to control them all. When I first heard that bacterial chemotaxis was one of the most well-understood behaviors in biology, I was intrigued to understand what that meant. So far most biological explanations had left me wanting more, and here stood a so-called "crown jewel" of biological understanding. After reading a bunch of papers, I decided to take a stab at building a computer simulation of how some people thought that bacterial chemotaxis might actually work. By building a simulation and tweaking individual variables, I thought that I would gain a better understanding of how bacteria chemotax. I'll describe bacteria chemotaxis in more detail in the next post, and present my simulation as the grand finale.

Read comments (4) - Comment

Ruggero - Jan 4, 2010, 3:26p
Excellent post.

Biological systems are far more complex than any of the system we've been able to come up with so far.

So far.

There'll be a time when the products of our minds will be more complex and smarter than us all. And probably at that time it won't make much sense anymore to talk about 'products of our minds' and 'us' because they will merge one into the other. If you think more carefully, this actually already happened. Do you wear contact lenses? Do you have a tooth filled? Do you have a hip replacement? Do you know of Oscar Pistorius? Technology is rough, but it's slowly integrating with biology. And not only at the macroscopical level. The most interesting works are in nanotechnolgy, where the distinction between an engineer and a chemist (or a biologist) becomes pretty hard to make.
Biological systems of course are still much smarter than robots. This is partly because biology writes information on DNA (about 3 nm), where current technology only goes down to 32 nm. And partly because we don't know how to handle matter properly yet. What is DNA if not a self-assembly material?

'Cleaner' substrates? There's nothing really clean even in engineering, believe me. 'Simpler' would sound much better.

Is there a basic biological principle we are missing? I don't know. I only know that there's a lot more to know about the language used in nucleic acids. If the principle is there, it has to be written down somewhere.

A question: does a virus chemotax?

nikhil - Jan 4, 2010, 8:00p
As far as I know, a virus doesn't have any ability to actively move through space. A bacterium, on the other hand, uses flagella as propellers to execute a biased random walk through space. So I guess that a single virus wouldn't be able to chemotax. I haven't really looked into it though, and perhaps the right experiment hasn't even been tried, so I could be wrong.

Sundar - Jan 10, 2010, 5:44p
Nice post, I do find biology interesting when written this way. I hated it because I did not want any part of dissection and infact, refused to in high school.

PS - engineers do not always deconstruct human made devices, sometimes it is also nature like "Big bang" - unless you are differentiating between engineers and scientists

nikhil - Jan 15, 2010, 12:44p
yep, i'm distinguishing engineers, who build things, from scientists, who try to understand how non-human-made things (nature, socieities, human minds) might work.

oh how vegetarian of you :)

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