Why Normal Matter More Than Sick

The new May issue of Wired (the "Get Smarter" issue) has an essay I wrote about why medical science should spend more time studying the baseline - i.e., what's "normal" - and less on the aberration.

Here's the gist:

For all sorts of conditions, there's often no definition of normal. In heart disease, for example, CT screening tests can spot abnormalities in arterial plaque — but no research exists on whether that information is actually predictive of heart disease or stroke. "We need to know normal variation," says Pat Brown, a professor of biochemistry at Stanford University School of Medicine. "It's really underappreciated as a part of science."

This essay came out of several conversations with Brown, an oncologist at Stanford who's one of those scientists whose knowledge seems to span into every possible corner - and can articulate relevance in clear, compelling terms. He has been ranting (in the best possible way) about the need to know normal for a while, and when I couldn't get him to write this essay himself, I did the next best thing: pulling as much of the idea out of his brain as I could muster.

And it's something that many scientists, particularly those working at the molecular and DNA level, are saying: We need to know more about the baseline. I spent the past couple days at the Institute for Systems Biology symposium (where Bill Gates gave the closing keynote), and many of the presentations touched on this theme: there's too much variation at the cellular level to be able to clearly say (in the plainest terms) this cell is bad and this one is good. Only when we understand the variations at a cellular or molecular level will we know when to intervene on disease, or whether treatments are working, and so forth. As the story makes clear, this is especially important for cancer right now - are we overtreating or undertreating? - but it will become a relevant issue for all intervention soon enough.

And push it forward: Should we know what's normal not just in the human population, but in our own body? For instance, a fellow from the ISB told me about an experiment that the institute conducted one day: They had several staff in and took blood samples, then went out and had lunch. After the meal, they took another blood draw. Sure enough, the before/after blood makeup was totally different - not just in terms of stuff like glucose levels but down to the protein level. Long/short: even in one person, it's difficult to know what's "normal" on a protein level. But the more we can discern these baselines, the more we'll know when to treat, and how, and even whether.

More on the symposium later, if I can manage.