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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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February 25, 2002

All the Not-So-Myriad Ways

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Posted by Derek

The mention of schizophrenia last week brought up something I've thought about since I worked in the field: the limited forms of mental illness. When you first read about insanity (or deal with them firsthand,) it's easy to think that everyone who's insane is sui generis.The varieties of symptoms seem limitless.

But the more I've thought about it, the more I think the opposite. There are only a set number of ways in which humans go insane. Think of any given case of dementia, and you can come up with plenty of similar ones: you have paranoids convinced that their thoughts are being read - by their TV, by aliens, by invisible beams - or that the people they see on the street are all agents. There are the people who let piles of paper and garbage crowd them out of their houses. And the obsessives convinced that they are good friends with, are going to marry, are already married to some celebrity. You'll certainly find differences among these and among the many other types. But they're variations on the same master templates, differences of degree rather than kind.

Contrast the familiar dementias with superficially similar ones that don't seem to exist, like an inverse paranoid: someone who's convinced that people are sneaking around behind his back, helping him out and doing him favors.

Now, the nuts-and-bolts biochemistry of the brain is overwhelmingly complex. That's one of the big reasons that drug development in the field is such a slog. But at a systems level, it may be that there are several broad pathological states that the neuronal net can fall into. These could be based on an uncorrectable excess (or deficiency) of signaling in some part of the network, or some defect of timing in the handoff of processing from one region to another.

It might be analogous to similar low-energy states of a chemical or physical system, local minima on a surface. There could be any number of genetic and/or environmental factors that push the brain into one of these conditions, just the same way that you can tumble into a hole by coming from any direction on the surface. But you end up in one of a set number of places, one defined hole or another.

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