Wednesday, June 25, 2008

Systems biology: everything's connected

On the second point of TCM, which is the theme of the week


"Systems biology" sounds complicated--hell, biology sounds complicated. It's the study of life, after all, and what could be more complicated? There are massive numbers of articles published on the opioid receptor, for instance, and that's on three different proteins with relatively well-defined roles. If that's one, imaginee how complicated a system must be.

But that's what the big picture is starting to look like: everything's connected. Jared Diamond illustrates this principle very well in the book Guns, Germs, and Steel, which I highly recommend reading if you like having your brains boggled. Chaos theory's butterfly effect, while formulated to describe a system's dependence on initial conditions, best illustrates the phenomena of a little change blowing up into something big.

Which is precisely what drugs do. You take a pill--by the time it gets into your stomach it's already dissolving. Maybe half of the active molecules make it through the acid bath. Then it gets neutralized, and absorbed into the bloodstream, where it may or may not bind to proteins in your blood, rendering them inactive. It has to get past the liver, which filters out all the crud that's in your blood; it get sloshed around by the heart, possibly ending up however many thousands of miles away from its site of action, all the while being degraded by the heat of the body and whatever enzymes are running rampant throughout your body, hell-bent on destroying any and al invaders. It's a wonder, if you think about it, that any drugs at all work, much less as well as they do.

"Well" might be pushing it--given the very long list of side effects of drugs such as Lexapro (which I've taken for a year) and the very short list of intended actions, let's just say that I don't know of a single boss who would accept that kind of performance from a person. Is this because the drug was specifically designed for the purpose of inhibiting one receptor? Is this why "dirty" drugs, which work on an array of receptors, are currently being explored as therapies?

This is systems biology: you can't touch one without touching everything. And in this respect, TCM, which strives more for "balance" than an actual treatment mechanism, has a lot to teach us in terms of how to view diseases. If you need an example, consider how the treatment paradigm for stomach ulcers has changed: it used to be that you drank milk, or chalk (how else to describe antacids?)--it was thought that the acid in the stomach was the problem, and you had to neutralize it. Or lessen it--I'm sure we all know of at least one person who has been told to "relax" because their ulcers would start "acting up". Then we figured out how to turn off the acid pumps in the stomach--good for the pain, bad for digestion. Then a single maverick doctor from Australia decides that Helicobacter pylori is actually the causative agent for ulcers, proves it by drinking a shot of the bugs. Stomach ulcers are now routinely treated with a course of antibiotics, with acid-lowering agents to manage the symptoms until they heal. But herbalists of all stripes, not just TCM practitioners, have been using licorice to manage ulcers. As far as how it works exactly isn't quite known--there are literally hundreds of active components in licorice, but the main compound, glycerrhyzic acid, is an anti-inflammatory agent--which might help the immune system destroy the bugs, as well as soothe some of the pain.

The point is not to suggest that herbs make for better medicine than drugs developed with a specific purpose in mind. It is merely that focusing on one aspect of the disease (stomach acid) can be counterproductive when trying to find new treatment regimens. It is likely that licorice, because it has hundreds of other active compounds, influences the body in ways that a specifically targeted drug cannot, and therefore "brings it into balance" again. It's like trying to center a tarp over a target using only rope. If you have one very strong rope, you can easily yank the tarp from A to B, but trying to center it can be very difficult. Whereas if you have lots of ropes, you can pull on it in all the right directions, and therefore center it quite easily.

Losing sight of the connections with everything else leads, ultimately, to a myopic view of health and the human body with a knowledge base that is still sorely lacking (ever wonder why we sleep? so do scientists). When you understand the connections, you don't eliminate the holes, but you see other ways to fill them in. Ultimately, nobody can know everything. But knowing more is never a bad thing.

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